Tribufos Summary Document

Registration Review: Initial Docket

March 2009

TABLE OF CONTENTS

Preliminary Work Plan (PWP)						  4

Fact Sheet										11

Glossary of Terms and Abbreviations					18

__________________________________________________________________

Support Documents

“Problem Formulation for Ecological Risk,      Species, and Drinking
Water Exposure Assessments in Support of the Registration Review of
Tribufos.”  December 10, 2008.

 “Tribufos:  Revised Human Health Assessment Scoping Document in
Support of Registration Review.”  February 20, 2009.

“Interim Reregistration Eligibility Decision for Tribufos.”
September 2000.  (Available from
http://www.epa.gov/pesticides/reregistration/REDs/tribufos_red.pdf)

“Risks of Tribufos Use to Federally Threatened California Red-legged
Frog.”  October 17, 2008.  (Available from   HYPERLINK
"http://www.epa.gov/espp/litstatus/effects/redleg-frog/tribufos/determin
ation.pdf" 
http://www.epa.gov/espp/litstatus/effects/redleg-frog/tribufos/determina
tion.pdf )

Screening Level Use Analysis (SLUA) for Tribufos.  June 5, 2008.

Appendix A for Tribufos.  July 1, 2008.

These and other supporting documents for tribufos may be found in the
docket EPA-HQ-OPP-2008-0883 at http://www.regulations.gov.I. 
Preliminary Work Plan – Tribufos

Introduction:

The Food Quality Protection Act of 1996 mandated a registration review
program.  All pesticides distributed or sold in the United States
generally must be registered by the Environmental Protection Agency
(EPA), based on scientific data showing that they will not cause
unreasonable risks to human health or the environment when used as
directed on product labeling.  The registration review program is
intended to make sure that, as the ability to assess risk evolves and as
policies and practices change, all registered pesticides continue to
meet the statutory standard of no unreasonable adverse effects to human
health or the environment.  Changes in science, public policy, and
pesticide use practices will occur over time.  Through the registration
review program, the Agency periodically reevaluates pesticides to make
sure that as change occurs, products in the marketplace can be used
safely.  Information on this program is provided at:
http://www.epa.gov/oppsrrd1/registration_review/. 

The Agency is implementing the registration review program pursuant to
FIFRA Section 3(g) and will review each registered pesticide every 15
years to determine whether it continues to meet the FIFRA standard for
registration.  Where assessments indicate risks above the Agency’s
level of concern (LOC), the Agency will consider benefits information
and data as required by FIFRA.  The public phase of registration review
begins when the initial docket is opened for each case.  The docket is
the Agency’s opportunity to state what it knows about the pesticide
and what additional risk analyses and data or information it believes
are needed to make a registration review decision.  After reviewing and
responding to comments and data received in the docket during this
initial comment period, the Agency will develop and commit to a final
work plan and schedule for the registration review of tribufos.  

Tribufos was the subject of a 2000 Interim Reregistration Eligibility
Decision (IRED), and in July 2006 the Reregistration Eligibility
Decision (RED) for tribufos was finalized upon completion of the
Organophosphorous (OP) Cumulative Risk Assessment.  Tribufos is an
organophosphate defoliant used on cotton crops.  There are no
residential or public recreational uses of tribufos.

Anticipated Risk Assessment and Data Needs:

The Agency anticipates updating and revising the ecological risk
assessment for tribufos (including an endangered species risk
assessment) and updating and revising the human health risk assessment. 
Additional data that the Agency anticipates needing to complete these
assessments are specified below.

Ecological Risk:

An ecological risk assessment (1996) and an updated drinking water
assessment (2000) were completed for the IRED (2000).  Eight ecological
studies were required during reregistration to address the data gaps. 
These data have been submitted; however, not all of the studies were
determined to be acceptable and additional data gaps have been
identified.

The environmental fate database for tribufos is currently complete with
two exceptions; an aerobic aquatic metabolism study is needed to
describe the fate of tribufos in surface water bodies, and an
octanol-air partition coefficient (KOA) study is also recommended in
order to describe the fate of tribufos in the atmosphere in support of
bioaccumulation modeling.  

While they will not be used for an exposure assessment, submission of
analytical methods in water and in sediment (and associated independent
laboratory validations) are       needed to support enforcement and
monitoring at the federal, state, and local levels.  The analytical
method in sediment data is needed, since tribufos is expected to
partition predominately to sediment in surface water bodies.  If data
are submitted indicating that the previously submitted analytical method
in soil is appropriate for measuring residues in sediment, then a
separate analytical method in sediment should not be necessary.  

