Sodium Ac iOu orfen Human H ea lth Risk Assess m ent DP No. D426393

UNITED STATES ENVIRONMENTAL PROTECTION AGENCY

WASH I NGTON, D.C. 20460

MEMORANDUM



### Date: Jun e 17

, 20 1 5 OFFICE OF
CHEMICAL SAFETY AND
POLLUTION PREVENTION

SUB JE CT: Sod ium Acifluorfen. Draft Human H eal th Risk Assess m e nt for Registration

Review

PC Code: 114402 OP Barc o dc: 426393

Deci sio n No.: 502693 Re g i st r ation No.: NA

Petition No.: NA Regulator y Act i on: R egis trati on Review Risk

Assessment

Ri sk Assessmen t Type: Single Chem ica l/ Aggregate Case No.: 2605

TXR No.: NA CAS No.: 62476-59

- 9

MRIO No.: NA 40 CFR: §180.383

FROM:

T HRO UGH:

TO: A l exan dra Gavelek, M.S.

, Biologist ' / ..! -'

, ' v-C 

## 4 

# ·<,_ c-Q 

# J

Ronnie J

. Bever Jr.

, PhD

, DABT

, Ifi ,' i fo l og i f-

# ~ 

# !)**r~** 

# fl

William Donovan

, PhD

, Chemist 

# e i'- 1l)\

Ri sk Assessment Branch V / VII

H ea lth Effects Division (7509P)

P e t e r Savoia, C h emis t 

# a_ -a__ · ·**'.I'~ ~**  William Irwin

, T ox i cologist**rJl~"N-iri..<...N** Michael Metzger, Branch Chief

Ri s k Assessment Branch V N II

H ea lth Effects Division (7509P)

Lata Venkateshwara, Chemical Review Manager

P es ti c id e Re-Evaluation Di v i s ion

Page 1 of 48Sod ium Acifluorfen Human Hea l t h Ri sk Assessment DP No. 0426393



### 1

. 0 E xecutive S umm ary

....... . .............. .. . .. ................................................................................ 4

2.0 HED R ecom m en dation s

. . ... ......... .. .. .. .......... ... . ... ................................................. .. ............ 7

2.1 D ata Defici e nci es

...... ........ ....... ........... ...... .. .. ...... ................................... .... .......... .. ........ . 7

2.2 To l era nc e Co n s id e rati o n s

.............................................................................................. 7

2.2.1 E nforcement A nal y tical Method

. .. .......... .. ............... .. ................ .. ............................. 7

2.2.2 Recommended Toleran ces

....... .. .......... . ... ... ................................................. .. .. . .. .. . .... 8

2.2.3 Int e rna t i o n a l H ar moniz a ti o n

...................................... ...... ......... ...... ........ ......... ......... 8

2.3 Label Re comme nd at ion s

................................ . ................................ .. ............................. 8
3.0 Introduction

.. . .. . ....... . ......... . .............. .. . ... . ... . ...... . ..... . ........ .. . ... . .. .. ............. .... .......... ............ 8

3. 1 C h em ic a l Id e nti ty

............................................................................................ .. . ... ........ . 9

3 .2 Physical /C h emica l C h a r acterist ic s

............................................................................. l 0
3.3 P est icide Use Patt e rn

.................................................................................. .. ................ I 

### 0
3.4 Anticipated Exposure Pathways

...... ...... .. .. ...... .. .. ..... ...... ............ ...... .......................... 11


### 3.5 Co n s id e ration of E nvironm e ntal Justice

..................... .... ........................................... 11


### 4.0 Ha za rd C har acte riz at i on a nd Do se -Re s pon se Assessment

.......................................... 12


### 4.1 Toxicology St udi es Available for Analy s i s

...... ............. .. .................................. .......... 12


### 4.2 Abso rption

, Di strib ution

, Metabolism

, & 

### Elimination {ADME)

............................. 13


### 4 .2. 1 Dermal Abso rpti on

..................................................................... ... ............ ..... .......... 13


### 4.3 Toxicolo g ical E ff ects

...................................................... .. ............ .. .............................. 13


### 4.4 Safety Factor for Infants and C hildr e n (FQPA Safety Fac tor)

.. .. ........................... 15


### 4.4.1 Com pl ete n ess of the Toxicology Database

.............................................................. 15



### 4.4.2 Ev iden ce of Ne ur otoxic it y

.......................................................................... ..... ......... 15


### 4.4.3 Ev id e nce of Sen s itivity /S u s ceptibility in the Developing or Youn g A nim a l.

....... 16



### 4.4

. 4 Re s idual U nc er t a inty in the Exposure Databa se

....................................... .. ........ .. 1 6



### 4.5 Toxicity E ndpoint a nd Point of Departure Se l ec tion s

.............................................. 1 6

4.5.1 Do se -Re s pon se Assess m e nt

....... . ............... .. .............. .. ............. . ............................... 16

4

. 5.2 Recommendation for Combining Routes of Exposures for Risk A ssess m e nt..

... 

### 18

4.5.3 Ca n ce r C l ass ific a tion and Risk A ss e ss ment Recommendation

............................ 

### 18

4

. 5.4 S umm ary of Point s of D epart ur e a nd Toxicity E ndpoint s Us ed in Human Ri s k

Assess m e nt

.. ........ ..... . ...... ..... ............. ....... .. .. .. .............. .. ............. ... ............ .. ............. . .............. 18


### 4.6 E ndocrin e Di sr upti o n

.. .. .. .. ..... ... . . .. .. .. ... . .. .... .. .. .. .......... .. .... ............ ........................... .... 20

5.0 Di eta r y Ex p os ur e a nd Risk Assessme n t..

....................................................................... 21


### 5. 1 M e tabolite / De gradate Re s idu e Profile

....................................................................... 21


### 5.1.1 S umma ry of Pl an t a nd A nimal Metabolism St udi es

............................................. 21


### 5

. 1.2 S ummary of Environmental De g r adat ion

... ......... .. ................................................ 22
5.1.3 Re s idues of Concern Summary and Ration a l e

...................................................... 22


### 5.2 Foo d R es idue Profil e

.......... ...... .......... ....................... ... ..... ........ ......... ...... . .. .. . ... ........... 22
5.3 Water Re s idue Profile

.. . .. .. .. .. .. . ... .. .. .......... ....... ...... .. .. .. .. .. ............ ... ............................. 23


### 5.4 Dietary Risk Assess ment..

............................................................... . ............. ... ...... .. .... 24


### 5.4

. 1 Description of Re s idue Dat a Use d in Dietary Assess m e nt

.................................... 24


### 5.4.2 Percent Cro p Treated Used in Dietary Asse ss m e nt

................................ .. ............ 24


### 5.4.3 A cut e Dietary Ri s k Asses s m ent

.. .. .. .. .. ... .......... .. ............ ...... .......... ........ ......... ......... 25
5.4.4 C hroni c Di etary Ri s k A ssess m e nt

........................................................................... 25

5.4

. 5 Ca n ce r Di e tary Ri s k Assess ment

.............. .. .............. .. ............................................. 25
5.4.6 S umma ry Table

......... .. .. .. .. . .... . . ... .. .. .. .. .. .... ... ............... . . ... ........ .. . ... ............ .. .... . .. .. .... 25

6. 0 R es idential (Non -Occupation a l ) Expos ure / Ri s k C haracteri zat ion

............................. 26

Page 2of48

### Sodium Acifluorfen Human Health Risk Assessment DP No. D 426393

Page 3 of 48 6.1 Residential Bystander Post

- application Inhalation Exposure

................................ . 26
6.2 Spray Drift

................................ ................................ ................................ .................... 26
7.0 Aggregate Exposure/Risk Characterization

................................ ................................ .. 28
7.1 Acute Aggregate Risk

................................ ................................ ................................ ... 28
7.2 Short

- Term Aggregate Risk

................................ ................................ ........................ 29
7.3 Intermediate

- Term Aggregate Risk

................................ ................................ ........... 29
7.4 Chronic Aggregate Risk

................................ ................................ .............................. 29
7.5 Cancer Aggregate Risk

................................ ................................ ................................ 29
8.0 Cumulative Exposure/Risk Characterization

................................ ............................... 29
9.0 Occupational Exposure/Risk Characterization

................................ ............................ 30
9.1 Short

- /Intermediate

- Term Handler Risk

................................ ................................ ... 30
9.2 Short

- /Intermediate

- Term Post

- Application Risk

................................ .................... 33
9.2.1 Dermal Post

- application Risk

................................ ................................ .................. 33
9.2.2 Inhalation Post

- application Risk

................................ ................................ ............. 34
10.0 Human Incidents/Epidemiology

................................ ................................ ..................... 35
11.0 References

................................ ................................ ................................ ......................... 35 Appendix A. Toxicology Profile and Executive Summaries

................................ .................. 37
A.1 Toxicology Data Requirements

................................ ................................ ................... 37
A.2 Toxicity Profiles

................................ ................................ ................................ ............ 37 Appendix B. Physical/Chemical Properties

................................ ................................ ............. 46 Appendix C. Review of Human Research

................................ ................................ ................ 47 Appendix D. International Tolerances and Maximum Residue Limits Sheet

..................... 48

### Sodium Acifluorfen Human Health Risk Assessment DP No. D 426393

Page 4 of 48 1.0 Executive Summary

HED has conducted a human health risk assessment to support registrations review for the active ingredient, sodium acifluorfen

. Sodium acifluorfen is a diphenyl ether used as a contact herbicide for selective pre

- and post

- emergence control of annual broa d

- leaf weeds and some

grasses

. The registered sodium acifluorfen products are liquid concentrates which are applied using ground or aerial equipment. The currently labeled uses include rice, peanuts, strawberries and soybeans. All residential products are cancelled or suspended. There are currently no registered residential uses.

The database of toxicology studies for sodium acifluorfen is complete and considered adequate
for risk assessment. Waivers were recommended by HASPOC for the subchronic inha lation and
subchronic neurotoxicity studies and the developmental neurotoxicity study (Craig, 2015, TXR# 0051465).

Sodium acifluorfen results in hematological effects (such as decreases in erythrocyte count, hematocrit, and/or mean cell volume), which wer e noted in dogs, rats, and mice. Additionally, the liver (dog, rat, and mouse) and kidney (rat and mouse) are also target organs of oral exposure, and effects in these organs were noted following both subchronic and chronic exposures. There was no progres sion of effects from subchronic to chronic dosing durations in the rat and mouse (no dog subchronic study).

There was quantitative fetal susceptibility demonstrated in the Sprague

- Dawley rat developmental study, but no susceptibility in the Wistar rat or rabbit developmental studies, nor in the reproduction study. In the Sprague

- Dawley rat developmental study, decreased body weights and increased incidences of clinical signs were observed in the maternal animal at the highest dose tested, whereas the fet al effects were observed at a lower dose and included decreased fetal body weight and increased incidence of slightly dilated lateral ventricles of the
brain. No adverse effects were noted in the Wistar rat dam or fetus nor in the rabbit dam or fetus.

In t he reproduction study in rats, parental toxicity (dilatation and necrosis of tubules in the outer medulla of kidneys in females) was noted at a lower dose than offspring toxicity (decreased body weights and increased renal pelvis dilatation). No effects on reproductive parameters were
observed.

The weight of evidence suggests that acifluorfen is not neurotoxic; effects appearing to be related to neurotoxicity are most likely due to systemic toxicity. No immunotoxicity was observed. In the dermal toxicity test, skin irritation was observed at all doses, and systemic toxicity was noted at the limit dose. An inhalation toxicity study was not submitted nor required. Sodium acifluorfen has low acute toxicity by the oral and dermal exposure routes

. However, it is a severe eye irritant and moderate dermal irritant. It is not considered a skin sensitizer.

Based on the toxicity, duration s of exposure, and uses of sodium acifluorfen , the following toxicity endpoints were selected:

### Sodium Acifluorfen Human Health Risk Assessment DP No. D 426393

Page 5 of 48 Acute dietary ( General Population, including Infants and Children ): acute PAD (a PAD) = 2.9 mg/kg/day derived from a NOAEL of 2 93 mg/kg in a n acute neurotoxicity study. LOAEL = 440 mg/kg based on de creased motor activity in female rats

. Acute dietary ( Females 13

- 49 years of age ) : acute PAD (a PAD) = 0.20 mg/kg/day
derived from a NOAEL of 20 mg/kg in a rat developmental s tudy. LOAEL = 90 mg/kg
based on increased incidence of slightly dilated lateral ventricles of the brain

. Chronic dietary (all populations) : chronic PAD (cPAD) = 0.0 13 mg/kg/day derived
from a NOAEL of 1.25 mg/kg/day in a rat reproduction study. LOAEL = 25 mg/kg/day
based on dilatation of tubules in the outer medulla of kidneys were noted in both generations in parental females

. In cidental oral exposures (short

- ter m): NOAEL = 25 mg/kg/day in a rat reproduction study . LOAEL = 125 mg/kg/day based on decreased pup body weights and renal pelvic
dilatation

. Dermal (short

- and intermediate

- term): NOAEL = 25 mg/kg/day in a rat reproduction study . LOAEL = 125 mg/kg/day ba sed on decreased pup body weights and renal pelvic
dilatation

. Dermal absorption factor = 18%. Inhalation (short

- and intermediate

- term): NOAEL = 1.25 mg/kg/day in a in a rat reproduction study. LOAEL = 25 mg/kg/day based on dilatation of tubules in the o uter medulla of kidneys were noted in both generations in parental females.

Sodium acifluorfen is a peroxisome proliferator and may induce liver tumors in mice. It is likely to be carcinogenic to humans at high enough doses to cause the biochemical and histopathological changes in livers of rodents associated with peroxisome proliferation , but unlikely to be carcinogenic at doses below those causing these changes

. EPA determined that

n on

- linear extrapolation be used for assessment ; t herefore, no separate Q 1 

### * based cancer aggregate assessment is required. The use of the non

- linear RfD approach will be protective of chronic effects including carcinogenicity.

For the occupational and residential risk assessments

, the level of concern (LOC) is for MOEs
less than 100 (10X intra

- species uncertainty factor and 10X interspecies uncertainty factor) . The FQPA safety factor has been reduced to 1X since the database is complete, points of departure are protective for all life stages, there is no clear evidence of ne urotoxicity, and exposure estimates are not likely to underestimate risk.

The residue chemistry database is complete with the exception of the need for analytical standard
submissions. The residues of concern for the tolerance expression and dietary risk assessment are acifluorfen acid, acifluorfen methyl ester, acifluorfen amine, and acifluorfen amine methyl

ester. There are adequate analytical methods available for tolerance enforcement. Tolerances

are based on crop field trial studies that showed res idue levels below the limit of quantitation (LOQ) in all raw agricultural commodities except rice straw, where residues slightly above the LOQ were found. These trials were supported by adequate storage stability studies. Processing
studies demonstrate t hat residues do not concentrate in processed commodities. Rotational crop studies form the basis for the recommended plant back intervals (PBIs) specified on the sodium
acifluorfen labels. There are no tolerances for livestock commodities as there is no e xpectation of finite residues in livestock tissue [40 CFR § 180.6(a)(3)].

