EPA REGISTRATION DIVISION COMPANY NOTICE OF FILING FOR 

PESTICIDE PETITIONS PUBLISHED IN THE FEDERAL REGISTER

(7/1/2007)

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

Manager, Team 23, 703-305-1243]

BASF Corporation

Petition No. 2E8065

EPA has received a pesticide petition (2E8065) 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 establishing a tolerance 

for combined residues 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 raw agricultural commodities sugarcane, cane at 0.03 parts per million (ppm)

and sugarcane, molasses at 0.075 parts per million (ppm) and sugarcane, refined sugar

at 0.045 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, soybean, 

and tomato and a confined rotational crop study are adequate to elucidate the 

nature of the residue in plants resulting from preplant/preemergence application, a 

postemergence-directed at the base of plants underneath the leaf canopy

application, and a pre-harvest/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 
2

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 Brazil were carried out to determine 

the magnitude of the residue following a postemergence over-the-top application of 

Saflufenacil applied for pre-harvest weed desiccation in sugarcane. Field trials were 

carried out using the maximum label rates, the maximum number of applications, 

and the minimum pre-harvest interval (PHI) for use in sugarcane. Detected 

combined residues of Saflufenacil plus metabolites in the crop commodities support 

the proposed import 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 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 pre-weaning 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, 
3

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 substancespecific 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 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 sexdependent 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. 
4

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 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 and proposed new import 

tolerances for sugarcane, cane at 0.03 ppm, sugarcane, molasses at 0.075 ppm, and 

sugarcane, refined sugar at 0.045 ppm.

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 new import 

tolerances for sugarcane, cane at 0.03 ppm, sugarcane, molasses at 0.075 ppm, and 

sugarcane, refined sugar at 0.045 ppm. 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 
5

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.

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 new import 

tolerances for sugarcane, cane at 0.03 ppm, sugarcane, molasses at 0.075 ppm, and 

sugarcane, refined sugar at 0.045 ppm. 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 chronic Population Adjusted Dose (cPAD) used for U.S. population and all subpopulations 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
6

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 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
7

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 

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

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
8

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

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 

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 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 
9

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.

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.