UNITED STATES ENVIRONMENTAL PROTECTION AGENCY 

WASHINGTON, D.C. 20460 

MEMORANDUM 

DATE: 24-JUN-2014 

OFFICE OF 

CHEMICAL SAFETY AND 

POLLUTION PREVENTION 

SUBJECT: Saflufenacil. Human-Health Risk Assessment in Support of Tolerances for 

Residues inion Barley, Wheat, Grass, and Olives. 

PC Code: 118203 DP Barcode: D418587 

Decision Nos.: 480698, 481309, & 486544 Registration Nos.: 7969-275, 7969-276, & 

7969-278 

Petition Nos.: 3F8l85, 3F8192, & 4F8229 Regulatory Action: Sec. 3 Registration 

Risk Assessment Type: Single Chemical/ Case No.: 7277 

Aggregate 

TXRNo.: NA CAS No.: 372137-35-4 

MRIDNo.: NA 40 CFR: § 180.649 

FROM: George 

Kelly M. 

F. 

Lowe, 

Kramer, 

Senior 

Ph.D., 

Environmental 

Senior Chemist Scientis~~, 

t 

Risk Assessment Branch 1 (RAB 1) . 

Health Effects Division (HED, 7509P) 

THROUGH: Charles W. Smith III, Branch Ch. 

RABl, HED (7509P) ---

TO: Kathryn Montague/Bethany Benbow, PM Team 23 

Registration Division (RD; 7505P) 

The HED of the Office of Pesticide Programs (OPP) is charged with estimating the risk to human 

health from exposure to pesticides. The RD of OPP has requested that HED evaluate hazard and 

exposure data and conduct dietary, occupational, residential, and aggregate exposure 

assessments, as needed, to estimate the risk to human health that will result from the proposed 

tolerances for residues inion barley, wheat, grass, and olives. The petitioner is BASF. 

A summary of the findings and an assessment of human-health risk resulting from the 

proposed/registered uses of saflufenacil are provided in this document. The risk assessment, 

residue chemistry, and dietary exposure assessment were provided by George Kramer (RAB1), 

the hazard characterization by Chester Rodriguez (RAB 1 ), the occupational/residential exposure 

assessment by Kelly Lowe (RAB 1 ), and the drinking water assessment by Mohammed Ruhman 

of the Environmental Fate and Effects Division (EFED). 

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Saflufenacil Human-Health Risk Assessment DP# 418587 

Table of Contents 

1.0 Executive Summary ..................................................................... ....................... ................ 4 

2.0 HED Recommendations ..................................................................................................... . 6 

2.1 Data Deficiencies ................................................................... ........... .... .... ......... ..... 7 

2.2 Tolerance Considerations ............................... ........ ................................................. 7 

2.2.1 Enforcement Analytical Method .............................................................. ............... 7 

2.2.2 Recommended Tolerances ........................ .............................................................. 7 

2.2.3 Revisions to Petitioned-For Tolerances .............................. .................................... 8 

2.2.4 International Harmonization ................................................................................... 9 

2.3 Label Recommendations ......................................................................................... 9 

3.0 Introduction ................................................................................. ....... ................................. 9 

3.1 Chemical Identity ................................ .................................................................... 9 

3.2 Physical/Chemical Characteristics ........................................................................ 1 0 

3.3 Pesticide Use Pattern ............................................................. ................................ 10 

3.4 Anticipated Exposure Pathways ........................................................................... 12 

3.5 Consideration of Environmental Justice .................................... ........................... 12 

4.0 Hazard Characterization and Dose-Response Assessment ......................... ............. ......... 13 

4.1 Toxicology Studies Available for Analysis ........................................................... 13 

4.2 Absorption, Distribution, Metabolism, and Excretion (ADME) ........ .................. 13 

4.2.1 Dermal Absorption ................................................................................................ 13 

4.3 Toxicological Effects ....... ..................................................................................... 14 

4.3.1 Summary of Toxicological Effects ....................................................................... 14 

4.4 Safety Factor for Infants and Children (FQPA SF) .. .... ........................................ 15 

4.4.1 Completeness ofthe Toxicology Database .......................... ................................. 15 

4.4.2 Evidence of Neurotoxicity ..... ............................................................................... 15 

4.4.3 Evidence of Sensitivity/Susceptibility in the Developing or Young Animal ....... 15 

4.4.4 Residual Uncertainty in the Exposure Database ......................... .... ...................... 15 

4.5 Toxicity Endpoint and Point of Departure Selections .......................................... 16 

4.5.1 Dose-Response Assessment. ....................................................................... .......... 16 

4.5 .2 Recommendation for Combining Routes of Exposures for Risk Assessment.. .... 17 

4.5.3 Cancer Classification and Risk Assessment Recommendation ......... ................... 17 

4.5.4 Summary of Points of Departure and Toxicity Endpoints Used in Human Risk 

Assessment... ............................ ................... ...................................................................... 1 7 

5.0 Dietary Exposure and Risk Assessment ............ ............... ........ ........................................ 18 

5.1 Residues of Concern Summary and Rationale ......................... ............................. 18 

5.2 Food Residue P·rofile ............................. .... ............................................................ 20 

5.3 Water Residue Profile ...................................................................................... .... . 21 

5.4 Dietary Risk Assessment ................................................................................. ..... 21 

5.4.1 Description of Residue Data Used in Dietary Assessment.. ....... ........ .................. 21 

5.4.2 Percent Crop Treated Used in Dietary Assessment .............................................. 21 

5 .4.3 Acute Dietary Risk Assessment.. .......................................................................... 21 

5.4.4 Chronic Dietary Risk Assessment ..................................................................... ... 22 

5.4.5 Cancer Dietary Risk Assessment.. ........................................................................ 22 

6.0 Residential (Non-Occupational) Exposure/Risk ............................................................... 22 

6.1 Residential Exposure/Risk Characterization ......................................................... 22 

6.2 Residential Bystander Post-Application Inhalation Exposure .............................. 22 

6.3 Spray Drift ............................................................................................................ 23 

7. 0 Aggregate Exposure/Risk Characterization .............................................................. .... .... 23 

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7.1 Acute Aggregate Risk ........................................................................................... 24

7.2 Chronic Aggregate Risk........................................................................................ 24

8.0 Cumulative Risk Characterization/Assessment ................................................................ 24

9.0 Occupational Exposure/Risk Characterization ................................................................. 24

9.1 Short- and Intermediate-Term Handler Risk ........................................................ 24

9.2 Short- and Intermediate-Term Post-Application Risk .......................................... 28

9.2.1 Dermal Post-Application Risk .............................................................................. 28

9.2.2 Inhalation Post-Application Risk.......................................................................... 28

9.3 Restricted Entry Interval....................................................................................... 29

10.0 References......................................................................................................................... 29

Appendix A. Toxicology Assessment.......................................................................................... 30

A.1 Toxicology Data Requirements for Saflufenacil ...................................................... 30

A.2 Toxicity Profiles........................................................................................................ 30

Appendix B. Physical/Chemical Properties................................................................................. 35

Appendix C. Review of Human Research ................................................................................... 36
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1.0 Executive Summary

Saflufenacil (BAS 800 H) is a broad-spectrum herbicide developed by BASF. It belongs to the 

herbicide mode-of-action Group 14 (cell membrane disruptors). Saflufenacil acts through the 

inhibition of protoporphyrinogen oxidase (PPO), resulting in cell membrane damage and 

subsequent plant death. BASF has submitted a proposal to amend the established tolerances for 

saflufenacil on wheat and barley (PP#3F8185). The amended tolerances on these crops are the 

result of the proposed harvest-aid/desiccation use pattern for Sharpen® Powered by Kixor®

Herbicide (EPA Reg. No. 7969-278 2.85 lb ai/gal; suspension concentrate (SC)); the currently 

registered uses are for preplant application. In addition, BASF has submitted a proposal for a 

new use of Sharpen® Powered by Kixor® Herbicide and Heat® Powered by Kixor® Herbicide 

(EPA Reg. No. 7969-297; 2.85lb ai/gal; SC) on grass group 17 as harvest aid/desiccant 

(PP#3F8192) and for a new use of Treevix® Powered by Kixor® Herbicide (EPA Reg. No. 7969-

276; 30%; water-dispersible granule (WG)) to the base of olive trees (PP#4F8229).

Hazard Assessment: Saflufenacil was well absorbed and rapidly excreted via the oral route in 

rat metabolism studies. Maximum blood concentrations were reached within one hour and 

declined rapidly thereafter. Elimination was primarily urinary in female rats and via the feces in 

male rats. The sex-dependent excretion resulted in male rats having up to 3X higher internal 

levels and being, in some cases, more sensitive to toxicity than females.

Saflufenacil exhibited low acute toxicity via the oral, dermal, and inhalation routes of exposure 

(Toxicity Category III or IV). It was slightly irritating to the eye (Toxicity Category III), but was 

not a dermal irritant or a dermal sensitizer.

Subchronic and chronic toxicity studies in rats, mice, and dogs identified the hematopoietic 

system as the primary target of saflufenacil. Consistent with its proposed mode of toxicity 

involving PPO inhibition and subsequent disruption of heme biosynthesis, decreased 

hematological parameters [red blood cells (RBC), hematocrit (Ht), mean corpuscular volume 

(MCV), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration 

(MCHC)] were seen at about the same dose level [lowest-observed adverse-effect levels 

(LOAELs) of 13-39 mg/kg/day] across species, except in the case of the dog, where the effects 

were seen at a slightly higher dose (LOAELs of 50-100 mg/kg/day). These effects occurred 

around the same dose level from short- through long-term exposures without increasing in 

severity. Effects were also seen in the liver (increased weight, centrilobular fatty change, 

lymphoid infiltrate) in mice, the spleen (increased spleen weight and extramedullary 

hematopoiesis) in rats, and in both of 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 short- through long-term exposures without increasing in severity. 

Increased fetal susceptibility was observed in the developmental toxicity studies in the rat and 

rabbit and in the two-generation reproduction study in the rat. Developmental effects (decreased 

fetal body weights and increased skeletal variations in rats and increased liver porphyrins in 

rabbits) occurred at doses that were not maternally toxic in the developmental studies, indicating 

increased quantitative susceptibility. In the two-generation reproductive toxicity study in rats, 

the reported offspring effects were more severe than the maternal effects at the same dose level, 

indicating evidence for increased qualitative susceptibility. An increased number of stillborn 

pups, decreased viability and lactation indices, decreased pre-weaning body weight, and changes 
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in hematological parameters occurred at the same dose level as maternal decrements in food 

intake, body weight, and changes in hematological parameters and organ weights indicative of 

anemia. 

Saflufenacil was 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 was neither mutagenic in bacterial cells nor clastogenic in rodents in vivo. 

Carcinogenicity studies in rats and mice showed no evidence of increased incidence of tumors at 

the tested doses. Saflufenacil is classified as “not likely carcinogenic to humans.”

Saflufenacil displayed no evidence of neurotoxicity in acute and subchronic neurotoxicity 

studies, did not produce any dermal or systemic effects in a 28-day dermal toxicity study, and 

failed to induce toxicity specific to the immune system in a recently submitted immunotoxicity 

study.

Dose-Response and Food Quality Protection Act (FQPA) Assessments: The RAB1 risk 

assessment team for saflufenacil determined that the FQPA Safety Factor (SF) should be reduced 

to 1X for all exposure scenarios for the following reasons (see Section 4.4 for a full discussion): 

the toxicological database is adequate for FQPA assessment, there is no evidence of 

neurotoxicity, there is low concern for offspring susceptibility, and there is no uncertainty in the 

exposure database.

A 100X uncertainty factor (UF) (10X for interspecies extrapolation and 10X for intraspecies 

variation) was incorporated into the acute reference dose (aRfD, 5.0 mg/kg) and chronic RfD 

(cRfD, 0.046 mg/kg/day). The acute population-adjusted dose (aPAD) and the chronic 

population-adjusted dose (cPAD) are equal to the acute and chronic RfDs, respectively, divided 

by the FQPA SF (1X). Saflufenacil is classified as “not likely carcinogenic to humans” by all 

relevant routes of exposure based on adequate studies in two animal species; therefore, cancer 

risk assessments are not required. In estimating margins of exposure (MOEs), the level of 

concern (LOC) is for MOEs <100 for the dermal and inhalation risk assessments. A 6% dermalabsorption factor (DAF) and a 100% inhalation-absorption factor were used in route-to-route 

extrapolations. 

Food Residue Profile: The nature of the residue is adequately understood in the subject crops. 

