### UNITED STATES ENVIRONMENTAL PROTECTION AGENCY

WAS H ING T ON

, D.C

. 20460

OFFICE OF CHEMICAL SAFETY

AND POLLUTION PREVENTION



### MEMORANDUM

Date:



### SUBJECT:

FROM: June 10,20 1 4

Flumiclorac Pentyl: Reg i strat i on Rev i ew Pre l iminary Risk Assessment.

PC Code: 128724 DP Barcode : D409809

Decision No.: 476006 Regist r ati o n No.: NA

Petition No.: NA Regu l atory Action : Registration Rev i ew
Risk Assessment Type : Single Case N o.: 7232

Chemical Aggregate

TXRNo.: N A CAS No.: 87546-18-7

MRIDNo.: NA 40 CFR: 1 80.477



### William H. Donovan, Ph.D., Risk

# As~~ss<J**)A.!,!:JL ~~** **~~** John Liccione, Ph.D.,**Tox c9log~** **t ~~**  

### Seyed Tadayon, Chem i st**~** 

### Risk Assessment Branch V

Health Effects Division (7509P)



### THROUGH: Matthew Lloyd, CIH, Indus t rial Hy tt g · ni

# ~ MichaelS. Metzger, Branch Chief 

## t-**"":fi.~:..Jh'<-v** 

### Risk Assessment Branc h V · Hea l th Effects Division (7509P)



### TO: Eric Miederhoff

, Chemical Review Manager

Risk Management and Imp l ementation B ranch III

Pesticide Re

- eva l uation Division (7508P)

As part of Registration Review, the Pesticide Re-eva l uation D iv i s i on (PRD) of OPP has requested that HED evaluate the hazard and exposure data and conduc t dietary, occupat i ona l

, residen t ial, and aggregate exposure assessments, as needed, to estimate the risk to human heal t h

that w i ll r esult from the registered uses of flumiclorac pentyl.

Page 1 of33

### EXECUTIVE SUMMARY

The Health Effects Division (l-IED) has evaluated the current databases for the act i ve ingredient

flumiclorac pentyl to support the reg i strat i on r eview of this active ingredient. Flumiclorac pentyl ((2-ch l oro

- 4-fluoro-5-(1 ,3,4,5,6, 7 -hexahydro-1 ,3

- dioxo-2H-isoindol-2-yl)phenoxy)acet i c acid, pentyl ester] is an N-phenylphthalimide derivative herbicide used for the contro l of broad l eaf

weeds.

Flumiclorac pentyl is registered for post-emergence application to field corn and soybeans, as a defoliant on cotton, as a Spring burndown herbicide prior to cotton, field corn, and soybean c r op

emergence, and for control ofbroadleafweeds, specifically morning glory and velvet leaf, in a variety of non-crop use sites including go l f courses, parks, recreational areas, residential areas,

sc hools, Christmas tree farms, sod fa r ms, ornamental nurseries, industr i a l areas, commercia l

areas, r igh t s-of-way, and habitat restoration and maintenance areas

. The residue chemistry and

occupat i onal/residentia l exposure databases are considered complete. The hazard and e xposure profiles for this active ingredient a r e adequately understood. Th ere are no d i etary (food and
water), res id ent i al, aggregate, or occupa t ional risks of concern associated with flumiclorac pentyl.

The tox i cology database for flumiclorac-pentyl is complete with t h e exception of a 28-day

inhalation toxicity study. Howe ver, the H azard and Science Policy Council (HASPOC)

recommended in favor of a waiver of th e inhala t ion study (TXR No. 0056913, dated March 20,
2014). In determining the need for a subc hronic inh alation study, EPA's Weigh t of Evide nce (WOE) decis i on process included both hazard and exposure cons i derat i ons as we ll as incorporation of a presumed lOX database uncertainty factor (UFos) fo r the l ack of t hi s study.
Thus, the Age n cy's level of concern in the HASPOC's WOE evaluation for inhalation exposure
risk assessment is a target MO E of 1,000 wh i ch includes th e 1 OX inter

- s pecies extrapolation,

1

OX intra-species variation, and the 1 OX UF oa

. In case of flumiclorac penty l

, all handler occupational (MOE;::: 250,000) and residentia l (MO E ;::: 2,000,000) inhalation MOEs were h igher

than the LOC of 10 00 when using an oral Point of Departure (POD). This indicates that the l ack

of an inhalation study does not reduce the overall confidence in the risk assessment or result i n

an uncertainty 

### (i.e., that study will not p r ov id e a POD sufficiently low to re sult in a risk of concern)

.



### Human Studies Review

This risk assessment r elies i n part on data from studies in which adul t human subjects were
inten tio nally exposed t o a pesticide or other chemical. These data, w hi ch i nclude studies from

the Pesticide H andlers Exposure Database Vers i on 1 .1 

### (PHED 1.1 ), the Agr i cultural Handler Exposure Task Force (AHETF) database, and t he Residential SOPs (lawns and turf) are s ubject

to ethics review pur s uan t to 40 CFR 26, have received tha t review, and are complia nt w i th

app li cable ethics requirements. F or certain studies that rev i ew may hav e included review by the

Human Studies Review Board. Descriptions o f data sources as well as gu i da nce on their use can
be found at**http: //** **www.epa.gov/pesticides/science/handler exp** **os ure** **data.h tm** **l** 

### and http: / / www

. e p a .g ov / p est i c id es / s ci e n ce/ po s t- a pp- ex po s ur e -da ta .html.

Page 2 o f33

### Page 3 of 33

Regulatory Recommendation There are no human health risks of concern identified for flumiclorac pentyl.

HED has evaluated the t olerances established for flumiclorac pentyl in 40 CFR § 180.477 and recommends no changes to tolerance levels, crop listings

, or the tolerance expression. Re

evaluation of the lives tock dietary burden confirms that no tolerances are needed for livestock commodities since flumiclorac pentyl uses may be classified under 40 CFR §180.6(a)(3); i.e., no expectation of finite residues in meat, milk, poultry or eggs.

INTRODUCTION

Flumiclorac pentyl is an N

- phenylphthalimide derivative herbicide used for the control of

broadleaf weeds. Its mode of action is through the accumulation of porphyrins in susceptible plants; the photosensitizing action of accumulated porphyrins may cause membrane lipid peroxidation which leads to irreversible damage of membrane function and structure in the plant.

T he most re cent comprehensive human health risk assessment for flumiclorac pentyl was prepared in support of the Tolerance Reassessment Eligibility Document (TRED) ( D302019

, J.

Liccione et. al., 6/28//05 ). In 2009, HED completed a Scoping Document that evaluated th e available data and risk assessments for flumiclorac pe ntyl (D3 68451 , W. Donovan et. al.

, 8 / 28 /09) and concluded that the only data needed were the standard toxicology studies required by the Revised Part 158 Toxicology Data Requirements for Conventional Pesticides. The Scoping Document also noted that the livestock dietary burden should be updated in registration

review to reflect the substantial reduction in the maximum amount of cotton gin byproducts fed

to livestock as reflected in the June 2008 update to Table 1. These topic s have been addressed in

this risk assessment.

As part of the current review, the flumiclorac pentyl risk assessment team revised the residue of concern determination for the drinking water assess ment. EFED has provided new estimated drinking water concentrations (EDWCs) for flumiclorac pentyl and these values have been incorporated into the current dietary and aggregate risk assessments.

USE INFORMATION

Flumiclorac pentyl is registered for po st

- emergence application to field corn and soybeans, as a defoliant on cotton, as a Spring burndown herbicide prior to cotton, field corn, and soybean crop

emergence , and for control of broadleaf weeds, specifically morning glory and velvet leaf, in a

vari ety of non

- crop use sites including golf courses, parks, recreational areas, residential areas, schools, Christmas tree farms, sod farms, ornamental nurseries, industrial areas, commercial areas, rights

- of

- way, and habitat restoration and maintenance areas

. Table 1 summarize s the

maximum use patterns considered in this assessment.

### Page 4 of 33

Ta ble 1 . Maximum Use Patterns for Current Uses of F lumiclorac P entyl

Product

Label (EPA Reg. No.);

Formulation Active

Ingredient (%) Use Max. Single App

. Rate (lbs a.i./A) Max.

Annual App. Rate (lbs a.i./A)

A App.

Interval (d ays ) PHI

(days) Additional

Application

Directions C

Resource (59639

- 82);

Emulsifiable

Concentrate Flumiclorac

pentyl ester ( 10.1 % by

wt. ) Field corn 0.040 0.054 14 10

- leaf stage Aerial or ground

Aerial applications may not exceed

0.054 lbs a.i./A. Do not apply by any irrigation
system.
12 hour REI

30

- day PBI Soybeans 0.081 0.11 60

Spring burndown [proposed use directions B ] 0.027 [0.081 B ] Not stated

[0.11 B ] Not stated

[7 B ] NA

Cotton 0.054 0.094 7 7

Stellar (59639

- 92);

Emulsifiable

Concentrate Flumiclorac

pentyl ester ( 7.6 % by wt. )

and lactofen (26.6% by wt.) Soybeans 0.038 0.055 14 60 Ground Do not apply by air or by any irrigation
system.
12 hour REI

30

- day PBI

Resource 80

WP (59639

- 100);

Wettable

Powder Flumiclorac

pentyl ester ( 80 % by wt. ) Corn 0.054 0.054

14 10

- leaf stage Ground Do not apply by air or by any irrigation
system.
12 hour REI

30

- day PBI Soybeans 0.081 0.11 60

V

- 10097 (59639

- 122);

Emulsifiable

Concentrate Flumiclorac

pentyl ester ( 0.576 % by

wt. ) and glyphosate (40.700% by wt.) Corn 0.014 0.028 14 10

- leaf stage Aerial or ground Do not apply by any irrigation

system. Cut stump treatments may be made on any site

listed on this label. Do not apply directly to or over ornamentals.

