  SEQ CHAPTER \h \r 1  

UNITED STATES ENVIRONMENTAL PROTECTION AGENCY

WASHINGTON, D.C.  20460

					

		                                                                      
                 Office of Prevention, Pesticides 

                                                                        
                      and Toxic Substances

January 24, 2008

SUBJECT: 	1,3-Dichloropropene: Proposed New Use for Drip Irrigation in
Vineyards: Revised HED Human Health Risk Assessment; DP Barcode:
D347789, PC Code: 029001

FROM:	Christine Olinger, Chemist/Risk Assessor 

		Elizabeth Mendez, Ph.D, Toxicologist/Risk Assessor

		Jeff Dawson ORE Assessor

		Reregistration Branch 1 

		and

		Dana Vogel, Chemist/Risk Assessor

		Registration Branch 1

Health Effects Division (7509P)

THRU: 	Michael S. Metzger, Chief

Reregistration Branch 1					

Health Effects Division (7509P)

TO:		Cynthia Giles-Parker, Chief

		Fungicide Branch

		Registration Division (7505P)

Dow Agrosciences has proposed new uses of 1,3-dichloropropene (1,3-D)
for use in established vineyards using drip irrigation.  HED prepared a
human health risk assessment for the proposed new uses in June 2007 (C.
Olinger et.al., 6/6/2007, DP Number D340059).  This revision provides
additional characterization on the aggregate exposure, bystander
exposure, and modifications to the drinking water assessment.

This risk assessment addresses both exposures in the general population
and for those occupationally exposed.  The key concerns for this
assessment were exposures in the general population which occur
primarily via inhalation for those in proximity to treated fields and
facilities (i.e., bystanders).  Dietary exposures from food and water
are also addressed.

HED has no concerns that would preclude granting a conditional
registration for the proposed use.  Confirmatory residue chemistry
studies are required before HED can recommend for an unconditional
registration as outlined in section 10 of the attached assessment.



Table of Contents

  TOC \o "1-8" \h \z \u    HYPERLINK \l "_Toc188948816"  1.0  	Executive
Summary	  PAGEREF _Toc188948816 \h  4  

  HYPERLINK \l "_Toc188948817"  2.0  Ingredient Profile	  PAGEREF
_Toc188948817 \h  11  

  HYPERLINK \l "_Toc188948818"  2.1	Structure and Nomenclature	  PAGEREF
_Toc188948818 \h  11  

  HYPERLINK \l "_Toc188948819"  2.2	Physical and Chemical Properties	 
PAGEREF _Toc188948819 \h  12  

  HYPERLINK \l "_Toc188948820"  2.3	Proposed New Use Directions	 
PAGEREF _Toc188948820 \h  12  

  HYPERLINK \l "_Toc188948821"  3.0	Hazard Characterization/Assessment	 
PAGEREF _Toc188948821 \h  13  

  HYPERLINK \l "_Toc188948822"  3.1	Hazard Characterization	  PAGEREF
_Toc188948822 \h  13  

  HYPERLINK \l "_Toc188948823"  3.1.1	Database Summary	  PAGEREF
_Toc188948823 \h  13  

  HYPERLINK \l "_Toc188948824"  3.1.2 Toxicological Effects	  PAGEREF
_Toc188948824 \h  13  

  HYPERLINK \l "_Toc188948825"  3.2	Absorption, Distribution,
Metabolism, Excretion (ADME)	  PAGEREF _Toc188948825 \h  14  

  HYPERLINK \l "_Toc188948826"  3.3	FQPA Considerations	  PAGEREF
_Toc188948826 \h  15  

  HYPERLINK \l "_Toc188948827"  3.3.1	Adequacy of the Toxicity Database	
 PAGEREF _Toc188948827 \h  15  

  HYPERLINK \l "_Toc188948828"  3.3.2	Evidence of Neurotoxicity	 
PAGEREF _Toc188948828 \h  15  

  HYPERLINK \l "_Toc188948829"  3.3.3	Developmental Toxicity Studies	 
PAGEREF _Toc188948829 \h  15  

  HYPERLINK \l "_Toc188948830"  3.3.4	Reproductive Toxicity Study	 
PAGEREF _Toc188948830 \h  15  

  HYPERLINK \l "_Toc188948831"  3.3.5	Additional Information from
Literature Sources	  PAGEREF _Toc188948831 \h  15  

  HYPERLINK \l "_Toc188948832"  3.3.6	Pre-and/or Postnatal Toxicity	 
PAGEREF _Toc188948832 \h  15  

  HYPERLINK \l "_Toc188948833"  3.3.6.1	Determination of Susceptibility	
 PAGEREF _Toc188948833 \h  15  

  HYPERLINK \l "_Toc188948834"  3.3.6.2	Degree of Concern Analysis and
Residual Uncertainties for Pre- and/or Postnatal Susceptibility	 
PAGEREF _Toc188948834 \h  16  

  HYPERLINK \l "_Toc188948835"  3.3.7	Recommendation for a Developmental
Neurotoxicity Study	  PAGEREF _Toc188948835 \h  16  

  HYPERLINK \l "_Toc188948836"  3.4	FQPA Safety Factor for Infants and
Children	  PAGEREF _Toc188948836 \h  16  

  HYPERLINK \l "_Toc188948837"  3.5	Hazard Identification and Toxicity
Endpoint Selection	  PAGEREF _Toc188948837 \h  16  

  HYPERLINK \l "_Toc188948838"  3.5.1    Acute Reference Dose (aRfD) -
Females age 13-49	  PAGEREF _Toc188948838 \h  16  

  HYPERLINK \l "_Toc188948839"  3.5.2	Acute Reference Dose (aRfD) -
General Population	  PAGEREF _Toc188948839 \h  17  

  HYPERLINK \l "_Toc188948840"  3.5.3	Chronic Reference Dose (cRfD)	 
PAGEREF _Toc188948840 \h  17  

  HYPERLINK \l "_Toc188948841"  3.5.4	Incidental Oral Exposure (Short-
and Intermediate-Term)	  PAGEREF _Toc188948841 \h  17  

  HYPERLINK \l "_Toc188948842"  3.5.5	Dermal Absorption	  PAGEREF
_Toc188948842 \h  17  

  HYPERLINK \l "_Toc188948843"  3.5.6	Dermal Exposure (Short-,
Intermediate- and Long-Term)	  PAGEREF _Toc188948843 \h  17  

  HYPERLINK \l "_Toc188948844"  3.5.7	Inhalation Exposure (Acute,
Short-, Intermediate- and Long-Term)	  PAGEREF _Toc188948844 \h  17  

  HYPERLINK \l "_Toc188948845"  3.5.7.1	Acute Inhalation Exposure	 
PAGEREF _Toc188948845 \h  18  

  HYPERLINK \l "_Toc188948846"  3.5.7.2	Short-term Inhalation Exposure	 
PAGEREF _Toc188948846 \h  18  

  HYPERLINK \l "_Toc188948847"  3.5.7.3	Intermediate-term Inhalation
Exposure	  PAGEREF _Toc188948847 \h  19  

  HYPERLINK \l "_Toc188948848"  3.5.7.4	Long-term Inhalation Exposure	 
PAGEREF _Toc188948848 \h  19  

  HYPERLINK \l "_Toc188948849"  3.5.8	Level of Concern for Margin of
Exposure	  PAGEREF _Toc188948849 \h  20  

  HYPERLINK \l "_Toc188948850"  3.5.9	Classification of Carcinogenic
Potential	  PAGEREF _Toc188948850 \h  20  

  HYPERLINK \l "_Toc188948851"  3.5.9.1	Quantification of Carcinogenic
Risk – Inhalation Exposures	  PAGEREF _Toc188948851 \h  20  

  HYPERLINK \l "_Toc188948852"  3.5.9.2	Quantification of Carcinogenic
Risk – Oral Exposures	  PAGEREF _Toc188948852 \h  21  

  HYPERLINK \l "_Toc188948853"  3.5.10	Recommendation for Aggregate
Exposure Assessments	  PAGEREF _Toc188948853 \h  21  

  HYPERLINK \l "_Toc188948854"  3.5.11	Summary of Toxicological Doses
and Endpoints for 1,3-Dichloropropene for Use in Human Risk Assessments	
 PAGEREF _Toc188948854 \h  21  

  HYPERLINK \l "_Toc188948855"  3.6	Endocrine Disruption	  PAGEREF
_Toc188948855 \h  23  

  HYPERLINK \l "_Toc188948856"  4.0	Public Health	  PAGEREF
_Toc188948856 \h  23  

  HYPERLINK \l "_Toc188948857"  5.0	Dietary Exposure/Risk
Characterization	  PAGEREF _Toc188948857 \h  24  

  HYPERLINK \l "_Toc188948858"  5.1	Pesticide Metabolism and
Environmental Degradation	  PAGEREF _Toc188948858 \h  24  

  HYPERLINK \l "_Toc188948859"  5.1.1	Metabolism in Primary Crops	 
PAGEREF _Toc188948859 \h  24  

  HYPERLINK \l "_Toc188948860"  5.1.2	Metabolism in Rotational Crops	 
PAGEREF _Toc188948860 \h  25  

  HYPERLINK \l "_Toc188948861"  5.1.3	Metabolism in Livestock	  PAGEREF
_Toc188948861 \h  25  

  HYPERLINK \l "_Toc188948862"  5.1.4	Analytical Methodology	  PAGEREF
_Toc188948862 \h  25  

  HYPERLINK \l "_Toc188948863"  5.1.5	Environmental Degradation	 
PAGEREF _Toc188948863 \h  25  

  HYPERLINK \l "_Toc188948864"  5.1.6	Toxicity Profile of Major
Metabolites and Degradates	  PAGEREF _Toc188948864 \h  26  

  HYPERLINK \l "_Toc188948865"  5.1.7	Pesticide Metabolites and
Degradates of Concern	  PAGEREF _Toc188948865 \h  26  

  HYPERLINK \l "_Toc188948866"  5.1.8	Drinking Water Residue Profile	 
PAGEREF _Toc188948866 \h  26  

  HYPERLINK \l "_Toc188948867"  5.1.9	Food Residue Profile	  PAGEREF
_Toc188948867 \h  28  

  HYPERLINK \l "_Toc188948868"  5.1.10	International Residue Limits	 
PAGEREF _Toc188948868 \h  29  

  HYPERLINK \l "_Toc188948869"  5.2	Dietary Exposure and Risk	  PAGEREF
_Toc188948869 \h  29  

  HYPERLINK \l "_Toc188948870"  5.2.1	Acute Dietary Exposure/Risk	 
PAGEREF _Toc188948870 \h  29  

  HYPERLINK \l "_Toc188948871"  5.2.2	Chronic Dietary Exposure/Risk	 
PAGEREF _Toc188948871 \h  29  

  HYPERLINK \l "_Toc188948872"  5.2.3	Cancer Dietary Risk	  PAGEREF
_Toc188948872 \h  30  

  HYPERLINK \l "_Toc188948873"  5.3	Anticipated Residue and Percent Crop
Treated (%CT) Information	  PAGEREF _Toc188948873 \h  31  

  HYPERLINK \l "_Toc188948874"  6.0 	Non-Occupational Exposure
Assessment and Characterization	  PAGEREF _Toc188948874 \h  31  

  HYPERLINK \l "_Toc188948875"  6.1	Bystander Exposures And Risks From
Near Field Sources	  PAGEREF _Toc188948875 \h  32  

  HYPERLINK \l "_Toc188948876"  6.2 	Ambient Bystander Exposure from
Multiple Regional Sources	  PAGEREF _Toc188948876 \h  35  

  HYPERLINK \l "_Toc188948877"  6.2.1	Exposures from Targeted Regional
Ambient Source Air Monitoring	  PAGEREF _Toc188948877 \h  35  

  HYPERLINK \l "_Toc188948878"  6.2.2	Exposures from Urban Background
Ambient Air Monitoring	  PAGEREF _Toc188948878 \h  38  

  HYPERLINK \l "_Toc188948879"  7.0	Aggregate Risk Assessment	  PAGEREF
_Toc188948879 \h  40  

  HYPERLINK \l "_Toc188948880"  7.1	Acute Aggregate Risk	  PAGEREF
_Toc188948880 \h  40  

  HYPERLINK \l "_Toc188948881"  7.2	Short-Term and Intermediate-Term
Aggregate Risk	  PAGEREF _Toc188948881 \h  40  

  HYPERLINK \l "_Toc188948882"  7.3	Long-Term Aggregate Risk	  PAGEREF
_Toc188948882 \h  41  

  HYPERLINK \l "_Toc188948883"  7.4	Cancer Aggregate Risk	  PAGEREF
_Toc188948883 \h  41  

  HYPERLINK \l "_Toc188948884"  8.0 	Cumulative Risk Assessment and
Characterization	  PAGEREF _Toc188948884 \h  42  

  HYPERLINK \l "_Toc188948885"  9.0	Occupational Exposures	  PAGEREF
_Toc188948885 \h  42  

  HYPERLINK \l "_Toc188948886"  9.1	Post-plant Drip Irrigation
Fumigations	  PAGEREF _Toc188948886 \h  43  

  HYPERLINK \l "_Toc188948887"  10.0	Data Needs and Label Requirements	 
PAGEREF _Toc188948887 \h  48  

  HYPERLINK \l "_Toc188948888"  10.1	Toxicology	  PAGEREF _Toc188948888
\h  48  

  HYPERLINK \l "_Toc188948889"  10.2	Residue Chemistry	  PAGEREF
_Toc188948889 \h  48  

  HYPERLINK \l "_Toc188948890"  10.3	Occupational and Residential
Exposure	  PAGEREF _Toc188948890 \h  49  

  HYPERLINK \l "_Toc188948891"  11.0	References	  PAGEREF _Toc188948891
\h  49  

  HYPERLINK \l "_Toc188948892"  Appendix A: Executive Summaries for
Critical Studies and Toxicological Profile	  PAGEREF _Toc188948892 \h 
50  

  HYPERLINK \l "_Toc188948893"  Appendix B: Methodologies for Inhalation
Risk Calculations	  PAGEREF _Toc188948893 \h  63  

  HYPERLINK \l "_Toc188948894"  Appendix C:  Summary Of Cordon® PERFUM
Buffer Distributions Based On Ventura California Weather And Data for
Post-plant Drip Irrigation Use in Vineyards Data	  PAGEREF _Toc188948894
\h  71  

  HYPERLINK \l "_Toc188948895"  Appendix D:  Summary Of 1,3-D Bystander
Exposure from Known Area Sources Estimated Using the Monitoring Method	 
PAGEREF _Toc188948895 \h  74  

  HYPERLINK \l "_Toc188948896"  Appendix E:  Model Information and
History	  PAGEREF _Toc188948896 \h  80  

 

1.0  	Executive Summary  TC \l1 "1.0  	Executive Summary 

					

The Health Effects Division (HED) of EPA's Office of Pesticide Programs
has evaluated the 1,3-dichloropropene (1,3-D) database and conducted a
human health risk assessment to support the proposed new uses of 1,3-D
in established vineyards.

Use Pattern

1,3-D is a soil fumigant containing an approximately equal mixture of
the cis and trans isomers of the active ingredient.   It is registered
as a pre-plant control for parasitic root-knot nematodes and other soil
pests and diseases for use on vegetables, fruits, nuts, turf, and other
field and nursery crops. The registrant has petitioned for a post-plant
drip irrigation use in vineyards to control nematodes and Phylloxera. 
1,3-D would be applied at a rate of 200 ppm via drip irrigation for an
effective application rate of approximately 18 lb ai/A up to twice a
year, one application during the growing season with a pre-harvest
interval (PHI) of 60 days, and a second application after harvest, but
no later than three weeks after harvest.  The proposed label also states
that applications should be made to vineyards that have been established
for at least three years.

Hazard Characterization

The toxicology database is considered to be adequate to support of the
proposed and existing uses of 1,3-D.  1,3-D showed moderate acute
toxicity by the oral and dermal exposure routes (Toxicity was Category
II), was moderately irritating to the eye and skin, and was a dermal
sensitizer in guinea pigs.  It is classified as Toxicity Category IV for
acute inhalation toxicity and produced tremors, convulsions, salivation,
lacrimation, diarrhea, lethargy and death at concentrations 647 ppm or
higher.

Consistent with the irritant properties of 1,3-D, there was evidence of
degenerative changes in the nasal olfactory epithelium and
histopathological changes of the respiratory epithelium in rats and mice
after subchronic inhalation exposure.  Following chronic inhalation
exposure, the olfactory region of the nasal cavity appeared to be the
target organ in rats while lung adenomas were induced in mice. 
Similarly, following oral exposure, 1,3-D induced histopathological
lesions in rats and/or mice including forestomach squamous cell
papillomas and carcinomas, liver masses/neoplastic nodules, urinary
bladder carcinomas, and alveolar/brochiolar adenomas.  Increases in
hematopoietic activity and decreased body weights were also noted in
dogs and mice, respectively.  Accordingly, 1,3-D has been classified as
“likely to be carcinogenic to humans” via both the oral and
inhalation routes.  As a result cancer potency factors (Q1*) have been
calculated for both routes of exposure.

The Food Quality Protection Act (FQPA) requires the Agency to consider
special sensitivities of the young to chemical exposure.  The 1,3-D risk
assessment team has reviewed the entire database for 1,3-D and
determined there are no residual uncertainties regarding exposure to
children at any developmental stage and recommends that the factor be
reduced to 1X.

Dose Response

Based on the toxicity profile and the major exposure routes of 1,3-D,
endpoints have been selected for the residential/bystander,
occupational, and dietary human health risk assessments.  No dermal
endpoints have been selected because of the very low dermal exposure
anticipated relative to the high inhalation exposures for this highly
volatile chemical.

For inhalation risk assessments, The Agency is currently using the
reference concentration (RfC) methodology to derive the human equivalent
concentration (HEC) for inhalation exposures in this risk assessment. 
Under the RfC methodology, endpoint selection is based on the HECs which
are derived from the NOAELs of the selected studies.  The specific
concentrations and endpoints for the exposure scenarios are summarized
below:  

  

Acute inhalation: HED selected an HEC of 75.7 ppm (non-occupational risk
assessment) or 227.0 ppm (occupational risk assessment) from the NOAEL
of 454 ppm based on decreased body weight in an acute inhalation
toxicity study in rats at the LOAEL of 583 ppm.  The selected
concentration and endpoint are applicable for a single exposure risk
assessment because the rats were treated for 4 hours only.  An
uncertainty factor (UF) of 30X defines the HED level of concern.

Short-term inhalation:   HED selected an HEC of 5.0 ppm
(non-occupational risk assessment) or 15.0 ppm (occupational risk
assessment) from the NOAEL of 20 ppm based on decreased body weight
gains in maternal rabbits in the developmental toxicity study.  An
uncertainty factor (UF) of 30X defines the HED level of concern.

Intermediate- term inhalation:  HED selected an HEC =  0.205 ppm 
(non-occupational risk assessment) or 0.86 ppm (occupational risk
assessment) from the NOAEL of 10 ppm in the 90-Day Inhalation Toxicity
in Rats based on nasal histopathology.  An uncertainty factor (UF) of
30X defines the HED level of concern.

Long- term inhalation:   HED selected an HEC =  0.182 ppm 
(non-occupational risk assessment) or 0.77 ppm (occupational risk
assessment) from the NOAEL of 5 ppm from the Chronic/ Carcinogenicity
Study in Mice based on nasal histopathology.  An uncertainty factor (UF)
of 30X defines the HED level of concern.

The Integrated Risk Information System’s (IRIS) Q1* of 4x10-6
(μg/m3)-1 [1.8x10-2 ppm-1] is based on male mouse lung adenomas in the
two-year combined chronic/carcinogenicity inhalation study.

Chronic and cancer endpoints have been selected for the dietary risk
assessments.  No hazard was identified for acute exposures via the oral
route.  For the chronic exposures HED based the endpoint on a chronic
study in rats where increased decreased body weight and hyperplasia of
the stomach was observed at the LOAEL of 12.5 mg/kg/day. The population
adjusted dose is based on the NOAEL of 2.5 mg/kg/day and a UF of 100. 
The 3-chloroacrylic acid (CAAC) and 3-chloroallyl alcohol (CAAL)
degradates are assumed to have the same toxicity as the parent.  For the
cancer assessment, 1,3-D and both degradates were assessed with the
parent using the parent’s oral Q1* of 1.22 x10-1 (mg/kg/day)-1 from
the two-year combined chronic/carcinogenicity study based on liver
tumors in Fischer 344 rats.

Dietary Exposure

The residues of concern in food and water are the parent compound and
the metabolites 3-chloroacrylic acid and 3-chloroallyl alcohol. 
Adequate analytical methods are available to enforce the tolerances.
Thirteen exaggerated rate crop field trials were conducted in support of
the proposed new use and generally show non-detectable residues of the
parent and metabolites at pre-harvest intervals much shorter than the
proposed new uses.  Residues at the limit of quantitation (0.003 ppm)
for one metabolite were observed in one trial conducted at a seasonal
rate approximately five times the proposed rate.  A dietary risk
analysis was conducted for the combined residues of the parent and
metabolites assuming all grapes are treated, residues of all but one
analyte at half the limit of detection and the other metabolite at the
limit of quantitation.  The analysis showed that all populations are
exposed to less than 1% of the population adjusted dose (PAD) for
chronic risk.  This is below the Agency’s level of concern (i.e., when
dietary exposure exceeds 100% of the PAD). The estimate cancer risk is
also below the level of concern.

Residues of concern in drinking water are the cis and trans isomers of
the parent, the 3-chloroacrylic acid (CAAC) and 3-chloroallyl alcohol
(CAAL) degradates.  The Environmental Fate and Effects Division (EFED)
provided the drinking water assessment using simulation models to
estimate the potential concentration of 1,3-D and the degradates in
surface water while tap water monitoring data were used to estimate
concentrations in ground water.

A dietary exposure analysis was conducted for the combined exposure from
food and water.  The chronic assessment for 1,3-D and the degradates
CAAC and CAAC showed that all populations are exposed to less than 1% of
the population adjusted dose for food plus water from ground water
sources and less than 5% of the population adjusted dose for food plus
water from surface water sources.  The cancer risk analysis for the
combined residues of parent and CAAC and CAAL degradates in food and
water from ground water sources did not exceed the level of concern. 
However, the cancer risk analysis for the combined residues of parent
and CAAC and CAAL degradates in food and water from surface water
sources based on modeling data exceeded the level of concern.  HED
considers these estimates to be highly conservative, and actual
exposures are likely to be much lower for a number of reasons.  First,
the models used to estimate the drinking water concentrations are not
designed for highly volatile chemicals such as 1,3-D.  Rather,
PRZM-EXAMS was designed more for chemicals whose main route of
dissipation is metabolism in soil and water.  When using this type of a
model for a chemical whose main route of dissipation is volatilization,
the results tend to be overestimates.  Moreover, because the existing
environmental fate data are insufficient to refine the model estimates,
many of the model inputs are likely to be overestimates, thus leading to
an overestimation of the surface water concentrations.  The limited
surface water monitoring data showed that in 123 samples from areas of
high use, 1,3-D and its degradates were not detected.  Most importantly,
however, HED does not expect concentrations of 1,3-D in drinking water
from surface water sources to be higher than drinking water from
groundwater sources because once introduced into ground water, 1,3-D is
shielded from many of the processes that can contribute to its more
rapid dissipation from surface water. Accordingly, HED expects that the
actual drinking water concentrations for 1,3-D and its degradates from
surface water sources to be much lower in drinking water than the model
estimates and no more than the concentration in drinking water from
ground water sources.

Non-Occupational (Bystander) Exposure

Releases of fumigants, such as 1,3-D, can be categorized in two distinct
manners including bystander exposures from single application sites
(i.e., treated farm fields) such as area sources (hereon discussed as
near field sources) and by ambient air monitoring data where residues
could result from many applications within a region (hereon discussed as
ambient sources).  

Exposures to bystanders from single post-plant agricultural field
fumigation events and their associated risks were calculated using the
distributional/probabilistic modeling method, as well as the monitoring
method. Distributional modeling was done with the PERFUM model.
Monitoring method results are based on using monitoring data directly
from field volatility studies. 

One field volatility study is available to address off-site exposure
from this use (MRID 45296101).   Using this field volatility study,
bystander exposure was modeled using the PERFUM model for the proposed
post-plant drip irrigation use on vineyard grapes (see section 6.1 for a
summary of results). The data used to assess the post-plant vineyard use
is considered to be minimally adequate for modeling purposes.  However,
the risk estimates for the 1,3-D pre-plant drip agricultural uses (all
of which are applied at much higher application rates) are not of
concern at 0 meters from treated fields, and the registrant has proposed
a 100 ft buffer zone, the Agency expects that the post-plant vineyard
use will not pose a risk of concern for bystanders.

Quantitative calculations were completed for acute exposures based on
monitoring data and the PERFUM model for a 24 hour duration.  However,
field volatility studies for 1,3-D indicate that peak emissions from
treated fields occur up to 72 hours after application.  The monitoring
method was used to calculate short-term and cancer risk for all 1,3-D
uses and all risk estimates calculated were below the level of concern
(LOC) for the proposed post-plant use.   At this time, the models cannot
readily be used to evaluate exposures for durations longer than 24 hours
and the monitoring data are temporally limited. 

Risks from ambient air were evaluated using monitoring data from
California.  These data reflect the existing pre-plant fumigations uses
that are applied at rates over 10 times the rate of the proposed
post-plant fumigation use.  Ambient levels of 1,3-D are not attributable
to a specific application event and as such, contributions to the
ambient samples may occur from multiple sources.  HED has evaluated the
available ambient monitoring data for 1,3-D.  These data consist of two
basic types that include targeted monitoring by the California Air
Resources Board (CARB) that occurred in a high use area during the
season of use.  The other types of data are collected as part of the
routine Toxic Air Contaminant (TAC) program and focus on background
levels in urban environments.  

