UNITED STA TES ENVIRONMENT AL PROTECTION AGENCY 

W ASHfNGTON, D.C. 20460 

MEMORANDUM 

Date: 19 June 2015 

OFFICE OF 

CHEMICAL SAFETY 

AND POLUTION PREVENSION 

Subject: Fluensulfone - Assessment of the Section 18 Use on Carrots in Michigan 

PC Code: 050410 DP Barcode: 0427229 

Decision No.: 503856 Registration No.: 66222-243 

Petition No.: l 5MI05 Regulatory Action: Section 18 

Risk Assessment Type: Single Chemical Aggregate Case No.: None 

TXR No.: NA CAS No.: 318290-98-1 

MRJO No.: None 40 CFR: 180.680 

From: 

Zaida 

Michael 

Figueroa

A. Doherty

, M.S., 

, Ph.D.

Indu

, 

stria

Senio

l H

r 

yg

Chemist 

ienist ;J 

UJ 

~~ 

~ 

Health Effects Division (HED; 7509P) ' 

Risk Assessment Branch II (RAB II) ~ 

Through: 

HED

Christina 

, RAB 

Swartz

II 

, Chief ~ 

To: Stacey Groce/Tawanda Maignan (Team 09) 

Marion Johnson, Chief 

Registration Division (RD; 7505P) 

Risk Integration, Minor Use, and Emergency Response Branch 

Introduction 

The Michigan Department of Agriculture has issued a crisis exemption for the use of 

fluensulfone to control a number of nematode species in carrot fields. This is the first Section 18 

exemption for this use. Under the exemption, up to 2,000 acres of carrot fields will be treated 

with the Nimitz® 480 EC formulation offluensulfone (EPA Registration No. 66222-243). The 

Section 18 documentation indicates that the use will be in counties of Lapeer, Montcalm, 

Newaygo, and Oceana. The use season is 14 April to 15 June 2015, and the crisis exemption was 

issued on 14 April 2015. 

Fluensulfone { 5-Chloro-2-[(3,4,4-tritluoro-3-buten-l-yl)sulfonyl]thiazole} is a nematicide 

registered in 2014 for use on cucurbit and fruiting vegetables, and the Agency has received a 

Section 3 request to register this ingredient for use on additional crops, including carrot. 

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Fluensulfone Aggregate Human Health Risk Assessment D427229 

Agency Memoranda Used to Support this Section 18 Exemption Risk Assessment 

D403767. M. Doherty, J. D' Agostino, Z. Figueroa. 18 June 2014. Fluensulfone - New Active 

Ingredient Human Health Risk Assessment of Proposed Uses on Cucurbit Vegetables and 

Fruiting Vegetables. 

D4038 13. M. Doherty. 4 June 2014. Fluensulfone. Petition for the Establishment of Permanent 

Tolerances and Registration for Use of the New Active Ingredient on Fruiting Vegetables 

(Crop Group 8-10) and Cucurbit Vegetables (Crop Group 9). Summary of Analytical 

Chemistry and Residue Data from the OECD Joint Review. 

D403814, Z. Figueroa, 18 July 2014. Fluensulfone. Occupational and Residential Exposure and 

Risk Assessment to Support the Registration of the New Active Ingredient on Cucurbits 

and Fruiting Vegetables. 

D418204, M. Doherty, 10 June 2014. Fluensulfone Acute and Chronic Aggregate Dietary (Food 

and Drinking Water) Exposure and Risk Assessments for the First Food Use Section 3 

Registration Action on Fruiting and Cucurbit Vegetables 

Assessment Summary 

Chemical Identity and Background Information. Fluensulfone { 5-Chloro-2-((3,4,4-trifluoro-3-

buten-1-yl)sulfonyl)thiazole} is the first nematicide in the fluoroalkenyl class and was registered 

as a new active ingredient in the U.S. in September of2014. It is registered for pre-plant 

application by broadcast spray or drip irrigation seven days prior to transplanting cucurbit and 

fruiting vegetables. Tolerances for residues in those crop groups are established at 0.50 ppm, 

with enforcement based solely on residues of the trifluorobutene sulfonic acid metabolite 

(expressed in terms of fluensulfone; 40 CFR 180.680). Risk assessments for fluensulfone are 

based on residues of the parent compound, per se, due to the low toxicity of the butene sulfonic 

acid and thiazole sulfonic acid metabolites. There are no Canadian or Codex MRLs for residues 

of fluensulfone in carrot at this time, and international harmonization is not an issue for this 

Section 18. 

Section I 8 Use Pattern Information. Under the specific exemption, fluensulfone is applied as a 

single, pre-plant application to carrot fields by broadcast spray, banded spray, or drip irrigation. 

Application will precede planting by no less than 14 days, and the applied material will be 

watered into the soil two to five days after application. The maximum application rate is 2.5 lb 

a.i./ A, with the rate prorated to the actual treated area in the case of banded spray application. 

Toxicological Information. The toxicology database for fluensulfone is complete for purposes of 

conducting an FQPA human health risk assessment. In mammals, exposure to fluensulfone 

results in effects on the hematopoietic system (decreased platelets, increased white blood cells, 

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Fluensulfone Aggregate Human Health Risk Assessment 0427229 

hematocrit, and reticulocytes), kidneys, and lungs. Changes in clinical chemistry as well as in 

body weight were also observed across multiple studies and species. In rats, pup loss was noted, 

with the majority of deaths occurring on post-natal day 2. Overall, the most sensitive endpoints 

for assessing human health risk are the increased pup-loss effects for acute dietary exposure; 

body weight, hematological and clinical chemistry changes for chronic dietary and dermal 

exposures (short/intermediate term); and clotting time, decreased thymus weight, and portal-ofentry effects (histopathology of the epiglottis and nasal cavity) for inhalation exposures 

(short/intermediate term). Given the overall completeness of the toxicity database, the lack of 

uncertainty regarding susceptibility of infants and children, and the conservatisms in the human 

health exposure estimates, HED has reduced the Food Quality Protection Act Safety Factor 

(FQPA SF) from lOX to IX. For assessing occupational oral and dermal exposures, the standard 

inter- and intra-species uncertainty factors of 1 OX are appropriate and result in a level of concern 

(LOC) of 100. For assessing occupational inhalation exposure, the interspecies (to account for 

differences between rats and humans) factor has been reduced to 3X; however, an additional 1 OX 

factor is required because a no-observed-adverse-affect level (NOAEL) was not found for the 

portal-of-entry effects, resulting in an LOC of 300. 

Table 1. Summary of Toxicological Doses and End points for use in Fluensulfone Dietary a nd NonOccupational Human Health Risk Assessments. 