### Sodium Acifluorfen Human Health Risk Assessment DP No. D 426393

Page 6 of 48 A risk assessment was conducted for dietary exposure which included all food commodities for the registered uses and estimated drinking water concentrations (EDWCs)

. Acute and chronic dietary analyses were performed using conservative assumptions ( i.e ., 100% crop treated,
tolerance

- level residues, and default processing factors). The resulting acute exposure estimates were less than HED’s level of concern (≤100% acute PAD) for all populations. The acute risk
estimate was < 1% of the aPAD for general U.S. population) and all population subgroups except females 13

- 49 years old

. A separate point of departure (PoD) was selected for females 13

- 49 years old and the estimated risk was 4.0% aPAD for this population subgroup. The chronic exposure estimates were also less than HED’s level of concern (≤100% chronic PAD) for general U.S. population (24% cPAD) and all population sub

- groups. The most highly exposed population subgroup was al l infants, at 62% cPAD. Water is the primary contributor to aggregate (food + water) dietary exposure to sodium acifluorfen, for both acute and chronic exposure scenarios.

Since there are no uses of sodium acifluorfen existing that would result in residential (non

occupational) exposure to the pesticide, short

- and intermediate

- term aggregate risk assessment are not required.

The acute and chronic aggregate risk assessment s include only food and drinking water

expos ure, and are equivalent to the acute and chronic dietary (food and water) risk assessments, respectively. The acute and chronic dietary risk estimates are not of concern for the general population and all population subgroups.

A spray drift assessment w as completed for sodium acifluorfen. The spray drift risk estimates are based on an estimated deposited residue concentration as a result of the screening level agricultural application scenarios. Children’s (1 to < 2 year old) dermal and incidental oral risk estimates from indirect exposure to sodium acifluorfen , related to spray drift, result in no buffers for groundboom or aerial applications. Risk estimates from groundboom and aerial applications are not of concern at the field edge.

Sodium aciflu orfen is a member of the diphenyl ether group of herbicides, which includes lactofen and oxyfluorfen. In addition, acifluorfen is a degradate of lactofen. EPA has some evidence that these compounds induce similar toxic effects but has not yet determined whether or not these compounds exhibit a common mechanism.

HED conducted occupational handler and post

- application exposure and risk assessments for all registered uses. Short

- and intermediate

- term MOEs for handlers (mixers/loaders and applicators) we re not of concern to HED as they exceeded the target MOE of 100 with the label

required PPE . The occupational post

- application exposure and risk estimates indicate that short

and intermediate

- term MOEs are not of concern to HED, also significantly exceed ing the target
MOE of 100.

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. 1 

### ”

1 http://www.hss.energy.gov/nuclearsafety/env/guidance/justice/eo12898.pdf

.

### Sodium Acifluorfen Human Health Risk Assessment DP No. D 426393

Page 7 of 48 This risk assessment relies in part on data from studies in which adult human subjects were intentionally exposed to a pesticide to determine their exposure. Appendix C provides additional information on the review of human research used to complete the risk assessment. There is no regulatory barrier to continued reliance on these studies, and all applicable requirements of EPA’s Rule for the Protection of Human Subjects of Research (40 CFR Part 26) have been
satisfied.

2.0 HED Recommendations

HED has examined the toxicology residue chemistry and exposure databases for sodium acifluorfen

. Pendin g resolution of the deficiency identified below, there are no other residue chemistry,
resident ial, occupational, or toxicology data deficiencies that would preclude the continuation of the

current registered uses of sodium acifluorfen and its metabolites as listed in Table 2.2.2

.

2.1 Data Deficiencies

860.1650 Submittal o f Analytical Reference Standards

Analytical standards for sodium acifluorfen are currently not available at the EPA National Pesticide Standards Repository (personal co mmunication with Theresa Cole, 6/3/15 ). The Repository has requested that the registrant provide analytical standards for sodium acifluorfen
and acifluorfen amine . They should be sent to the Analytical Chemistry Lab, which is located at Fort Meade, to the attention of either Theresa Cole or Thuy Ng uy en at the following address:

USEPA National Pesticide Standards Repository/Analytical Chemistry Branch/OPP 701 Mapes Road Fort George G. Meade, MD 20755

- 5350

(Note that the mail will be returned if the extended zip code is not used.)

2.2 Toleranc e Considerations

2.2.1 Enforcement Analytical Method

Adequate methods are available for enforcement of tol erances of acifluorfen in plant commodities. The Pesticide Analytical Manual (PAM) Volume II lists a gas chromatography/electron capture detector (GC/ECD) method, designated as Method I, for the enforcement of tolerances in plant commodities. Briefly, residues of sodium acifluorfen and acifluorfen amine are extracted with acetonitrile (ACN):1.0 N HCl (7:3, v:v). The extract is partitioned into tolue ne and evaporated to dryness, then dissolved in methanol, washed with heptane (oily crops only), and concentrated to dryness. The dried residue is dissolved in ethyl ether and subjected to methylation with diazomethane to convert acifluorfen and acifluorfe n amine to the corresponding methyl esters, followed by derivatization with heptafluorobutyramide (HFBA) to convert the methyl ester of acifluorfen amine to the HFBA derivative. The resulting

### Sodium Acifluorfen Human Health Risk Assessment DP No. D 426393

Page 8 of 48 residues are purified on a Florisil column prior to GLC analysis . Method I determines residues of sodium acifluorfen, acifluorfen, acifluorfen amine, and any other compounds that can be converted to acifluorfen methyl ester or the HFBA derivative. Identifications are confirmed by GLC/MS (Method A in PAM II). The stated detection limit of Method I is 0.01

- 0.02 ppm.

2.2. 2 Recommended Tolerances

The residue definition needs modification to be consistent with recent guidance on tolerance expressions (S. Knizner, 5/27/09). The appropriate language is described below.

(a) General. Tolerances are e stablished for residues of the herb icide sodium acifluorfen (s odium
5

- [2

- chloro

- 4

- (trifluoromethyl)phenoxy]

- 2

- nitrobenzoate ) , including its metabolites and degradates, in or on the commodities in the table below. Compliance with the tolerance levels specified below is to be determined by measuring only the sum of acifluorfen acid ( 5

- [2

- chloro

4

- (trifluoromethyl)phenoxy]

- 2

- nitrobenzoic acid ) , acifluorfen methyl ester (m ethyl 5

- [2

- chloro

- 4

- (trifluoromethyl)phenoxy]

- 2

- nitrobenzoate ), acifluorfen amine, ( 5

- [2

- chloro

- 4

- (trifluoromethyl)phenoxy]

- 2

- aminobenzoic acid ), and acifluorfen amine methyl ester(m ethyl 5

- [2

- chloro

- 4

- (trifluoromethyl)phenoxy]

- 2

- aminobenzoate ), calculated as the stoichiometric equivalent of acifluorfen acid , in or on the commodit ies

.

Table 2.2. 2

. Tolerance Summary for Sodium Acifluorfen.

Commodity Established Tolerance (ppm) Recommended

Tolerance (ppm) Comments

Correct Commodity Definition

Peanut 0.1 0.10 Rice, grain 0.1 0.10 Rice, straw 0.2 0.20 Soybean, seed 0.1 0.10 Strawberry 0.05 0.05



### Tolerance levels for sodium acifluorfen should be expressed using the number of significant figures recommended in Table 2.2. 2

.

2.2. 3 International Harmonization

No Codex Maximum Residue Limits (MRLs) have been established for sodium acifluorfen. One
Canadian MRL for the registered early season use of sodium acifluorfen on soybeans has been established at 0.02 ppm (see Appendix D)

. Although the U.S. and Canada ar e harmonized with respect to residue definition for sodium acifluorfen, t he established U.S. tolerance is 0.1 ppm. Harmonization at 0.02 ppm is not possible given the 0.1 ppm limit of quantitation (LOQ) of the analytical method used to analyze the soybean field trial samples.

2.3 Label Recommendations

None.

3.0 In troduction

### Sodium Acifluorfen Human Health Risk Assessment DP No. D 426393

Page 9 of 48 3.1 Chemical Identity

Table 3. 1. Chemical Identity

Common Name Sodium Acifluorfen

IUPAC name Sodium 5

- (2

- chloro

- α,α,α

- trifluoro

- p

- tolyloxy)

- 2

- nitrobenzoate

CAS name S odium 5

- [2

- chloro

- 4

- (trifluoromethyl)phenoxy]

- 2

- nitrobenzoate

PC Code 114402
CAS registry number 62476

- 59

- 9

Case No. 2605

Chemical Structure

Chemical Identity for Acifluorfen Metabolites

Common Name Acifluorfen; Acifluorfen Acid

IUPAC name 5

- (2

- chloro

- α,α,α

- trifluoro

- p

- tolyloxy)

- 2

- nitrobenzoic acid

CAS name 5

- [2

- chloro

- 4

- (trifluoromethyl)phenoxy]

- 2

- nitrobenzoic acid

PC Code 114401
CAS registry number 50594

- 66

- 6

Chemical Structure

Common Name Acifluorfen amine

CAS name 5

- [2

- chloro

- 4

- (trifluoromethyl)phenoxy]

- 2

- aminobenzoic acid

Chemical Structure

Common Name Acifluorfen methyl ester

CAS name M ethyl 5

- [2

- chloro

- 4

- (trifluoromethyl)phenoxy]

- 2

- nitrobenzoate

Chemical Structure

### Sodium Acifluorfen Human Health Risk Assessment DP No. D 426393

Page 10 of 48 Table 3. 1. Chemical Identity

Common Name Acifluorfen amine methyl ester

CAS name Methyl 5

- [2

- chloro

- 4

- (trifluoromethyl)phenoxy]

- 2

- aminobenzoate

Chemical Structure



### 3.2 Physical/Chemical Characteristics

Sodium acifluorfen rapidly dissociates to the acifluorfen anion and is expected to be completely dissociated during tank mixture and prior to application. The acifluorfen anion is persistent in soil (aerobic soil metabolism half

- life 170 days) and in aerobic aquatic environments (estimated
aerobic half

- life 117 days); it is less persistent in anaerobic conditions (aquatic half

- life estimated to be 2.75 days). Volatilization does not appear to be a significant dissipation pathway for acifluorfen (vapor pressure is <1.33 x 10

- 5 

### Pa; Henry's Law constant is 7.65 x 10

- 10 

### atm

m 3 

### /m ol). Acifluorfen is not expected to bioaccumulate because of its low K ow



### .

Refer to Appendix B for the physi cal/ chemical properties of sodium acifluorfen.

3.3 Pesticide Use Pattern

Refer to Table 3.3 for a summary of use directions for sodium acifluorfen.

Table 3

. 3 . Summary of Directions for Use of Sodium Acifluorfen.

Applic. Timing, Type, and Equip. Formulation

[EPA Reg. No.] Applic.

Rate (lb ai/A) Max. No.

Applic. per
Season Max.

Seasonal Applic. Rate (lb ai/A) PHI

(days) Use Directions and

Limitations

Peanut

Preemergence, at cracking,
or postemergence Broadcast or
banded foliar
Ground/Aerial 2 lb/gal SC

[7969

- 76] [83520

- 24] [82534

- 2] [70506

- 60] 0.375 2 (at 0.25 lb/A) 0.50 75 A minimum retreatment interval of 15 days is specified. PBIs for rotational crops: immediate for registered crops, 40 days for small grains and 100 days for other crops.

Rice

Late tillering to early boot
Broadcast
Ground/Aerial 2 lb/gal SC

[7969

- 76] [83520

- 24] [82534

- 2] [70506

- 60] 0.25 1 0.25 50 A minimum retreatment interval of 15 days is specified. PBIs for rotational crops: immediate for registered crops, 40 days for

### Sodium Acifluorfen Human Health Risk Assessment DP No. D 426393

Page 11 of 48 Table 3

. 3 . Summary of Directions for Use of Sodium Acifluorfen.

Applic. Timing, Type, and Equip. Formulation

[EPA Reg. No.] Applic.

Rate (lb ai/A) Max. No.

Applic. per
Season Max.

Seasonal Applic. Rate (lb ai/A) PHI

(days) Use Directions and

Limitations

small grains and 100 days for other crops. Soybean

Postemergence
Broadcast or
banded foliar
Ground/Aerial 2 lb/gal SC

[7969

- 76] [83520

- 24] [82534

- 2] [70506

- 60] 0.375 2 (at 0.25 lb/A) 0.50 50 A minimum retreatment interval of 15 days is specified. For banded applications, a minimum
bandwidth of 15 inches and a
minimum of 15 gal/A are specified. PBIs for rotational crops: immediate for registered crops, 40 days for small grains and 100 days for other crops. Strawberry

Postemergence
Broadcast or
banded foliar
Ground/Aerial 2 lb/gal SC

[83520

- 24] [82534

- 2] [70506

- 60] 0.375 2 0.75 60 A minimum retreatment interval of 15 days is specified. PBIs for rotational crops: immediate for registered crops, 40 days for small grains and 100 days for other crops.



### 3.4 Anticipated Exposure Pathways

Humans may be exposed to sodium acifluorfen in food and drinking water, since sodium acifluorfen may be applied directly to growing crops and application may result in sodium acifluorfen reaching surface and ground water sources of drinking water. There a re no residential uses of sodium acifluorfen, so there is not likely to be exposure in residential or non

occupational settings. There is potential for spray drift exposure following agricultural applications of sodium acifluorfen. In an occupational set ting, applicators may be exposed while handling the pesticide prior to application, as well as during application. There is a potential for
post

- application exposure for workers re

- entering treated fields. This risk assessment considers
all of the aforem entioned exposure pathways based on the existing uses of sodium acifluorfen.

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://www.eh.doe.gov/oepa/guidance/ justice/eo12898.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 USDA under the National

### Sodium Acifluorfen Human Health Risk Assessment DP No. D 426393

Page 12 of 48 H ealth and Nutrition Examination Survey, What We Eat in America, (NHANES/WWEIA) 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, e thnic 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 ba sed on home use of pesticide products and associated risks for adult applicators and for toddlers, youths, and adults entering or playing on treated areas post

- application are evaluated. Further considerations are currently in development as OPP has commi tted 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

- R esponse Assessment

4.1 Toxicology Studies Available for Analysis

The toxicology database for sodium acifluorfen provides a robust characterization of the hazard potential of this pesticide. The toxicology studies for sodium acifluorfen are summarized in Appendix A.1. There are studies available for toxicity endpoint selection , which include:

S ubchronic oral toxicity studies in rats and mice
C hronic oral toxicity studies in rats and dogs
C arcinogenicity studies in rats and mice

M utagenicity battery

D evelopmental studies in rats and rabbits

R eproduction stud y in rats Acute neurotoxicity study in rats Dermal toxicity study in rabbits Metabolism study in rats Immunotoxicity studies in rat s

A waiver was recommended by Hazard and Science Policy Council (HASPOC) for the inhalation toxicity study and subchronic and developmental neurotoxicity studies (Craig, 2015, TXR# 0051465). The last risk assessment was performed in 2002 (Farwell, 2002, D279497). Since the scoping document (Goodlow, 2010, D 370342 ), a developmental study in rats, an immunotoxicity study in female mice, and an acute neurotoxicity study were submitted. The studies available for consideration of sodium acifluorfen toxicity pr ovide a comprehensive database, with routes of administration that are consistent with potential exposure scenarios.

To support Registration Review , a search of the open literature was conducted for toxicity studies involving sodium acifluorfen using a d atabase of the National Library of Medicine’s TOXNET System and the Google scholar search. No additional studies relevant to HED’s
human health risk assessments were found.