Organization for Economic Co-operation and Development (OECD) tolerance-calculation 

procedures and the submitted residue data sets were used to calculate the HED-recommended 

tolerances. There are no residue chemistry issues that would preclude establishing permanent

tolerances for residues of saflufenacil, as outlined in Table 2.2.2.

Exposure/Risk Assessment Characterization: Acute and chronic dietary risk assessments were 

conducted using the Dietary Exposure Evaluation Model - Food Consumption Intake Database 

(DEEM-FCID, ver. 3.16) which incorporates consumption data from the United States 

Department of Agriculture (USDA) National Health and Nutrition Examination Survey, What 

We Eat in America, (NHANES/WWEIA; 2003-2008). The acute and chronic analyses assumed 

100% crop treated (CT), DEEM 7.81 default processing factors, and tolerance-level or tolerancelevel residues adjusted to account for the residues of concern for risk assessment for all foods. 

Drinking water was incorporated directly into the dietary assessments using the concentration for 

surface water generated by Tier I Rice modeling. The resulting acute dietary (food + drinking 
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water) risk estimates using the DEEM-FCID model at the 95th percentile [<1% aPAD for all 

infants (<1-year old), the most highly exposed population subgroup] are not of concern (<100% 

aPAD). The chronic dietary risk assessment shows that the chronic dietary risk estimates are not 

of concern (i.e., <100% cPAD). The chronic dietary risk estimate for the highest exposed 

population subgroup, all infants (<1-year old), is 20% of the cPAD. 

There are no residential uses proposed or currently registered for saflufenacil. Therefore, a 

residential risk assessment was not conducted.

Since there are no residential exposures expected from the proposed or registered saflufenacil 

uses, the aggregate exposure assessment takes into consideration dietary food + drinking water 

exposure only. The acute and chronic dietary estimates represent acute and chronic aggregate 

risk, respectively.

There is potential for occupational handler short- and intermediate-term exposure resulting from 

the proposed uses of saflufenacil. Potential occupational handler exposure scenarios include 

mixing/loading liquids for aerial and ground applications, applications via aerial and ground 

equipment, and flagging. The occupational handler exposure and risk estimates indicate that the 

short- and intermediate-term dermal and inhalation combined MOEs are not of concern to HED 

(i.e., MOE > 100). At the baseline level of personal protection (i.e., no gloves and no respirator), 

all scenarios result in combined MOEs (dermal + inhalation) ≥ 250.

The occupational post-application dermal exposure and risk estimates are greater than the LOC 

of 100 on the day of application, ranging from 3,000 to 5,200 depending on crop and activity. 

Since the post-application assessment is not a concern on Day 0 (12 hours following 

application), the restricted-entry interval (REI) is based on the acute toxicity of saflufenacil 

technical material. Saflufenacil is classified as Toxicity Category III for acute oral, acute dermal 

toxicity, and acute eye irritation. It is classified as Toxicity Category IV for acute inhalation 

toxicity and acute dermal irritation. It is not a dermal sensitizer. Therefore, the acute toxicity 

categories for this chemical require a 12-hour REI under 40 CFR §156.208 (c) (2) (iii). The 12-

hour REI, which currently appears on the labels, is adequate for the proposed uses.

Based on the Agency's current practices, a quantitative non-cancer occupational post-application 

inhalation exposure assessment was not performed for saflufenacil at this time. If new policies 

or procedures are put into place, the Agency may revisit the need for a quantitative occupational 

post-application inhalation exposure assessment for saflufenacil.

This risk assessment relies in part on data from studies in which adult human subjects were 

intentionally exposed to a pesticide or other chemical. Please refer to Appendix C for a 

discussion of the human study data used in this risk assessment. 

2.0 HED Recommendations

Pending submission of revised Section Fs, there are no other residue chemistry, occupational, or 

toxicology data deficiencies that would preclude the establishment of permanent tolerances for 

residues of saflufenacil and it metabolites and degradates as outlined in Table 2.2.2. 
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2.1 Data Deficiencies

860.1550 Proposed Tolerances (PP#s 3F8185 & 3F8192)

 The petitioner is requested to submit revised Section Fs specifying revised tolerances, as 

presented in Table 2.2.2.

2.2 Tolerance Considerations

2.2.1 Enforcement Analytical Method

The petitioner has submitted two liquid chromatography/mass spectroscopy/mass spectroscopy 

(LC-MS/MS) analytical methods for the determination of residues of the parent and its 

metabolites in/on plant and livestock commodities. BASF Method D0603/02 was developed for 

determination of residues of saflufenacil and its metabolites M800H11 and M800H35 in 

different plant matrices using LC-MS/MS. The limit of quantitation (LOQ) was 0.01 ppm for 

each analyte in food matrices and 0.025 ppm for each analyte in feed matrices. BASF analytical 

Method No. L0073/01 was developed for determination of saflufenacil in livestock matrices 

using LC-MS/MS. The LOQ was 0.01 ppm in all matrices. These methods were used as the 

data-collection methods in the analysis of samples for residues of concern from the various 

studies associated with the current petitions. Each method has been adequately validated by the 

petitioner as well as by independent laboratories and were adequately radiovalidated using 

weathered samples obtained from metabolism studies.

HED has determined that Methods D0603/02 and L0073/01 are suitable enforcement methods 

for the plant and livestock commodities associated with this petition, respectively, as defined in 

SOP No. ACB-019 (9/15/08). 

2.2.2 Recommended Tolerances

The proposed uses and the submitted data support the following permanent tolerances for 

residues of saflufenacil in or on the commodities summarized in Table 2.2.2. 

Table 2.2.2. Tolerance Summary for Saflufenacil.

Commodity

Proposed 

Tolerance (ppm)

HED-Recommended 

Tolerance (ppm)

Correct Commodity 

Definition/Comments

PP#3F8185

Barley, bran 1.53 1.5

Barley, grain 1 1.0

Barley, straw 15 15

Grain, aspirated fractions - 50 Grain, aspirated grain fractions

Grain, cereal group 15 

(except barley and wheat 

grain) 

0.03 0.03

Grain, cereal, forage, fodder 

and straw group 16 (except 

barley, wheat and rice straw) 

0.10 0.10 Grain, cereal, forage, fodder and 

straw group 16 (except barley and 

wheat straw)

Wheat, grain 0.6 0.60

Wheat, straw 6 6.0
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Table 2.2.2. Tolerance Summary for Saflufenacil.

Commodity

Proposed 

Tolerance (ppm)

HED-Recommended 

Tolerance (ppm)

Correct Commodity 

Definition/Comments

PP#3F8192

Grass forage 15 15

Grass hay 20 20

Grass seed screenings 0.9 0.15

Grass straw 1.5 0.15

Cattle, fat 0.05 0.04

Cattle, liver 45 50

Cattle, meat byproducts, 

except liver

0.5 0.30

Cattle, meat - 0.02

Goat, fat 0.05 0.04

Goat, liver 45 50

Goat, meat byproducts, 

except liver

0.5 0.30

Goat, meat - 0.02

Sheep, fat 0.05 0.04

Sheep, liver 45 50

Sheep, meat byproducts, 

except liver

0.5 0.30

Sheep, meat - 0.02

Horse, fat 0.05 0.04

Horse, liver 45 50

Horse, meat byproducts, 

except liver

0.5 0.30

Horse, meat - 0.02

Hog, fat 0.05 0.01 0.01 ppm is the currently 

established value

Hog, liver 45 2.0

Hog, meat byproducts, 

except liver

0.5 0.02 0.02 ppm is the currently 

established value

PP#4F8229

Olive 0.03 0.03

2.2.3 Revisions to Petitioned-For Tolerances

HED is recommending for the following revisions to the petitioned-for tolerances: 1) the value 

for barley bran should be rounded to 1.5 ppm; 2) the commodity definition “Grain, cereal, 

forage, fodder, and straw group 16 (except barley, wheat and rice straw)” should be revised to 

“Grain, cereal, forage, fodder and straw group 16 (except barley and wheat straw)” as rice straw 

is not a significant livestock feed item; 3) the HED-recommended values for grass straw and 

seed screenings are lower because the petitioner included data from trials in which the samples 

were harvested at a significantly shorter preharvest interval (PHI) than that allowed on the label; 

4) the existing tolerance of 10 ppm for residues in/on grain, aspirated fractions should be 

increased to 50 ppm; and 5) the recommended tolerances for residues in livestock, calculated by 

HED based on the maximum reasonably balanced diets (MRBDs) and the results of the ruminant 

feeding study, differ from the petitioned-for tolerances, especially in hog commodities (where 

the petitioner over-estimated residues as a result of using the cattle MRDB).
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2.2.4 International Harmonization

There are Codex maximum residue limits (MRLs) established for residues of saflufenacil per se

in wheat and barley (as members of the cereal grain crop group) grain, straw, and fodder; and 

livestock commodities. Canadian MRLs are established for residues of saflufenacil and its 

metabolites in/on wheat and barley grain (as members of the cereal grain crop group) and for 

residues of saflufenacil per se in/on livestock commodities. Harmonization is not possible as the 

U.S. use pattern (harvest-aide/burndown application) results in significantly higher residues than 

the Codex/Canadian use pattern (pre-emergence application). In addition, the U.S. and Canadian 

residue definition for crops contains additional metabolites not included in the Codex residue 

definition.

2.3 Label Recommendations

None

3.0 Introduction

3.1 Chemical Identity

TABLE 3.1. Saflufenacil Nomenclature.

Chemical Structure

Common name Saflufenacil

Company experimental name BAS 800 H (synonyms: AC 433 379, BASF Reg. No. 4054449)

IUPAC name N'-[2-chloro-4-fluoro-5-(3-methyl-2,6-dioxo-4-(trifluoromethyl)-3,6-dihydro-1(2H)-

pyrimidinyl)benzoyl]-N-isopropyl-N-methylsulfamide

CAS name 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

CAS registry number 372137-35-4

End-use product (EP) BAS 800 04 H (342 g ai/L SC formulation)

Chemical Structure

Common name M800H11

Chemical name N-[2-chloro-5-(2,6-dioxo-4-(trifluoromethyl)-3,6-dihydro-1(2H)-pyrimidinyl)-4-

fluorobenzoyl]-N'-isopropylsulfamide

Chemical Structure

Common name M800H35

Chemical name N-[4-chloro-2-fluoro-5-({[(isopropylamino)sulfonyl]amino}carbonyl)phenyl]urea

F Cl

N

N

O

O

CH3

F

F

F

O

N

H

S

N

O

O

CH3

CH3

CH3

F Cl

N

N

H

O

O

F

F

F

O

N

H

S

N

H

O

O

CH3

CH3

F Cl

N

H

O

O

N

H

S

N

H

O

O

CH3

CH3 H2N
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3.2 Physical/Chemical Characteristics

Saflufenacil is a broad-spectrum herbicide developed by BASF. It belongs to the herbicide 

mode-of-action Group 14 (cell membrane disruptors). Saflufenacil acts through the inhibition of 

PPO, resulting in cell membrane damage and subsequent plant death. Saflufenacil is a uracil 

herbicide that is expected to be mobile to highly mobile. Its major routes of degradation are 

alkaline hydrolysis and biodegradation in aerobic soil. The compound is expected to degrade 

with a half-life of 1 to 5 weeks in aerobic soil environments and a half-life of 7 to 15 weeks (2 to 

4 months) in aerobic aquatic environments. Its vapor pressure is 4.5 x 10-15 Pa at 20 oC. 

Because it is a low-volatile herbicide, saflufenacil could be less prone to atmospheric transport 

than more-volatile herbicides. A summary of the physicochemical properties can be found in 

Appendix B. 

3.3 Pesticide Use Pattern

BASF has submitted draft labels for Sharpen® Powered by Kixor® Herbicide (EPA Reg. No. 

7969-278), Heat® Powered by Kixor® Herbicide (EPA Reg. No. 7969-297), and Treevix®

Powered by Kixor® Herbicide (EPA Reg. No. 7969-276). A summary of the proposed use 

patterns is detailed in Table 3.3.1. 

Table 4. Summary of Directions for Use of Saflufenacil.

Applic. 

Timing, Type, 

and Equip.

EPA 

Reg. 

No.

Max Single 

App. Rate 

(lb ai/A)

Max. # Apps 

per year

Max Seasonal 

App. Rate (lb 

ai/A) 

RTI 

(days)

PHI 

(days) Use Directions and Limitations

Barley, Wheat, and Triticale (PP# 3F8185)

Harvest aid/

Desiccation

7969-

278 

2 fl. oz./A

(0.045 lbs. 

ai/A)

2 per crop

season

2 fl. oz./A

(0.045 lbs. 

ai/A)

NS 3 -A single app. of 2.0 fl. oz./A or 

sequential apps. of 1.0 fl. oz./A may 

be made, but do not exceed 2.0 fl. 

oz./A in a cropping season from 

desiccation uses.