Exposure/ Point of Uncertainty/ RID, PAD, Study and Toxicological Effects 

Scenario Departure FQPA Safety Level of 

Factors Concern for 

Risk 

Assessment 

Acute Dietary Offspring UFA= !Ox Acute RfO = 2-generation reproduction - rat 

(All NOA EL= UFH= IOx 0.16 mg/kg/day Offspring LOAEL = 122.0/ 169.1 

Populations, 16.2/23.0 FQPA SF= Ix mg/kg/day (M/F) based on an increase in 

including mg/kg/day aPAD = 0.16 pup loss between PNO I and 4 in the FI 

Infants and (M/F) mg/kg/day and F2 offspring with the majority of 

Children and deaths occurring on day 2. 

Females 13-49 

years of age) 

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Fluensulfone Aggregate Human Health Risk Assessment 0427229 

Table 1. Summary of Toxicological Doses a nd Endpoints for use in Fluensulfone Dietary and NonOccupational Human Health Risk Assessments. 

Exposure/ Point of Uncertainty/ RfD, PAD, Study and Toxicological Effects 

Scenario Departure FQPA Safety Level of 

Factors Concern for 

Risk 

Assessment 

Chronic NOAEL = 3.1 UFA= IOx Chronic RID = Co-critical 90-day dog and chronic dog 

Dietary (All mg/kg/day UFH= IOx 0.03 

Populations) FQPA SF= Ix mg/kg/day Chronic: LOAEL = 16 mg/kg/day based 

on decreased body weight, increased 

cPAD = 0.03 mean hemoglobin concentration 

mg/kg/day distribution width, and increased 

relative and absolute reticulocyte 

counts in both sexes, decreased 

prothrombin time in males and 

increased platelets in females. 

Subchronic: NOAEL = 1.6 mg/kg/day 

LOAEL = 17.1 mg/kg/day based on 

decreased body weight in females and 

increased relative and absolute 

reticulocyte counts, decreased 

bilirubin, decreased albumin, decreased 

A/G ratio, increased TSH, and 

pigmented Kupffer cells in both sexes. 

Incidental Oral A dose and endpoint for incidental oral exposure were not selected because there are presently no 

All Durations residential uses for fluensulfone. 

Denna! All There are presently no residential uses for fluensulfone. 

Durations 

Inhalation All There are presently no residential uses for tluensulfone. 

Durations 

Cancer (oral, Classification: Suggestive evidence of carcinogenicity in humans based on lung tumors in 

dennal, inhal.) female rats. The RfD is 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 detennine risk associated with lower environmentally relevant human 

exposures. NOAEL = no observed adverse effect level. LOA EL = lowest observed adverse effect level. UF = 

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

among members of the human population (intraspecies). UFL = use ofa LOAEL to extrapolate a NOAEL. FQPA SF 

= FQPA Safety Factor. PAD = population adjusted dose (a = acute, c = chronic). RfD = reference dose. 

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Fluensulfone Aggregate Human Health Risk Assessment 0427229 

Table 2. Summary of Toxicological Doses and Endpoints for use in Fluensulfone Occupational Human 

Health Risk Assessments. 

Exposure/ Point of Departure Uncertainry Level of Study and Toxicological Effects 

Scenario Factors Concern for 

MOE 

Dermal Short- NOA EL= 3. 1 mg/kg/day UF,,= IOx Occupational Co-critical 90-day dog and chronic 

and UFH= IOx LOC for MOE dog 

Intermediate- OAF = 40.9% = 100 

Term (1 -30 Chronic: LOAEL = 16 mg/kg/day 

days and 1-6 based on decreased body 

months) weight, increased mean 

hemoglobin concentration 

distribution width, and 

increased relative and absolute 

reticu locyte counts in both 

sexes, decreased prothrombin 

time in males and increased 

platelets in females. 

Subchronic: NOAEL = 1.6 

mg/kg/day LOAEL = 17. l 

mg/kg/day based on decreased 

body weight in females and 

increased relative and absolute 

reticulocyte counts, decreased 

bilimbin, decreased albumin, 

decreased A/G ratio, increased 

TSH, and pigmented Kupffer 

cells in both sexes. 

Inhalation NOA EL= not established UFA=3x Occupational 90-day inhalation toxiciry - rat 

Short- and (<0.04 mg/L) UF11= lOx LOC for MOE LOAEL = 0.04 mg!L (lowest dose 

Intermediate- UFL"" IOx = 300 tested) based on we ight loss in 

Term ( 1-30 3HEC = 0.00429 mg!L males, prolonged prothrombin time 

days and 1-6 bHED = 0.244 mg/kg/day in fema les, decreased thymus 

months) (low breathing rate), weight in males, histopathological 

= 0.491 mg/kg.day changes in the epiglottis in both 

(medium breathing rate), sexes, and histopathological 

= 0.853 mg/kg/day changes in the nasal cavity of 

(high breathing rate) males. 

Cancer (oral, Classification: Suggestive evidence of carcinogen icity in humans based on lung tumors in 

dermal, inhal.) female mice. The RID is protective of potentia l 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 with lower environmentally relevant human exposures. NOA EL 

= no observed adverse effect level. LOA EL = lowest observed adverse effect level. UF = uncertainty factor. UFA = extrapolation 

from animal to human (interspecies). UFH = potential variation in sensitivity among members of the human population 

(intraspecies). UFL = use of a LOA EL to extrapolate a NOAEL. MOE = margin of exposure. LOC = level of concern. OAF = 

dennal absorption factor 

• HEC = rat OAEL x (daily duration adjustment) x weekly daily duration adjustment x RDDR 

=0.04 mg/L x (6 hr/8 hr) x ( I) x 0. 143 = 0.00429 mg/L. 

b HED = HEC x human specific conversion factor x activity factor for the exposure scenario x daily duration 

= 0.00429 mg/L x 11 .8 L/hr-kg x (0.6. 1.2. and 2.1 for low. medium, and high. respectively) x 8 hr. 

Page 5 of20 
Fluensulfone Aggregate Human Health Risk Assessment D427229 

Occupational Exposure and Risk Information. Occupational exposures and risks from the use of 

fluensulfone on cucurbit and fruiting vegetables were estimated in the last risk assessment, with 

margins of exposure (MO Es) ranging from 81 to 270 for dermal exposure (level of concern is 

dermal MOE < l 00) and from 290 to 1,300 for inhalation exposure (level of concern is 

inhalation MOE < 300). Exposure inputs are the same for carrot as those used in the previous 

assessment for cucurbit and fruiting vegetables. Therefore, HED is translating the previous 

occupational handler assessment to this Section 18 assessment. 

HED notes that in the previous occupational assessment, use of personal protective 

equipment (PPE) in the form of chemical-resistant gloves and engineering controls was 

necessary to achieve dermal MOEs above the LOC. The Section 18 label for use on carrot 

should specify the same PPE as is listed on the Section 3 label for cucurbit and fruiting 

vegetables. 