### Sodium Acifluorfen Human Health Risk Assessment DP No. D 426393

Page 13 of 48 4.2 Absorption, Distribution, Metabolism, & Elimination (ADME)

The ADME was evaluated in male and female Fischer 344 rats following three oral dosages (single low at 1 6

- 17 mg/kg, single high at 116 mg/kg, and multiple low at 10

- 12 mg/kg daily for 14 days) and an intravenous dosage (11

- 15 mg/kg). Sodium acifluorfen is rapidly ( peak blood concentration [ t max 

### ] = 0.5

- 5.4 h) and almost completely absorbed (bioavailability ~ 80

- 97%) into the systemic circulation. The terminal excretion half

- life (t 1/2 β 

### ) = 3.7

- 8.9 h

. Very little radioactivity was detectable in tissues of rats 96 hours af ter administration of each of four dosage regimens. Excluding the gastrointestinal system, the highest percentage of residues were isolated in the liver and kidneys of males and livers of females at 96 hours. The rad ioactivity recovered in
urine and feces in female animals, 96 hours after a dministration, was 60

- 82% and 5

- 23% of the dose, respectively. In contrast, the radioactivity recovered in urin e and feces in male rats was
46

- 58% and 21

- 41% of the dose, respectively. The major radioactive component pre sent in blood (95

- 98%), urine (95%), and bile (93%) was unchanged acifluorfen. The major component in
feces was the amine metabolite

, which accounted for 60

- 80% of the radioactivity.

4.2.1 Dermal Absorption

No acceptable dermal absorption studies are ava ilable for acifluorfen. However, a dermal absorption study conducted in rats for structurally

- related oxyfluorfen (shown below) is available, and reported a dermal absorption factor (DAF) of 18%.

Oxyfluorfen Sodium Acifluorfen

Based on chemical structure, and physical properties, sodium acifluorfen is expected to have a lower potential for dermal penetration as it is in its more polar, ionized form, and has a lower log Kow (1.55 and 4.75 for sodium a cifluorfen and oxyfluorfen, respectively). Additionally, in vitro modeling was conducted on both sodium acifluorfen and the un

- ionized acifluorfen molecule using the CDC/NIOSH Finite Dose Skin Permeation Calculator 2 

### . Based on the available physical/chemica l properties, the dermal absorption following a 10

- hour exposure to either molecule did not exceed 18%, with the ionized molecule having a dermal absorption of < 5%.

Therefore, the DAF factor of 18% from structurally

- related oxyfluorfen is considered a conservative estimate and acceptable for use in risk assessment.

4.3 Toxicological Effects

The herbicidal mode of action for sodium acifluorfen is the inhibition of p rotoporphyrinogen IX oxidase (protox ), leading to an accumulation of protoporphyrinogen IX. This inhibition leads to cell membrane disruption through reactive oxygen species in the presence of light. Blockage of the porphyrin pathway at this site inhibits synthesis of both chlorophylls and heme

. Heme is a

2 http://www.cdc.gov/niosh/topics/skin/finiteskinpermcalc.html

### Sodium Acifluorfen Human Health Risk Assessment DP No. D 426393

Page 14 of 48 feedback regulator of the porphyrin pathway. Hematological effects (such as decreases in erythrocyte count, hematocrit, and/or mean cell volume) were noted in dog, rat, and mice.

T he liver (dog, rat, and mouse) and kidney (rat and mouse) are also target organs of oral exposure, and effects in these organs were noted following both subchronic and chronic exposures. Indications of liver toxicity included findings such as increased liver weight, hypertro phy, clinical chemistry findings, urinary urobilinogen, focal necrosis; proliferation of oval or bile duct cells, and fatty infiltration. Indications of kidney toxicity include increases in the following parameters: kidney weight; serum electrolytes, BUN, and creatinine; and urinary
nitrate.

There was no progression of effects in the rat and mouse from subchronic to chronic dosing durations (no dog subchronic study). This observation may be in part attributed to short half

- life of this chemical (t 1/2 β 

### = 3 .7

- 8.9 h), and because the t max 

### is reached quickly, within 0.5

- 5.4 h.

There was quantitative fetal susceptibility demonstrated in the Sprague

- Dawley rat developmental study, but no susceptibility in the Wistar rat or rabbit developmental studies, nor
in t he reproduction study. In the Sprague

- Dawley rat developmental study, decreased body weights and increased incidences of clinical signs were observed in the maternal animal at the highest dose tested, whereas the fetal effects were observed at a lower dos e and included decreased fetal body weight and increased incidence of slightly dilated lateral ventricles of the
brain. In the developmental studies, n o adverse effects were noted in the Wistar rat dam or fetus nor in the rabbit dam or fetus. In the reprod uction study in rats, parental toxicity (dilatation and necrosis of tubules in the outer medulla of kidneys in females) was noted at a lower dose than offspring toxicity (decreased body weights and increased renal pelvis dilatation). No effects on reproduc tive parameters were observed.

Acifluorfen was negative in several genetic toxicology studies but was weakly mutagenic in a bacterial reverse mutation assay with metabolic activation and was weakly recombinogenic in Saccharomyces cerevisiae without metabo lic activation. The Mechanism of Toxicity Assessment Review Committee concluded that the currently available data are considered to be sufficient to support peroxisome proliferation as one of the key events in the mode of action of
acifluorfen

- induced liv er tumors in mice according to the criteria recommended by International Life Sciences Institute (Kidwell, 2003, TXR No. 0052014 

### ). Sodium acifluorfen is likely to be carcinogenic to humans at high enough doses to cause the biochemical and histopathological changes in livers of rodents, but unlikely to be carcinogenic at doses below those causing these changes.

Evidence possibly related to neurotoxicity was noted in the 180 mg/kg/day dams in a rat developmental study based on increased incidence of clinic al signs (25 rats observed/dose with a total of 375 animal days; incidence reported as # rats affected/total animal days): excessive salivation (19/39), urine

- stained fur (14/30), and decreased motor activity (4/4). Increased incidences of slightly
dilated lateral ventricles of the brain were noted in the fetuses at 90 mg/kg/day (litters: 42.1% treated vs 9.5% controls; fetuses: 13.9% treated vs 2.4% controls). A similar incidence was noted at 180 mg/kg/day (litters: 31.6%; fetuses: 14.7%). In the acute n eurotoxicity study in females during the
0

- 10 minute interval of Days 0 (treated) and 1

, ambulatory and total (fine + ambulatory) motor

### Sodium Acifluorfen Human Health Risk Assessment DP No. D 426393

Page 15 of 48 activities were decreased (p≤0.05) by 27

- 44 % at 440 and 660 mg/kg. No other evidence in the
database indicated neurotoxicity . Weight of evidence indicates that acifluorfen is unlikely to be
neurotoxic. This conclusion is based on the following: 1) indications of treatment

- related toxicity
in the ACN are well

- characterized, and effects on motor activity could be an indication of systemic toxicity from the bolus dose; 2) the slight effect observed in fetuses in a developmental toxicity study with Sprague

- Dawley rats (dilated brain ventricles) were not reproduced in another developmental toxicity study with Wistar rats nor in developmental toxicity studies with rabbits; 3) decreased motor activity was observed at relatively high doses and may be a result of a systemic effect rather than a neurotoxic effect; and 4) there was no indication of treatment

related neurotoxici ty observed in any studies for structurally

- related chemicals ( fomesafen, lactofen, and oxyfluorfen) , except for decreased motor activity in an acute neurotoxicity study with fomesafen at the same dose where general systemic toxicity (body weight loss) was
observed.

No immunotoxicity was observed. In the dermal toxicity test, skin irritation was observed at all doses, and systemic toxicity was noted at the limit dose. An inhalation toxicity study was not submitted, and the HASPOC recommended that this s tudy be waived.

Sodium acifluorfen has low acute toxicity by the oral and dermal exposure routes (toxicity category III, LD 50 

### ≥ 1370 mg/kg). However, it is a severe eye irritant (toxicity category I) and moderate dermal irritant (toxicity category II). It is not considered a skin sensitizer.

4.4 Safety F actor for Infants and Children (FQPA Safety Factor)

HED recommends that the 10x FQPA Safety Factor (for the protection of infants and children)
be reduced to 1x for reasons detailed in the subsection s below . The toxicological database for
sodium acifluorfen is complete with regard to pre

- and postnatal toxicity, neurotoxicity, and immunotoxicity ; there are no residual uncertainties. Additionally, the dietary exposure
assessment is based on conservat ive, health

- protective assumptions that ensure that exposures to
sodium acifluorfen are not underestimated.

4.4 .1 Completeness o f the Toxicology Database

The toxicology database is complete, and the toxicology studies are adequate for assessing increased susceptibility under FQPA (see Appendix A.1). D evelopmental toxicity studies in rats
and rabbits and a reproductive toxicity stud y in rats are available. An acute neurotoxicity study in rats and immunotoxicity study in rats are available. Waive rs were recommended by HASPOC for the subchronic inhalation and neurotoxicity studies and the developmental neurotoxicity study (Craig, 2015, TXR# 0051465).

4.4.2 Evidence of N eurotoxicity

Weight of evidence indicates that sodium acifluorfen is unlikely to be neurotoxic. This conclusion is based on the following: 1) indications of treatment

- related toxicity in the ACN are well

characterized , and effects on motor activity could be an indication of systemic toxicity from the
bolus dose ; 2) the slight effect observed in fetuses in a developmental toxicity study with

### Sodium Acifluorfen Human Health Risk Assessment DP No. D 426393

Page 16 of 48 Sprague

- Dawley rats (dilated brain ventricles) were not reproduced in another developmental toxicity study with Wistar rats nor in developmental toxicity studies with rabbits; 3) decreased

motor a ctivity was observed at relatively high doses and may be a result of a systemic effect rather than a neurotoxic effect; and 4 ) there was no indication of treatment

- related neurotoxicity observed in any studies for structurally

- related chemicals ( fomesafen

, lactofen, and oxyfluorfen )

, except for decreased motor activity in an acute neurotoxicity study with fomesafen at the same dose where general systemic toxicity (body weight loss) was observed

.

4.4.3 Evidence o f Sensitivity/Su sceptibility in the Developing o r Young Animal

There is evidence of increased susceptibility following in utero exposure to sodium acifluorfen
in the Sprague Dawley rat developmental toxicity study. However, there is low concern because
effects are well

- characterized with c lear NOAEL/LOAEL values and the chosen points of departure for risk assessment for each exposure scenario are protective for these effects

.

4.4.4 Residual Uncertainty in the Exposure Datab ase

There are no residual uncertainties in the exposure database. The dietary exposure estimates
assumed 100% of percent of crop treated

, tolerance

- level residue in food and upper

- bound drinking water estimates based on modeling

, which are considered conservative assumptions ( see Section 5.4.1 ) . HED is confident that the dietary risk is not underestimated. Additionally, since
the non

- dietary exposure and risk estimates are based on several conservative assumptions, HED is confident that the exposure estimates are not underestimated . The assum ptions are detailed in
Section s 6.0 and 9.0

.

4.5 Toxicity Endpoint and Point of D eparture Selections

4.5.1 Dose

- Response Assessment

Since the last risk assessment, an acute neurotoxicity study has been received which allows the
determination of the acut e dietary point of departure for the general population. Furthermore,
short

- and intermediate

- term oral endpoints must now be considered due to the possibility of spray drift

. T he detailed description of the toxicity studies used for selecting toxicity end points and points of departure for various exposure scenarios are presented in A ppendix A.4.

Acute Dietary Endpoint (General Population, including Infants and Children): The acute dietary endpoint for the general population was from an acute neurotoxicity study in rats. Decreased motor activity was observed in female rats at a LOAEL of 440 mg/kg. The acute Population Adjusted Dose (aPAD) of 2.9 mg/kg/day is based on a NOAEL of 293 mg/kg with a
100

- fold uncertainty factor (10X inter species and 10X intraspecies ) applied and an FQPA SF of
1.

Acute Dietary Endpoint (Females 13

- 49 years of age): The acute dietary endpoint for women of
child

- bear ing age was from a rat developmental study. The developmental LOAEL was 90 mg/kg/day based on increased incidence of slightly dilated lateral ventricles of the brain . These anatomical variations are considered to be possibly due to a single exposure; ther efore, this

### Sodium Acifluorfen Human Health Risk Assessment DP No. D 426393

Page 17 of 48 finding is suitable for an acute endpoint. The aPAD of 0.20 mg/kg is based on a NOAEL of 20 mg/kg/day with a 100

- fold uncertainty factor (10X interspecies and 10X intraspecies) applied and an FQPA SF of 1.

Chronic Dieta ry Endpoint: The chronic dietary endpoint was from a dilatation of tubules in the outer medulla of kidneys were noted in both generations in parental females. This study is appropriate for the duration of concern and protective of ef fects seen in all species following long

- term exposure . The chronic PAD (cPAD) of 0.013 mg/kg/day is based on a NOAEL of 1.25 mg/kg/day with a 100

- fold uncertainty factor (10X interspecies and 10X intra species ) ap plied and an FQPA SF of 1.

Short

- Term Inc idental Oral Endpoints (residential due to spray drift): The endpoint selected for
short

- term incidental oral exposure scenarios was from a reproduction toxicity study in Sprague

Dawley rat. The offspring NOAEL was 25 mg/kg/day. The LOAEL was 125 mg/kg/ day based
on decreased pup body weights and renal pelvic dilatation. As it is unknown exactly how long treatment must continue to result in the nephrotoxicity observed in the reproduction study, it was assumed that the toxicity may result from short

- term e xposure in order to be protective of this possibility. The study is protective of effects seen in all species following sub

- chronic exposure. The standard 100X UF was applied to account for interspecies extrapolation and intra

- species
variation. A margin of exposure (MOE) of 100 is considered adequate for the level of concern. The FQPA SF is 1 for residential exposures. This study is appropriate for the sentinel population of ages 1

- 2, which is subject to the greatest exposure due to hand

- to

- mouth feeding.

Short

- Term Dermal Endpoints (residential due to spray drift): The endpoint selected for short

term dermal exposure scenarios was from a reproduction toxicity study in rat. The offspring NOAEL was 25 mg/kg/day. The LOAEL was 125 mg/kg/day bas ed on decreased pup body weights and renal pelvic dilatation. The dermal toxicity study in rabbits was considered; however, quantitative susceptibility was observed in the rat developmental study. The dermal toxicity study did not evaluate findings in the fetus or offspring. The developmental NOAEL in the rat study (20 mg/kg/day) is similar to the offspring point of departure, and effects were seen as similar doses (90

- 125 mg/kg/day); therefore, the selected endpoint is also protective of the developmental effects seen in rats. Using the reproduction study allows a common endpoint with incidental oral exposure and inhalation exposures (nephrotoxicity). A common endpoint allows aggregate assessment to be performed, resulting in a more protective risk assessm ent than using the developmental study for a point of departure. Consequently, the developmental study was considered to be supportive of the reproduction study. The chosen endpoint is thus protective of offspring and fetal effects, as well as all effects observed in the dermal toxicity study. The parental kidney effect seen in the reproduction study is not of concern, since kidney was evaluated in the route specific dermal study. The reproduction study is protective of the sentinel population for residenti al exposure (children exposed due to spray drift). The standard 100X UF was applied to account for interspecies extrapolation and intra

- species variation. A margin of exposure (MOE) of 100 is considered adequate for the level of concern. The FQPA SF
is 1 for residential exposures. The dermal absorption factor is estimated to be 18% (see Section 4.2.1).