12 hour REI

30

- day PBI Soybeans 0.042 0.042 60

Spring burndown [proposed use directions B ] 0.028 Not stated [0.056 B ] Not stated

[7 B ] NA

Golf courses, parks, recreational areas, residential areas, schools,

Christmas tree farms, sod farms, ornamental nurseries, industrial areas, commercial areas, rights

of

- way, habitat restoration

and maintenance areas [proposed use directions B ] 0.028 Not stated [0.056 B ] Not stated

[7 B ] NA

A Labels provide seasonal application rate limits that approximate annual limits

. B Proposed [bracketed and footnoted] label directions are intended for the next stamped label. The current label

directions are not bracketed.

C REI = Re

- entry Interval; PBI = Plant

- back Interval.

### Page 5 of 33

HAZARD CONSIDERATIONS

Available studies for flumiclorac

- pentyl include: 1) subchronic oral toxicity stud y in the rat , 2) chronic/carcinogenicity studies in rats and mice

, 3) subchronic and chronic oral t oxicity studies in the dog , 4) developmental a nd reproduct ion studies in rats, 5) a developmental study in

rabbits , 6) acute neurotoxicity and subchronic neurotoxicity studies in the rat, 7) an immunotoxicity study, 8) a 21

- day dermal study in the rat, 9) acute “six

- pack” studies, 10)

several metabolism studies in the rat, and 11) a mutagenicity battery.

The toxicological database for flumiclorac pentyl is considered complete for characterization of potential developmental, reproductive, carcinogenetic, mutagenic, neurotoxic, and immunotoxic

effects.

Toxicit y in the dogs was manifested as significant decreases in body weight (males) and alterations in activated partial thromboplastin time (females), a measurement of clotting time in the plasma. Prolongation of activated partial thromboplastin time was noted in female dogs administered 1000 mg/kg/day for 90 days or for 1 year. Long

- term administration of flumiclorac at high doses to female rats resulted in urinary incontinence, increased water consumption, increased urine volume and increased kidney weights. Male rats treated with high doses displayed increased squamous epithelial cells in urinary se diment, increased urine volume and increased kidney weights.

N o dermal or systemic toxicity was observed in rats in the 21/28 day dermal toxicity up to the

lim it dose (1000 mg/kg/day).

There is no concern for increased quantitative or qualitative susceptibility of the young following

in utero (rats and rabbits) and pre

- and post

- natal exposure (rats) to flumiclorac pentyl . Also, there is no evidence of developmental toxicity, reproductive toxicity, neurotoxicity, or immunotoxicity at dose levels that do not exceed the limit dose. The Food Quality Protection Act (FQPA) safety factor has been reduced to 1X.

Flumiclorac pe ntyl is negative for carcinogenicity in rats and mice, and it did not show any genotoxic potential (classified as not likely to be carcinogenic to humans ).

Flumiclorac pentyl has low acute toxicity with no deaths occurring near the limit dose in oral,

in halation, and dermal studies. Clinical signs of toxicity suggestive of irritation were observed only in animals treated by inhalation. The chemical caused slight eye irritation, which cleared

after 24 hours. It is a dermal sensitizer.

Flumiclorac penty l metabolism in the rat shows low tissue accumulation (highest in blood, plasma, and kidney), rapid excretion in urine and feces, and extensive metabolic transformation consisting of (1) cleavage of the ester linkage, (2) cleavage of the imide bond, (3) hy droxylation, and (4) sulfonation.

An acute reference dose (aRfD) was not established, since an endpoint attributable to a single exposure was not identified from the available database. A chronic reference dose (cRfD) of 1.0

### Page 6 of 33

mg/kg/day was established f or flumiclorac pentyl based on the NOAEL of 100 mg/kg/day in the chronic dog study and an uncertainty factor of 100 (10X for interspecies extrapolation and 10X for intraspecies variation). Decreased body weight gain in males, and increased clotting time (males and females), and increased globulin levels and alpha

- 2 fraction of the serum protein electrophoresis occurred in this study at the LOAEL of 1000 mg/kg/day.

The flumiclorac pentyl toxicity profile tables are included in this memo in Appendix A. The toxicity endpoints for risk assessment are shown in Table s 2 and 3.

Table 2 . Toxicological Doses and Endpoints for F lumiclorac

- Pentyl for Use in Dietary and Non

- Occupational

Human Health Risk Assessments

Exposure/

Scenario Point of Departure Uncertainty/FQP A Safety Factors RfD, PAD, Level of

Concern for Risk

Assessment Study and Toxicological

Effects

Acute Dietary (General population) No appropriate endpoint identified for this population.

Acute Dietary (Females 13

- 49 years of age) No appropriate endpoint identified for this population.

Chronic Dietary (All Populations) NOAEL= 100

mg/kg/day Total UF: 100X

UF A = 10x

UF H =10x FQPA SF=1x Chronic RfD = 1.0

mg/kg/day

cPAD

= 1.0 mg/kg/day Chronic Dog

LOAEL = 1000 mg/kg/day

based on decreased body weight gain (males), increased clotting time (males and females), and increased globulin levels and increased alpha

- 2 fraction of the serum protein electrophoresis (females)

Incidental Oral ( all durations ) NOAEL= 100

mg/kg/day Total UF: 100X

UF A = 10x

UF H =10x FQPA SF=1x Chronic RfD = 1.0

mg/kg/day

cPAD

= 1.0 mg/kg/day Chronic Dog

LOAEL = 1000 mg/kg/day based on decreased body weight gain (males), increased clotting time (males and females), and increased globulin levels and increased alpha

- 2 fraction of the serum protein electrophoresis (females)

Dermal ( all durations) No hazard quantitation is required for any duration. No systemic effects were observed in the 21

- day

dermal rat study at dose levels up to 1000 mg/kg/day. There are no developmental or reproductive toxicity concerns. There are no long

- term dermal exposures to flumiclorac pentyl in humans.

### Page 7 of 33

Table 2 . Toxicological Doses and Endpoints for F lumiclorac

- Pentyl for Use in Dietary and Non

- Occupational

Human Health Risk Assessments

Exposure/

Scenario Point of Departure Uncertainty/FQP A Safety Factors RfD, PAD, Level of

Concern for Risk

Assessment Study and Toxicological

Effects

Inhalation ( all

duration s) NOAEL= 100

mg/kg/day Total UF: 100X

UF A = 10x

UF H =10x FQPA SF=1x Chronic RfD = 1.0

mg/kg/day

cPAD

= 1.0 mg/kg/day Chronic Dog

LOAEL = 1000 mg/kg/day based on decreased body weight gain (males), increased clotting time (males and females), and increased globulin levels and increased alpha

- 2 fraction of the serum protein electrophoresis (females) Cancer (oral, dermal, inhalation) Classification: “Not likely to be carcinogenic to humans.”

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 with 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). U F H = potential variation in sensitivity among members of the human population (intraspecies). PAD = population adjusted dose (a = acute, c = chronic). RfD = reference dose.

Table 3. Summary of Toxicological Doses and Endpoints for Flumiclorac

- Pentyl 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 ( all durations) No hazard quantitation is required for any duration. No systemic effects were observed in the

21

- day dermal rat study at dose levels up to 1000 mg/kg/day. There are no developmental or reproductive toxicity concerns. There are no long

- term dermal exposures to flumiclorac pentyl

in humans.

Inhalation (all durations) NOAEL=

100 mg/kg/day

(100% absorption assumed) UF A =10x

UF H =10x Occupational

LOC for MOE =

100 Chronic Dog

LOAEL = 1000 mg/kg/day based on decreased body weight gain (males), increased clotting time (males and females), and increased globulin levels and increased alpha

- 2 fraction of the serum protein electrophoresis (females) Cancer (oral, dermal, inhalation) Classification: Not likely to be carcinogenic to human s. The cRfD is considered protective of

potential cancer effects.

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). DAF = dermal absorption factor. MOE = margin of exposure. LOC = level of concern.