-MSO plus ammonium-based adjuvant 

are required for optimum desiccation 

activity.

-Make GROUND application at a 

minimum spray volume of 10 gallons 

per acre.

-Make Aerial application at a min. 

spray volume of 5 gallons per acre.

Grass Grown for Pasture & Rangeland (forage, silage and hay) (PP# 3F8192)

Broadcast 

burndown

apps. to 

established 

stands during 

dormant 

period.

For cool and 

warm-season 

grasses

7969-

278 

7969-

297

4 fl. oz./A

(0.090 lbs. 

ai/A)

2 per dormant 

season

4 fl. oz./A

(0.090 lbs. 

ai/A)

14 N/A -Apply 1.0 to 2.0 fl. oz./A as a 

broadcast burndown spray to emerged 

weeds in the dormant season.

-MSO plus AMS is required. 

In-season 

growing period 

postemergence 

broadcast burndown apps. to 

established

cool-season

7969-

278

7969-

297

2 fl. oz./A

(0.045 lb 

ai/A) 

2 per Inseason2 fl. oz./A

(0.045 lb 

ai/A)

14 0 -Apply 1.0 to 2.0 fl. oz./A as a 

broadcast burndown spray to emerged 

weeds in growing season (Spring after 

greenup and before weeds reach max. 

size).

-MSO at 1% v/v is required.
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Table 4. Summary of Directions for Use of Saflufenacil.

Applic. 

Timing, Type, 

and Equip.

EPA 

Reg. 

No.

Max Single 

App. Rate 

(lb ai/A)

Max. # Apps 

per year

Max Seasonal 

App. Rate (lb 

ai/A) 

RTI 

(days)

PHI 

(days) Use Directions and Limitations

grass

In-season 

growing 

period

postemergence 

broadcast 

burndown 

apps. to 

established 

warm-season

grasses

7969-

278

7969-

297

2 fl. oz./A

(0.045 lb 

ai/A)

(except 

Bermudagrass 

is just 1 fl. 

oz./A)

2 per Inseason

(except 

Bermudagrass 

is just 1 

app/in-season

2 fl. oz./A

(0.045 lb 

ai/A)

(except 

Bermudagrass 

is just 1 fl. 

oz./A)

14 0 -Apply 1.0 to 2.0 fl. oz./A as a 

broadcast burndown spray to emerged 

weeds in growing season (Spring after 

greenup and before weeds reach max. 

size).

-DO NOT exceed 1 fl. oz./A for inseason apps to forage Bermudagrass.

-MSO at 1% v/v.

Split program 

for established 

stands of 

warm and 

cool-season 

grasses

7969-

278

7969-

297

Split program (dormant + in-season) apps. may be made, but do not exceed the maximum cumulative 

amount of 6.0 fl. oz./A (0.134 lb ai) per crop season (up to 4.0 fl. oz./A/dormant period and 2.0 fl. 

oz./A/in-season).

-All sequential applications must be separated by 14 days.

-DO NOT apply to mixed stands containing forage legumes or other desirable broadleaf species 

(including alfalfa & clover).

-DO NOT apply to stands containing annual forage species (e.g., forage sorghum, Sudangrass).

Grasses Grown for Seed (PP# 3F8192)

Broadcast 

burndown 

apps. in newly 

planted grass 

stands grown 

for seed

7969-

278

2.0 fl. oz./A

(0.045 lb 

ai/A)

2 2.0 fl. oz./A

(0.045 lb 

ai/A)

14 50 -Apply to new seedling grass fields 

after the first tiller is established in 

cool-season grasses and after the first 

rhizome or stolon is established in 

warm-season grasses.

-Burndown applications require an 

adjuvant system (MSO at 1% v/v).

Broadcast 

postemergence 

apps. in 

established 

grass stands 

grown for seed

7969-

278

2.0 fl. oz./A

(0.045 lb 

ai/A)

2 2.0 fl. oz./A

(0.045 lb 

ai/A)

14 50 -Apply postemergence apps to 

established grass fields any time after 

spring greenup to 1 week before boot 

stage.

-Postemergent applications require an 

adjuvant system (MSO at 1% v/v).

Dormant 

apps. in

established 

grass seed 

stands

7969-

278

4.0 fl. oz./A

(0.090 lb 

ai/A)

2 4.0 fl. oz./A

(0.090 lb 

ai/A)

NS 50 -Apply to established grass seed 

stands in the dormant season.

-Sequential app. may be made for 

residual control in the dormant season.

-An adjuvant system is required for 

optimum burndown activity.

-DO NOT apply more than a max. cumulative amount of 6.0 fl. oz./A per cropping season on established grass seed stands.

-DO NOT apply more than a max. cumulative amount of 4.0 fl. oz./A per cropping season on seedling grass seed stands.

-Treated forage and hay may be grazed and/or fed to livestock- no pre-harvest or pre-grazing interval.

-Treated grass straw remaining after seed harvest may be used as livestock bedding and/or grazed/fed to livestock.

-Grass seed screenings in treated fields may be fed to livestock.

Pre-emergence Broadleaf Weed Control in newly planted Cool-Season Grass Stands [forage & seed production] (PP# 

3F8192)

Preplant, 

preplant 

incorporated, 

or 

preemergence 

in the fall or 

spring while 

establishing

new stands of

cool-season 

grasses

7969-

278

4.0 fl. oz./A

(0.090 lb 

ai/A)

2 6.0 fl. oz./A

(0.134 lb 

ai/A)

NS 0 -Apply as a broadcast spray to the soil 

surface before grasses emerge. If 

burndown of established weeds is 

desired, add an adjuvant system.

-Sequential/Split apps can be made, 

but not to exceed a max. cumulative 

amount of 6.0 fl. oz./A/cropping 

season (preplant/in-season).

-No preharvest or pregrazing interval 

for forage and hay.
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Table 4. Summary of Directions for Use of Saflufenacil.

Applic. 

Timing, Type, 

and Equip.

EPA 

Reg. 

No.

Max Single 

App. Rate 

(lb ai/A)

Max. # Apps 

per year

Max Seasonal 

App. Rate (lb 

ai/A) 

RTI 

(days)

PHI 

(days) Use Directions and Limitations

Olive Trees (PP#4F8229)

Post, Directed 

to Orchard 

Floor

7969-

276

1.0 fl. oz./A

(0.044 lb 

ai/A)

3 3.0 fl. oz./A

(0.132 lb 

ai/A)

21 0 A fourth application during dormancy 

is permitted.

NS = not specified; PHI = preharvest interval; RTI = retreatment interval; AMS = ammonium sulfate; MSO = methylated seed 

oil.

Conclusions: The proposed use patterns are adequate to allow evaluation of the residue data 

submitted in support of these petitions. 

3.4 Anticipated Exposure Pathways

RD has requested that HED evaluate hazard and exposure data and conduct dietary, 

occupational, residential, and aggregate exposure assessments, as needed, to estimate the risk to 

human health that will result from the tolerance petitions for residues in/on barley, wheat, grass, 

and olives. Humans may be exposed to saflufenacil in food and drinking water, since 

saflufenacil may be applied directly to growing crops and application may result in saflufenacil 

reaching surface and ground water sources of drinking water. There are no residential uses of 

saflufenacil, so exposure in residential or non-occupational settings is not likely. In an 

occupational setting, applicators may be exposed while handling the pesticide prior to 

application, as well as during application. There is also a potential for post-application exposure 

for workers re-entering treated fields. 

This risk assessment considers all of the aforementioned exposure pathways based on the 

proposed new uses of saflufenacil and considers the existing registered uses as well for the 

dietary and residential exposure assessments. 

3.5 Consideration of Environmental Justice

Potential areas of environmental justice concerns, to the extent possible, were considered in this 

human health risk assessment, in accordance with U.S. Executive Order 12898, “Federal Actions 

to Address Environmental Justice in Minority Populations and Low-Income Populations,” 

(http://epa.gov/compliance/ej/resources/policy/exec_order_12898.pdf). As a part of every 

pesticide risk assessment, OPP considers a large variety of consumer subgroups according to 

well-established procedures. In line with OPP policy, HED estimates risks to population 

subgroups from pesticide exposures that are based on patterns of that subgroup’s food and water 

consumption, and activities in and around the home that involve pesticide use in a residential 

setting. Extensive data on food consumption patterns are compiled by the U.S. Department of 

Agriculture (USDA) under the National Health and Nutrition Examination Survey, What We Eat 

in America, (NHANES/WWEIA; 2003-2008) and are used in pesticide risk assessments for all 

registered food uses of a pesticide. These data are analyzed and categorized by subgroups based 

on age, season of the year, ethnic group, and region of the country. Additionally, OPP is able to 

assess dietary exposure to smaller, specialized subgroups and exposure assessments are 

performed when conditions or circumstances warrant. Whenever appropriate, non-dietary 

exposures based on home use of pesticide products and associated risks for adult applicators and 

for toddlers, youths, and adults entering or playing on treated areas postapplication are evaluated. 
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Further considerations are currently in development as OPP has committed resources and 

expertise to the development of specialized software and models that consider exposure to 

bystanders and farm workers as well as lifestyle and traditional dietary patterns among specific 

subgroups.

4.0 Hazard Characterization and Dose-Response Assessment

Saflufenacil is a pre- and post-emergence herbicide that acts by inhibiting the enzyme PPO, 

leading to disruption of chlorophyll biosynthesis, and ultimately bleaching of emerging foliar 

tissue. PPO is a key enzyme in porphyrin biosynthesis for the production of chlorophyll in 

plants and heme in mammals. When PPO is inhibited in mammals, hemoglobin biosynthesis is 

reduced, resulting in anemia and accumulation of different porphyrins and their precursors in 

various organs. 

4.1 Toxicology Studies Available for Analysis

The toxicology database for saflufenacil is complete and adequate for hazard characterization, 

toxicity endpoint selection, and FQPA SF evaluation. In previous risk assessments (Kramer et 

al., DP# 384602; 04-AUG-2011) and in the current assessment, an oral toxicity study is used for 

the inhalation endpoint. The HED Hazard and Science Policy Council (HASPOC) concluded, 

based on a weight-of-evidence approach, that a 28-day inhalation toxicity study is not required at 

this time (A. Dunbar, 02-AUG-2013; TXR #0056720).

4.2 Absorption, Distribution, Metabolism, and Excretion (ADME)

In rat metabolism/pharmacokinetic studies via the oral route, radiolabeled saflufenacil was well 

absorbed and rapidly excreted. Following a single dose and regardless of the dose administered, 

maximum blood concentrations were reached within 1 hour of dosing and declined rapidly 

thereafter. Excretion of saflufenacil was essentially complete within 96 hours, with the majority 

eliminated within the first 24-48 hours. The blood and plasma data demonstrated that the 

majority of the saflufenacil residues occurred in the plasma and were not bound to cellular 

elements of the blood such as red blood cells. Following single or repeated low- and high-dose 

administration, the main route of elimination in male rats was via the feces, whereas urinary 

excretion was the major route of elimination in females. There was significantly higher biliary 

excretion of saflufenacil residues in males than in females. This sex-dependent difference in 

excretion was more pronounced at the low-dose level and resulted in males having up to 3X

higher internal exposures than females as measured by the plasma area under the concentrationtime curve (AUC). Increasing the administered dose by a factor of 25 resulted in less than 

proportional increases in plasma AUC values at 6.1 in males and 12.4 in females. Saflufenacil 

residues remained very low in tissues at 168 hours after dosing, occurring mainly in carcass, 

liver, skin, and gut contents. 

4.2.1 Dermal Absorption

A DAF of 6% was estimated for saflufenacil based on the highest degree of skin penetration at 

the lowest dose tested in a rat dermal absorption study. Immediately after a 10-hour exposure, 

the estimated DAF was 3.4%. However, about 50% of the radioactivity remaining at the end of 

exposure penetrated through the skin during a 120-hour (5-day) observational period, indicating 
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Page 14 of 36

that skin-bound residues of saflufenacil are available for dermal absorption. With skin-bound 

residues included, a DAF of 6% should be applied for converting oral doses to dermal equivalent 

doses to assess the potential risk associated with dermal exposures to saflufenacil.