In order to conduct a comprehensive risk assessment during registration
review, the following data are needed: avian acute oral toxicity
(passerine); terrestrial plant toxicity; and sediment toxicity for
invertebrates.  

Although acceptable acute avian oral toxicity data were submitted for
mallard duck and bobwhite quail, data are not available for a passerine
species.  The available acute oral toxicity data for mallard ducks and
bobwhite quails indicates that tribufos may be moderately toxic to birds
on an acute oral exposure basis, and there is evidence from other OPs
(e.g., dimethoate) that passerines are significantly more sensitive to
at least some OPs when compared to the upland and game bird species
tested. 

While acceptable Tier II terrestrial plant studies are available for
tribufos, the plant species studied (i.e., annual dicots and monocots)
are not expected to be as sensitive to tribufos as other plants (e.g.,
woody deciduous trees and shrubs) due to its mechanism of action. 
Available toxicity studies were conducted on plants that do not form
abscission zones, and data from these studies may underestimate the
potential toxicity of tribufos to non-target plants that do form
abscission zones.  Therefore, additional terrestrial plant toxicity
studies on plants expected to be sensitive to tribufos’ mode of action
are expected to be required.  

The fate properties of tribufos indicate it can potentially partition to
the sediment, and no sediment toxicity data are available for review;
therefore, toxicity to benthic invertebrates is unknown.  Sediment
toxicity data are expected to be required to assess risk to the benthic
invertebrate community from tribufos.  

The Agency has not conducted a risk assessment that supports a complete
endangered species determination.  The ecological risk assessment
planned during registration review will allow the Agency to determine
whether tribufos’s use has “no effect” or “may affect”
federally listed threatened or endangered species (listed species) or
their designated critical habitats.  When an assessment concludes that a
pesticide’s use “may affect” a listed species or its designated
critical habitat, the Agency will consult with the U.S. Fish and
Wildlife Service and/or National Marine Fisheries Service (the
Services), as appropriate.

The Agency completed endangered species assessments evaluating the
potential effects of tribufos on the California red-legged frog (Rana
aurora draytonii) consistent with court orders and settlements, Center
for Biological Diversity v. Johnson, et al.,No. 02-1580  (N.D. Cal.,
October 20, 2006).  The Agency concluded in October 2008 that tribufos
is Likely to Adversely Affect the California red-legged frog and
initiated formal consultation with the US Fish and Wildlife Service
regarding this determination.

EPA anticipates needing the following guideline studies in order to
conduct a complete ecological risk assessment for the registration
review of tribufos:  

835.4300 - Aerobic Aquatic Metabolism

835.6200 - Analytical Methods (and Associated Independent Laboratory
Validations) for Residues in Water and Sediment

850.2100 - Avian Acute Oral Toxicity Test (Passerine)

850.1735 - Sediment Toxicity Testing on Freshwater Invertebrates

850.1740 - Sediment Toxicity Testing on Marine Invertebrates

Non-guideline - Partition Coefficient (n-Octanol/Air)

Non-guideline - Terrestrial Plant Toxicity Test

The Agency seeks additional use and usage information to refine the
ecological risk assessment as well as information on
benefits/alternatives to inform risk management decisions.  See
“Guidance for Commenters” section below.

Please refer to the December 10, 2008 document “Problem Formulation
for Ecological Risk, Endangered Species, and Drinking Water Exposure
Assessments in Support of the Registration Review of Tribufos” in the
registration review docket (EPA-HQ-OPP-2008-0883) for a detailed
discussion of the anticipated risk assessment needs.

Human Health Risk: 

The human health risk assessment conducted in support of the 2000 IRED
was the primary source used for the 2009 “Tribufos:  Revised Human
Health Assessment Scoping Document in Support of Registration Review.”
  EPA completed its reevaluation of tribufos with the release of the OP
Cumulative Risk Assessment (CRA) in July 2006.  The CRA did not result
in any changes to tribufos registrations.

Should the Agency determine that new information on tribufos is
available which could potentially impact the CRA, the Agency will
revisit the CRA.

The toxicity database for tribufos is largely complete, with the
exception of a comparative cholinesterase (CCA) study and an
immunotoxicity study.  The CCA is an outstanding requirement from the
IRED. 