For the targeted ambient monitoring assessment, none of the risks
(acute, short-term, intermediate-term, chronic) exceed HED’s level of
concern for 1,3-D.  Chronic exposure estimates should be considered as
rangefinder estimates of exposure because the available monitoring data
were not specifically designed for this purpose. Few of the cancer risk
estimates exceed HED’s level of concern (typically cancer risks
greater than 1 x 10-6).  For those locations where risks slightly
exceeded the level, monitoring in the following year showed risks well
below the level of concern, so there is no concern over a lifetime of
exposure.  Also, since sampling was done in the high use season, air
concentrations used for the cancer risk assessment are not expected to
be of concern for exposures which could occur throughout the year.  

HED also considered exposure resulting from urban background air
concentrations. None of the estimated risks (acute, short-term,
intermediate-term, chronic, or cancer) exceed HED’s levels of concern.
 Because of the large number of non-detectable residues observed in
these monitoring data, a chronic risk assessment is probably less
germane than a short- or intermediate-term assessment for 1,3-D. 
However, chronic exposure to urban background ambient air incorporating
non-detectable (ND) residues as ½ LOD is assessed as a upper bound of
exposure and is assumed to present a conservative assessment of risk. 

Aggregate Exposure Assessment

When there are potential residential exposures to a pesticide, the Food
Quality Protection Act (FQPA) requires consideration of the aggregate
exposures from three major pathways: oral, dermal and inhalation
exposures provided there is common toxicity among the various routes. 
Although 1,3-D is not used in residential settings, due to the
volatility of 1,3-D residential exposure may occur when 1,3-D is applied
to fields near residential areas.  Accordingly, the only residential
exposures will be inhalation exposures.  Dietary exposure may occur from
food from the proposed new use on grapes and from water as a result of
the proposed new use and the existing pre-plant fumigations.

For the acute, short-, intermediate-, and long-term assessments the
toxicity endpoints selected for inhalation and dietary exposures should
not be aggregated as there is not a common toxicity observed.  1,3-D has
been classified as likely to be carcinogenic to humans via the oral and
inhalation routes.  However, the types of tumors observed in the
inhalation and oral studies were different.  Therefore, the oral and
inhalation exposures should not be aggregated.  The aggregate exposure
from food and water sources is discussed in the Dietary Exposure section
of this summary.

Occupational Exposure

Mixer/Loader/Applicator Exposure

HED has no new data for worker exposure resulting specifically from the
post-plant drip irrigation application of 1,3-D.  However, mixing and
loading techniques for the proposed use are expected to be similar to
loading techniques assessed for the existing agricultural uses of 1,3-D.
 The exposure for these loading methods was assessed in the most recent
Reregistration Eligibility Document (RED).  Specifically, air
concentration levels from 1,3-D-specific worker exposure monitoring
studies were used to estimate occupational exposure for workers using
bulk/mini-bulk loading.  The occupational assessment presents risk with
and without the use of OV respirators.  However, mitigation on current
1,3-D labels requires the use of half-face respirators with either an
organic-vapor-removing cartridge with a prefilter approved for
pesticides or a canister approved for pesticides (also referred to as OV
respirators) for all occupational workers before and during a 5 day REI.
 The use of OV respirators, which decreases exposure levels by a factor
of at least 10, and adequately addresses occupational risk.  It should
be noted that the study data used to estimate bulk and mini-bulk loader
exposure are based on a much higher application rate than the proposed
application rate for the post-plant vineyard use. For this reason,
loader exposure for the proposed post-plant use is expected to be
significantly lower than that assessed for bulk and mini-bulk loading
for the existing pre-plant uses of 1,3-D.

 

Since 1,3-D is formulated as a liquid there is some potential for dermal
and eye contact.  The use of mitigation controls such as personal
protective equipment (PPE) and closed transfer systems minimizes the
potential but does not eliminate it.  However, the high vapor pressure
of 1,3-D makes quantifying any potential low level dermal exposures very
difficult.  Although 1,3-D may be irritating to the skin and eyes, no
dermal endpoints of concern were selected for risk assessment purposes. 
Since realistic quantification of dermal risk is not possible, PPE for
dermal protection should be based on the acute toxicity of the end-use
product as described in the Worker Protection Standard and mitigation
measures for dermal exposure (i.e. PR Notice 93-7, 1995 label
amendments, 9/30/98 agreement with Dow). 

Post-application Exposure

One field volatility study is available to address off-site exposure
from this use (MRID 45296101).   Using this field volatility study,
acute occupational post-application exposure is modeled using the PERFUM
model for the proposed post-plant drip irrigation use on vineyard grapes
(see section 6.1 for a summary of results). 

Environmental Justice Considerations

Potential areas of environmental justice concerns, to the extent
possible, were considered in this human health risk assessment, in
accordance with U.S. Executive Order 12898, "Federal Actions to Address
Environmental Justice in Minority Populations and Low-Income
Populations,"   HYPERLINK
"http://www.epa.gov/compliance/resources/policies/ej/exec_order_12898.pd
f" 
http://www.epa.gov/compliance/resources/policies/ej/exec_order_12898.pdf
.

As a part of every pesticide risk assessment, OPP considers a large
variety of consumer subgroups according to well-established procedures. 
In line with OPP policy, HED estimates risks to population subgroups
from pesticide exposures that are based on patterns of that subgroup’s
food and water consumption, and activities in and around the home that
involve pesticide use in a residential setting.  Extensive data on food
consumption patterns are compiled by the USDA under the Continuing
Survey of Food Intake by Individuals (CSFII) and are used in pesticide
risk assessments for all registered food uses of a pesticide.  These
data are analyzed and categorized by subgroups based on age, season of
the year, ethnic group, and region of the country.  Additionally, OPP is
able to assess dietary exposure to smaller, specialized subgroups and
exposure assessments are performed when conditions or circumstances
warrant.  Whenever appropriate, non-dietary exposures based on home use
of pesticide products and associated risks for adult applicators and for
toddlers, youths, and adults entering or playing on treated areas
postapplication are evaluated.  Further considerations are currently in
development as OPP has committed resources and expertise to the
development of specialized software and models that consider exposure to
bystanders and farm workers as well as lifestyle and traditional dietary
patterns among specific subgroups.  This assessment specifically
addresses exposure to bystanders and those living near fields that may
be treated with 1,3-dichloropropene.

Review of Human Research

This risk assessment does not rely on any data from studies in which
human subjects were intentionally exposed to a pesticide or other
chemical.

Regulatory Recommendations

The registrant should submit a revised Section F proposing tolerances
for the combined residues of cis-1,3-dichloropropene,
trans-1,3-dichloropropene cis-3-chloroacrylic acid, trans-
3-chloroacrylic acid, cis-3-chloroallyl alcohol , and
trans-3-chloroallyl alcohol  at 0.018 ppm.  Pending submission of a
revised Section F there are no residue chemistry issues that would
preclude granting a conditional registration on grapes, or establishment
of tolerances for the combined residues of cis-1,3-dichloropropene,
trans-1,3-dichloropropene cis-3-chloroacrylic acid,
trans-3-chloroacrylic acid, cis-3-chloroallyl alcohol, and
trans-3-chloroallyl alcohol, as follows: 

	Grapes	0.018 ppm

HED recommends that conversion of a conditional registration to an
unconditional registration may be considered upon submission of the
following confirmatory analytical method, storage stability, and field
volatility studies described below.

 860.1340 Residue Analytical Methods

An independent laboratory validation is required for the tolerance
enforcement method that determines the 3-chloroacrylic acid and
3-chloroallyl alcohol metabolites.

OPPTS Guideline 860.1360 Multiresidue Methods

Multiresidue method data are required for 1,3-dichloropropene and its
3-chloroacrylic acid and 3-chloroallyl alcohol metabolites.

OPPTS Guideline 860.1380 Storage Stability

A storage stability study demonstrating stability of 1,3-dichloropropene
and its 3-chloroacrylic acid and 3-chloroallyl alcohol metabolites in
grapes for at least 154 days is required.

2.0  Ingredient Profile  TC \l1 "2.0   Ingredient Profile 	

1,3-dichloropropene (1,3-D) is currently registered for use as a soil
fumigant on numerous field and nursery crops.  1,3-D products are liquid
formulations containing 63.5 to 97.5% of the active ingredient 1,3-D. 
1,3-D is a mixture of the cis and trans isomers, with approximately
equal quantities of the two isomers.

The registered products may be applied by drip irrigation (Telone EC),
and row and broadcast applications (Telone II, Telone, C-17, Telone
C-35, Telone C-15).  Several 1,3-D products (Telone C-17 and Telone
C-35) also contain the fumigant chloropicrin (trichloronitromethane). 

Broadcast applications of 1,3-D for control of nematodes and garden
symphylans are made at rates up to 259 lbs ai/A for vegetables up to 202
lbs ai/A for  field crops and up to 366 lbs ai/A for fruit and nut
crops.  These are the highest label applications rates available for
agricultural use of 1,3-D.

The Agency has issued registrations for 1,3-D on golf courses.  The
end-use product, Curfew® is a liquid formulation.  Curfew® is injected
into turf 5 inches deep, at a rate of 5 gallons per acre.

In addition to the agricultural and golf course fumigation uses, the
registrant requested a turf farm use.  In this document, the turf farm
use was not assessed.  HED asked that the registrant submit additional
label language to clarify the turf farm use patterns.  To date, HED has
not received a revised label from the registrant.

2.1	Structure and Nomenclature  TC \l2 "2.1	Structure and Nomenclature 

Cordon™, Telone™

Compound Structure		

Common name	cis-CAAL	trans-CAAL

IUPAC name	(EZ)-3-chloroprop-2-en-1-ol

CAS registry number	4643-05-4	4643-06-5

Compound Structure		

Common name	cis-CAAC	trans-CAAC

IUPAC name	(EZ)-3-chloroacrylic acid

CAS name	1609-93-4	2345-61-1



2.2	Physical and Chemical Properties  TC \l2 "2.2	Physical and Chemical
Properties 	

Table 2.2.	Physicochemical Properties of the Technical Grade Test
Compound 1,3-Dichloropropene.

Parameter	Value	Reference

Boiling point	104 (C for cis isomer;

112.6 (C for trans isomer	1,3-Dichloropropene Reregistration Eligibility
Decision Document (12/1998)

pH	Not available

	Density	1.209 g/mL at 25 (C	1,3-Dichloropropene Reregistration
Eligibility Decision Document (12/1998)

Water solubility	2,180 mg/L for cis isomer;

2,320 mg/L for trans isomer

	Solvent solubility	Not available

	Vapor pressure	34.3 mm Hg for cis isomer at 25 (C;

23.0 mm Hg for trans isomer at 25 (C	1,3-Dichloropropene Reregistration
Eligibility Decision Document (12/1998)

Dissociation constant, pKa	Not available

	Octanol/water partition coefficient, Log(KOW)	Not available

	UV/visible absorption spectrum	Not available

	

Proposed New Use Directions

The registrant is proposing a new uses to suppress nematodes and grape
Phylloxera in established vineyards using drip irrigation.  The most
recent revision to the label, dated 12/18/07, includes a 100 foot buffer
zone between the edge of the field and occupied structures.

Table 2.3.  Summary of Directions for Proposed New Use of
1,3-Dichloropropene

Applic. Timing, Type, and Equip.	Formulation

[EPA Reg. No.]	Applic. Rate 

(lb ai/A)	Max. No. Applic. per Season	Max. Seasonal Applic. Rate

(lb ai/A)	PHI

(days)	Use Directions and Limitations

Grapes



Drip irrigation	

Cordon®

[62719-GAG]	

17.7	

2	

35.4	

60	Only one application may be made during the growing season; another
application may be made within three weeks after the fruit is harvested.
 Product should not be applied to vines planted within the previous
three years.



The application rates were calculated using product density and other
information.  The label specifies the drip irrigation solution should
have a maximum concentration of 200 ppm, and that no more than 4 gallons
of the Cordon product may be used per acre per year.

3.0	Hazard Characterization/Assessment  TC \l1 "4.0	Hazard
Characterization/Assessment 

3.1	Hazard Characterization  TC \l2 "	4.1	Hazard Characterization 

3.1.1	Database Summary  TC \l3 "		4.1.1	Database Summary 

Studies Available and Acceptable (animal, human, and general literature)
Acceptable studies are available via both the inhalation and oral route
including: 1) acute inhalation study; 2) inhalation developmental
toxicity studies in rats and rabbits, 3) subchronic inhalation toxicity
studies in rats and mice; 4) chronic toxicity/carcinogenicity studies
via both oral and inhalation routes in rats, mice and dogs; and 5)
inhalation multigeneration reproductive toxicity study.

Metabolism, toxicokinetic, mode of action data

A guideline oral metabolism study in rats and a pharmacokinetic study
have been conducted in the rat and the mouse.  These studies indicate
that 1,3-D is rapidly absorbed and distributed.  There was rapid
elimination in the urine and as CO2 in expired air and small amounts in
the feces.  Nine metabolites were isolated from urine with two being
identified as 1,3-DCP-mercapturic acid and the sulfoxide derivative. 

The registrant has proposed that 1,3-D exposure may lead to lung and
liver tumorigenesis through a mode of action (MOA) other than
mutagenicity.  In two mechanistic studies submitted to the HED, the
registrant has proposed that 1,3-D exerts its tumorigenic effects by
acting as an initiator and/or promoter.  However, the data from these
studies was insufficient to fully support this proposed MOA.   Given the
evidence of mutagenicity (gene mutations in bacteria and cultured
mammalian cells in conjunction with clastogenic activity and sister
chromatid exchanges in several mammalian cell lines and induction of DNA
strand breaks both in vitro and in vivo) seen in the 1,3-D data base,
mutagenicity is considered a plausible MOA.  As a result of these
observations, the HED has concluded that 1,3-D should remain classified
as likely to be carcinogenic to humans  using the linear approach (Q1*)
for quantification of risk.

Sufficiency of studies/data

The currently available toxicological database for 1,3-D is adequate for
selecting endpoints for risk assessment purposes.

3.1.2 Toxicological Effects  TC \l3 "4.1.2 Endpoints 

		

1,3-D showed moderate acute toxicity by the oral and dermal exposure
routes (Toxicity was Category II), was moderately irritating to the eye
and skin, and was a dermal sensitizer in guinea pigs.  It is classified
as Toxicity Category IV for acute inhalation toxicity and produced
tremors, convulsions, salivation, lacrimation, diarrhea, lethargy and
death at concentrations 647 ppm or higher.  Historically, OPP has
classified agricultural pesticides into four acute toxicity categories
ranging from Toxicity Category I (extremely toxic) to Toxicity Category
IV (minimally toxic).  These toxicity categories reflect the doses or
concentrations that are lethal to 50% of the test animals in the group
or severely irritating.  Acute toxicity studies, however, seldom
evaluate other endpoints such as histopathology or clinical chemistry.
As a result, a compound classified as Category IV may nevertheless be
acutely toxic even in the absence of mortality by eliciting effects
ranging from slight changes in clinical chemistry or portal of entry
effects to severe effects such as convulsions, ataxia, tissue necrosis,
etc.

The major routes of exposure to 1,3-D are the inhalation and oral (food
and drinking water) routes. 

The pattern of toxicity attributed to 1,3-D exposure via the inhalation
route includes histopathology findings in the nasal cavity (e.g.,
degeneration of the olfactory epithelium) and non-glandular stomach, as
well as generalized systemic toxic effects (body weight, body weight
gain, and food consumption decrements).  In addition, 1,3-D chronic
inhalation exposure resulted in an increased incidence of
bronchioloalveolar adenomas.  Based on this finding, 1,3-D has been
classified as “likely to be carcinogenic to humans” via the
inhalation route.  The cancer potency factor for humans was calculated
by IRIS to be 4 x 10-6 (μg/m3)-1.  

Oral exposure to 1,3-D led to an increase in histopathological findings
of the non-glandular stomach, increased liver weights, mycrocytic
anemia, increased hematopoiotic activity, and decreases in body weight
and body weight gain.  After chronic oral exposure, 1,3-D caused
increases in the incidences of basal cell hyperplasia in the
non-glandular stomach, squamous cell papillomas and carcinomas of the
forestomach, and neoplastic nodules in the liver.  Based on these
findings, 1,3-D has been classified as “likely to be carcinogenic to
humans” via the oral route.

		

Several mutagenicity studies with 1,3-D show that this compound acts as
a genotoxic agent consistent with the carcinogenicity pattern seen
throughout the database by both oral and inhalation routes. 

In addition to the parent compound (1,3-D), two degradates were
identified, 3- chloroallyl alcohol and 3- chloroacrylic acid.  These
degradates are assumed to have toxicity equal to the parent compound. 
Consequently, the risk assessment for the parent compound will be
protective of the potential toxic effects elicited by the two
degradates. 

3.2	Absorption, Distribution, Metabolism, Excretion (ADME)

Pharmacokinetics studies were conducted in Fischer 344 rats and B6C3F1
mice via the oral route.  The primary route of excretion for both
species was the urine.  Following oral administration, most of the
radiolabel was found in the stomach and gastrointestinal tract with
lesser amounts in the kidneys, liver, urinary bladder, skin, fat, blood
and carcass.  Oral administration also depleted the
non-protein-sulfhydryl contents of several tissues including the
non-glandular stomach (both time- and dose-dependent).  Dose-related
increases in macromolecular bindings were noted in several organs with
the highest binding sites being found in the non-glandular stomach. The
two major urinary metabolites were identified as 1,3-DCP-mercapturic
acid and its sulfoxide (or sulfone) derivative. 

In another study with Fischer 344 rats, gavage administration of 1,3-D
for 14 days resulted in rapid absorption from the gastrointestinal tract
with distribution to all tissues examined.  Highest concentrations
appeared in the non-glandular stomach and urinary bladder.  There was
rapid elimination in the urine, as carbon dioxide in expired air and
small amounts in the feces.  Nine metabolites were isolated from urine
with two being identified as 1,3-D-mercapturic acid and the sulfoxide
derivative.  No parent compound was present in the urine.

3.3	FQPA Considerations

3.3.1	Adequacy of the Toxicity Database  TC \l3 "3.3.1	Adequacy of the
Toxicity Database 

The database is adequate to characterize potential pre- and/or
post-natal risk for infants and children.  Acceptable/guideline studies
for developmental toxicity studies in rats and rabbits, and a
reproduction study in rats were available for FQPA assessment.  A
summary of the toxicity studies that have been submitted for 1,3-D may
be found in Appendix A to this document.

3.3.2	Evidence of Neurotoxicity  TC \l3 "3.3.2	Evidence of Neurotoxicity


There was no evidence of neurotoxicity observed in the toxicology
database.  Although specific neurotoxicity studies have not been
submitted, there are no indications of neurotoxicity in any of the
acute, subchronic, and toxicity studies.

3.3.3	Developmental Toxicity Studies  TC \l3 "3.3.3	Developmental
Toxicity Studies 

Rabbit and rat inhalation developmental toxicity studies have submitted.
 Developmental toxicity was not observed in either study at any dose,
but maternal toxicity was observed at all doses in the rat study, and at
the mid- and high-doses in the rabbit study.

als in the respiratory tract enter the blood stream more readily than
chemicals in the gastrointestinal tract (GI) since only ~ 2μM separate
the chemical in the alveolar space of the lung and the blood stream
while several cellular layers separate the chemicals in the lumen of the
GI tract from the blood stream.

3.3.4	Reproductive Toxicity Study  TC \l3 "3.3.4	Reproductive Toxicity
Study 

An inhalation rat reproduction study has been submitted and is discussed
in Appendix A.  Although local and systemic effects were observed in the
parent, no effects were observed in the offspring, and no effects on
reproduction were observed.

3.3.5	Additional Information from Literature Sources

A literature search did not reveal additional information that would
impact the risk assessment.

3.3.6	Pre-and/or Postnatal Toxicity  TC \l3 "3.3.6	Pre-and/or Postnatal
Toxicity 

3.3.6.1	Determination of Susceptibility  TC \l4 "3.3.6.1	Determination
of Susceptibility 

There is no concern for increased quantitative and/or qualitative
susceptibility after in utero or postnatal exposure to
1,3-dichloropropene in developmental toxicity studies in rats and
rabbits, or a reproduction study in rats. 

3.3.6.2	Degree of Concern Analysis and Residual Uncertainties  TC \l4
"3.3.6.2	Degree of Concern Analysis and Residual Uncertainties  for Pre-
and/or Postnatal Susceptibility

The purposes of the Degree of Concern analysis are: (1) to determine the
level of concern for the effects observed when considered in the context
of all available toxicity data; and (2) to identify any residual
uncertainties after establishing toxicity endpoints and traditional
uncertainty factors to be used in the risk assessment.  If residual
uncertainties are identified, then HED determines whether these residual
uncertainties can be addressed by a FQPA safety factor and, if so, the
size of the factor needed.

There is no evidence (quantitative or qualitative) of increased
susceptibility and no residual uncertainties with regard to pre- and/or
postnatal toxicity following in utero exposure to rats or rabbits and
pre and/or post-natal exposures to rats.  Therefore, it is recommended
that the FQPA safety factor be reduced to 1X and no additional safety
factors are needed (section 3.4).

3.3.7	Recommendation for a Developmental Neurotoxicity Study  TC \l3
"3.3.7	Recommendation for a Developmental Neurotoxicity Study 

There was no evidence of neurotoxicity observed following acute,
subchronic, or chronic exposure to 1,3-dichloropropene, and no clinical
signs of neurotoxicity were observed following pre-natal or postnatal
exposure; therefore, a developmental neurotoxicity study is not
warranted at this time.

FQPA Safety Factor for Infants and Children

Based on the hazard and exposure data, the 1,3-dichloropropene risk
assessment team has recommended that the FQPA Safety Factor be reduced
to 1X.  There is a complete toxicity database for 1,3-dichloropropene
and exposure data are complete or are estimated based on data that
reasonably account for potential exposures. There is no evidence of
susceptibility following in utero and/or postnatal exposure in the
developmental inhalation toxicity studies in rats or rabbits, and in the
2-generation inhalation rat reproduction study. There are no residual
uncertainties concerning pre- and post-natal toxicity and no
neurotoxicity concerns.  The chronic and cancer dietary food exposure
assessments assume 100% crop treated for grapes, the commodity of
interest. The drinking water exposure assessment is based on
conservative models and monitoring data. The residential exposure
assessment is not likely to underestimate bystander exposure. Based on
these data and conclusions, the FQPA Safety Factor can be reduced to 1X.

3.5	Hazard Identification and Toxicity Endpoint Selection  TC \l2 "3.5
Hazard Identification and Toxicity Endpoint Selection 

The primary exposure pathways for 1,3-D are via inhalation, food, and
drinking water.  Exposures via the inhalation route may be acute (less
than 24 hours), short-term (1-30 days), or intermediate- term (1 month-
6 months) in duration.  At this time the Agency does not anticipate
long-term (> 6 months) exposures.  Exposure via food and drinking water
may; however, be long-term (> 6 months). 

3.5.1    Acute Reference Dose (aRfD) - Females age 13-49  TC \l3 "3.5.1 
  Acute Reference Dose (aRfD) - Females age 13-49 

No appropriate endpoint attributable to a single exposure (dose) was
identified from oral toxicity studies for females 13+.

3.5.2	Acute Reference Dose (aRfD) - General Population  TC \l3 "3.5.2
Acute Reference Dose (aRfD) - General Population 

No appropriate endpoint attributable to a single exposure (dose) was
identified from oral toxicity studies for the general population.  

3.5.3	Chronic Reference Dose (cRfD)   TC \l3 "3.5.3	Chronic Reference
Dose (cRfD) 

Study Selected:  Combined Chronic Toxicity/Carcinogenicity (B6C3F1 mice)

MRID No.:  43757901

Executive Summary:  See Appendix A, Guideline § 870.3700.

Dose and Endpoint for Risk Assessment: NOAEL = 2.5 mg/kg/day based on
lower body weights and decreased body weight gain (both sexes) seen at a
LOAEL = 12.5 mg/kg/day.

Uncertainty Factor(s): 100X [10 interspecies; 10X intraspecies]

Comments about Study/Endpoint/Uncertainty Factors:  The route and
duration of exposure are appropriate for selection of the chronic
dietary endpoint.

3.5.4	Incidental Oral Exposure (Short- and Intermediate-Term)   TC \l3
"3.5.4	Incidental Oral Exposure (Short- and Intermediate-Term) 

1,3-Dichloropropene is not used in residential settings, so incidental
oral exposures are not expected.  Also the volatile nature of 1,3-D
reduces the potential for significant residues of 1,3-D and its
degradates in the upper layer of soil that may be consumed by young
children.

3.5.5	Dermal Absorption  TC \l3 "3.5.5	Dermal Absorption 

Dermal absorption data have not been submitted for 1,3-dichloropropene.

3.5.6	Dermal Exposure (Short-, Intermediate- and Long-Term)   TC \l3
"3.5.6	Dermal Exposure (Short-, Intermediate- and Long-Term) 

Dermal toxicity studies have not been submitted for 1,3-D.  Since 1,3-D
is formulated as a liquid there is some potential for dermal and eye
contact.  The use of mitigation controls such as personal protective
equipment (PPE) and closed transfer systems minimizes the potential but
does not eliminate it.  However, the high vapor pressure of 1,3-D makes
quantifying any potential low level dermal exposures very difficult. 
Although 1,3-D may be irritating to the skin and eyes, no dermal
endpoints of concern were selected for risk assessment purposes.  Since
realistic quantification of dermal risk is not possible, PPE for dermal
protection should be based on the acute toxicity of the end-use product
as described in the Worker Protection Standard and mitigation measures
for dermal exposure (i.e. PR Notice 93-7, 1995 label amendments, 9/30/98
agreement with Dow).