4.3 Toxicological Effects

4.3.1 Summary of Toxicological Effects

The effects observed following repeated oral exposures to saflufenacil are consistent with the 

proposed mode of toxicity involving inhibition of PPO in mammals, resulting in disruption of 

heme biosynthesis. Toxicological effects from subchronic and chronic toxicity studies in rats, 

mice and dogs consisted of decreased hematological parameters (RBC, Ht, MCV, MCH, and 

MCHC) at approximately the same dose level (13-39 mg/kg/day), except in the case of the dog, 

where the effects were seen at a slightly higher dose (50-100 mg/kg/day). In line with the 

ADME findings suggesting that male rats achieve a greater systemic exposure than females, 

males were the most sensitive sex in mice and rats, with LOAELs approximately 3-4X lower 

than their female counterparts. The hematological effects resulting from oral exposures to 

saflufenacil occurred around the same dose level from short- through long-term exposures 

without increasing in severity. Toxic effects were also seen in the liver (increased organ weight, 

centrilobular fatty change, lymphoid infiltrate) in mice, the spleen (increased organ weight and 

extramedullary hematopoiesis) in rats, and in both of 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 short- through long-term exposures without a progression in 

severity. 

Evidence for increased pre- and/or postnatal susceptibility was noted from the developmental 

toxicity studies in the rat and rabbit and in the two-generation reproduction study in the rat. 

Decreased fetal body weights and increased skeletal variations occurred at doses (20 mg/kg/day) 

that were not maternally toxic in the developmental study in rats. Similarly, in rabbits, increased 

liver porphyrins in fetuses were observed at doses (200 mg/kg/day) that were not maternally 

toxic. In the two-generation reproductive toxicity study in rats, there was evidence of increased 

qualitative susceptibility based on an increased number of stillborn pups, decreased pup viability 

and lactation indices, decreased pre-weaning body weight and/or body-weight gain, and changes 

in hematological parameters at the same dose level as less severe maternal effects consisting of 

decrements in food intake, body weight, body-weight gain, and changes in organ weights and 

hematological parameters indicative of anemia. 

In an acute neurotoxicity (ACN) study in rats, a decrease in motor activity was observed on the 

day of dosing at the limit dose (2000 mg/kg/day) in males only. However, the finding was not 

accompanied by any 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 (SCN) study, systemic toxicity (anemia) was seen at 1000 ppm (66.2 

mg/kg/day) and 1350 ppm (101 mg/kg/day) in males and females, respectively. There was no 

evidence of neurotoxicity or neuropathology in either the acute or subchronic neurotoxicity 

study.

In a 28-day dermal toxicity study in rats, saflufenacil did not induce any type of dermal or 

systemic toxicity up to the limit dose of 1000 mg/kg bw/day.
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Based on the results of acute toxicity studies, saflufenacil was ranked low for acute toxicity 

(Toxicity Category III or IV) via the oral, dermal, and inhalation route of exposure. It was not 

classified as a dermal irritant or dermal sensitizer. 

In a 28-day immunotoxicity study in mice, saflufenacil failed to induce toxicity specific to the 

immune system at the highest dose tested (i.e., 52 mg/kg bw/day). 

Saflufenacil was 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 was neither mutagenic in bacterial cells nor clastogenic in rodents in vivo. 

Carcinogenicity studies in rats and mice showed no evidence of increased incidence of tumors at 

the tested doses. Saflufenacil is classified as “not likely carcinogenic to humans.”

4.4 Safety Factor for Infants and Children (FQPA SF)

The saflufenacil risk assessment team recommends that the FQPA SF be reduced to 1X for all 

exposure scenarios based on the following rationale: the toxicological database is adequate for 

FQPA assessment, there is no evidence of neurotoxicity, there is low concern for offspring 

susceptibility, and there is no uncertainty in the exposure database.

4.4.1 Completeness of the Toxicology Database

The toxicology database for saflufenacil is complete and adequate for FQPA SF consideration. 

4.4.2 Evidence of Neurotoxicity

There was no evidence of neurotoxicity or neuropathology in the acute and subchronic 

neurotoxicity study. The decrease in motor activity observed in the ACN study on the day of 

dosing at the limit dose (2000 mg/kg/day) in males is considered a reflection of a mild and 

transient general systemic toxicity and not a substance-specific neurotoxic effect. No neurotoxic 

effects were seen in the SCN study. 

4.4.3 Evidence of Sensitivity/Susceptibility in the Developing or Young Animal

The concern for increased susceptibility following prenatal or postnatal exposure is low because 

clear no-observed adverse-effect levels (NOAELs)/LOAELs were established for the 

developmental effects seen in rats and rabbits as well as for the offspring effects seen in the twogeneration reproductive toxicity study. Further, the dose-response relationship for the effects of 

concern are also well characterized and being used for assessing risks. The point of departure for 

risk assessments would be protective of the developmental and offspring effects. 

4.4.4 Residual Uncertainty in the Exposure Database

There are no additional residual uncertainties with respect to exposure data. The dietary food 

exposure assessment utilizes recommended tolerance-level residues and 100% CT information 

for all commodities. By using these screening-level assessments, acute and chronic 

exposures/risks will not be underestimated. The dietary drinking water assessment utilizes 

values generated by models and associated modeling parameters that are designed to provide 
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conservative, health-protective, high-end estimates of water concentrations. There are no 

registered residential uses of saflufenacil; therefore, residential exposures are not anticipated. 

4.5 Toxicity Endpoint and Point of Departure Selections

4.5.1 Dose-Response Assessment

Acute Dietary Endpoint (General population including infants and children): An acute dietary

endpoint was established for this population group based on decreased motor activity observed at 

the LOAEL of 2000 mg/kg bw in male rats in the ACN study. The NOAEL was 500 mg/kg bw. 

A combined UF of 100 was applied to account for interspecies (10X) and intraspecies (10X) 

extrapolation. The FQPA SF was reduced to 1X for this exposure scenario (see Section 4.4). 

Thus, the aPAD is estimated at 5.0 mg/kg bw.

Acute Dietary Endpoint (Females 13-49 years old): An acute dietary endpoint, separate from 

that defined above, was not established for this population group. The developmental effects 

following saflufenacil exposure are unlikely to be the result of a single dose event. The skeletal 

variations (e.g., misshapen bones, delays in ossification, and wavy ribs) observed in the prenatal 

developmental study in the rat are not considered to be the result of a single dose. The process of 

bone deposition begins with cartilage deposition followed by calcification and does not occur 

during a single day. Unlike supernumerary ribs or missing bones, which may be caused by the 

activation or inactivation of genes and could be the outcome of a single exposure, the process of 

bone deposition occurs over several days and, therefore, is not considered appropriate for this 

endpoint.

Chronic Dietary Endpoint: This endpoint was based on decreases in red blood cells, 

hemoglobin, and hematocrit as well as porphyria observed in males in the satellite group 

(sacrificed at 10 months) at the LOAEL of 13.8 mg/kg bw/day in a mouse 

chronic/carcinogenicity study. The NOAEL is 4.6 mg/kg bw/day. A combined UF of 100 was 

applied to account for interspecies (10X) and intraspecies (10X) extrapolation. The FQPA SF 

was reduced to 1X for this exposure scenario (see Section 4.4). Thus, the cPAD is estimated at 

0.046 mg/kg bw/day. This point of departure is protective of the developmental and offspring 

effects. 

Dermal (Short- and Intermediate-Term): Although a 28-day dermal toxicity study with nonpregnant adult rats yielded no evidence of toxicity (dermal or systemic), there is concern for 

developmental toxicity following exposure to saflufenacil. Decreased fetal weights and 

increased skeletal variations were observed in the rat oral prenatal developmental toxicity study 

at the LOAEL of 20 mg/kg/day (NOAEL of 5 mg/kg/day). The concern for developmental 

toxicity is also supported by findings at higher doses from the rabbit developmental toxicity 

study and the rat two-generation reproductive toxicity study. A DAF of 6% was estimated based 

on a dermal penetration study in rats. Thus, the equivalent dermal NOAEL based on the rat 

prenatal developmental toxicity study can be estimated at 83.3 mg/kg/day. The LOC is 100 

based on a combined UF of 100 applied to account for interspecies (10X) and intraspecies (10X) 

extrapolation.

Inhalation (Short- and Intermediate-Term): The inhalation risk for saflufenacil is being assessed 

using the rat prenatal developmental toxicity study with 100% absorption assumed via the 
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inhalation route. The HASPOC decided, based on a weight-of-evidence approach, that a 28-day 

inhalation toxicity study is not required at this time (TXR #0056720). The effects in the rat 

prenatal developmental toxicity study consisted of decreased fetal weights and increased skeletal 

variations at the LOAEL of 20 mg/kg/day (NOAEL of 5 mg/kg/day). The LOC is 100 based on 

a combined UF of 100 applied to account for interspecies (10X) and intraspecies (10X) 

extrapolation. 

4.5.2 Recommendation for Combining Routes of Exposures for Risk Assessment

Dermal and inhalation exposures should be combined since the dermal and inhalation endpoints 

are based on the same study.

4.5.3 Cancer Classification and Risk Assessment Recommendation

Carcinogenicity studies in rats and mice showed no evidence of increased incidence of tumors at 

the tested doses. Saflufenacil is classified as “not likely carcinogenic to humans”; therefore, a 

cancer risk assessment is not required.

4.5.4 Summary of Points of Departure and Toxicity Endpoints Used in Human Risk 

Assessment

Table 4.5.4.1. Summary of Toxicological Doses and Endpoints for Saflufenacil for Use in Dietary Human-Health 

Risk Assessments.

Exposure

Scenario

Point of 

Departure

UFs/

FQPA SF

RfD, PAD, 

LOC for Risk 

Assessment

Study and Toxicological Effects

Acute Dietary 

(General 

Population, 

including 

Infants and 

Children)

NOAEL = 500 

mg/kg bw

UFA = 10X

UFH = 10X

FQPA SF = 1X

aRfD = 5.0 

mg/kg

aPAD = 5.0 

mg/kg

Acute Neurotoxicity Study - rats

NOAEL = 500 mg/kg bw.

LOAEL = 2000 mg/kg bw based on decreased 

motor activity representing mild and transient 

systemic toxicity in males. 

Chronic 

Dietary (All 

Populations)

NOAEL = 4.6 

mg/kg/day

UFA = 10X

UFH = 10X

FQPA SF = 1X

cRfD = 0.046 

mg/kg/day

cPAD = 0.046 

mg/kg/day

Chronic/Carcinogenicity (mouse)

NOAEL = 4.6 mg/kg bw/day.

LOAEL = 13.8 mg/kg bw/d based on 

decreased red blood cells, hemoglobin, 

hematocrit, and porphyria observed in the 

satellite group.

Cancer (oral, 

dermal, 

inhalation)

Classification: Not likely carcinogenic to humans based on the lack of tumors in the mouse and rat 

carcinogenicity studies and lack of mutagenicity.

NOAEL = no-observed adverse-effect level. LOAEL = lowest-observed adverse-effect level. UF = uncertainty 

factor. UFA = extrapolation from animal to human (interspecies). UFH = potential variation in sensitivity among 

members of the human population (intraspecies). MOE = margin of exposure. LOC = level of concern. FQPA SF 

= FQPA Safety Factor. PAD = population-adjusted dose (a = acute, c = chronic). RfD = reference dose. 
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Table 4.5.4.2. Summary of Toxicological Doses and Endpoints for Saflufenacil for Occupational Human-Health 

Risk Assessment.

Exposure/

Scenario

Point of 

Departure

UFs/

FQPA SF

LOC for Risk 

Assessment Study and Toxicological Effects

Dermal Shortand 

IntermediateTerm (1-30 

days and 1-6 

months, 

respectively)

NOAEL = 5 

mg/kg/day

Dermal 

absorption 

factor = 6%

UFA = 10X

UFH = 10X

FQPA SF = 

1X

Occupational LOC 

for MOE = 100

Developmental study -Rat

NOAEL = 5 mg/kg bw/day.

LOAEL = 20 mg/kg bw/day based on 

decreased fetal bodyweight and increased 

skeletal variations. 

Inhalation 

Short- and 

IntermediateTerm (1-30 

days and 1-6 

months, 

respectively)

NOAEL = 5 

mg/kg/day

Inhalationabsorption = 

Assumed to 

be equivalent 

with oral 

absorption

UFA = 10X

UFH = 10X

FQPA SF = 

1X

Occupational LOC 

for MOE = 100

Developmental study -Rat

NOAEL = 5 mg/kg bw/day.

LOAEL = 20 mg/kg bw/day based on 

decreased fetal bodyweight and increased 

skeletal variations. 

Cancer (oral, 

dermal, 

inhalation)

Classification: Not likely carcinogenic to humans based on the lack of tumors in the mouse and rat 

carcinogenicity studies and lack of mutagenicity. 

