  SEQ CHAPTER \h \r 1 

UNITED STATES ENVIRONMENTAL PROTECTION AGENCY

WASHINGTON, D.C. 20460      

	OFFICE OF PREVENTION, PESTICIDES

                                                                        
                   AND TOXIC SUBSTANCES

	

MEMORANDUM

Date:  		24 March 2009

SUBJECT:	Penoxsulam:  Chronic Aggregate Dietary (Food and Drinking
Water) Exposure and Risk Assessment to Evaluate the Requested New Uses
on Grapes and Tree Nuts

PC Code:  119031	DP Barcode:  D360419

Decision No.:  394768	Registration No.:  62719-ANG

Petition No.:  8F7369	Regulatory Action:  Section 3 Registration

Risk Assessment Type:  Single chemical, aggregate	Case No.:  NA

TXR No.:  NA	CAS No.:  219714-96-2

MRID No.:  None	40 CFR:  180.605



FROM:	Michael A. Doherty, Ph.D., Chemist

Risk Assessment Branch II

Health Effects Division (7509P)

THROUGH:	Thurston Morton, Chemist

Anant Parmar, Biologist

Dietary Exposure Science Advisory Council (DESAC)

Health Effects Division (7509P)

Christina Swartz, Branch Chief

Risk Assessment Branch II

Health Effects Division (7509P)

TO:		Michael A. Doherty, Ph.D., Chemist

Risk Assessment Branch II

Health Effects Division (7509P)

Philip Errico/Joanne Martin (Team 23)

Herbicide Branch

Registration Division (7505P)

Executive Summary

 conducted using the Dietary Exposure Evaluation Model DEEM-FCID™,
Version 2.03 which uses food consumption data from the U.S. Department
of Agriculture’s Continuing Surveys of Food Intakes by Individuals
(CSFII) from 1994-1996 and 1998.  The analysis was completed to evaluate
the impact on dietary exposure of the requested uses of penoxsulam on
grapes and tree nuts.

No endpoint attributable to a single exposure was identified in the
toxicological database for penoxsulam; therefore, acute dietary exposure
is not of concern for this chemical.

The chronic dietary exposure assessment is highly health protective.  It
is based on tolerance-level residues, assumes 100% crop treated, and
incorporates default processing factors for processed food forms.  In
addition, conservative estimates of residues in drinking water,
equivalent to the aquatic application rate, were incorporated in the
assessment.  Risk estimates derived from these parameters are below
HED’s level of concern [i.e., < 100% of the chronic
population-adjusted dose (cPAD)] for all population subgroups.

Penoxsulam has been classified as having “suggestive evidence of
carcinogenicity, but not sufficient to assess human carcinogenic
potential.”  As such, the chronic assessment is believed to be
protective of potential carcinogenic effects; therefore, cancer risk is
not a concern for penoxsulam.

There are no dietary exposure considerations that preclude granting the
requested uses of penoxsulam on grapes and tree nuts.

I.	Introduction

Dietary risk assessment incorporates both exposure and toxicity of a
given pesticide.  For acute and chronic assessments, the risk is
expressed as a percentage of a maximum acceptable dose (i.e., the dose
which HED has concluded will result in no unreasonable adverse health
effects).  This dose is referred to as the population adjusted dose
(PAD).  The PAD is equivalent to point of departure (POD, NOAEL, LOAEL,
e.g.) divided by the required uncertainty or safety factors.

For acute and non-cancer chronic exposures, HED is concerned when
estimated dietary risk exceeds 100% of the PAD.  HED is generally
concerned when estimated cancer risk exceeds one in one million.
References which discuss the acute and chronic risk assessments in more
detail are available on the EPA/pesticides web site:  “Available
Information on Assessing Exposure from Pesticides, A User’s Guide,”
21-JUN-2000, web link:      HYPERLINK
"http://www.epa.gov/fedrgstr/EPA-PEST/2000/July/Day-12/6061.pdf" 
http://www.epa.gov/fedrgstr/EPA-PEST/2000/July/Day-12/6061.pdf  ; or see
SOP 99.6 (20-AUG-1999).

The most recent dietary risk assessment for penoxsulam was conducted in
2007 by W. Cutchin (5 June 2007, D339186).

II.	Residue Information

Tolerances for residues of penoxsulam, per se, [40 CFR 180.605] have
been established for fish (0.01 ppm), crustaceans (0.01 ppm), mollusks
(0.02 ppm), rice grain (0.02 ppm), and rice straw (0.50 ppm).  For the
currently requested uses, adequate field trial data have been submitted
for grapes, almonds, and pecans.  The data support tolerances of 0.01
ppm in grape and tree nut (including pistachio) commodities.