A new drinking water exposure assessment is anticipated to be needed for
registration review to incorporate the latest modeling methods.

A new dietary risk assessment is anticipated to be needed for
registration review, which will include updated drinking water estimated
environmental concentrations (EECs), updated percent crop treated
information, and revised anticipated residue levels taking into account
the revised dietary burden to ruminants.  Additionally, any changes to
toxicity endpoints or safety factors will also be incorporated.  

The updated dietary assessment will also include a reassessment of
tribufos tolerance levels for livestock commodities.  The only
tribufos-treated livestock feedstuff, cotton gin byproducts, has had a
significant reduction in the percent of diet (25 to 5%), resulting in a
lower dietary burden, which may in turn result in lower tolerance levels
than previously recommended.  

Since there are no currently registered residential or public
recreational uses for tribufos, a residential risk assessment is not
required at this time.

The most recent aggregate assessment (Human Health Risk Assessment for
Tribufos, June 2000) considered only food and water, as there are no
residential uses of tribufos.  

A new aggregate risk assessment may be needed in registration review due
to the identified data gaps in the toxicity database and likely
revisions to drinking water estimates, percent crop treated information,
and anticipated residue levels.  

Occupational handler and post-application risk estimates (inhalation and
dermal exposure) have been updated in the February 20, 2009 “Tribufos.
 Revised Human Health Assessment Scoping Document in Support of
Registration Review” based on current labels incorporating mitigation
measures required in the 2000 IRED. 

During reregistration, a biomonitoring study was required to obtain
exposure values to refine occupational risk estimates.  However, the
registrants requested, and the Agency agreed, to postpone the study
until after the required developmental neurotoxicity (DNT) study was
submitted and reviewed.  The Agency has completed its review of
submitted studies, and concludes the toxicity data did not eliminate the
need for additional exposure data.  Therefore, a biomonitoring study or
a similar study that provides exposure data that can be used to refine
occupational handler and post-application risk estimates is required and
was called in by letter to the technical registrant in February, 2009.  

A new occupational assessment is anticipated to be needed for
registration review, which will include risk estimates based on the
required tribufos biomonitoring or equivalent data, as well as any new
toxicity data that apply.

There are no maximum residue levels (MRLs) established for tribufos in
Canada, Mexico, or through Codex; thus, there are no international
harmonization issues.

Please refer to the February 20, 2009 “Tribufos:  Revised Human Health
Assessment Scoping Document in Support of Registration Review” in the
registration review docket (EPA-HQ-OPP-2008-0883) for a detailed
discussion of the anticipated risk assessment needs.

Timeline:

EPA has created the following estimated timeline for the completion of
the tribufos registration review.

Registration Review for Tribufos – Projected Registration Review
Timeline

Activities	Estimated Yr/Mon

Opening the docket

Open Docket and Public Comment Period	2009 – March

Close Public Comment	2009 – May

Case Development

Develop Final Work Plan (FWP)	 2009 – Aug.

Issue DCI	 2010 – April - June

Data Submission	 2012 – April - June 

Preliminary Risk Assessments and Open Public Comment Period	 2013 –
Oct. - Dec. 

Close Public Comment Period	 2014 – Jan. - March

Registration Review Decision

Proposed Registration Review Decision 	 2014– April - June

Public Comment Period 	 2014 – July - Sept.

Final Registration Review Decision and Begin Post-Decision Follow-up	
2015

Total (years)	 6



Guidance for Commenters:

The public is invited to comment on EPA’s preliminary registration
review work plan and rationale.  The Agency will carefully consider all
comments as well as any additional information or data provided in a
timely manner prior to issuing a final work plan for the tribufos case.

Tribufos is not identified as a cause of impairment for any water bodies
listed as impaired under section 303(d) of the Clean Water Act, based on
information provided at
http://iaspub.epa.gov/tmdl/waters_list.impairments?p_impid=3.  The
Agency invites submission of water quality data for this pesticide.  To
the extent possible, data should conform to the quality standards in
Appendix A of the “OPP Standard Operating Procedure:  Inclusion of
Impaired Water Body and Other Water Quality Data in OPP’s Registration
Review Risk Assessment and Management Process” (see 
http://www.epa.gov/oppfead1/cb/ppdc/2006/november06/session1-sop.pdf),
in order to ensure they can be used quantitatively or qualitatively in
pesticide risk assessments.