3.5.7	Inhalation Exposure (Acute, Short-, Intermediate- and Long-Term)  
TC \l3 "3.5.7	Inhalation Exposure (Short-, Intermediate- and Long-Term) 

The critical effects of 1,3-D exposure via the inhalation route are
decreased body weight for acute exposures, and histopathological lesions
in the olfactory region of the nasal cavity for longer term exposures. 
In this risk assessment, endpoint selection will be based on the
endpoints occurring at the lowest HECs (which may or may not be the
lowest animal NOAEL) derived using the RfC methodology.  In this
methodology, different HECs may be calculated for the same experimental
NOAEL due to: 1) the different algorithms used to derive HECs for
systemic versus portal of entry effects; or 2) the time adjustments
conducted for non-occupational versus occupational exposure scenarios. 
The differences between systemic versus portal of entry effects, arise
from the use of different calculations to estimate the inhalation risk
to humans which are dependent on the regional gas dose ratio (RGDR).  In
the case of systemic versus portal of entry effects, different RGDRs are
derived for each type of toxicity.  For non-occupational versus
occupational exposure, the differences arise because while it is
presumed that non-occupational exposure may occur 24 hours/day, 7
days/week; occupational exposure occurs only during the course of an
average workweek (8 hours/day and 5 days/week).  For further details on
the critical studies used for endpoint selection and the 1,3-D  toxicity
profile the reader is referred to Appendix A.  For additional
information on the methodologies used in this risk assessment and the
HEC arrays, please refer to Appendix B.  The toxicity endpoints selected
for risk assessment are presented below.

		

3.5.7.1	Acute Inhalation Exposure

For the acute inhalation scenario, two acute inhalation rat studies were
selected for establishing the toxicity endpoints for risk assessment.  A
brief synopsis of the studies and rationale for their use is provided
below:

Executive Summaries:   In one acute inhalation study (MRID No.
40220903), Wistar rats were exposed to Telone II at 454, 647, 699, 762,
832 or 958 ppm for 4 hours (whole body exposure).  In a second study
(MRID 41672201), Fischer 344 rats were exposed to cis- 1, 3
dichloropropene at 0, 583, 771, or 1020 ppm for 4 hours (whole body
exposure).  The NOAEL = 454 ppm based on decreased body weights at the
LOAEL of 583 ppm. 

The exposure concentration selected for this risk assessment will be
protective of the marginally decreased body weight seen during days 2
through 7 at 583 ppm and the clinical signs and mortality seen at ≥647
ppm. An UF of 30X defines HED’s level of concern in accordance with
guidance provided in the RfC methodology.

		

3.5.7.2	Short-term Inhalation Exposure

											

The short-term inhalation risk assessment was based on the findings from
the following subchronic inhalation studies:  

 

Study Selected:  Developmental Toxicology (Inhalation) in Rabbits		

									

Executive Summary (2 weeks): In a developmental toxicity study (MRID
001444715 and 00152848), New Zealand rabbits (17-24 females/group) were
exposed to concentrations of 1,3-D (90.1%) at 0, 20, 60 or 120 ppm
(equivalent to approximately 0, 0.091, 0.272 or 0.545 mg/L) 6 hours/day
during gestation days 6 through 18.  The maternal NOAEL was 20 ppm
(0.091 mg/L).  The maternal LOAEL was 60 ppm (0.272 mg/L) based on
decreased body weight gains compared with controls.  The developmental
NOAEL was 120 ppm (0.545 mg/L).  The developmental LOAEL was >120 ppm (>
0.545 mg/L, HDT).		

Dose and Endpoint for Risk Assessment: HEC = 5.0 ppm (non-occupational
exposure) or 15.0 ppm (occupational exposure) based on decreased body
weight gains.  Although a lower HEC was identified in the dominant
lethal study assay (HEC =2.5 or 7.5 ppm for non-occupational and
occupational risk assessments, respectively), the HEC from the
developmental toxicity study in rabbits was used.  The lower HECs
identified in the dominant lethal assay appear to be an artifact of dose
selection/dose spread since clear NOAELs were identified at 30 ppm (HEC
= 5.3 or 22.5 ppm for non-occupational and occupational exposure,
respectively) in 30-day inhalation toxicity studies in rats and mice. 
Thus the Agency has concluded that use of the HECs from the
developmental toxicity study in rabbits would be protective of the
decreased body weights seen at 60 ppm (HEC = 15 or 45 ppm for
non-occupational and occupational exposure, respectively) in the
dominant lethal assay.  An UF of 30x defines HED’s level of concern.		
		

3.5.7.3	Intermediate-term Inhalation Exposure

											

13-Week Inhalation Toxicity in Rats; OPPTS 870.3100 [§84-4]

Executive Summary:  In a subchronic (13-week) subchronic toxicity study,
Fischer 344 rats (10 sex/group) were exposed to concentrations of Telone
II at 0, 10, 30, 90 or 150 ppm, 6 hours/day, 5 days/week for 13 weeks.
Both sexes of rats at 90 and 150 ppm exhibited significant decreases in
body weights while rats at 30, 60 and 150 ppm exhibited
treatment-related histopathological lesions in the nasal turbinates. 
The NOAEL was 10 ppm (0.045 mg/L) and the LOAEL was 30 ppm (0.136 mg/L),
based on histopathological lesions in the nasal turbinates.

Dose and Endpoint for Risk Assessment: HEC of 0.205 ppm
(non-occupational risk assessment) or 0.86 ppm (occupational risk
assessment) based on histopathological lesions in the nasal turbinates. 
The duration of exposure in the 13-week inhalation toxicity studies in
rats is appropriate for this risk assessment.  In addition, this study
yields the lowest HEC of the studies available for consideration for
this risk assessment.  An UF of 30x defines HED’s level of concern.

3.5.7.4	Long-term Inhalation Exposure

In a chronic toxicity/carcinogenicity study (MRID No. 40312301), B6C3F1
mice (50/sex/group plus 10/sex/group for the 6- and 12-month interim
sacrifices) were exposed by whole-body inhalation to Telone II (92.1%)
at concentrations of 0, 5, 20 or 60 ppm (equivalent to approximately 0,
0.023, 0.091 or 0.272 mg/L) 6 hours/day, 5 days/week for a total of 510
days over a two-year period.  For chronic toxicity, the NOAEL was 5 ppm
(0.023 mg/L) and the LOAEL was 20 ppm (0.091 mg/L) based on urinary
bladder hyperplasia and hypertrophy/hyperplasia of the nasal respiratory
mucosa.		

Dose and Endpoint for Risk Assessment: HEC of 0.182 ppm
(non-occupational risk assessment) or 0.77 ppm (occupational risk
assessment) based on hypertrophy/hyperplasia of the nasal respiratory
mucosa.  The duration of exposure in the Chronic/Carcinogenicity
toxicity study in mice is appropriate for this risk assessment.  In
addition, this study yields the lowest HEC of the studies available for
consideration for this risk assessment. 

3.5.8	Level of Concern for Margin of Exposure

When conducting inhalation risk assessments, the magnitude of the UFs
applied is dependent on the methodology used to calculate risk.  This
risk assessment is based on the RfC methodology developed by the Office
of Research and Development (ORD) for the derivation of RfCs and HECs
for use in the MOE calculations.  Since the RfC methodology takes into
consideration the pharmacokinetic (PK) differences but not the
pharmacodynamic (PD) differences, the UF for interspecies extrapolation
may be reduced to 3X (to account for the PD differences) while the UF
for intraspecies variation is retained at 10X.  Thus, the UF when using
the RfC methodology is customarily 30X.

Table 3.1.  Summary of Levels of Concern for Risk Assessment.

Route	Short-Term

(1 - 30 Days)	Intermediate-Term

(1 - 6 Months)	Long-Term

(> 6 Months)

Occupational (Worker) Exposure

Dermal	N/A	N/A	N/A

Inhalation	30	30	30

Residential Exposure

Dermal	N/A	N/A	N/A

Inhalation	30	30	30

Incidental Oral	N/A	N/A	N/A

		

For dietary and drinking water risk assessments, an UF of 100X is
applied (10X for interspecies extrapolation, 10X intraspecies variation)
since no dosimetric adjustments have been considered to translate the
experimental NOAELs/LOAELs (from animal studies) to human equivalent
doses.  Consequently, the differences in PK and PD between animals and
humans have not been accounted for in these risk assessments. 

3.5.9	Classification of Carcinogenic Potential  TC \l3 "3.5.10
Classification of Carcinogenic Potential 

3.5.9.1	Quantification of Carcinogenic Risk – Inhalation Exposures

The HED Cancer Peer Review Committee evaluated the toxicological
database of 1,3-D and classified this chemical as “Likely to be
carcinogenic to humans” based on the data from a 2-year inhalation
bioassay in mice, where increased incidence of bronchioloalveolar
adenomas were observed.

HED has adopted the Integrated Risk Information System’s (IRIS) method
to derive the unit risk for inhalation exposure to1,3-D.  The
duration-adjusted HECs and tumor incidences were used to calculate the
unit risk.   The Q1* is 4 x 10-6 μg/m3 or 1.8 x10-2 ppm-1.

		

3.5.9.2	Quantification of Carcinogenic Risk – Oral Exposures

The oral Q1* for 1,3-D comes from the NTP studies where there were
increased tumors in both sexes of rats (Fischer 344) and mice (B6C3F1). 
The Q1 * was revised in 1997 to 1.22 x 10-1 (mg/kg/day)-1 and is based
on forestomach, liver, adrenal, and thyroid tumors observed in male
rats. 

3.5.10	Recommendation for Aggregate Exposure Assessments  TC \l3 "3.5.9
Recommendation for Aggregate Exposure Risk Assessments 

As per FQPA, 1996, when there are potential residential exposures to a
pesticide, aggregate risk assessment must consider exposures from three
major pathways: oral, dermal and inhalation exposures.  Although 1,3-D
is not used in residential settings, due to the volatility of 1,3-D
residential exposure may occur when 1,3-D is applied to fields near
residential areas.  Accordingly, the only residential exposures will be
inhalation exposures.  Dietary exposure may occur from food from the
proposed new use on grapes and from water as a result of the proposed
new use and the existing pre-plant fumigations.

≤11%) and was not considered toxicologically relevant.  Thus, exposure
through this route would not significantly contribute to the risk of
eliciting body weight impairments after 1,3-D exposure.  Additionally,
the exposures via the inhalation route are much greater than dietary
exposures, so contribution of the dietary exposures to the aggregate
exposure is insignificant.

1,3-D has been classified as likely to be carcinogenic to humans via the
oral and inhalation routes.  However, the types of tumors observed in
the inhalation and oral studies were different.  Therefore, the oral and
inhalation exposures should not be aggregated.

3.5.11	Summary of Toxicological Doses and Endpoints for
1,3-Dichloropropene for Use in Human Risk Assessments

Table 3.2. Summary of Toxicological Dose and Endpoints for Use in
1,3-Dichloropropene Dietary Risk Assessments

Exposure/

Scenario	Point of Departure	Uncertainty/

FQPA Safety Factors	Population Adjusted Dose	Study and Toxicological
Effects

1,3-D Combined with Degradates: 3-Chloroallyl Alcohol and 3-
Chloroacrylic Acid  

Acute Dietary Exposure (any Subpopulation)	NA	NA	NA	No hazard was
identified attributable to a single exposure.

Chronic Dietary Exposure	NOAEL = 2.5 mg/kg/day

UF = 100 

	UFA= 10x

UFH=10x

FQPA SF= 1x

	Chronic PAD = 0.025 mg/kg/day	2- Year Combined Chronic/Carcinogenicity
study -Rats 

LOAEL = 12.5 mg/kg/day

Decreased body weight gain, increased incidence of basal cell
hyperplasia of nonglandular stomach mucosa 

Cancer (oral)

	Classified as “likely to be carcinogenic in humans.  

Q1 * =  1.22x 10-1 (mg/kg/day)-1	2- Year Combined
Chronic/Carcinogenicity study -Rats

Combined forestomach, liver, mammary thyroid, adrenal, urinary, lung
tumors, multistage model, 3/4 scaling factor. 

UF = uncertainty factor. NOAEL = no observed adverse effect level. LOAEL
= lowest observed adverse effect level. RfD = reference dose. UFA =
extrapolation from animal to human (interspecies).  UFH = potential
variation in sensitivity among members of the human population
(intraspecies). NA = Not Applicable



Table 3.3. Summary of Toxicological Dose and Endpoints for Use in
1,3-Dichloropropene Human Health Inhalation Risk Assessment
(Non-Occupational)

Exposure

Scenario	Point of Departure	HED HECs	Study and Toxicological Effects

Acute	NOAEL = 454 ppm

LOAEL = 583 ppm	75.67 ppm

UF = 30	Acute Inhalation Studies -Rats  Clinical signs, decreased body
weight (mortality observed at >647 ppm)

Short-Term  Inhalation (1 to 30 days) 	NOAEL = 20 ppm

(maternal)

LOAEL = 30 ppm	5.0 ppm

UF = 30	Developmental  Inhalation Toxicity Study -Rabbit 

maternal decreased body weight gains

Intermediate -term Inhalation (1-6 months)	NOAEL = 10 ppm	0.205 ppm

UF = 30	13-week inhalation in rats, nasal effects

Long-Term Inhalation (>6 months)	NOAEL = 5 ppm

LOAEL = 20 ppm	0.182 ppm

UF = 30	Chronic-Oncogenicity Study in Mice

nasal histopathology

Cancer 	Classification: Likely to be carcinogenic to humans   Q1 * = 4 x
10-6 (μg/m3)-1

UF = uncertainty factor; EC = Human equivalent concentration; NOAEL = no
observed adverse effect level; LOAEL = lowest observed adverse effect
level; NA = Not Applicable



Table 3.4. Summary of Toxicological Dose and Endpoints for Use in
1,3-Dichloropropene Human Health Inhalation Risk Assessment
(Occupational)

Exposure

Scenario	Point of Departure	HED

HECs	Study and Toxicological Effects

Acute	NOAEL = 454 ppm

LOAEL = 583 ppm	227.0 ppm

UF = 30	Acute Inhalation Studies -Rats  Clinical signs, decreased body
weight (mortality observed at >647 ppm)

Short-Term  Inhalation (1 to 30 days) 	NOAEL = 20 ppm

(maternal)

LOAEL = 30 ppm	15.0 ppm

UF = 30	Developmental  Inhalation Toxicity Study -Rabbit 

Maternal decreased body weight gains

Intermediate-Term Inhalation (1 to 6 months)	NOAEL = 10 ppm

LOAEL = 30 ppm	0.86 ppm

UF = 30	13-week Inhalation Toxicity -Rats Histopathological lesions in
olfactory region of nasal cavity

Long-Term Inhalation (>6 months)	NOAEL = 5 ppm

LOAEL = 20 ppm	0.77 ppm

UF = 30	Chronic-Oncogenicity Study in Mice

nasal histopathology

UF = uncertainty factor; HEC = Human equivalent concentration;  NOAEL =
no observed adverse effect level; LOAEL = lowest observed adverse effect
level; NA = Not Applicable,



3.6	Endocrine Disruption  TC \l3 "		4.1.4	Endocrine Disruption 

EPA is required under the FFDCA, as amended by FQPA, to develop a
screening program to determine whether certain substances (including all
pesticide active and other ingredients) “may have an effect in humans
that is similar to an effect produced by a naturally occurring estrogen,
or other such endocrine effects as the Administrator may designate.” 
Following recommendations of its Endocrine Disruptor and Testing
Advisory Committee (EDSTAC), EPA determined that there was a scientific
basis for including, as part of the program, the androgen and thyroid
hormone systems, in addition to the estrogen hormone system.  EPA also
adopted EDSTAC’s recommendation that the Program include evaluations
of potential effects in wildlife.  For pesticide chemicals, EPA will use
FIFRA and, to the extent that effects in wildlife may help determine
whether a substance may have an effect in humans, FFDCA authority to
require the wildlife evaluations.  As the science develops and resources
allow, screening of additional hormone systems may be added to the
Endocrine Disruptor Screening Program (EDSP).

When additional appropriate screening and/or testing protocols being
considered under the Agency’s EDSP have been developed,
1,3-dichloropropene may be subjected to further screening and/or testing
to better characterize effects related to endocrine disruption.

4.0	Public Health  TC \l1 "5.0	Public Health 

An analysis of incidents related to 1,3-D use was completed by HED that
considered data from the OPP Incident Data System, Poison Control
Center, and California Pesticide Illness Surveillance Program.  This
analysis is provided below.  

According to several reports in the Incident Data System, Poison Control
Center, and California Pesticide Illness Surveillance Program, 1,3-D may
cause skin injury described as blistering, burning sensation, or dermal
irritation.  All of the incidents, however, were related to accidental
exposures resulting from spills due to equipment malfunctions or misuse
(use of inadequate protective devices).  Spills of 1,3-D have also been
associated with respiratory effects in relatively large numbers of
people in the vicinity of the spill as reviewed by Albrecht (1987).

One report obtained from the Incident Data System described an incident
in which 1,3-D was injected into the soil and twelve residents in two
adjacent houses reported burning/watery eyes and sore throats.  One
child reported coughing.  The report further states that the applicator
complied with the established 100 foot buffer zone; however, the buffer
was insufficient to prevent symptoms among residents living adjacent to
the field.  As a result of this incident, the County Agricultural
Commissioner (CAC) “conditioned the permit for fumigant use at the
site to require written notice to the occupants and maintenance of a
300-foot buffer zone.”  

HED has recently produced an update as of March 16, 2007 that focuses on
incident data collected from CDPR, Poison Control Centers, NIOSH SENSOR,
and other 6(a)(2) data.  This update can be found below.  [Note:  HED is
also in the process of preparing a comprehensive incident data
assessment for seven soil fumigants, including 1,3-D].

(1) California data. From 2002-2004, California occupational
surveillance data contained a total of 101 new incidents for 1,3-D, all
occurring in 2004. By comparison, for three other soil fumigants over
the same time period, there was a downward trend over time.
Metam–sodium had a total of 428 (’02=384, ‘03=61 and ‘04=4)
reported incidents; Chloropicrin had 192 total incidents (‘03=191,
‘04=1) and Methyl Bromide had 413 total incidents (‘02=391,
‘03=18, and ‘04=4) incidents.  The downward trend for three of four
soil fumigants suggests the possibility of positive results from worker
outreach/education and/or CDPR regulatory changes. However, the fact
that the 1,3-dichloropropene incidents were seen to increase at 101
incidents in ’04 suggests the possibility of use pattern changes.
Reasons for the temporal patterns observed are being further explored
with CA DPR incident data providers. 

(2) NIOSH SENSOR data: Currently, twelve states report occupational
poisoning incidents to a central database. The states are CA, WA, OR,
NY, AZ, LA, TX, NM, FL, NC, MI, IA. For the time period ’98-’03
covering 5899 total incident cases, 3 incidents were for 1,3-D,
including all males. States reporting are as follows: CA=1 incident,
LA=1, an MI=1. Underreporting is a known problem from the literature.
Due to underreporting, there are generally few duplicates found among
the multiple data sources. Matching the exact dates, locations, and
other incident case details eliminates duplicate incident cases.

(3) Poison Control Center (PCC) data: This is the only source of
National incident coverage, encompassing 61 poison centers that report
in a standard format. Only PCC reports data on children, as well as
occupational and non-occupational cases, symptom severity and medical
outcome, including death.  For the time period ’92-’05, PCC reported
66 1,3-D incidents, 24 occupational, 40 non-occupational, and 3
children. There were no deaths reported in recent years.

(4) 6(a)(2) and other data: A comprehensive incident data assessment for
seven soil fumigants, including 1,3-D is in preparation. 1,3-D [Telone,
Telone II, D-D (dichloropropene)] was among the fumigants studied in the
interagency Agricultural Health Study (AHS), (see   HYPERLINK
"http://www.aghealth.org"  www.aghealth.org ). No chemical specific
reports have been published to date on 1,3-D. When published, these
results and results from the other data sources will be used to update
the EPA assessment.

In summary, at a time when other soil fumigant incidents declined in CA
(2002-2005), possibly due to a combination of changing use patterns,
state/local regulatory changes, and/or better worker education and
outreach, there were 101 1,3-D CA incidents in (2004). CADPR in their
2003 annual accomplishments reported doing ten outreach trainings with
growers and applicators. These sessions were designed to prevent
large-scale incidents.

5.0	Dietary Exposure/Risk Characterization  TC \l1 "5.0	Dietary
Exposure/Risk Characterization 

5.1	Pesticide Metabolism and Environmental Degradation

5.1.1	Metabolism in Primary Crops  TC \l3 "5.1.1	Metabolism in Primary
Crops 

  SEQ CHAPTER \h \r 1 The qualitative nature of the residue in plants is
adequately understood based on soybean, tomato, and sugar beet
metabolism studies.  Although the studies involved pre-plant
applications, they were conducted at application rates more than 20
times the rate proposed for this use.  In studies with tomatoes and
soybean, no parent, 3-chloroallyl alcohol (CAAL), or 3-chloroacrylic
acid (CAAC) metabolites were detected, and incorporation into natural
plant constituents was demonstrated.  In the study with sugar beets,
parent and metabolites were also not detected, and the parent compound
was shown to have been metabolized and incorporated into sucrose.

5.1.2	Metabolism in Rotational Crops  TC \l3 "5.1.2	Metabolism in
Rotational Crops 

An acceptable confined rotational crop study was conducted with wheat,
lettuce, carrots, and radishes.  The results were in agreement with
those from primary plant metabolism studies, showing extensive
incorporation of radiolabelled residues into natural plant biochemical
constituents.  No plant-back restriction is required.

5.1.3	Metabolism in Livestock  TC \l3 "5.1.3	Metabolism in Livestock 

There are no livestock feed items associated with this request;
therefore, no residue chemistry data are required under this guideline
topic.

5.1.4	Analytical Methodology  TC \l3 "5.1.4	Analytical Methodology 

The method submitted for the determination of parent is suitable for
data collection and enforcement.  The method submitted for the
determination of CAAL and CAAC is acceptable for data collection and is
tentatively acceptable for enforcement.  An independent laboratory
validation (ILV) for the metabolite method, Method GRM 99.18, is
required to confirm that it is suitable for tolerance enforcement. 
Multi-residue method data are not available for 1,3-dichloropropene.
These data are required for the parent and metabolites.

5.1.5	Environmental Degradation

The cis and trans isomers of 1,3-dichloropropene (1,3-D) are highly
volatile and mobile under most environmental conditions.  The major
hydrolysis degradates, 3-chloroallyl alcohol and 3-chloroacrylic acid,
are both mobile and persistent.  The primary routes of 1,3-D dissipation
in the field appear to be volatilization, leaching, abiotic hydrolysis,
and aerobic soil metabolism.  In air, 1,3-D does not degrade through
direct photolysis; however, there can be degradation through
free-radical (OH and ozone) processes.  In water, hydrolysis is
temperature dependent with an increase in stability at lower
temperatures.  This seems to indicate that in warm climates, degradation
will occur more rapidly than in cooler climates.  According to
laboratory mobility studies, 1,3-D is mobile in a variety of soils
including loamy sand (Kd= 0.23) and sand (Kd= 0.32).  1,3-D is also
mobile in clay soils (Kd= 0.42 and 1.09) which is highly unusual for
most pesticides.  These mobility data, in addition to ground-water
monitoring information, have clearly demonstrated that 1,3-D is highly
mobile in soil.

As mentioned above, 1,3-D is highly volatile.  The factors influencing
the volatility of 1,3-D from a field plot include, but are not limited
to: soil organic matter, wind speed, soil moisture content, depth of
incorporation-injection, soil temperature and soil porosity.  Wind is a
major factor in the dispersion of 1,3-D as higher concentrations are
measured at night.  During the day, an increase in wind velocity also
increases vapor dispersion and lowers the measurable amount of material.

1,3-D has two major degradates: cis and trans isomers of 3-chloroallyl
alcohol and 3-chloroacrylic acid.  The 3-chloroallyl alcohol is the
major hydrolysis degradation product and is formed at 72% of applied. 
The 3-chloroacrylic acid is produced through aerobic soil metabolism at
lower and variable amounts depending on the soil type.  In studies
submitted to the Agency, 3-chloroacrylic acid formed at 1% - 6% of
applied.

The most recent risk assessment (C. Olinger, 6/6/07) included
consideration of drinking water exposure to a manufacturing impurity,
1,2-dichloropropane.  The registrants have modified the manufacturing
process to reduce the concentration of the impurity.  HED has recently
reviewed the Confidential Statements of Formula (CSFs) for all technical
registrants of 1,3-D, and none list 1,2-dichloropropane as an impurity
greater than 0.1% (C. Olinger, 12/14/07).  Therefore, EFED and HED no
longer have any concerns over the potential for 1,2-dichloropropane to
reach drinking water, and all risk estimates have been removed from the
risk assessment.

5.1.6	Toxicity Profile of Major Metabolites and Degradates TC \l3 "5.1.7
Toxicity Profile of Major Metabolites and Degradates 

In December 2004 members of the 1,3-D risk assessment team met to
discuss the toxicity of the 1,3-D degradates, the cis and trans isomers
of 3-chloroacrylic acid and 3-chloroallyl alcohol.  The acute and
subchronic toxicity studies indicate that the toxicity of the degradates
is within the same order of magnitude as the parent compound and
generally exhibit similar effects at high doses.  1,3-D has been shown
to be mutagenic in bacteria and mammalian cell lines, has the ability to
form reactive epoxides, and is carcinogenic in rats and mice.  The
limited data on CA-alcohol and CA-acid provide conflicting evidence that
the degradates are weakly or non-mutagenic.  Nevertheless, the ability
to form the same reactive epoxide is a possibility of the degradates. 
For these reasons, the degradates will continue to be included in the
chronic and cancer dietary exposure and risk assessments.