Tolerance-level residues were used for all entries in the assessment,
except for fish, crustaceans, and mollusks, for which residue values
include the 5-hydroxy metabolite of penoxsulam; and it was assumed that
all crops/foods with existing or proposed tolerances were treated (i.e.,
100% CT).  Although processing studies with penoxsulam-treated grapes
showed no concentration of residues upon processing, default processing
factors from DEEM 7.81 were used for grape juice and wine (1.2X), and
raisins (4.3X).

 Drinking Water Data

The Environmental Fate and Effects Division (EFED) has provided HED with
Tier 1 modeled estimates of penoxsulam residues of concern in drinking
water based on the use pattern for turf grass (J. Wolf, 2 December 2008,
D355676).  Based on the turf grass use pattern (0.09 lb a.i./A),
residues of penoxsulam are not expected to be greater than 0.023 ppm
(Table 1).  Penoxsulam is registered for control of aquatic weeds.  For
that use pattern, the maximum application rate is 150 ppb (0.15 ppm) in
the water column.  For this assessment, HED has used 0.15 ppm as a
high-end estimate of penoxsulam residues in drinking water.  The
0.15-ppm value is likely to be an overestimate of actual residues in
drinking water.  Residues were incorporated in the DEEM-FCID into the
food categories “water, direct, all sources” and “water, indirect,
all sources.”

Table 1.  Summary of Residue Estimates for Penoxsulam in Drinking Water.

Duration	Aquatic Use, ppm	Turf Use



Surface Water, ppm	Ground Water, ppm

Acute	0.15	0.0094	0.0233

Chronic	0.15	0.00092	0.0233



FCID™ Program and Consumption Information

The penoxsulam chronic dietary exposure assessment was 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.  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 cPAD.  This procedure is performed for each
population subgroup.

V.	Toxicological Information

The review team for penoxsulam has examined the available toxicological
data, and confirms the findings previously made regarding doses and
endpoints for use in dietary risk assessment (Table 2).   The review
team notes that due to revisions in the data requirements for
pesticides, an immunotoxicity study is now required for penoxsulam. 
Although this study now represents a datagap, there were no signs of
immunotoxicity in the currently available data and there is no need for
a database uncertainty factor.

The FQPA SF has been reduced to 1x based on the following:

There was no toxicologically significant evidence of neurotoxicity in
either the acute or chronic neurotoxicity study.

No definitive quantitative or qualitative susceptibility was observed in
either of the developmental rat or rabbit studies.

Significant dose-related effects in the two-generation reproduction
study were limited to the delay in preputial separation.  No other
endpoints of reproductive toxicity or offspring growth and survival were
affected by treatment, and offspring effects were observed in the
presence of parental toxicity at similar doses.

Dietary exposure estimates are based on health-protective assumptions to
assure that exposure estimates do not underestimate actual exposures
that may occur.

Table 2.  Summary of Toxicological Doses and Endpoints for Penoxsulam
for Use in Dietary Exposure Assessment

Exposure

Scenario	Point of Departure, UF 	FQPA SF and Level of Concern for Risk
Assessment	Study and Toxicological Effects

Acute Dietary

(all populations)	None

UF = N/A	N/A	No toxicological endpoint attributable to a single exposure
was identified in the available toxicology studies on penoxsulam.

Chronic Dietary

(all populations)	NOAEL= 14.7 mg/kg/day

UF = 100

Chronic POD = 0.147 mg/kg/day	FQPA SF = 1x

cPAD = 

Chronic POD

 FQPA SF

= 0.147 mg/kg/day	1-Year Chronic Feeding Study in Dogs. LOAEL = 46.2
mg/kg/day based on multi-focal hyperplasia of the pelvic epithelium of
the kidney.

Cancer (oral, dermal, inhalation)	 Suggestive Evidence of
Carcinogenicity, but Not Sufficient to Assess Human Carcinogenic
Potential

Point of Departure (POD) = A data point or an estimated point that is
derived from observed dose-response data and  used to mark the beginning
of extrapolation to determine risk associated with lower environmentally
relevant human exposures.  NOAEL = no observed adverse effect level. 
LOAEL = lowest observed adverse effect level.  UF = uncertainty factor. 
FQPA SF = FQPA Safety Factor.  PAD = population adjusted dose (a =
acute, c = chronic).  N/A = not applicable.

