EPA REGISTRATION DIVISION COMPANY NOTICE OF FILING FOR PESTICIDE PETITIONS 

PUBLISHED IN THE FEDERAL REGISTER

(7/1/2007)(Rice Tolerance Petition, December 2012)

EPA Registration Division contact: Kathryn Montague, Herbicide Branch, Product Manager, 

Team 23, 703-305-1243

BASF Corporation

2F8129

EPA has received a pesticide petition (2F8129) 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), 21 U.S.C. 346a(d), to 

amend 40 CFR part 180.649 by amending tolerances for residues of Saflufenacil, including its 

metabolites and degradates, in or on the raw agricultural commodities rice straw at 0.30 parts 

per million (ppm). Compliance with the tolerances 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)-pyrimidinyl]-4-fluoro-N-[[methyl(1-methylethyl)amino]sulfonyl]benzamide, and its 

metabolites N-[2-chloro-5-(2,6-dioxo-4-(trifluoromethyl)-3,6-dihydro-1(2H)-pyrimidinyl)-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 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, soybean, and 

tomato and a confined rotational crop study are adequate to elucidate the nature of the 
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residue in plants resulting from preplant/preemergence application, a postemergencedirected at the base of plants underneath the leaf canopy application, and a preharvest/desiccant application. An additional nature of residue study was conducted with a 

postemergence application in rice as a representative monocot (grass) species. The 

metabolism of Saflufenacil in plants following a postemergence application is similar to the 

metabolism of Saflufenacil in plants following a preplant/preemergence application. 

Therefore, 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 spectrometry (LCMS/MS) methods D0603/02 

(plants) and L0073/01 (livestock)) is available to enforce the tolerance expression.

3. Magnitude of residues. Field trials in the US were carried out to determine the 

magnitude of the residue following sequential applications of Saflufenacil made 

preplant/preemergence followed by postemergence in rice. Field trials were carried out using

the maximum label rates, the maximum number of applications, and the minimum preharvest interval (PHI) for use in both drilled-/dry-seeded rice and water-seeded rice cultures. 

Detected combined residues of Saflufenacil plus metabolites in the crop commodities support 

the proposed 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. Genotoxicty. 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. Increased fetal and offspring susceptibility 

to Saflufenacil were observed in the developmental toxicity studies in the rat and rabbit and 
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in the 2–generation reproduction study in the rat. Developmental effects such as decreased 

fetal body weights and increased skeletal variations occurred at doses that were not 

maternally 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 maternally 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 preweaning body weight 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 identified the hematopoietic system as the target organ of saflufenacil. 

Protoporphyrinogen oxidase inhibition in the mammalian species may result in disruption of 

heme synthesis which in turn causes anemia. In these studies, decreased hematological 

parameters (red 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 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 for 

Saflufenacil. 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 by 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, systemic toxicity (anemia), but no evidence of neurotoxicity, was seen in 

males and females. 

There was no evidence of immunotoxity in the toxicity database for Saflufenacil. In the 

immunotoxicity study conducted in male mice, systemic toxicity (signs of anemia and liver 
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effects) was seen, but the effects were not indicative of immunotoxicity. There were no 

effects on sheep red blood cell (SRBC) IgM antibody titers or immune system organ weights 

(spleen and thymus) in the treated mice. In the 90-day oral toxicity study in rats, the increase 

in spleen weight seen only in rats is attributable to an increased clearance of defective RBCs 

(i.e., defective hemoglobin synthesis) 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 rapidly excreted. The maximum concentration of Saflufenacil in blood and plasma was 

reached within 1 hour (h) of dosing and declined rapidly 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 orally 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 mainly 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 

system, degradation of the N-methyl-N-isopropyl group to NH2, and cleavage of the uracil ring, 

forming a sulfonylamide 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 specific tests have been conducted with Saflufenacil to 

determine whether the chemical may have an effect in humans that is similar to an effect 
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produced by 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 

Saflufenacil produces any 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 

Saflufenacil and metabolites M800H11 and M800H35. The current established tolerance 

values are listed in the U.S. 40 CFR § 180.649. This analysis includes all the crops with 

established tolerances, plus the proposed import tolerances (pending EPA review, submitted 

July 2012) for sugarcane, cane at 0.03 ppm, sugarcane, molasses at 0.075 ppm, and sugarcane, 

refined sugar at 0.045 ppm, plus the proposed amended tolerance values on rice 

commodities.

i. Food.

Acute Dietary Exposure Assessment

Acute dietary exposure estimates were conducted using the currently established tolerances 

for Saflufenacil (40 CFR 180.649), plus the proposed import tolerances (pending EPA review, 

submitted July 2012) for sugarcane, cane at 0.03 ppm, sugarcane, molasses at 0.075 ppm, and 

sugarcane, refined sugar at 0.045 ppm, plus the proposed amended tolerance values on rice 

commodities. 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 (DEEMFCID) software. 

