NOTICE OF FILING FOR PESTI CI DE PETITION (PP#0F7744) PUBLISHED IN THE

FEDERAL REGISTER EPA Registration Division contact: Kathry n Montague , Herbicide Branch, Product Manager , Team 23, 703 - 305 - 1243 BASF Corporation Pe sticide Petition #0F7744 EPA has received a pesticide petition ( 0F7744 ) from BASF Corporation , 26 Davis Drive, P.O. Box 13528, Research Triangle Park, North Carolina 27709 - 3528 proposing, pursuant to section 408(d) of the Federal Food, Drug, and Cosmet ic Act (FFDCA), 21 U.S.C. 346a(d), to amend 40 CFR part 180. 649 by establishing a tolerance for combined residues of S aflufenacil (2 - chloro - 5 - [3,6 - dihydro - 3 - methyl - 2,6 - dioxo - 4 - (trifluorometh yl ) - 1(2H) - py rimidinyl] - 4 - fluoro - N - [[methyl(1 - methylethyl)amino]sul fonyl]benzamide ) and its metabolites N - [2 - chloro - 5 - (2,6 - dioxo - 4 - (trifluorometh yl ) - 3,6 - dihydro - 1(2H) - py rimidinyl) - 4 - fluorobenzo yl ] - N' - isopropylsulfamide and N - [4 - chloro - 2 - fluoro - 5 - ({[(isopropylamino)sulfonyl]amino} carbon yl )phenyl]urea, calculated as the st oichiometric equivalent of S aflufenacil in or on the raw agricultural commodity oilseeds, cottonseed subgroup 20C, gin b y products at 3.5 parts per million (ppm) and commodity oilseeds, cottonseed subgroup 20C, undelinted seed at 0.2 parts per million (ppm ) and commodity oilseeds, sunflower subgroup 20B, seed at 1 . 0 parts per million (ppm) and commodity pea, vines at 8 . 0 parts per million (ppm) and commodity soy bean, aspirated grain fractions at 4 . 52 parts per million (ppm) and commodity

soy bean, hulls at 0 . 42 parts per million (ppm) and commodity soy bean, seed at 0. 1 parts per million (ppm) and commodity vegetable, legume, subgroup 6C, beans, dry

at 0. 5 parts per million (ppm) and commodity vegetable, legume, subgroup 6C, peas, dry

at 0. 1 parts per million (ppm) . EPA has determined that the petition contains data or information regarding the elements set forth in section 408 (d)(2) of FDDCA; however, EPA has not fully evaluated the sufficiency of the submitted data at this time or whether the data supports granting of the petition. Additional data may be needed before EPA rules on the petition. A. Residue Chemistry 1. Plant metabolism . Previously submitted metabolism data for corn, so yb ean, and tomato and a confined rotational crop study are adequate to elucidate the nature of the residue in plants resulting from preplant/preemergence application. The residues of concern for the tolerance expression and risk assessment consist of Saflufenacil, M800H11, and M800H35 . An additional nature of residue study was conducted on soy bean with a postemergence application in support of the proposed uses as harvest aid / desiccation. T he metabolism of Saflufenacil in plants following a postemergence2

application is similar to the metabolism of Saflufenacil in plants following a preplant/preemergence application. 2. Analy tical method. Adequate enforcement methodology (liquid chromatograph y/mass spectrometry /mass spectrometry

(L CMS/MS) methods D0603/02 (plants) and L0073/01 (livestock)) is available to enforce the t olerance expression . 3. Magnitude of residues. Field trials were carried out to determine the magnitude of the residue following a postemergence application of Saflufenacil made for harvest aid / desiccation uses in/on legumes vegetables (crop sub group 6 C dry beans and dry

peas ), soy bean, and cotton . The number and locations of field trials are in accordance with OPPTS Guideline 860.1500. Field trials were carried out using the maximum label rates, the maximum number of applications, and the minimum pre - harvest interval (PHI) for all the crops. Detected combined residues of Saflufenacil plus metabolites in all crops support the proposed tolerances. B. Toxicological Profile 1. Acute toxicity . Saflufenacil has low acute toxicity via the oral, derm al, and inhalation routes of exposure. It is slightly irritating to the eye but is neither a dermal irritant nor sensitizer . 2. Genotoxicty . Saflufenacil is weakl y clastogenic in the in vitro chromosomal aberration assay

in V79 cells in the presence o f S9 activation; however, the response was not evident in the absence of S9 activation. It is neither mutagenic in bacterial cells nor clastogenic in rodents in vivo .