Due to the use pattern and application timing (i.e., applied as a pre-plant broadcast application 

prior to transplanting), no post-application exposure is expected for workers re-entering treated 

areas. Fluensulfone is classified as Toxicity Category III via the dermal route and Toxicity 

Category IV for skin and eye irritation potential. It is a skin sensitizer. The REI of 12 hours 

listed on the label is adequate to protect agricultural workers from post-application exposures to 

fluensulfone. 

Dietary Exposure Information. The registrant has petitioned the Agency to register fluensulfone 

for use on a number of additional crops, including carrots. In order to support that registration 

request, the registrant provided data from supervised residue trials in carrot. Those data show 

quantifiable residues of fluensulfone as well as the sulfonic acid metabolites in carrots harvested 

from fluensulfone-treated fields. In estimating dietary risk, HED used the maximum average 

field trial fluensulfone residue value from the carrot study, the residue levels used in the previous 

dietary assessment for fluensulfone (0.0 1 ppm for cucurbit and fruiting vegetables), and an 

assumption of 100% crop treated for all commodities. Modeled estimates of residues in drinking 

water are the same as those used in the previous Section 3 risk assessment and are considered to 

be conservative, and therefore protective of potential residues in drinking water resulting from 

the Section 18 use on carrots. The resulting screening-level dietary risk estimates across all 

representative population groups range from 2% to 8% of the PAD for acute exposure and from 

3% to 11 % of the PAD for chronic exposure, and all dietary risk estimates are not of concern. 

Residential Exposure Information. At this time, there are no uses for fluensulfone that would 

result in direct non-dietary exposure in a residential or recreational setting. 

Aggregate Risk Information. Aggregate risk estimates are equivalent to the dietary risk estimates 

and are not of concern for all population groups/scenarios. 

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Fluensulfone Aggregate Human Health Risk Assessment D427229 

Cumulative Risk Informal ion. The Agency has not made a determination that fluensulfone shares 

a common mechanism of toxicity with other compounds and has not conducted a cumulative risk 

assessment which includes tluensulfone. 

Conclusions. HED has no objection to the issuance of this Section 18 exemption. The available 

data support a tolerance for residues of fluensulfone in/on carrot (as measured by residues of the 

BSA metabolite expressed in parent-equivalents) at 2.0 ppm. RD should ensure that the Section 

18 label for use on carrot has the same PPE as is currently listed on the Section 3 label for use on 

cucurbit and fruiting vegetables. 

Toxicological Considerations 

For complete details, see 0403767, M. Doherty el al., 18 June 2014. 

The hematopoietic system was the major target of fluensulfone activity in rats, dogs, and mice. 

Effects on the hematopoietic system included increased white blood cells (rats and mice), 

increased hematocrit (mice), decreased platelets (mice), and increased reticulocytes (dogs) in 

subchronic dietary studies at the lowest observable effect levels (LOAEL) with additional effects 

on the hematopoietic system observed at hjgher doses. Effects on the hematopoietic system were 

also observed in chronic dietary studies for all species and, in the case of the chronic rat and dog 

studies, these effects were observed at the LOAELs. Effects on the hematopoietic system are 

consistent with results from rat metabolism studies which demonstrated that tluensulfone can 

react with the free thiol moiety of globin, forming a covalent linkage to the thiazole group 

displacing butene sulfinic acid. This led to slower elimination of the thiazole portion of 

fluensulfone from whole blood (time from dose to 50% of peak concentration, DTso = 6-9 days) 

compared to plasma (DT so= 16-17 hours). 

Other effects commonly observed in the toxicological database in all three species included 

changes in clinical chemjstry parameters and decreased body weights, both of which were often 

seen at the LOAELs in subchronic and chronic studies. Altered clinical chemistry parameters 

included decreased plasma alanine amino transferase (ALA T, rats and dogs), increased 

cholesterol (rats), increased triglycerides (rats), increased phospholipids (rats), increased 

bilirubin (mice) or decreased bilirubin (dogs), decreased protein (dogs), decreased albumin and 

albumin/globulin ratio (dogs), decreased glucose (dogs), and increased TSH (dogs) in subchronic 

studies. For the hematological, clinical chemistry, and body weight effects observed in all three 

species, the dog appeared to be slightly more sensitive than mice and rats. 

Fluensulfone also caused effects on the kjdney in male rats; however, the effects are consistent 

with accumulation of a.-2-microglobulin which has been deemed not relevant to humans 

(USEPA 1991). 

Effects on the lung were observed following chronic dietary exposure in mice and rats. These 

effects consisted of an increased incidence and severity of lung interstitial inflammation in the 2-

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Fluensulfone Aggregate Human Health Risk Assessment D427229 

year rat study and an increased incidence of bronchiolization (change from flattened epithelium 

to cuboidal epithelium) in the 18-month mouse study. 

Fluensulfone also appeared to cause portal-of-entry effects in rats. This included the forestomach 

(diffuse basal cell hyperplasia) and pharynx (mononuclear infiltrates) in dietary subchronic 

studies; the epiglottis (squamous metaplasia, epithelial hyperplasia, and focal mononuclear cell 

infiltrates) and nasal cavity (squamous epithelial hyperplasia) in the 90-day inhalation study; and 

an increased incidence/severity of acanthosis/hyperkeratosis in the 28-day dermal study. The 

dermal effects were considered adaptive due to the moderate degree of acanthosis/hyperkeratosis 

observed. 

Discoloration of teeth was noted in two subchronic toxicity studies, and increased levels of total 

fluoride were observed with a strong dose-response across numerous studies. Neither the 

discoloration nor the increased flouride levels are considered adverse (i.e., severe dental 

fluorosis); however, they do indicate that exposure to tluensulfone may contribute to overall 

fluoride exposure. Residue data (see previous risk assessment) demonstrate that total fluoride 

levels are indistinguishable between fluensulfone-treated and untreated crops; therefore, HED 

has concluded that for the assessed uses, fluensulfone is not a source of fluoride exposure. 

There was no evidence of immunotoxicity in the available studies, which included a guideline 

immunotoxicity study in the rat. There is limited evidence that fluensulfone results in effects on 

the nervous system. Decreased locomotor activity, decreased spontaneous activity, decreased 

rearing, and impaired righting response was observed only on Day l following acute exposure in 

the acute neurotoxicity study. In contrast, no evidence suggestive of neurotoxicity was observed 

in any other study, including a subchronic neurotoxicity study. Following dermal exposure for 

28-days, systemic effects including increased reticulocytes and increased cholesterol were 

observed, but only at a dose twice that of the limit dose. 

There was evidence of increased qualitative susceptibility of pups to the effects of fluensulfone. 