The resulting exposure estimates were compared against the Saflufenacil acute Population 

Adjusted Dose (aPAD) of 5 mg/kg b.w./day for all populations. This endpoint is based on the 

NOAEL of 500 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.
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Table 1. Results for Saflufenacil Acute Dietary Exposure Analysis Considering all 

Proposed Tolerances using DEEM-FCID at the 95th Percentile, food only

Population Exposure Estimate %aPAD

Subgroups (mg/kg b.w./day)

U.S. Population 0.001313 0.03

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 analysis 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 estimates were conducted using the currently established tolerances 

for Saflufenacil (40 CFR 180.649), plus the proposed import tolerances (pending EPA review, 

submitted July 2012) for sugarcane, cane at 0.03 ppm, sugarcane, molasses at 0.075 ppm, and 

sugarcane, refined sugar at 0.045 ppm, plus the proposed amended tolerance values on rice 

commodities. 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 (DEEMFCID) software. 
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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 exposed 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 Saflufenacil Chronic Dietary Exposure Analysis Considering all 

Proposed Tolerances using DEEM-FCID, food only

Population Exposure Estimate %cPAD

Subgroups (mg/kg b.w./day)

U.S. Population 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 2.6

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 analysis 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 Saflufenacil 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 
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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’s) for Saflufenacil 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 Saflufenacil 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 

Saflufenacil 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, respectively. Drinking 

water exposure accounts for less than 1% of the aPAD and 1% of the cPAD for all populations. 

Table 3. Results for Saflufenacil Acute Water Exposure Analysis 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 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 0.01

Table 4. Results for Saflufenacil Chronic Water Exposure Analysis Considering the 

Maximum Estimated Chronic Drinking Water Concentration using DEEM-FCID 
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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 from 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 Exposure and Risk of Saflufenacil. 

Population Subgroup Food Exposure 

(mg/kg/day)

Water 

Exposure 

(mg/kg/day)

Total Exposure 

(mg/kg/day)

% aPAD

U.S. Population 0.001313 0.000423 0.001736 0.03

All Infants (< 1 yr old) 0.002468 0.001535 0.004003 0.08

Children 1-2 years 0.003014 0.000664 0.003678 0.07

Children 3-5 years 0.002407 0.000607 0.003014 0.06
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Children 6 – 12 years 0.001485 0.000422 0.001907 0.04

Youth 13-19 years 0.000949 0.000343 0.001292 0.03

Adults 20-49 years 0.000772 0.000392 0.001164 0.02

Adults + 50 0.000679 0.000354 0.001033 0.02

Females 13-49 years 0.001313 0.000423 0.001736 0.03

aPAD = 5 mg/kg bw/day

Short- and Intermediate-Term Aggregate Exposure and Risk (food, water, and residential)

Short- and intermediate-term aggregate risk assessments include exposure from food, water, 

and residential uses. There are no residential uses for Saflufenacil, 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 Saflufenacil 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 Saflufenacil

Population Subgroup Food Exposure 

(mg/kg/day)

Water Exposure 

(mg/kg/day)

Total 

Exposure 

(mg/kg/day)

% cPAD

U.S. Population 0.000459 0.000053 0.000512 1.1

All Infants (< 1 yr old) 0.001051 0.000173 0.001224 2.7

Children 1-2 years 0.001537 0.000078 0.001615 3.5

Children 3-5 years 0.001196 0.000073 0.001269 2.8

Children 6 – 12 years 0.000716 0.000051 0.000767 1.7
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Youth 13-19 years 0.000413 0.000038 0.000451 1.0

Adults 20-49 years 0.000328 0.000049 0.000377 0.8

Adults + 50 0.000298 0.000052 0.000350 0.8

Females 13-49 years 0.000459 0.000053 0.000512 1.1

cPAD = 0.046 mg/kg bw/day. 

2. Non-dietary exposure. The term ‘‘residential exposure’’ is used to refer to nonoccupational, 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 Saflufenacil to share a common mechanism of 

toxicity with any other substances, and Saflufenacil does not appear to produce a toxic 

metabolite produced by other substances. For the purposes of this tolerance petition, 

therefore, EPA will assume that Saflufenacil does not have a common mechanism of toxicity 

with other substances.

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.
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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 proposed uses.

F. International Tolerances

There are no Codex maximum residue limits (MRLs) established for residues of

Saflufenacil and its metabolites in crops or livestock commodities. The residue definition and 

harmonized MRLs are established for residues of Saflufenacil and its metabolites in similar 

crops and livestock commodities in Canada.