3. Reproductive and developmental toxicity . In creased fetal and offspring susceptibil ity

t o S aflufenacil were observed in the developmental toxicity studies in the rat and rabbit and in the 2

– generation reproduction study i n the rat. Developmental effects such as decreased fetal body w eights and increased skeletal variations occurred at do ses that were not maternall y toxic in the developmental study i n rats, indicating increased quantitative susceptibility . In rabbits, developmental effects such as increased liver porph yrins were observed at doses that were not maternall y toxic, indicating increased quantitative susceptibility . In the 2

– generation reproduction study i n rats, offspring effects such as increased number of stillborn pups, decreased viability and lactation indices, decreased pre - weaning body w eight and/or body - weight gain, and c hanges in hematological parameters were observed at a dose resulting in less severe maternal toxicity

( decreased food intake, body weight/weight gain and changes in hematological parameters and organ weights indicative of anemia), indicating increased qual itative susceptibility . 4. Subchronic toxicity . Short - term, subchronic, and chronic toxicity studies in rats, mice, and dogs identified the hematopoietic system as the target organ of saflufenacil. Protoporphyrinogen oxidase inhibition in the mammalian species may result in disruption of heme sy

nthesis which in turn causes anemia. In these studies, decreased3

hematological parameters (red blood cells (RBC), hematocrit (Ht), mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), and mean corpusc ular hemoglobin concentration (MCHC)) were seen at about the same dose level across species, except in the case of the dog, where the effects were seen at a slightly higher dose. These effects occurred around the same dose level from the short - term through long - term exposures without increasing in severity. Effects were also seen in the liver (increased weight, centrilobular fatty change, and lymphoid infiltrate) in mice, the spleen (increased spleen weight and extramedullary hematopoiesis) in rats, and in both these organs (increased iron storage in the liver and extramedullary hematopoiesis in the spleen) in dogs. These effects also occurred around the same dose level from the short term through long - term exposures without increasing in severity . No dermal toxicity was seen at the limit dose in a 28

– day dermal toxicity

study in rats. There was no evidence of neurotoxicity or neuropathology

in the toxicity

database fo r S aflufenacil. In the acute neurotoxicity study , a decrease in motor activity was observed on the first day

of dosing at the limit dose in males only . The finding was not accompanied b y an y other neuropathological changes and was considered a reflection of a mild and transient general sy stemic toxicity and not a substance - specific neurotoxic ef fect. In the subchronic neurotoxicity study , s ys temic toxicity

(anemia), but no evidence of neurotoxicity , was seen in males and females. There is no evidence of i mmunotoxity in the S aflufenacil database. The increase in spleen weight seen onl y in rats i n the 90

– day oral toxicity

study is attributable to an increased clearance of defective RBCs (i.e., defective hemoglobin s ynthesis) and is thus an indication of toxicity

to the hematopoietic s ys tem rather than to the immune sy stem . 5. Chronic toxicity . Carcinogenicity studies in rats and mice showed no evidence of increased incidence of tumors at the tested doses. Saflufenacil is classified as ‘‘not likely to be carcinogenic to humans. 6. Animal metabolism. Rat metabolism data indicate that Saflufen acil is well absorbed and rapidl y excreted. The maximum concentration of Saflufenacil in blood and plasma was reached within 1 hour (h) of dosing and declined rapidl y after 24 h. Excretion of orally

dosed Saflufenacil was essentially complete within 96 h , with the majority eliminated within the first 24 to 48 h. There was a sex - dependent difference in the excretion of orall y administered Saflufenacil. The main route of elimination in male rats was via the feces, while urinary excretion was the major route of elimination in females. The sex - dependent excretion was more pronounced at the low - dose level than at the high - dose level. Also, males had significantly higher biliary

excretion of Saflufenacil residues than females. Exhalation was not a relevant excretion pathway of Saflufenacil. At 168 h after dosing, Saflufenacil residues remaining in tissues were very low and occurred mainl y in carcass, liver, skin, and gut contents. The parent molecule and 3 major metabolites were identified and isolated fro m urine and feces. There were no significant gender differences in metabolic profiles. Saflufenacil was metabolized by

