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### UNITED STATES ENVIRONMENTA L PROTECTION A GENCY

WASHINGTON, D.C. 20460 OFFICE OF PREVENTION, PESTICIDE

AND TOXIC SUBSTANCES 

### MEMORANDUM Date: 15 October 2009 SUBJECT: Nicosulfuron

– Dietary Exposure and Risk Analy sis to Evaluate a New Use Request for Grasses. PC Code: 12 9008 DP Barcode: D 369742 MRID No.: NA Registration No. : 352 - IRO Petition No.: 8F7501 Regulatory Action: Section 3 Assessment Type: Dietary

– Single Chemical Registration Case No.: NA T XR No. : None CAS No.: 111991 - 09 - 4 Decision No.: 404568 40 CFR 180. 454 

### FROM: Michael A. Dohert y, Ph.D., Senior Chemist Risk Assessment Branch II Health Effects Division (7509P) 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: M ichael A. Dohert y, Ph.D., Senior Chemist Risk Assessment Branch II Health Effects D ivision (7509P) Mindy Ondish/Jim Tompkins (RM 25) Herbicide Branch Registration Division (7505 P) Executive Summary A chronic combined dietary ( food + drinking water) exposure and risk assessment was con ducted using the Dietary Exposur e Evaluation Model DEEM - FCIDTM, Version 2.03 which use s food consumption data from the U.S. Department of Agriculture’s Continuing Survey s of Food Intakes by

Individuals (CSFII) from 1994 - 1996 and 1998. The analysis was completed toPage 2 of 7



### evaluate a requested us e 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 analy sis assumes tolerance - level residues and 10 0% crop treated for all foods (corn, meat, and milk commodities). Even with these highl y conservative assumptions, the resulting risk estimates are le ss 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 concer

n s 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 i s 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 dep arture (POD, NOAEL , LOAEL, e.g.) divided by the required uncertainty

or safet y factors. For acute and non - cancer chronic exposures, HED is concerned when estimated dietary risk exceeds 100% of the PAD. HED is generall y concerned when estimated cancer ris k 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 : 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 c onducted by D. Hrd y ( 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. T he recommended tolerances for livestock commodities ( of cattle, horses, and sheep onl y) are 0.01 ppm for meat and fat, 0.05 ppm for meat by products, and 0.01 ppm for milk. A de fault processing factor of 1.5 from DEEM 7.78 was used for corn sy rup, and it w as assumed that 100% of foods in the assessment had residue s of nicosulfuron ( i.e. , 100% crop treated). The inputs used in the assessment are provided in Attachment 1. III. 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 RiskPage 3 of 7



### Assessment” by

L . Liu (28 July

2004; D301842, D302623, D302624) and incorporated directl y 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 cons idered 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: http://www.epa.gov/oppefed1/models/water/ . IV. DEEM - FCIDTM Program and Consumption Information The nicosulfuron chronic dietary exposure assessment wa s conducted using the Dietary Exposure Evaluation Model software with the Food Commodity Intake Database DEEM FCIDTM, Version 2.03 , which incorporates consumption data from USDA’s Continuing Survey s of Food Intakes b y Ind ividuals (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 day s. 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 anal ys is of the 1994 - 96, 98 CSFII consumption data, which took into account dietary

patterns and survey

re spondents, HED concluded that it is most appropriate to report risk for the following population subgroups: the general U.S. population, all infants (<1 ye ar old), children 1 - 2, children 3 - 5, children 6 - 12, youth 13 - 19, adults 20 - 49, females 13 - 49, and adu lts 50+ y ears 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 dail y 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 generall y 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 an y additional safet y factors are required to account for these data gaps given the available data and effec ts observed. The doses and endpoints for dietary risk assessment are summarized in Table 1.Page 4 of 7

Table 1 . Summary of Toxicological Doses and Endpoints for Nicosulfuron for Use in Dietary Hum an Health Risk Assessments Exposure/ Scenario Point of

Departure Uncertainty and

FQPA Safety Factors RfD & PAD,

for Risk Assessment Study and Toxicological Effects Ac ute Dietary ( All p opulation s ) An endpoint of concern attributable to a single dose was not identified .

Chronic Dietary (All Populations) N OAEL= 125

mg /kg/day UF A= 10x

UF H = 10x FQPA SF= 1 x Chronic RfD =

cPAD = 1.25 mg/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 tumor i gen ic

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. UF A = e xtrapolation from animal to human (interspecies). UF H = 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 - FCIDTM anal ys es 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 y ear 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 e stimates 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 Ac ute ( 95th Percentile) Chronic Cancer Exposure (mg/kg/day) % aPAD E xposure (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 y ears old 0.000766 <1 Children 6 - 12 y ears old 0.000540 <1 Youth 13 - 19 y ears old 0.000362 <1 Adults 20 - 49 y ears old 0.000225 <1 Adults 50+ years old 0.000151 <1 Fem ales 13 - 49 y ears old 0.000226 <1 N/A = Not ApplicablePage 5 of 7



### VII. Characterization of Inputs/Outputs This assessment is a screening - level evaluation. The inputs and assumptions used in this assessment are highl y conservative with respect to dietary exposure and the exposure estimates presented in Table 2 are likely to overestimate an y 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 reques t ed 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.Page 6 of 7



### Attachment 1. Summary of input values for the chronic dietary assessment of nicosulfuron. U.S. Environmental Protection Age ncy 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, d ried 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 1.00 0 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 1.00 0 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 1.00 0 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 1.000Page 7 of 7



### 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 n ame: 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 - 20 09/11:44:06/8 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% Non - nursing infants 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% Yout h 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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