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), 21 

U.S.C. 346a(d), to amend 40 CFR part 180.649 by establishing import tolerances for 

residues of saflufenacil, including its metabolites and degradates, in or on the raw 

agricultural commodities banana, whole fruit at 0.03 parts per million (ppm) and coffee, 

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)-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 

residue in plants resulting from preplant/preemergence application or a postemergencedirected at the base of plants underneath the 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 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 Central and South America were carried 

out to determine the magnitude of the residue following a postemergence-directed spray

at the base of plants underneath the leaf canopy of Saflufenacil applied for weed control 
2

in banana, coffee and mango plantations. 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 preharvest interval (PHI) for each of the crops. Detected combined residues of Saflufenacil 

plus metabolites in the crop 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 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, 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 
3

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 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.
4

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 

tolerance values are listed in the U.S. 40 CFR § 180.649. This analysis includes 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 subgroup 6C beans and peas, soybean, cotton, and canola) plus the 

proposed tolerance values for banana, coffee and mango.

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 pending proposed tolerances for 

soybean, soybean hulls, legume vegetables crop subgroup 6C dried shelled pea and bean 

(except soybean), cotton undelinted seed, cotton gin byproducts, crop group 7 foliage of 

legume vegetables group (based on pea vine data), crop group 20A oilseeds rapeseed, 

plus the currently 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 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 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 intraspecies 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
5

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 were conducted using the currently established tolerances for 

Saflufenacil (40 CFR 180.649), plus the pending proposed tolerances for soybean, 

soybean hulls, legume vegetables crop subgroup 6C dried shelled pea and bean (except 

soybean), cotton undelinted seed, cotton gin byproducts, crop group 7 foliage of legume 

vegetables group (based on pea vine data), crop group 20A oilseeds rapeseed, plus the 

currently 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 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 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

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
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) 

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
7

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 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 0.00400 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 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. 
8

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 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 13-19 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 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 nondietary 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.
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 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.