Decreased pup weight, decreased spleen weight, and an increase in post-natal pup loss [postnatal days (PND) 1-4] were observed in the rat two-generation reproductive toxicity study at a 

dose causing decreased body weight in the parents. The findings in the pups were considered 

more severe than those seen in the maternal animals. No evidence of increased quantitative or 

qualitative susceptibility was seen in developmental toxicity studies in rats and rabbits. In the rat 

developmental toxicity study, decreased fetal weight was observed in the presence of decreased 

body weight in maternal animals. In the rabbit developmental toxicity study, decreased fetal 

weight and incomplete ossification of digit 5 of the medial phalanx in both forelimbs were 

observed in the presence of decreased body weight in maternal animals. 

Chronic dietary exposure to fluensulfone in female mice resulted in an increased incidence of 

lung adenomas and carcinomas. The Cancer Assessment Review Committee (CARC) classified 

fluensulfone as having "Suggestive Evidence of Carcinogenicity" based on an increased 

incidence of alveolar/bronchiolar adenomas and carcinomas in the lung of mid- and high-dose 

Page 8 of20 
Fluensulfone Aggregate Human Health Risk Assessment D427229 

female mice in the oncogenicity study. All genotoxicity studies that were conducted on 

fluensulfone and three of its metabolites (thiazole sulfonic acid; TSA, butene sulfonic acid; BSA, 

and methyl sulfone; MeS) were negative, except for MeS with Salmonella typhimurium strain 

TA 100 in the absence of metabolic activation during a bacterial reverse mutation assay. 

Testing in acute lethality studies with fluensulfone technical-grade material resulted in low 

toxicity classifications via the oral (Toxicity Category III), dermal (Toxicity Category III), and 

inhalation (Toxicity Category IV) routes of exposure. Fluensulfone technical-grade material was 

not an irritant to eyes (Toxicity Category IV) or skin (Toxicity Category IV) but was a skin 

sensitizer. Similar results were obtained in acute lethali ty studies with an emulsifiable 

concentrate formulation ( 480 EC). 

Oral acute lethality studi es were also conducted with the metabolites MeS, BSA, or TSA, each at 

2000 mg/kg bw. By the oral route of exposure, MeS was of moderate toxicity (Toxicity Category 

II) and both BSA and TSA were of low toxicity (Toxicity Category III). HED notes that all 

animals treated with BSA or TSA survived the entire study period and that the toxicity category 

for those metabolites is based on the dosing level rather than on actual LDso estimates. 

Furthermore in the BSA and TSA acute toxicity studies, body weights of all animals were within 

the normal range, no macroscopic findings were recorded at necropsy, and no clinical signs were 

observed except in three animals which exhibited slightly ruffled fur two hours after 

administration of TSA, which persisted up to the three-hour observation in two animals. In 28-

day oral toxicity studies with BSA and TSA, no treatment-related effects were observed at any 

dose (limit-dose = 1000 mg/kg/day). 

Safety Factor/or Infants and Children (FQPA Safety Factor) 

The toxicology and the exposure databases for fluensulfone support a reduction of the required 

1 OX FQPA SF to IX based on the following considerations: the completeness of the toxicity 

database including adequate studies to assess the potential susceptibility in the young; there is 

no indication of quantitative susceptibility in the developmental and reproductive toxicity 

studies, and there are no residual uncertainties concerning pre- or post-natal toxicity; the 

endpoints and doses chosen for risk assessment are protective of the qualitative susceptibility 

observed in the 2-generation reproduction study; acute and subchronic neurotoxicity studies 

(ACN and SCN) are available. In addition, all endpoints used in the risk assessment are 

protective of the evidence of neurotoxicity observed in the ACN, and a developmental 

neurotoxicity study is not required. The dietary assessment is based on reliable data and 

conservatively modeled drinking water residues, and will not underestimate exposure. Finally, 

there are no registered or requested uses for fluensulfone that would result in residential 

exposure. 

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Fluensulfone Aggregate Human Health Risk Assessment 0427229 

Occupational Exposure Considerations 

There is a potential for occupational exposure associated with handler activities (i.e., mixing, 

loading, and applying). Given that the Section 18 use pattern requires soil-incorporated 

application 14 days before planting, no post-application exposure is expected for workers reentering treated areas. The duration of exposure for the uses on cucurbit and fruiting vegetables 

is expected to be short-term (1-30 days) and intermediate-term (1-6 months). For the Section 18 

use, similar durations of exposure may occur. Long-term exposures (greater than 6 months) are 

not anticipated. 

The occupational handler (mixer, loader, applicator) exposure and risk estimates from the 

previous assessment are summarized in Table 3. Note that in order to mitigate occupational risk 

issues, the originally proposed application rate of 3.5 lb a.i./ A was reduced to 2.5 lb a.i./ A on the 

registered Section 3 label, which matches the application rate on the Section 18 label. 

Table 3. Short- and Intermediate-Term Occupational Handler Non-Cancer Exposure and Risk Estimates 

for Fluensulfonc. Taken from 0403814, Z. Fi2ueroa, 18 Julv 2014. 

Exposure Mitigation Application Area Dermal Dermal Inhalation Inhalation 

Scenario Level" Rateb Treated< Dosed MOE• Doser MOES 

(mg/kg/day) (mg/k,g/day) 

Mixing/Loading Baseline 1.75 lb ai/A 350 A 0.69 5 0.00168 290 

Liquids for Engineering 0.0269 120 0.000635 770 

Chemigation Controls 

(AHETF/PHED) Baseline 2.50 lb ai/A 0.9870 3.1 0.002400 200 

Engineering 0.0385 81 0.000908 540 

Controls 

Mixing/Loading Baseline 1.75 lb ai/A 80A 0. 157 20 0.000384 1,300 

Liquids for Single Layer, 0.0269 120 0.000384 1.300 

Groundboom Gloves, No 

{AHETF/PHED) Respirator 

Baseline 2.50 lb ai/A 0.2250 14 0.000548 900 

Single Layer, 0.0384 81 0.000548 900 

Gloves, No 

Respirator 

Applying Baseline 1.75 lb ai/A 80 A 0.0562 60 0.000595 410 

Liquids for Single Layer, 0.0115 270 0.000595 410 

Groundboom Gloves, 

Application No Respirator 

{AHETF/PHED) Baseline 2.50 lb ai/A 0.0803 40 0.00085 290 

Single Layer, 0.0165 190 0.00085 290 

Gloves, 

No Respirator .. a. M111ga11 on level or PPE. Baseline = long-sleeved shirt. long pants. shoes. socks. no gloves. no rcsp1raor. 

b. Application Rates based on proposed use on label (3.5 lb ai/A for all crops). 

c. Exposure Science Advisory Council Policy No. 9.1. 

d. Dermal Dose (mg/kg/day)= Daily Unit Exposure (μg/lb ai) x Dermal Absorption Factor (40.9%) x Application Rate (lb ai/gal) x Arca Treated 

I Body Weight (80 kg). 

c. Dermal MOE= NOA EL (3.1 mg/kg/day) I Dermal Daily Doic (mg/kg/day). LOC = 100. 

f. Inhalation Dose (mg/kg/day)= Daily Unit Exposure (μg/lb ai) x Application Rate (lb ai/acre) x Acres Treated I Body Weight (80 kg). 

g. Inhalation MOE= HED (0.491 mg/kg/dayMA. or 0.244 mg/kg/dny .. ) / Inhalation Daily Dose (mg/kg/day). LOC = 300. 