Through the registration review process, the Agency intends to solicit
information on trade irritants and, to the extent feasible, take steps
toward facilitating irritant resolution.  Growers and other stakeholders
are asked to comment on any trade irritant issues resulting from lack of
Maximum Residue Limits (MRLs) or disparities between U.S. tolerances and
MRLs in key export markets, providing as much specificity as possible
regarding the nature of the concern.

EPA seeks to achieve environmental justice, the fair treatment and
meaningful involvement of all people, regardless of race, color,
national origin, or income, in the development, implementation, and
enforcement of environmental laws, regulations, and policies.  To help
address potential environmental justice issues, the Agency seeks
information on any groups or segments of the population who, as a result
of their location, cultural practices, or other factors, may have
atypical, unusually high exposure to tribufos compared to the general
population.  Please comment if you are aware of any sub-populations that
may have atypical, unusually high exposure compared to the general
population.

Stakeholders are also specifically asked to provide information and data
in the following areas for tribufos: 

1.  description of the effect, if any, an REI greater than 7 days would
have on the ability 

	of growers to perform the necessary post-application activities for
registered uses

2.  typical application rates 

3.  description of tank mixes and frequency of use versus application of
tribufos alone 

4.  available tribufos alternatives (active ingredients and product
names)

5.  limitations in the effectiveness of alternatives

6.  difference in application costs between tribufos and available
alternatives

7.  information on usage subsequent to June 2008

8.  confirmation on the following label information

sites of application

formulations

application methods and equipment

maximum application rates

frequency of application, application intervals, and maximum number of
applications per season

geographic limitations on use

use or potential use distribution (e.g., acreage and geographical
distribution of relevant crops)

median and 90th percentile reported use rates (lbs ai/acre) from usage
data – national, state, and county

application timing (date of first application and application intervals)
by crop – national, state, and county

sub-county crop location data

directly acquired county-level usage data (not derived from state level
data)

maximum reported use rate (lbs ai/acre) from usage data – county

percent crop treated – county

median and 90th percentile number of applications – county

total pounds per year – county

the year the pesticide was last used in the county/sub-county area

the years in which the pesticide was applied in the county/sub-county
area

state or local use restrictions

ecological incidents (non-target plant damage and avian, fish,
reptilian, amphibian and mammalian mortalities) not already reported to
the Agency

monitoring data

Next Steps:

After the 60-day public comment period closes, the Agency will review
any comments received in a timely manner and then issue a Final Work
Plan for this pesticide.

II.  FACT SHEET

 

Background Information:

Tribufos registration review case number:  2145

Tribufos PC code:  074801

Tribufos CAS No.:  78-48-8

Tribufos was first registered for use in the United States in 1961.

The technical registrant for tribufos is Bayer CropScience.

There are currently three end-use products and one technical product
registered.

There are multiple tolerances for use of tribufos on food and feed crops
in 40 CFR § 180.262.  While tribufos is only registered for use on
cotton, cotton is considered a food use, since cottonseed oil is
consumed.  In addition, cotton gin byproducts are a livestock feedstuff
and contribute to our diet through meat and milk consumption.

The Tribufos IRED was completed in September 2000, and the RED was
finalized in July 2006 upon completion of the OP cumulative risk
assessment.

All tribufos labels have been amended to include the risk mitigation
measures specified in the 2000 IRED.

Special Review and Reregistration Division Chemical Review Manager: 
Molly Clayton, clayton.molly@epa.gov 

Registration Division Contacts:  Mindy Ondish, ondish.mindy@epa.gov and
Jim Tompkins, tompkins.jim@epa.gov

Use & Usage Information:  (For additional details on label rates and use
sites, refer to the Appendix A for Tribufos in the tribufos docket.) 

Tribufos is an OP herbicide registered for use on cotton as a defoliant.

Tribufos is formulated as an emulsifiable concentrate.

Applications are limited to foliar applications via ground and aerial
equipment.

The maximum single and seasonal application rate is 1.9 pounds active
ingredient per acre (lbs a.i./A) in California and Arizona; the maximum
rate in states other than CA and AZ is 1.1 lbs a.i./A.  

There are no residential or public recreational uses of tribufos.

Approximately 2.5 million pounds of tribufos per year are applied
nationally to cotton in the US (30% crop treated).