NOAEL = no-observed adverse-effect level. LOAEL = lowest-observed adverse-effect level. UF = uncertainty 

factor. UFA = extrapolation from animal to human (interspecies). UFH = potential variation in sensitivity among 

members of the human population (intraspecies). MOE = margin of exposure. LOC = level of concern. 

5.0 Dietary Exposure and Risk Assessment 

An overview of the metabolism and environmental degradation of saflufenacil can be found in 

the 22-JUL-2009 human-health risk assessment (L. Austin, et al., D367317).

5.1 Residues of Concern Summary and Rationale

Plants (Primary Crops): The previously submitted metabolism data for corn, soybean, and 

tomato were adequate to elucidate the nature of the residue in plants resulting from pre-plant/preemergence application. The main reactions involved in the metabolic pathway of saflufenacil 

were N-demethylation at the uracil ring, stepwise degradation (N-dealkylation) of the N-methylN-isopropyl group, hydrolytic cleavage of the uracil ring generating a urea side chain, and 

hydroxylation of the phenyl ring. The HED ROCKS determined that residues of concern for the 

tolerance expression and risk assessment consist of saflufenacil, M800H11, and M800H35 

(Memo, B. Daiss, 01-JUN-2009; D359645). The metabolic pathway of radiolabeled saflufenacil 

in soybean following a late-season post-emergence treatment follows the same initial pathways, 

but is not as extensive. No new metabolites were observed following post-emergence treatment; 

however, an additional major metabolite (M800H02), that is not included in the tolerance 

expression, was observed in soybean seed. As the structure of M800H02 is closely related to the 

parent compound and it is the precursor of the regulated metabolite M800H11, HED concluded

that M800H02 is a residue of concern for risk-assessment purposes in seed commodities

following late-season post-emergence treatment.

Subsequently, the petitioner submitted a rice metabolism study following post-emergence foliar 
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application of saflufenacil. The combined residues of saflufenacil, M800H11, and M800H35 

(the current residues of concern for the tolerance expression and risk assessment) in rice forage 

were 71-89% of the total radioactive residue (TRR). The only other major metabolite was 

M800H02, which accounted for 4-16% of the TRR in forage. In rice grain, the combined 

residues of saflufenacil and all identified metabolites was <10% of the TRR (≤0.01 ppm). HED 

thus concludes that the current tolerance expression adequately accounts for the residues of 

concern following post-emergence foliar application to rice and related crops (i.e., cereal grains 

and grass). Additional metabolism data may be required to support foliar application to crops 

other than grasses and legume vegetables.

Plants (Rotational Crops): The metabolism of saflufenacil in rotational crops appears to be 

consistent with the pathway observed in the plant metabolism studies. The previously submitted 

confined and field rotational crop data are adequate to satisfy the data requirements for 

application rates up to 0.137 lb ai/A (1X). The available data indicate that residues of 

saflufenacil and its metabolites M800H11 and M800H35 were each <LOQ in/on all rotational 

crop matrices at a 120-day PBI. These data support the labeled rotational crop restriction of 4 

months for all non-labeled crops. Unless the petitioner requests PBIs shorter than 120 days, no 

additional data are required, and tolerances for inadvertent residues in/on rotational crops need 

not be established in conjunction with the currently proposed uses. 

Livestock: The nature of the residue in livestock is adequately understood based on acceptable 

metabolism studies conducted on lactating goats and laying hens. Saflufenacil was metabolized 

by several dealkylation steps occurring at two different sites in the molecule (N-isopropyl-Nmethylsulfamide side chain and at the uracil ring) and via hydrolytic opening of the uracil ring 

(goat only). In the ruminant metabolism study, saflufenacil was a major residue in all matrices. 

M800H04, a ring opening product, was the only significant metabolite (>10% total radioactive 

residue, TRR) found (liver). In the poultry metabolism study, saflufenacil was a major residue in 

all matrices and no significant metabolites were found. The HED ROCKS determined that 

saflufenacil per se is the only residue of concern for the tolerance expression and risk assessment 

(Memo, B. Daiss, 01-JUN-2009; D359645). The decision to exclude the plant metabolites 

M800H11 and M800H35 as residues of concern in livestock was based on the low potential for 

exposure associated with the previously proposed uses and should be reevaluated if additional 

proposed uses result in a significant increase in the livestock dietary burden. The proposed postemergence uses will result in a significant increase in the livestock dietary burden; however, 

metabolites M800H11 and M800H35 are not major residues in crops following desiccation 

application. M800H02 does not need to be included as a residue of concern as its concentration 

in the subject crops is >6X lower than the parent compound. HED thus concludes that 

saflufenacil per se is still the only residue of concern for the tolerance expression and risk 

assessment in livestock. 

Drinking Water: Saflufenacil is slowly photolyzed in water (half-life of 57 days at pH 5) and 

on soil (half-lives of 83 and 87 days) at 22 °C. In addition, the compound is relatively stable to 

hydrolysis at pH 5, almost stable at pH 7 (half-life of 248 days), and readily hydrolyzed at pH 9 

(half-life of 4.9 days). Therefore, alkaline hydrolysis is a major degradation route for 

saflufenacil in high pH environments.

Saflufenacil biodegrades in 1 to 5 weeks in aerobic soil (half-lives of 8.5-34 days) and less 

quickly in aerobic aquatic environments of pH 5.6 to 6.4 (half-lives of 50 and 107 days). 
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Therefore, aerobic soil metabolism is another major degradation route for saflufenacil that will 

operate in the environment at any pH value.

Dissipation occurred with half-lives of 2.4 to 22 days in terrestrial field dissipation studies 

conducted in the continental U.S., which is consistent with the submitted, laboratory-derived 

data. Dissipation was slower in Canadian field plots (half-lives of 25 days and >>20 days).

Major degradates that are structurally similar to the parent compound include M01, M02, M04, 

M07, M08, M15, M22, and the soil photolysis product number 8. Major cleavage products of 

saflufenacil include M26, trifluoroacetic acid, M31, M33, and TFP. Another major aqueous 

photolysis product was isolated as well (unknown 3/4/7/6), but not identified. Major degradates 

that did not decline in amount in unsterile study conditions include M7, M29, and product 8 (see 

Appendix B: Metabolism Assessment, Table B.1.2 of L. Austin, et al., 22-JUL-2009; D367317).

Table 5.1. Summary of Metabolites and Degradates to be Included in the Risk Assessment.

Matrix Residues Included in Risk 

Assessment

Residues Included in 

Tolerance Expression

Plants

Registered/proposed 

Primary Crops (preplant 

application)*

Saflufenacil + M800H11, 

M800H35

Saflufenacil + M800H11, 

M800H35

Registered/proposed 

Primary Crops (foliar 

application)

Saflufenacil + M800H11, 

M800H02, M800H35

Rotational Crops Saflufenacil + M800H11, 

M800H35

Livestock

Ruminants

Saflufenacil Saflufenacil

Poultry

Drinking Water

Saflufenacil + M800H01, 

M800H02, M800H07, M800H08, 

M800H15, M800H22, Product 8

Not Applicable

* Plus post-emergence foliar application to cereal grains and grasses.

5.2 Food Residue Profile

The new uses/use patterns associated with the subject result in significant increases in the 

livestock MRBDs. Consequently, the petitioner submitted new ruminant and poultry feeding 

studies. The feeding study data indicate that the established tolerances should be increased in all 

livestock commodities except hog meat, fat, and meat byproducts, except liver; and that there is 

no reasonable expectation of finite residues in poultry commodities. 

The submitted crop field trial data are adequate to fulfill data requirements. The available data 

will support the proposed use patterns. The residue data were analyzed using the OECD 

tolerance-calculation procedures. The HED-recommended tolerances differed from the 

petitioner-for tolerances in some cases (Table 2.2.2). A revised Section F is requested.

The submitted wheat and barley processing studies are adequate to fulfill data requirements. A 

tolerance is required for barley bran, and the established aspirated-grain fractions tolerance (10 

ppm) for the combined residues of saflufenacil and its metabolites M800H11 and M800H35 

should be increased to 50 ppm.
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The previously submitted confined and field rotational crop data are adequate to satisfy data 

requirements for application rates up to 0.137 lb ai/A (1X). The available data indicate that 

residues of saflufenacil and its metabolites M800H11 and M800H35 (residues of concern in 

rotational crops) were each <LOQ in/on all rotational crop matrices at a 120-day PBI. These 

data support the labeled rotational crop restriction of 4 months for all non-labeled crops. 

5.3 Water Residue Profile

The Estimated Drinking Water Concentrations (EDWCs) used in the dietary exposure risk 

assessment were provided by EFED in a memorandum dated 12-MAR-2014 (Memo, M. 

Ruhman; DP# 414485). Water residues were incorporated directly into the DEEM-FCID in the 

food categories “water, direct, all sources” and “water, indirect, all sources.”

Screening EDWCs (Table 5.3) of saflufenacil were generated by Tier I Rice modeling for 

surface water and with Pesticide Root Zone Model-Ground Water (PRZM-GW) for ground 

water. Modeled application rates represent the maximum use patterns for dry-seeded rice: the 

1

st application at planting, the second application 14 days after planting and flooding at 45 days 

after planting. Remaining model input parameters were chosen according to current guidance 

(USEPA, 2002). EDWCs reflect exposure to saflufenacil and all degradates of concern in 

drinking water (Table 5.1). 

Table 5.3. Tiered EDWCs for Proposed Saflufenacil Uses.

Source (Tier: Model) 1-in-10-year Peak Exposure 

(ppb)

1-in-10-year Annual Mean 

Exposure (ppb)

Surface water (Tier I: Rice Model) 133

(used in acute analysis)

120

(used in chronic analysis)

Ground water (Tier II: PRZM GW) 69.2 51.5

5.4 Dietary Risk Assessment

5.4.1 Description of Residue Data Used in Dietary Assessment

The unrefined acute and chronic analyses assumed DEEM 7.81 default concentration factors and 

tolerance-level residues for all commodities [except for cottonseed; sunflower subgroup 20B; 

soybean, seed; vegetable, legume, subgroup 6C, pea and bean (except soybean); and rapeseed 

subgroup 20A for which the recommended tolerance levels were multiplied by a correction 

factor to account for a metabolite of concern which is not included in the tolerance expression]. 

Drinking water was incorporated directly into the dietary assessment using the concentration for 

surface water generated by Tier I Rice modeling. 

5.4.2 Percent Crop Treated Used in Dietary Assessment

The acute and chronic dietary analyses assumed 100% CT for all commodities. 

5.4.3 Acute Dietary Risk Assessment

The acute dietary risk for food and drinking water utilized <1% of the aPAD for the U.S. 

population. The acute dietary risk for the highest exposed population subgroup, all infants (<1-
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year old), is <1% of the aPAD at the 95th percentile. A summary table of acute dietary exposure 

and risk for saflufenacil can be found in Section 5.4.6. Although further refinement to the 

analysis is not required at this time, future assessments could be refined using average field trial 

values, use of empirical processing factors, incorporation of %CT data, or monitoring data. 

5.4.4 Chronic Dietary Risk Assessment

The chronic dietary risk for food and drinking water utilized 9.2% of the cPAD for the U.S. 

population. The chronic dietary risk for the highest exposed population subgroup, all infants 

(<1-year old), is 20% of the cPAD. A summary table of chronic dietary exposure and risk for 

saflufenacil can be found in Section 5.4.6. Although further refinement to the analysis is not 

required at this time, future assessments could be refined using average field trial values, use of 

empirical processing factors, incorporation of %CT data, or monitoring data. 

5.4.5 Cancer Dietary Risk Assessment

Saflufenacil is classified as “not likely carcinogenic to humans.” Therefore, cancer risk is not a 

concern for this chemical.

5.4.6 Summary Table

Table 5.4.6. Summary of Dietary (Food and Drinking Water) Exposure Risk for Saflufenacil.

Population Subgroup

Acute Dietary

(95th Percentile) Chronic Dietary

Dietary Exposure 

(mg/kg/day) % aPAD Dietary Exposure(mg/kg/day) % cPAD

General U.S. Population 0.010106 <1 0.004223 9.2

All Infants (<1-year old) 0.026582 <1 0.009099 20

Children 1-2 years old 0.017044 <1 0.008368 18

Children 3-5 years old 0.013965 <1 0.006993 15

Children 6-12 years old 0.010852 <1 0.004872 11

Youth 13-19 years old 0.008383 <1 0.003409 7.4

Adults 20-49 years old 0.009103 <1 0.003946 8.6

Adults 50-99 years old 0.007781 <1 0.003679 8.0

Females 13-49 years old 0.009078 <1 0.003759 8.2

*The values for the highest exposed population for each type of risk assessment are bolded.