### Sodium Acifluorfen Human Health Risk Assessment DP No. D 426393

Page 18 of 48 Short

- and Intermediate

- Term Dermal Endpoints (occupational): The endpoint selected for
short

- term dermal exposure scenarios was from a reproduction tox icity study in rat. The offspring NOAEL was 25 mg/kg/day. The LOAEL was 125 mg/kg/day based on decreased pup body weights and renal pelvic dilatation. The standard 100X UF was applied to account for interspecies extrapolation and intra

- species variation. A margin of exposure (MOE) of 100 is considered adequate for risk assessment level of concern. The dermal absorption factor is estimated to be 18%. This study was chosen for the reasons provided above for dermal residential endpoints. Considering the simi lar NOAEL/LOAEL values in the rat developmental study, the reproduction study is also protective of pregnant workers.

Short

- and Intermediate

- Term Inhalation Endpoints (occupational): The endpoint selected for
short

- and intermediate

- term inhalation ex posure scenarios was from a reproduction study in rats. The parental NOAEL was 1.25 mg/kg/day. At the study LOAEL of 25 mg/kg/day, dilatation of tubules in the outer medulla of kidneys were noted in both generations in parental females. No route specific study was available. As it is unknown exactly how long treatment must continue to result in the nephrotoxicity observed in the reproduction study, it was assumed that the toxicity may result from short

- term exposure in order to be protective of this possi bility. This endpoint is the most protective endpoint for these exposure scenarios. The standard 100X UF was applied to account for interspecies extrapolation and intraspecies variation. A margin of exposure (MOE) of 100 is considered adequate for the lev el of concern. Toxicity by the inhalation route is
considered to be similar to the oral route.

Carcinogenicity: Sodium acifluorfen is considered likely to be carcinogenic to humans at high enough doses to cause the biochemical and histopathological change s in livers of rodents, but unlikely to be carcinogenic at doses below those causing these changes.

4.5.2 Recommendation for Combining Routes of Exposures for Risk Assessment

For short

- term exposures, a specific toxic effect (nephrotoxicity) is common to oral, dermal, and inhalation routes; therefore, these routes can be combined for risk assessment. For intermediate

term exposures, a specific toxic effect (nephrotoxicity) is c ommon to dermal and inhalation routes; therefore, these routes can be combined. Long

- term occupational exposures are not expected. The endpoint selections for sodium acifluorfen are listed in Table 4.5.4

.

4.5.3 Cancer Classification and Risk Assessment Recommendation

T he Cancer Assessment Review Committee (CARC) considered s 

### odium acifluorfen as “ likely to be carcinogenic to humans at high enough doses to cause the biochemical and histopathological changes in livers of rodents, but unlikely to be carcinogenic at doses below those causing these changes ” (Kidwell, 2003, TXR# 0052014)

. EPA determined that no n

- linear extrapolation be
used for assessment

. The non

- linear RfD approach will be protective for chronic effects

, including carcinogenicity.

4. 5

. 4 Summary of Points of Departure and Toxicity Endpoints Used in Human Risk
Assessment

### Sodium Acifluorfen Human Health Risk Assessment DP No. D 426393

Page 19 of 48 Table 4.5.4.1. Summary of Toxicological Doses and Endpoints for Sodium Acifluorfen for Use in Dietary

and Non

- Occupational Human Health Risk Assessments

Exposure/
Sce nario Point of

Departure Uncertainty/

FQPA Safety

Factors RfD, PAD,

Level of
Concern for
Risk
Assessment Study and Toxicological Effects

Acut e Dietary ( General Population, including
Infants and Children) NOAEL=

293 mg/kg UF A =10 x

UF H =10 x FQPA SF= 1 x Acute RfD =

2.9 mg/kg

a PAD = 2.9 mg/kg 49318001, Acute neurotoxicity

LOAEL = 440 mg/kg based on decreased motor activity in females

Acut e Dietary ( Females 13

- 49 years of age) NOAEL=

20 mg/kg/day UF A =10 x

UF H =10 x FQPA SF= 1 x Acute RfD =

a PAD = 0.20 mg/kg 00122743, Rat developmental

Developmental LOAEL = 90 mg/kg/day
based on increased incidence of slightly
dilated lateral ventricles of the brain

Chronic Dietary (All Populations) NOAEL=

1.25 mg/kg/day UF A =10 x

UF H =10 x FQPA SF= 1 x Chronic RfD

= cPAD =
0.013 mg/kg/day 00155548, Rat reproduction

Parental LOAEL = 25 mg/kg/day based
on dilatation of tubules in the outer
medulla of kidneys in parental females of
both generations (33/35 (P1) and 28/40 (F1) treated parents vs 0/35

- 41 controls) ; one occurrence of t ubular epithelial
necrosis was noted in the P1 females (compared to 0 controls)

Incidental
Oral Short

Term (1

- 30 days) NOAEL=

25 mg/kg/day UF A =10 x

UF H =10 x FQPA SF= 1 x Residential

LOC for
MOE = 100

No residential

uses. Accounts for spray drift. 00155548, Rat reproduction

Offspring LOAEL = 125 mg/kg/day decreased body weight (both generations ; ↓6

- 26% ) and increased incidence of dilatation of the renal pelvis in the F2 generation

Dermal Short

Term (1

- 30 days) NOAEL=

25 mg/kg/day

DAF=18% UF A =10 x

UF H =10 x FQPA SF= 1 x Residential

LOC for
MOE = 100

No residential

uses. Accounts for spray drift. 00155548, Rat reproduction

Offspring LOAEL = 125 mg/kg/day decreased body weight (both generations ; ↓6

- 26% ) and increased incidence of dilatation of the renal pelvis i n the F2 generation
00122743, Rat developmental is supportive

Cancer (oral, dermal, inhalation) Classification: likely to be carcinogenic to humans at high enough doses to cause the

biochemical and histopathological changes in livers of rodents, but unlikely to be carcinogenic at doses below those causing these changes. The non

- linear RfD approach wi ll be protective for
chronic effects

, including carcinogenicity.
Point of Departure (POD) = A data point or an estimated point that is derived from observed dose

- response data and used to mark the beginning of extrapolation to determine risk associated w ith lower environmentally relevant human exposures. NOAEL = no observed adverse effect level. LOAEL = lowest observed adverse effect level. UF = uncertainty factor. UF A = extrapolation from animal to human (interspecies). UF H = potential variation in

### Sodium Acifluorfen Human Health Risk Assessment DP No. D 426393

Page 20 of 48 sensitivity among members of the human population (intraspecies). UF L = use of a LOAEL to extrapolate a
NOAEL. UF S = use of a short

- term study for long

- term risk assessment. UF DB = to account for the absence of key data (i.e., lack of a critical study). FQPA SF = FQPA Safety Factor. PAD = population adjusted dose (a = acute, c = chronic). RfD = reference dose. MOE = margin of exposure. LOC = level of concern. N/A = not applicable. DAF = dermal absorption factor.

Table 4.5.4.2. Summary of Toxicolo gical Doses and Endpoints for Sodium Acifluorfen for Use in Occupational Human Health Risk Assessments

Exposure/
Scenario Point of

Departure Uncertainty

Factors Level of Concern

for Risk
Assessment Study and Toxicological Effects

Dermal Short

and
Intermediate

Term (1

- 30 days and 1

- 6
months ) NOAEL=

25 mg/kg/day

DAF=18% UF A =10 x

UF H =10 x Occupational

LOC for MOE =
100 00155548, Rat reproduction

Offspring LOAEL = 125 mg/kg/day decreased body weight (both generations ; ↓6

- 26% ) and increased incidence of dilatation of the renal pelvis in the F2 generation
00122743, Rat developmental is supportive

Inhalation
Short

- and
Intermediate

Term (1

- 30 days and 1

- 6
months ) NOAEL=

1.25 mg/kg/day UF A =10 x

UF H =10 x Occupational

LOC for MOE =
100 00155548, Rat reprodu ction

Parental LOAEL = 25 mg/kg/day based
on dilatation of tubules in the outer
medulla of kidneys in parental females of
both generations (33/35 (P1) and 28/40 (F1) treated parents vs 0/35

- 41 controls) ; one occurrence of tubular epithelial
necrosis was noted in the P1 females (compared to 0 controls)

Cancer (oral, dermal, inhalation) Classification: likely to be carcinogenic to humans at high enough doses to cause the

biochemical and histopathological changes in livers of rodents, but unlikely to be carcinogenic at doses below those causing these changes. The non

- linear RfD approach wi ll be protective for
chronic effects

, including carcinogenicity.
Point of Departure (POD) = A data point or an estimated point that is derived from observed dose

- response data and used to mark the beginning of extrapolation to determine risk associated w ith lower environmentally relevant human exposures. NOAEL = no observed adverse effect level. LOAEL = lowest observed adverse effect level. UF = uncertainty factor. UF A = extrapolation from animal to human (interspecies). UF H = potential variation in sensitivity among members of the human population (intraspecies). UF L = use of a LOAEL to extrapolate a
NOAEL. UF S = use of a short

- term study for long

- term risk assessment. UF DB = to account for the absence of key data (i.e., lack of a critical study). MOE = margin of exposure. LOC = level of concern. N/A = not applicable.



### 4.6 Endocrine Disruption

As required by FIFRA and FFDCA, EPA reviews numerous studies to assess potential adverse outcomes from exposure to chemicals. Collectively, these studies include acute, subchronic and chronic toxicity, including assessments of carcinogenicity, neurotoxicity, developmental, reproductive, and general or systemic toxicity. These studies include endpoints which may be susceptible to endocrine influence, including effects on endocrine target organ histopathology, organ weights, estrus cyclicity, sexual maturation, fertility, pregnancy rates, reproductive loss, and sex ratios in offspring. For ecological hazard assessments, EPA evaluate s acute tests and chronic studies that assess growth, developmental and reproductive effects in different

### Sodium Acifluorfen Human Health Risk Assessment DP No. D 426393

Page 21 of 48 taxonomic groups. As part of its preliminary re

- registration decision for sodium acifluorfen , EPA
reviewed these data and selected the most sensitive endpoints for relevant risk assessment scenarios from the existing hazard database. However , as required by FFDCA section 408(p),
sodium acifluorfen is subject to the endocrine screening part of the Endocrine Disruptor Screening Program (EDSP).

EPA has developed the EDSP to determine whether certain substances (including pesticide active and other ingredients) may have an effect in humans or wildlife similar to an effect produced by a “naturally occurring estrogen, or other such endocrine effects as the Administrator may designate.” The EDSP employs a two

- tiered approach to making the statutorily required determinations. Tier 1 consists of a battery of 11 screening assays to identify the potential of a chemical substance to interact with the estrogen, and rogen, or thyroid (E, A, or T) hormonal systems. Chemicals that go through Tier 1 screening and are found to have the potential to interact with E, A, or T hormonal systems will proceed to the next stage of the EDSP where EPA will determine which, if any, of the Tier 2 tests are necessary based on the available data. Tier 2 testing is designed to identify any adverse endocrine

- related effects caused by the substance, and
establish a dose

- response relationship between the dose and the E, A, or T effect.

Und er FFDCA section 408(p), the Agency must screen all pesticide chemicals. Between October 2009 and February 2010, EPA issued test orders/data call

- ins for the first group of 67 chemicals, which contains 58 pesticide active ingredients and 9 inert ingredient s. A second list of chemicals identified for EDSP screening was published on June 14, 2013 3 

### and includes some pesticides scheduled for registration review and chemicals found in water

. Neither of these lists should be construed as a list of known or likely endocrine disruptors. List 2 represents the next
set of chemicals for which EPA intends to issue test orders/data call

- ins in the near future. For
further information on the status of the EDSP, the policies and procedures, the lists of chemicals,
future lists, the test guidelines and the Tier 1 screening battery, please visit our website 4



### .

5.0 Dietary Exposure and Risk Assessment

5.1 Metabolite/Degradate Residue Profile

5.1.1 Summary of Plant and Animal Metabolism Studies

The requirements for plant metabolism are fulfilled. Adequate studies are available for depicting
the metabolism in rice, peanuts, and soybeans. Major metabolites in crops included acifluorfen, acifluorfen amine and several conjugated metabolites. Toler ances for plant commodities are currently expressed in terms of the combined residues of sodium acifluorfen and its metabolites, including the corresponding acid, methyl ester, and amino analogues. These data are adequate to cover all registered crop uses

.

3 See http://www.regulations.gov/#!documentDetail;D=EPA

- HQ

- OPPT

- 2009

- 0477

- 0074 for the final second list of chemicals.

4 http://www.epa.gov/endo/

### Sodium Acifluorfen Human Health Risk Assessment DP No. D 426393

Page 22 of 48 Adequate studies are available for depicting the metabolism in ruminants and poultry , although tolerances are not required in livestock commodities as there is no expectation of finite residues in livestock tissue [ 40 CFR § 180.6(a)( 3 ) ]

.

5.1.2 Summar y of Environmental Degradation D426465. A. Shelby. Acifluorfen: Drinking Water Assessment for Registration Review



### Sodium acifluorfen rapidly dissociates to the acifluorfen anion and is expected to be completely dissociated during tank mixture and prior t o application. The acifluorfen anion is persistent in soil (aerobic soil metabolism half

- life 170 days) and in aerobic aquatic environments (estimated
aerobic half

- life 117 days); it is less persistent in anaerobic conditions (aquatic half

- life
estimated to be 2.75 days). The acifluorfen ion is mobile to moderately mobile; K oc 

### ’s range from
50 to 199 mL/g

. Adsorption and desorption were strongly correlated with soil clay content.
Acifluorfen unde rgoes photolytic degradation in water with a half

- lives ranging from 21.7 hours to 352 hours depending on the pH and buffer systems used. With metabolic persistence and mobility in soil, acifluorfen is expected to dissipate and accumulate in groundwater. Acifluorfen in surface water is expected to dissipate t hrough photolysis and anaerobic aquatic metabolism. Acifluorfen may degrade rapidly in surface water bodies with clear and/or shallow water that is able to transmit adequate light. It is stable to hydrolysis, and photodegradation on soil is not a major de gradation route in the environment. Volatilization does not appear to be a significant dissipation pathway for acifluorfen (vapor pressure is <1.33 x 10

- 5 

### Pa; Henry's Law constant is
7.65 x 10

- 10 

### atm m 3 

### /mol). Acifluorfen is not expected to bioaccumulate in aquatic organisms
because of its low K ow



### .

5.1.3 Residues of Concern Summary and Rationale

The residues to be regulated and of toxicological concern in plants are those in the current tolerance expression, i.e ., the parent compound (sodium salt is not ex pected to be present), acifluorfen acid, acifluorfen amine, and the methyl esters of the acid and the amine. As 40 CFR § 180.6(a)(3) is applicable for livestock, there is no need to define residues of concern in
livestock commodities. The residue of conce rn to be used for the assessment of drinking water exposure is acifluorfen acid (D426465, A. Shelby, 4/29/2015). This information is summarized
in Table 5.1.3.