Ecological Risk Assessment Status:

The following are key findings of the most recent ecological risk
assessment for tribufos.  Please refer to the “Problem Formulation for
Ecological Risk, Endangered Species, and Drinking Water Exposure
Assessments in Support of the Registration Review of Tribufos”,
December 10, 2008 for a detailed discussion of the anticipated risk
assessment needs.  

Summary of Risks:

An ecological risk assessment (1996) and an updated drinking water
assessment (2000) were completed for the Tribufos IRED.

The 2000 IRED identified acute and chronic risks to birds, mammals, and
aquatic invertebrates (both freshwater and estuarine/marine).  Acute
risks to estuarine/marine fish, but not freshwater fish, were also
identified.  Neither risks to fish from chronic exposure to tribufos nor
risks to plants could be fully evaluated due to a lack of data.  Eight
ecological studies were required during reregistration and seven
additional ecological studies are expected to be required for
registration review to address the data gaps and associated uncertainty.
 

Contributing reasons for risk include tribufos's high toxicity to
aquatic organisms, stability to abiotic routes of degradation, and
limited biotic degradation.

The primary degradate of tribufos does not retain the organophosphate
substructure of the parent compound and is not expected to be as toxic
as tribufos.  Therefore, tribufos alone is the residue of concern for
the ecological risk, endangered species, and drinking water exposure
assessments.

Mitigation measures (including reduction of application rates) specified
in the 2000 IRED were expected to lower ecological risks.  The
ecological risk assessment planned for registration review will reflect
mitigation measures specified by current tribufos labels.

The Agency completed endangered species assessments evaluating the
potential effects of tribufos on the California red-legged frog (Rana
aurora draytonii) consistent with court orders and settlements, Center
for Biological Diversity v. Johnson, et al.,No. 02-1580  (N.D. Cal.,
October 20, 2006).  The Agency concluded in October 2008 that tribufos
is Likely to Adversely Affect the California red-legged frog and
initiated formal consultation with the US Fish and Wildlife Service
regarding this determination.

Human Health Risk Assessment Status:

The following are key findings of the most recent human health risk
assessments for tribufos.  Please refer to the February 20, 2009
“Tribufos.  Revised Human Health Assessment Scoping Document in
Support of Registration Review” for a detailed discussion of the
anticipated risk assessment needs for human health.  

Tribufos risk assessments rely in part on data from studies in which
adult human subjects were occupationally exposed to a pesticide to
determine their dermal and inhalation exposure.  These studies have all
been reviewed by the Agency and found on the basis of available evidence
to have been neither fundamentally unethical nor significantly deficient
relative to standards of ethical research conduct prevailing when they
were conducted.  There is no regulatory barrier to reliance on these
studies, and all applicable requirements of EPA’s Rule for the
Protection of Human Subjects of Research (40 CFR Part 26) have been
satisfied.

Hazard Characterization:

As with other OPs, the principal toxic effects induced by tribufos are
related to its cholinesterase-inhibiting activity.  Evidence of
anticholinesterase activity occurs by all routes (oral, dermal, and
inhalation) and exposure durations (acute, subchronic and chronic).

By the oral and dermal routes, technical tribufos is placed in Toxicity
Category II and by the inhalation route, Category III.  Primary skin and
eye irritation are both assigned to Toxicity Category IV.  It is not a
dermal sensitizer.  Tribufos is classified as unlikely to be a human
carcinogen at low doses, since all tumor increases in mice occurred only
at the highest dose tested and were accompanied by severe cholinesterase
(ChE) inhibition and increased mortality.

For the tribufos risk assessment prepared in 2000, an extra 10X safety
factor was retained because of data gaps for acute and subchronic
neurotoxicity studies in the rat and for a DNT study.  All of these
studies have been submitted to the Agency, reviewed, and found to be
acceptable.  However, a CCA study is required for OP pesticides, such as
tribufos, that inhibit ChE.  The CCA study is required whether or not a
series 870.6300 DNT study has been submitted unless the Agency agrees
that the DNT study contains equivalent CCA data.  For tribufos, the DNT
study was determined not to contain equivalent CCA data, so the CCA
study is still required.

The Agency expects to require an immunotoxicity study under the revised
40 CFR Part 158.  Once the immunotoxicity and CCA studies have been
reviewed, the Agency will need to reevaluate the toxicity endpoints used
for risk assessment purposes and revisit the sensitivity and safety
factor determinations.

