Document ID: EPA-HQ-OPP-2009-0057-0009
Agency: epa
Document Type: Supporting & Related Material
Title: 
Posted Date: 2010-04-07T04:00Z

UNITED STATES ENVIRONMENTAL PROTECTION AGENCY

WASHINGTON, D.C. 20460      

	OFFICE OF PREVENTION, PESTICIDE

	AND TOXIC SUBSTANCES

	

  SEQ CHAPTER \h \r 1 MEMORANDUM

	Date:	15 October 2009

	SUBJECT:	Nicosulfuron – Dietary Exposure and Risk Analysis to
Evaluate a New Use Request for Grasses. 

PC Code:  129008	DP Barcode:  D369742

MRID No.:  NA	Registration No.:  352-IRO

Petition No.:  8F7501	Regulatory Action:  Section 3

Assessment Type:  Dietary – Single Chemical	Registration Case No.:  NA

TXR No.:  None	CAS No.:  111991-09-4

Decision No.:  404568	40 CFR 180.454

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

		Risk Assessment Branch II

		Health Effects Division (7509P)  SEQ CHAPTER \h \r 1 

	THROUGH:	P. Yvonne Barnes, Biologist

		Nancy Dodd, Chemist

		Dietary Exposure Science Advisory Council

		Richard A. Loranger, Ph.D., Senior Scientist

		Risk Assessment Branch II

		Health Effects Division (7509P)

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

		Risk Assessment Branch II

		Health Effects Division (7509P)

		Mindy Ondish/Jim Tompkins (RM 25)

		Herbicide Branch

		Registration Division (7505 P)  SEQ CHAPTER \h \r 1   SEQ CHAPTER \h
\r 1 

Executive Summary

e 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 a requested use on grasses. 
Although the action does not affect any human foods directly, the use,
if granted, will result in new tolerances for residues in meat and milk
commodities.

No hazards associated with acute dietary exposure were identified for
nicosulfuron; therefore, only a chronic evaluation was conducted.  The
analysis assumes tolerance-level residues and 100% crop treated for all
foods (corn, meat, and milk commodities).  Even with these highly
conservative assumptions, the resulting risk estimates are less than 1%
of the chronic population-adjusted dose (cPAD) for all population
subgroups.  Generally HED is concerned when risk estimates exceed 100%
of the cPAD.  Nicosulfuron is not a carcinogen; therefore, there are no
cancer concerns associated with this herbicide.  There are no dietary
exposure considerations that would preclude granting the requested use.

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 nicosulfuron was conducted
by D. Hrdy (20 November 2004, D302694).

II.	Residue Information

Existing and recommended tolerance-level residues [40 CFR §180.454]
have been used for all food commodities in this assessment.  The
existing tolerances are 0.1 ppm for all corn commodities.  The
recommended tolerances for livestock commodities (of cattle, horses, and
sheep only) are 0.01 ppm for meat and fat, 0.05 ppm for meat byproducts,
and 0.01 ppm for milk.  A default processing factor of 1.5 from DEEM
7.78 was used for corn syrup, and it was assumed that 100% of foods in
the assessment had residues of nicosulfuron (i.e., 100% crop treated). 
The inputs used in the assessment are provided in Attachment 1.

 Drinking Water Data

The drinking water residues used in the dietary risk assessment were
provided by the Environmental Fate and Effects Division (EFED) in the
following memorandum: Tier 1 Estimated Environmental Concentrations of
Nicosulfuron, for Use in Human Health Risk Assessment” by L. Liu (28
July 2004; D301842, D302623, D302624) and incorporated directly into
this dietary assessment.  Water residues were incorporated in the
DEEM-FCID into the food categories “water, direct, all sources” and
“water, indirect, all sources.”   Estimates were derived based on
the use on corn and are considered worst-case.  The surface water
estimate of 0.685 ppb (0.000685 ppm) is greater than the groundwater
estimate (0.056 ppb) and was used in the assessment.  The models (FIRST
and SCIGROW) are conservative with respect to protecting human health. 
Both of the models and their full descriptions are available at the EPA
internet site:   HYPERLINK "http://www.epa.gov/oppefed1/models/water/" 
http://www.epa.gov/oppefed1/models/water/ .

IV.	DEEM-FCID™ Program and Consumption Information

The nicosulfuron 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, 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 cPAD.  This procedure is performed for each
population subgroup.

V.	Toxicological Information

The toxicological database for nicosulfuron is generally complete for
purposes of human health risk assessment.  New data are required to
satisfy revised requirements [40 CFR Part 158]; nevertheless, HED does
not believe that any additional safety factors are required to account
for these data gaps given the available data and effects observed.  The
doses and endpoints for dietary risk assessment are summarized in Table
1.

Table 1.  Summary of Toxicological Doses and Endpoints for Nicosulfuron
for Use in Dietary Human Health Risk Assessments

Exposure/

Scenario	Point of Departure	Uncertainty and FQPA Safety Factors	RfD &
PAD, for Risk Assessment	Study and Toxicological Effects

Acute Dietary

(All populations)	An endpoint of concern attributable to a single dose
was not identified.