5.1.7	Pesticide Metabolites and Degradates of Concern

Table 5.1  Summary of Metabolites and Degradates to be included in the
Risk Assessment and Tolerance Expression

Matrix	Residues included in Risk Assessment	Residues included in
Tolerance Expression

Plants

	Primary Crop	cis and trans isomers of the parent, 3-chloroallyl
alcohol, and 3-chloroacrylic acid	cis and trans isomers of the parent,
3-chloroallyl alcohol, and 3-chloroacrylic acid.

	Rotational Crop	Not Applicable	Not Applicable

Livestock

	Ruminant	Not Applicable	Not Applicable

	Poultry	Not Applicable	Not Applicable

Drinking Water

	cis and trans isomers of the parent, 3-chloroallyl alcohol, and
3-chloroacrylic acid	Not Applicable



5.1.8	Drinking Water Residue Profile TC \l3 "5.1.9	Drinking Water
Residue Profile 

Surface Water Sources.  The Agency currently lacks sufficient surface
water-related exposure data from monitoring to complete a quantitative
drinking water from surface water exposure analysis for 1,3-D. 
Therefore, the Agency is presently relying on model-generated Estimated
Drinking Water Concentrations (EDWCs).  The maximum application rates
and relevant environmental fate parameters for 1,3-D were used in the
screening model PRZM/EXAMS for EDWCs in surface water. The output of the
screening model represent estimates of the concentrations that might be
found in surface water due to the use of 1,3-D as a pre-plant soil
fumigant and are presented in Table 5.2.  The concentrations of the
degradates 3-chloroallyl alcohol and 3-chloroacrylic acid, were
estimated as well.  The EDWCs from the existing pre-plant fumigation
uses was used as a screening level assessment for drinking water
exposure because the application rate is approximately 20x that of the
proposed new use, and the FQPA requires the Agency to consider all
exposures when setting tolerances.

With respect to 1,3-D, preliminary results of an “edge-of-field”
runoff study conducted in the tobacco growing region of Virginia
indicate that a small percentage (less than 0.003 percent) of the total
mass of 1,3-D applied reaches surface water under a high-end simulated
runoff scenario shortly after application.  Limited USGS National Water
Quality Assessment (NAWQA) surface water monitoring data are available
for 1,3-D and its degradates.  NAWQA data available from several high
use states (CA, FL, ID, OR and WA) showed no detects in 123 samples.

Although the Environmental Fate and Effects Division (EFED) has provided
modeled EDWCs for use in the drinking water exposure assessment, they
have also characterized the estimate as an overestimate of actual
drinking water concentrations (Eckel, 2008).  As described in Section
5.1.5, the major dissipation process for 1,3-D is volatilization.  The
volatilization routines in PRZM were improved in the most recent version
that EFED uses (3.12.2, dated May 12, 2005), but still only model
volatilization at room temperature and it has not been subjected to a
quality assurance review to ensure that it performs as expected. 
Volatilization will be faster at summer outdoor temperatures, so this
important process is not captured adequately.  Thus, PRZM-EXAMS does not
adequately model the major dissipation process for 1,3-D.  The
usefulness of PRZM-EXAMS exposure estimates is also limited by the
quality and quantity of the input data describing the fate processes. 
The current database for 1,3-D is not adequate to do a refined exposure
assessment.  The lack of aerobic aquatic metabolism data and soil
metabolism studies on additional soils has led to overestimates of
degradation rates (i.e. much slower degradation rates than the limited
available data suggest) that would lead to overestimates of modeled
drinking water outputs.  Also, data on the indirect photolysis of 1,3-D
are not available, and information on reactions with hydroxyl radicals
in air indicate that this could be an important route of dissipation in
water.  EFED has requested additional environmental fate data that would
allow further refinement of the surface water assessment.

Groundwater Sources.  Sufficient data for tap water from groundwater
wells are available for 1,3-D and its degradates 3-chloroacrylic acid
(CAAC) and 3-chloroallyl alcohol (CAAL).  A total of 518 wells were
selected in the Central Columbia Plateau, Upper Snake River Basin, North
Platte River, Albermarle-Pamlico Sound, and the Georgia/Florida basins.
The wells were intended to be among the most vulnerable wells available
for sampling in each region because they were in high use areas, were
among the shallowest in each region, and were located in close proximity
to fields that had received 1,3-D application in the recent past. 1,3-D
and its two metabolites were not found above 0.145 ppb in 5,800 samples.
 A total of 65 of 518 measured taps demonstrated detectable (>0.015 to
0.023 ppb) levels of 1,3-D or one of its metabolites at some point
during the study, with only three wells having more than one detection
(maximum was two detections).   To be conservative, in all chronic
calculations, the Limit of Detection was used when the chemical was "not
detected."  As a point of comparison, the modeled estimates of 1,3-D in
groundwater using SCI-GROW, ranged from 738 ppb to 1340 ppb.  Like the
surface water model, SCI-GROW is not designed for highly volatile
chemicals such as 1,3-D and its degradates.

Surface Water (μg/L)	Groundwater  (μg/L)

	Cancer/chronic	Cancer/chronic

Combined 1,3-D and Degradates 1,3	16.2	0.14 2

1 Estimated drinking water concentrations are based on PRZM/EXAMS data.

2 Estimated drinking water concentrations are based on monitoring data
and include parent and degradates.

3 Degradates include cis and trans isomers of both 3-chloroallyl alcohol
and 3-chloroacrylic acids





5.1.9	Food Residue Profile

Thirteen crop field trials were conducted to support this use and were
conducted at exaggerated rates, at a seasonal rate approximately five
times the rate of the pre-harvest application rate.  The field trials
are representative of typical grape growing areas in the US, as most of
the trials were conducted in California, two in Washington, and two in
New York.  Most of the pre-harvest intervals ranged from 6-30 days,
which is considerably shorter than the proposed 60-day PHI.  The
analytical methods used were appropriate for the parent and metabolites
and showed good recoveries.  The residue data are not supported by
adequate storage stability data, although supplemental data on soybeans
give some indication of stability for the storage intervals of the
submitted study.  The residue data are sufficient to support the
proposed use, provided the registrant submits a grape storage stability
study for all residues of concern, which reflects a minimum storage
interval of 154 days.

Residues of the parent (cis and trans isomers) were non-detectable (at
an LOD of approximately 0.9 ppb) in all trials with a pre-harvest
interval exceeding 21 days.  Residues of the metabolites 3-chloroacrylic
acid (CAAC) and 3-chloroallyl alcohol  (CAAL) were generally
non-detectable at most sites at all pre-harvest intervals with the
exception of one trial in Washington and one trial in California.

Residues of the metabolite 3-chloroacrylic acid (CAAC) were
non-detectable at all sites and all PHIs with the exception of the
samples from one Washington trial.  Residues of cis-CAAC were detectable
but below the LOQ of 0.003 ppm at a PHI of 74 days.  Residues of
cis-CAAL were detectable at all PHIs at this site as well up to a level
of 0.005 ppm.  Cis-CAAL was also detected at one CA site at a PHI of 28
days, but residues were below the LOQ of 0.003.  Residues of trans-CAAC
and trans-CAAL were not detectable at any site at any PHI.

These trials reflect four pre-harvest applications at rates of
approximately 1.3 times the proposed single application rate and
pre-harvest intervals much shorter than the proposed uses.  The proposed
use directions specify only one application prior to harvest.  HED does
not expect quantifiable residues when 1,3-D is used in accordance with
the use directions, and is recommending for a tolerance at the combined
limits of quantitation for all of the residues of concern, or 0.018 ppm.
 The residue data show that the actual residues are likely to be
considerably lower.

Processing studies are not available.  However, none are required as
exaggerated rate data showed that is unlikely that residues at the
proposed PHI will be detectable.  Due to the volatile nature of the
residues of concern, residues are likely to dissipate during processing.
 However, should residues concentrate during processing, they will be
below the recommended tolerance.

5.1.10	International Residue Limits TC \l3 "5.1.11	International Residue
Limits 

There are no Canadian or Codex Maximum Residue Limits for residues of
1,3-dichloropropene in any commodity.

5.2	Dietary Exposure and Risk TC \l2 "5.2  Dietary Exposure and Risk 

e conducted using the Dietary Exposure Evaluation Model software with
the Food Commodity Intake Database (DEEM-FCID™, Version 2.03), which
incorporates consumption data from USDA’s Continuing Surveys of Food
Intakes by Individuals (CSFII), 1994-1996 and 1998.  The 1994-96, 98
data are based on the reported consumption of more than 20,000
individuals over two non-consecutive survey days.  Foods “as
consumed” (e.g., apple pie) are linked to EPA-defined food commodities
(e.g. apples, peeled fruit - cooked; fresh or N/S; baked; or wheat flour
- cooked; fresh or N/S, baked) using publicly available recipe
translation files developed jointly by USDA/ARS and EPA.  For chronic
exposure assessment, consumption data are averaged for the entire U.S.
population and within population subgroups, but for acute exposure
assessment are retained as individual consumption events.  Based on
analysis of the 1994-96, 98 CSFII consumption data, which took into
account dietary patterns and survey respondents, HED concluded that it
is most appropriate to report risk for the following population
subgroups: the general U.S. population, all infants (<1 year old),
children 1-2, children 3-5, children 6-12, youth 13-19, adults 20-49,
females 13-49, and adults 50+ years old.

For chronic dietary exposure assessment, an estimate of the residue
level in each food or food-form (e.g., orange or orange juice) on the
food commodity residue list is multiplied by the average daily
consumption estimate for that food/food form to produce a residue intake
estimate.  The resulting residue intake estimate for each food/food form
is summed with the residue intake estimates for all other food/food
forms on the commodity residue list to arrive at the total average
estimated exposure.  Exposure is expressed in mg/kg body weight/day and
as a percent of the chronic population adjusted dose (cPAD).  This
procedure is performed for each population subgroup.

5.2.1	Acute Dietary Exposure/Risk  TC \l3 "5.2.1  Acute Dietary
Exposure/Risk 

No appropriate endpoint attributable to a single exposure (dose) was
identified from oral toxicity studies for females 13+ or the general
population.

5.2.2	Chronic Dietary Exposure/Risk  TC \l3 "5.2.2  Chronic Dietary
Exposure/Risk 

HED is concerned when dietary risk exceeds 100% of the PAD.  The
DEEM-FCID™ analyses estimate the dietary exposure of the U.S.
population and various population subgroups.  The results of the chronic
dietary analyses are reported in Table 5.3.  The dietary exposure is
less than 1% of the population adjusted dose for all population groups
for food alone and food plus tap water from ground water sources, and is
less than 5% of the population adjusted dose for all population groups
for food plus water from surface water sources.  The most highly exposed
sub-group is infants, if the surface water value is used, and children
aged 1-2 if the tap water value is used.

Table 5.3.  Summary of Chronic Dietary Exposure and Risk for
1,3-Dichloropropene

Population Subgroup	Chronic Dietary

Food Only	Chronic Dietary

Food and Water – Ground Water Sources 2	Chronic Dietary

Food and Water 2 - Surface Water Sources

	Dietary Exposure (mg/kg/day)	% cPAD1	Dietary Exposure

(mg/kg/day)	% cPAD1	Dietary Exposure

The tap water value (0.14 μg/L) was used in this assessment for ground
water exposure and 16.2 μg/L for the drinking water from surface water
sources.

Cancer Dietary Risk

HED is generally concerned when cancer risks exceed 1 x 10-6.  Because
of the uncertainties regarding estimation of cancer potency and human
exposure, risk estimates ranging from 1 to 3 x10-6 are generally
considered indistinguishable.  The results of the cancer dietary risk
analyses are presented in Table 5.4.  The estimated cancer risk for food
alone and food and drinking water from groundwater sources is below
HED’s level of concern for 1,3-D and its degradates.  

Although risk for drinking water from surface water sources for 1,3-D
exceeds the negligible standard, based on characterization of the model
estimates provided by EFED, HED considers the risk estimates to be an
overestimate, and likely to be no more than those of ground water
sources.  As discussed in Section 5.1.8, the surface water model,
PRZM-EXAMS is not designed for chemicals such as 1,3-D where
volatilization is the primary route of dissipation.  Insufficient data
are available to further refine the inputs to the model, leading to the
assumption of much slower degradation in the environment by the model
than is likely.  The limited surface water monitoring data available for
high use areas did not show any detects of 1,3-D and its degradates.  

Historically, EFED’s concern about exposure to 1,3-D in drinking water
has been from ground water exposure sources.  This is due to very high
application rates (hundreds of pounds per acre) for the existing
pre-plant fumigation uses, and its high mobility in soil (and thus
potential to leach to ground water).  Once introduced into ground water,
1,3-D is shielded from many of the processes that can contribute to its
more rapid dissipation from surface water.  These include photolysis,
volatilization to the atmosphere from the surface of water bodies,
volatilization due to the motion of flowing water (both during run-off
and stream flow), and the greater availability of oxygen for biological
metabolism.  All of these processes combined make it likely that
exposure from surface water sources will be less than that from ground
water sources (Eckel 2008).  Because the cancer risk from ground water
sources is below the Agency’s level of concern without the benefit of
these processes to aid dissipation, HED believes that the cancer risk
from surface water sources will also be below the Agency’s level of
concern based on its likely dissipation from surface water sources.  

Table 5.4.  Summary of Cancer Dietary Exposure and Risk for
1,3-Dichloropropene

Population Subgroup	Chronic Dietary

Food Only	Chronic Dietary

Food and Water 1

	Dietary Exposure (mg/kg/day)	Risk	Dietary Exposure

The tap water value (0.14 μg/L) was used in this assessment for ground
water exposure and 16.2 μg/L (combined 1,3-D and degradates) for the
drinking water from surface water sources for combined 1,3-D and
degradates.

5.3	Anticipated Residue and Percent Crop Treated (%CT) Information TC
\l2 "5.3 Anticipated Residue and Percent Crop Treated (%CT) Information 

The dietary assessment assumes all grapes consumed in the US are treated
with 1,3-dichloropropene.  Residues of the parent compound isomers and
three of the four degradates were assumed to be at ½ the limit of
detection (0.001 ppm) since residues were non-detectable in all field
trials at shorter pre-harvest intervals (PHI) than the proposed use. 
Residues at the proposed PHI in one trial of one degradate were at the
limit of quantitation (0.003 ppm), so the LOQ was used.  The degradates
were assumed to have equal toxicity to the parent compound, so the total
anticipated residue used in the dietary assessment for the chronic and
cancer analyses was 0.0055 ppm.

										

6.0 	Non-Occupational Exposure Assessment and Characterization  TC \l1
"6.0 	Non-Occupational Exposure Assessment and Characterization 

This section describes the potential exposure scenarios associated with
the post-plant use of 1,3-D.  [Note:  1,3-D is also registered for
pre-plant agricultural uses.  For details of the bystander exposure
related to the existing uses, please see the Phase 5 1,3-D RED].  These
include residential bystander exposure from two key sources: known
sources (e.g., at the edge of a treated field), as well as from many
sources within a region (e.g., ambient air).  There are no residential
uses of 1,3-D by homeowners so this aspect of the risk assessment
focuses on those types of exposures that may occur to bystanders
resulting from agricultural uses of 1,3-D.

Residential bystander exposure may occur because of emissions from
treated fields.  These emissions can travel to non-target areas and will
be referred to simply as bystander risks in this assessment.  Bystander
exposures can occur as a result of being in contact with residues that
were emitted from a known source (near field) and also from multiple
sources within a localized region (ambient).  For clarity, a known
source in this assessment is intended to represent area sources from a
single application (e.g., a treated farm field). Exposures from near
field sources for bystanders (resulting from the proposed use) are
described below in Section 6.1 and ambient air exposures are described
below in Section 6.2.

6.1	Bystander Exposures And Risks From Near Field Sources

The Agency’s calculation of bystander exposures and risks from known
sources has been an iterative process based on the ability to provide
additional predictive capabilities yet consider all possible sources of
information that could be used to characterize the overall risk picture
associated with a chemical.  This approach is also consistent with
general Agency guidance on the use of air models.

Three main sources of information have been used for assessing bystander
risks.  Each source has a unique level of predictive capability but each
result has been carefully considered in context with each other in order
to develop an overall characterization of the risks associated with
1,3-D use.  Each method is described in detail in Section 6.1.1 from the
Phase 5 RED.:  Methods Used To Calculate Bystander Exposures And Risks
From Known Sources along with a description of how they were used and
how they should be interpreted in the context of this assessment. 
Regardless of which approach is utilized, it is clear that there can be
possible human health effects associated with the use of soil fumigant
chemicals based on calculated risk estimates.

Exposures to bystanders from a single post-plant drip irrigation
fumigation and their associated risks, calculated using the PERFUM
modeling approach, have been used to assess the new use of 1-3,D and
they are presented in this section.  These exposures were also analyzed
using the actual field study data (i.e, the Monitoring Method.  See
appendices for further details pertaining to these analyses).  Because
of the refinements offered by the modeling approaches, it is believed
that those results should be considered as the most appropriate for
evaluating the risks associated with 1-3,D applications.

Appendices C through E contain the following information:

Appendix C.  PERFUM Analysis: Appendix D summarizes the results of the
analysis (i.e., various combinations of meteorological data and
flux/application methods) and provides a summary of outputs generated by
PERFUM for the 1,3-D product, Telone II.  It does not contain detailed
input and output files needed to complete calculations with PERFUM.  If
so required, these can be provided for review and validation purposes.
It should be noted that PERFUM results for all products yield the same
results and were not produced for each product. 

Appendix D.  Analysis of Data for Agricultural Field Uses: Appendix E
contains the analysis of the available 1,3-D monitoring data. [Note:
This appendix also contains a summary table that provides risk
calculations based on the data.]

Appendix E.  Model Information and History.

The analyses which were completed using PERFUM are based on combinations
of flux and meteorological data.  In addition, the impact of field size
and shape, application rates, “whole vs. maximum buffer” statistics,
and target concentrations (i.e., HECs coupled with uncertainty factor)
were evaluated.  The field sizes and shapes that were considered
include:

1 acre (square, rectangle oriented on its side, rectangle oriented on
its end);

40 acres (square).

The application rates that were considered include 100 percent of the
maximum rate and, to evaluate a range, 75, 50, and 25 percent of the
application rate were also considered.   [Note: PERFUM outputs for the
25 percent rate were generated and are available but not summarized at
this point.] In all cases, results for both maximum and whole buffer
statistics were evaluated to allow for a broader range of risk
characterization. 

The risk estimates presented below represent results for the acute
duration of exposure because they compare 24 hour concentrations
calculated with PERFUM to the acute HEC.  Results for selected
percentiles of exposure are reported.  Additional analysis based on
other percentiles of exposure could be completed if so needed. 

		

It should be acknowledged that a myriad of micro-environmental
conditions and factors can impact how 1,3-D will volatilize and disperse
from any given treated field on a particular day.  With this premise, it
would be logical to evaluate basic factors which could influence flux
(e.g., soil type, soil temperature, percent water, etc.) and also
micro-climates (e.g., topography) and thus ultimately impact results. 
PERFUM, however, cannot easily address specific changes in these factors
because it is not a 1st Principles Model where the approach would be to
build a predictive tool from basic fate characteristics.  Instead,
PERFUM is an empirical model which utilizes field study and actual
meteorological data to predict results and since field study data are
the basis for the PERFUM predictions it follows that results based on
empirical monitoring and those calculated with PERFUM would be similar
(see guidance pertaining to air model validation at
http://www.epa.gov/scram001/guidance/guide/appw_03.pdf for additional
information).

It should also be acknowledged that the nomenclature incorporated into
PERFUM uses the term “buffer zone” which equates to the distance
downwind at which a specific target concentration (i.e., combination of
HEC and UF) is met based on the desired statistical parameters.  The use
of this term does not imply any regulatory decision.  In the context of
this risk assessment, it should only be considered as the predicted
distance for a specific target concentration.  A number of differing
factors were considered to evaluate the sensitivity of the results to
changes in various inputs.	

It is clear that given the number of possible permutations of PERFUM
inputs and ways of presenting the outputs that there are many possible
approaches for interpreting the results.  The central goal, however, is
to quantify how potential risks change with factors such as application
method, distance from the treated field, percentile of exposure,
selected statistical basis (i.e., whole vs. maximum buffer approach),
application rate, and field size/shape.  Each of these factors has been
considered and very detailed results pertaining to each are available in
the appendices referenced above. 

Table 6.1 summarizes the results for the combination of Ventura
California meteorological data and post-plant drip irrigation field
volatility study on vineyard grapes (MRID #45296101). Similar to the
results for the pre-plant uses of 1,3-D, the PERFUM modeling results for
post-plant vineyard use indicates that acute risk do not exceed HED’s
level of concern at 0 meters from treated fields.  The Agency has some
concerns with the quality of this study.  First, the application rate
used in the study was 5.4 lbs ai/acre, while the maximum application
rate allowable is 17.7 lbs ai/acre.  In general, the Agency believes
that scaling down from the maximum application rate is acceptable,
assuming a linear relationship between application rate and flux rate.
The Agency has concerns with the practice of scaling up flux rates to
the maximum application rate, as it is unclear if soil saturation may
occur that causes more off-gassing (flux) than expected.  Additionally,
while flux rates were calculated from this study data, the regression
analysis for most periods yielded poor r-squared values and reordering
of the data was required.  This is a standard practice, but a better
designed study probably would have yielded better results.  A smaller
field and samplers placed closer to the edges of the field (e.g., the
samplers in this study were roughly 300 ft away - most studies have
samplers around 30 ft away) would have produced a higher quality of
data.  As a result, the Agency has low confidence in the flux rates
obtained from this study. 

However, since the risk estimates for the 1,3-D pre-plant drip
agricultural uses (all of which are applied at much higher application
rates) are not of concern at 0 meters from treated fields, and the
proposed label specifies a buffer zone of 100 ft, the Agency expects
that the post-plant vineyard use will not pose a risk of concern for
bystanders.  

Table 6.1  Buffer Distances for Ventura CA Weather and Post-Plant Drip
Irrigation Flux

Percentiles	Max (17.75 lb ai/A)	75% (13.31 lb ai/A)	50% (8.87 lb ai/A)

	1 Acre Square	40 Acre Square	1 Acre Square	40 Acre Square	1 Acre Square
40 Acre Square

Maximum Buffer Distances (meters)

50	0	0	0	0	0	0

75	0	0	0	0	0	0

90	0	0	0	0	0	0

95	0	0	0	0	0	0

97	0	0	0	0	0	0

99	0	0	0	0	0	0

99.9	0	0	0	0	0	0

99.99	0	0	0	0	0	0

Whole Field Buffer Distances (meters)

50	0	0	0	0	0	0

75	0	0	0	0	0	0

90	0	0	0	0	0	0

95	0	0	0	0	0	0

97	0	0	0	0	0	0

99	0	0	0	0	0	0

99.9	0	0	0	0	0	0

99.99	0	0	0	0	0	0

		

6.2 	Ambient Bystander Exposure from Multiple Regional Sources  TC \l3
"6.1.3 	Ambient Bystander Exposure form Multiple Regional Sources 

Ambient levels of 1,3-D are not attributable to a specific application
event; rather, contributions to the ambient samples may occur from
multiple sources.  For example, it is possible that bystanders could be
exposed to 1,3-D air emissions resulting from applications to multiple
fields in a geographic area, particularly if they live in or frequent
agricultural areas where there is significant use, such as in a
strawberry growing region of California. 

Exposures from ambient air that occur from multiple regional sources of
1,3-D were estimated from monitoring data collected to represent
conditions at a regional level.   The California Air Resources Board
(CARB) generated most of the data considered in this analysis.  CARB is
a widely recognized institution for these types of programs and it is
part of the California Environmental Protection Agency.  CARB conducts
air monitoring studies for various types of chemicals throughout
California.  These studies conducted by CARB can generally be
categorized as one of two types including: (1) targeted monitoring
typically completed upon request to provide information related to
specialized issues such as fumigant exposures in areas of high use
during the season of use; and  (2)  routine monitoring for select
pollutants via established networks in order to better quantify
exposures in the general population (i.e., CARB established its Toxic
Air Contaminant monitoring program or TAC for routinely quantifying
toxic chemicals in air in urban areas). 

For ease and clarity, the HED has opted by convention to describe the
available ambient bystander data used in this assessment as follows:

(1) “CARB Data”:  includes targeted monitoring data generated by
CARB focused on areas of high 1,3-D use in the season of use; and

(2) “TAC Data”:  includes data from CARB’s Toxic Air Contaminant
Network for 1,3-D that quantifies background levels in non-agricultural,
urban environments.  	

6.2.1	Exposures from Targeted Regional Ambient Source Air Monitoring  TC
\l4 "6.1.3.1	Exposures From Regionally Targeted Regional Ambient Source
Air Monitoring 

For the targeted ambient air analysis, HED evaluated different durations
of exposure with data ranging from single day acute exposures to chronic
exposures.

Samples were collected 1 to 4 times per week from each station over the
course of the use season.  For the 24 hr TWA results, the values are the
maximum values monitored.  Targeted ambient air monitoring was done for
7 to 9 weeks during season of high use in California. The monitoring
period was 7 weeks for Kern County in 2000 and 9 weeks for Kern County
in 2001.   Samples were taken for 8 weeks in Monterey and Santa Cruz
Counties in 2000 and 2001. 