Dietary (Food and Water):

The most recent tribufos dietary risk assessment was conducted for the
IRED in 2000.  Anticipated residues used in the assessment incorporated
field trial data, processing study data, and percent crop treated
information.  The acute and chronic dietary exposures were determined to
be well below the Agency’s LOC.  

The updated dietary assessment will also include a reassessment of
tribufos tolerance levels for livestock commodities.  The only
tribufos-treated livestock feedstuff, cotton gin byproducts, has had a
significant reduction in the percent of diet (25 to 5%), resulting in a
lower dietary burden, which may in turn result in lower tolerance levels
than previously recommended.  

In the 2000 assessment, the EECs in drinking water were based on surface
water models available at that time.  During registration review, the
EEC values for tribufos will be updated using the latest modeling
methods.  

A new dietary risk assessment will be needed for registration review,
which will include new drinking water EECs, updated percent crop treated
information, and revised anticipated residue levels taking into account
the revised estimated dietary burden to ruminants.  Additionally, any
changes to toxicity endpoints or safety factors will also be
incorporated. 

Residential:

 

Since there are no currently registered residential or public
recreational uses for tribufos, a residential risk assessment is not
required at this time.

Aggregate:

The aggregate assessment in the Human Health Risk Assessment for
Tribufos (June 2000), considered only food and water, since there are no
residential uses of tribufos.  Both the acute and chronic aggregate
analyses showed no risks of concern.  However, in view of the identified
data gaps in the toxicity database and likely revisions to drinking
water estimates, percent crop treated information and anticipated
residue levels, a new aggregate risk assessment may be needed in
registration review.  

Occupational:

Handler:

The potential occupational handler exposure routes for tribufos are
dermal and inhalation.  An exposure assessment for the short-term (1-30
days) and intermediate-term (1-6 months) exposure duration is relevant
for current tribufos registrations; chronic exposures are not
anticipated based on the use pattern for tribufos.  

In the most recent Human Health Risk Assessment (2000), Pesticide
Handler's Exposure Data (PHED), as well as chemical-specific handler
study data, were used to assess four major occupational handler exposure
scenarios. 

Prior to the 2000 IRED, the maximum registered application rate for
tribufos was 1.875 lbs ai/A.  The IRED specified risk mitigation
measures including a reduction in the application rate from 1.875 lbs
ai/A to 1.125 lbs ai/A for cotton, with the exception of California and
Arizona.  These two states grow hardier varieties of cotton and, thus,
require more defoliant.  These mitigation measures were specified to
address risks of concern for occupational handlers and workers entering
treated areas (post-application exposure).  Current labels reflect the
change in application rates.  

Handler risk estimates (inhalation and dermal exposure) have been
updated in “Tribufos.  Revised Human Health Assessment Scoping
Document in Support of Registration Review”, February 20, 2009, based
on current labels incorporating mitigation measures specified in the
2000 IRED.   Inhalation risk estimates for all worker scenarios are
above the target margin of exposure (MOE) of 100 and, therefore, are not
of concern to the Agency.  

In the 2009 occupational assessment, some of the dermal risk estimates
for handlers using engineering controls (closed systems for mixers,
loaders, and applicators) fall below the dermal target MOE of 300. 
There are dermal risks of concern for handlers with engineering controls
at both the 1.125 lbs ai/A and 1.875 lbs ai/A application rates for two
scenarios: mixing/loading liquids for aerial applications and applying
liquids via aerial equipment.  Occupational handler risk estimates for
all other scenarios, at both application rates, were below the
Agency’s LOC (MOEs >300).  In the majority of applications, tribufos
is tank-mixed with other defoliants at a much lower rate (0.50 to 0.75
lbs ai/A).  Therefore, actual occupational exposure values are likely
much lower than those assessed.  

Post-Application:

The tribufos restricted entry interval (REI) was changed from 24 hours
to 7 days per the 2000 IRED to address post-application risks of concern
to workers.  Occupational post-application risk estimates for tribufos
were updated in the December 18, 2008 “Tribufos.  Human Health
Assessment Scoping Document in Support of Registration Review,” based
on current labels incorporating mitigation measures specified in the
IRED.  Given the physical and chemical properties of tribufos,
inhalation exposure is not likely to be a concern 7 days after
treatment.  Therefore, only short- and intermediate-term
post-application dermal exposures were assessed.