Page 10 of20 
Fluensulfone Aggregate Human Health Risk Assessment 0 427229 

Residue Chemistry Considerations 

For details regarding the core residue chemistry studies, see 0403813 (M. Doherty, 4 June 

2014). 

Metabolic Fate. Studies depicting the nature of the residues in target crops (tomato, potato, and 

lettuce), rotational crops (radish, lettuce, and wheat) and livestock (laying hens and lactating 

goats) consistently show fluensulfone to be cleaved at the sulfonyl moiety, presumably via 

glutathione conjugation, resulting in both halves of the molecule having a sulfonyl functional 

group. Parent fluensulfone was identified only in poultry fat and in rotational lettuce, radish 

foliage, and wheat hay, forage and straw at short plant-back intervals (30 days). With the 

exception of poultry fat, fluensulfone was not a major residue in any matrix. In both target and 

rotational crops, the cleavage products form thiazole sulfonic acid (TSA) and butene sulfonic 

acid (BSA). The butene sulfonic acid may then be oxidized to form smaller compounds that are 

incorporated into natural plant components or mineralized to C02. In livestock, the majority of 

the radiolabel was excreted. Retained fluensulfone is extensively metabolized, with the 

radioactivity being associated primarily with amino acids and triglycerides. Thiazole methyl 

sulfone and butene sulfinic acid were identified in livestock studies, but were observed only in 

excreta. In the rat metabolism study, significant residues were thiazole mercapturate, thiazole 

glucuronide, thiazole sulfonic acid, butene sulfinic acid, and butene sulfonfo acid. These are all 

consistent with the glutathione-conjugation process noted in the other metabolism studies. 

Fl uensulfone was not detected as a significant residue (i.e., < 0.1 % of the applied dose) in rats. 

Toxicology data for the TSA and BSA metabolites show that they are non-toxic at levels 

expected in foods. As a result, inclusion of the parent compound in risk assessment, even at the 

limit of quantitation, is considered adequate to address risks that may be present from dietary 

exposure to TSA and BSA. 

Enforcement of tolerances should be via measurement of residues of BSA only. The parent 

compound alone is a poor indicator of misuse due to the lack of consistently quantifiable 

residues. The metabolites TSA and BSA both appear at quantifiable levels in the crop field trials 

and are good candidates for marker compounds. The TSA metabolite may persist from one year 

to the next; therefore, the potential for TSA to accumulate makes BSA a better indicator of 

misuse. 

Table 4. Summary of Metabolites and Degradates to be included in the Risk Assessment and Tolerance 

Expression of Fluensulfone. 

Matrix Residues Included in Risk Assessment Residues Included in Tolerance Expression 

Plants Primary Crop Fluensulfone BSA·, as parent equivalent 

Rotational Crop Fluensulfone BSA·, as parent equivalent 

Livestock Ruminant None None 

Poultry None None 

Page 11 of20 
Fluensulfone Aggregate Human Health Risk Assessment 0427229 

Ta ble 4. Summary of Metabolites a nd Degradates to be included in t he Risk Assessment a nd Toler ance 

Expression of Fluensulfone. 

Matrix Residues included in Risk Assessment Residues lncluded in Tolerance Expression 

Drinking Water Fluensulfone + Mes· + deschloro- Not Applicable 

fluensulfone, expressed as parent 

equivalent 

• BSA refers to the butene sulfonic acid metabolite (3,4,4-trifluoro-but-3-ene-l-sulfonic acid; Company Code M3627); MeS refers to the methyl sulfone metabolite (5-chloro-2-methyl sulfonyl thiazole; Company Code M3626). 

Analytical Methods. An analytical method suitable for enforcement purposes has been approved 

by the Agency (0403813, M. Doherty, 4 June 2014). That same method was used in the field 

trials for carrot and was shown to be appropriate for that crop. The method has an LOQ, defined 

as the lower limit of method validation, of 0.01 ppm. For carrot, the method has a calculated 

LOQ of 0.005 ppm. 

Residue Chemistry. The registrant submitted a study volume (MRID 4955361 3) depicting crop 

field trials conducted in carrot. The study was submitted in support of several newly petitionedfor uses. In that study, 1 field trial was conducted each in Florida, Texas, New Mexico, Ohio, 

Washington, Nova Scotia, and Quebec; two trials were conducted in Ontario, and three trials 

were conducted in California (12 trials total). A granular formulation of fluensulfone was applied 

at 3.6 lb a.i./A (nominal), 6-8 days prior to planting. The applied material was incorporated into 

the soil by tilling. Carrots were harvested at maturity and sent to Golden Pacific Laboratories for 

analysis. Samples were stored frozen for up to 526 days; and residues were shown to be stable 

based on concurrent storage stability data. Residues inion carrot ranged from <0.01 to 0.495 ppm 

for fluensulfone and from <0.01 to 1.24 ppm for BSA. 

The results from the field trials may overestimate residues in/on carrot treated as part of the 

Section 18 exemption due to the exaggerated rate (3.6 vs. 2.5 lb a.i./ A), use of a granular rather 

than a liquid product, and the shorter pre-plant interval (7 vs. 14 days). Using the results from the 

field trials as input to the OECD MRL/tolerance calculation procedures results in a tolerance for 

residues of fluensulfone (based on BSA as parent-equivalent) of 2.0 ppm. 

Processed Food and Feed. There are no significant processed food/feed items associated with 

carrot. 

Meal, Milk, Poultry, and Eggs. Carrot culls may be fed to dairy cattle. At this time, there are no 

other livestock feedstuffs associated with registered uses of fluensulfone. Studies delineating the 

metabolism of fluensulfone in livestock commodities indicates that the parent compound is 

cleaved forming BSA as an intermediate compound. Metabolism continues such that 

fluensu lfone, and by extension BSA, is further broken down into its constituent components and 

incorporated into natural products. Based on OPP's understanding of the metabolism of 

fluensulfone in livestock animals and on the low proportion of carrot culls as a livestock feed 

item (maximum of 10% in a reasonably balanced modeled diet), there is no expectation of finite 

Page 12 of20 
Fluensulfone Aggregate Human Health Risk Assessment D427229 

residues of BSA in livestock commodities, including milk; therefore, tolerances for residues of 

tluensulfone in livestock commodities are not needed at this time [40 CFR 180.6(a)(3)]. 

