COMPANY NOTICE OF FILING OF PETITION TO ESTABLISH IMPORT

TOLERANCES FOR SAFLUFENACIL EPA Registration Division contact: Kathryn Montague , Herbicide Branch, Product Manager , Team 23, 703 - 305 - 1243 BASF Corporation (PP 0E7806) EPA has received a pesticide petition ( 0F7806 ) 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 Cosmetic Act (FFDCA), 2 1 U.S.C. 346a(d), to amend 40 CFR part 180. 649 by establishing import tolerance s for residues of s aflufenacil , including its metabolites and degradates, in or on the raw agricultural commodities banana, whole fruit at 0. 03 parts per million (ppm) and coffe e, green bean at 0.03 ppm and mango, fruit at 0.03 ppm . Compliance with the tolerance levels is to be determined by measuring only

the sum of saflufenacil, 2 - chloro - 5 - [3,6 - dihydro - 3 - methyl - 2,6 - dioxo - 4 - (trifluoromethyl) - 1(2H ) - py rimidinyl] - 4 - fluoro -N

- [[m ethyl(1 - methylethyl)amino]sulfonyl]benzamide, and its metabolites N - [2 - chloro - 5 - (2,6 - dioxo - 4 - (trifluoromethyl) - 3,6 - dihydro - 1(2H ) - py rimidinyl) - 4 - fluorobenzoyl] -N'- isopropylsulfamide and N - [4 - chloro - 2 - fluoro - 5 - ({[(isopropylamino)sulfonyl]amino}carbonyl )phenyl]urea, calculated as the stoichiometric equivalent of saflufenacil, in or on the commodities. 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 f ully 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 m etabolism 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 or a postemergence directed at the base of plants underneath th e leaf canopy . application. The residues of concern for the tolerance expression and risk assessment consist of Saflufenacil, M800H11, and M800H35 . 2. Analytical method. Adequate enforcement methodology (liquid chromatography/mass spectrometry /mass spe ctrometry

(L CMS/MS) methods D0603/02 (plants) and L0073/01 (livestock)) is available to enforce the tolerance expression . 3. Magnitude of residues. Field trials in Central and South America were carried out to determine the magnitude of the residue fol lowing a postemergence - directed spray at the base of plants underneath the leaf canop y of Saflufenacil applied for weed control2

in banana, coffee and mango plantations . The number and locations of field trials are in accordance with OPPTS Guideline 860.150 0. Field trials were carried out using the maximum label rates, the maximum number of applications, and the minimum pre harvest interval (PHI) for each of the crop s . Detected combined residues of Saflufenacil plus metabolites in the crop support the propos ed tolerances. B. Toxicological Profile 1. Acute toxicity. Saflufenacil has low acute toxicity via the oral, dermal, and inhalation routes of exposure. It is slightly irritating to the eye but is neither a dermal irritant nor sensitizer . 2. Gen otoxicty. Saflufenacil is weakly clastogenic in the in vitro chromosomal aberration assay

in V79 cells in the presence of 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 susceptibility

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

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

–generation reproduction study in 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 changes 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 qualitative susceptibility . 4. Subchronic toxicity. Short - term, subchronic, and chronic toxicity studies in rats, mice, and dogs identif

ied the hematopoietic s ys tem as the target organ of saflufenacil. Protoporphy

rinogen oxidase inhibition in the mammalian species may result in disruption of heme s ynthesis which in turn causes anemia. In these studies, decreased hematological parameters (r ed blood cells (RBC), hematocrit (Ht), mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), and mean corpuscular hemoglobin concentration (MCHC)) were seen at about the same dose level across species, except in the case of the dog, where the e ffects 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 ly

mphoid 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 exposures3

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 neuropatholo gy

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 any other neuropathological changes and was considered a reflection of a mild and transient general systemic toxicity and not a substance - specific neurotoxic effect. In the subchronic neurotoxicity study , s ys temic toxicity

(anemia), but no evidence of neurotoxicity , was seen in males and female s. There was no evidence of immunotoxity in the toxicity

database for Saflufenacil. In the immunotoxicity

study conducted in male mice, s ystemic toxicity (signs of anemia and liver effects) w as seen, but the effects were not indicative of immunotoxicity . There were no effects on sheep red blood cell (SRBC) IgM antibody titers or immune sy stem organ weights (spleen and thymus) in the treated mice. In the 90 - day oral toxicity

study in rats, the increase in spleen weight seen onl y in rats is attributable to an increased clearance of defective RBCs (i.e., defective hemoglobin sy nthesis) and is thus an indication of toxicity to the hematopoietic system rather than to the immune system . 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 Saflufenacil is well absorbed and rapidl y excreted. The max imum 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 exc retion 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 from urine and feces. There were no significant gender differences in metabolic profiles. Saflufenacil was metabolized by

three major transformation steps, which were demethylation of the uracil ring s ys tem, degradation of the N - methyl -N