### Page 8 of 33

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, neurotoxicit y, 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 maturatio n, fertility, pregnancy rates, reproductive loss, and sex ratios in offspring. For ecological hazard assessments, EPA evaluates acute tests and chronic studies that assess growth, developmental and reproductive effects in different taxonomic groups. As par t of its reregistration decision for flumiclorac pentyl , 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), flumiclorac p entyl 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 wil dlife 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 batt ery of 11 screening assays to identify the potential of a chemical substance to interact with the estrogen, androgen, 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 cause d by the substance, and

establish a dose

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

Under 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 ingredients. A second list of chemicals identified for EDSP screening was published on June 14, 2013 1 

### and includes some pesticides scheduled for registrati on review and chemicals found in water. Neither of these lists should be construed as a list of known or likely endocrine disruptors.

METABOLISM CONSIDERATIONS

The 2005 TRED identified parent flumiclorac pentyl as the only residue of concern in plants and livestock. For drinking water the residue of concern was flumiclorac pentyl and IMCA. The flumiclorac pentyl risk assessment team has confirmed the earlier decision for plants and

livestock. However , as detailed recently (D417544, W. Donovan and J. Liccione, 27

- JAN

2014), in consultation with EFED, the residue of concern for drinking water has been expanded to include the following: flumiclorac pentyl, IMCA, 031

- HA, IMCA

- HA, IMFP, IMFP

- HA, and

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

- HQ

- OPPT

- 2009

- 0477

- 0074 for the final second list of

chemicals.

### Page 9 of 33

SAT IMFP

- HA (Appendix E). The decision to include the a dditional degradates was based on the structural similarity to the parent compound and the relative abundance of these compounds

found in soil and water studies. Table 4 summaries the residues of concern selected for flumiclorac pentyl.

Table 4

. Summary of Metabolites and Degradates to be included in the Risk

Assessment and Tolerance Expression

Matrix Residues included in Risk Assessment Residues included in

Tolerance E xpression

Plants Flumiclorac pentyl Flumiclorac pentyl

Livestock Flumiclorac pentyl Flumiclorac pentyl

Drinking

Water F lumiclorac pentyl

, IMCA

, 031

- HA, IMCA

- HA,

IMFP, IMFP

- HA, and SAT IMFP

- HA Not Applicable



### RESIDUE CHEMISTRY CONSIDERATIONS

The f lumiclorac pentyl residue chemistry database is complete

. The nature and magnitude of the residue in plants has been adequately delineated. The residue of concern in plants and livestock is the parent compound only. Adequate storage stability, method validation data and processing

studies have been submitted. An a dequate GC/NPD ( Gas C hromatography /Nitrogen

- Phosphorus

Detector ) analytical method , which has undergone suc c es s ful independent laboratory validation (ILV) and successful EPA/BEAD validation, is available to enforce the established tolerances. The stability of flumiclorac pentyl in frozen storage is matrix dependent, with stability to two years in soybean, 30

- 45 days in corn, and 2

- 4 months in cotton matrices. Processing studies for corn, soybean, and cotton indicate residue concentration in so ybean hulls as reflected by the 0.02 ppm tolerance level for this processed commodity. Confined rotational crop studies showed low

levels o f residue uptake supporting a 30

- day plant back interval (PBI) for unlabeled crops.

The 2009 flumiclorac pentyl scoping document note d that all residue chemistry data requirements had been met and that the livestock dietary burden should be updated in registration review to reflect the reduced usage of cotton gin byproducts as a feedstuff. Appendix D presents

the updated dietary burden calculations for flumiclorac pentyl based on current procedures. The

maximum diet ary burden to cattle is now 0.044 ppm, which is significantly less than the previous

value of 0.7 3 ppm. Thus

, the previous conclusion that there is no reasonable expectation of

finite residues in livestock commodities is s trengthen ed w hen using current procedures. Since 2009, no new crop uses have been requested fo r flumiclorac pentyl; accordingly , the residue chemistry database for flumiclorac pentyl remains complete.

### Page 10 of 33

No CODEX or Canadian MRLs have been set for flumiclorac pentyl (Appendix C) . As a result, no international harmonization issues are expected.



## Water Residue Profile

Environmentally, flumiclorac pentyl has very low water solubility and is expected to degrade quickly through multiple fate processes (with half

- lives of hours to several days) under

environmental conditions. T here are no monitoring data available, thus drinking water concentrations were estimated using models.

The fl umiclorac pentyl residues of concern (ROC) in drinking water include the parent compound and the six major degradates with an intact imido/carboxamido bridge: flumiclorac acid (IMCA) , 031

- HA, IMCA

- HA, IMFP, IMFP

- HA, and SAT IMFP

- HA (USEPA, 2014).

EFED mad e use of the Total Residues of Concern (TRC) modeling approach to estimate aquatic exposure with the ROC half

- lives, the soil mobility of flumiclorac acid, and the physical/chemical properties of flumiclorac pentyl (D414425, G. Orrick, 04

- MAR

- 2014)

. The

T RC approach was selected because there are multiple degradates of concern, none of which have a full environmental fate data profile.

S urface and ground water EDWCs for use in the human health risk assessment for flumiclorac pentyl are shown in Table 5

. The surface water EDWCs are recommended for use in the dietary assessments since these values are protective for potential ground water residue levels. Thus, the

recommended acute EDWC is 9.0 ppb and the chronic EDWC is 1.3 ppb , as indicated by Tier 1

c omputer modeling results.

Table 5

. Summary of Estimated Surface Water and Ground W ater Concentrations for F lumiclorac pentyl

Scenario Surface Water Conc., ppb a 

### Ground W ater Conc., ppb b



### Acute 9.0 0.5

Chronic (non

- cancer) 1.3 0.45

a 

### From the Tier I FIRST model ( Soybeans ( 0.11 lbs a.i./A) )

b 

### From the Tier I PRZM

- GW model ( Soybeans ( 0.11 lbs a.i./A ) ) [acute] and Tier I SCI

- GROW model [chronic]

Highest value for use in risk assessment is in bolded



## Dietary Risk Assessment

A chronic aggregate dietary food and drinking water exposure and risk assessment was conducted using the Dietary Exposure Evaluation Model software with the Food Commodity Intake Database (DEEM

- FCID) Version 3.16. This software uses 2003

- 2008 food consump tion data from the U.S. Department of Agriculture’s (USDA’s) National Health and Nutrition Examination Survey, What We Eat in America, (NHANES/WWEIA).

### Page 11 of 33

No acute dietary exposure and risk analysis was performed since there were no appropriate

studies iden tified in the toxicology database that demonstrated evidence of toxicity attributable to a single dose. The chronic dietary exposure and risk analysis was based on tolerance

- level residues, 100% crop treated assumptions , and default processing factors (1 for all commodities

except field corn syrup/syrup

- babyfood where 1.5 was used)

. Estimates of residues in drinking water were directly incorporated in the assessm ents

. Using conservative assumptions, the chronic dietary risk estimates were < 1% of the chronic population adjusted dose (cPAD) for all population subgroups (see Table 6). Generally, HED is concerned when dietary risk estimates exceed 100% of the PAD; therefore, the chronic dietary risk estimates for flumiclor ac pentyl are below HED’s level of concern (LOC) for all population subgroups, including those comprised of

infants and children.

Table 6 . Summary of Estimated Dietary (Food + Drinking Water) Exposures and Risk for Flumiclorac pentyl



### Population Subgroup cPAD, mg/kg/day 

### Chronic Estimates

Dietary Exposure (mg/kg/day) % cPAD U.S. Population

1 0.000057 <1 All infants (< 1 year old ) * 0.000123 <1

Children 1

- 2 yrs old 0.000107 <1

Children 3

- 5 yrs old 0.000103 <1

Children 6

- 12 yrs old 0.000075 <1

Youth 13

- 19 yrs old 0.000054 <1

Adults 20

- 49 yrs old 0.000053 <1

Adults 50

- 99 yrs old 0.000043 <1

Females 13

- 49 yrs old 0.000051 <1
*The subpopulation with the highest risk estimates

.



### Residential (Non

- Occupational) Exposure/Risk Characterization

F lumiclorac pentyl may be applied in residential settings (EPA Reg. No. 059639

- 122 ) . HED determined that adults and children (toddlers) could potentially be exposed to flumiclorac pentyl based on occupational use in the following use sit es: golf courses, parks, recreational areas, lawns and turf, on ornamental plants and school grounds. No dermal or inhalation assessment was conducted since no dermal endpoint was selected and outdoor postapplication inhalation exposure is anticipated to be negligible. A residential handler assessment has been included to cover the possibility of non

- occupational applications around residential premises since the product is not a restricted use product. The residential handler and residential post

- applic ation exposure assessments have been conducted according to HED’s 2012 Residential Standard Operating Procedures (SOPs) 2



### .


## Residential Handler Exposure

The registered uses of flumiclorac pentyl on turf and ornamentals may result in residential

handler ex posure. Residential handler exposure is expected to be short

- term in duration as

2 Available: http://www.epa.gov/pesticides/science/residential

- exposure

- sop.html

### Page 12 of 33

intermediate

- or long

- term exposures are not likely because of the intermittent nature of applications by homeowners. Residential handlers are assumed to be wearing short

- sl eeved shirts, short pants, shoes and socks during application of flumiclorac pentyl ( i.e., no protective equipment). The assessments were conducted assuming the maximum application rate (0. 028 lbs ai/acre, 0.00 56 lbs ai/gallon) and used unit exposure values and estimates for area treated or amount handled along with algorithms taken from HED’s 2012 Residential SOPs.