Table 5.1.3 Summary of Metabolites and Degradates to be included in th e Risk
Assessment and Tolerance Expression

Matrix Residues included in Risk Assessment Residues included in Tolerance Expression

Plants Acifluorfen acid, acifluorfen methyl ester,

acifluorfen amine, and acifluorfen amine methyl ester Acifluorfen acid, acifluorfen methyl ester, acifluorfen amine, and acifluorfen amine methyl

ester

Livestock Not Applicable Not Applicable

Drinking Water Acifluorfen acid Not Applicable



### 5 .2 Food Residue Profile

### Sodium Acifluorfen Human Health Risk Assessment DP No. D 426393

Page 23 of 48 The residue chemistry database is adequate for supporting regulatory conclusions, tolerance reassessment, and for the purposes of this risk assessment. The crop field trial results
demonstrate that residues of sodium aciflu or fen are not expected in the raw agricultural
commod ities (RACs) of the registered crops, as all trial samples had <LOQ residues , except for rice straw, a livestock feedstuff . Further, exaggerated rate processing studies showed that residue concentration does not occur in processed commodities. These resi due studies were supported by storage stability data for plant commodities (peanut, rice, soybean, and strawberry). Storage stability data for animal commodities are not needed as magnitude of the residue data for meat, milk, poultry, and eggs are not req uired (40 CFR § 180.6(a)(3)). Sufficient rotational crop studies were conducted to support the following plant

- back intervals (PBIs) for rotational crops: 40 days for small grains and 100 days for other crops. Registered crops may be replanted immediately.

5.3 Water Residue Profile D426465. A. Shelby. Acifluorfen: Drinking Water Assessment for Registration Review



### R evised estimated drinking water concentrations (EDWCs) were determined by the Environmental Fate and Effects Division (EFED) for d ietary assessment

. Based on groundwater modeling results from Pesticide Root Zone Model

– Ground Water ( PRZM

- GW ) , the maximum EDWC for sodium acifluorfen for acute, chronic and 30 year exposure assuming maximum application rates for current uses is 146 ppb for the 1 in 10 year peak, annual average, and 30 year annual average concentrations

.

T he acute EDWC for use on rice is 218 ppb and the chronic EDWC for use on rice is 88 ppb

. The level of 218 ppb is higher than the acute EDWC recommended for use by HED in this assessment but significant dilution and degradation can be expected to occur with acifluorfen concentrations expected to be lower than the acute groundwater EDWC for strawberries (146 ppb) before reaching a drinking water intake. Therefore, the a cute EDWC recommended for use by HED is 146 ppb.

This maximum EDWC is derived from the strawberry use on the Wisconsin Sands PRZM

- GW scenario. Surface water modeling resulted in lower EDWCs. The maximum estimated surface exposure concentration for acifluorfen is 66.8 ppb for acute exposure

.

Table 5. 3 Summary of Estimated Surface Water and Groundwa ter Concentrations

for Acifluorfen

Scenario Surface Water Conc., ppb a Groundwater Conc., ppb b

Acute 66.8 146

Chronic (non

- cancer) 9.67 146

a From the Tier II PRZM

- EXAMS

- Index Reservoir model.

b From the PRZM

- GW model.



### Acifluorfen is a rapidly forming degradate of the registered pesticide active ingredient lactofen (PC Code 128888). Acifluorfen and lactofen have similar soybean, peanut, and strawberry use patterns in common. Given the overlap in residues and use pattern, acifluorfen has the potential

### Sodium Acifluorfen Human Health Risk Assessment DP No. D 426393

Page 24 of 48 to be in surface water or groundwater as a result of an application of either active ingredient. However, maximum label u se rates for each lactofen use are half or less than the respective acifluorfen application rate for the same use site. Therefore, groundwater EDWCs derived from the acifluorfen use pattern are conservative with respect to expected groundwater EDWCs for
l actofen.

5.4 Dietary Risk Assessment

5.4.1 Description of Residue Data Used in Dietary Assessment

Established tolerances for sodium acifluorfen are listed under 40 CFR § 180.383. These values
form the basis for the residue levels used in the acute and chronic analyses, together with default processing factors. The residue chemistry database for sodium acifluorfen indicates no residue concentration in processed commodities from rice, soybean, or peanut (D252560, W. Hazel, 05

- MAY

- 2000). Thus, all proce ssing factors were set to a default of one (1).

Acifluorfen is a degradate of two registered herbicides, lactofen and sodium acifluorfen.
Acifluorfen and lactofen have similar soybean, peanut, and strawberry use patterns in common.
Because the maximum use rates for lactofen are no more than half the corresponding acifluorfen

rate s, and no acifluorfen residues were found in foods from the field trial studies, HED considers the use of acifluorfen tolerance level residues to include any potential food contributions to total
acifluorofen exposure from lactofen.

The drinking water residues used in the dietary risk assessment were provided by the Environmental Fate and Effects Division (EFED) in the following memorandum: “ Acifluorfen: Drinking W ater Assessment for Registration Review” ( D 426465

, A. Shelby, 0 4 /2 9/2015 ) and incorporated directly into this dietary assessment. Water residues were incorporated in the

DEEM

- FCID into the food categories “water, direct, all sources” and “water, indirect, all
sources.”

EFED provided surface and ground water modeling results for registered acifluorfen crop uses. As the ground water models gave higher water concentrations than the surface water models, ground water results form the basis for the EDWCs re commended for use in the current dietary assessment. The rice use was modeled using the Pesticides in Flooded Application Model (PFAM); however, water concentrations from the rice use are expected to be lower than the ground water EDWCs from the strawberr y use, due to dilution and degradation effects involved with acifluorfen treated rice paddy water.

Groundwater EDWCs were calculated from PRZM

- GW for uses on soybean, peanut , and strawberry with six groundwater scenarios

, which are intended to broadly rep resent vulnerable, shallow unconsolidated aquifers across the United States. The highest ground water estimate for acifluorfen came from the strawberry use pattern in WI sands (146 ppb) and was used in both the acute and chronic dietary analyses.

5.4.2 Percent Crop Treated Used in Dietary Assessment

### Sodium Acifluorfen Human Health Risk Assessment DP No. D 426393

Page 25 of 48 For the acute and chronic dietary analyses, 100% crop treated was assumed for all crops.

5.4.3 Acute Dietary Risk Assessment

An unrefined acute dietary (food and drinking water) exposure assessment was conducted for all
established uses of sodium acifluorfen. Maximum e stimated drinking water concentrations (EDWCs) from the Environmental Fate and Effects Division (EFED) were also included. No percent crop treated (%CT) refinements were utilized ( i.e. , 1 00% CT was assumed for all crops). Tolerance level residues along with default processing factors were used where appropriate. At
the 95 th 

### percentile of exposure, the estimated risk was < 1% of the acute population adjusted dose (aPAD) for the U.S. popul ation and all population subgroups except females 13

- 49 years old

. . A separate point of departure (PoD) was selected for females 13

- 49 years old and the estimated
risk was 4.0% of the aPAD for this population subgroup. A food only analysis demonstrate d that water is the primary contributor to aggregate (food + water) dietary exposure to sodium
acifluorfen.

5.4.4 Chronic Dietary Risk Assessment

An unrefined chronic dietary exposure analysi s was performed for all established uses of sodium
acifluorfen . Tolerance level residue s, 100% CT assumptions, and default processing factors
were used . The estimated risk was 24% of the chronic population adjusted dose (cPAD) for the U.S. population. The most highly exposed population subgroup was all infants at 62% of the cPAD. A food only analysis demonstrated that water is the primary contributor to aggregate (food + water) dietary exposure to sodium acifluorfen.

5.4.5 Cancer Dietary Risk Assessment

Sodium acifluorfen was classified as “ likely to be carci nogenic to humans at high enough doses to cause the biochemical and histopathological changes in livers of rodents, but unlikely to be carcinogenic at doses below those causing these changes. EPA determined that non

- line ar extrapolation be used for assessment ; t herefore, no separate Q 1 

### * based cancer dietary exposure assessment was required.

The chronic RfD of 0.013 mg/kg/day is protective of both cancer and non

- cancer effects. A non

cancer chronic dietary risk assessment was completed as descri bed in Section 5.4.4.; risk levels

were below the LOC of 100% cPAD and are considered protective for both non

- cancer and
cancer risk.

5.4.6 Summary Table

Table 5.4.6 summarizes the results of the acute and chronic dietary analyses conducted for
sodium acifluorfen. Although highly conservative assumptions were used in these dietary assessments, risk levels do not exceed HED’s level of concern of 100% aPAD or 100% cPAD.

### Sodium Acifluorfen Human Health Risk Assessment DP No. D 426393

Page 26 of 48 Table 5.4.6 . Summary of Dietary (Food and Drinking Water) Exposure and Risk for Sodium
Acifluorfen.

Population Subgroup Acute Dietary (95th Percentile) Chronic Dietary Cancer

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

General U.S. Population 0.008117 < 1 0.003153 24
All Infants (<1 year old) * 0.025328 < 1 0.008113 62



### N/A N/A Children 1

- 2 years old 0.012729 < 1 0.004678 36

Children 3

- 5 years old 0.010161 < 1 0.003939 30

Children 6

- 12 years old 0.007742 < 1 0.002818 22

Youth 13

- 19 years old 0.006794 < 1 0.002307 18

Adults 20

- 49 years old 0.007963 < 1 0.003132 24

Adults 50

- 99 years old 0.007107 < 1 0.003084 24

Females 13

- 49 years old * 0.008066 4.0 0.003112 24 *The subpopulation(s) with the highest risk estimates

.



### 6.0 Residential (Non

- Occupational) Exposure/Risk Characterization

There are no registered residential uses at this time. The previously registered products with residential uses have been cancelled or suspended.

6.1 Residential Bystander Post

- application Inhalation Exposure

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 F ederal Insecticide, Fungicide, and Rodenticide Act Scientific Advisory Panel (SAP) in December 2009, and received the SAP’s final report on March 2, 2010 (http://www.epa.gov/scipoly/SAP/meetings/2009/120109meeting.html). The agency has evaluated the SAP r eport and has developed a Volatilization Screening Tool and a subsequent Volatilization Screening Analysis (http://www.regulations.gov/#!docketDetail;D=EPA

- HQ

- OPP

- 2014

- 0219). During r egistration r eview, the agency will utilize this analysis to determine if data (i.e., flux studies, route

- specific inhalation toxicological studies) or further analysis is required for sodium
acifluorfen.

6.2 Spray Drift

Off

- target movement of pesticides can occur via many types of pathways, and it is governed by a variety of factors. Sprays that are released and do not deposit in the application area end up off

target and can lead to exposures to those it may directly contact. They can also deposit on surfaces where contact with residues can eventually lead to indirect exp osures ( e.g. , children playing on lawns where residues have deposited next to treated fields). The potential risk estimates from these residues can be calculated using drift modeling onto 50

- feet wide lawns coupled with methods employed for residential ris k assessments for turf products.

### Sodium Acifluorfen Human Health Risk Assessment DP No. D 426393

Page 27 of 48 The approach to be used for quantitatively incorporating spray drift into risk assessment is based on a premise of compliant applications which, by definition, should not result in direct exposures
to individuals because o f existing label language and other regulatory requirements intended to prevent them. 5 

### Direct exposures would include inhalation of the spray plume or being sprayed directly. Rather, the exposures addressed here are thought to occur indirectly through co ntact with impacted areas, such as residential lawns, when compliant applications are conducted. Given this premise, exposures for children (1 to 2 years old) and adults who have contact with turf where residues are assumed to have deposited via spray dri ft, thus resulting in an indirect exposure, are the focus of this analysis analogous to how exposures to turf products are
considered in risk assessment.

In order to evaluate the drift potential and associated risks, an approach based on drift modeling coupled with techniques used to evaluate residential uses of pesticides was utilized. Essentially, a residential turf assessment based on exposure to deposited residues has been completed to address drift from the agricultural applications of sodium aciflu orfen

. In the spray drift scenario, the deposited residue value was determined based on the amount of spray drift that may occur at varying distances from the edge of the treated field using the AgDrift (v2.1.1) model and the Residential Exposure Assessme nt Standard Operating Procedures Addenda 1: Consideration of Spray Drift Policy . Once the deposited residue values were determined, the remainder of the spray drift assessment was based on the algorithms and input values specified in the recently revised ( 2012) Standard Operating Procedures For Residential Risk Assessment (SOPs)

.

A screening approach was developed based on the use of the AgDrift model in situations where specific label guidance that defines application parameters is not available. 6

, 7 

### AgDrift is appropriate for use only when applications are made by aircraft, airblast orchard sprayers, and ground boom sprayers. When AgDrift was developed, a series of screening values (i.e., the Tier 1 option) were incorporated into the model and repres ent each equipment type and use under varied conditions. The screening options specifically recommended in this methodology were selected because they are plausible and represent a reasonable upper bound level of drift for common application methods in ag riculture. These screening options are consistent with how spray drift is considered in a number of ecological risk assessments and in the process used to develop drinking water concentrations used for risk assessment. In all cases, each scenario is to
b e evaluated unless it is not plausible based on the anticipated use pattern (e.g., herbicides are not typically applied to tree canopies) or specific label prohibitions (e.g., aerial applications are not allowed). Tables 6.2.1 and 6.2.2 provide the screening level drift

- related risk estimates.

The spray drift risk estimates are based on an estimated deposited residue concentration, as a result of the screening level agricultural application scenarios. Sodium acifluorfen can be applied via ground boom and aerial equipment. The spray drift assessment was completed assuming the maximum single application rate of 0.375 lb ai/acre; this is protective of all applications at a lower rate. Chemical

- specific TTR data were not available; there fore, default assumptions were used to estimate transferable residue.

5 This approach is consistent with the requirements of the EPA’s Worker Protection Standard.

6 http://www.agdrift.com/

7 Note that for many cases the scenarios outlined in the screening approach represent actual use practice so risk assessors sho uld
be awar e and characterize these appropriately.

### Sodium Acifluorfen Human Health Risk Assessment DP No. D 426393

Page 28 of 48 The recommended drift scenario screening level options are listed below:

 Ground boom applications are based on the AgDrift option for high boom height and using very fine to fine spr ay type using the 90 th 

### percentile results.

 Aerial applications are based on the use of AgDrift Tier 1 aerial option for a fine to medium spray type and a series of other parameters which will be described in more detail below (e.g., wind vector assumed to be 10 mph in a downwind direction for entire application/drift event). 8



### Spray drift exposure is possible for adults and children. Adults may have short

- term dermal exposure and children may have short

- term dermal and incidental oral exposure from spray drift. The applicable Level of Concern is 100, so MOEs < 100 would be of concern. Exposures were considered for 50 feet wide lawns where the nearest side of the property was directly adjoining the treated field (at field edge). Res ults are presented in Tables 6.6.1 and 6.6 .2; no risk estimates of concern were identified at field edge for adults or children.

Table 6.2 .1 Adult Risk Estimates (MOEs) Related to Indirect Exposure to Spray Drift for Sodium Acifluorfen for the Dermal Route of Exposure

Crop/Ra te Group Spray Type/ Nozzle Configuration Appl. Rate (lb ai/A) TTR (μg/cm 2 ) MOE At Field Edge

Groundboom High Boom Very fine to
Fine 0.375 0.0417 5,300

Aerial Fine to Medium 3,800

Table 6.2 .2 Children (1<2 years old) Risk Estimates (MOEs) Related to Indirect Exposure to Spray Drift for Sodium Acifluorfen for the Combined Dermal and Oral Route of Exposure

Crop/Rate Group Spray Type/ Nozzle Configuration Appl. Rate (lb ai/A) TTR (μg/cm 2 ) MOE At Field Edge

Groundboom High Boom Very fine to
Fine 0.375 0.0417 2,400

Aerial Fine to Medium 1,700



### 7.0 Aggregate Exposure/Risk Characterization

In accordance with the FQPA, HED must consider and aggregate (add) 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 variou s sources, HED considers both the route and duration of exposure.