three major transformation steps, which were demethylation of the4

uracil ring s ys tem, degradation of the N - methyl - N - isopropyl group to N H 2 , and cleavage of the uracil ring, forming a sulfon yl amide group. The metabolism of Saflufenacil in the animals is well understood. 7. Metabolite toxicology . No metabolites of toxicological concern are identified. 8. Endocrine disruption. No spec ific tests have been conducted with S aflufenacil to determine whether the chemical may have an effect in humans that is similar to an effect produced b y a naturally occurring estrogen or other endocrine effects. However, there were no significant findings in other relevant toxicity studies (e.g., sub - chronic and chronic toxicity , developmental toxicity and multi - generation reproductive studies) which would suggest that S aflufenacil produces an y endocrine disruption. C. Aggregate Exposure 1. Dietary exposure. Exposure assessments were conducted to evaluate the potential risk due to acute and chronic dietary exposure of the U.S. population to combined residues of S aflufenacil and metabolites M800H11 and M800H35. The current tolerance values are listed in the U.S. 40 CFR § 180.649. Th is analy sis include s all the crops with established tolerances values as of June 2010 plus the proposed tolerance values for legumes vegetables (crop sub group 6 C beans and peas) , soy bean, and c otton . i. Food. Acute Diet ary

Exposure Assessment Acute dietary

exposure estimates were conducted using the currently established tolerances for S aflufenacil (40 CFR 180.649) and currentl y proposed tolerances for soy bean, soy bean hulls, legume vegetables crop subgroup 6C dried shel led pea and bean (except soy

bean), cotton undelinted seed, cotton gin by products, crop group 7 foliage of legume vegetables group (based on pea vine data) , and higher residue levels in meat - by products (except liver) from goat, hog, sheep, horse, cattle, and liver from cattle, goat, hog, sheep, and horse based on the re - calculation of the feed burden containing feedstuffs with proposed tolerances . The assessment was conducted using tolerance values, default process factors, and 100% crop treatment factors. The consumption data was from the USDA Continuing Survey of Food Intake by

Individuals (CSFII 1994 - 1996, 1998) and the EPA Food Commodity Ingredient Database (FCID) using Exponent's Dietary Exposure Evaluation Module (DEEM - FCID) software. The result ing exposure estimates were compared against the S aflufen a cil acute Population Adjusted Dose (aPAD) of 5 mg/kg b.w./day for all populations. This endpoint is based on the NOAEL of 5 00 mg/kg/day with the standard inter - and intra species uncertainity

facto rs of 100X and an FQPA safet y factor of 1. The expos ure for all sub - population was less than 1.0 % utilization of the aPAD. The results of the acute dietary assessment are presented in Table 1. Table 1. Results for S aflufenacil Acute Dietary E xposure Ana ly sis Considering all Proposed Tolerances using DEEM - FCID at the 95 th Percentile , food onl y5 Population Exposure Estimate %aPAD Subgroups (mg/kg b.w./day) U.S. Population 0.001322 0.03 All Infants (< 1 ye ar old) 0.002475 0.05 Children (1 - 2 years old) 0.002974 0.06 Children (3 - 5 years old) 0.002383 0.05 Children (6 - 12 years old) 0.001457 0.03 Youth (13 - 19 years old) 0.000949 0.02 Adults (20 - 49 years old) 0.000759 0.02 Adults (50+ years old) 0.000702 0.01 Females (13

– 49 years old) 0.000744 0.01 The results of the anal ys is show that for all populations, the estimated exposures are well below the Agency 's level of concern (< 100% aPAD). Additional refinements in the dietary risk assessment (i.e. utilizing anticipated residue values, percent crop treated values) would further reduce the estimated exposure values. Chronic Dietary

Exposure Assessment Chronic dietary

exposure were conducted using the currently established tolerances for Sa flufenacil (40 CFR 180.649) and currentl y proposed tolerances for soy bean, soy bean hulls, legume vegetables crop subgroup 6C dried shelled pea and bean (except soy bean), cotton undelinted seed, cotton gin by products, crop group 7 foliage of legume vegetables group (based on pea vine data), and higher residue levels in meat - by - products (except liver) from goat, hog, sheep, horse, cattle, and liver from cattle, goat, hog, sheep, and horse based on the re - calculation of the feed burden containing feedstuffs with proposed tolerances. The assessment was conducted using t olerance values, default process factors, and 100% crop treatment factors. The consumption data was from the USDA Continuing Survey