The quantitative exposure/risk assessment developed for residential handlers is based on the following scenarios:

 Mixing/Loading/Applying Liquid to turf and ornamentals with Hose

- End Sprayer

 Mixing/Loading/Applying Liquid to turf and ornamentals with Manually

- pressurized

handwand

 Mixing/Loading/Applying Liquid to turf and ornamentals with Backpack

 Mixing/Loading/Apply ing Liquid to turf and ornamentals with a Sprinkler Can

Since no dermal hazard was identified for flumiclorac pentyl in the toxicological database, only quantitative inhalation exposure assessments were conducted for residential handlers. Inhalation

marg ins of exposure (MOEs) are above the LOC of 100 for all scenarios assessed and are not of concern (MOEs ≥ 100). Short

- term inhalation residential handler estimated exposure and risk

estimates are shown in Table 7 below.

Table 7 . Short

- Term Residential Handler Non

- cancer Exposure and Risk Estimates for Flumiclorac pentyl

Exposure Scenario Level of

Concern Inhalation

Unit Exposure (mg/lb ai) Maximum

Application

Rate 1 (lbs ai/gallon or lb ai/A ) Area Treated

or Amount

Handled Daily 2 (gallons or A ) Inhalation

Dose (mg/kg/day) 3 MOE 4

Mixer/Loader/Applicator Manually

- pressurized

handwand

100 0.018 0.0056 5 gal

. 0.0000063 16,000,000

Hose

- end Sprayer 0.0014 0.028 lb ai/A 0.5 A 0.0000039 26,000,000 Backpack 0.14 0.0056 5 gal

. 0.000049 2 ,000,000

Sprinkler can 0.0 22 0.028 lb ai/A 0.023 A ( 1000 ft 2 ) 0.0000 0018 570 ,000,000

1 Based on registered label s. 2 Based on HED’s 2012 Residential SOPs

3 Inhalation Dose = Inhalation Unit Exposure (mg/lb ai) × Application Rate (lb ai/acre or gal) × Area Treated or Amount Handled (A/day or gallons/day) ÷ BW (80 kg)

4 Inhalation MOE = Inhalation NOAEL ( 100 mg/kg/day) ÷ Inhalation Dose (mg/kg/day)



## Post

- Application Exposure

There is the potential for post

- application exposure for indiv iduals exposed as a result of being in an environment that has been previously treated with flumiclorac pentyl. The quantitative exposure/risk assessment for residential post

- application exposures i nclude s the following

scenario:

 Incidental ingestion (i.e., hand

- to

- mouth, object

- to

- mouth, soil ingestion exposure) from

contact with treated turf

### Page 13 of 33

Residential Post

- application Exposure for Turf Use

Residential Post

- application Exposure Data and Assumptions for Turf Use A series of assumptions and exp osure factors served as the basis for completing the residential

post

- application risk assessment. Each assumption and factor is detailed in the 2012 Residential

SOPs 2



### .

Chemical

- specific TTR Data

There is no chemical specific TTR data available for flum iclorac pentyl.

Combining Exposure and Risk Estimates

There is n o potential hazard via the dermal route f or flumiclorac pentyl. Only incidental oral risk

estimate s were quantitatively assessed

. The incidental oral scenarios (i.e., hand

- to

- mouth and object

- to

- mouth) should be considered inter

- related and it is likely that they occur interspersed

amongst each other across time. Combining these scenarios would be overly

- conservative

because of the conservative nature of each individual assessment.

Summary of Residential Post

- application Non

- Cancer Exposure and Risk Estimates for Turf Use The residential post

- application risk estimates are not of concern for flumiclorac pentyl (MOEs are greater than the level of concern of 100) for all incidental or al scenarios.

Table 8

. Residential Post

- application Non

- cancer Exposure and Risk Estimates for F lumiclorac pentyl

Lifestage Post

- application Exposure

Scenario Application

Rate (lb ai/A) 1 Dose

(mg/kg/day) 2 MOEs 3 Combined

Routes Combined

MOEs Use Site Route of Exposure

1 to <2 years Turf Hand

- to

- Mouth

0.028 0.0004 2 5 0,000

NA NA Object

- to

- Mouth 0.000001 7,700,000
Soil Ingestion 0.00000095 110,000,000

1 Based on registered label

. 2 Dose equations can be found in Appendix F

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



## Residential Risk Estimates for Use in Aggregate Assessment

Table 9 shows the residential risk estimates that are recommended for use in the aggregate

assessment for flumiclorac pentyl

.

 The recommended residential exposure for use in the adult (male and female) aggregate assessment reflects inhalation exposure from mixing/loading/applying the liquid flumiclorac pentyl formulation with a backpack sprayer.

 The recommended residential exposure for use in the children aggregate assessment reflects oral exposure from hand

- to

- mouth activity on turf.

### Page 14 of 33

Table 9 . Recommendation for the Short

- Term Residential Exposures for the Flumiclorac pentyl Aggregate

Assessme nt 1

Lifestage Residential Dose (mg/kg/day) 2 MOE 3

Dermal Oral Inhalation Total Dermal Oral Inhalation Total

Short

- Term

Adult Handler N/A NA 0.000049 0.000049 N/A NA 2,000,000 2,000,000

Children 1

- 2 NA 0.0004 NA 0.0004 NA 250,000 NA 250,000

1 Bolded risk estimates should contribute to the residential exposure portion of the aggregate assessment.

2 Residential Dose = the highest dose for each applicable lifestage of all scenarios assessed from Tables 7 and 8. Total = dermal + oral +

inhalation

. 3 Residential MOE = the MOEs associated with the h ighest doses identified in Tables 7 and 8. . Total = 1 ÷ (1/Dermal MOE) + (1/Inhalation MOE) + (1/Oral MOE ) )

. 

## Residential Bystander Post

- application Inhalation Exposure

Based on the Agency's current practices, a quantitative post

- application inhalation exposure assessment was not performed for flumiclorac pentyl at this time primarily because of the low acute inhalation toxicity (Toxicity Category IV), low vapor pressure ( 1 x 10

- 7 

### mm Hg @ 22.4 oC), and the low registered use rate (0. 081 lb ai/A). However, volatilization of pesticides may be a source of post

- application inhalation exposure to individuals nearby pesticide applications. The Agency sought expert advice and input on issues related to volatilization of pesticides from its Federal Insecticide, Fungicide, and Rodenticide Act Scientific Advisory Panel (SAP) in December 2009, and received the SAP’s final report on March 2, 2010 3 

### . The Agency is in the process of e valuating the SAP report and may, as appropriate, develop policies and procedures to identify the need for and, subsequently, the way to incorporate post

- application inhalation exposure into the Agency's risk assessments. If new policies or procedures are developed, the Agency may revisit the need for a quantitative post

- application inhalation exposure assessment

for flumiclorac pentyl



## Spray Drift

Spray drift is always a potential source of exposure to residents nearby to spraying operations. This is par ticularly the case with aerial application, but, to a lesser extent, could also be a potential source of exposure from the ground application method employed for flumiclorac pentyl

. The Agency has been working with the Spray Drift Task Force, EPA Regional Offices and State Lead Agencies for pesticide regulation and other parties to develop the best spray drift management practices (see the Agency’s Spray Drift website for more information 4 

### ). The Agency has completed its evaluation of the new database submi tted by the Spray Drift Task Force, a membership of U.S. pesticide registrants, and is developing a policy on how to appropriately apply the data and the AgDRIFT computer model to its risk assessments for pesticides applied by air, orchard airblast and gro und hydraulic methods. After the policy is in place, the Agency may impose further refinements in spray drift management practices to reduce

off

- target drift with specific products with significant risk estimates associated with drift.

It is noted that t he 0.028 lb ai/acre application rate for turf was modeled to estimate post

application residential exposure of toddlers. As this rate is similar to the agricultural application

3 Available: http://www.epa.gov/scipoly/SAP/meetings/2009/120 109meeting.html

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

### Page 15 of 33

rates, this scenario is protective of any exposure of farm children via spray drift from agricultural flumiclorac pentyl applications.

Aggregate Exposure/Risk Characterization

In accordance with the FQPA, HED must aggregate pesticide exposures and risks from three major sources: food, drinking water, and residential exposures. In an aggregate assessment, exposures from relevant sources are added together and compared to quantitative estimates of hazard (e.g., a NOAEL or PAD), or the risks themselves can be aggregated. When aggregating exposures and risks from various sources, HED considers both the route and duration of exposure. For flumiclorac pentyl , potential exposures from food, drinking water, and residential scenarios were aggregated. This assess ment incorporates the changes in the new Residential SOPs implemented in January of 2012.



## Acute Aggregate Risk

An acute aggregate risk assessment is not required for flumiclorac pentyl as no toxic effects attributable to a single dose were identified.