At the reduced application rate (1.125 lbs ai/A) and the 7 day REI, the
MOEs for post-application activities are above the target dermal MOE of
300 and, therefore, are not of concern to the Agency.

Post-application dermal risks of concern still remain for most
activities at the higher application rate of 1.875 lbs ai/A (used in CA
and AZ only) with the current REI of 7 days. 

A biological monitoring study required during reregistration and later
placed on hold pending the outcome of additional hazard assessment was
called in by the Agency in February 2009.  This data will be used to
refine exposure estimates in a new occupational assessment, which is
expected to be conducted during registration review.

Cumulative:

Tribufos has been identified as a member of the OP class of chemicals
that share a common mode of action, and the OP CRA was completed in
2006.  No cumulative risks of concern for tribufos were identified in
that assessment and no additional mitigation was specified.  Should the
Agency determine that new information on tribufos is available which
could potentially impact the OP CRA and result in a risk of concern, the
Agency will revisit this assessment.

Incidents:

Ecological:

A review of the Agency’s Ecological Incident Information System
(EIIS), completed on June 18, 2008, identified one incident associated
with tribufos, involving damage to 53 acres of lettuce in Riverside,
California in 2004.  The damage was described as “uniform
throughout” the field, although the specific type of damage to the
lettuce was not specified in the incident report.  Damage was attributed
to spray drift of tribufos and diuron that had been legally applied by
air to a cotton field adjacent to the damaged lettuce field.  The
damaged lettuce tested positive for tribufos (50 ppb).  No other residue
information was provided in the report.

Human Health:

In October 2008 the Agency conducted a review of the OPP Incident Data
System (IDS) for reports of tribufos poisoning incidents occurring in
the United States from 2000 to the present.  Two incidents were cited: a
5 year old female reported vomiting, diarrhea, muscle weakness,
tachycardia, hypertension, pulmonary infiltrates, and miosis; and an
adult (18-64) male reported hypertension, malaise, headache,
coughing/choking, dyspnea/shortness of breath.  The effects seen in the
incidents were consistent with the type of toxicological effects that
are seen in the animal studies for tribufos.  There were no further
details on how they were exposed.

Tolerances and International Harmonization: 

There are no MRLs established for tribufos in Canada, Mexico, or through
Codex; thus, there are no international harmonization issues.

Benefits:

In making the 2000 reregistration decision, the Agency, under FIFRA,
considered the benefits of tribufos and the availability of
alternatives.  The Agency concluded that the risk reduction measures
specified by the RED, combined with quantifiable benefits of tribufos to
the cotton industry and lack of viable alternatives, were adequate to
justify the continued use of tribufos.  During registration review, the
Agency will re-examine benefits and alternatives for scenarios that
exceed the Agency’s LOC. 

Data Call-In Status:

The 2000 Tribufos IRED and corresponding GDCI (GDCI-074801-17860)
required several studies, some of which remain outstanding.  The
following studies are still required in order to conduct comprehensive
ecological and human health risk assessments in registration review:

850.1400 – Early Life Stage Toxicity of Tribufos to the Fathead Minnow


	A study titled “Early Life Stage Toxicity of Tribufos to the Fathead
Minnow (Pimephales promelas)” (MRID 45863703) was submitted by Bayer
CropScience to the Agency in October 2002 in response to the GDCI.  In
December 2008, EPA notified Bayer by letter that the study could not be
used for risk quotient (RQ) calculations because a high level of
analytical variation was observed in the mean results and that a new
study was required.  The study is due 12 months from the date of that
letter, or December 18, 2009.

870.6300 – Comparative Cholinesterase Assay

The DNT requires an evaluation of the comparative sensitivity in
juvenile and adult rats, which is examined in a CCA.  The DNT study
previously submitted for tribufos (MRID 45499501) did not meet the
required CCA components for assessing cholinesterase inhibition in
fetuses and pups.  EPA notified Bayer CropScience by letter in January
2009 that the CCA data are outstanding and that Bayer must submit a
protocol to the Agency for review prior to initiation of the study.  The
protocol is due July 15, 2009; the CCA study is due January 15, 2011.

875.1500 – Biological Monitoring

In 2001 the registrants requested, and the Agency agreed, to postpone
the biomonitoring study due date until after the required DNT was
submitted and reviewed.  The Agency has since completed its review of
that data, and the data does not negate the need for the biological
monitoring study.  In February 2009, EPA notified Bayer by letter that a
biomonitoring study or a similar study that provides exposure data that
can be used to refine occupational handler and post-application risk
estimates is required and is due by February 25, 2012.  