Rotational Crop Restrictions. The Section 18 label specifies that only crops on the registered 

label may be planted into a field within l year of applying the product. 

International Residue Limits. At this time, there are no CODEX or Canadian MRLs that will 

impact the setting of tolerances for this Section 18 exemption. 

Dietary Exposure Analysis 

Acute and chronic aggregate dietary (food and drinking water) exposure and risk assessments 

were conducted using the Dietary Exposure Evaluation Model software with the Food 

Commodity Intake Database (DEEM-FCfD) Version 3.16, which uses 2003-2008 food 

consumption data from the U.S. Department of Agriculture's National Health and Nutrition 

Examination Survey, What We Eat in America, (NHANES/WWEIA). 

As previously noted, the residue of concern for dietary risk assessment is the parent compound 

fluensulfone. The maximum fluensulfone residue observed in the carrot field trials was 0.495 

ppm. HED has updated the previous dietary exposure and risk assessment (D4 l 8204, M. 

Doherty, 10 June 2014) to reflect a 0.5-ppm residue level on all carrot (i.e., I 00% crop treated). 

As an estimated drinking water concentration of fluensulfone, HED used the values previously 

provided by EFED: 77.6 ppb for acute and 52.5 ppb for chronic (D417634, J. Lin, January 2014). 

The dietary exposure and risk estimates should be considered screening-level estimates that 

likely overestimate actual exposures to fluensulfone that may result from the Section 18 use on 

carrot. Generally, HED is concerned when dietary risk estimates exceed I 00% of the populationadjusted dose for any of the representative populations within the consumption database (general 

U.S. population, infants, children 1-2 years old, children 3-5 years old, children 6-12 years old, 

youth 13-1 9 years old, adults 20-49 years old, adults 50-99 years old, and females 13-49 years 

old). For fluensulfone, the dietary risk estimates are not of concern for all population groups and 

for both acute and chronic exposure scenarios (Table 5). Complete input and output listings for 

the dietary exposure analysis are provided in Attachments 2-5. 

Table 5. Summa ry of Acute and Chronic Dietary Exoosure a nd Risk Estima tes for Fluensulfo ne. 

Acute (95th Percentile) Chronic 

Population Subgroup Exposure, mg/kg/day Risk, % aPAD Exposure, mg/kg/day Risk,% cPAD 

Total US Population 0.0045 2 0.001 2 4 

All Infants 0.0138 8 0.0034 11 

Children 1-2 0.0072 4 0.00 19 6 

Children 3-5 0.0058 3 0.0015 5 

Children 6-12 0.0042 2 0.0011 4 

Youth 13-1 9 0.0036 2 0.0009 3 

Adults 20-49 0.0043 2 0.0012 4 

Page 13 of20 
Fluensulfone Aggregate Human Health Risk Assessment 0427229 

Ta ble 5. Summa rv of Acute and Chronic Dietarv Exposure and Risk Estimates for Fluensulfo ne. 

Acute (95th Percentile) Chronic 

Population Subgroup Exposure, mg/kg/day Risk,% aPAD Exposure, mg/kg/day Risk,% cPAD 

Adults 50-99 0.0039 2 0.0012 4 

Female 13-49 0.0043 2 0.0012 4 

Residential Exposure 

At this time, there are no registered uses of fluensulfone that will result in direct residential 

exposure. 

Spray Drift 

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

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

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

for fluensulfone. The Agency has been working with the Spray Drift Task Force (a task force 

composed of various registrants which was developed as a result of a Data Call-In issued by 

EPA), EPA Regional Offices and State Lead Agencies for pesticide regulation and other parties 

to develop the best spray drift management practices (see the Agency's Spray Drift website for 

more information) 1

• The Agency has also developed a policy on how to appropriately consider 

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

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

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

concurrently. The approach is outlined in the revised (20 12) Standard Operating Procedures for 

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

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

of indirect non-occupational exposure to drift. 

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 Federal insecticide, Fungicide, and Rodenticide Act 

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

March 2, 20 I 0 (http://www.epa.gov/scipoly/SAP/meetings/2009/l 20 I 09meeting.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= EP A-H Q-0PP-2014-0219). During Registration 

Review, the Agency will use this analysis to determine if data (i.e., flux studies, route-specific 

inhalation toxicological studies) or further analysis is required for fluensulfone. 

1 Available: http://www.epa.gov/oppOOOO l /factsheets/spraydrift.htm. 

Page 14of20 
Fluensulfone Aggregate Human Health Risk Assessment D427229 

Aggregate Risk 

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 various sources, HED considers both the route and 

duration of exposure. 

As previously noted, there are no residential uses for fluensulfone at this time; therefore, dietary 

(food and water) exposure is the only pathway appropriate for assessment. Aggregate risk 

estimates are equivalent to the dietary risk estimates discussed above and are not of concern. 

Cumulative Risk 

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

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

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

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

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

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

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

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

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

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

Attachments 

1. Summary of OECD MRL([olerance Calculation Procedures 

2. Inputs to the Acute Dietary Assessment 

3. Inputs to the Chronic Dietary Assessment 

4. Summary of the Acute Dietary Assessment Results 

5. Summary of the Chronic Dietary Assessment Results 

Page 15 of20 
Fluensulfone Aggregate Human Health Risk Assessment 

Attachment 1. Summary of OECD MRLff olerance Calculation Procedures 

BSA as Fluensulfone 

Carrot 

USA 

Preplant 2.5 lb ai/A 

Total number of data (n) 

Percentage of censored data 

Number of non-censored data 

Lowest residue 

Highest residue 

Median residue 

Mean 

Standard deviation (SD) 

Correction factor for censoring (CF) 

Proposed MRL estimate 

- Highest residue 

- Mean + 4 SD 

- CF x 3 Mean 

Unrounded MRL 

Rounded MRL 

Residues (mg/kg) n 

< 0 . 01 1 

0 . 059 1 

0 . 091 1 

0 . 130 1 

0 . 184 1 

0 . 217 1 

0 . 276 1 

0 . 336 1 

0 . 371 1 

0 . 457 1 

0 . 708 1 

1. 20 1 

Page 16 of20 

12 

8% 

11 

0 . 010 

1 . 204 

0 . 247 

0 . 337 

0 . 335 

0 . 944 

1 . 204 

1. 676 

0 . 955 

1. 676 

2 

0427229 
Fluensulfone Aggregate Human Health Risk Assessment 

Attachment 2. Inputs to the Acute Dietary Assessment 

Filename : Acute Fluen PRZM-G~I Sl8 separate . rOB 

Chemical : Fluensulfone Systemic 

RfD(Chronic) : . 03 mg/kg bw/day NOEL(Chronic) : 0 mg/kg bw/day 

RfD(Acute) : . 18 mg/kg bw/day NOEL(Acute) : 0 mg/kg bw/day 

Date created/last modified : 05- 29-2015/21 : 49 : 49 Program ver . 3 . 16, 03-0B-d 