## Short

- Term Aggregate Risk

There is a potential for short

- term exposure to flumiclorac pentyl via dietary and residential exposure pathways. To estimate short

- term aggregate risk, HED therefore combined chronic dietary (food and water) exposures (as a measure of average background dietary exposure) with

short

- term residential exposures. These pathways lead to exposure via oral and inhalation routes only, since no dermal hazard has been identified for flumiclorac pentyl

The most conservative residential exposure scenario was chosen for the adult population which reflects inhalation exposure from mixing/loading/applying the liquid flumiclorac pentyl

formu lation with a backpack sprayer

. For background dietary exposure, the adult sub

- population with the highest exposure , adults 20

- 49 years old

, was chosen since this is protective for all other

adult sub

- populations. There is potential for residential exposure to children through several

post

- application scenarios following turf treatment. Calculated h and

- to

- mouth activity provides the highest exposure and dose estimate for children 1

- 2 years old, so this exposure scenario was aggregated with background dietary exposure to assess short

- term aggregate risk to children.

Shor t

- term aggregate margins of exposure for adults and children are above the LOC of 100 and are not of concern (MOEs ≥ 100). Short

- term estimated exposures and risks are shown below in

Table 10

.

### Page 16 of 33

Table 10 . Short

- Term Aggregate Risk Calculations

Populati on Short

- Term Scenario

NOAEL mg/kg/day LOC 1 Max

Allowable Exposure 2 mg/kg/day Average

Food and

Water Exposure 3 mg/kg/day Residential

Exposure 4 mg/kg/day Total

Exposure 5 mg/kg/day Aggregate

MOE (food, water, and residential) 6

Adult 20

- 49 100 100 1 0.000053 0 .000 0 49 0.00 0 102 9 8 0,000

Children 1

- 2 100 100 1 0.000107 0.0004 0.000507 200,000

1 Intraspecies factor= 10x; Interspecies factor = 10x

2 Maximum Allowable Exposure (mg/kg/day) = NOAEL ( 100 mg/kg/day)/LOC (100)

3 Average food and water exposure for adults = chronic dietary exposure for adults 20

- 49 (the highest exposed adult

sub

- population) ; for children = chronic dietary exposure for children 1

- 2 years old , since all infants are assumed to have negligible residenti al postapplication exposure to residues following turf applications

. See Table 6.

4 Residential Exposure = Inhalation exposure for adults; oral exposure for children. See Table 9

. 5 Total Exposure = Avg Food & Water Exposure + Residentia l Exposure)

6 Aggregate MOE = NOAEL / (Avg Food & Water E xposure + Residential Exposure)



## Chronic Aggregate Risk

As there are no uses that are expected to result in long

- term residential exposure, long

- term (chronic) aggregate risk includes only chronic dietary (food a nd water) exposure. As noted previously , there are no chronic dietary risks of concern for flumiclorac pentyl

.

Cumulative Exposure/Risk Characterization

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

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

to flumiclorac pentyl and any other substances and flumiclorac pentyl does not appear to produce a toxic metabolite produced by other substances. For the purposes of this action, therefore, EPA has not assumed that flumiclorac pentyl has a common mechanism of toxicity with other substances. For information regarding EPA’s efforts to determine which chemicals have a common mechanism of toxicity and to evaluate the cumulative effect s of such chemicals, see the policy statements released by EPA’s Office of Pesticide Programs concerning common mechanism determinations and procedures for cumulating effects from substances found to have a common mechanism on EPA’s website at http://www.e pa.gov/pesticides/cumulative/.

Occupational Exposure/Risk Characterization

An occupational exposure and risk assessment was conducted to support the registered uses of flumiclorac pentyl

.



## Short

- /Intermediate

- Term Handler Risk

Flumiclorac pentyl is an N

- phenylphthalimide derivative herbicide used for the control of

broadleaf weeds. Application methods, maximum application rates and use sites were summarized previously in Table 1

. The occupational exposure and risk assessment generally

addresses risks to workers exposed in an occupational setting via the dermal and inhalation routes of exposure. However, since no dermal hazard was identified in the toxicity database for

### Page 17 of 33

flumiclorac pentyl , a quantitative dermal assessment is not required and risks were quantitatively assessed for inhalation exposure only. Based on the registered use pattern of flumiclorac pentyl

, short

- and intermediate

- term exposures are anticipated

. Long

- term exposure is not expected for

the registered use patterns.

Estimates of inhalation exposure were calculated for various levels of personal protective equipment (PPE). Results are presented for “baseline” level of attire defined as a single layer of clothing consisting of a long sleeved shirt, long pants, shoes plus socks, no protective gloves, and no respirator , as well as closed system ( i.e. , engineering control)

. For aerial applicators, closed cockpit was assessed (i.e., engineering control). Wettable powder formulation is packaged in water soluble bags (i.e., engineering control). The flumiclorac pentyl product labels direct mixers, loaders, applicators and other handlers to wear long

- sleeved shirts, long pants, protective eyewear, chemical

- resistant gloves, and shoes plus socks.

All application equipment must use lock and load engineering controls. All wettable powder formulations must be packaged in water soluble bags. Closed cabs are required for all ground equipment.

All occupational handler scenarios assessed for the regist ered uses of flumiclorac pentyl resulted in estimated inhalation margins of exposure (MOEs) above the LOC of 100 for all scenarios assessed and, therefore, are not of concern (MOEs ≥100). Occupational handler risk

estimates are shown in Table 11.

### Page 18 of 33

T able 1 1. Occupational Handler Non

- Cancer Exposure and Risk Estimates for Flumiclorac Pentyl.

Exposure

Scenario Crop or Target Inhalation Unit Exposure
(μg/lb ai) 1 Maximum

Application

Rate 2 Area

Treated

or Amount

Handled Daily 3 Inhalation

Baseline Dose (mg/kg/day) 4 MOE 5

Mixer/Loader

Aerial Corn, Cotton 0.219 0.054 lb ai/acre 1200 0.000178 560,000

Soybeans 0.081lb ai/acre 0.000266 380,000

Sod 0.028 lb ai/acre 350 0.0000269 3,700,000

Corn, Cotton 0.24 (WP in

WSB) 0.054 lb ai/acre 1200 0.000195 510,000
Soybeans 0.081lb ai/acre 0.000291 340

, 000

Groundboom Corn, Cotton 0.219 0.054 lb ai/acre 200 0.0000296 3,400,000

Soybeans 0.081lb ai/acre 0.0000444 2,300,000

Sod 0.028 lb ai/acre 80 0.00000614 16,000,000

Corn, Cotton 0.24

(WP in WSB) 0.054 lb ai/acre 200 0.0000324 3,100,000
Soybeans 0.081lb ai/acre 0.0000486 2

, 100

, 000

Chemigation Corn, Cotton 0.219 0.054 lb ai/acre

350 0.0000518 1,900,000

Soybeans 0.081lb ai/acre 0.0000776 1,300,000

Sod 0.028 lb ai/acre 0.0000269 3,700,000

Corn, Cotton 0.24

(WP in WSB) 0.054 lb ai/acre 0.0000568 1,800,000
Soybeans 0.081lb ai/acre 0.000085 1,200,000
Applicator

Aerial Corn, Cotton 0.0049 0.054 lb ai/acre 1200 0.0000 04 2

, 5 00,000

Soybeans 0.081lb ai/acre 0.0000 0 6 1 7

, 0 00,000

Sod 0.028 lb ai/acre 350 0.00000 06 1 70 ,0 00,000

Groundboom Corn, Cotton

0.043 0.054 lb ai/acre 200 0.0000459 2,200,000

Soybeans 0.081lb ai/acre 0.0000689 1,500,000

Sod 0.028 lb ai/acre 80 0.00000953 10,000,000 Flagger
Flagger All crops 0.35 0. 081 lb ai/acre 350 0.000124 810,000
Mixer/Loader/Applicator
Backpack (broadcast foliar) Ornamentals and turf 140

0.00 56 lb ai/gal 40 gals 0.000393 250,000

Manually

pressurized

Handwand (broadcast foliar) Ornamentals and turf 30 40 gals 0.000084 1,200,000

Mechanically

pressurized Handgun (broadcast foliar) Ornamentals and turf 3.9 1000 gals 0.000273 370,000

1 Based on the “Occupational Pesticide Handler Unit Exposure Surrogate Reference Table” (September 2012); Level of mitigation: Baseline.

2 Based on registered label (Reg. No. 59639

- 122 , 59639

- 100 and 59639

- 82 VALENTV

- 10097TM HERBICIDE ).

3 Exposure Science Advisory Council Policy #9.1.

4 Inhalation Dose = Dermal Unit Exposure (μg/lb ai) × Conversion Factor (0.001 mg/μg) × Applica tion Rate (lb ai/acre or gal) × Area Treated or Amount Handled Daily (A or gal/day) ÷ BW (kg) (see appendix F)

.

### Page 19 of 33

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



## Short

- /Intermediate

- Term Post

- Application Risk

Dermal Post

- appl ication Risk

There is the potential for post

- application exposure to workers as a result of registered uses of flumiclorac pentyl . However, since no dermal hazard was identified in the toxicity database for flumiclorac pentyl , a quantitative occupational post

- application dermal risk assessment was not completed.