The exposure concentrations for these intervals have been reported as
the mean weekly means for samples collected during each calendar week
over the course of the use season. This approach was taken in order to
statistically weigh equally each week’s contribution to the overall
seasonal mean because of differing numbers of samples in some weeks. 
Concentrations over the course of a season monitored in these studies
did not vary extensively so calculation of average concentrations for
shorter durations (e.g., 4 weeks) or even the use of an overall mean of
all samples are not expected to be dramatically different estimates used
in this assessment.   It should be noted that the statistical summaries
of the available data were completed by DPR and that the Agency reviewed
and concurred with this approach.  There are many possible ways to
calculate exposure estimates given the available data for completing a
short- and intermediate-term assessment.  For example, a TWA over an
entire season could be calculated or weekly TWAs could be calculated and
then averaged over a season.  The Agency agrees with DPR’s use of the
mean of weekly means because it does not weigh results for the number of
samples collected in a week (i.e., most weeks had 4 samples but some had
3) and it does not require a data filling procedure for the days missing
each week (i.e., usually Wed., Sat., and Sun with most applications
early in the weekend because of near school buffer issues).  

For the targeted ambient monitoring data, the acute Margins of Exposure
(MOEs) are calculated by comparing the maximum 24 hour TWA to the acute
HEC.  For short- and intermediate-term risks, MOEs are calculated by
comparing the mean of weekly mean estimates (as calculated by CDPR) to
the HEC selected for short- and intermediate-term exposure.   Since
sampling was done in the high use season, air concentrations used for
risk assessment are expected to be protective for exposures which could
occur throughout the year.  

Chronic exposure estimates were also calculated using the targeted
regional source ambient data.  These calculations should be considered
as rangefinder estimates of exposure only, because of a lack of
monitoring studies specifically designed for this purpose. 
Specifically, short- and intermediate-term estimates were amortized to
reflect a potential for exposure of 180 days out of each calendar year
in order to calculate chronic estimates of exposure.  This was based on
the approximate use patterns for 1,3-D over a year in high use areas. 
Results based on all of these calculations, as indicated above, do not
represent a risk concern to the Agency and in most cases risks were far
below the target level of concern (e.g., by orders of magnitude).  There
were no ambient monitoring studies targeting areas of high use that
collected air samples over an entire year that would be considered
representative of a chronic exposure pattern.  In these studies the
focus was more on the actual season of use so these data were typically
collected for only 9 weeks or so which represents the duration of the
typical application season.  However, in order to be able to evaluate
the possibility of chronic exposures in high use areas the Agency
utilized the seasonal mean of means from the high use areas and supposed
that exposures could be maintained at this rate for a sustained period
of 6 months which is twice as long as a normal application season.  This
approach does have some uncertainty associated with it but the Agency
believes that this approach does not underestimate exposure because
monitoring data were collected in the season of use in areas of high
use.  Additionally, risks calculated based on this method, as indicated
above, are typically well below the Agency’s level of concern.  In
addition to using the targeted monitoring data, the Agency also used the
urban background monitoring data to calculate chronic risks.  In this
case, the data were intentionally designed to be used to evaluate
longer-term exposure levels.  Many of the samples collected in this
network did not even contain measurable residues over the course of the
monitoring years in question but chronic risks were still evaluated as a
precautionary measure.  As indicated above, risks based on these results
tended to be at least two orders of magnitude lower that the Agency’s
level of concern.

For cancer risk assessment, the lifetime average daily exposure (LADE)
is calculated using the mean of weekly means and assumes that exposure
lasts the length of the longest monitoring period (9 weeks / 63 days). 
Cancer risk is then calculated by multiplying the LADE by the
non-occupational Q1*.  This approach is limited by the available data.

None of the acute, short-, intermediate- term, or chronic MOEs for
ambient air exposure during the high-use season exceed HED’s level of
concern for 1,3-D (MOEs less than 30).  Cancer risk for multiple sources
(ambient air exposure) of 1,3-dichloropropene was estimated from
monitoring data collected from over 20 sites over multiple years.  These
sites were in areas of high use and urban environments. The cancer risk
estimates for all but one monitoring site, in a high use area, ranged
from 2 x 10-6 to 9 x 10-8, which are below the Agency’s level of
concern.  The monitoring data for this site resulted in a risk estimate
of 6 x 10-6, which does exceed the Agency’s level of concern. 
However, the data for this site in the following year was almost two
orders of magnitude lower.  Therefore, over a lifetime of exposure, the
risk estimates would likely be below the level of concern.  The results
are summarized in Table 6.2.

Table 6.2   Results of 2000 Through 2001 California Ambient Monitoring
In High Use Areas During Season Of Use

CA.

County	Site	Dates & 

Mon.

Days (N)	24 Hr. TWAs (ppm)

Maximum	7-9 Week 1 (mean of means) (ppm)	Acute MOE2	Short-term MOE3
Interm-term MOE3	Chronic MOE4	Cancer Risk5

Kern	ARB	7/19 - 8/31/2000	0.00139	0.00021	54000	24000	980	1800	4.66e-07



6/30 - 8/30/2001	0.00015	0.00004	504000	125000	5100	9200	8.88e-08

	SHA	7/19 - 8/31/2000	0.00089	0.00012	85000	42000	1700	3100	2.66e-07

	CRS	7/19 - 8/31/2000	0.02825	0.00293	2700	1700	70	130	6.50e-06



6/30 - 8/30/2001	0.00060	0.00004	126000	125000	5100	9200	8.88e-08

	MVS	7/19 - 8/31/2000	0.00798	0.00039	9500	12800	530	950	8.66e-07



6/30 - 8/30/2001	0.00164	0.00019	46000	26000	1100	1900	4.22e-07

	VSD	7/19 - 8/31/2000	0.00319	0.00035	24000	14000	600	1100	7.77e-07



6/30 - 8/30/2001	0.00795	0.00044	9500	11000	460	840	9.76e-07

	MET	7/19 - 8/31/2000	0.00922	0.00056	8207	8900	370	660	1.24e-06



6/30 - 8/30/2001	0.00300	0.00018	25000	28000	1100	2100	4.00e-07

	ARV	6/30 - 8/30/2001	0.0211	0.00099	3600	5100	210	370	2.20e-06

Monterey and Santa Cruz	CHU	9/11 - 11/2/2000	0.00096	0.00009	79000	56000
2300	4100	2.00e-07



9/8 - 11/7/2001	0.00040	0.00005	189000	100000	4100	7400	1.11e-07

	OAS	9/11 - 11/2/2000	0.00032	0.00004	236000	125000	5100	9200	8.88e-08

	SAL	9/11 - 11/2/2000	0.00008	0.00001	946000	500000	20500	36900	2.22e-08



9/8 - 11/7/2001	0.00032	0.00005	236000	100000	4100	7400	1.11e-07

	LJE	9/11 - 11/2/2000	0.00007	0.00001	1081000	500000	20500	36900
2.22e-08



9/8 - 11/7/2001	0.00108	0.00007	70100	71400	2900	5300	1.55e-07

	PMS	9/11 - 11/2/2000	0.00079	0.00006	96000	83000	3400	6200	1.33e-07



9/8 - 11/7/2001	0.00092	0.00009	82200	56000	2300	4100	2.00e-07

	MES	9/8 - 11/7/2001	0.0047	0.00025	16100	20000	820	1500	5.55e-07

	SES	9/11 - 11/2/2000	0.00006	0.00001	1260000	500000	20500	36900
2.22e-08



9/8 - 11/7/2001	0.00023	0.00004	329000	125000	5100	9200	8.88e-08

1 samples taken for 7 and 9 weeks for Kern County in 2000 and Kern
County in 2001, respectively.   Samples taken for 8 weeks in Monterey 

and Santa Cruz Counties in 2000 and 2001.

2  Acute MOE = HEC (75.67 ppm)/Maximum 24 hour TWA.

3  Short-,Intermediate-term = HEC (5.0 ppm, 0.205 ppm, and 0.182 ppm for
short-, intermediate- and chronic, respectively)/7/8/9 week average. 

4 Chronic MOE = HEC (0.182 ppm)/mean of weekly means. Chronic exposure
is amortized for 180 days of exposure per year. 

5  Cancer Risk = Q1*(1.8 x 10-2 ppm-1)  x LADE (mean of weekly means x
63 days exposure during study/365 days per year x 50 years/70 year
lifetime).				

6.2.2	Exposures from Urban Background Ambient Air Monitoring  TC \l4
"6.1.3.2	Exposures From Urban Background Ambient Air Monitoring 

In 2002, CARB added 1,3-D to its list of toxic air contaminants for
which it routinely screens (see
http://www.cdpr.ca.gov/docs/empm/pubs/tac/monitoring.htm). 

The 2002 CARB monitoring sites are located throughout California in
urban environments that included urban areas such as Long Beach,
Burbank, Los Angeles, Fremont, Fresno, San Francisco and San Jose.  The
statistical summaries of the 2002/2003 CARB monitoring data are provided
in Table 6.3.

(   HYPERLINK
"http://www.arb.ca.gov/adam/toxics/statepages/tdcpstate.html, and
http://www.arb.ca.gov/adam/toxics/statepages/cdcpstate.html" 
http://www.arb.ca.gov/adam/toxics/statepages/tdcpstate.html, and
http://www.arb.ca.gov/adam/toxics/statepages/cdcpstate.html ).

HED calculated acute, short- intermediate-term and chronic MOEs as well
as cancer risk for urban background exposure to 1,3-D.  None of the
estimated MOEs or cancer risks exceeds HED’s levels of concern.  
Acute risks (MOEs) were calculated by comparing the maximum 24 hour TWA
to the acute HEC.  The median is compared to the selected HECs to
calculate short- and intermediate-term risk (MOEs). 

Chronic MOEs are calculated by comparing the median to the chronic HEC.
Since the Agency considers chronic exposures as those lasting for 180
days or longer, estimates of chronic exposure are amortized by 180 days
of exposure per year.  Chronic exposures (i.e., exposures at some level
6 months or so to every day over the course of a year) in and around
most of the monitored urban sites probably do not occur. For the
majority of sites, few residues were detected above the limit of
detection (LOD). Based on these monitoring data, a chronic risk
assessment is probably less germane than a short- or intermediate-term
assessment because of the use patterns for 1,3-D.  However, chronic
exposure to urban background ambient air is assessed as an upper bound
of exposure and is assumed to present a conservative assessment of risk.
 

HED calculates cancer risk based on an estimate of lifetime average
daily exposure. To represent the average exposure an individual may
receive over a lifetime, the lifetime average daily exposure (LADE) is
calculated using the mean or average daily exposure.    The LADE is then
multiplied by the non-occupational Q1* to determine cancer risk. HED
amortized the average daily exposure by 180 days based on the assumption
assumed that individuals may be exposed to average urban background air
concentrations chronically (i.e., 180 days per year), for 50 years. As
described above, since the likelihood of chronic exposure is expected to
be low, this assessment is considered conservative.

Table 6.3  Results of 2002 & 2003 California Ambient Monitoring In Urban
Areas

Site	Year	N	Results of Annual 1,3 Dichloropropene (ppm)1	MOEs	Cancer
Risk6



	Min	Median	Mean2	90th %tile	Max	acute-term3	short-term4	interm-term4
chronic5

	Statewide	2003	503	0.0001	0.0001	0.0001	0.0001	0.0014	54000	50000	2100
3700	6.3e-07

	2002	440	0.0001	0.0001	0.0001	0.0001	0.0009	84100	50000	2100	3700
6.3e-07

Azusa	2003	28	0.0001	0.0001	0.0001	0.0001	0.0001	757000	50000	2100	3700
6.3e-07

	2002	27	0.0001	0.0001	0.0001	0.001	0.0001	757000	50000	2100	3700
6.3e-07

Burbank	2003	26	0.0001	0.0001	--	0.0001	0.0001	757000	--	--	3700	6.3e-07

	2002	30	0.0001	0.0001	0.0001	0.0001	0.0001	757000	50000	2100	3700
6.3e-07

Calexico	2003	30	0.0001	0.0001	0.00014	0.00025	0.0004	189200	35714	1500
3700	6.3e-07

	2002	29	0.0001	0.0001	0.00015	0.0001	0.0009	84100	33333	1400	3700
6.3e-07

Chula Vista	2003	28	0.0001	0.0001	--	0.0001	0.0001	757000	--	--	3700
6.3e-07

	2002	29	0.0001	0.0001	0.0001	0.0001	0.0001	757000	50000	2100	3700
6.3e-07

El Cajon	2003	30	0.0001	0.0001	0.0001	0.0001	0.0001	757000	50000	2100
3700	6.3e-07

	2002	28	0.0001	0.0001	0.0001	0.0001	0.0001	757000	50000	2100	3700
6.3e-07

Los Angeles	2003	29	0.0001	0.0001	0.0001	0.0001	0.0001	757000	50000	2100
3700	6.3e-07

	2002	21	0.0001	0.0001	--	0.0001	0.0001	757000	--	--	3700	6.3e-07

Long Beach	2003	27	0.0001	0.0001	0.0001	0.0001	0.0001	757000	50000	2100
3700	6.3e-07

	2002	25	0.0001	0.0001	0.0001	0.0001	0.0001	757000	50000	2100	3700
6.3e-07

Riverside	2003	30	0.0001	0.0001	0.0001	0.0001	0.0001	757000	50000	2100
3700	6.3e-07

	2002	25	0.0001	0.0001	--	0.0001	0.0001	757000	--	--	3700	6.3e-07

Simi Valley	2003	31	0.0001	0.0001	0.0001	0.0001	0.00015	504500	50000
2100	3700	6.3e-07

	2002	26	0.0001	0.0001	0.0001	0.0001	0.0001	757000	50000	2100	3700
6.3e-07

Bakersfield	2003	29	0.0001	0.0001	0.10006	0.0001	0.0014	54100	31250	1300
3700	6.3e-07

	2002	29	0.0001	0.0001	0.00014	0.00025	0.0005	151000	35714	1500	3700
6.3e-07

Chico	2003	31	0.0001	0.0001	0.0001	0.0001	0.0001	757000	50000	2100	3700
6.3e-07

	2002	29	0.0001	0.0001	0.0001	0.0001	0.0001	757000	50000	2100	3700
6.3e-07

Fremont	2003	30	0.0001	0.0001	0.0001	0.0001	0.0001	757000	50000	2100
3700	6.3e-07

	2002	27	0.0001	0.0001	0.0001	0.0001	0.0001	757000	50000	2100	3700
6.3e-07

Fresno	2003	31	0.0001	0.0001	0.00011	0.0001	0.0005	151000	45455	1900
3700	6.3e-07

	2002	30	0.0001	0.0001	0.00011	0.0001	0.0006	126000	45455	1900	3700
6.3e-07

Roseville	2003	31	0.0001	0.0001	0.0001	0.0001	0.0001	757000	50000	2100
3700	6.3e-07

	2002	29	0.0001	0.0001	0.0001	0.0001	0.0001	757000	50000	2100	3700
6.3e-07

San Francisco	2003	31	0.0001	0.0001	0.0001	0.0001	0.0001	757000	50000
2100	3700	6.3e-07

	2002	15	0.0001	0.0001	--	0.0001	0.0001	757000	--	--	3700	6.3e-07

San Jose - 4th Street	2003	0	--	--	--	--	--	--	--	--	--	--

	2002	8	0.0001	--	--	--	0.0001	757000	--	--	--	--

San Jose - Jackson St.	2003	31	0.0001	0.0001	0.0001	0.0001	0.0001	757000
50000	2100	3700	6.3e-07

	2002	6	0.0001	--	--	--	0.0001	757000	--	--	--	--

Stockton	2003	30	0.0001	0.0001	0.0001	0.0001	0.00025	303000	50000	2100
3700	6.3e-07

	2002	27	0.0001	0.0001	0.0001	0.0001	0.0003	252000	50000	2100	3700
6.3e-07

Mexicali – Mexico	2003	17	0.0001	0.0001	--	0.0001	0.0001	757000	--	--
3700	6.3e-07

	2002	19	0.0001	0.0001	--	0.0001	0.0001	757000	--	--	3700	6.3e-07

Rosarito – Mexico	2003	30	0.0001	0.0001	0.0001	0.0001	0.0001	757000
50000	2100	3700	6.3e-07

	2002	25	0.0001	0.0001	--	0.0001	0.0001	757000	--	--	3700	6.3e-07

1 Concentrations were derived by summing the concentrations of cis and
trans 1,3-D.  0.0002 LOD = 0.0001 cis 1,3-D + 0.0001 trans 1,3-D. 
Values below LOD assumed to be ½ LOD.

2 Means shown only for years with data in all 12 months.

3 Acute MOE = HEC (75.67 ppm)/maximum air concentration value.

4 Short- and Intermediate-term MOE = HEC (5.0 ppm for short-term and
0.205 ppm for intermediate-term)/mean air concentration value.  

5 Chronic MOE = HEC (0.182 ppm)/median air concentration value. Chronic
exposure is amortized for 180 days of exposure per year.

6 Cancer Risk = Q1*(1.8 x 10-2  ppm-1)  x LADE (median air concentration
value x 180 days of exposure/365 days per year x 50 years/70 year
lifetime).

7.0	Aggregate Risk Assessment  TC \l1 "7.0	Aggregate Risk Assessment 

In accordance with the FQPA, HED must consider and aggregate pesticide
exposures and risks from three major sources: food, drinking water, and
residential exposures. In an aggregate assessment, exposures from
relevant sources are added together and compared to quantitative
estimates of hazard (e.g., a NOAEL or PAD), or the risks themselves can
be aggregated. When aggregating exposures and risks from various
sources, HED considers both the route and duration of exposure.

7.1	Acute Aggregate Risk   TC \l2 "7.1	Acute Drinking Water Risk 

No dietary acute endpoints were identified, so the only acute exposures
quantitatively assessed were the bystander inhalation exposures.  The
bystander assessments for inhalation exposures are presented in sections
6.1 and 6.2.

7.2	Short-Term and Intermediate-Term Aggregate Risk  TC \l2 "7.2	Chronic
Drinking Water Risk 

As previously discussed in section 3.5.9, the toxicity endpoints for
inhalation and dietary exposures are different, so it would be
inappropriate to aggregate exposures from these pathways.  The bystander
assessments for inhalation exposures are presented in sections 6.1 and
6.2.  The aggregated dietary risk for food and water exposures is
discussed in section 5.2.

		

7.3	Long-Term Aggregate Risk

As previously discussed in section 3.5.9, the toxicity endpoints for
inhalation and dietary exposures are different, so it would be
inappropriate to aggregate exposures from these pathways. The bystander
assessments for inhalation exposures are presented in section 6.2.  The
aggregate dietary risk assessment for food and water exposures is
discussed in section 5.2.2.  The combined exposure is less than the
level of concern, with the combined food and drinking water (from ground
water sources) at less than 1% of the PAD for all populations, and the
combined food and drinking water (from surface water sources) at less
than 5% of the PAD for all populations.

  TC \l2 "7.2	Chronic Drinking Water Risk 

7.4	Cancer Aggregate Risk  TC \l2 "7.2	Chronic Drinking Water Risk 

As previously discussed in section 3.5.9, the tumors identified in the
carcinogenicity studies from for inhalation and dietary studies are
different, so it would be inappropriate to aggregate exposures from
these pathways for the cancer assessment.  The bystander cancer
assessments for inhalation exposures are presented in Section 6.2.

The aggregated food and water assessment is discussed in section 5.2.3.
These risks represent upper bound risks for a person living in
agricultural area(s) where 1,3-D is used extensively or where a person
obtains drinking water from an aquifer that led directly from an area
where 1,3-D is used.  HED is generally concerned when cancer risks
exceed 1 x 10-6.  Because of the uncertainties regarding estimation of
cancer potency and human exposure, risk estimates ranging from 1 to 3
x10-6 are generally considered indistinguishable.  The results of the
cancer dietary risk analyses are presented in Table 5.4.  The estimated
cancer risk for food alone and food and drinking water from groundwater
sources is below HED’s level of concern for 1,3-D and its degradates. 


Although risk for drinking water from surface water sources for 1,3-D
exceeds the negligible standard, based on characterization of the model
estimates provided by EFED, HED considers the risk estimates to be an
overestimate, and likely to be similar those of ground water sources. 
As discussed in Section 5.1.8, the surface water model, PRZM-EXAMS is
not designed for chemicals such as 1,3-D where volatilization is the
primary route of dissipation.  Insufficient data are available to
further refine the inputs to the model, leading to the assumption of
much slower degradation in the environment by the model than is likely. 
The limited surface water monitoring data available for high use areas
did not show any detects of 1,3-D and its degradates.  

Historically, EFED’s concern about exposure to 1,3-D in drinking water
has been from ground water exposure sources.  This is due to very high
application rates (hundreds of pounds per acre) for the existing
pre-plant fumigation uses, and its high mobility in soil (and thus
potential to leach to ground water).  Once introduced into ground water,
1,3-D is shielded from many of the processes that can contribute to its
more rapid dissipation from surface water.  These include photolysis,
volatilization to the atmosphere from the surface of water bodies,
volatilization due to the motion of flowing water (both during run-off
and stream flow), and the greater availability of oxygen for biological
metabolism.  All of these processes combined make it likely that
exposure from surface water sources will be less than that from ground
water sources (Eckel 2008).  Because the cancer risk from ground water
sources is below the Agency’s level of concern without the benefit of
these processes to aid dissipation, HED believes that the cancer risk
from surface water sources will also be below the Agency’s level of
concern based on its likely dissipation from surface water sources.

Cancer risk for multiple sources (ambient air exposure) of
1,3-dichloropropene was estimated from monitoring data collected from
over 20 sites over multiple years.  These sites were in areas of high
use and urban environments. The cancer risk estimates for all but one
monitoring site, in a high use area, ranged from 2 x 10-6 to 9 x 10-8,
which are below the Agency’s level of concern.  The monitoring data
for this site resulted in a risk estimate of 6 x 10-6, which does exceed
the Agency’s level of concern.  However, the data for this site in the
following year was almost two orders of magnitude lower.  Therefore,
over a lifetime of exposure, the risk estimates would likely be below
the level of concern.  In more populated urban environments air
concentrations were below the analytical limit of detection in 21 of 28
site/year combinations considered.  In the remaining, values were
measured but did not result in cancer risks of concern.  Therefore, the
Agency does not have a concern for the cancer risk from
1,3-dichloropropene.

8.0 	Cumulative Risk Assessment and Characterization  TC \l1 "8.0 
Cumulative Risk Assessment and Characterization 

Unlike other pesticides for which EPA has followed a cumulative risk
approach based on a common mechanism of toxicity, EPA has not made a
common mechanism of toxicity finding as to 1,3-D and any other
substances and 1,3-D does not appear to produce a toxic metabolite
produced by other substances. For the purposes of this reregistration
action, therefore, EPA has not assumed that 1,3-D has a common mechanism
of toxicity with other substances. For information regarding EPA’s
efforts to determine which chemicals have a common mechanism of toxicity
and to evaluate the cumulative effects of such chemicals, see the policy
statements released by EPA’s Office of Pesticide Programs concerning
common mechanism determinations and procedures for cumulating effects
from substances found to have a common mechanism on EPA’s website at
http://www.epa.gov/pesticides/cumulative/.

9.0	Occupational Exposures  TC \l1 "9.0	Occupational Exposures  

This section of the risk assessment focuses on potential exposures and
risk to occupational handlers, to occupational reentry workers who could
be exposed when entering 1,3-D-treated areas to perform crop-production
tasks, and to occupational bystanders who could be exposed when
performing crop-production tasks near (but not inside) 1,3-D-treated
areas.  This assessment describes the occupational exposures for the
proposed new use only.  The occupational assessment for the existing
uses may be found in the most recent risk assessment associated with the
RED (Vogel, 2007).

Since the majority of 1,3-D is used seasonally with typical applications
lasting 2 weeks, 1 to 2 times per year, it is expected that the majority
of worker exposure will be acute and short-term in duration. Due to
model limitations, the PERFUM model was only used to calculate
post-application exposure for the acute durations.  Monitoring data were
used to calculate post-application acute, short-term and cancer risk
(see Appendix E).  However, there is potential for use by commercial
applicators as well as private growers. Since commercial applicators may
apply 1,3-D to many fields over the course of the use season, they are
expected to have a longer durations of  exposure  than private growers.
Therefore, acute, short- and intermediate-term exposures are assessed
for commercial mixer, loaders, and applicators of 1,3-D (see Section 9.0
of the Phase 5 RED).  

It should be noted that the RfC methodology used to calculate inhalation
risk incorporates an adjustment for expected duration of exposure. It is
presumed that exposure occurs during the course of an average work week
(8 hours of work per day and 5 days per week).  For this reason, the
worker assessment is considered conservative for both private growers
and commercial applicators.

				

Since 1,3-D is formulated as a liquid there is some potential for dermal
and eye contact.  The use of mitigation controls such as personal
protective equipment (PPE) and closed transfer systems (as required on
the Cordon™ label) minimizes the potential but does not eliminate it. 
Although 1,3-D may be irritating to the skin and eyes, no dermal
endpoints of concern were selected for risk assessment purposes. 
However, the high vapor pressure of 1,3-D also makes quantifying any
potential low level exposures very difficult.  Therefore, a quantitative
dermal exposure assessment has not been completed.

	

9.1	Post-plant Drip Irrigation Fumigations

Mixer/Loader/Applicator Exposure

The registrant has proposed a post-plant drip irrigation use of 1,3-D in
established vineyards.  HED has no new data for worker exposure
resulting specifically from the post-plant drip irrigation application
of 1,3-D.  However, mixing and loading techniques for the proposed use
are expected to be similar to loading techniques assessed for the
existing agricultural uses of 1,3-D.  Specifically, exposure for bulk
and mini-bulk loading methods were assessed in the most recent RED.  No
data are available to assess drip irrigation applicator exposure;
however, since this type application is closed system, exposure is
expected to be negligible.  