6.0 Residential (Non-Occupational) Exposure/Risk

6.1 Residential Exposure/Risk Characterization

Saflufenacil has no registered or proposed residential uses; therefore, a quantitative nonoccupational exposure assessment was not performed.

6.2 Residential Bystander Post-Application Inhalation Exposure

Based on the Agency's current practices, a quantitative post-application inhalation exposure 

assessment was not performed for saflufenacil at this time primarily because of the low acute 

inhalation toxicity (Toxicity Category IV) and the low vapor pressure (4.5 x 10-15 Pa, 20°C). 
Saflufenacil Human-Health Risk Assessment DP# 418587

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However, volatilization of pesticides may be a source of post-application inhalation exposure to 

individuals nearby pesticide applications. The Agency sought expert advice and input on issues 

related to volatilization of pesticides from its Federal Insecticide, Fungicide, and Rodenticide Act 

(FIFRA) Scientific Advisory Panel (SAP) in December 2009, and received the SAP’s final report 

on March 2, 20101. The Agency is in the process of evaluating the SAP report and may, as 

appropriate, develop policies and procedures to identify the need for and, subsequently, the way 

to incorporate post-application inhalation exposure into the Agency's risk assessments. If new 

policies or procedures are developed, then the Agency may revisit the need for a quantitative 

post-application inhalation exposure assessment for saflufenacil.

6.3 Spray Drift

Spray drift is a potential source of exposure to those nearby pesticide applications. This is 

particularly the case with aerial application, but, to a lesser extent, spray drift can also be a 

potential source of exposure from the ground application methods (e.g., groundboom and 

airblast) employed for saflufenacil. The Agency has been working with the Spray Drift Task 

Force (a task force composed of various registrants which was developed as a result of a Data 

Call-In issued by EPA), EPA Regional Offices and State Lead Agencies for pesticide regulation 

and other parties to develop the best spray drift management practices (see the Agency’s Spray 

Drift website for more information).2 The Agency is also taking means to address quantitatively

and qualitatively spray drift as a potential source of exposure in risk assessments for pesticides 

through existing programs such as AgDRIFT® and chemical-specific properties of pesticides. 

The potential for spray drift will be quantitatively evaluated for each pesticide during the 

Registration Review process that ensures that all uses for that pesticide will be considered 

concurrently. The Agency has also developed a policy on how appropriately to consider spray 

drift as a potential source of exposure in risk assessments for pesticides. 

The potential for spray drift will be quantitatively evaluated for each pesticide during the 

Registration Review process that ensures that all uses for that pesticide will be considered 

concurrently. The approach is outlined in the revised (2012) Standard Operating Procedures 

For Residential Risk Assessment (SOPs) - Residential Exposure Assessment Standard Operating 

Procedures Addenda 1: Consideration of Spray Drift3. This document outlines the 

quantification of indirect non-occupational exposure to drift. 

7.0 Aggregate Exposure/Risk Characterization

In accordance with the FQPA, HED must consider and aggregate pesticide exposures and risks 

from three major sources: food, drinking water, and residential exposures. In an aggregate 

assessment, exposures from relevant sources are added together and compared to quantitative 

estimates of hazard (e.g., a NOAEL or PAD), or the risks themselves can be aggregated. When 

aggregating exposures and risks from various sources, HED considers both the route and 

duration of exposure.

For saflufenacil, aggregate exposure and risk assessments were assessed by incorporating the 

 

1 Available: http://www.epa.gov/scipoly/SAP/meetings/2009/120109meeting.html

2 Available: http://www.epa.gov/opp00001/factsheets/spraydrift.htm 

3 Available: http://www.regulations.gov/#!documentDetail;D=EPA-HQ-OPP-2013-0676-0001
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drinking water directly into the dietary-exposure assessment for the following scenarios: acute 

and chronic aggregate exposure (food + drinking water). Short-, intermediate-, and long-term 

aggregate-risk assessments were not performed because there are no registered or proposed uses 

of saflufenacil that result in residential exposures. A cancer aggregate-risk assessment was not 

performed because saflufenacil is not a carcinogen and cancer risk is not a concern.

7.1 Acute Aggregate Risk

The acute aggregate risk assessment takes into account average exposure estimates from dietary 

consumption of saflufenacil (food and drinking water). The acute dietary exposure estimates are 

not of concern to HED (<100% cPAD) for the general U.S. population and all population 

subgroups (see Table 5.4.6). 

7.2 Chronic Aggregate Risk

The chronic aggregate risk assessment takes into account average exposure estimates from 

dietary consumption of saflufenacil (food and drinking water). The chronic dietary exposure 

estimates are not of concern to HED (<100% cPAD) for the general U.S. population and all 

population subgroups (see Table 5.4.6). 

8.0 Cumulative Risk Characterization/Assessment

Unlike other pesticides for which EPA has followed a cumulative risk approach based on a 

common mechanism of toxicity, EPA has not made a common mechanism of toxicity finding as 

to saflufenacil and any other substances and saflufenacil does not appear to produce a toxic 

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

EPA has not assumed that saflufenacil has a common mechanism of toxicity with other 

substances. For information regarding EPA’s efforts to determine which chemicals have a 

common mechanism of toxicity and to evaluate the cumulative effects of such chemicals, see the 

policy statements released by EPA’s Office of Pesticide Programs concerning common 

mechanism determinations and procedures for cumulating effects from substances found to have 

a common mechanism on EPA’s website at http://www.epa.gov/pesticides/cumulative/.

9.0 Occupational Exposure/Risk Characterization

9.1 Short- and Intermediate-Term Handler Risk

The occupational handler exposure and risk estimates indicate that the short- and intermediateterm dermal and inhalation combined MOEs are not of concern to HED (i.e., MOE > 100). At 

the baseline level of personal protection (i.e., no gloves and no respirator), all scenarios result in 

combined MOEs (dermal + inhalation) ≥ 250.

HED has no data to assess exposures to pilots using open cockpits. The only data available is for

exposure to pilots in enclosed cockpits. Therefore, risks to pilots are assessed using the 

engineering control (enclosed cockpits) and baseline attire (long-sleeve shirt, long pants, shoes, 

and socks); per the Agency’s Worker Protection Standard stipulations for engineering controls, 
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pilots are not required to wear protective gloves for the duration of the application. With this 

level of protection, there are no risk estimates of concern for applicators.

The Agency matches quantitative occupational exposure assessment with appropriate 

characterization of exposure potential. While HED presents quantitative risk estimates for 

human flaggers where appropriate, agricultural aviation has changed dramatically over the past 

two decades. According the 2012 National Agricultural Aviation Association (NAAA) survey of 

their membership, the use of Global Positioning System (GPS) for swath guidance in agricultural 

aviation has grown steadily from the mid-1990s. Over the same time period, the use of human 

flaggers for aerial pesticide applications has decreased steadily from ~15% in the late 1990s to 

only 1% in the most recent (2012) NAAA survey. The Agency will continue to monitor all 

available information sources to best assess and characterize the exposure potential for human 

flaggers in agricultural aerial applications.
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Table 9.1. Occupational Handler Non-Cancer Exposure and Risk Estimates for Saflufenacil. 

Exposure Scenario Crop or Target

Dermal Unit 

Exposure

(μg/lb ai)1

Inhalation Unit 

Exposure

(μg/lb ai)1

Maximum 

Applic.

Rate (lb 

ai/A)2

Area Treated 

(acres)3

Dermal

(LOC = 100)

Inhalation

(LOC = 100)

Total

(LOC = 100)

Mitigation Level Mitigation Level Dose 

(mg/kg/day)4 MOE5 Dose (mg/kg/day)6 MOE7 MOE8

Mixer/Loader

Aerial application of liquid 

formulation

Forage Grasses Grown in 

Pastures and 

Rangeland, or in Fields 

Grown for Forage, 

Silage and Hay 

Production

220

(baseline)

0.219

(baseline) 0.089

1200 0.0204 250 0.000339 15,000 250

Groundboom application of 

liquid formulation 200 0.00341 1,500 0.0000565 88,000 1,500

Groundboom application of dry 

flowable formulation Olive trees 227(baseline)

8.96

(baseline) 0.044 80 0.000695 7,200 0.000457 11,000 4,400

Commercial Impregnation of 

Dry Bulk Fertilizers (closed 

system)

Forage Grasses Grown in 

Pastures and 

Rangeland, or in Fields 

Grown for Forage, 

Silage and Hay 

Production

8.6 (engineering 

control)

0.083 

(engineering 

control)

0.89 lb ai/ton 960 tons 0.00639 780 0.00103 4,900 670

On-farm Impregnation of Dry 

Bulk Fertilizers

220

(baseline)

0.219

(baseline) 0.089 160 0.00272 1,800 0.0000452 110,000 1,800

Applicator

Aerial spray application

Forage Grasses Grown in 

Pastures and 

Rangeland, or in Fields 

Grown for Forage, 

Silage and Hay 

Production

2.08

(engineering 

control)

0.0049

(engineering 

control) 0.089

1200 0.000193 26,000 0.00000758 660,000 25,000

Groundboom spray application 78.6

(baseline)

0.34

(baseline)

200 0.00122 4,100 0.0000877 57,000 3,800

Olive trees 0.044 80 0.000241 21,000 0.0000174 290,000 20,000

Commercial Impregnation of 

Dry Bulk Fertilizers

Forage Grasses Grown in 

Pastures and 

Rangeland, or in Fields 

Grown for Forage, 

Silage and Hay 

Production

9.9

(baseline)

1.2

(baseline) 0.089

320 0.000245 20,000 0.000496 10,000 6,700

On-farm Impregnation of Dry 

Bulk Fertilizers 160 0.000123 41,000 0.000248 20,000 13,000

Flagger

Flagger for aerial spray 

application

Forage Grasses Grown in 

Pastures and 

Rangeland, or in Fields 

Grown for Forage, 

Silage and Hay 

Production

11

(baseline)

0.35

(baseline) 0.089 350 0.000298 17,000 0.000158 32,000 11,000
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Table 9.1. Occupational Handler Non-Cancer Exposure and Risk Estimates for Saflufenacil. 

Exposure Scenario Crop or Target

Dermal Unit 

Exposure

(μg/lb ai)1

Inhalation Unit 

Exposure

(μg/lb ai)1

Maximum 

Applic.

Rate (lb 

ai/A)2

Area Treated 

(acres)3

Dermal

(LOC = 100)

Inhalation

(LOC = 100)

Total

(LOC = 100)

Mitigation Level Mitigation Level Dose 

(mg/kg/day)4 MOE5 Dose (mg/kg/day)6 MOE7 MOE8

Mixer/Loader/Applicator

Mixing/loading/applying dry 

flowables via backpack 

applications Olive trees 

(ground-directed)

8260 2.58

0.00044 lb 

ai/gallon 40 gallons

0.000126 40,000 0.000000658 7,600,000 40,000

Mixing/loading/applying dry 

flowables via manuallypressurized handwand 

applications

100,000 30 0.00153 3,300 0.00000765 650,000 3,300

1 Based on the “Occupational Pesticide Handler Unit Exposure Surrogate Reference Table” (March 2013); Level of mitigation: Baseline, Eng. Controls.

2 Based on proposed labels (Reg. No. 7969-278, 7969-276, and 7969-297).

3 Exposure Science Advisory Council Policy #9.1 and petitioner information.

4 Dermal Dose = Dermal Unit Exposure (μg/lb ai) × Conversion Factor (0.001 mg/μg) × Application Rate (lb ai/acre) × Area Treated (A/day) × DAF (6%) ÷ BW (69 kg).

5 Dermal MOE = Dermal NOAEL (5 mg/kg/day) ÷ Dermal Dose (mg/kg/day).

6 Inhalation Dose = Inhalation Unit Exposure (μg/lb ai) × Conversion Factor (0.001 mg/μg) × Application Rate (lb ai/acre) × Area Treated (A/day) ÷ BW (69 kg).

7 Inhalation MOE = Inhalation NOAEL (5 mg/kg/day) ÷ Inhalation Dose (mg/kg/day).

8 Total MOE = NOAEL (5 mg/kg/day) ÷ (Dermal Dose + Inhalation Dose).
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9.2 Short- and Intermediate-Term Post-Application Risk

9.2.1 Dermal Post-Application Risk

A post-application exposure assessment has not been conducted for the proposed use on olive 

trees since the use directions indicate that the product is to be applied to the base of the tree trunk 

and is not to contact the foliage. Currently, HED has no transfer coefficients or other data to 

assess post-application dermal exposures to soil by occupational workers. In general, such 

exposures are considered negligible. Therefore, for the soil-directed uses, post-application 

exposures and risks to occupational workers were not assessed. 