of Food Intake by

Individuals (CSFII 1994 - 1996, 1998) and the EPA Food Commodity

Ingredient Database (FCID) using Exponent's Dietary Exposure Evaluation Module (DEEM - FCID) software. The chronic Population Adjusted Dose (cPAD) used for U.S. population and all sub populations is 0.046 mg/kg bw/day . This endpoint is based on the NOAEL value of 4.6 using the standard inter - and intra - species uncertainity factors of 100X and with a FQPA safet y factor of 1. The most highly expos ed population sub - group was children 1 - 2 years of age which utilized 3.2 % cPAD. The results of the chronic dietary assessment are presented in Table 2 . Table 2. Results for S aflufenacil Chronic Dietary E xposure Analy sis Considering all Proposed Tolerances using DEEM - FCID , food only

Population Exposure Estimate %cPAD Subgroups (mg/kg b.w./day) U.S. Population 0.000448 1.06 All Infants (< 1 ye ar ol d) 0.001039 2.3 Children (1 - 2 years old) 0.001472 3.2 Children (3 - 5 years old) 0.001171 2.5 Children (6 - 12 years old) 0.000698 1.5 Youth (13 - 19 years old) 0.000398 0.9 Adults (20 - 49 years old) 0.000319 0.7 Adults (50+ years old) 0.000302 0.7 Females (13 - 49 years old) 0.000315 0.7 The results of the anal ys is show that for all populations, the exposures are far below a level of concern (< 100% cPAD). Additional refinements in the chronic dietary risk assessment (i.e. utilizing anticipated residue v alues and percent crop treated values) would further reduce the estimated exposure values. ii. Drinking water . All S aflufenacil uses were examined at maximum use rates, maximum number of applications, and all proposed application methods to determine which use would result in the highest water concentrations. The highest water concentrations occurred from the Mississippi corn scenario (model) from an aerial application at 0.134 lb ai/A. Based on results from the PRZM/EXAMS and SCI - GROW models estimate s, the highest acute Estimated Drinking Water Concentrations (EDWC) for S aflufenacil were estimated to be 8.1 ug/L(ppb) in surface water and 0.36 ug/L in ground water. The highest chronic EDWC’s for S aflufenacil were estimated to be 2.5 ug/L in surface w ater and 0.36 ug/L in ground water. Drinking water exposure contributions were assessed based on the maximum estimated S aflufenacil water concentrations (acute 8.1 ug/L, chronic 2.5 ug/L), and water consumption and body

weights reported in CSFII, using DEEM - FCID software. The acute and chronic estimated water exposure values are summarized in Tables 3 and 4, respectivel y. Drinking water exposure accounts for less than 1 % of the aPAD and 1 % of the cPAD for all populations. Table 3. Results for S afluf enacil Acute Water Exposure Anal ys is Considering the Maximum Estimated Acute Drinking Water Concentration using DEEM - FCID

Population Water Exposure Estimate % aPAD Subgroups (mg/kg b.w./day) U.S. Population 0.000423 0.01 All Infants (< 1 ye ar old) 0. 001535 0.03 Children (1 - 2 years old) 0.000664 0.01 Children (3 - 5 years old) 0.000607 0.01 Children (6 - 12 years old) 0.000422 0.01 Youth (13 - 19 years old) 0.000343 0.01 Adults (20 - 49 years old) 0.000392 0.017

Adults (50+ years old) 0.000354 0.01 Femal es (13 - 49 years old) 0.000394 0.01 Table 4. Results for S aflufenacil Chronic Water Exposure Analy sis Considering the Maximum Estimated Chronic Drinking Water Concentration using DEEM - FCID

Population Water Exposure Estimate %cPAD Subgroups (mg/kg b.w./ day) U.S. Population 0.000053 0.1 All Infants (< 1 ye ar old) 0.000173 0.4 Children (1 - 2 years old) 0.000078 0.2 Children (3 - 5 years old) 0.000073 0.2 Children (6 - 12 years old) 0.000051 0.1 Youth (13 - 19 years old) 0.000038 0.1 Adults (20 - 49 years o ld) 0.000049 0.1 Adults (50+ years old) 0.000052 0.1 Females (13 - 49 years old) 0.000049 0.1 Acute Aggregate Exposure and Risk (food and water) The aggregate acute risk includes exposure of Saflufenacil from food and water (Table 5). The results demons trate that there are no safety concerns for an y subpopulation based on the proposed uses and the results meet the FQPA standard of reasonable certainty of no harm. Table 5. Estimated Acute Aggregate Exposure and Risk of S aflufenacil . Population Subgroup aPAD