Inhalation Post

- application Risk

Based on the Agency's current practices, a quantitative post

- application inhalation exposure assessment was not performed for flumiclorac pentyl at this time prim arily because of the low acute inhalation toxicity (Toxicity Category IV), low vapor pressure ( < 1 x 10

- 7 

### mm Hg @ 22.4 oC), and the low registered use rate (0. 081 lb ai/A). However, there are multiple potential sources of post

- application inhalation expos ure to individuals performing post

- application activities in previously treated fields. These potential sources include volatilization of pesticides and resuspension of dusts and/or particulates that contain pesticides. The Agency sought expert

advice an d input on issues related to volatilization of pesticides from its Federal Insecticide, Fungicide, and Rodenticide Act Scientific Advisory Panel (SAP) in December 2009, and received the SAP’s final report on March 2, 2010 5 

### . The Agency is in the process of evaluating the SAP report as well as available post

- application inhalation exposure data generated by the ARTF and may, as appropriate, develop policies and procedures, to identify the need for and, subsequently, the way to incorporate occupational post

- ap plication inhalation exposure into the Agency's risk assessments. If new policies or procedures are put into place, the Agency may revisit the need for a quantitative occupational post

- application inhalation exposure assessment

for flumiclorac pentyl

.

A lthough a quantitative occupational post

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

- application exposure. Therefore, it is expected that these handler inhalation exposure estimates would be protective of most occupational post

- application inhalation exposure scenarios. Inhalation risks f or handlers were not of concern.

Additionally, the Worker Protection Standard (WPS) for Agricultural Pesticides contains requirements for protecting workers from inhalation exposures during and after greenhouse applications through the use of ventilation requirements [40 CFR 170.110, (3) (Restrictions associated with pesticide applications)]. It is assumed that the user will have met the ventilation requirement within the 12 hour REI (unless there is no ventilation capability, then the user must

wait 24 hours). It is reasonable to assume that based on the WPS ventilation requirements, postapplication inhalation exposure will be negligible.

5 Available: http://w ww.epa.gov/scipoly/SAP/meetings/2009/120109meeting.html

### Page 20 of 33

References

Author Barcode Date Title

U. Habiba TXR No.

00 56913 3/20 /2014 Flumiclorac pentyl: Summary of Hazard and Science Policy Council (HASPOC) Meeting of February 27, 2014:

R ecommendations on the Need for a Subchronic Inhalation Toxicity Study.

S. Tadayon D4 18485 3/16 /2014 Flumiclorac pentyl . Chronic Aggregate Dietary (Food and Drinking Water) Exposure and Risk Assessment in Support of Registration Review.

G. Orrick D414245 3/4/2014 Flumiclorac

- pentyl: Drinking Water Exposure Assessment for Registration Review

W. Donovan

and J.

Liccione D417544 1/24/2014 Flumiclorac Pentyl. Recommendation for the Residue of Concern in Drinking Water.

W. Donovan

et. al. D3 68451 8/28 /2009 Flumiclorac Pentyl: Revised Human Health Assessment Scoping Document in Support of Registration Review.

W. Donovan D365080 6/10/2009 Flumiclorac Pentyl. Poultry Metabolism Study Sample Storage Information Submitted In Response to a Condition of Registration.

M. Hawkins

and J.

Cordova -- 5/7/2009 Updated Review of Flumiclorac Incident Reports

J. Liccione et

al. D302019 6/28/2005 Flumiclorac Pentyl: HED Chapter of the Tolerance Reassessment Eligibility Decision Document (TRED).

W. Donovan D308674 6/24/2005 Flumiclorac Pentyl: Summary of Residue Chemistry Data for the Tolerance Reassessment Eligibility Decision (TRED)

Document and a Petition (PP#3F6767) for the Establishment of

Tolerances on Cotton.

W. Donovan D302003 6/24/2005 Flumiclorac Pentyl Tolerance Reassessment Eligibility Decision (TRED). Product Chemistry Considerations. R. Travaglini D301998 6/9/2005 Residential Exposure Assessment for the Tolerance Reassessment Eligibility Decision (TRED) Document for

Flumiclorac

- pentyl. R. Loranger

-- 7/27/1994 HED Metabolism Committee Meeting of 7/13/1994. Flumiclorac Pentyl (Resource).

### Page 21 of 33

A ppendix A. Toxicology Profile and Executive Summaries

A.1 Toxicology Data Requirements
The requirements (40 CFR 158.340) for food use for flumiclorac pentyl are shown below 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

................................ ..................... y es

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

no yes

yes

yes

no

no

870.3700a Developmental Toxicity (rodent)

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

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

................................ ................................ . y es

yes

yes yes

yes

yes

870.4100a Chronic Toxicity (rodent)

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

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

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

................................ ................... 870.4300 Chronic/Oncogenicity (rat)

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

yes

yes

yes

yes yes

yes

yes

yes

yes

870.5100 Mutagenicity

— Gene Mutation

- bacterial

..................... 870.5375 Mutagenicity

— Structural Chromosomal Aberrations

... 870.5395 Mutagenicity

— Micronucleus

................................ ........ 870.5550 Mutagenicity

— Unscheduled DNA Synthesis

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

yes

yes

yes yes

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 Develop. Neurotoxicity

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

no

yes

yes

no -

- yes

yes

-

870.7485 General Metabolism

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

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

................................ ............................. y es

no

yes yes

yes

yes

Special Studies for Ocular Effects

Acute Oral (rat)

................................ ........................... Subchronic Oral (rat)

................................ .................. Six

- month Oral (dog)

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

no

no -

-

-

### Page 22 of 33

Acute Toxicity of Flumiclorac

- Pentyl

Guideline No./Study Type MRID Results Toxicity Category

870.1100 Acute oral toxicity (rat) (S

- 23031) 42169812 LD 50 = >5000 mg/kg IV

870.1100 Acute oral toxicity (rat) (V

- 23031 0.83 EC) 42169813 LD 50 = 4.1 g/kg (m)

LD 50 = 3.2 g/kg (f)

LD 50 = 3.6 g/kg (both) III

870.1200 Acute dermal toxicity (rat) (S

- 23031) 42169814 LD 50 = >2000 mg/kg III

870.1200 Acute dermal toxicity (rat) (V

- 23031 0.83 EC) 42169815 LD 50 = >2000 mg/kg III

870.1300 Acute inhalation toxicity (rat) (S

- 23031) 42169816 LC 50 = >5.94 mg/L IV

870.1300 Acute inhalation toxicity (rat) (V

- 23031 0.83 EC) 42169817 LC 50 = 5.51 mg/L IV

870.2500 Acute dermal irritation [rabbit] (V

- 23031 0.83 EC) 42169820 moderate II

870.2600 Skin sensitization (guinea pig) (S

- 23031) 42169822 extreme (Maximization method) Sensitizer

870.2600 Skin sensitization (guinea pig) 42 883902 Not a dermal sensitizer NA

N A = Not Applicable

### Page 23 of 33

Subchronic, Chronic, and Other Toxicity Studies for Flumiclorac

- Pentyl

Guideline No./ Study Type MRID No. (year)/

Classification /Doses Results

870.3100

90

- Day oral toxicity (rat) 42169823 (1990)

42310801 (addendum) Acceptable/guideline M: 0, 6.6, 67, 664, 1359 mg/kg/d F: 0, 7.4, 73.8, 726, 1574 mg/kg/d NOAEL =  1359/1574 mg/kg/day (M/F)

LOAEL = not identified

870.3150

90

- Day oral toxicity (dog) 42169827 (1991)

42310802 (addendum) Acceptable/guideline M&F: 0, 10, 100, 1000 mg/kg/d NOAEL = 100 mg/kg/day LOAEL = 1000 mg/kg/day based on increased clotting time

in females.

870.3200

21/28

- Day dermal toxicity 42825815 (1991)

Acceptable/guideline M&F: 0, 100, 300, 1000 mg/kg/day NOAEL = 1000 mg/kg/day (limit dose)

870.3250

90

- Day dermal toxicity N/A N/A

870.3465

90

- Day inhalation toxicity Study requirement

waived N/A

870.3700a

Prenatal developmental (rat) 42169832 (1990)

42169831 (range

- finding, 1990) Acceptable/guideline F: 0, 50, 500, 1500 mg/kg/d (GD 6

- 15) Maternal NOAEL =  1500 mg/kg/day

LOAEL = not identified Developmental NOAEL =  1500 mg/ kg/day

LOAEL = not identified

870.3700b

Prenatal developmental (rabbit) 42169830 (1991)

42169829, 42169828 (range

- finding, 1990) Acceptable/guideline F: 0, 100, 200, 400, 800 mg/kg/d (GD 6

- 19) Materna l NOAEL = 400 mg/kg/day LOAEL = 800 mg/kg/day based on mortality Developmenta l NOAEL =  800 mg/kg/day

LOAEL = not determined

870.3800 Reproduction and fertility effects (rat) 42169835 (1991)

42169834 (range

- finding, 1990) Acceptable/guideline M: 0, 16, 781, 1610 mg/kg/d F: 0, 18, 925, 1869 mg/kg/d Parental/Systemic NOAEL = 16/18 mg/kg/day (M/F) LOAEL = 781/925 mg/kg/day (M/F) based on increased kidney weight in males and females and nephropathy in

males. Reproductive NOAEL =  1610/1869 mg/kg/day (M/F)

LOAEL = not identified. Offspring NOAEL = 781/925 mg/kg/day (M/F) LOAEL = 1610/1869 mg/kg/day (M/F) based on decreased body weight/body weight in F 2 pups.
870.4100b Chronic toxicity (dog) 42825817 (1992)

Acceptable/guideline M&F: 0, 10, 100, 1000 mg/kg/d NOAEL = 100 mg/kg/day

LOAEL = 1000 mg/kg/day based on decreased body weight gain in male; increased clotting time, increased globulin levels, and increased alpha

- 2 fraction of the serum protein electrophoresis in females.