VI.	Results/Discussion 

FCID™ analyses estimate the dietary exposure of the U.S. population
and various population subgroups.  The results, reported in Table 3, are
for the general U.S. Population, all infants (<1 year old), children
1-2, children 3-5, children 6-12, youth 13-19, females 13-49, adults
20-49, and adults 50+ years.  Risk estimates are below HED’s level of
concern for all population subgroups.  The highest risk estimate (7.1%
cPAD) is for the group made up of infants (< 1 year old).

Table 3.  Summary of Dietary (Food + Drinking Water) Exposure and Risk
for Penoxsulam.

Population Subgroup	Acute Dietary	Chronic Dietary	Cancer

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

(mg/kg/day)	% cPAD	Dietary Exposure

(mg/kg/day)	Risk

General U.S. Population	N/A	N/A	0.003176	2.2	N/A	N/A

All Infants (< 1 year old)

	0.010391	7.1



Children 1-2 years old

	0.004745	3.2



Children 3-5 years old

	0.004430	3.0



Children 6-12 years old

	0.003049	2.1



Youth 13-19 years old

	0.002295	1.6



Adults 20-49 years old

	0.002964	2.0



Adults 50+ years old

	0.003116	2.1



Females 13-49 years old

	0.002950	2.0



The population subgroup with the highest exposure/risk estimate is
bolded.

VII.	Characterization of Inputs/Outputs

The chronic dietary exposure and risk values provided in Table 3
represent very conservative, health protective estimates that
overestimate any actual exposures that may occur.

VIII.	Conclusions

Based on highly conservative estimates of residue levels and frequency
of occurrence, there are no dietary risk issues associated with the
penoxsulam that would preclude granting the requested uses or
establishing tolerances for residues in/on grapes and tree nuts.

An aggregate human health risk assessment is being issued as a separate
document.

IX.	List of Attachments

Attachment 1.    Summary of Input Values for the Penoxsulam Chronic
Dietary Exposure Analysis.

Attachment 2.  Results of the Penoxsulam Chronic Dietary Exposure
Analysis.



Attachment 1.  Summary of Input Values for the Penoxsulam Chronic
Dietary Exposure Analysis.

Filename: G:\Briefcase\Chemistry Reviews\!DEEM
Runs\Penoxsulam\119031c2008.R98

Chemical: Penoxsulam

RfD(Chronic): .147 mg/kg bw/day  NOEL(Chronic): 0 mg/kg bw/day

RfD(Acute): 0 mg/kg bw/day  NOEL(Acute):  0 mg/kg bw/day

Date created/last modified: 12-17-2008/14:25:20/8          Program ver.
2.03

------------------------------------------------------------------------
--------

  EPA    Crop                                   Def Res     Adj.Factors 
 Comment

  Code    Grp  Commodity Name                    (ppm)       #1    #2   

-------- ---- -------------------------------  ----------  ------ ------
 -------