EPA Crop 

Code Grp Commodity Name 

Def Res 

(ppm) 

010107B000 lAB 

010107B001 lAB 

0101079000 lAB 

OB01374000 BA 

OB01375000 SA 

OS01375001 SA 

OS01376000 SA 

OS01376001 SA 

OS01377000 SA 

OB01377001 SA 

OS0137SOOO SA 

080137S001 SA 

OB01379000 SA 

OB013SOOOO BA 

OS0214SOOO SBC 

0B02234000 BBC 

OB02270000 SB 

OB02270001 BB 

0802271000 8B 

OB02271001 SB 

0802272000 BBC 

OS02272001 SBC 

OB02273000 BBC 

0901075000 9A 

0901187000 9A 

0901399000 9A 

0901400000 9A 

0902021000 9B 

09020SSOOO 9B 

0902102000 9B 

0902135000 9B 

090230SOOO 9B 

0902309000 9B 

0902356000 9B 

0902356001 9B 

0902357000 9B 

0902357001 96 

S601000000 B6A 

S602000000 S6B 

Carrot 

Carrot-baby food 

Carrot, juice 

Tomatillo 

Tomato 

Tomato-baby food 

Tomato, paste 

Tomato, paste-babyfood 

Tomato , puree 

Tomato, puree - babyfood 

Tomato , dried 

Tomato, dried-babyfood 

Tomato, juice 

Tomato, Tree 

Eggpl ant 

Okra 

Pepper, bell 

Pepper, bell- babyfood 

Pepper, bell, dried 

Pepper, bell, dried-babyfood 

Pepper, nonbell 

Pepper, nonbell- babyfood 

Pepper, nonbell , dried 

Cantaloupe 

Honeydew melon 

Watermelon 

Watermelon , juice 

Balsam pear 

Chayote , fruit 

Chinese waxgourd 

cucumber 

Pumpkin 

Pumpkin , seed 

Squash , summer 

Squash , summe r-baby food 

Squash , winter 

Squash, winter-babyfood 

Water, direct, all sources 

Water, indirect, all sources 

0 . 500000 

0 . 500000 

0 . 500000 

0 . 010000 

0 . 010000 

0 . 010000 

0 . 010000 

0 . 010000 

0 . 010000 

0 . 010000 

0 . 010000 

0 . 010000 

0 . 010000 

0 . 010000 

0 . 010000 

0 . 010000 

0 . 010000 

0 . 010000 

0 . 010000 

0 . 010000 

0 . 010000 

0 . 010000 

0 . 010000 

0 . 010000 

0 . 010000 

0 . 010000 

0 . 010000 

0 . 010000 

0 . 010000 

0 . 010000 

0 . 010000 

0 . 010000 

0 . 010000 

0 . 010000 

0 . 010000 

0 . 010000 

0 . 010000 

0 . 077600 

0 . 077600 

Page 17of20 

Ad j . Factors commen t 

81 #2 

1. 000 

1 . 000 

1 . 000 

1 . 000 

1 . 000 

1 . 000 

1 . 000 

1 . 000 

1 . 000 

1.000 

1. 000 

1 . 000 

1 . 000 

1 . 000 

1 . 000 

1 . 000 

1 . 000 

1 . 000 

1. 000 

1 . 000 

1 . 000 

1 . 000 

1 . 000 

1 . 000 

1 . 000 

1 . 000 

1 . 000 

1. 000 

1 . 000 

1 . 000 

1 . 000 

1 . 000 

1 . 000 

1 . 000 

1 . 000 

1 . 000 

1 . 000 

1 . 000 

1 . 000 

1 . 000 

1 . 000 

1 . 000 

1 . 000 

1 . 000 

1 . 000 

1 . 000 

1 . 000 

1 . 000 

1 . 000 

1 . 000 

1 . 000 

1 . 000 

1 . 000 

1 . 000 

1 . 000 

1 . 000 

1 . 000 

1 . 000 

1 . 000 

1 . 000 

1 . 000 

1 . 000 

1 . 000 

1 . 000 

1 . 000 

1 . 000 

1.000 

1 . 000 

1 . 000 

1 . 000 

1 . 000 

1 . 000 

1 . 000 

1 . 000 

1 . 000 

1 . 000 

1 . 000 

1 . 000 

D427229 
Fluensulfone Aggregate Human Health Risk Assessment 

Attachment 3. Inputs to the Chronic Dietary Assessment 

Filename : Chronic Fluen PRZM-GW SlB separate . r oe 

Chemical : Fluensulfone Systemic 

RfD(ChronicJ: . 03 mg/kg bw/day NOEL(ChronicJ : 0 mg/kg bw/day 

RfD(Acu te) : . lS mg/kg bw/day NOEL(Acute) : 0 mg/kg bw/day 

Date created/last modified : 05-29- 2015/21 : 50 : 21 Program ver. 3 . 16, 03-0S-d 

EPA Crop 

Code Grp Commodity Name 

Def Res 

(ppm) 