Chronic Dietary (All Populations)	NOAEL=125 mg/kg/day	UFA= 10x

UFH= 10x

FQPA SF= 1x	Chronic RfD = 

cPAD = 1.25mg/kg/day	Oral toxicity – dog

NOAEL = 125 mg/kg/day based upon decreased body weight gain in males and
the statistically significant increase in the relative liver and kidney
weights of males at the LOAEL of 500 mg/kg/day.  Supported by the NOAEL
of 100 mg/kg/day/LOAEL 500 mg/kg/day in the rabbit developmental
toxicity study.

Cancer (oral, dermal, inhalation)	Classification:  “Not likely to be
Carcinogenic to Humans” based on lack of tumorigenic effects in rodent
(rats and mice) bioassays at the limit doses and lack of mutagenic
effects in the in vitro and in vivo genotoxicity assays.

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. 
UFA = extrapolation from animal to human (interspecies).  UFH =
potential variation in sensitivity among members of the human population
(intraspecies).  FQPA SF = FQPA Safety Factor.  PAD = population
adjusted dose (a = acute, c = chronic).  RfD = reference dose.

VI.	Results/Discussion 

As stated above, for acute and chronic assessments, 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 reported in Table 2 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.  Cancer risk is determined for the general U.S.
population only.  All dietary risk estimates are less than 1% of the
cPAD and, therefore, are not of concern.

 

Table 2.  Summary of Dietary (Food + Drinking Water) Exposure and Risk
for Nicosulfuron.

Population Subgroup	Acute (95th Percentile)	Chronic	Cancer

	Exposure (mg/kg/day)	% aPAD	Exposure

(mg/kg/day)	% cPAD	Exposure

(mg/kg/day)	Risk

General U.S. Population	N/A	N/A	0.000300	<1	N/A	N/A

All Infants (< 1 year old)

	0.000454	<1

Children 1-2 years old

	0.000835	<1

Children 3-5 years old

	0.000766	<1

Children 6-12 years old

	0.000540	<1

Youth 13-19 years old

	0.000362	<1

Adults 20-49 years old

	0.000225	<1

Adults 50+ years old

	0.000151	<1

Females 13-49 years old

	0.000226	<1

N/A = Not Applicable

VII.	Characterization of Inputs/Outputs

This assessment is a screening-level evaluation.  The inputs and
assumptions used in this assessment are highly conservative with respect
to dietary exposure and the exposure estimates presented in Table 2 are
likely to overestimate any actual dietary exposures to nicosulfuron.  

VIII.	Conclusions

There are no dietary exposure considerations that would preclude
establishing tolerances for residues of nicosulfuron or granting the
requested uses.

IX.	List of Attachments

Attachment 1.  Summary of input values for the chronic dietary
assessment of nicosulfuron.

Attachment 2.  Results of the chronic dietary exposure and risk
assessment for nicosulfuron.

Attachment 1.  Summary of input values for the chronic dietary
assessment of nicosulfuron.

U.S. Environmental Protection Agency                                
Ver. 2.00

DEEM-FCID Chronic analysis for NICOSULFURON                      
1994-98 data

Residue file: C:\Documents and Settings\mdoherty\My Documents\Chemistry
Reviews\Nicosulfuron\129008 - 2009 Chronic.R98

                                                           Adjust. #2
NOT used

Analysis Date 09-30-2009             Residue file dated:
09-30-2009/11:44:06/8

Reference dose (RfD) = 1.25 mg/kg bw/day

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

Food Crop                                       Residue      
Adj.Factors      Comment

EPA Code  Grp  Food Name                          (ppm)       