The proposed use on wheat and barley is for application of saflufenacil as a harvest 

aid/desiccant. As such, postapplication exposure to foliage is not expected because harvesting is 

done mechanically. Therefore, occupational post-application dermal exposure was not assessed 

at this time.

The proposed uses on grass/forage are not specifically soil directed and, therefore, could result in 

potential post-application exposures. These exposures have been assessed.

The short- and intermediate-term post-application exposure scenarios associated with the 

proposed uses for saflufenacil are summarized in Table 9.2.1. All scenarios resulted in MOEs 

greater than the LOC of 100 (ranging from 3,000 to 5,200) on day 0 (12 hours after application) 

and, therefore, are not of concern to HED.

Table 9.2.1. Occupational Post-application Non-Cancer Exposure and Risk Estimates for Saflufenacil.

Crop/Site Activities

Transfer 

Coefficient 

(cm2/hr)

Proposed 

Application 

Rate (lb ai/A)

DFR1 Dermal Dose 

(mg/kg/day)2

MOE3

(LOC = 

100)

Short- and Intermediate-term

Forage crop

Scouting 1,100

0.045 0.13

0.00097 5,200

Irrigation (hand set) 1,900 0.00167 3,000

1 DFR = Application Rate × F × (1-D)t × 4.54E8 μg/lb × 2.47E-8 acre/cm2; where F = 0.25 and D = 0.10 per day. 

2 Daily Dermal Dose = [DFR (μg/cm2) × Transfer Coefficient × 0.001 mg/μg × 8 hrs/day × dermal absorption (6%)]  BW (69 kg).

3 MOE = POD (5 mg/kg/day) / Daily Dermal Dose. 

9.2.2 Inhalation Post-Application Risk

Based on the Agency's current practices, a quantitative occupational post-application inhalation 

exposure assessment was not performed for saflufenacil at this time primarily because of the low 

acute inhalation toxicity (Toxicity Category IV) and low vapor pressure (4.5 x 10-15 Pa, 20°C). 

However, there are multiple potential sources of post-application inhalation exposure to 

individuals performing post-application activities in previously treated fields. These potential 

sources include volatilization of pesticides and resuspension of dusts and/or particulates that 

contain pesticides. The Agency sought expert advice and input on issues related to volatilization 

of pesticides from its FIFRA SAP in December 2009, and received the SAP’s final report on 

March 2, 20104. The Agency is in the process of evaluating the SAP report as well as available 

post-application inhalation exposure data generated by the Agricultural Reentry Task Force 

(ARTF) and may, as appropriate, develop policies and procedures, to identify the need for and, 

 

4 Available: http://www.epa.gov/scipoly/SAP/meetings/2009/120109meeting.html
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subsequently, the way to incorporate occupational post-application inhalation exposure into the 

Agency's risk assessments. If new policies or procedures are put into place, the Agency may 

revisit the need for a quantitative occupational post-application inhalation exposure assessment 

for saflufenacil.

Although a quantitative occupational post-application inhalation exposure assessment was not 

performed, an inhalation exposure assessment was performed for occupational/commercial 

handlers. Handler exposure resulting from application of pesticides outdoors is likely to result in 

higher exposure than post-application inhalation exposure. Therefore, it is expected that these 

handler inhalation exposure estimates would be protective of most occupational post-application

inhalation exposure scenarios.

9.3 Restricted Entry Interval

The REI specified on the proposed label is based on the acute toxicity of saflufenacil. 

Saflufenacil is classified as Toxicity Category III for acute oral, acute dermal toxicity, and acute 

eye irritation. It is classified as Toxicity Category IV for acute inhalation toxicity and acute 

dermal irritation. It is not a dermal sensitizer. Short- and intermediate-term post-application risk 

estimates were not a concern on day 0 (12 hours following application) for all post-application 

activities. Under 40 CFR §156.208 (c) (2) (iii), ais classified as Acute III or IV for acute dermal, 

eye irritation and primary skin irrigation are assigned a 12-hour REI. Therefore, the [156 subpart 

K] Worker Protection Statement interim REI of 12 hours is adequate to protect agricultural 

workers from post-application exposures to saflufenacil. 

10.0 References

Previous Risk Assessments: L. Austin, et al., 22-JUL-2009; D367317. G. Kramer, et al.; 19-

APR-2011; D380636. G. Kramer, et al.; 23-JAN-2014; D405506

HASPOC Memo: A. Dunbar, 02-AUG-2013; TXR #0056720

Chemistry Memo: G. Kramer, 24-JUN-2014; D414003

Drinking Water Memo: M. Ruhman, 12-MAR-2014; D414485

Dietary Memo: G. Kramer, 24-JUN-2014; D418585

Occupational and Residential Exposure Assessment Memo: K. Lowe, 24-JUN-2014; D418586

List of Appendices:

Appendix A. Toxicology Profile

Appendix B. Physical/Chemical Properties

Appendix C. Review of Human Research

cc: G. Kramer (RAB1)

RDI: RAB1 (4/2/14)

G.F. Kramer:S10957:PY-S:(703)305-5079:7509P:RAB1
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Appendix A. Toxicology Assessment

A.1 Toxicology Data Requirements for Saflufenacil

Test Technical

Required Satisfied

870.1100 Acute Oral Toxicity.......................................................

870.1200 Acute Dermal Toxicity ..................................................

870.1300 Acute Inhalation Toxicity..............................................

870.2400 Primary Eye Irritation....................................................

870.2500 Primary Dermal Irritation ..............................................

870.2600 Dermal Sensitization......................................................

yes

yes

yes

yes

yes

yes

yes

yes

yes

yes

yes

yes

870.3100 Oral Subchronic (rodent)...............................................

870.3150 Oral Subchronic (nonrodent) .........................................

870.3200 21-Day Dermal ..............................................................

870.3250 90-Day Dermal ..............................................................

870.3465 90-Day Inhalation..........................................................

yes

yes

yes

no

no

yes

yes

yes

-

yes1

870.3700a Developmental Toxicity (rodent)...................................

870.3700b Developmental Toxicity (nonrodent).............................

870.3800 Reproduction .................................................................

yes

yes

yes

yes

yes

yes

870.4100a Chronic Toxicity (rodent) ..............................................

870.4100b Chronic Toxicity (nonrodent)........................................

870.4200a Oncogenicity (rat)..........................................................

870.4200b Oncogenicity (mouse)....................................................

870.4300 Chronic/Oncogenicity....................................................

yes

yes

yes

yes

yes

yes

yes

yes

yes

yes

870.5100 Mutagenicity—Gene Mutation - bacterial.....................

870.5300 Mutagenicity—Gene Mutation - mammalian................

870.5xxx Mutagenicity—Structural Chromosomal Aberrations...

870.5xxx Mutagenicity—Other Genotoxic Effects.......................

yes

yes

yes

yes

yes

yes

yes

yes

870.6100a Acute Delayed Neurotox. (hen) .....................................

870.6100b 90-Day Neurotoxicity (hen)...........................................

870.6200a Acute Neurotox. Screening Battery (rat) .......................

870.6200b 90-Day Neurotox. Screening Battery (rat).....................

870.6300 Develop. Neuro..............................................................

no

no

yes

yes

no

-

-

yes

yes

no

870.7485 General Metabolism ......................................................

870.7600 Dermal Penetration........................................................

870.7800 Immunotoxicity .............................................................

yes

yes

yes

yes

yes

yes

1 Waived by the HASPOC (A. Dunbar, 02-AUG-2013; TXR #0056720).

A.2 Toxicity Profiles

Table A.2.1. Acute Toxicity Profile – Saflufenacil.

Guideline No. Study Type MRID(s) Results

Toxicity 

Category Purity

870.1100 Acute oral [rat] 47128101 LD50 >2000 mg/kg 

bw

III 93.8%

870.1200 Acute dermal [rat] 47128102 LD50 >2000 mg/kg III 93.8%

870.1300 Acute inhalation [rat] 47128103 LC50 >5.3 mg/L IV 93.8%

870.2400 Acute eye irritation [White New 

Zealand rabbit]

47128105 minimal irritation III 93.8%

870.2400 Acute eye irritation [White New 

Zealand rabbit]

47128104 minimal irritation III 93.8%

870.2500 Acute dermal irritation [rabbit] 47128106 slightly irritating IV 93.8%

870.2600 Skin sensitization [Guinea Pig] 47128107 not a sensitizer N/A 93.8%
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Table A.2.2. Subchronic, Chronic, and Other Toxicity Profile for Saflufenacil.

Guideline No./Study Type MRID No. 

(year)/Classification/Doses Results

870.3100

28-Day Oral Toxicity feeding-mice

47128110 (2007)

Acceptable/non-guideline

0, 50, 150, 450, 1350, or 4050 ppm 

M\F: 0, 12.8/17.9, 36.6/63.4, 

112/153.1, 335/446, 882/1630 mg/kg 

bw/day

LOAEL = 36.6 mg/kg bw/day (males) based 

on increased alanine aminotransferase, 

aspartate aminotransferase, urea and total 

bilirubin, decreased hemoglobin (Hb) and Ht,

and increased liver weight and centrilobular 

fatty change. 

NOAEL = 12.8 mg/kg bw/day. 

LOAEL = 153.1 mg/kg bw/day (females) 

based on moderate centrilobular fatty change 

in the liver. 

NOAEL = 63.4 mg/kg bw/day.

870.3100

28-Day Oral Toxicity feeding-rat

47128108 (2007)

Acceptable/non-guideline

0, 50, 150, 450, 1350, or 4050 ppm 

M = 0, 4.5, 13.4, 39.2, 117, 357

F = 0, 5.0, 15.9, 43.6, 130.4, 376 

mg/kg bw/day

LOAEL = 39.2 mg/kg bw/day (males) based 

on decreased Hb, MCV, and MCH. 

NOAEL =13.4 mg/kg bw/day. 

LOAEL = 130.4 mg/kg bw/day (females) 

based on decreased Hb, Ht, MCV, and MCH. 

NOAEL = 43.6 mg/kg bw/day.

870.3100

90-Day Oral Toxicity feeding-mice

47128111 (2007)

Acceptable/guideline

0, 15 (males only), 50, 150, 450, and 

1350 (females only) ppm 

M = 0, 3.6, 12.4, 36.7, 109.1

F = 0, 17.6, 51.8, 156.6, 471.2 mg/kg 

bw/day

LOAEL = 36.7 mg/kg bw/day (males) based 

on multiple hematological changes, liverweight increases with centrilobular fatty 

change and lymphoid infiltrate in males.

NOAEL = 12.4 mg/kg bw/day. 

LOAEL = 156.6 mg/kg/day (females) based 

on increased liver weight with centrilobular 

fatty change and lymphoid infiltrate. 

NOAEL = 51.8 mg/kg/day.

870.3100

90-Day Oral Toxicity feeding-rat

47128109 (2007)

Acceptable/guideline

0, 50, 150, 450 (males), 1350, or 

4050 (females) ppm 

M =0, 3.5, 10.5, 32.3, 94.7

F = 0, 4.3, 12.6, 110.5, 344.7 mg/kg 

bw/day

LOAEL = 32.3 mg/kg bw/day (M) and 110.5 

mg/kg bw/day (F) based on multiple 

hematological effects and increased spleen 

weight and extramedullary hematopoiesis. 

NOAEL = 10.5 (M), 12.6 mg/kg bw/day (F).

870.3150

28-Day Oral Toxicity feeding-dog

47128112 (2005)

Acceptable/non-guideline

0, 30, 100, or 300 mg/kg bw/day

LOAEL = 100 mg/kg bw/day based decreased 

mean corpuscular volume, MCH, and MCHC, 

bone marrow hyperplasia, increased iron 

storage in the liver and extramedullary 

hematopoiesis in the spleen. 

NOAEL = 30 mg/kg bw/day.

870.3150

90-Day Oral Toxicity feeding-dog

47128113 (2006)

Acceptable/guideline

0, 10, 50, or 150 mg/kg bw/day

LOAEL = 50 mg/kg bw/day based on lower 

MCV and MCH values in both sexes.

NOAEL = 10 mg/kg bw/day.

870.3200

21/28-Day dermal toxicity (rat)

47128114 (2006)

Acceptable/guideline

0, 100, 300, or 1000 mg/kg

LOAEL was not established.

NOAEL = 1000 mg/kg bw/day.

870.3700a

Prenatal developmental in (rat)

47128115 (2007)

Acceptable/guideline

0, 5, 20, or 60 mg/kg/day

Maternal NOAEL = 20 mg/kg/day.

LOAEL = 60 mg/kg/day based on decreased 

Hb, Ht, MCV, and MCH.