As noted above, bulk and mini-bulk loading exposure was evaluated in the
Phase 5 RED for 1,3-D.  The data evaluated in the recent RED is the only
data available to assess exposure for loading of 1,3-D.  It should be
noted that the study data used to estimate bulk and mini-bulk loader
exposure are based on a much higher application rate than the proposed
application rate for the post-plant vineyard use. For this reason,
loader exposure for the proposed post-plant use is expected to be
significantly lower than that assessed for bulk and mini-bulk loading
for the existing pre-plant uses of 1,3-D.

Exerted from the Phase 5 RED:

As a result of the March 1992 Data Call-In (DCI), DowElanco submitted
final reports of worker air monitoring studies conducted in 1992 and
1993 at the Moses Lakes, Washington, Buckeye, Arizona, and Hookerton,
North Carolina (MRID 42946201, 42845602).  These studies monitored
loaders, applicators and workers involved in drum and bulk loading and
related applications of various 1,3-D products.  Studies were conducted
in accordance with product label directions and utilizing regional
commercial application techniques associated with application of Telone
II and Telone C-17.  As a result of the Special Review negotiations
between DowElanco and EPA, drum loading of 1,3-D products was phased out
in late 1996.  A delivery method known as mini-bulk was promoted as
replacement for drum loading.  Subsequently, Dow submitted a study
conducted in Ainger, North Carolina, in which mini-bulk cylinder were
used (MRID 43880401).    These three studies were evaluated in the 1998
1,3-D RED to determine exposure and risk for workers involved in 1,3-D
loading and applications.

For the loaders and applicators, two kinds of samples were collected:
four hour samples, and task-specific short duration (4 to 46 minutes)
samples.  The four hour samples provided inherently time- weighted
average air concentrations over a major fraction of a work day, while
the task-specific samples measured the air concentrations associated
only with high-contact activities.  For product loaders, these
activities were the actual loading events.  The 4-hour loader samples
included the loading events, and the time spent on site between loading
events.  In the most recent Ainger, NC worker monitoring study, only
short-term task specific samples were collected.  Sampling occurred only
when workers were actively engaged in loading.  Because the number of
monitored replicates at each site was small, HED pooled the results from
different sites, to obtain the largest possible sample sizes for each
exposure scenario.   Details of the worker monitoring studies are
described in detail in the 1998 RED.   

Data evaluated in the 1998 RED was not modified.  The air concentration
values are the same as those used in Table 7 of the 1998 RED document. 
However, in the 1998 RED, estimates for commercial handlers and private
growers were presented separately, assuming that private grower will
perform both loading and application and spend most of their work day
engaged in application rather than loading. Exposures estimates for
growers were based on the air concentration for application rather than
loading. Estimates of exposure for commercial loaders and applicators
were presented separately, assuming 5 to10 hours per work day.  

The current document provides assessments of commercial loader and
applicator exposure only, for each task monitored (as listed in Table 7
of the 1998 RED document).  Since commercial applicators may apply 1,3-D
to many fields over the course of the use season, they are expected to
have a more exposure than private growers.   To support this assumption,
HED used estimates of daily and yearly work hours as supplied by the
Agency’s Biological and Economic Analysis Division (BEAD).  BEAD
determined that the Total Lifetime Work Hours were 500 hours for private
farmers/growers (5 hrs/day x 10 days/year x 10 years/lifetime) and 3200
hours for commercial handlers (8 hrs/day x 20 days/year x 20
years/lifetime).  HED used BEAD’s assessment of lifetime work hours
for commercial handlers (8 hrs/day x 20 days/year x 20 years/lifetime)
as the basis for the current assessment. Since the estimate lifetime
work hours for commercial handlers are greater than that of the private
growers, the current worker assessment is considered conservative for
both private growers and commercial applicators. 

Acute risks (MOEs) are calculated by comparing the maximum air
concentration level of 1,3-D at an individual sample point to the
toxicological human equivalent concentration (HEC) selected for acute
exposures. To calculate the short-and intermediate-term risks to 
handlers, the  mean air concentration level of 1,3-D are calculated
across all sites for each different handler task and method of
application.  This mean air concentration levels are compared to the HEC
selected for short- and intermediate-term. Cancer risk is calculated by
multiplying the LADE by the occupational Q1*.  The LADE used for cancer
risk assessment assumes 20 days of exposure per year for 20 years per
lifetime.

Table 14 summarizes the risks for loading activities and applicators
involved in pre-plant broadcast and row applications.  Overall, the data
indicate that risks exceed HED’s level of concern for workers involved
in 1,3-D loading and application when no respiratory protection is used.
 OV respirators, which reduce exposure levels by a factor of 10, are
also considered and reduce exposure do not exceed HED’s level of
concern for most workers involved in 1,3-D application with these
devices.  However, even with the use of OV respirators, which are
required on current 1,3-D labels, the intermediate-term MOEs for bulk
loading exceed HED’s LOC (LOC is for MOEs less than 30).  It is likely
that the risk estimates for bulk loading is conservative because this
assessment assumes that this activity is done over the course of a
normal work week, 8 hours per day, 5 days per week.  The available
monitoring study indicates that actual loading activities comprise a
small part of the entire work day (approximately 15 minutes to 1 hour). 
However, since this assessment is for commercial applicators and BEAD
information indicates that commercial applicators can work for 8 hours
/day, HED will use these current inputs until data are available to
support refinements to ensure HED does not underestimated risk.  Data
which indicated the division of work for commercial applicators (i.e.,
time spent loading and time spent applying) could be used to refine the
bulk loading risk estimates.  Note that if bulk loading only occurs for
one hour (or less) per day, the intermediate-term bulk loading risk
would not exceed the LOC. 

Table 14:  1,3-D Air Concentrations Monitoring Data for Agricultural
Workers as listed in the 1998 RED



Activity	

Sample Duration	

Study Site	

Total reps	

Max	Air Concentration (ppm)	MOE

	Cancer Risk3





	Mean	Median	acute1	Short2	interm2

	Bulk Loadinga	4 hrs	WA, AZ	10	1.29	0.35	0.14	176.35	42.38 

	2.43

(24.3)4	1.2E-04

(1.2E-05)4

 Bulk Loadinga	task only	WA, AZ	10	7.05	2.35	1.05	32.20

	6.38

(64)4	0.37

(4) 4	6.6E-04

(6.6E-05)4

Mini-bulk Loadinga	task only	NC	12	0.26	0.10	0.10	886.51

	148.98

	8.54

(85.4)4	2.4E-05

(2.4E-06)4

Bulk, Mini-bulk, and Drum Applicationb	4 hrs & task	WA, AZ, NC	28	1.43
0.29	0.25	158.96

	50.86

	2.92

(29.2)4	1.34E-04

(1.3E-05)4

a With use of dry disconnects

b With use of end-row spill control

1  Acute MOE = HEC (227 ppm)/maximum air concentration value.	

2  Short- and Intermediate-term MOE = HEC (15 ppm for short-term and
0.86 ppm for intermediate-term)/mean air concentration value.  

3  Cancer Risk = Q1*(1.8 x 10-2 ppm) x ( 8 hours/24 hours -) x LADE
(median air concentration value x 20 days/365 days per year x 20
years/70 year lifetime).

4 () = addition of OV respirator.

Occupational Bystander Exposure

One field volatility study is available to address post-application
exposure from this use (MRID 45296101).  Using this field volatility
study, modeling is done for the post-plant drip irrigation using the
PERFUMS model. The resulting buffer distances were estimated to be zero
(see section 6.1 for details).  However, the Agency has some concerns
with the quality of this study.  First, the application rate used in the
study was 5.4 lbs ai/acre, while the maximum application rate allowable
is 17.74 lbs ai/acre.  In general, the Agency believes that scaling down
from the maximum application rate is acceptable, assuming a linear
relationship between application rate and flux rate.  However, the
Agency has concerns with the practice of scaling up flux rates to the
maximum application rate, as it is unclear if soil saturation may occur
that causes more off-gassing (flux) than expected.  Additionally, while
flux rates were calculated from this study data, the regression analysis
for most periods yielded poor r-squared values and reordering of the
data was required.  This is a standard practice, but a better designed
study probably would have yielded better results.  A smaller field and
samplers placed closer to the edges of the field (e.g., the samplers in
this study were roughly 300 ft away whereas most studies have samplers
approximately 30 ft away) would have produced a higher quality of data. 
As a result, the Agency has low confidence in the flux rates obtained
from this study.  

ble post-plant study only monitored air concentrations of 1,3-D at 300
feet from the treated field, HED recommends that the Cordon™ label
require a buffer distance of 300 feet until the requested confirmatory
field volatility data for this use are received and reviewed.

The Agency has limited data (i.e, one field volatility study) to assess
the post-plant drip irrigations use.  However, the Agency has additional
field volatility data for the existing pre-plant drip irrigation use of
1,3-D, which is very similar to the proposed post-plant drip irrigation
use.  To further characterize the potential risks resulting from the
proposed use, the HED has provided a summary of risk results for the
pre-plant irrigation uses.  This assessment indicates low concern for
occupational bystander exposure resulting from the existing drip
irrigation uses.  Additionally, it should be noted that the proposed
post-plant drip irrigation uses  are applied at significantly lower
application rates than the existing pre-plant drip irrigation uses.  For
this reason, exposure and risk related to the proposed use is expected
to be significantly lower than that of the pre-plant drip irrigation
uses (presented below).

Exerted from the Phase 5 RED:  Pre-plant Drip Irrigation Applications: 
TC \l3 "Pre-plant Drip Irrigation Applications:  HED has no data for
worker exposure resulting from the drip irrigation application of 1,3-D.
 However, there are field volatility data available to address off-site
exposure from this use.  The ISCST3 Model is used to estimate
occupational bystander exposures following/during a single pre-plant
drip irrigation application of 1,3-D to outdoor agricultural fields. 
The model allows HED to examine the effect of several variables,
including field size, emission ratios, wind speed, and atmospheric
stability.  Air concentration levels estimated by the ISCST3 Model are
based on the assumption that occupational bystanders would be exposed
during an eight-hour work day.  [Details of the ISCST3 analysis are
available in Appendix C. ]. Table 17 shows the acute risks (MOEs)
estimated by comparing the toxicological human equivalent concentration
of concern to the estimated air concentration levels.  Generally, risks
do not exceed HED’s level of concern ((LOC is for MOEs less than 30).
Although the ISCST3 model assessment is considered be a high-end
estimate of actual exposure, HED does not have data to refine the
current assessment.  

As noted above, the modeling analysis done for the existing pre-plant
drip irrigation use indicates that there is low concern for acute
occupational bystander exposure resulting from 1,3-D application.
However, field volatility studies for 1,3-D indicate that peak emissions
from treated fields occur up to 72 hours after application.  At this
time, the models cannot readily be used to evaluate exposures of longer
duration.  When appropriate distributional models are available,
short-term, intermediate-term and cancer risk may be reassessed with
models that can better estimate longer term, average exposures (e.g., a
SOFEA© analysis based on existing uses). 

Table 17. ISCST3 MOEs At Selected Distances Downwind For Occupational
Exposure to Pre-Plant Agricultural Field Fumigations, Telone EC

App. Meth.	ER

(%)	Fld

Size

(A)	DW Dist.

(M)	Differing  Meteorological Conditions





1 m/s

2.3 mph	1.4 m/s

3.1 mph	1.8 m/s

4 mph	2.2 m/s

5 mph	2.7 m/s

6 mph	3.1 m/s

7 mph	3.6 m/s

8 mph	4.0 m/s

9 mph	4.5 m/s

10 mph	4.5 m/s

10 mph





Stab D	Stab C	Stab C	Stab C	Stab C	Stab C	Stab C	Stab C	Stab C	Stab B

Drip Irrigation, Raised Bed, Untarped	7.8	1	25	105	228	293	359	441	505
588	650	732	1040





	100	238	565	727	889	1083	1253	1444	1600	1825	3059





	500	1316	4727	6118	7429	8667	10400	11556	13000	14857	34667





5	25	67	148	190	233	286	328	381	423	477	675





	100	130	296	381	466	571	658	765	846	954	1405





	500	406	1253	1600	1962	2419	2737	3250	3586	4000	8667





10	25	57	126	162	198	243	279	324	360	405	575





	100	102	235	302	370	454	520	605	671	754	1106





	500	279	782	1010	1238	1507	1733	2000	2261	2537	5200





20	25	49	109	140	171	210	241	280	310	350	498





	100	82	190	245	299	366	421	488	545	612	889





	500	203	536	689	839	1030	1182	1368	1529	1733	3250





40	25	42	95	122	149	183	211	244	272	305	439





	100	67	157	202	246	302	348	403	448	505	743





	500	153	395	507	619	759	874	1020	1130	1268	2261



Drip Irrigation, Raised Bed, Tarped	2.2	1	25	375	813	1051	1284	1576	1793
2080	2311	2600	3714





	100	852	2000	2600	3152	3852	4522	5200	5778	6500	10400





	500	4727	17333	20800	26000	34667	34667	52000	52000	52000	104000





5	25	241	531	680	832	1020	1169	1368	1507	1705	2419





	100	462	1061	1368	1651	2039	2364	2737	3059	3355	4952





	500	1444	4522	5778	6933	8667	9455	11556	13000	14857	34667





10	25	203	450	578	707	867	1000	1156	1284	1444	2039





	100	365	839	1083	1316	1625	1857	2167	2419	2667	4000





	500	1000	2811	3586	4333	5474	6118	7429	8000	8667	17333





20	25	174	388	500	612	748	860	1000	1106	1253	1793





	100	294	680	874	1072	1316	1507	1733	1926	2167	3152





	500	727	1926	2476	2971	3714	4160	4952	5474	6118	11556





40	25	151	340	437	533	654	754	874	972	1095	1576





	100	240	562	722	881	1083	1238	1444	1600	1793	2667





	500	545	1405	1825	2213	2737	3152	3586	4000	4522	8000





		

10.0	Data Needs and Label Requirements  TC \l1 "10.0	Data Needs and
Label Requirements 

10.1	Toxicology  TC \l2 "10.1	Toxicology 

No additional studies are required at this time.

10.2	Residue Chemistry  TC \l2 "10.2	Residue Chemistry 

The following confirmatory studies are needed to support an
unconditional registration.

860.1340 Residue Analytical Methods

An independent laboratory validation is required for the tolerance
enforcement method that determines the 3-chloroacrylic acid and
3-chloroallyl alcohol metabolites.

OPPTS Guideline 860.1360 Multiresidue Methods

Multiresidue method data are required for 1,3-dichloropropene and its
3-chloroacrylic acid and 3-chloroallyl alcohol  metabolites.

OPPTS Guideline 860.1380 Storage Stability

A storage stability study demonstrating stability of 1,3-dichloropropene
and its 3-chloroacrylic acid and 3-chloroallyl alcohol  metabolites in
grapes for at least 154 days is required.

10.3	Occupational and Residential Exposure  TC \l2 "10.3	Occupational
and Residential Exposure 

No additional studies are required at this time.

References

Abel, S., 6/26/00; D260209 and D260210 (Environmental Fate Assessment).

Eckel, W., 1/18/08, Characterization of the Drinking Water Assessment
for Telone.

Olinger, C.; 5/24/2007; DP D318734; Amended Registration for Grapes: 
Summary of Analytical Chemistry and Residue Data.

Olinger, C.; 6/13/07; DP D340060; Amended Registration for Grapes: 
Summary of Analytical Chemistry and Residue Data.

Olinger, C.; 12/14/07; DP Barcode: D346778; Follow-up on Proposed New
Use for Drip Irrigation in Vineyards: Drinking Water and Residential
Assessments.

Vogel, D. et al; 4/12/2007; DP D337328; 1,3-Dichloropropene: HED Human
Health Risk Assessment for Phase 5.

Appendix A: Executive Summaries for Critical Studies and Toxicological
Profile  TC \l1 "Appendix A

Executive Summaries for Critical Studies and

 Toxicological Profile 



Acute Inhalation Exposure 

Critical Studies: Acute Inhalation Studies - Rats

					

EXECUTIVE SUMMARY:   In one acute inhalation study (MRID No.4022093),
Wistar rats were exposed to Telone II at 454, 647, 699, 762, 832 or 958
ppm for 4 hours (whole body exposure).  The mortality rates were as
follows: 0, 20, 30, 50, 100 and 100% at 454, 647, 699, 762, 832 and 958
ppm dose levels, respectively. In a second study (MRID 41672201),
Fischer 344 rats were exposed to cis- 1, 3 dichloropropene at 0, 583,
771, or 1020 ppm for 4 hours (whole body exposure).  No animals died at
583 ppm; however, body weight loss (13% decrease in body weight) during
days 2 through 7 was seen in rats exposed to this concentration. Rats 
regained their weight on day 8. At 1020 ppm, all exposed animals died
immediately following the exposure and 771 ppm exposed animals died
during the 14 day observation period.  Accordingly, 454 ppm or an HEC of
75.67 ppm (non-occupational risk assessment) or 227.0 ppm (occupational
risk assessment) was selected as the NOAEL  based on decreased body
weights at the LOAEL of 583 ppm. 

						

	Short-term Inhalation Exposure

Critical Study: Developmental Toxicity Study - Rabbits

EXECUTIVE SUMMARY :  In a developmental toxicity study (MRID 001444715
and 00152848), New Zealand rabbits (17-24 females/group) were exposed to
aerosol concentrations of 1,3-D (90.1%) at 0, 20, 60 or 120 ppm
(equivalent to approximately 0, 0.091, 0.272 or 0.545 mg/L) 6 hours/day
during gestation days 6 through 18.  The maternal NOAEL was 20 ppm
(0.091 mg/L).  The maternal LOAEL was 60 ppm (0.272 mg/L) based on
decreased body weight gains compared with controls.  The developmental
NOAEL was 120 ppm (0.545 mg/L).  The developmental LOAEL was >120 ppm (>
0.545 mg/L, HDT).  No Telone II related malformations were reported. 

		

	Intermediate-term Inhalation Exposure

Critical Study: 13-Week Inhalation Toxicity Study - Rats

EXECUTIVE SUMMARY: In a subchronic (13-week) toxicity study (MRID
00146461)  Fischer 344 rats (10 sex/group) were exposed to
concentrations of Telone II at 0, 10, 30, 90 or 150 ppm, 6 hours/day, 5
days/week for 13 weeks. Both sexes of rats at 90 and 150 ppm exhibited a
significant decreases in body weights while rats at 30, 60 and 150 ppm
exhibited treatment-related histopathological lesions in the nasal
turbinates.  The NOAEL was 10 ppm (0.045 mg/L) and the LOAEL was 30 ppm
(0.136 mg/L), based on histopathological lesions in the nasal
turbinates.

Long-term Inhalation Exposure

Critical Study: Chronic toxicity/carcinogenicity study - Mice

EXECUTIVE SUMMARY:  In a chronic toxicity/carcinogenicity study (MRID 
40312301), B6C3F1 mice (50/sex/group plus 10/sex/group to 6- and
12-month exposure groups) were exposed by whole-body inhalation to
Telone II (92.1%) at aerosol concentrations of 0, 5, 20 or 60 ppm
(equivalent to approximately 0, 0.023, 0.091 or 0.272 mg/L) 6 hours/day,
5 days/week for a total of 510 days over a two-year period.  There was
no effect on survival (at least 80% in each group).  There was a
statistically significant decrease in body weight gain in 60 ppm males
(3-9%) and females (2-11%).  Urinary bladder effects were noted
primarily in females at 20 and 60 ppm (slight, moderate or marked
roughened, irregular and opaque surfaces were reported in 20/50 at 20
ppm and 30/49 at 60 ppm compared with 3/50 slight in the control group).
 Hypertrophy and hyperplasia of the nasal respiratory mucosa (very
slight/slight) were observed in most 60 ppm mice of both sexes and in 20
ppm females.  Degeneration of olfactory epithelium (very slight/slight)
was noted in most 60 ppm mice of both sexes.  Hyperplasia of the
epithelial lining of the nonglandular portion of the stomach was
observed in 60 ppm males (0, 5, 20 and 60 ppm: males = 0, 3, 1 and 8;
females = 0, 0, 0 and 2).  For chronic toxicity, the NOEL was 5 ppm
(0.023 mg/L) and the LOEL was 20 ppm (0.091 mg/L) based on urinary
bladder hyperplasia and hypertrophy/hyperplasia of the nasal respiratory
mucosa.  Hyperplasia of the epithelial lining of the nonglandular
portion of the stomach was observed in a higher incidence compared with
controls in 60 ppm males and, to a lesser extent, 60 ppm females.  There
was evidence of carcinogenicity.  Bronchioloalveolar adenomas appeared
in a higher incidence in 60 ppm males only compared with controls (0, 5,
20 and 60 ppm = 9/50, 6/50, 13/50 and 22/50).  Although the lung tumors
noted in the mouse inhalation study were benign, tumor induction was
dose dependent, tumor incidence was outside the range of historical
controls and the tumor type was also seen in the mouse oral bioassay.

Discussion of Tumor Data: Telone II was associated with a significant
positive dose related trend in lung bronchioloalveolar adenomas (benign
tumors) in male mice.  A pair-wise comparison at the top dose, 60 ppm,
showed a significant increase of bronchioloalveolar adenomas from
control (22/60 of animals at risk (37%) versus control of 9/57 of
animals at risk (16%)).  Historical control data from seven studies
indicated a control range of 7-32% for lung bronchioloalveolar adenoma;
this included a 20% control incidence from another 2 year inhalation
study.  The incidence of lung tumors in male mice in this study was
outside the historical range.  While there were some increases in the
incidences of other tumor types (benign lacrimal gland tumors in males
and mesenteric lymph node lymphosarcomas in females), these were not
considered convincing by the Peer Review Committee to be of great
concern (Memo from Kerry Dearfield to Herman Toma, Second Peer Review of
Telone II, dated December 8, 1989).  The only agreed upon tumor of
concern was the increase in lung tumors in male mice after inhalation
exposure.  It was noted that female mice in the NTP study also had a
dose related increase in lung tumors after an oral exposure.

Chronic Oral Exposure

Critical Study:  Combined Chronic Toxicity/Carcinogenicity Study in Rats

EXECUTIVE SUMMARY:  In a chronic toxicity/carcinogenicity study (MRID
43763501), Telone II (96% a.i.) was administered as microcapsules by
dietary admix to Fischer 344 rats (60/sex/group with 10/sex/group
sacrificed at 12 months) at levels of 0, 2.5, 12.5 or 25 mg/kg/day for
two years. Body weight gains were decreased for males (8 and 21%) and
females (15 and 25%) at 12.5 and 25 mg/kg/day compared to controls. Food
consumption was decreased in females at 25 mg/kg/day. There was an
increase in liver masses/nodules in males only at 12.5 and 25 mg/kg/day.
There was an increased incidence of basal cell hyperplasia of the
nonglandular mucosa of the stomach of both sexes at the 12- and 24-month
sacrifices at 12.5 and 25 mg/kg/day. For chronic toxicity, the NOEL was
2.5 mg/kg/day and the LOEL was 12.5 mg/kg/day based on a decrease in
body weight gain compared with controls and an increase in the incidence
of basal cell hyperplasia of the nonglandular mucosa of the stomach.
There was evidence of carcinogenicity. The incidences of rats with
primary hepatocellular adenomas were as follows respectively (0, 2.5,
12.5 or 25 mg/kg/day): males = 2/50, 1/50, 6/50 and 9/50; females =
0/50, 0/50, 0/50 and 4/50. These data indicate that exposure to Telone
II increases the incidence of these tumors in males at the two highest
doses and in females at the highest dose. The highest dose tested in
this study (25 mg/kg/day) was considered adequate to assess the
carcinogenic potential of 1,3-D in rats.

Discussion of Tumor Data:  The incidences of rats with primary
hepatocellular adenomas were as follows respectively (0, 2.5, 12.5 or 25
mg/kg/day): males = 2/50, 1/50, 6/50 and 9/50; females = 0/50, 0/50,
0/50 and 4/50. These data indicate that exposure to Telone II increases
the incidence of these tumors in males at the two highest doses and in
females at the highest dose.

EXECUTIVE SUMMARY: In a study reported by the National Toxicology
Program (NTP) in 1985 (MRID 0014669), 1,3-D (89.0% a.i.) was
administered in corn oil (with 1.0% epichlorohydrin as a stabilizer)  by
gavage to Fischer 344 rats (52/sex/group) at doses of 0, 25 or 50
mg/kg/day three times per week for 104 weeks.  A total of 77 rats per
sex was used for each dose group, including those sacrificed for
examination during the course of testing.  Basal cell or epithelial
hyperplasia of the forestomach was reported.  The NTP concluded that
there was “clear evidence of carcinogenicity” for males and “some
evidence of  carcinogenicity” for females.  

Discussion of Tumor Data:  Statistically significant increases in the
incidence of the following tumors were observed in the highest dose
tested (HDT) by pairwise comparison with controls: 

1) forestomach squamous cell papillomas in males and females;

2) combined forestomach squamous cell papillomas and carcinomas combined
in males; and

3) liver neoplastic nodules in males and combined neoplastic nodules and
hepatocellular carcinomas in males.

The increased incidence of forestomach tumors was accompanied by a
statistically significant positive trend for forestomach basal cell
hyperplasia in male and female rats of both treatment groups (25 and 50
mg/kg).  There were also positive trends for other tumors in rats (i.e.,
in females, mammary gland adenomas or fibromas and thyroid gland
follicular cell adenomas or carcinomas; in males, adrenal gland
pheochromocytomas).  The highest dose tested in rats (50 mg/kg) appeared
to be adequate for carcinogenicity testing.    

	 In 1992, the registrant conducted a second feeding study using
timed-released (microencapsulated) doses of 1,3-D in food since the
stomach tumors seen in the NTP study coincided with the area where the
feeding tube was inserted.  In addition, the NTP study results may have
been confounded by the presence of a stabilizer, epichlorohydrin, which
is a known carcinogen.   