(mg/kg/day) Food

Exposure (mg/kg/day) Water

Exposure (mg/kg/day) Total

Exposure (mg/kg/day) %

aPAD U.S. Population 5 0.001322 0.000423 0.00175 0.03 All Infants (< 1 yrold) 5 0.002475 0.001535 0.00401 0.08 Children 1 - 2 years 5 0.002974 0.00066 4 0.00364 0.07 Children 3 - 5 years 5 0.002383 0.000607 0.00299 0.06 Children 6

– 12 years 5 0.001457 0.000422 0.00188 0.04 Youth 13 - 19 years 5 0.000949 0.000343 0.00129 0.03 Adults 20 - 49 years 5 0.000759 0.000392 0.00115 0.02 Adults + 50 5 0.000702 0.0 00354 0.00106 0.02 Females 13 - 49 years 5 0.000744 0.000394 0.00114 0.02 Short - and Intermediate - Term Aggregate Exposure and Risk (food, water, and residential)8

Short - and intermediate - term aggregate risk assessments include exposure from food, water, and residential uses. There are no residential uses for S aflufenacil , therefore, a short - and intermediate - term aggregate risk assessment is not required. Chronic Aggregate Exposure and Risk (food and water) The aggregate chronic risk includes exposure of S aflufenacil from food and water (Table 6). The results demonstrate there are no safet y concerns for an y subpopulation based on the proposed uses and the results meet the FQPA standard of reasonable certainty of no harm. Table 6. Estimated Chronic A ggregate Exposure and Risk of S aflufenacil Population Subgroup cPAD

(mg/kg/day) Food Exposure

(mg/kg/day) Water Exposure

(mg/kg/day) Total

Exposure (mg/kg/day) % cPAD U.S. Population 0.046 0.000448 0.000053 0.00050 1.1 All Infants (< 1 yrold) 0.046 0.0 01039 0.000173 0.00121 2.6 Children 1 - 2 years 0.046 0.001472 0.000078 0.00155 3.4 Children 3 - 5 years 0.046 0.001171 0.000073 0.00124 2.7 Children 6

– 12 years 0.046 0.000698 0.000051 0.00075 1.6 Youth 13 - 19 years 0.046 0.000398 0.000038 0.00044 0.9 Ad ults 20 - 49 years 0.046 0.000319 0.000049 0.00037 0.8 Adults + 50 0.046 0.000302 0.000052 0.00035 0.8 Females 13 - 49 years 0.046 0.000315 0.000049 0.00036 0.8 2. Non - dietary

exposure. The term ‘‘residential exposure’’ is used to refer to non occupat ional, non - dietary exposure (e.g., for lawn and garden pest control, indoor pest control, termiticides, and flea and tick control on pets). Saflufenacil is not registered for any specific use patterns that would result in residential exposure. Therefore, a non dietary exposure and risk evaluation was not conducted. D. Cumulative Effects Section 408(b)(2)(D)(v) requires that, when considering whether to establish, modify , or revoke a tolerance, the Agency consider “available information'' concerning the cumulative effects of a particular pesticide's residues and “other substances that have a common mechanism of toxicity ." EPA has not found S aflufenacil to share a common mechanism of toxicity

with any other substances, and S aflufenacil does not appear to produce a toxic metabolite produced b y other substances. For the purposes of this tolerance petition , therefore, EPA will assume that S aflufenacil does not have a common mechanism of toxicity

with other substances. E. Safet y Determination9 1. U.S. population. Based on the current risk assessments, EPA may conclude that there is a reasonable certainty that no harm will result to the general population from aggregate exposure to Saflufenacil residues from the proposed uses. 2. Infants and childre n. Based on the current risk assessments, EPA may conclude that there is a reasonable certainty that no harm will result to infants and children from aggregate exposure to Saflufenacil residues from the proposed uses. F. International Tolerances The re are no Codex maximum residue limits (MRLs) established for residues of S aflufenacil and its metabolites in crops or livestock commodities. The residue definition and harmonized MRL s are established for residues of S aflufenacil and its metabolites in sim ilar crops and livestock commodities in Canada .