### Page 24 of 33

Subchronic, Chronic, and Other Toxicity Studies for Flumiclorac

- Pentyl

Guideline No./ Study Type MRID No. (year)/

Classification /Doses Results

870.4200b Carcinogenicity (mouse) 42883905 (1992)

Acceptable/ guideline M: 0, 31.5, 307.9, 731.4 mg/kg/d F: 0, 37.8, 368.1, 850.2 mg/kg/d NOAEL =  731.4/850.2 mg/kg/day (M/F)

LOAEL = not identified

no evidence of carcinogenicity

870.4300

Chronic/Carcino

genicity (rat) 42883906 (1992)

Acceptable/guideline M: 0, 3.5, 35.4, 360.4, 744.9 mg/kg/d F: 0, 4.3, 43.6, 443.8, 919.4 mg/kg/d NOAEL = 360.4 mg/kg/day ( ♂ ); 43.6 mg/kg/day (F)

LOAEL = 744.9 mg/kg/day ( ♂ ) based on increased squamous epithelial cells in urinary sediment and increased kidney weights; 443.8 mg/kg/da y ( ♀ ) based on urinary incontinence, increased water consumption, increased urine volume and increased kidney weights.

no evidence of carcinogenicity

Gene Mutation

870.5100 ( Salmonella typhimurium ) 42169836 (1989)

A cceptable/ non guideline negative up to 5000 μg/plate with and without metabolic

activation

Cytogenetics

870.5375 (CHO) 42169838 (1989)

A cceptable/ non guideline negative for chromosome aberration up to 400 μg/mL with metabolic activation; weak, positive response without

activation

Micronucleus

870.5395 (mouse) 42169837 (1990)

Acceptable/guideline negative at doses up to 5000 mg/kg

Unscheduled DNA Synthesis

870.5550 (rat hepatocytes) 42169839 (1989)

Acceptable/guideline negative at concentration up to 300μg/mL in cultured rat hepatocytes

870.6200a Acute neurotoxicity screening battery 4892340 3 and 48923405

(2012)

Acceptable/guideline NOAEL = 2000 mg/ kg bw/day

LOAEL = not identified.

870.6200b

Subchronic neurotoxicity screening battery 48923401 and 48923404

(2012)

Acceptable/guideline NOAEL = 969 and 1255 mg/ kg bw/day for males and

females.

LOAEL = not identified.

870.6300 Developmental neurotoxicity not required

870.7485

Metabolism and pharmacokinetics (rat) 42825822 ( 1 993)

42825823 (1993)

A cceptable/guideline R apid absorption and excretion; major metabolic route is deesterification to a phenoxyacetic acid derivative followed by cleavage of the imide moiety or hydroxylation and/or

sulfonation reactions

870.7800 Immunotoxicity 48923406 The LOAEL for immunotoxicity was not identified. The

male CD

- 1 mouse NOAEL for immunotoxicity was 7000 ppm (1340 mg/kg bw/day).

### Page 25 of 33

Appendix B. Physical/Chemical Properties

Table B. Physical/Chemical Properties of Flumiclorac P entyl

Structure

Common Name Flumiclorac pentyl

IUPAC Name Pentyl (2

- chloro

- 5 (cyclohex

- 1

- ene

- 1,2

- dicarboximido)

- 4

- fluorophenoxy) acetate

CAS Name Pentyl[2

- chloro

- 4

- fluoro

- 5

- (1,3,4,5,6,7

- hexahydro

- 1,3

- dioxo

- 2H

- isoindol

- 2

- yl)phenoxy]acetate

CAS Number 87546

- 18

- 7
Melting Point Range 88.9

- 90.1  C

pH 6.03 at 25  C

Density 1.3316 g/mL at 20  C

Water solubility 0.189 mg/L at 25  C

Solvent solubility in g/L @

20 o C Solvent g/100 mL at 25  C:

hexane 0.328

n

- octanol 1.60

methanol 4.78

Solvesso 150 27.1

acetonitrile 58.9

acetone 59.0 tetrahydrofuran 69.7

N

- methyl 2

- pyrrolidinone 134.0 methylene chloride 288.0

Vapor pressure <1 x 10

- 7 mm Hg at 22.4  C

Dissociation constant, pK

a No dissociation at pH  7; flumiclorac pentyl decomposes at pH  9.

Octanol/water partition

coefficient Log P OW = 4.99 at 19.7

- 21.0  C

UV/visible absorption

spectrum 

max = 226 and 284 nm @ pH =7

### Page 26 of 33

Appendix C. International Residue Limit Status

Table C. Summary of US and International Tolerances and Maximum Residue Limits for

Flumiclorac P entyl (128724) Residue Definition :
US Canada Mexico 1 

### Codex

40 CFR 180.477 :

Plant: parent only [flumiclorac pentyl] 

### None None



### Commodit

y Tolerance (ppm) /Maximum Residue Limit (mg/kg)

US Canada Mexico 1 

### Codex
Corn, field, forage 0.01

Corn, field, grain 0.01

Corn, field, stover 0.01

Cotton, gin byproducts 3.0

Cotton, undelinted seed 0.2

Soybean, hulls 0.02

Soybean, seed 0.01



### Completed: M. Negussie; 03/05/14

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

### Page 27 of 33

Appendix D. Revised Dietary Burden Calculations for Flumiclorac P entyl

.

Table 5.3.4.1. Calculation of Dietary Burdens of Flumiclorac Pentyl Residues to Livestock.

Feedstuff Type 1 % Dry

Matter 2 % Diet 2 Indicate if

HAFT or

Median Residue Level

(ppm) Dietary

Contribution (ppm) 3

Beef Cattle (R = 15%; CC = 80%; PC = 5%)

Soybean, meal PC 92 5 Median 0.005 0.00027

Corn, field, grain CC 88 80 Median 0.005 0.00454

Corn, field, forage R 40 10 HAFT 0.01 0.0025

Cotton gin byproducts R 90 5 Median 0.66 0.0367

TOTAL BURDEN

-- -- 100

-- 0.0440

Dairy Cattle (R = 45%; CC = 45%; PC = 10%)

Cotton, undelinted seed PC 88 10 Median 0.03 0.00341

Corn, field, grain CC 88 45 Median 0.005 0.00256

Corn, field, forage R 40 4 5 HAFT 0.01 0.0113

TOTAL BURDEN

-- -- 100

-- 0.0172

Swine (CC = 85%; PC = 15%)

Corn, field, grain CC 88 85 Median 0.005 0.00425

Cotton, meal PC 89 15 Median 0.03 0.0045 0

TOTAL BURDEN

-- -- 100

-- 0.00875

Poultry (CC = 75%; PC = 25%)

Corn, field, grain CC 88 75 Median 0.005 0.00375

Soybean, meal PC 92 5 Median 0.005 0.00025

Cotton, meal PC 89 20 Median 0.03 0.0060

TOTAL BURDEN

-- -- 100

-- 0.010 0

1 R: Roughage; CC: Carbohydrate concentrate; PC: Protein concentrate.

2 Table 1 Feedstuffs (July 2008).

3 Contribution = ([tolerance /% DM] X % diet) for beef and dairy cattle; contribution = ([tolerance] X % diet) for poultry and swine.

### Page 28 of 33

Appendix E. Flumiclorac Pentyl Residues of Concern in Drinking Water.