	In a chronic toxicity/carcinogenicity study (MRID No. 43763501), Telone
II (96% a.i.) was administered as microcapsules by dietary admix to
Fischer 344 rats (60/sex/group with 10/sex/group sacrificed at 12
months) at levels of 0, 2.5, 12.5 or 25 mg/kg/day for two years.  

	Body weight gains were decreased for males (8 and 21%) and females (15
and 25%) ar 12.5 and 25 mg/kg/day compared to controls.  Food
consumption was decreased in females at 25 mg/kg/day.  There was an
increase in liver masses /nodules in males only at 12.5 and 25
mg/kg/day.  There was an increased incidence of basal cell hyperplasia
of the nonglandular mucosa of the stomach of both sexes at the 12- and
24-month sacrifices at 12.5 and 25 mg/kg/day.  For chronic toxicity, the
NOAEL was 2.5 mg/kg/day and the LOAEL was 12.5 mg/kg/day based on a
decrease in body weight gain compared with controls and an increase in
the incidence of basal cell hyperplasia of the nonglandular mucosa of
the stomach.  There was evidence of carcinogenicity.  

Discussion of Tumor Data:  The incidences of rats with primary
hepatocellular adenomas were as follows respectively (0, 2.5, 12.5 or 25
mg/kg/day): males = 2/50, 1/50, 6/50 and 9/50; females = 0/50, 0/50,
0/50 and 4/50.  These data indicate that exposure to 1,3-D increases the
incidence of these tumors in males at the two highest doses and in
females at the highest dose.  The highest dose tested in this study (25
mg/kg/day) was considered adequate to assess the carcinogenic potential
of 1,3-D in rats.  

Critical Study: Combined Chronic Toxicity/Carcinogenicity Study in Mice

EXECUTIVE SUMMARY: In a study with B6C3F1 mice (50/sex/group) reported
by the NTP in 1985 (MAID 00146469), Telone II (89.0 % a.i.) was
administered in corn oil (with 1.0% epichlorohydrin)  by gavage at doses
of 0, 25 or 50 mg/kg/day three times per week for 104 weeks.  The study
in males was not considered to be adequate because of the mortality of
controls at weeks 48-51(25/50, myocarditis) and the 104-week survival
for males (8/50, 28/50 and 31/50).  Squamous cell papillomas of the
forestomach (0/50, 1/50 and 2/50 for females), squamous cell carcinomas
of the forestomach (0/50, 0/50 and 2/50 for females), transitional cell
carcinomas of the urinary bladder 0/50, 8/50 and 21/48 for females) and
alveolar/bronchiolar adenomas (0/50, 3/50 and 8/50 for females) were
seen.  In males, the study was considered to be inadequate for
carcinogenicity (due to mortality of controls).  For females, there was
clear evidence of carcinogenicity”. 

Discussion of Tumor Data:   A statistically elevated incidence of the
following tumors was observed at either HDT or a both dose levels:

 

1) forestomach squamous cell papillomas or papillomas and carcinomas
combined in males and females, and squamous cell carcinomas in females;

2) urinary bladder transitional cell carcinomas in males and females;

3) lung adenomas or adenomas and carcinomas combined in males and
females.

	Several deficiencies were noted in the mouse study, including excessive
mortality in control males and inadequate randomization procedures at
the study initiation.  The highest dose tested appears to have been
excessive.  While this study was not used for quantitatively estimating
1,3-D’s carcinogenic potential, the Agency has included the stomach,
bladder and lung effects in its weight-of-the-evidence findings.  



Toxicity Profile

Guideline No./ Study Type	MRID No./ Classification /Doses	Results

Subchronic Toxicity Studies*

870.3100

90-Day oral toxicity rodents

[Fischer 344 rats]	42954802 

Acceptable/guideline

0, 5, 15, 50 or 100mg/kg/day in diet

	NOAEL = 5 mg/kg/day 

LOAEL = 15 mg/kg/day based on hyperkeratosis and/ or basal cell
hyperplasia in the non-glandular portion of the stomach (both sexes) 

870.3100

90-Day oral toxicity rodents

[B6C3F1 mice] 	42954801 

Acceptable/guideline 0,15, 50, 100 or 175 mg/kg/day in diet

	NOAEL = 15 mg/kg/day

LOAEL = 50 mg/kg/day based on decreased body weights and body weight
gain (both sexes)

870.3100

90-Day oral toxicity nonrodent 

	See 870.4100b, below

	870.3465

30-Day inhalation toxicity rodent [Fischer 344 rats]	00039685 

Acceptable/guideline 

0, 3, 10 or 30 ppm (0, 0.0136, 0.045 or 0.136 mg/L) 6 hours/day, 5
days/week 	NOAEL = 30 ppm (0.136 mg/L), highest dose tested 

LOAEL = >30 ppm

870.3465

30-Day inhalation toxicity rodent [CD-1 mice] 	00039685 

Acceptable/guideline 

0, 3, 10 or 30 ppm (0, 0.0136, 0.045 or 0.136 mg/L) 6 hours/day, 5
days/week 	NOAEL = 30 ppm (0.045 mg/L), highest dose tested 

LOAEL = >30 ppm (0.136 mg/L)

870.3465

90-Day inhalation toxicity rodent [Fischer 344 rats] 	00146461 

Acceptable/guideline 

0, 10, 30, 90 or 150  ppm (0, 0.045,  0.136, 0.408,or 0.680 mg/L) 6
hours/day, 5 days/week 	NOAEL = 10 ppm (0.045 mg/L)

LOAEL =  30 ppm (0.136 mg/L) based on histopathological lesions in the
nasal turbinates 

870.3465

30-Day inhalation toxicity rodent [B6C3F1 mice]	00146461 

Acceptable/guideline 

0, 10, 30, 90 or 150  ppm (0, 0.045,  0.136, 0.408,or 0.680 mg/L) 6
hours/day, 5 days/week	NOAEL = 10 ppm (0.045 mg/L)

LOAEL =  30 ppm (0.136 mg/L) based on histopathological lesions in the
nasal turbinates



Developmental and Reproductive Toxicity Studies*

870.3700a

Prenatal developmental in rodents

[Fischer 344  rats]	00144715, 00152848 

Acceptable/guideline 

0, 20, 60 or 120  ppm (0, 0.091,  0.272 or 0.545 mg/L) by inhalation 6
hours/day during gestation days 6 through 15	Maternal NOAEL = <20 ppm
(0.091 mg/L) LOAEL = 20 ppm (0.091 mg/L) based on decreased body weight
gain and food consumption

Developmental NOAEL <120 ppm (0545 mg/L), highest concentration tested 

LOAEL =120 ppm (0545 mg/L) based on increased delay in ossification of
the vertebral centra

870.3700b

Prenatal developmental in nonrodents

[New Zealand White Rabbit]	00144715, 00152848 

Acceptable/guideline 

0, 20, 60 or 120  ppm (0, 0.091,  0.272 or 0.545 mg/L) by inhalation 6
hours/day during gestation days 6 through 18	Maternal NOAEL = 20 ppm
(0.091 mg/L) LOAEL = 60 ppm (0.272 mg/L) based on decreased body weight
gain

Developmental NOAEL 120 ppm (0545 mg/L), highest concentration tested 

LOAEL >120 ppm (0545 mg/L)

870.3800

Reproduction and fertility effects

[Fischer 344 rats]	40312401, 40835301

Acceptable/guideline

 0, 10, 30 or 90  ppm (0, 0.045, 0.136, or 0.408 mg/L) by inhalation 6
hours/day, 5 days/week 

  ♂♀ parents after weaning and continued for 12 weeks, 5 days/week
Parental/Systemic NOAEL = 30 ppm (0.136 mg/L)

 LOAEL = 90 ppm (0.408 mg/L) based on decreased body weight gain,
microscopic non-glandular stomach lesions and hyperplasia of the nasal
respiratory epithelium with focal degeneration of the olfactory tissue 

Reproductive NOAEL = 90 ppm (0.408 mg/L), highest concentration tested  

LOAEL >90 ppm (0.408 mg/L)

Offspring NOAEL = 90 ppm (0.408 mg/L), highest concentration tested  

LOAEL >90 ppm 



Chronic Toxicity Studies*

870.4100b

Chronic toxicity nonrodent

[Beagle dog]	42441001 

Acceptable/guideline

0, 0.5, 2.5 or 15 mg/kg/day microcapsules by dietary admix 	NOAEL = 2.5
mg/kg/day

LOAEL = 15 mg/kg/day  based on decreased body weight gain, microcytic
anemia, an increase in hematopoietic activity in both sexes and possible
increased liver weights in males 



870.4300

Combined Chronic Oral  Toxicity/Carcino-genicity for 2 year rat study 

[Fischer 344 rats]	43763501 

Acceptable/guideline

0, 2.5, 12.5 or 25 mg/kg/day microcapsules by dietary admix	Chronic
Toxicity NOAEL = 2.5 mg/kg/day

LOAEL = 12.5 mg/kg/day based on decreased body weight gain and an
increase in the incidence of basal cell hyperplasia of the non-glandular
mucosa of the stomach

Carcinogenicity:  Increased incidence of rats with primary
hepatocellular adenomas: 0, 2.5, 12.5 and 25 mg/kg/day = ♂ 2/50, 1/50,
6/50 and 9/50;  ♀ 0/50, 0/50, 0/50 and 4/50

870.4300

Combined Chronic Toxicity/Carcinogenicity (104 week)

[Fischer 344 rats]	00146469, NTP study

Acceptable/guideline 

0, 25 or 50 mg/kg/day by oral gavage 3 times/week for 104 weeks 	Chronic
Toxicity NOAEL = not established 

LOAEL = 25 mg/kg/day based on increased tumor incidence 

lomas of the forestomach: 0, 25 and 50 mg/kg/day = ♂ 1/52, 1/52  and
9/52;  ♀ 0/52, 2/52, 3/52.  Squamous cell carcinomas: ♂ 0/52, 0/52 
and 4/52.  Neoplastic nodules of the liver: ♂ 1/52, 6/52  and 7/52:
♀ 6/52, 6/52, 10/52. 

NTP concluded that there was “clear evidence of carcinogenicity” in
males and “some evidence” of carcinogenicity in females

870.4300

Combined Chronic Toxicity/Carcino-genicity (104 week)[B6C3F1 mice]
43757901 

Acceptable/guideline

0, 2.5, 25 or 50 mg/kg/day microcapsules by dietary admix	Chronic
toxicity NOAEL = 2.5 mg/kg/day

 LOAEL = 25 mg/kg/day based on lower body weights and decreased body
weight gain (both sexes)

Carcinogenicity: No evidence of carcinogenicity but study not adequate
for assessment due to several deficiencies in conduct.

870.4300

Combined Chronic Toxicity/Carcino-genicity (104 week)[B6C3F1 mice]
00146469, NTP study

Acceptable/guideline 

0,  25 or 50 mg/kg/day by oral gavage 3 times/week for 104 weeks 
Chronic Toxicity NOAEL = not established 

LOAEL = 25 mg/kg/day based on increased mortality in males 

nd 50 mg/kg/day = ♀ 0/50, 1/50, 2/50.  Squamous cell carcinomas of
thee forestomach:  ♀ 0/50, 0/50, 2/50. Transitional cell carcinomas of
the urinary bladder: ♀ 0/50, 8/50, 21/50.

Alveolar/bronchiolar adenomas: ♀ 0/50, 3/50, 8/50.

In ♂, study was inadequate for carcinogenicity.

NTP concluded that there was “clear evidence of carcinogenicity” in
females

870.4300

Combined Chronic Toxicity/Carcino-genicity (2 years) [Fischer 344 rats]
40312201  Acceptable/guideline

0, 5, 20  or 60  ppm (0, 0.023, 0.091 or 0.272 mg/L) by inhalation 6
hours/day, 5 days /week for 509 days  	Chronic Toxicity NOAEL = 20 ppm
(0.091 mg/L)

LOAEL = 60 ppm (0.272 mg/L) based on histopathological changes in nasal
tissue (males and females) and a suggestion of decreased body weight
gain (first year of the study only) 

 

There was no evidence of carcinogenicity



870.4300

Combined Chronic Toxicity/Carcino-genicity (2 years) [B6C3F1 mice]
40312301  Acceptable/guideline

0, 5, 20  or 60  ppm (0, 0.023, 0.091 or 0.272 mg/L) by inhalation 6
hours/day, 5 days /week for 510 days  	Chronic Toxicity NOAEL = 5 ppm
(0.023 mg/L)

LOAEL = 20 ppm (0.091 mg/L) based urinary bladder hyperplasia, and
hypertrophy/hyperplasia of the nasal respiratory mucosa

Carcinogenicity: Increased incidence of bronchioloalveolar adenomas: 0,
5, 20 or 60 ppm  = ♂ 9/50, 6/50, 13/50 or 22/50. Although the lung
tumors were benign, tumor induction was concentration dependent, the
tumor incidence was dose dependent, the tumor incidence was outside of
the historical controls, and the tumor type was seen in the mouse oral
bioassay.

Genotoxicity Studies

Gene Mutation

870.5300 

In vitro mammalian cell in culture gene mutation assay

Chinese hamster ovary (CHO) cells	47020332

Acceptable/guideline

50-250 µM -S9

 to cytotoxicity (≥200 µM -S9) or the highest dose tested +S9 

Gene Mutation

870.5300

Drosophila melanogaster sex-linked recessive lethal mutations 	00146469
(1985)

Acceptable/guideline

0, 5750 ppm/feeding	Positive: Induction of sex-linked recessive lethal
mutations but negative for the induction of reciprocal translocations at
 5750 ppm National Toxicology Program (NTP); Valencia et al., Environ
Mutagenesis 7:325-348.

Gene Mutation

870.5300

Host Mediated assay 	00039688 

Acceptable/guideline

0, 30, 60 mg/kg (oral gavage administration at 1, 2 & 3 hrs) 	Negative
up to the highest dose tested 

Cytogenetics 

870.5375

In vitro mammalian cytogenetics assay

CHO cells	NTP (1989)

Acceptable/Guideline

4.91-49.1 µg/mL -S9 (Trial 1)

 50-100 µg/mL -S9 (Trial 2)

10-50 µg/mL +S9 (Trial 1 only)	Negative up to concentrations causing
50% reduction in cell confluency (≥50 µg/mL ± S9)NTP: Loveday  et
al., Environ Mutagenesis 13:6–94.

Cytogenetics 

870.5395

In vivo mouse

micronucleus assay 	259101 (1985)

Acceptable/guideline

0, 38, 115, 380 mg/kg  	Negative up to a lethal dose (380 mg/kg)

Cytogenetics 

870.5450

Dominant Lethal Mutation in Sprague Dawley Rats 	44302801 (1997)

Acceptable/guideline

0-150 ppm, 7 da/wk, 10 wks (whole body inhation)	Negative up to the
LOAEL of 150 ppm, based on adverse effects on body weight.   

Other Effects 

870.5500

Bacterial DNA repair 

Bacillus subtilis H15 & M45	00039688 (1978)

Acceptable/guideline

50-1,250 µg/well	Positive: Preferential inhibition of the DNA repair
deficient strain at 1250 µg/well

Other Effects 

870.5550 

Unscheduled DNA Synthesis Primary rat hepatocytes	00146467(1985)

Acceptable/guideline

3x10-3 to 1x 10-6M	Negative up to a cytotoxic level (3 x 10-4 M)



Other Effects 

870.5900

In vitro sister chromatid exchange(SCE)

↑in SCE induction at 30-50  µg/mL -S9 & 10 -30 µg/mL +S9. These
levels were not cytotoxic.

METABOLITES OF 1,3-DICHLOROPROPENE

Gene Mutation

870.5100 

In vitro bacterial reverse gene mutation assay Salmonella  typhimurium
TA98, TA100, TA1535, TA1537

Escherichia coli WP2 (uvrA)	44940327 (1999) 3-Chloroacrylic acid

Acceptable/guideline

500 - 5000 µg/plate ±S9	Negative in independently performed
preincubation assays up to the limit concentration

Gene Mutation

870.5100 

In vitro bacterial reverse gene mutation assay Salmonella  typhimurium
TA98, TA100, TA1535, TA1537

Escherichia coli WP2 (uvrA)	44940326 (1999) 3-Chloroallyl alcohol

Acceptable/guideline

33.3 - 5000 µg/plate ±S9	Negative in independently performed
preincubation assays up to the limit concentration

Gene Mutation

870.5300 

In vitro mammalian cell in culture gene mutation assay

mouse lymphoma L5178Y	44940311 (1999) 3-Chloroallyl alcohol

Acceptable/guideline

Trial 1:12.5- 925 µg/mL -S9; 1.5-100 µg/mL +S9

↑ MF at 400 and 500  µg/mL -S9 & 75 and 100 µg/mL +S9: no difference
in the induction of small or large mutant colonies

Cytogenetics 

870.5395

In vivo mouse (CD-1) micronucleus assay	44940312 (1999) 3-Chloroacrylic
acid

Acceptable/guideline

62.5-250 mg/kg (♂)

62.5-200 mg/kg (♀)	Negative up to overtly toxic (death and/or
decreased activity) highest doses 

MECHANISM STUDIES

Gene Mutation

In vitro bacterial reverse gene mutation assay Salmonella  typhimurium
TA100  plus mouse lung homogenate	44460501 

Unacceptable               /non-guideline

100-450 µg/plate - metabolic activation;

̊C under N2) or +S9 because of low level microsomal/oxidative proteins
in the lung preparation 

Gene Mutation

In vivo with transgenic Big Blue B6C3F1 mice gene mutation assay target
gene (lacI) 	44470501 Unacceptable /non-guideline

0, 10, 60, 150 ppm (via whole body inhalation) 6 hrs/da, 5 da/wk, 2 wks
Negative in lung and liver tissue but test system uncertainties weaken
the understanding of the negative response. 

Other Mutagenic Effects  

In vitro DNA binding assays	44446301 Unacceptable /non-guideline

11 mM reacted w calf thymus DNA ± S9 (Aroclor 1254-induced rat liver)
± GSH	Inconclusive -S9; negative +S9 ± GSH but uncertainties regarding
use of optimum conditions 

Mechanism of Tumorigenicity

♂B6C3F1 mice & ♂ Fischer 344 rats	44446302 Unacceptable

/non-guideline

0, 5,12.5, 25, 100 mg/kg (oral gavage-rats) 3, 12 26 days

0, 10, 30, 60, 150 ppm (whole body inhalation- mice)  6 hrs/da, 5 da/wk,
2 wks	RATS:. No mortality or clinical signs  S ↓GSH at 25 & 100 mg/kg
(adaptive process) but liver tumors were seen in the 2-yr bioassay at
12.5 mg/kg.  No conclusion possible for apoptosis or cell proliferation
because of variability in data.  No conclusion possible for DNA adduct
formation because of variability in data & small sample size.

MICE:   No mortality or clinical signs.  Data show conjugation of 1,3-D
w GSH in lung tissue, no clear effect  on cell proliferation or
apoptosis in bronchiole epithelium or bladder transitional cells or DNA
adduct formation in lungs  but extreme variability and small sample size
compromised the findings.

Concerns regarding whether a biological effective dose was achieved. 

GSH Activity in Several Mammalian Cell Lines: ♂B6C3F1 mice & ♂
Fischer 344 rats primary rat hepatocytes, CHO cells, Chinese hamster
lung cells, Salmonella typhimurium 	44460503 Unacceptable

/non-guideline

GSH measurements in cell lines reacted with various substrates:
13C-1,3-D; 4-chloro-1,3-dinitrobenzene; para-nitro-phenylethylbromide;
trans-4-phenyl-3-buten-2-one	No conclusions relative to the correlation
between physiological levels of GSH and mitigation of  mutagenicity

Low level GSH activity with S. typhimuruim but conflicting results with
various mammalian cell lines (i.e.,  high & low level GSH activity with
cell lines producing negative mutagenicity data and high GSH activity
with 2 cell lines that were positive in standard mutagenicity assays)

Bioavailabity of Microencapsulated Telone II in Female Rats	44460502
Unacceptable

/non-guideline 

Phase I: 25 mg/kg 13C-1,3D coadministered w 25 mg/kg microencap-sulated
1,3-D sampled at 1,3,5,10,15, 20, 30,40,50,or 60 min.

Phase II:  25 or 50 mg/kg 13C-1,3D + microencap-sulated 1,3-D; 25 or 50
mg/kg 13C-1,3D + 7.5 or 15 mg/kg  microencap-sulated 1,3-D	No
conclusions because of unclear study design, technical deficiencies and
biased treatment of the data.

Initiation-Promotion: Mechanism of Mouse Lung Tumors

♂A/J mice	45897502B&D  Unacceptable

/non-guideline 

16 mg/kg vinyl carbamate(VC)  (initiator) ± 0, 60 ppm 1,3-D (whole body
inhalation 6 hrs/da, 5 da/wk, 25 wks) 	Lung adenomas in 1,3-D alone 26%
vs 10% in air control suggest initiating event. Lack of ↑total tumors
for VC-treated alone vs. VC + 1.3-D does not support a promoter role for
1,3-D 

Initiation-Promotion: Mechanism of Rat Liver Tumors  ♂ Fischer 344
rats	45897502C&D Unacceptable

/non-guideline 

100 mg/kg diethylnitrosamine (DEN, initiator) + 0, 25 mg/kg/da 1,3-D; 80
mg/kg phenobarbital (PB, promoter); or 5-10 mg/kg 2-acetylaminofluorene
(2-AAF, complete carcinogen)  	Data do not  support a promotional role
for 1,3-D.





  SEQ CHAPTER \h \r 1 Appendix B: Methodologies for Inhalation Risk
Calculations

1,3-Dichloropropene (Telone II) Array



  SEQ CHAPTER \h \r 1 METHODOLOGIES FOR INHALATION RISK CALCULATIONS

In evaluating the risks that a compound may pose to human health after
exposure via the inhalation route, different methodologies have been
historically used by the USEPA and the California Department of
Pesticide Regulation (CDPR).  The Agency’s approach to calculating
risks due to inhalation exposure is based on the 

guidance methodology developed by the Office of Research and Development
(ORD) for the derivation of inhalation reference concentrations (RfCs)
and human equivalent concentrations (HECs) for use in margin of exposure
(MOE) calculations (RfC methodology).   The two approaches differ in
their use of species-specific parameters to derive HECs.  Therefore, the
differences noted in the risk assessments of each organization are due,
in part, to their use of different methodologies and use of different
uncertainty factors (UFs).  The Agency’s approach to calculating risks
due to inhalation exposure is based on the guidance methodology
developed by the Office of Research and Development (ORD) for the
derivation of inhalation reference concentrations (RfCs) and human
equivalent concentrations (HECs) for use in margin of exposure (MOE)
calculations (RfC methodology).  An example of CDPR’s methodology, and
the species-specific parameters used in this approach can be found in
the CDPR website and their 1,3-D risk assessment, Appendix G at the
following web address:    HYPERLINK http://www.cdpr.ca.gov
www.cdpr.ca.gov/docs/dprdocs/methbrom/append_g.pdf .  As OPP understands
the importance to harmonize, to the extent possible, with other
regulatory agencies, this risk assessment will present HECs derived
using both methodologies.

The RfC methodology applies a dosimetric adjustment that takes into
consideration not only the differences in ventilation rate (MV) but also
the physicochemical properties of the inhaled compound, the type of
toxicity observed (e.g. systemic vs. port of entry) and the 
pharmacokinetic (PK) but not pharmacodynamic (PD) differences between
animals and humans.

Based on the RfC guidance (1994), the methodology for RfCs derivation is
an estimate of the quantitative dose-response assessment of chronic
non-cancer toxicity for individual inhaled chemicals and includes
dosimetric adjustment to account for the species-specific relationships
of exposure concentration to deposited/delivered dose. This adjustment
is influenced by the physicochemical properties of the inhaled compound
as well as the type of toxicity observed (e.g. systemic vs. port of
entry), and takes into consideration the PK differences between animals
and humans.  Though the RfC methodology was developed to estimate
toxicity of inhaled chemicals over a lifetime, it can be used for other
inhalation exposures (e.g. acute and short-term exposures) since the
dosimetric adjustment incorporates mechanistic determinants of
disposition that can be applied to shorter duration of exposures
provided the assumptions underlying the methodology are still valid. 
These assumptions, in turn, vary depending on the type of toxicity
observed and will be discussed later on in this document.  Thus the
derivation of a HEC for inhaled gases is described by the following
equation:

   ADVANCE \u 13 

Where:

PODstudy: Point of departure identified in the critical toxicology study

Danimal exposure: Duration of animal exposure (hrs/day; days/wk)

Danticipated exposure: Anticipated human duration of exposure (hrs/day;
days/wk)

RGDR: Regional Gas Dose Ratio

For gases eliciting both port of entry and systemic effects,
calculations to estimate  the inhalation risk to humans are dependent on
the regional gas dose ratio (RGDR).  In the case of systemic effects,
the RGDR is defined as the ratio of the blood:gas partition coefficient
of the chemical for the test species to humans (Hb/g animal/Hb/g human).
 When this ratio is unknown or when the Hb/g animal > Hb/g human a
default value of  1.0 is used as the RGDR.  This default is based on the
observation that for chemicals where partition coefficient data are
available in both rats and humans the RGDR value has usually been
comparable or slightly higher than 1.  Thus, the use of an RGDR of 1
results in a protective calculation of the inhalation risk.   Some of
the key assumptions fundamental to the use of the RfC methodology to
derive a HEC based on systemic effects include:

1) all the concentrations of inhaled gas within the animal’s body are
periodic with respect to time (i.e. periodic steady state - the
concentration vs time profile is the same for every week).  Periodicity
must be attained for at least 90% of the exposure.

2) in the respiratory tract, the air, tissue, capillary blood
concentration are in equilibrium with respect to each other.

3)systemically, the blood and tissue concentrations are in equilibrium
with respect to each other.