Developmental NOAEL = 5 mg/kg/day. 

LOAEL = 20 mg/kg/day based on decreased 

fetal body weights and increase in skeletal 

variations. 
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Table A.2.2. Subchronic, Chronic, and Other Toxicity Profile for Saflufenacil.

Guideline No./Study Type MRID No. 

(year)/Classification/Doses Results

870.3700b

Prenatal developmental in (rabbit)

47128116 (2006)

Acceptable/guideline

0, 50, 200, or 600 mg/kg/day

Maternal NOAEL = 200 mg/kg bw/day.

LOAEL = 600 mg/kg bw/d based on mortality 

and increased necropsy findings.

Developmental NOAEL = 50 mg/kg/day 

LOAEL = 200 mg/kg/day based on increased 

liver porphyrins.

870.3800

Reproduction and fertility effects

(rat)

47128117 (2007)

acceptable/guideline

0, 5, 15, or 50 mg/kg bw/day

Parental Systemic NOAEL = 15 mg/kg/day.

Parental Systemic LOAEL = 50 mg/kg/day 

based on decreased food intake, body weight, 

and changes in hematological parameters and 

organ weights indicative of anemia.

Reproduction NOAEL = M/F 50 mg/kg/day.

Reproduction LOAEL was not established.

Offspring NOAEL = 15 mg/kg/day.

Offspring LOAEL = 50 mg/kg/day based on 

decreased number of live born pups, increased 

number of stillborn pups, decreased viability 

and lactation indices, decreased pre-weaning 

body weight, and changes in hematological 

parameters.

870.4300b

Chronic Toxicity

(dog)

47128118 (2007)

Acceptable/guideline 

0, 5, 20, or 80 mg/kg bw/day

LOAEL = 80 mg/kg bw/day based on 

decreased albumin, MVH, and MCH.

NOAEL = 20 mg/kg bw/day.

870.4300

Chronic/Carcinogenicity

(rat)

47128120 (2007)

Acceptable/guideline

0, 20, 100, 250 (males), 500 or 1000 

(females) ppm 

M = 0, 0.9, 4.8, 12.0, 24.2

F = 0, 1.3, 6.2, 31.4, 63.0 mg/kg 

bw/day

LOAEL = 31.4 mg/kg bw/day (females) 

based on decreased Hb, Ht, MCV, and MCH. 

NOAEL = 6.2 mg/kg bw/day (females).

LOAEL was not established in males. 

NOAEL = 24.2 mg/kg bw/day.

No evidence of carcinogenicity.

870.4300

Chronic/Carcinogenicity

(mouse)

47128119 (2007)

Acceptable/guideline

0, 1 (males), 5, 25, 75, or 150 

(females) ppm

M = 0, 0.2, 0.9, 4.6, 13.8

F = 0, 1.2, 6.4, 18.9, 38.1 mg/kg 

bw/day

satellite groups: 

M = 0, 14.2

F = 0, 39.0 mg/kg bw/d

NOAEL = 4.6 mg/kg bw/day (males) and 

18.9 mg/kg bw/day (females). 

LOAELs = 13.8 mg/kg bw/day (males) and 

38.1 mg/kg bw/day (females) based on 

decreased red blood cells, Hb, and Ht and 

porphyria observed in the satellite group.

No evidence of carcinogenicity.

Gene Mutation

870.5100 

In vitro Bacterial Gene Mutation 

47128121 (2005)

Acceptable/guideline

0, 20, 100, 500, 2500, or 5000 

μg/plate (saflufenacil hydrate)

There was no evidence of induced mutant 

colonies over background.

Gene Mutation

870.5100 

In vitro Bacterial Gene Mutation

47128122 (2005)

Acceptable/guideline

0, 20, 100, 500, 2500, or 5000

μg/plate (saflufenacil anhydrate)

There was no evidence of induced mutant 

colonies over background.

Gene Mutation

870.5300 

In vitro Mammalian Cells Gene 

Mutation (Chinese Hamster Ovary 

Cells) 

47128123 (2005)

Acceptable/guideline

0, 312.5, 625, 1250, 2500, or 5000 

μg/mL

There was no evidence of induced mutant 

colonies over background.

Cytogenetics 47128124 (2005) Saflufenacil was considered clastogenic in 
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Table A.2.2. Subchronic, Chronic, and Other Toxicity Profile for Saflufenacil.

Guideline No./Study Type MRID No. 

(year)/Classification/Doses Results

870.5375 

In vitro Mammalian Cytogenetics

chromosomal aberration assay- V79 

cells

Acceptable/guideline

0, 5, 10, and 20 ug/ml without S9 

activation 

0, 10, 20, and 40 ug/ml with S9 

activation

vitro in V79 cells in the presence of S9 

metabolic activation. Saflufenacil was not 

clastogenic in the absence of metabolic 

activation.

Cytogenetics-other

870.5395 In Vivo Mammalian 

Cytogenetics - Erythrocyte 

Micronucleus assay in mice

47128125 (2005)

Acceptable/guideline

0, 500, 1000, or 2000 mg/kg bw

There was no increase in the frequency of 

micronucleated immature erythrocytes in 

mouse bone marrow.

870.5550 Other Genotoxicity-In vivo

unscheduled DNA synthesis (rat)

47128126 (2005)

Acceptable/guideline

single oral dose of 1000, or 2000 

mg/kg bw 

Negative

870.6200a

Acute neurotoxicity battery (rat)

47128127 (2007)

Acceptable/Guideline

0, 125, 500, or 2000 mg/kg bw

Systemic LOAEL was 2000 mg/kg bw 

(males) based on the decreased motor activity 

representing mild and transient systemic 

toxicity. 

Systemic LOAEL was not established for 

females. 

Systemic NOAEL = 500 (M) and 2000 (F) 

mg/kg bw.

There was no evidence of neurotoxicity.

870.6200b

Subchronic neurotoxicity (rat)

47128128 (2007)

Acceptable/Guideline

0, 50, 250, 1000 (males), or 1350 

(females) ppm

M = 0, 3.3, 16.6, 66.2

F = 0, 3.9, 19.4, 101.0 mg/kg bw/d

Systemic NOAEL = 16.6 (males), 19.4 

(females) mg/kg bw/day. 

Systemic LOAEL = 66.2 (males) and 101 

(females) mg/kg bw/day based on decreased 

Hb, Ht, MCV, and MCH.

There was no evidence of neurotoxicity. 

870.7485

Metabolism and pharmacokinetics

(rat)

47128130, 47128129 (2007)

4, 20, or 100 mg/kg bw (single oral 

dose)

5 or 100 mg/kg bw (single dose)

100 mg/kg for 14 days

Saflufenacil was rapidly absorbed, 

distributed, and excreted. Regardless of the 

dose administered, maximum concentration of 

saflufenacil in blood and plasma was reached 

within 1 h of dosing and declined rapidly after 

24 h. Excretion of orally dosed saflufenacil 

was essentially complete within 96 h; the 

majority was eliminated within the first 24 to 

48 h. Demonstrating that the majority of the 

saflufenacil residues occurred in the plasma 

and were not bound to cellular elements of the 

blood. There was a sex-dependent difference 

in the excretion of orally administered 

saflufenacil. Following single low- and highdose administration or a repeat high-dose 

administration, the main route of elimination 

in male rats was via the feces, while urinary 

excretion was the major route of elimination 

in females. There was significantly higher 

biliary excretion of saflufenacil residues in 

males than in 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. Saflufenacil was metabolized 

by three major transformation steps: 

demethylation of the uracil ring system, 

degradation of the N-methyl-N-isopropyl 
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Table A.2.2. Subchronic, Chronic, and Other Toxicity Profile for Saflufenacil.

Guideline No./Study Type MRID No. 

(year)/Classification/Doses Results

group to NH2, and cleavage of the uracil ring, 

forming a sulfonylamide group. The 

predominant metabolites were M800H01, 

M800H03, M800H07, and the parent 

compound. Other minor metabolites were 

M800H05, M800H16, M800H17, M800H18, 

M800M19, and M800M20. There were no 

significant sex differences in metabolic 

profiles.

870.7600

Dermal penetration

(rat)

47128214 (2007)

Acceptable/guideline

1.1723 mg/cm2, 0,1172 mg/cm2and 

0.0117 mg/cm2

11.723, 1.172 and 0.117 mg/rat

Dermal absorption is 6%.

870.7800 

Immunotoxicity

(mice)

48233701 (2010)

Acceptable/guideline

0, 50, 125, and 250 ppm (0, 10, 27, 

and 52 mg/kg/day)

LOAEL for systemic toxicity was 125 ppm 

(or 27 mg/kg bw/day) based on significant 

changes in pathological and clinical pathology 

parameters. The NOAEL for systemic 

toxicity was 50 ppm (10 mg/kg bw/day).

The LOAEL for immunotoxicity was not 

identified.

The NOAEL for immunotoxicity is the 

highest dose tested of 250 ppm (52 mg/kg 

bw/day).

Comparative Bioavailability/Toxicity 

Study (rat)

47128133 (2005)

Acceptable/non-guideline

0 or 1350 ppm

The bioavailability and toxicity potential of 

the hydrated and anhydrated forms of 

saflufenacil were similar.

Mechanistic study – total porphyrin 

analysis in rat

47128132 (2006)

Acceptable/non-guideline

0, 10, 50, or 1000 ppm (♂ = 0, 0.8, 

4.1, 80.6; ♀ = 0, 0.9, 4.6, 89.5 mg/kg 

bw/day, respectively)

Total porphyrins in feces and liver provided 

the most reliable and sensitive data. 

Statistically significant effects on porphyrin 

metabolism could be detected at exposure 

concentrations well below those associated 

with adverse hematological effects.

NOAEL= 4.1 mg/kg/day.

LOAEL = 80.6 mg/kg/day based on decreased 

Hb, Ht, MCV, MCH, and MCHC.

Mechanistic study-porphyrin analysis 

supplementary (rat)

47128131 (2005)

Acceptable/non-guideline

0, 1, 5, or 25 ppm (♂ = 0, 0.1, 0.4, 

2.0; ♀ = 0, 0.1, 0.5, 2.3 mg/kg 

bw/day

Dietary administration of saflufenacil at 25 

ppm caused an increase in porphyrin in feces 

of male (237%) and female (61%) rats, while 

saflufenacil at 5 ppm caused an increase in 

fecal porphyrin only in males. There were no 

effects on hematology parameters.
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Appendix B. Physical/Chemical Properties

Table B.1. Physicochemical Properties of Technical Grade Saflufenacil.

Parameter Value

Melting point Average = 189.9 °C, peak max = 193.4 °C

pH 4.43 of 1% solution at 25 °C

Bulk Density (ambient 

temp.) 0.661 kg/L (free fall), 0.736 kg/L (packed)

Water solubility (20 °C) in g/100 mL:

0.0025 in water (pH = 5); 0.0014 in pH 4 buffer; 0.21 in pH 7 buffer; not determined due to 

degradation in pH 9 buffer

Solvent solubility (20 °C) in g/100 mL: 

19.4 acetonitrile; 24.4 dichloromethane; 55.4 N,N-dimethylformamide; 27.5 acetone; 6.55 ethyl 

acetate; 36.2 tetrahydrofuran; 35.0 butyrolactone; 2.98 methanol; 0.25 isopropyl alcohol;

0.23 toluene; <0.01 1-octanol; <0.005 n-heptane

Vapor pressure at 20/25 °C 20 °C = 4.5 x 10-15 Pa

25 °C = 2.0 x 10-15 Pa

Dissociation constant (pKa) 4.41

Octanol/water partition 

coefficient Mean Log Pow = 2.6 (Pow = 368.3)

UV/visible absorption 

spectrum

wavelength maximum: λmax = 271.6 nm

extinction coefficient: ε = 9709 L/mol-cm

Reference: BASF Registration Document Number (DocID) 2005/1026464.
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Appendix C. Review of Human Research

This risk assessment relies in part on data from studies in which adult human subjects were 

intentionally exposed to a pesticide or other chemical. These data, which include studies from 

the Pesticide Handlers Exposure Database (PHED) 1.1, the Agricultural Handler Exposure Task 

Force (AHETF) database, and the ARTF database are (1) subject to ethics review pursuant to 40 

CFR §26, (2) have received that review, and (3) are compliant with applicable ethics 

requirements. For certain studies, the ethics review may have included review by the Human 

Studies Review Board. Descriptions of data sources, as well as guidance on their use, can be 

found at the Agency website5. 

 

5 http://www.epa.gov/pesticides/science/handler-exposure-data.html and 

http://www.epa.gov/pesticides/science/post-app-exposure-data.html