14000030 14   Almond                             0.010000   1.000  1.000
 

14000031 14   Almond-babyfood                    0.010000   1.000  1.000
 

14000040 14   Almond, oil                        0.010000   1.000  1.000
 

14000041 14   Almond, oil-babyfood               0.010000   1.000  1.000
 

14000590 14   Brazil nut                         0.010000   1.000  1.000
 

14000680 14   Butternut                          0.010000   1.000  1.000
 

14000810 14   Cashew                             0.010000   1.000  1.000
 

14000920 14   Chestnut                           0.010000   1.000  1.000
 

14001550 14   Filbert                            0.010000   1.000  1.000
 

14001560 14   Filbert, oil                       0.010000   1.000  1.000
 

80001570 F    Fish-freshwater finfish            0.014000   1.000  1.000
 

80001580 F    Fish-freshwater finfish, farm ra   0.014000   1.000  1.000
 

80001610 F    Fish-shellfish, crustacean         0.014000   1.000  1.000
 

80001620 F    Fish-shellfish, mollusc            0.028000   1.000  1.000
 

95001750 O    Grape                              0.010000   1.000  1.000
 

95001760 O    Grape, juice                       0.010000   1.200  1.000
 

95001761 O    Grape, juice-babyfood              0.010000   1.200  1.000
 

95001770 O    Grape, leaves                      0.010000   1.000  1.000
 

95001780 O    Grape, raisin                      0.010000   4.300  1.000
 

95001790 O    Grape, wine and sherry             0.010000   1.200  1.000
 

14001850 14   Hickory nut                        0.010000   1.000  1.000
 

14002130 14   Macadamia nut                      0.010000   1.000  1.000
 

14002690 14   Pecan                              0.010000   1.000  1.000
 

14002820 14   Pistachio                          0.010000   1.000  1.000
 

15003230 15   Rice, white                        0.020000   1.000  1.000
 

15003231 15   Rice, white-babyfood               0.020000   1.000  1.000
 

15003240 15   Rice, brown                        0.020000   1.000  1.000
 

15003241 15   Rice, brown-babyfood               0.020000   1.000  1.000
 

15003250 15   Rice, flour                        0.020000   1.000  1.000
 

15003251 15   Rice, flour-babyfood               0.020000   1.000  1.000
 

15003260 15   Rice, bran                         0.020000   1.000  1.000
 

15003261 15   Rice, bran-babyfood                0.020000   1.000  1.000
 

14003910 14   Walnut                             0.010000   1.000  1.000
 

86010000 O    Water, direct, all sources         0.150000   1.000  1.000
 

86020000 O    Water, indirect, all sources       0.150000   1.000  1.000
 

15004050 15   Wild rice                          0.020000   1.000  1.000
 

Attachment 2.  Results of the Penoxsulam Chronic Dietary Exposure
Analysis.

U.S. Environmental Protection Agency                                
Ver. 2.00

DEEM-FCID Chronic analysis for PENOXSULAM                       (1994-98
data)

Residue file name: C:\Documents and Settings\mdoherty\My
Documents\Chemistry Reviews\!DEEM Runs\Penoxsulam\119031c2008.R98

                                                 Adjustment factor #2
NOT used.

Analysis Date 12-17-2008/14:25:56     Residue file dated:
12-17-2008/14:25:20/8

Reference dose (RfD, Chronic) = .147 mg/kg bw/day

========================================================================
=======

                    Total exposure by population subgroup

------------------------------------------------------------------------
-------

                                                    Total Exposure

                                        
-----------------------------------

          Population                         mg/kg             Percent
of   

           Subgroup                       body wt/day             Rfd   
   

--------------------------------------   -------------      
---------------

U.S. Population (total)                     0.003176                
2.2%

U.S. Population (spring season)             0.003148                
2.1%

U.S. Population (summer season)             0.003411                
2.3%

U.S. Population (autumn season)             0.003070                
2.1%

U.S. Population (winter season)             0.003071                
2.1%

Northeast region                            0.002902                
2.0%

Midwest region                              0.003208                
2.2%

Southern region                             0.003017                
2.1%

Western region                              0.003640                
2.5%

Hispanics                                   0.003606                
2.5%

Non-hispanic whites                         0.003097                
2.1%

Non-hispanic blacks                         0.003015                
2.1%

Non-hisp/non-white/non-black                0.003911                
2.7%

All infants (< 1 year)                      0.010391                
7.1%

Nursing infants                             0.003858                
2.6%

Non-nursing infants                         0.012870                
8.8%

Children 1-6  yrs                           0.004455                
3.0%

Children 7-12 yrs                           0.002888                
2.0%

Females 13-19 (not preg or nursing)         0.002233                
1.5%

Females 20+ (not preg or nursing)           0.003167                
2.2%

Females 13-50 yrs                           0.003070                
2.1%

Females 13+ (preg/not nursing)              0.003086                
2.1%

Females 13+ (nursing)                       0.004392                
3.0%

Males 13-19 yrs                             0.002336                
1.6%

Males 20+ yrs                               0.002845                
1.9%

híP

萏֠萑褐葞֠葠褐摧▚®

됂逃$愂Ĥ摧▚®

"

(

,

M

U

V

n

o

†

Ú

,

L

M

o

‡

¹

Ù

Ú

ù

híP

摧灮 

摧灮 

瑹֋d

瑹ౝf

戆

戆

&

&

&

摧㔌Ø欀罤

摧灒ò

摧灒ò

摧灒ò

摧灒ò

摧灒ò

摧灒ò

摧灒ò

摧灒ò

摧灒ò

&

@

Seniors 55+                                 0.003114                
2.1%

Children 1-2 yrs                            0.004745                
3.2%

Children 3-5 yrs                            0.004430                
3.0%

Children 6-12 yrs                           0.003049                
2.1%

Youth 13-19 yrs                             0.002295                
1.6%

Adults 20-49 yrs                            0.002964                
2.0%

Adults 50+ yrs                              0.003116                
2.1%

Females 13-49 yrs                           0.002950                
2.0%

------------------------------------------------------------------------
-------

Penoxsulam (119031)	Dietary Exposure and Risk Assessment	DP Number: 
360419

 PAGE   8 

Page   PAGE  1  of   NUMPAGES  8 

DRAFT – Confidential, Internal, and Deliberative Material

[Chemical Name]	Dietary Exposure and Risk Assessment	DP Number:
[xxxxxxx]

PC Code:  [xxxxxx]		