In the case of 1,3-Dichloropropene, the physicochemical properties and
metabolism data for the compound indicate that these conditions (i.e.
periodicity and equilibrium between different compartments) will be
achieved in a very short period of time.  Under these conditions,
therefore, the use of the RfC methodology to estimate acute inhalation
risk is appropriate.    

When the critical toxic effect in a study occurs in the respiratory
tract (i.e port of entry effects), the RGDR is not related to the
blood:gas partition coefficient of the compound but rather the ratio of
the minute volume (MV) to the surface area (SA) of the affected region. 
In these instances, attaining periodicity or equilibrium between the
compartments is not critical (since the effect is a function of the
direct interaction between the inhaled compound and the affected region
in the respiratory tract) and the RGDR may be calculated using the
following equation:

   ADVANCE \u 19 

Where:

MV animal: Minute volume for the test species (varies depending on body
weight)

SA animal: Surface area of the affected region in animals

MV human: Minute volume for humans (default value is 13.8 l/min)

SA human: Surface area of the affected region in humans

The MV animal is calculated using the allometric scaling provided in
USEPA (1988a).  The equation for calculation of the MV animal is:

lnMV animal = b0 + b1ln(BW)

Where:

ln MV animal : natural logarithm of the minute volume

b0 : species specific intercept used in the algorithm to calculate
minute volumes based on body weight

b1: species specific coefficient used in the algorithm to calculate
minute volumes based on body weight

ln BW: natural logarithm of the body weight (expressed in kg)

The values for the species-specific parameters used to calculate the MV
animal based on body weight and the values for the surface areas of
various regions of the respiratory tract (extrathoracic, thoracic, and
pulmonary) are provided in the EPA document “Methods for Derivation of
Inhalation Reference Concentrations and Application of Inhalation
Dosimetry” (1994).

The magnitude of the UFs applied is dependent on the methodology used to
calculate risk.  When using the methodology developed by CDPR, a 100X UF
is applied (10X for interspecies extrapolation and 10X for intraspecies
variation).  In contrast, the RfC methodology takes into consideration
the PK differences but not the PD differences.  Consequently, the UF for
interspecies extrapolation may be reduced to 3X (to account for the PD
differences) while the UF for intraspecies variation is retained at 10X.
 Thus, the UF when using the RfC methodology is customarily 30X.

The HED Arrays for 1,3-D may be found on the following pages.

¶ Bolded studies used for endpoint selection

‡ 3X UF for LOAEL to NOAEL extrapolation is being recommended due to
the mild nature of effects (decreased body weight) noted at the LOAEL

* Input parameters for the derivation of RGDRs were obtained from
“Methods for Derivation of Inhalation Reference Concentrations and
Application of Inhalation Dosimetry” (USEPA, 1994) Tables 4-4, 4-5,
and 4-6.

Key for Array Table

LOAEL: Lowest observed adverse effect level

NOAEL: No observed adverse effect level

Da: Daily animal exposure (hrs/day)

Dh: Anticipated daily human exposure (hrs/day)

Wa: Weekly animal exposure (days/week)

Wh: Anticipated weekly human exposure (days/week)

RGDR: Regional Gas Dose Ratio

HEC: Human Equivalent Concentration

inter: interspecies extrapolation uncertainty factor

intra: intraspecies variation uncertainty factor

UF: Other uncertainty factor(s)



¶ Bolded studies used for endpoint selection

‡ 3X UF for LOAEL to NOAEL extrapolation is being recommended due to
the mild nature of effects (decreased body weight) noted at the LOAEL

§ Offspring were not directly exposed to the compound

* Input parameters for the derivation of RGDRs were obtained from
“Methods for Derivation of Inhalation Reference Concentrations and
Application of Inhalation Dosimetry” (USEPA, 1994) Tables 4-4, 4-5,
and 4-6.

Key for Array Table

LOAEL: Lowest observed adverse effect level

NOAEL: No observed adverse effect level

Da: Daily animal exposure (hrs/day)

Dh: Anticipated daily human exposure (hrs/day)

Wa: Weekly animal exposure (days/week)

Wh: Anticipated weekly human exposure (days/week)

RGDR: Regional Gas Dose Ratio

HEC: Human Equivalent Concentration

inter: interspecies extrapolation uncertainty factor

intra: intraspecies variation uncertainty factor

UF: Other uncertainty factor(s)

Appendix C:  Summary Of Cordon® PERFUM Buffer Distributions Based On
Ventura California Weather And Data for Post-plant Drip Irrigation Use
in Vineyards Data



	

\Appendix D:  Summary Of 1,3-D Bystander Exposure from Known Area
Sources Estimated Using the Monitoring Method

Summary of Bystander Exposure from Known Area Sources Estimated Using
the Monitoring Method

When assessing bystander exposure to 1,3-D, HED evaluated pre-plant
agricultural field fumigations; post-plant drip irrigation fumigations
and turf fumigations.

The use of the field volatility data in this assessment is based on the
previous bystander exposure review of 1,3-D.  Details of study quality
and data analysis can be found in the following memo; REVISED
Post-application Non-occupational Bystander Risk Estimates for Proposed
Label Change from 300 to 100 foot Buffer Zone for Telone II, Telone
C-17, and Telone C-35, S.Weiss, D284547, 11/1/02).

In summary, twenty studies, with field volatility data collected near
1,3-D treated fields, have been submitted to the Agency since 1989. 
Some of the studies (MRID#s 426973-01, 427742-01, 428456-01) reflect
application methods that are no longer used, and therefore are not
included in this assessment.  Eleven of the studies are used to estimate
risk for bystander exposure from the broadcast and row uses of 1,3-D.   
Several studies (MRID#s 447956-02, 451129-02, 452961-01) are used to
estimate use drip application methods.  Bystander inhalation exposure
estimates for the turf uses of 1,3-D are based on air concentration
measurements reported in field volatility studies, MRID 451207-01 and
451207-02. One field volatility study is available to address off-site
exposure resulting from the post-plant use.  Bystander inhalation
exposure estimates are based on air concentration measurements reported
in this study, (MRID 452961-01).  Study descriptions are available in
Appendix A of Memo, S.Weiss, D284548, 11/1/02.  	

Generally, HED calculates non-cancer risks (i.e. acute, short-,
intermediate-term, and chronic exposure) using maximum label application
rates and cancer risks using “typical” rates.  The registrant
suggests that the field volatility study were conducted at typical
rates(from 96 to 224 lb ai/A).   BEAD states these rates would be
typical for all crops except for tree/vine crops and pineapples. Since
these two crops only accounted for about 9 percent of the total pounds
of 1,3-D applied , the rates in the field volatility studies cover the
majority of current uses.   However, HED risk estimates must reflect the
entire range of potential exposures, including those at the high end of
the exposure distribution.   Therefore, when appropriate, risk
calculations are adjusted to account for the maximum label application
rate (linear extrapolation) and risks are calculated for both the
typical and maximum rates.  Cancer risk is calculated based on typical
rates only.

	

Acute MOEs are calculated by comparing the maximum 24 hour time-weighed
average (TWA) from each field volatility study to the toxicological
human equivalent concentration (HEC) selected for acute risk assessment.
 

Consistent with the most recent review of bystander exposure (Memo,
S.Weiss, D284548, 11/1/02), the consecutive seven day average air
concentration were also estimated from each field volatility study.  The
highest average seven day average each direction is compared to the
selected HEC to estimate short-term risk for bystanders.  

This is consistent with the pattern of toxicity observed in short-term
guideline toxicity studies.  In the study used for the short-term risk
assessment - the developmental toxicity study in rabbits - the endpoint
of concern is a decrease in body weight gain.  This effect was not
observed until several days after exposure began suggesting that a
multiple-day rolling average is appropriate to assess risks. 

In the field volatility studies, 1,3-D peak offgassing occurs 1 to 3
days after application. Additionally since 1, 3-D products are used only
1 to 2 times per field each year, the majority of bystander exposure
resulting directly from treatment of agricultural fields is expected to
be  acute or short-term.  Intermediate-term exposure (consecutive
exposures lasting 30 days to several months) is expected to be less
likely.  Chronic exposure is not expected since it unlikely that
bystanders will be continually exposed to significant concentrations of
1,3-D for 6 consecutive months or longer. 

Cancer risks are calculated using  the average air concentration for all
locations (extrapolated from each field volatility study). It is assumed
that the number of days of exposure per year is equal to the number of
days that samples were taken in each study (i.e. 7 to 21 days).  Since 
inter-year and seasonal variability in wind direction will prevent any
single location from being predominately down wind, using the average
air concentration of all directions is appropriate to assess cancer risk
resulting from a lifetime of exposure. 

None of the acute or short-term risks exceed HED’s LOC.  Using the
average air concentrations, several of the estimated cancer risks exceed
HED’s LOC for cancer for the existing pre plant uses (generally 1 x
10-6).   Since a particular field is not likely to be treated more than
once or twice each year, and a bystander is not likely to be present
downwind of the field during this entire period, every year for 50
years, after every application, this assessment is expected to provide
an upper-end estimate of cancer risk.  Bystander exposure resulting from
the agricultural and golf course uses of 1,3-D are summarized in Tables
E1 through E3.

Table E1.  Acute Non-Cancer Risk for Bystander Exposures Based on Field
Volatility Data	Maximum 24 hr TWA Air Concentration 

	

Acute MOE1

	

Study Location/	

MRID#	

Formulation	Application  Rate









study

(g/A)	

label max

(g/A)



#





Distance

(m)	study

(ppm)	label max

(ppm)











study	label max

Broadcast Applications

2	Imperial Valley, CA; 1989	422657-01	Telone II	12.1	35	30	0.008	0.022
9800	3400

3	Salinas Valley, CA; 1992	425451-01	Telone II	12.3	35	30	0.009	0.027
8100	2800

16	Collier County, FL; 1999	451207-02	Telone II	5.12	35	30	0.018	0.125
4100	610

17	Highlands County, FL; 1998	451207-01	Telone II	5.19	35	30	0.070	0.469
1100	160

18	Waushara County, WI; 2001	454002-03	Telone II	26.8	35	61	0.015	0.020
4900	3800

16	Collier County, FL; 1999	451207-02	Telone II	5.12	35	61	0.010	0.070
7400	1100

17	Highlands County, FL; 1998	451207-01	Telone II	5.19	35	61	0.018	0.124
4100	610

Row Applications

7	San Joaquin Valley, CA; 1995	 442585-01	Telone II	12.6	35	30	0.016
0.097	4800	780

19	Immokalee, FL; 2001	454002-02	Telone II	28.40	35	30	0.041	0.050	1900
1500

19	Naples, FL; 2001	454002-02	Telone II	25.30	35	30	0.138	0.191	550	400

6	Moses Lake, WA; 1992	 NR424663-01	Telone II	*	*	91	0.191	--	400	--

Drip Irrigation Application

8	Rio Grande Valley, TX 1998	447956-02	Telone EC	8.65	18	30	0.054	0.112
1400	670

15	Douglas, GA; 2000	451129-02	In-Line	24.6	20.5	30	0.047	0.039	1600
1900

8	Rio Grande Valley, TX 1998	447956-02	Telone EC	8.65	18	91	0.021	0.044
3600	1700

15	Douglas, GA; 2000	451129-02	In-Line	24.6	20.5	91	0.019	0.016	3900
4700

20	Gilroy, CA, 1998 (post-plant)	 452961-01	Telone II	5.4	17.74	91	0.001
--	54000	--

1  Acute MOE = HEC (75.67 ppm)/maximum 24 hour TWA



Table E2.  Short-Term 1,3-D Risk for Bystander Exposures Based on Field
Volatility Data



	Application Rate	Highest 7-day Air

concentration	Short-term MOE1



#	Study Location/	MRID#	Formulation

	Distance

(m)	study

(g/A)	Label max

(g/A)	study

(ppm)	label max

(ppm)











study	label max

Broadcast Applications 

2	Imperial Valley, CA; 1989	422657-01	Telone II	30	12.1	35	0.006	0.017
870	300

3	Salinas Valley, CA; 1992	425451-01	Telone II	30	12.3	35	0.004	0.011
1300	470

16	Collier County, FL; 1999	451207-02	Telone II	30	5.12	35	0.003	0.018
1900	270

17	Highlands County, FL; 1998	451207-01	Telone II	30	5.19	35	0.013	0.085
400	60

18	Waushara County, WI; 2001	454002-03	Telone II	61	26.8	35	0.008	0.010
640	490

16	Collier County, FL; 1999	451207-02	Telone II	91	5.12	35	0.0003	0.002
14000	2100

17	Highlands County, FL; 1998	451207-01	Telone II	91	5.19	35	0.006	0.039
870	130

Row Applications

7	San Joaquin Valley, CA; 1995	 442585-01	Telone II	30	12.6	35	0.006
0.034	900	150

19	Immokalee, FL; 2001	454002-02	Telone II	30	28.40	35	0.024	0.029	210
170

19	Naples, FL; 2001	454002-02	Telone II	30	25.30	35	0.058	0.080	90	60

6	Moses Lake, WA; 1992	NR424663-01	Telone II	91	*	*	0.078	–	60

	

Drip Irrigation Applications

	Rio Grande Valley, TX 1998	447956-02	Telone EC	30	8.65	18	0.012	0.025
420	200

15	Douglas, GA; 2000	451129-02	In-Line	30	24.6	20.5	0.015	0.012	330	400

8	Rio Grande Valley, TX 1998	447956-02	Telone EC	91	8.65	18	0.005	0.011
980	470

15	Douglas, GA; 2000	451129-02	In-Line	91	24.6	20.5	0.006	0.005	900	1100

20	Gilroy, CA, 1998 (post-plant)	 452961-01	Telone II	91	5.4	17.74
0.0003

16000

	1 Short-term MOE = HEC(5.0 for short-term)/highest 7 day air
concentration.



Appendix E:  Model Information and History

Industrial Source Complex 3 (ISC3)

ISC3 (http://www.epa.gov/scram001/dispersion_alt.htm) was developed by
the U.S. Environmental Protection Agency (EPA) as a replacement for
ISC2.  ISC3 is a steady-state Gaussian plume model which can be used to
assess pollutant concentrations from a wide variety of sources including
point and area sources.  ISC3 operates in both long-term and short-term
modes.  OPP has operated the model in short-term mode in its fumigant
assessments and used the designation ISCST3.  ISCST3 allows for three
different types of outputs: (1) summaries of high values (highest,
second highest, etc.) by receptor for each averaging period and source
group combination, (2) summaries of overall maximum values (e.g., the
maximum 50) for each averaging period and source group combination, and
(3) tables of concurrent values summarized by receptor for each
averaging period and source group combination for each day of data
processed. The third output option was used when OPP ran the ISCST3
model.  These outputs can be produced all the way down to an hourly
basis.

Up until the end of 2005, ISC3 was the Agency's recommended air
dispersion model for steady state sources.  It should be noted that ISC3
can still be used as an alternative to the recommended models in
Appendix W in regulatory applications with case-by-case justification
(see Appendix W to 40 CFR Part 51, Section 3.2).

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e of the main weaknesses of ISCST3 is in its treatment of calm periods. 
A calm period in ISCST3 is when the wind speed is less than 1.0 m/s. 
When this occurs, ISCST3 assumes that there is no wind blowing and
assigns a wind speed of 0.0 m/s and this can result in a
misrepresentation of the fumigant plume.  For the Agency's fumigant
assessments, ISCST3 was run using the "regulatory option" for addressing
calm periods.  

American Meteorological Society/Environmental Protection Agency
Regulatory Model (AERMOD)

AERMOD (http://www.epa.gov/scram001/dispersion_prefrec.htm#aermod) was
developed by American Meteorological Society (AMS) and the U.S.
Environmental Protection Agency (EPA).  ISC was replaced by AERMOD as
the preferred air dispersion model for near-field, steady state sources
in the Agency's Guidelines on Air Quality Models as of December 9, 2005.
 AERMOD is a Gaussian plume model which can be used to assess pollutant
concentrations from a wide variety of sources including point and area
sources.  AERMOD incorporates air dispersion based on planetary boundary
layer turbulence structure and scaling concepts, including treatment of
both surface and elevated sources, and both simple and complex terrain. 
The AERMOD modeling system consists of two pre-processors and the
dispersion model.  The meteorological preprocessor AERMET, uses
meteorological data and surface characteristics to calculate boundary
layer parameters (e.g. mixing height, friction velocity, etc.) needed to
run AERMOD.  The terrain pre-processor AERMAP both characterizes the
terrain and generates receptor grids for AERMOD.  AERMOD allows for
three different types of outputs: (1) summaries of high values (highest,
second highest, etc.) by receptor for each averaging period and source
group combination, (2) summaries of overall maximum values (e.g., the
maximum 50) for each averaging period and source group combination, and
(3) tables of concurrent values summarized by receptor for each
averaging period and source group combination for each day of data
processed.  These outputs can be produced all the way down to an hourly
basis.

As the replacement to ISC3, AERMOD currently contains new or improved
algorithms for: 1) dispersion in both the convective and stable boundary
layers; 2) plume rise and buoyancy; 3) plume penetration into elevated
inversions; 4) computation of vertical profiles of wind, turbulence, and
temperature; 5) the urban nighttime boundary layer; 6) the treatment of
receptors on all types of terrain from the surface up to and above the
plume height; 7) the treatment of building wake effects; 8) an improved
approach for characterizing the fundamental boundary layer parameters;
and 9) the treatment of plume meander.  Many of these improvements have
little to no effect on OPP's approach to modeling fumigant applications
as area sources.

AERMOD allows for the conservative assessment of concentrations of
fumigants coming off of treated fields under specific meteorological and
application conditions.  However, AERMOD has a similar weakness to ISC3
in its treatment of calm periods.  A calm period in AERMOD is when the
wind speed is less than 1.0 m/s.  When this occurs, AERMOD assumes that
there is no wind blowing and assigns a wind speed of 0.0 m/s and this
can result in a misrepresentation of the fumigant plume.  Also, AERMOD
does not allow for the probabilistic treatment of variables such as the
meteorological conditions.

CALPUFF

CALPUFF (http://www.epa.gov/scram001/dispersion_prefrec.htm#calpuff) is
a non-steady-state meteorological and air quality modeling system
developed by the Atmospheric Studies Group at TRC Solutions.  It is
maintained by the model developers and distributed by TRC
(http://www.src.com/html/calpuff/calpuff1.htm).  CALPUFF v.5 has been
adopted by the Agency in its Guideline on Air Quality Models as the
preferred model for assessing long range transport of pollutants and on
a case-by-case basis for certain near-field applications involving
complex meteorological conditions (i.e., non-steady state).  The
modeling system consists of three main components and a set of
preprocessing and postprocessing programs.   The main components of the
modeling system are CALMET (a diagnostic 3-dimensional meteorological
model), CALPUFF (an air quality dispersion model), and CALPOST (a
postprocessing package).

The output files that CALPUFF creates for each run include unformatted
data files containing grids of time-averaged concentrations,
time-averaged dry deposition fluxes, and time-averaged wet deposition
fluxes.  These outputs in CALPUFF v.5 can be produced all the way down
to an hourly basis.  The post-processing program CALPOST is designed to
produce ranked tabulations of averages of selected concentration data
from these data files. CALPOST writes a text file containing the input
data summary and output tables.

Although CALPUFF v.5 is on the Agency's guideline for air models, there
is also currently a CALPUFF v.6 that has not yet been reviewed by the
Agency.  CALPUFF v.6 includes a number of technical enhancements over
v.5 but the major one that could have effects on OPP's modeling of
fumigant emissions is the option to use subhourly (i.e., 1 minute, 5
minute, etc.) meteorological data.

Probabilistic Exposure and Risk model for FUMigants (PERFUM)

PERFUM (http://www.exponent.com/practices/health/PERFUM.html) was
developed to address the issue of bystander exposures following
agricultural applications of fumigants.  The core of the PERFUM modeling
system is the US EPA dispersion model ISCST3 which at the time PERFUM
was developed was the Agency's recommended air dispersion model for
steady state sources.  ISCST3 as described above calculates
concentrations but is not designed to determine a buffer zone.  PERFUM
was designed to specifically take the ISCST3 outputs and use them to
produce buffer zone outputs in a distributional format.

PERFUM allows users to develop an understanding of the distributions of
potential bystander exposures and thus more fully characterize the range
of risks resulting to bystanders around treated fields.  ISCST3 is an
integral part of the PERFUM model and the basic physics and code of
ISCST3 remain unchanged.  PERFUM essentially provides ISCST3 with daily
meteorological data over 5 years as well as flux estimates within the
uncertainty of those data.  PERFUM then uses this information to create
distributional outputs for pre-defined receptor locations.

Fumigant Emissions Modeling System (FEMS)

FEMS (http://www.sullivan-environmental.com) was developed to address
the issue of bystander exposures following agricultural applications of
fumigants.  FEMS allows the user to define a number of options prior to
running the model including: the fumigant to be applied, the frequency
of fumigation, the sealing method employed, field size and shape,
consecutive day/contiguous field applications, application season, the
averaging time for the concentrations, and the dispersion model used
(ISCST3, CALPUFF v.5, or CALPUFF v.6).  FEMS also allows the user to
include Monte Carlo treatments of all the key model inputs like
meteorological conditions, emissions data, day the application starts,
etc.  

Once the core dispersion model is selected, FEMS simulates the
application of a fumigant and it's off-gassing over a 4 day simulation
using 4 hour time steps.  The model estimates fumigant concentrations at
various receptors beyond the perimeter of the applied field that are
matched to the averaging time of interest for the user.  Aside from
estimating the fumigant concentrations, FEMS keeps track of the number
of times that concentrations exceed the concentration of concern at each
receptor.

Once FEMS completes the modeling simulation, the distribution of
concentrations is computed for each receptor.  FEMS produces two main
outputs.  The first is a frequency distribution that looks at the number
of times that concentrations exceed the concentration of concern at each
receptor.  The second involves establishing the distributions of
concentrations for each receptor and then taking the maximum number of
periods per averaging time of interest above the concentration of
concern and computing them as a function of distance from the field. 
Buffer zones are then established based on the most conservative
concentrations that were modeled as a function of distance.

Soil Fumigant Exposure Assessment System (SOFEA)

SOFEA (http://www.epa.gov/oscpmont/sap/meetings/2004/index.htm) was
developed to evaluate and manage human inhalation exposure potential
associated with agricultural applications of fumigants.  SOFEA
calculates fumigant concentrations in air arising from volatility losses
from treated fields for entire agricultural regions using multiple
sources (treated fields), GIS information, agronomic specific variables,
user specified buffer zones and field intervals.  SOFEA uses a modified
version of ISCST3 as its dispersion model.   SOFEA also uses Monte Carlo
techniques to vary the following parameters: weather information, field
size, application date, application rate, application method, pesticide
degradation rates in air, sealing method, field re-treatment, and buffer
setbacks.

Multi-year, multiple field simulations can be conducted with SOFEA using
random field placement in all agricultural areas or by selectively
placing fields in historical or prospective use areas.  Regional land
use information can be used to refine the placement of treated fields,
dispersion calculations, and exposure assessments.  SOFEA has been
previously used for regulatory decision making in California.

Symphylans are small, many -legged soil dwelling
arthropods.഍ഃЍ഍ഃЍ഍഍慐敧ጠ倠䝁⁅㈔―景ጠ丠䵕䅐
䕇⁓㠔ᔴ഍慐敧ጠ倠䝁⁅ㄔ―景ጠ丠䵕䅐䕇⁓㠔ᔴ഍഍
慐敧ጠ倠䝁⁅㘔―景ጠ丠䵕䅐䕇⁓㠔ᔴ഍慐敧ጠ倠䝁⁅
㌔―景ጠ丠䵕䅐䕇⁓㠔ᔴ഍഍慐敧ጠ倠䝁⁅㘔―景ጠ丠
䵕䅐䕇⁓㠔ᔴ഍慐敧ጠ倠䝁⁅㜔―景ጠ丠䵕䅐䕇⁓㠔ᔴ
഍഍慐敧 漠⁦ጠ丠䵕䅐GES \* arabic \* MERGEFORMAT  84 

Page   PAGE  32  of   NUMPAGES  84 

 of    NUMPAGES \* arabic \* MERGEFORMAT  84 

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6ᔶ漠⁦–啎偍䝁卅ᐠ㐸ക഍倍条⁥ 景†–啎偍䝁卅
尠‪牡扡捩尠‪䕍䝒䙅剏䅍⁔㠔ᔴ഍倍条⁥–䅐䕇ᐠ〷
―景ጠ丠䵕䅐䕇⁓㠔ᔴ഍഍慐敧
漠⁦ጠ丠䵕䅐䕇⁓⩜愠慲楢⁣⩜䴠剅䕇但䵒呁ᐠ㐸ക഍
慐敧ጠ倠䝁⁅㜔ᔳ漠⁦–啎偍䝁卅ᐠ㐸ക഍倍条⁥ 景
†–啎偍䝁卅尠‪牡扡捩尠‪䕍䝒䙅剏䅍⁔㠔ᔴ഍倍条
⁥–䅐䕇ᐠ㘷―景ጠ丠䵕䅐䕇⁓㠔ᔴ഍഍慐敧
漠⁦ጠ丠䵕䅐䕇⁓⩜愠慲楢⁣⩜䴠剅䕇但䵒呁ᐠ㐸ക഍
慐敧ጠ倠䝁⁅㜔ᔹ漠⁦–啎偍䝁卅ᐠ㐸ക഍䐍䅒呆䤠呎
剅䅎⁌䕄䥌䕂䅒䥔䕖䄠䑎䌠乏䥆䕄呎䅉ൌ倍条⁥ 景†
–啎偍䝁卅尠‪牡扡捩尠‪䕍䝒䙅剏䅍⁔㠔ᔴ഍倍条⁥
–䅐䕇ᐠ㐸  of   NUMPAGES  84 

 

 

 