- isopropyl group to NH 2 , and cleavage of the uracil ring, forming a sulfo nylamide group. The metabolism of Saflufenacil in the animals is well understood. 7. Metabolite toxicology . No metabolites of toxicological concern are identified.4 8. Endocrine disruption . No specific 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 any endocrine disruption. C. Aggregate Exposure 1. Dietary exposure. E xposure 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. This analysis include s all the crops with established tolerances values as of November 2010 , plus the proposed tolerance values (pending EPA review, submitted June 2010 and July 2010 for legumes vegetables crop sub group 6 C beans and peas , soy bean, c otton , and canola) plus the p roposed tolerance value s for banana, coffee and mango . i. Food. Acute Dietary

Exposure Assessment Acute dietary

exposure estimates were conducted using the currently established tolerances for S aflufenacil (40 CFR 180.649) , plus the pending proposed t olerances 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) , crop group 20A oi lseeds rapeseed, plus the currentl y proposed tolerances for banana, coffee, mango , and plus the 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 Fo od 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 resulting exposure estimates were compared against the S aflufen acil 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

factors of 100X and an FQPA safety factor of 1. The exposure 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 Analysis Considering all Proposed Tolerances using DEEM - FCID at the 95 th Percentile , food onl y

Population Exposure Estimate %aPAD Subgroups (mg/kg b.w./day) U.S. Population 0.001313 0.035 All Infants (< 1 year old) 0.002468 0.05 Children (1 - 2 years old) 0.003014 0.06 Children (3 - 5 years old) 0.002407 0.05 Children (6 - 12 years old) 0.001485 0.03 Youth (13 - 19 years old) 0.000949 0.02 Adults (20 - 49 years old) 0.000772 0.02 Adults (50+ years old) 0.000679 0.01 Females (13

– 49 years old) 0.000759 0.02 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) , plus the pending 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), crop group 20A oilseeds rapeseed, plus the currentl y proposed tolerances for banana, c offee, mango, and plus the 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 C ommodity 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 safety factor of 1. The most highly expos ed population sub - group was children 1 - 2 years of age which utilized 3. 3 % cPAD. The results of the chronic dietary assessment are presented in Table 2. Table 2. Results for S aflufenacil Chronic Dietary Exposure Analy sis Considering all Proposed Tolerances using DEEM - FCID , food only

Population Exposure Estimate %cPAD Subgroups (mg/kg b.w./day) U.S. P opulation 0.000459 1.0 All Infants (< 1 year old) 0.001051 2.3 Children (1 - 2 years old) 0.001537 3.3 Children (3 - 5 years old) 0.001196 2.66 Children (6 - 12 years old) 0.000716 1.6 Youth (13 - 19 years old) 0.000413 0.9 Adults (20 - 49 years old) 0.000328 0 .7 Adults (50+ years old) 0.000298 0.6 Females (13 - 49 years old) 0.000321 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 values 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 estimates, 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 water 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 aflufenacil 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. Populati on 0.000423 0.01 All Infants (< 1 year 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. 01 Adults (50+ years old) 0.000354 0.01 Females (13 - 49 years old) 0.000394 0.017

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 year 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 old) 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 f rom food and water (Table 5). The results demonstrate that there are no safety concerns for any subpopulation based on the proposed uses and the results meet the FQPA standard of reasonable certainty of no harm. Table 5. Estimated Acute Aggregate Expo sure 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 0.001313 0.000423 0.00174 0.03 All Infants (< 1 yr old) 5 0.002468 0.001535 0.0 0400 0.08 Children 1 - 2 years 5 0.003014 0.000664 0.00368 0.07 Children 3 - 5 years 5 0.002407 0.000607 0.00301 0.06 Children 6

– 12 years 5 0.001485 0.000422 0.00191 0.04 Youth 13 - 19 years 5 0.000949 0.000343 0.00129 0.03 Adults 20 - 49 years 5 0.000772 0 .000392 0.00116 0.02 Adults + 50 5 0.000679 0.000354 0.00103 0.02 Females 13 - 49 years 5 0.000759 0.000394 0.00115 0.02 Short - and Intermediate - Term Aggregate Exposure and Risk (food, water, and residential) Short - and intermediate - term aggregate risk a ssessments 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.8

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 safety concerns for any subpopulation based on the proposed uses and the results meet the FQPA standard of reasonable certainty of no harm. Table 6. Estimated Chronic Aggregate 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 0.000459 0.000053 0.00051 1.1 All Infants (< 1 yr old) 0.046 0.001051 0.000173 0.00122 2.7 Children 1 - 2 years 0.046 0.001537 0.000078 0.00162 3.5 Children 3 - 5 years 0.046 0.001196 0.000073 0.00127 2.8 Children 6

– 12 years 0.046 0.000716 0.000051 0.00077 1.7 Youth 13 - 1 9 years 0.046 0.000413 0.000038 0.00045 1.0 Adults 20 - 49 years 0.046 0.000328 0.000049 0.00038 0.8 Adults + 50 0.046 0.000298 0.000052 0.00035 0.8 Females 13 - 49 years 0.046 0.000321 0.000049 0.00037 0.8 ] 2. Non - dietary exposure . The term ‘‘residential exposure’’ is used to refer to non occupational, 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 Agen cy 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 oth er 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 su

bstances. E. Safety Determination 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.9 2. Infants and children . 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 propo sed uses. F. International Tolerances There 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 res idues of S aflufenacil and its metabolites in similar crops and livestock commodities in Canada .