 

Labels:

 

Below is a table of registration numbers for the tribufos case.  Labels
can be obtained from the Pesticide Product Label System (PPLS) website: 
 HYPERLINK "http://oaspub.epa.gov/pestlabl/ppls.home" 
http://oaspub.epa.gov/pestlabl/ppls.home .

Registration #	Registration Name	Company Name	% Active Ingredient

264-720	DEF Technical	Bayer Crop Science LP	97.9

264-730	DEF 6 Emulsifiable Defoliant	Bayer Crop Science LP	70.5

5481-504	Folex 6 EC	AMVAC Chemical Corporation	70.5

34704-867	DFT 6 EC Cotton Defoliant	Loveland Products, Inc.	70.5

III.  GLOSSARY AND TERMS AND ABBREVIATIONS

AChE			Acetylcholinesterase

AGDCI		Agricultural Data Call-In

ai			Active Ingredient

aPAD			Acute Population Adjusted Dose

CCA			Comparative Cholinesterase Assay

ChE			Cholinesterase

CFR			Code of Federal Regulations

cPAD			Chronic Population Adjusted Dose

CRA			Cumulative Risk Assessment

CSF			Confidential Statement of Formula

CSFII			USDA Continuing Surveys for Food Intake by Individuals

DCI			Data Call-In

DEEM		Dietary Exposure Evaluation Model

DFR			Dislodgeable Foliar Residue

DNT			Developmental Neurotoxicity

EC			Emulsifiable Concentrate Formulation

EDWC		Estimated Drinking Water Concentration

EEC			Estimated Environmental Concentration

EPA			Environmental Protection Agency

EUP			End-Use Product

FDA			Food and Drug Administration

FIFRA		Federal Insecticide, Fungicide, and Rodenticide Act

FFDCA		Federal Food, Drug, and Cosmetic Act

FQPA			Food Quality Protection Act

GLN			Guideline Number

IR			Index Reservoir

KOA 			Octanol-Air Partition Coefficient 

LAA			Likely to Adversely Affect

LC50			Median Lethal Concentration.  A statistically derived
concentration of a substance that can be 	expected to cause death in 50%
of test animals.  It is usually expressed as the weight of substance 
per weight or volume of water, air or feed, e.g., mg/l, mg/kg or ppm.

LD50			Median Lethal Dose.  A statistically derived single dose that can
be expected to cause death in 	50% of  the test animals when
administered by the route indicated (oral, dermal, 	inhalation).  It is 
expressed as a weight of substance per unit weight of animal, e.g.,
mg/kg.

LOC			Level of Concern

LOAEL		Lowest Observed Adverse Effect Level

µg/g			Micrograms Per Gram

µg/L			Micrograms Per Liter

mg/kg/day		Milligram Per Kilogram Per Day

mg/L			Milligrams Per Liter

MOE			Margin of Exposure 

MRID			Master Record Identification (number).  EPA's system of recording
and tracking studies 	submitted.

MUP			Manufacturing-Use Product

NOAEL		No Observed Adverse Effect Level

OPP			EPA Office of Pesticide Programs

OPPTS		EPA Office of Prevention, Pesticides and Toxic Substances

PAD			Population Adjusted Dose

PCA			Percent Crop Area

PDP			USDA Pesticide Data Program

PHED			Pesticide Handler's Exposure Data 

PHI			Preharvest Interval

ppb			Parts Per Billion

PPE			Personal Protective Equipment

ppm			Parts Per Million

PRZM/EXAMS	Tier II Surface Water Computer Model  

Q1*			The Carcinogenic Potential of a Compound, Quantified by the EPA's
Cancer Risk Model

RED			Reregistration Eligibility Decision

REI			Restricted Entry Interval

RfD			Reference Dose

RQ			Risk Quotient

SCI-GROW		Tier I Ground Water Computer Model

SAP			Science Advisory Panel

SF			Safety Factor

SLC			Single Layer Clothing

TGAI			Technical Grade Active Ingredient

USDA		United States Department of Agriculture

USGS			United States Geological Survey

UF			Uncertainty Factor

UV			Ultraviolet 

WPS			Worker Protection Standard

 PAGE   

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Docket Number EPA-HQ-OPP-2008-0883						

www.regulations.gov		