7.1 Acute Aggregate Risk

8 AgDrift allows for consideration of even finer spray patterns characterized as very fine to fine. However, this spray pattern was not selected as the common screening basis since it is used less commonly for most agriculture.

### Sodium Acifluorfen Human Health Risk Assessment DP No. D 426393

Page 29 of 48 The acute aggregate risk assessment includes food and water exposure only. The acute food plus drinking water risk estimates are not of concern to HED for the general population and all population subgroups. Refer to section 5.4.3 for a detailed discussion of the chronic dietary risk

assessment.

7.2 Short

- Term Aggregate Risk

Since there are no uses for sodium acifluorfen that would result in residential (non

- occupational) exposure, a short

- term aggregate risk assessment is not required.

7.3 Intermediate

- Term Aggregate Risk

Since there are no uses for sodium acifluorfen th at would result in residential (non

- occupational)

exposure , an intermediate

- term aggregate risk assessment is not required.

7.4 Chronic Aggregate Risk

The chronic aggregate risk assessment includes food and water exposure only. The chronic food plus drinking water risk estimates are not of concern to HED for the general population and all population sub

- groups. Refer to section 5.4.4 for a detailed discussion of the chronic dietary risk

assessment.

7.5 Cancer Aggregate Risk

Sodium acifluorfen was c lassified as “ likely to be carcinogenic to humans at high enough doses to cause the biochemical and histopathological changes in livers of rodents, but unlikely to be carcinogenic at doses below those causing these changes. EPA determined that non

- linear

e xtrapolation b e used for assessment ; t herefore, no separate Q 1 

### * based cancer aggregate assessment is required.

A non

- cancer chronic dietary risk assessment was completed as described in Section 5.4.4; risk
levels were below the LOC of 100% cPAD and are considered protective for both non

- cancer and cancer risk.

8.0 Cumulative Exposure/Risk Characterization

Sodium acifluorfen is a member of the diphenyl ether group of herbicides, which includes lactofen and oxyfluorfen. In addition, acifluorfen is a degra date of lactofen ( acifluorofen exposure from lactofen is addressed in Section 5.3 and 5.4.1) . EPA has some evidence that these compounds induce similar toxic effects but has not yet determined whether or not these compounds exhibit a common mechanism

. Fo r this assessment of acifluorfen, therefore, EPA
will not conduct a cumulative risk assessment.

### Sodium Acifluorfen Human Health Risk Assessment DP No. D 426393

Page 30 of 48 9.0 Occupational Exposure/Risk Characterization

An occupational exposure and risk assessment was completed to include all registered uses of
sodium acifluorfen.

9.1 Short

- /Intermediate

- Term Handler Risk

HED uses the term “ handlers ” to describe those individuals who are involved in the pesticide application process. HED believes that there are distinct job functions or tasks related to applications and exposure s can vary depending on the specifics of each task. Job requirements (amount of chemical used in each application), the kinds of equipment used, the target being treated, and the level of protection used by a handler can cause exposure levels to differ in a manner specific to each application event.

Based on the anticipated use patterns and current labeling, types of equipment and techniques that can potentially be used, occupational handler exposure is expected from the registered uses. The quantitati ve exposure/risk assessment developed for occupational handlers is based on the following scenarios:

 Mixing/loading L/SC/EC in support of aerial application to typical and high

- acreage field

crops

 Mixing/loading L/SC/EC in support of ground boom application to typical and high

acreage field crops

 Applying spray via aerial application to typical and high

- acreage field crops

 Applying spray via ground boom application to typical and high

- acreage field crops

 Flagging in support of aerial application

 Mixing/loading/applying L/SC/EC via mechanically

- pressurized handgun

A series of assumptions and exposure factors served as the basis for completing the occupational
handler risk assessments. Maximum application rates were assumed. The standard values

re commended for use in predicting handler exposure that are used in this assessment, known as “unit exposures”, are outlined in the “Occupational Pesticide Handler Unit Exposure Surrogate
Reference Table 9 

### ” . Area treated assumptions are from Exposure Science Advisory Council Policy #9.1.

Occupational handler combined dermal and inhala tion MOEs range from 99 to 33,000 with baseline PPE (single layer clothing, no gloves, and no respirator for all scenarios

, except aerial applicator where engineering controls were used). The one scenario with an MOE < 100 (mixing/loading in support of a erial application to high acreage field crop) was not of concern with the addition of gloves. Since gloves are currently required on the registered labels, there are no occupational handler risk estimates of concern for registered uses.

9 Available: http://www.epa.gov/opp00001/science/handler

- exposure

- table.pdf

### Sodium Acifluorfen Human Health Risk Assessment DP No. D426393

Page 31 of 48 Table 9.1

. Occupational Handler Non

- Cancer Exposure and Risk Estimates for Sodium Acifluorfen

.

Exposure Scenario Crop or Target Level of

Concern Dermal Unit

Exposure (μg/lb ai) 1 Inhalation Unit

Exposure (μg/lb ai) 1 Maximum

Application
Rate 2 Area
Treated or
Amount
Handled Daily 3 Dermal Inhalation Total

Mitigation
Level Mitigation

Level Dose (mg/kg/day) 4 MOE 5 Dose (mg/kg/day) 6 MOE 7 MOE 8

Mixer/Loader

Mixing/loading, L/SC/EC, Aerial, Broadcast Typical

Field Crop

100 SL/No G: 220 No R: 0.219 0.375 350 acres 0.065 380 0.000359 3,500 340

High Acreage Field Crop SL/No G: 220 No R: 0.219 0.375 1200 a c res 0.223 110 0.00123 1,000 99

SL/G: 3 7.6 0.038 660 400

SL/No G: 220 No R: 0.219 0.25 0.149 170 0.000821 1,500 150

Mixing/loading, L/SC/EC,
Groun d boom Ty p ical

Field Crop SL/No G: 220 No R: 0.219 0.375 80 acres 0.0149 1,700 0.0000821 15,000 1,500

High Acreage Field Crop SL/No G: 220 No R: 0.219 0.375
200 acres 0.0371 670 0.000205 6,100 600

SL/No G: 220 No R: 0.219 0.25 0.0248 1,000 0.000138 9,100 900

Applicator

Applicator, Spray, Aerial Typical Field Crop

100 Eng. Control:
2.08 Eng. Control:

0.0049 0.375 350 acres 0.000614 41,000 0.00000804 160,000 33,000

High Acreage Field Crop Eng. Control:
2.08 Eng. Control:

0.0049 0.375

1200 acres 0.00211 12,000 0.0000276 45,000 9,500

Eng. Control:
2.08 Eng. Control:

0.0049 0.25 0.0014 18,000 0.0000184 68,000 14,000

Applicator, Spray,
Groundboom Typical

Field Crop SL/ No G: 78.6 No R: 0.34 0.375 80 acres 0.00531 4,700 0.000128 9,800 3,200

High Acreage Field Crop SL/ No G: 78.6 No R: 0.34 0.375
200 acres 0.0133 1,900 0.000319 3,900 1,300

SL/ No G: 78.6 No R: 0.34 0.25 0.00884 2,800 0.000213 5,900 1,900

Mixer/Loader/Applicator

Mixer/Loader/Applicator, L/SC/EC, Mechanically

pressurized handgun Typical Field Crop 100 SL/ No G:
1300 No R: 3.9 0.01875 lb ai/gallon (20 gal

H 2 O/A) 1000

gallons 0.0549 460 0.000914 1,400 350

Flagger

Flagging in support of Typical/ 100 SL/ No G: 11 No R: 0.35 0.375 350 acres 0.00324 7,700 0.000574 2,200 1,700

### Sodium Acifluorfen Human Health Risk Assessment DP No. D426393

Page 32 of 48 Table 9.1

. Occupational Handler Non

- Cancer Exposure and Risk Estimates for Sodium Acifluorfen

.

Exposure Scenario Crop or Target Level of

Concern Dermal Unit

Exposure (μg/lb ai) 1 Inhalation Unit

Exposure (μg/lb ai) 1 Maximum

Application
Rate 2 Area
Treated or
Amount
Handled Daily 3 Dermal Inhalation Total

Mitigation
Level Mitigation

Level Dose (mg/kg/day) 4 MOE 5 Dose (mg/kg/day) 6 MOE 7 MOE 8

aerial application High Acreage Field Crop SL/ No G: 11 No R: 0.35 0.25 0.00217 12,000 0.000383 3,300 2,600

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

2 Based on registered labels (See Section 4.0).
3 Exposure Science Advisory Council Policy #9.1.

4 Dermal Dose = Dermal Unit Exposure (μg/lb ai) × Conversion Factor (0.001 mg/μg) × Application Rate (lb ai/acre or gal) × Area Treated or Am ount Handled (A or gal/day) × DAF (18%) ÷ BW (80kg).
5 Dermal MOE = Dermal NOAEL (25 mg/kg/day) ÷ Dermal Dose (mg/kg/day).

6 Inhala tion Dose = Inhalation Unit Exposure (μg/lb ai) × Conversion Factor (0.001 mg/μg) × Application Rate (lb ai/acre or gal) × Ar ea Treated or Amount Handled (A or gal/day) ÷ BW (80kg).

7 Inhalation MOE = Inhalation NOAEL (1.25 mg/kg/day) ÷ Inhalation Dose (mg /kg/day).
8 Total MOE = 1 ÷ (1/Dermal MOE + 1/Inhalation MOE).

### Sodium Acifluorfen Human Health Risk Assessment DP No. D426393

Page 33 of 48 9.2 Short

- /Intermediate

- Term Post

- Application Risk

HED uses the term post

- application to describe exposures that occur when individuals are present in an environment that has been previously treated with a pesticide (also referred to as re

entry exposure). Such exposures may occur when workers enter previously treated areas to perform job functions, i ncluding activities related to crop production, such as scouting for pests or harvesting. Post

- application exposure levels vary over time and depend on such things as the type of activity, the nature of the crop or target that was treated, the type of pes ticide application, and the chemical’s degradation properties. In addition, the timing of pesticide applications, relative to harvest activities, can greatly reduce the potential for post

- application exposure.

9.2.1 Dermal Post

- application Risk

HED has determined that there are potential exposures to persons entering treated sites (e.g., harvesters) after application of sodium acifluorfen is complete. A series of assumptions and exposure factors served as the basis for completing the occupational post

- application risk

assessments. Maximum application rates were assumed. The standard values recommended for use in predicting post

- application exposure that are used in this assessment, known as “transfer coefficients”, are presented in the ExpoSAC Po licy 3 10 

### ”

. There are DFR data available on soybean plants treated with sodium acifluorfen (D270366, T. Dole, 2/13/01). The results of the
post

- application occupational exposure and risk assessment indicate that risk estimates are not a concern on the day of application (12 hours following the end of the application). HED concurs
with the default 48

- hr REI.

The table below summarizes the occupational post

- application risk estimates for the registered applications of sodium acifluorfen

. The occupational po st

- application exposure and risk
estimates indicate that short

- and intermediate

- term MOEs are not of concern to HED (i.e.,
MOEs > 100). Occupational post

- application dermal MOEs range from 1,000 to 41,000 and are not of concern (LOC = 100).

Table 9.2

. Occupational Post

- application Non

- Cancer Exposure and Risk Estimates for Sodium
Acifluorfen.

Crop/Site Activities Transfer Coefficient (cm 2 /hr) DFR/TTR 1

(Day 0) Dermal Dose

(mg/kg/day) 2 MOE 3

Short

- and Intermediate

- term

Peanuts Hand weeding 70

0.72 0.0009 28,000

Scouting 210 0.0027 9,200

Irrigation 1900 0.0246 1,000

Rice Hand weeding 70 0.48 0.0006 41,000

Scouting 1100 0.0095 2,600

Soybeans Hand weeding 70 0.72 0.0009 28,000

Scouting 1100 0.0142 1,800

10 Available: h ttp://www.epa.gov/pesticides/science/exposac_policy3.pdf

### Sodium Acifluorfen Human Health Risk Assessment DP No. D426393

Page 34 of 48 Table 9.2

. Occupational Post

- application Non

- Cancer Exposure and Risk Estimates for Sodium
Acifluorfen.

Crop/Site Activities Transfer Coefficient (cm 2 /hr) DFR/TTR 1

(Day 0) Dermal Dose

(mg/kg/day) 2 MOE 3

Short

- and Intermediate

- term

Strawberries Hand weeding 70 0.72 0.0009 28,000

Scouting 210 0.0027 9,200

1 DFR from chemical

- specific study. The DFR was adjusted for the different application rate for rice.

2 Daily Dermal Dose = [DFR (μg/cm2) × Transfer Coefficient × 0.001 mg/μg × 8 hrs/day × dermal absorption (%)] ÷ BW (kg). 3 MOE = POD (25 mg/kg/day) / Daily Dermal Dose. Daily Dermal Dose = [DFR/TTR (μg/cm 2 ) × TC × 0.001 mg/μg × 8 hrs/day × dermal absorption factor (%)]  BW (kg).



### Restricted Entry Interval The REI specified on the proposed label is based on the acute toxicity of sodium acifluorfen. Sodium acifluorfen is classified as Toxicity Category III via the dermal route, Toxicity Category II for skin irritation potential, and Toxicity Category I for a cute eye irritation. It is not a skin
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), ai’s classified as Acute Category I for acute dermal, eye irritation or primary skin irritation are assigned a 48

- hour REI. Therefore, the [156 subpart K] Worker Protection Statement interim REI of 48 hours is adequate to protect agricultural workers from

pos t

- application exposures to sodium acifluorfen

.

9.2.2 Inhalation Post

- application Risk

There are multiple potential sources of post

- application inhalation exposure to individuals performing post

- application activities in previously treated fields. The se 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 Federal Insecticide, Fung icide, and Rodenticide Act Scientific Advisory Panel (SAP) in December 2009, and received the SAP’s final report on March 2, 2010 ( http://www.epa.gov/scipoly/SAP/meetings/2009/120109meeting.html ). The agency has evaluated the SAP report and has developed a Volatilization Screening Tool and a subsequent Volatilization Screening Analysis ( http://www.regulations.gov/#!docketDetail;D=EPA

- HQ

OPP

- 2014

- 0219 ). During Registratio n Review, the agency will utilize this analysis to determine if data (i.e., flux studies, route

- specific inhalation toxicological studies) or further analysis is required for sodium acifluorfen

.

In addition, the Agency is continuing to evaluate the availa ble post

- application inhalation exposure data generated by the Agricultural Reentry Task Force. Given these two efforts, the Agency will continue to identify the need for and, subsequently, the way to incorporate occupational post

- application inhalation e xposure into the agency's risk assessments.

Although a quantitative occupational post

- application inhalation exposure assessment was not performed, an inhalation exposure assessment was performed for occupational/commercial handlers. Handler exposure res ulting from application of pesticides outdoors is likely to result in higher exposure than post

- application exposure. Therefore, it is expected that these handler

### Sodium Acifluorfen Human Health Risk Assessment DP No. D426393

Page 35 of 48 inhalation exposure estimates would be protective of occupational post

- application inhalatio n exposure scenarios.

10.0 Human Incidents/Epidemiology D426519. Sodium Acifluorfen: Tier I Update Review of Human Incidents/Epidemiology for Draft Risk Assessment.
S. Recore. 4/2/15.