Code Name/ Synonym Chemical Name Chemical Structure

Flumiclorac

- pentyl

S

- 23031

V

- 23031 Pentyl 2

- chloro

- 4

- fluoro

- 5

- (3,4,5,6

- tetrahydrophthalimido)phenoxyacetate

CAS No.: 87546

- 18

- 7

Formula: C 21 H 23 ClFNO 5 MW: 423.87 g/mol



### 031

- HA Pentyl 2

- chloro

- 4

- fluoro

- 5

- (2

- carboxycyclohexenylcarboxanido)phenoxyacetate

Formula: C 21 H 25 ClFNO 6 MW: 441.89 g/mol



### Flumiclorac acid

IMCA 2

- chloro

- 4

- fluoro

- 5

- (3,4,5,6

- tetrahydrophthalimido)phenoxyacetic acid

CAS No.: 87547

- 04

- 4

Formula: C 16 H 13 ClFNO 5 MW: 353.74 g/mol



### IMCA

- HA N

- (5

- carboxymethoxy

- 4

- chloro

- 2

- fluorophenyl)

- 3,4,5,6

- tetrahydrophthalamic acid

Formula: C 16 H 15 ClFNO 6 MW: 371.75 g/mol



### IMFP N

- (4

- chloro

- 2

- fluoro

- 5

- hydroxyphenol)

- 3,4,5,6

- tetrahydrophthalimide

Formula: C 14 H 11 ClFNO 3 MW: 295.70 g/mol



### IMFP

- HA N

- (4

- chloro

- 2

- fluoro

- 5

- hydroxyphenyl)

- 3,4,5,6

- tetrahydrophthalamic acid

Formula: C 14 H 13 ClFNO 4 MW: 313.72 g/mol



### SAT IMFP

- HA N

- (4

- chloro

- 2

- fluoro

- 5

- hydroxyphenyl) hexahydrophthalamic acid

Formula: C 14 H 15 ClFNO 4 MW: 315.73 g/mol

### Page 29 of 33

Appendix F . Summary of Occupational and Residential Non

- cancer Algorithms

OCCUPATIONAL NON



## - CANCER HANDLER ALGOR ITHMS



### Potential daily exposures for occupational handlers are calculated using the following formulas:

E=UE * AR * A * 0.001 mg/ug

where:

E = exposure (mg ai/day),

UE = unit exposure (μg ai/lb ai),

AR = maximum application rate according to proposed label (lb ai A or lb ai/gal), and

A = area treated or amount handled (e.g., A/day, gal/day).

The daily do ses are calculated using the following formula:

ADD= E * AF

BW

where:

ADD = average daily dose absorbed in a given scenario (mg ai/kg/day),

E = exposure (mg ai/day),

AF = absorption factor (inhalation), and

BW = body weight (kg).

Margin of Exposure: Non

- cancer risk estimates for each application handler scenario are calculated using a Margin of Exposure (MOE), which is a ratio of the toxicological endpoint to the daily dose of concern. The daily i nhalation dose received by occupational han dlers is compared to the appropriate POD (i.e., NOAEL) to assess the risk to occupational handlers for each exposure route. All MOE values are calculated using the following formula:

MOE= POD

ADD

where:

MOE = margin of exposure: value used by HED to r epresent risk estimates (unitless),

POD = point of departure (mg/kg/day), and

ADD = average daily dose absorbed in a given scenario (mg ai/kg/day).

### Page 30 of 33

Post

- application Hand

- to

- Mouth Exposure Algorithm

– Physical Activities on Turf Exposure from hand

- to

- mouth activity is calculated as follows (based on the algorithm utilized in

the SHEDS

- Multimedia model):

E = [HR * ( F

M 

### * SA H 

### ) * (ET * N_Replen) * (1

- (1

- SE ) (Freq_HtM/N

- Replen) 

### )]

W here :

E = exposure (mg/day); HR = hand residue loading (mg/cm 2 

### );

FM = fraction hand surface area mouthed / event (fraction/event); SAH = typical surface area of one hand (cm 2 

### ); ET = exposure time (hr/day); N_Replen = number of replenishment intervals per hour (intervals/hour); SE = saliva extraction factor (i.e., mouthing re moval efficiency); and Freq_HtM = number of hand

- to

- mouth contacts events per hour (events/hour).

and

where:

HR = hand residue loading (mg/cm 2 

### );

Fai hands 

### = fraction ai on hands compared to total surface residue from dermal tra nsfer coefficient study (unitless); DE = dermal exposure (mg); and

SA H 

### = typical surface area of one hand (cm 2 

### ).

Dose, normalized to body weight, is calculated as:

where:

D = dose (mg/kg

- day);

E = exposure (mg/day); and

BW = body weight (kg).

Table F

- 1 : Turf (Physical Activities)

– Inputs for Residential Post

- application Hand

- to

- Mouth Exposure
Algorithm

Notation Exposure Factor

(units) Point Estimate(s)

Fai hands Liquid formulations 0.06

### Page 31 of 33

Table F

- 1 : Turf (Physical Activities)

– Inputs for Residential Post

- application Hand

- to

- Mouth Exposure
Algorithm

Notation Exposure Factor

(units) Point Estimate(s)

Fraction of ai on hands from

dermal transfer coefficient study (unitless) Granular formulations 0.027

DE Dermal exposure (mg) Calculated

SA H Typical surface area of one hand (cm 2 ), children 1 < 2 years old 150

AR Application rate (mass active ingredient per unit area) See table 1

HR Residue available on the hands (mg/cm 2 ) Calculated via (DE * Fai hands )/SA H

F M Fraction hand surface area mouthed (fraction/event) 0.127

N_Replen Replenishment intervals per hour (intervals/hr) 4

ET Exposure time (hrs/day) 1.5

SE Saliva extraction factor (unitless) 0.48
Freq_HtM Hand

- to

- mouth events per hour (events/hr) 13.9

BW Body Weight (kg) Children 1 < 2 years old 11



### Post

- application Object

- to

- Mouth Exposure Algorithm

– Physical Activities on Turf Exposure from object

- to

- mouth activity is calculated as follows (based on the algorithm utilized

in SHEDS

- Multimedia):

E = [OR* CF1 * SAM O 

### * (ET * N_Replen) * (1

- (1

- SE O 

### ) (Freq_OtM/N_Replen) 

### )]

where:

E = exposure (mg/day); OR = chemical residue loading on the object on day “t” (ug/cm 2 

### );

CF1 = weight unit conversion factor (0.001 mg/μg);

SAM O 

### = area of the object surface that is mouthed (cm 2 

### /event); ET = exposure time (hr/day); N_Replen = number of replenishment intervals per hour (intervals/hour);

SE O 

### = saliva extraction factor (i.e., mouthi ng removal efficiency); and Freq_OtM = number of object

- to

- mouth contact events per hour (events/hour).

and

OR = AR * F O 

### * CF2 * CF3

where:

OR = chemical residue loading on the object (μg/cm 2 

### ); AR = application rate (lbs ai/ft 2 

### or lb ai/acre);

F O 

### = fraction of residue available on the object (unitless); CF2 = weight unit conversion factor (4.54 x 10 8 

### μg/lb); and CF3 = area unit conversion factor (1.08 x 10

- 3 

### ft 2 

### /cm 2 

### or 2.47 x 10

- 8 

### acre/cm 2 

### ).

Dose, normalized to body weight, is calculated as:

### Page 32 of 33

where:

D = dose (mg/kg

- day);

E = exposure (mg/day); and

BW = body weight (kg).

Table F

- 2 : Turf (Physical Activities)

– Inputs for Residential Post

- application Object

- to

- Mouth Exposure

Algorithm

Notation Exposure Factor

(units) Point Estimate(s)

AR Application rate (to turf)

(mass active ingredient per unit area) See table 1

F O Fraction of AR as OR following application 1 0.01

SAM O Surface area of object mouthed

(cm 2 /event) 10

N_Replen Replenishment intervals per hour (intervals/hour) 4

SE O Saliva extraction factor

(fraction) 0.48

ET Exposure time

(hours per day) 1.5

Freq_OtM Object

- to

- mouth events per hour (events/hr) 8.8

BW Body Weight (kg) Children 1 < 2 years old 11

1 This SOP assumes that all of the residue on the turf could be transferred to the object (e.g., object residue is equal to turf transferable residue).



### Post

- application Incidental Soil Ingestion Exposure Algorithm

– Physical Activities on Turf Exposure from incidental soil ingestion is calculated as follows:

E = SRt * SIgR * CF1

where: E = exposure (mg/day); SRt = soil residue on day "t" (μg/g); SIgR = ingestion rate of soil (mg/day); and CF1 = weight unit conversion factor (1 x 10

- 6 

### g/μg).

and

SRt = AR * FS * (1

- F D 

### ) t 

### * CF2 * CF3 * CF4

where:

SR t 

### = soil residue on day "t" (μg/g); AR = application rate (lbs ai/ft 2 

### or lb ai/acre); FS = fraction of ai available in uppermost cm of soil (fraction/cm);

F D 

### = fraction of residue that dissipates daily (unitless); T = post

- application day on whic h exposure is being assessed;

### Page 33 of 33

CF2 = weight unit conversion factor (4.54 x 10 8 

### μg/lb); CF3 = area unit conversion factor (1.08 x 10

- 3 

### ft 2 

### /cm 2 

### or 2.47 x 10

- 8 

### acre/cm 2 

### ); and CF4 = soil volume to weight unit conversion factor (0.67 cm 3 

### /g soil).

Dose, normaliz ed to body weight, are calculated as:

where :
D = dose (mg/kg

- day);

E = exposure (mg/day); and

BW = body weight (kg).

Table F

- 3 : Turf (Physical Activities)

– Inputs for Residential Post

- application Incidental Soil Ingestion Exposure

Algorithm

Notation Exposure Factor

(units) Point Estimate(s)

AR Application rate (mass active ingredient per unit area) See table 1

FS Fraction of AR available in uppermost 1 cm of soil (unitless) 1

F D Daily residue dissipation (fraction) 0.1

SIgR Soil ingestion rate (mg/day) 50

BW Body weight (kg) Children 1 < 2 years old 11