                                                             #1        
#2 

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

21000440 M    Beef, meat                         0.010000   1.000     
1.000   

21000441 M    Beef, meat-babyfood                0.010000   1.000     
1.000   

21000450 M    Beef, meat, dried                  0.010000   1.920     
1.000   

21000460 M    Beef, meat byproducts              0.050000   1.000     
1.000   

21000461 M    Beef, meat byproducts-babyfood     0.050000   1.000     
1.000   

21000470 M    Beef, fat                          0.010000   1.000     
1.000   

21000471 M    Beef,fat-babyfood                  0.010000   1.000     
1.000   

21000480 M    Beef, kidney                       0.050000   1.000     
1.000   

21000490 M    Beef, liver                        0.050000   1.000     
1.000   

21000491 M    Beef, liver-babyfood               0.050000   1.000     
1.000   

15001200 15   Corn, field, flour                 0.100000   1.000     
1.000   

15001201 15   Corn, field, flour-babyfood        0.100000   1.000     
1.000   

15001210 15   Corn, field, meal                  0.100000   1.000     
1.000   

15001211 15   Corn, field, meal-babyfood         0.100000   1.000     
1.000   

15001220 15   Corn, field, bran                  0.100000   1.000     
1.000   

15001230 15   Corn, field, starch                0.100000   1.000     
1.000   

15001231 15   Corn, field, starch-babyfood       0.100000   1.000     
1.000   

15001240 15   Corn, field, syrup                 0.100000   1.500     
1.000   

15001241 15   Corn, field, syrup-babyfood        0.100000   1.500     
1.000   

15001250 15   Corn, field, oil                   0.100000   1.000     
1.000   

15001251 15   Corn, field, oil-babyfood          0.100000   1.000     
1.000   

15001260 15   Corn, pop                          0.100000   1.000     
1.000   

15001270 15   Corn, sweet                        0.100000   1.000     
1.000   

15001271 15   Corn, sweet-babyfood               0.100000   1.000     
1.000   

23001690 M    Goat, meat                         0.010000   1.000     
1.000   

23001700 M    Goat, meat byproducts              0.050000   1.000     
1.000   

23001710 M    Goat, fat                          0.010000   1.000     
1.000   

23001720 M    Goat, kidney                       0.050000   1.000     
1.000   

23001730 M    Goat, liver                        0.050000   1.000     
1.000   

24001890 M    Horse, meat                        0.010000   1.000     
1.000   

27002220 D    Milk, fat                          0.010000   1.000     
1.000   

27002221 D    Milk, fat - baby food/infant for   0.010000   1.000     
1.000   

27012230 D    Milk, nonfat solids                0.010000   1.000     
1.000   

27012231 D    Milk, nonfat solids-baby food/in   0.010000   1.000     
1.000   

27022240 D    Milk, water                        0.010000   1.000     
1.000   

27022241 D    Milk, water-babyfood/infant form   0.010000   1.000     
1.000   

27032251 D    Milk, sugar (lactose)-baby food/   0.010000   1.000     
1.000   

29003120 M    Rabbit, meat                       0.010000   1.000     
1.000   

26003390 M    Sheep, meat                        0.010000   1.000     
1.000   

26003391 M    Sheep, meat-babyfood               0.010000   1.000     
1.000   

26003400 M    Sheep, meat byproducts             0.050000   1.000     
1.000   

26003410 M    Sheep, fat                         0.010000   1.000     
1.000   

26003411 M    Sheep, fat-babyfood                0.010000   1.000     
1.000   

26003420 M    Sheep, kidney                      0.050000   1.000     
1.000   

26003430 M    Sheep, liver                       0.050000   1.000     
1.000   

86010000 O    Water, direct, all sources         0.000685   1.000     
1.000   

86020000 O    Water, indirect, all sources       0.000685   1.000     
1.000   

Attachment 2.  Results of the chronic dietary exposure and risk
assessment for nicosulfuron.

U.S. Environmental Protection Agency                                
Ver. 2.00

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

Residue file name: C:\Documents and Settings\mdoherty\My
Documents\Chemistry Reviews\Nicosulfuron\129008 - 2009 Chronic.R98

                                                 Adjustment factor #2
NOT used.

Analysis Date 09-30-2009/11:44:41     Residue file dated:
09-30-2009/11:44:06/8

Reference dose (RfD, Chronic) = 1.25 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)                     0.000300                
0.0%

U.S. Population (spring season)             0.000302                
0.0%

U.S. Population (summer season)             0.000315                
0.0%

U.S. Population (autumn season)             0.000295                
0.0%

U.S. Population (winter season)             0.000288                
0.0%

Northeast region                            0.000273                
0.0%

Midwest region                              0.000325                
0.0%

Southern region                             0.000294                
0.0%

Western region                              0.000308                
0.0%

Hispanics                                   0.000351                
0.0%

Non-hispanic whites                         0.000291                
0.0%

Non-hispanic blacks                         0.000316                
0.0%

Non-hisp/non-white/non-black                0.000278                
0.0%

All infants (< 1 year)                      0.000454                
0.0%

Nursing infants                             0.000134                
0.0%

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                         0.000576                 0.0%

Children 1-6  yrs                           0.000773                
0.1%

Children 7-12 yrs                           0.000517                
0.0%

Females 13-19 (not preg or nursing)         0.000310                
0.0%

Females 20+ (not preg or nursing)           0.000181                
0.0%

Females 13-50 yrs                           0.000247                
0.0%

Females 13+ (preg/not nursing)              0.000248                
0.0%

Females 13+ (nursing)                       0.000239                
0.0%

Males 13-19 yrs                             0.000412                
0.0%

Males 20+ yrs                               0.000215                
0.0%

Seniors 55+                                 0.000147                
0.0%

Children 1-2 yrs                            0.000835                
0.1%

Children 3-5 yrs                            0.000766                
0.1%

Children 6-12 yrs                           0.000540                
0.0%

Youth 13-19 yrs                             0.000362                
0.0%

Adults 20-49 yrs                            0.000225                
0.0%

Adults 50+ yrs                              0.000151                
0.0%

Females 13-49 yrs                           0.000226                
0.0%

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

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