### Sodium acifluorfen was previously reviewed in 2009 (S. Recore, 11/24/2009, D370339). At the time, no sodium acifluorfen incidents were found in Main IDS for the single chemical sodium acifluorfen reviewing data from 2002 to 2009. It was concluded that “ Because there are no incident cases identified, there does not a ppear to be a risk concern at this time that would warrant further investigation.”

The current IDS analysis from January 1, 2010 through March 26, 2015, shows no incidents reported involving sodium acifluorfen in Main IDS and one incident, classified as minor severity, reported to Aggregate IDS. Further , a query of SENSOR

- Pesticides 1998

- 2011 identifies no incidents involving sodium acifluorfen.

The Agricultural Health Study (AHS) is also a potential source of information associated with human health effects associated with certain pesticides. Sodium acifluorfen is included in the AHS, but is only in phase III and the data is not currently availa ble. Therefore this study does not provide information for this report.

Based on the low frequency and mostly low severity of incident cases reported for sodium
acifluorfen in both IDS and NIOSH SENSOR

- Pesticides, there does not appear to be a concern

at this time that would warrant further investigation. The Agency will continue to monitor the incident and epidemiology information and if a concern is triggered, additional analysis will be
conducted.

11.0 References

Author Barcode Date Title

W. Donovan D 427185 5/18/15 Sodium Aciflu or fen

. Acute and Chronic Aggregate Dietary (Food and Drinking Water) Exposure and Risk Assessments for Registration Review.

A. Gavelek D427186 6/17/15 Sodium Acifluorfen. Occupational and Residential Exposure
Assessment for Registration Review A. Shelby D426465 4/29/15 Acifluorfen: Drinking Water Assessment for Registration Review.

S. Recore D426319 4/2/15 Sodium Acifluorfen: Tier I Update Review of Human Incidents/Epidemiology for Draft Risk Assessment.

T. Goolow et al. D370342 3/23/10 Sodium Acifluorfen. Human Health Assessment Scoping Document in Support of Registration Review.

F. Fort D279845 12/18/01 Sodium Acifluorfen. Revised Product and Residue Chemistry Chapters of the Reregistration Eligibility Decision

F. Fort D279844 12/18/01 Sodium Acifluorfen. Response to Registrant Comments Regarding
the Product and Residue Chemistry Chapters of the Reregistration Eligibility Decision

F. Fort D279173 12/6/01 Sodium Acifluorfen. Dietary Exposure Analyses for the HED Preliminary Human Health Risk Assessment.

### Sodium Acifluorfen Human Health Risk Assessment DP No. D426393

Page 36 of 48 Author Barcode Date Title

T. Dole D279482 11/13/01 Sodium Acifluorfen: Second Revised Occupational and Residential Exposure and Risk Assessment for the Reregistration Eligibility Decision (RED) Document

K. Farwell D291742 7/14/03 Sodium Acifluorfen. Revision to the HED Chapter of the Reregistration Eligibility Decision Document

T. Dole D270365 2/14/01 Review of Acifluorfen (Blazer) Groundboom Mixer/Loader/Applicator Exposure and Biomonitoring Study (MRID 423615

- 01) for use in Acifluorfen exposure and

assessment

T. Dole D270366 2/13/01 Review of Acifluorfen (Blazer) Foliar Dislodgeable Residues on Soybeans (MRID 440911

- 01) and Storage Stability of
Acifluorfen

- Amine in Foliar Dislodging Solution (MRID 440911

- 02) for use in Acifluorfen exposure and assessment

K. Farwell D279497 1/15/02 Sodium Acifluorfen. HED Chapter for the Reregistration Eligibility Decision Document.

K. Farwell D274255 4/27/01 Sodium Acifluorfen. HED Chapter for the Reregistration Eligibility Decision Document

K. Farwell D252555 5/31/00 Sodium Acifluorfen. HED Chapter for the Reregistration Eligibility Decision Document.

B. Tarplee None 9/29/99 Acifluorfen : Report of the FQPA Safety Factor Committee . TXR

No. 013764

P. Chin None 4/7/99 Acifluorfen : Report of the Hazard Identification Assessment
Review Committee . TXR No. 013308

NA None 9/2003 Reregistration Eligibility Decision for Sodium Acifluorfen

E. Craig None 5/7/15 Sodium Acifluorfen: Summary of Hazard and Science Policy Council (HASPOC) Meeting of February 19, 2015:
Recommendations on the Need for a Subchronic and Developmental Neurotoxicity Studies and a Subchr onic Inhalation Toxicity Study.

### Sodium Acifluorfen Human Health Risk Assessment DP No. D426393

Page 37 of 48 A ppendix A

. Toxicology Profile and Executive Summaries

A.1 Toxicology Data Requirements

The requirements (40 CFR 158.500) for food

- use for sodium acifluorfen are in Table 1. Use of the new guideline numbers does not imply that the new (1998) guideline protocols were used.

Study 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 28

- Day Dermal

................................ .............................. 870.3250 90

- Day Dermal

................................ .............................. 870.3465 90

- Day Inhalation

................................ .......................... yes

yes
yes

no

yes yes

yes a

yes

- yes b

870.3700a Developmental Toxicity (rodent)

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

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

................................ ................................ . yes

yes

yes y es

yes

yes

870.4100a Chronic Toxicity (rodent)

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

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

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

................................ ................... yes

no

yes

yes yes

- yes

yes

870.5100 Mutagenicity

— Bacterial reverse mutation assay

.................... 870.5300 Mutagenicity

— In vitro mammalian cell gene mutation test

....... 870.5375 Mutagenicity

— In vitro mammalian chromosome aberration test 870.5395 Mutagenicity

— Mammalian erythrocyte micronucleus test

........ yes

yes

yes

yes y es c

yes

yes

yes

870.6100a Acute Delayed Neurotoxicity (hen)

............................... 870.6100b 90

- Day Neurotoxicity (hen)

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

................. 870.6200b 90

- Day Neurotoxicity Screening Battery (rat)

.............. 870.6300 Developmental Neurotoxicity

................................ ....... no

no

yes

yes

yes -

- yes

yes b

yes b

870.7485 General Metabolism

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

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

................................ ............................. yes

yes

yes y es

yes

yes

a Test was not submitted but is not required at this time because the toxicological data requirements for the 90

- day feeding study in non

- rodents are satisfied by the 1

- year feeding study in dogs.

b A waiver for this study was obtained from HASPOC (Craig, 2 015, TXR# 0051465)

.

c Over 20 mutagenicity studies were submitted. A select number are presented in the Toxicity Profile table. Requirements for the mutagenicity battery were satisfied.



### A.2 Toxicity Profile s

Table A.2.1 Acute Toxicity Profile

– Acifluorfen 2S a

### Sodium Acifluorfen Human Health Risk Assessment DP No. D426393

Page 38 of 48 Guideline No. Study Type MRID(s) Results Toxicity Category

870.1100 Acute oral

- Rat 00122724 LD 50 = 2025 mg/kg ♂

LD 50 = 1370 mg/kg ♀ III

870.1200 Acute dermal

- Rat 00061626 LD 50 > 2000 mg/kg III

870.1300 Acute inhalation

- Rat 00061627 LC 50 > 6.9 mg/L IV

870.2400 Acute eye irritation

- Rabbit 00061628 Severe eye irritant I

870.2500 Acute dermal irritation

- Rabbit 00061629 Moderate to severe erythema II

870.2600 Skin sensitization

- Guinea Pig 46683402 Not a sensitizer NA

a Purity of 20.2

- 23.25% a.i.



### Table A.2.2 Sub

- chronic, Chronic and Other Toxicity Profile

- Sodium Acifluorfen

Guideline
No. Study Type MRID No. (year)/
Classification /Doses Results

870. 3 05 0 28

- Day oral

toxicity (mouse) 45323503 ( 1983 )

Acceptable, guideline ♂♀: 0, 59, 181, 522, 1286, 2471, 4983 ppm ♂♀: 0, 8.8, 27, 78, 193, 371, 747 mg/kg/day based on 1 ppm = 0.15 mg/kg/day

83.9% a.i. NOAEL = 2 7 mg/kg/day LOAEL = 78 mg/kg/day based on increased absolute and relative liver weight and histological chan ges in liver (# treated/10 vs 0/10 controls): slight to moderate multifocal acidophilia (2

- 3), multifocal cell disassociation (1 each sex), multifocal hepatocellular hypertrophy (7

- 10), and diffuse hepatocellular hypertrophy (1 female)
At 193 mg/kg/day, in creased absolute and relative liver weight and histological changes in
liver ( # treated/10 vs 0/10 controls): slight to moderate multifocal acidophilia (10 each sex)

, multifocal cell disassociation (8

- 9)

, diffuse cell disassociation (2 males), multifo cal

h epatocellular hypertrophy (7

- 10) , diffuse hepatocellular hypertrophy (2 each sex ) , and coagulative necrosis (1 each sex)
At 371 and/or 747 mg/kg/day, histological findings in the liver were more pronounced. Serum ALT, AST, and cholesterol were increased, and serum glucose was decreased. Body weights were decreased. In the kidney, increased organ weight, mitotic increase, and nuclear enlargement was noted.

### Sodium Acifluorfen Human Health Risk Assessment DP No. D426393

Page 39 of 48 Table A.2.2 Sub

- chronic, Chronic and Other Toxicity Profile

- Sodium Acifluorfen

Guideline
No. Study Type MRID No. (year)/
Classification /Doses Results

870. 3100 90

- Day oral

toxicity (Fischer 344 rat) 00122730 ( 1982 )

Acceptable, guideline ♂♀: 0, 20, 80, 320, 1250, 2500, 5000 ppm ♂♀: 0, 2, 8, 32, 125, 250,
500 mg/kg/day based on 1 ppm = 0.1 mg/kg/day

Tackle 2S, 20.4

- 23.6% a.i. NOAEL = 32 mg/kg/day
LOAEL = 1 25 mg/kg/day based on decreases in hematology parameters (erythrocyte count [↓11%] and hem atocrit concentration [↓11%) in

males ) , increases in liver and kidney weights,
and increased incidence of hypertrophy of liver
cells

A t 2500 and 5 000 ppm , c hanges in body weights, hematology (erythrocyte count and hemoglobin concentration), clinical chemistry (se rum electrolytes, calcium and phosphorou s; SGPT and alkaline phosphatase activities; BUN, creatinine, total serum protein, albumin, and globulin concentrations), urine (n itrate and urobilinogen content) , liver and kidney weights (absolute and relative), and histopathologic changes in the liver (increased cellular hypertrophy, cell death, mitotic activity, and proliferation of oval or bile duct cells) were noted.
Note: Although the effects observed at 125 mg/kg/day are probably not adverse, this study was not updated as it is not essential to risk

assessment.

870. 3100 90

- Day oral

toxicity (mouse) 00252826 ( 1982 )

Una cceptable, guideline ♂♀: 0, 20, 80, 320, 1250, 2500, 5000 ppm ♂♀: 0, 3, 12, 48, 187.5, 375, 750 mg/kg/day based on 1 ppm = 0.15 mg/kg/day
Tackle 2S, 20.4

- 23.2% a.i. NOAEL = 48 mg/kg/day
LOAEL = 187.5 mg/kg/day based on fatty
infiltration of the liver in males (17/20 treated vs 5/20 controls) and females (17/20 treated vs 8/18 controls)
Changes in mean body weights, hematology (to tal white blood cell numbers, MCV, reticulocyte counts), clinical chemistry (SGPT, SAP, serum glucose), liver weights (absolute and relative), and histopathologial changes i n the l iver (hypertrophy, increased m itotic activity, individ ua l cell death, focal necrosis)

w ere noted in males and females at the 2 500
and 5 000 ppm dose at 30 and 90 days.
Upgradable if t he registrant submit ted the following: a) individual animal histopathology and b) explain "water mechanical problems" and "cage flooding by equipment malfunction."
TXR0003963 says that (b) was explained but
individual histo logy was not received as of
1989. This study is not essential to risk

assessment.

870. 3150 90

- Day oral

toxicity (dog) Not submitted and not

required -

### Sodium Acifluorfen Human Health Risk Assessment DP No. D426393

Page 40 of 48 Table A.2.2 Sub

- chronic, Chronic and Other Toxicity Profile

- Sodium Acifluorfen

Guideline
No. Study Type MRID No. (year)/
Classification /Doses Results

870. 3200 21

- Day dermal

toxicity (rabbit) 00122731 ( 1981 )

Acceptable, non

- guideline ♂♀: 0, 100, 300, 1000 mg/kg/day ; high dose reduced to 500 mg/kg/day on Day 4 by which time 4
rabbits/sex were dead

Tackle 2S, 21.1% a.i NOAEL = 300 mg/kg/day LOAEL = 1000 mg/kg/day based on mortality
Skin irritation (based on erythema and edema scores) was noted at the lowest dose tested.
19/20 animals at the high dose died by Day 8, resulting in the study effectively having only 2 dose groups for evaluation. In addition, histopathologic al ex aminations were l imited to
the liver and kidneys in all animals and to organs with gross lesions

.

870. 3250 90

- Day dermal

toxicity (species) Not submitted and not

required -

870. 3465 90

- Day inhalation

toxicity (species) Not submitted and not

required -

870. 3700a Prenatal

developmental (SD rat) 00122743 (1981)

Acceptable, guideline 0, 20, 90, 180 mg/kg/day
GD 6

- 19 Tackle “2S” (22.4% a.i.) Maternal NOAEL = 90 mg/kg/day
LOAEL = 180 mg/kg/day based on decreased body weights and increased incidence of clinical signs, such as excessive salivation,
urine

- stained fur of the abdomen, rales,
decreased motor activity and chromodacryorrhea
Developmental NOAEL = 20 mg/kg/day
Developmental LOAEL = 90 mg/kg/day based
on decreased fetal body weight and increased
incidence of slightly dilated lateral ventricles of
the brain
At 180 mg/kg/day, the effect on body weight was magnified while the incidence of brain
effect remained similar.

870. 3700a Prenatal

developmental (Wistar rat) 49297001 ( 2015 )

Acceptable, non

- guideline 0, 30, 60, 90 mg/kg/day
GD 5

- 19
Acifluorfen Sodium TC (43.4% a.i.) Maternal NOAEL = 90 mg/kg/day
LOAEL was not observed

Developmental NOAEL = 90 mg/kg/day
LOAEL was not observed
The animals could have tolerated a higher dose.

870. 3700b Prenatal

developmental (rabbit) 00122744 ( 1980 )

Acceptable, non

- guideline 0, 3, 12, 36 mg/kg/day
GD 6

- 29 Tackle “2S” (22.4% a.i.) Materna l NOAEL = 36 mg/kg/day
LOAEL was not observed
Developmental NOAEL = 36 mg/kg/day
LOAEL was not observed

The animals could have tolerated a higher dose.

### Sodium Acifluorfen Human Health Risk Assessment DP No. D426393

Page 41 of 48 Table A.2.2 Sub

- chronic, Chronic and Other Toxicity Profile

- Sodium Acifluorfen

Guideline
No. Study Type MRID No. (year)/
Classification /Doses Results

870. 3700b Prenatal

developmental (rabbit) 00107485 ( 1979 )

Unacceptable, guideline 0, 20, 60, 180 mg/kg/day
GD 7

- 19 (39.8% a.i.) Materna l NOAEL = 20 mg/kg/day
LOAEL = 60 mg/kg/day based on clinical signs observed during GD 7

- 19: anorexia (9/15 treated vs 5/15 controls) , depression (5/15 vs 1/15 control), and dyspnea (1/15 vs 0/15 controls).
At 180 mg/kg/day, excessive mortality was observed (11/15 treated vs 1/15 controls).
Developmental NOAEL = 60 mg/kg/day
LOAEL = 180 mg/kg/day based on fetal resorptions
Considered unacceptable, because i t was not stated how often the dose formulations were prepared. Furthermore, n o concentration or stability data were submitted . Consequently,
there is no way to verify the actual

c oncentration of the test material given to the
does.