010107SOOO lAB 

010107S001 lAB 

0101079000 lAB 

080137 4000 SA 

OS01375000 SA 

OS01375001 SA 

OS01376000 SA 

OS01376001 BA 

OS01377000 SA 

OS01377001 SA 

OS0137SOOO SA 

OS0137S001 SA 

OS01379000 BA 

OS013SOOOO SA 

OS0214SOOO SBC 

OS0223 4000 SBC 

OS02270000 SB 

OS02270001 SB 

0802271000 SB 

OS02271001 SB 

0802272000 SBC 

OS02272001 BBC 

OS02273000 BBC 

0901075000 9A 

09011S7000 9A 

0901399000 9A 

0901400000 9A 

0902021000 9B 

09020SSOOO 9B 

0902102000 9B 

0902135000 9B 

090230S000 9B 

0902309000 9B 

0902356000 9B 

0902356001 9B 

0902357000 9B 

0902357001 9B 

8601000000 S6A 

S602000000 S6B 

Carrot 

Carrot- baby food 

Carrot, juice 

Tomatillo 

Tomato 

Tomato-baby food 

Tomato , paste 

Tomato, paste- babyfood 

Tomato , puree 

Tomato , puree-babyfood 

Tomato, dried 

Tomato, dried-babyfood 

Tomato , juice 

Tomato, Tree 

Eggplant 

Okra 

Pepper, bell 

Pepper, bell- babyfood 

Pepper, bell , dried 

Pepper, bell, dried-babyfood 

Pepper, nonbell 

Pepper, no nbell-babyfood 

Pepper, nonbell, dried 

Cantaloupe 

Honeydew melon 

Wa termelon 

Watermelon, juice 

Balsam pear 

Chayote, fruit 

Chinese waxgourd 

Cucumber 

Pumpkin 

Pumpkin , seed 

Squash , summer 

Squash, summer-babyfood 

Squash, winter 

Squash , winter-babyfood 

Water, direct, all sources 

Water, indirect, all sources 

0 . 500000 

0 . 500000 

0 . 500000 

0 . 010000 

0 . 010000 

0 . 010000 

0 . 010000 

0 . 010000 

0 . 010000 

0 . 010000 

0 . 010000 

0 . 010000 

0 . 010000 

0 . 010000 

0 . 010000 

0 . 010000 

0 . 010000 

0 . 010000 

0 . 010000 

0 . 010000 

0 . 010000 

0 . 010000 

0 . 010000 

0 . 010000 

0 . 010000 

0 . 010000 

0 . 010000 

0 . 010000 

0 . 010000 

0 . 010000 

0 . 010000 

0 . 010000 

0 . 010000 

0 . 010000 

0 . 010000 

0 . 010000 

0 . 010000 

0 . 052500 

0 . 052500 

Page 18 of20 

Adj . Factors Comment 

#1 #2 

1 . 000 

1 . 000 

1 . 000 

1 . 000 

1 . 000 

1 . 000 

1 . 000 

1 . 000 

1 . 000 

1 . 000 

1.000 

1 . 000 

1 . 000 

1.000 

1 . 000 

1 . 000 

1 . 000 

1 . 000 

1 . 000 

1 . 000 

1.000 

1 . 000 

1 . 000 

1 . 000 

1 . 000 

1 . 000 

1 . 000 

1 . 000 

1 . 000 

1 . 000 

1 . 000 

1 . 000 

1 . 000 

1 . 000 

1. 000 

1 . 000 

1 . 000 

1. 000 

1 . 000 

1.000 

1 . 000 

1 . 000 

1 . 000 

1 . 000 

1 . 000 

1 . 000 

1 . 000 

1 . 000 

1 . 000 

1.000 

1 . 000 

1 . 000 

1 . 000 

1 . 000 

1 . 000 

1 . 000 

1 . 000 

1.000 

1 . 000 

1 . 000 

1 . 000 

1 . 000 

1 . 000 

1 . 000 

1 . 000 

1 . 000 

1 . 000 

1 . 000 

1 . 000 

1 . 000 

1.000 

1 . 000 

1 . 000 

1 . 000 

1 . 000 

1 . 000 

1 . 000 

1 . 000 

0427229 
Fluensulfone Aggregate Human Health Risk Assessment D427229 

Attachment 4. Summary of the Acute Dietary Assessment Results 

OPP Health Effects Division Ver . 3 . 16, 03-08-d 

DEEM-FCID ACUTE Ana lysis for FLUENSULFONE SYSTEMIC NHANES 2003- 2008 2- 0ay 

Residue file : Acute Fluen PRZM-GW Sl8 separate . roe 

Adjustment factor #2 NOT used . 

Analysis Date : 05- 29-2015/21 : 52 : 50 Residue file dated : 05- 29-2015/21 : 49 : 49 

RAC/FF intake summed over 24 hours 

Run Corrunen t : "" 

Surrunary calculations--per capita : 

95th Percentile 99th Percentile 99 . 9th Percentile 

Exposure % aRf D Exposure % aRfD Exposure % aRfD 

---------- -------- ---------- -------- ---------- -------- Total us Population : 

0 . 004466 2 . 48 0 . 007375 4 . 10 0 . 013782 7 . 66 

All Infants: 

0 . 013766 7 . 65 0 . 019161 10 . 65 0 . 026334 14 . 63 

Children 1- 2 : 

0 . 007188 3 . 99 0 . 011105 6 . 17 0 . 024770 13 . 76 

Children 3- 5 : 

0 . 005774 3 . 21 0 . 008336 4 . 63 0 . 013205 7 . 34 

Children 6- 12 : 

0 . 004210 2 . 34 0 . 007023 3 . 90 0 . 010497 5 . 83 

Youth 13-19 : 

0 . 003600 2 . 00 0 . 005865 3 . 26 0 . 008811 4 . 89 

Adults 20- 49 : 

0 . 004267 2 . 37 0 . 006300 3 . 50 0 . 009049 5 . 03 

Adults 50- 99 : 

0 . 003862 2 . 15 0 . 005791 3 . 22 0 . 0088 45 4 . 91 

Female 13-49 : 

0 . 004329 2 . 41 0 . 006373 3 . 54 0 . 008770 4 . 87 

Page 19 of20 
Fluensulfone Aggregate Human Health Risk Assessment 

Attachment 5. Summary of the Chronic Dietary Assessment Results 

OPP Health Effects Division 

DEEM-FCID Chronic analysis for FLUENSULFONE SYSTEMIC 

Residue file name : Chronic Fluen PRZM-GW Sl8 separate . roe 

Ver . 3 . 16, 03-08 - d 

NHANES 2003-2008 2-day 

Adjustment factor #2 NOT used . 

Analysis Date 05- 29-2015/21 : 51 : 32 Residue file da ted: 05-29-2015/21 : 50 : 21 

Reference dose (RfD, Chronic) = . 03 mg/kg bw/day 

Total exposure by population subgroup 

Total Exposure 

Population 

Subgroup 

Total US Population 

Hispanic 

Non-Hisp-White 

Non-Hisp-Black 

Non-Hisp-Other 

Nursing Infants 

Non-Nursing Infants 

Female 13+ PREG 

Children 1-6 

Children 7-12 

Male 13-19 

Female 13-19/NP 

Male 20+ 

Female 20+/NP 

Seniors 55+ 

All Infants 

Female 13-50 

Children 1-2 

Children 3-5 

Children 6- 12 

Youth 13-19 

Adults 20-49 

Adults 50-99 

Female 13-49 

mg/ kg 

body wt/day 

0 . 001195 

0 . 001155 

0 . 001227 

0 . 000970 

0 . 001411 

0 . 001452 

0 . 004293 

0 . 001097 

0 . 001658 

0 . 001027 

0 . 000812 

0 . 000901 

0 . 001090 

0 . 001233 

0 . 001143 

0 . 003416 

0 . 001164 

0 . 001921 

0 . 001549 

0 . 001084 

0 . 000857 

0 . 001166 

0 . 001161 

0 . 001163 

Page 20 of20 

Percent of 

Rfd 

4 . 0% 

3.8% 

4 . 1% 

3 . 2% 

4.7% 

4 . 8% 

14 . 3% 

3 . 7% 

5 . 5% 

3 . 4% 

2 . 7% 

3. 0% 

3 . 6% 

4 . 1% 

3 . 8% 

11. 4% 

3 . 9% 

6 . 4% 

5 . 2% 

3 . 6% 

2 . 9% 

3 . 9% 

3 . 9% 

3.9% 

0427229