870. 3800 Reproduction and

fertility effects (SD rat) 00155548 ( 1986 )

Acceptable, guideline ♂♀: 0, 25, 500, 2500 ppm ♂♀: 0, 1.25, 25, 125 mg/kg/day based on 1 ppm = 0.0 5 mg/kg/day
Tackle Parental/Systemic NOAEL = 1.25 mg/kg/day
LOAEL = 2 5 mg/kg/day based on dilatation of
tubules in the outer medulla of kidneys in
females of both generations (33/35 (P1) and 28/40 (F1) treated vs 0/35

- 41 controls) At 125 mg/kg/day, increased mortality was noted in both generations, as well as decreased body weight. Renal tubular necrosis was also
observed.
Reproductive NOAEL = 12 5 mg/kg/day
LOAEL was not observed
Offspring NOAEL = 25 mg/kg/day
LOAEL = 125 mg/kg/day decreased body weight (both generations ; ↓6

- 26% ) and
increased incidence of dilatation of the renal pelvis in the F2 generation (litters: 38% treated vs 7% controls; pups: 7% treated vs 1% controls)

.

870. 4100a Chronic toxicity

(rat) Not submitted. See

870.4300. -

### Sodium Acifluorfen Human Health Risk Assessment DP No. D426393

Page 42 of 48 Table A.2.2 Sub

- chronic, Chronic and Other Toxicity Profile

- Sodium Acifluorfen

Guideline
No. Study Type MRID No. (year)/
Classification /Doses Results

870. 4100b Chronic toxicity

(dog) 00131162 (1983 )

Una cceptable, guideline Upgradable ♂♀: 0, 20, 300, 4500 ppm ♂♀: 0, 0.5, 7.5, 112.5 mg/kg/day based on 1 ppm = 0.02 5 mg/kg/day

Tackle 2S NOAEL = 7.5 mg/kg/day
LOAEL = 112.5 mg/kg/day based on decreased body weight gain, increased absolute and relative liver and kidney weights, changes in hematology, biochemistry, and urinalysis parameters and increased incidence of microscopic changes in the liver

Reasons f or this classification are the purity of
the test s ubstance was not adequately identified in the text of the report and stability of the test
substanc e in dog chow was not reported.

H owever, a new study is not required because when this study and the data of another chronic feeding study in dog (MRID 00107 484) with Blazer are analyzed together, they provide a reasonable understanding of the chronic toxicity of acifluorfen in dogs. The previous
chronic feeding study in dog (MRID 00107484 ; 1978) was cl assified as core guideline data.

870. 4100b Chronic toxicity

(dog) 00107484 (1978 )

Acceptable, guideline ♂♀: 0, 50, 300, 1800,
5400 ppm ♂♀: 0, 1.25, 7.5, 45, 135 mg/kg/day based on 1 ppm = 0.02 5 mg/kg/day

Blazer NOAEL = 1.25 mg/kg/day
LOAEL = 7.5 mg/kg/day based on coagulation
effects

T here were changes in hematological and biochemical parameters related to effects in the liver in dogs at 45 and 135 mg/kg/day when compared to the controls. Histopathologically,

treatment

- related alterations were observed in the liver, kidney, gall bladder, and eyes . The

D ER was not available, this information was
extracted from the review of A. Arce dated May 2, 1979 in HED Doc. No. 001099.

870. 4200 a Carcinogenicity

(rat) Not submitted. See

870.4300. -

870. 4200 b Carcinogenicity

(mouse) 00122732 ( 1982 )

A cceptable, guideline ♂♀: 0, 625, 1250, 2500

ppm ♂: 0, 119, 259, 655 mg/kg/day ♀: 0, 143, 313, 711 mg/kg/day Tackle 2S, 24% a.i. NOAEL not determined
LOAEL = 119 mg/kg/day based on reduced body weight, increased absolute and relative liver weights, and changes in hematologic
parameters (decreased MCV, decreased segmented neutrophil counts, increased RBC counts, and increased lymphocyte counts)
increase in the incidence of liver tumors ( adenomas, carcinomas, and
adenomas/carcinomas combined ) and stomach tumors ( papillomas) in both sexes

### Sodium Acifluorfen Human Health Risk Assessment DP No. D426393

Page 43 of 48 Table A.2.2 Sub

- chronic, Chronic and Other Toxicity Profile

- Sodium Acifluorfen

Guideline
No. Study Type MRID No. (year)/
Classification /Doses Results

870. 4200 b Carcinogenicity

(mouse) 00082897 ( 1979 )

Acceptable, guideline
when considered in conjunction with MRID
00122732 ♂♀: 0, 7.5, 45, 270 ppm ♂♀: 0, 1.125, 6.75, 40.5 mg/kg/day based on 1 ppm = 0.1 5 mg/kg/day

Blazer (39.4

- 40.5% a.i.) NOAEL = 6.75
LOAEL = 40.5 mg/kg/day based on increased absolute and relative liver weights, increased relative kidney weights, and increased levels of alkaline phosphatase and glutamic pyruvic
transaminase activities
increase in the incidence of liver tumors (primary adenomas) in 40.5 mg/kg/day
females

870. 4 3 00 Combined

Chronic Toxicity/ Carcinogenicity (Fischer 344 rat) 00128253 ( 1983 )

Acceptable, guideline ♂♀: 0, 25, 150, 500, 2500, 5000 ppm ♂♀: 0, 1.25, 7.5, 25, 125,
250 mg/kg/day based on 1 ppm = 0.05 mg/kg/day
Tackle (19.1

- 25.6% a.i.) N OAEL = 25 mg/kg/day
LOAEL = 125 mg/kg/day based on reduced body weight, increased absolute and relative liver weights and increased kidney weights,
increased incidence of nephritis/pyelonephritis,
increased incidence of acidophilic cells in the liver, and related changes in clinical chemistry
parameters no evidence of carcinogenicity

870.5275 Genotoxicity

Sex

- linked
recessive lethal test in Drosophila melanogaster 00122737 (198 1 )

Acceptable, guideline
1.5% Tackle 2S solutions
for 2 or 24 hours Tackle 2S is positive in Y chromosome loss and dominant lethal mutations assays and negative in somatic reversion of white

- ivory, bithorax test of Lewis, and sex

- linked lethals

assays.

870.5300 Genotoxicity

In vitro
mammalian cell gene mutation in the thymidine
kinase locus in mouse lymphoma
cells 00122739 (198 0 )

Una cceptable, guideline
+S9: 25

- 387.3 μg/ml

- S9: 18

- 127.6 μg/ml Not mutagenic. Test chemical did not cause
forward mutations

. Upgradable pending submission of positive
control data.

870.5385 Genotoxicity

In v iv o mammalian
chromosome aberration assay 00122741 (1981)

Acceptable, guideline 0, 0.37, 1.11, or 1.37 mg/kg/day Tackle 2s (23.6% a.i.) for 5 consecutive days Not mutagenic. No increase in clastogenic activity.

870.5450 Genotoxicity

Rodent dominant lethal assay 00122738 (1981)

Acceptable, guideline 80, 360, 800 mg/kg/day
Tackle 2S Not mutagenic. No clear indication of an
adverse effect in the nine calculated indices.

### Sodium Acifluorfen Human Health Risk Assessment DP No. D426393

Page 44 of 48 Table A.2.2 Sub

- chronic, Chronic and Other Toxicity Profile

- Sodium Acifluorfen

Guideline
No. Study Type MRID No. (year)/
Classification /Doses Results

870.5550 Genotoxicity

Unscheduled DNA synthesis assay in primary rat hepatocytes 00122742 (19 81 )

Acceptable, guideline

0.10

- 50.00 μg/mL Tackle Not mutagenic. There were no indications of UDS activity.

870.5550 Genotoxicity

Unscheduled DNA synthesis assay in primary rat hepatocytes 41761103 (1990)

Acceptable, guideline

0.25, 0.75, 2.5, 7.5, 25 μg/mL Not mutagenic. There were no indications of UDS activity.

870.5575 Genotoxicity

Mitotic gene
conversion in

S. cerevisiae 00148272 (1981)

Acceptable, guideline

±S9: 0 .03

- 15 mg/plate
Tackle Mutagenic. A n increase in rec ombination frequency was obtain ed in an initial test at 1.5 mg/plate without the activation system and at a 3 mg/plate with activation; toxicity was observed at 7.5 mg/plate . A repeat assay found
a dose

- related increase in recombination frequency without activation and a positive result (not dose

- related) with activation.

870.620 0a Acute

neurotoxicity screening battery

(Wistar rat) 49318001 ( 2014 )

Acceptable, non

- guideline ♂♀: 0, 293, 440, 660 mg/kg
Acifluorfen Sodium TC (43.40% a.i.) N OAEL = 293 mg/kg
LOAEL = 440 mg/kg based on decreased (27

- 44%) ambulatory motor and total motor
activities in females
The study is upgradable to guideline pending the submission of satisfactory positive control data for the FOB and motor activity assays.

870. 6200b Subchronic

neurotoxicity screening battery Not submitted and not

required -

870. 6300 Developmental

neurotoxicity Not submitted and not

required -

### Sodium Acifluorfen Human Health Risk Assessment DP No. D426393

Page 45 of 48 Table A.2.2 Sub

- chronic, Chronic and Other Toxicity Profile

- Sodium Acifluorfen

Guideline
No. Study Type MRID No. (year)/
Classification /Doses Results

870.7485 Metabolism and

pharmacokinetics (rat) 00122746 (19 8 2)

Acceptable, non

- guideline single 16

- 17 mg/kg sing le 116 mg/kg
10

- 12 mg/kg /day for 14 days Single intravenous 11

- 15 mg/kg Compound is rapidly (t
max = 0.5

- 5.4 h) and almost completely absorbed (bioavailability ~
80

- 97%) into the systemic circulation. Very little radioactivity was detectable in tissues of

rats 96 hours after ad m inistration of each of the four dosage regimens. The radioacti v ity
recovered in urine and feces in female animals, 96 hours after administration, was 60

- 82 % and
5

- 23% of the dose, respectively. In contrast, the radioactivity recovered in urine a nd feces in
male rats was 46

- 58% and 21

- 41% of the dose, respectively. The major radioactive component present in blood (95

- 98%), urine (95%), and bile (93%) was unchanged a c ifluorfen. The major component in feces was the amine
metabolite which accounted for 60

- 80% of the
radioactivit y.

Classified as non

- guideline due to low overall recovery of radioactivity (70.9

- 92.5%).

870. 7600 Dermal

penetration (rat) 00156020 ( 1986 )

Una cceptable, guideline ♂♀: 2.1

- 3.3, 0.21

- 0.33,
0.021

- 0.034 mg/cm 2

Tackle ( 20.3 % a.i.) Total dermal penetration of Tackle following 10 hours exposure was 0.02% for each dose as calculated by addition of the quantities in urine, feces, carcass and blood. However, significantly large amounts of dose remained on the skin (2.3, 20 and 43.5% of the respective doses) after washing with deionized water and may be available for absorption.

The guidelines were not followed: the chemical should have been placed on no less than 10 cm 2

of the rat’s skin instead of 4.9 cm 2 . T his minimal area is necessary for even spreading of the dose formulation. From this study, a dermal penetration of 0.02% does not correctly approximate what was observed in the dermal toxicity study.

870. 7800 Immunotoxicity

(rat) 49321301 (2014)

Acceptable, guideline 0, 500, 1500, 2500

, 3750

ppm adjusted 43.4% a.i. to 0, 81, 244, 408, 681 mg/kg/day Systemic NOAEL = 408 mg/kg/day

Systemic LOAEL = 681 mg/kg/day based on reduced body weights and body weight gains.

Immunotoxicity NOAEL = 681 mg/kg/day

Immunotoxicity LOAEL was not determined.

### Sodium Acifluorfen Human Health Risk Assessment DP No. D426393

Page 46 of 48 Appendix B

. Physical/Chemical Properties

Table B1. Physico

- Chemical Properties of Sodium Acifluorfen

Parameter Value Reference

Molecular Weight (g/mol) 361.66 D426465, A. Shelby,
4/29/2015 Physical State Light yellow powder (solid)

D165551, F. Toghrol,
5/5/1992 Melting Point ( °C) 274

- 278
Water solubility (25 °C , pH 7 ) 61 g/100 g

Solvent solubility (25°C) Octanol 5.37 g/100 mL Methanol 64.15 g/100 mL
Hexane <5 x 10

- 5 g/100 mL
Vapor pressure (25°C) <1.33 x 10

- 5 Pascal

Dissociation constant, pKa 3.86

pH 5.45 Octanol/water partition coefficient, log

K OW (25°C , pH 7 ) 1.55

Organic Carbon Soil Partition Coefficient (mL/g o.c.) K oc = 109 D426465, A. Shelby,
4/29/2015 Aerobic Soil Half

- life (Days) 173
Aerobic Aquatic Half

- life (Days) 114

UV/visible absorption spectrum (pH 7.9) 204 nm

- 2.75 x 10 4 Ɛ (L/(mol x cm))

259 nm

- 6.06 x 10 3 ”

282 nm

- 8.05 x 10 3 ”

300 nm

- 6.76 x 10 3 ” D323251, T. Goodlow,
2/8/2006

### Sodium Acifluorfen Human Health Risk Assessment DP No. D426393

Page 47 of 48 Appendix C

. Review of Human Research

Human Studies Review 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 Version 1.1 ( PHED 1.1 ) ; the Agricultural Handler Exposure Task Force ( AHETF ) database; the Outdoor Residential Exposure Task Force (ORETF) database; and /or the Agricultural Reentry Task Force ( ARTF ) database; are (1) subject to ethics review purs uant 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 guida nce on their use, can be found at the Agency website 11



### .

11 http://www.epa.gov/pesticides/science/handler

- exposure

- data.html and http://www.epa.gov/pesticides/science/post

- app

- exposure

- data.html

### Sodium Acifluorfen Human Health Risk Assessment DP No. D426393

Page 48 of 48 Appendix D. International Tolerances and Maximum Residue Limits Sheet



### Sodium Acifluorfen (PC Code 114402 )
Summary of US and International Tolerances and Maximum Residue Limits

Residue Definition :
US Canada Mexico 1 Codex


### 40 CFR 180. 383 : Sodium acifluorfen, sodium 5

- [2

- chloro

- 4

- (trifluoromethyl)phenoxy]

- 2

- nitrobenzoate, and its metabolites (the corresponding acid, methyl ester, and amino analogues) sodium 5

- [2

- chloro

- 4

- (trifluoromethyl)phenoxy ]

- 2

- nitrobenzoate, including the metabolites consisting of the corresponding acid, methyl ester and amino analogues None



### Commodity Tolerance (ppm) /Maximum Residue Limit (mg/kg)

US Canada Mexico 1 

### Codex

Peanut 

### 0.1 Rice, grain 

### 0.1 Rice, straw 0.2 Soybean, seed 0.1 0.02 Strawberry 0.05

Completed: M. Negussie; 06/09/15

1 Mexico adopts US tolerances and/or Codex MRLs for its export purposes.