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O ~ Q 71 ~ 

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PROI,G~\ 

Registration UecIlsIlon for Fluensulfone 

A nematicide for use on fruiting vegetables (crop group 8) and 

cucurbits (crop group 9) 

Approved b 

Date: r 
Il a Summary 

The U.S. Environmental Protection Agency referred to hereafter as EPA, is granting the 

unconditional registration under section 3(c)(5) of the Federal Insecticide, Fungicide, and 

Rodenticide Act (FIFRA) of the new active ingredient, fluensulfone, formulated as a techn.cal 

and one end use product (Fluensulfone 480 EC Nematicide). Fluensulfone is the first nematicide 

in the fluroalkenyl class. The proposed uses include fruiting vegetables, Crop Group 8; atud 

cucurbit vegetables, Crop Group 9. The end-use product formulation is an emulsifiable 

concentrate (EC). Methods of application include broadcast, banded, and drip irrigation 

applications followed by either mechanical soil incorporation (broadcast, banded) or delivery via 

water (drip irrigation) to a 6-8 inch depth. The maximum single application rate is 2.5 lbs a.i./A., 

with a yearly maximum of 3.5 lbs a.i./A for sites that permit multiple crop cycles per year. 

The database submitted to support the Human Health Risk and Ecological Risk assessmerits is 

complete. For occupational scenarios, short-term (1-30 days) and intermediate-term (1-6 

months) dermal exposures of concern may occur from mixing/loading activities for chemi,;ation 

applications. These risk concerns have been addressed with the requirement of additional 

personal protective equipment (PPE), engineering controls, and a reduction in the maximlim 

single application rate as discussed in section 7.2.3 Mitigation and Labeling Requirements. The 

reduced maximum single application rate also applies to ground broadcast and banded 

applications to address the need for additional PPE requirements during application. 

The screening-level Ecological Risk Assessment identified potential risk concerns for dirF:ct 

effects to birds, mammals and terrestrial semi-aquatic listed dicot plants. Requiring a lower 

boom height and coarser droplet spectra for ground spray applications, as well as the 

consideration of variable dietary requirements (birds and mammals) and the types of food likely 

to be present during fluensulfone applications, reduced the risk profile for these taxonomic 

groups. Further, relative to the alternative registered products, the Agency believes fluens.ulfone 

has a lower hazard profile. The current alternatives consist of soil fumigants and an n-metllyl 

carbamate. 

2> 1Requested Action 

On April 13, 2012, EPA received an application to register products containing the new 4,_ :ive 

ingredient, fluensulfone, a nematicide, for use on cucumbers, melons (cantaloupes, waterr ::lon. 

honeydew), squash, tomatoes, okra, eggplant, and peppers (bell and non-bell). 

Applicant: Makhteshim Agan of North America (d.b.a. ADAMA) 

3. ChernicalInformation 

C'luemical Narne: Fluensulfone: 5-chloro-2-[(3,4,4-trifluoro-3-buten-1-}!l)sulfonyl] thiazc e 

EPA PC Code: 050410 

Pa~c : of'23 
Chemical Abstracts Service (CAS) Number: 318290-98-1 

Mode of Action: Fluensulfone is a pyrazole nematicide, and is the first nematicide in the 

fluoroalkenyl class. It targets root-knot (Meloidogyne spp.), sting (Belonolaimus spp.), and lesion 

nematodes (Pratylenchus spp.). Fluensulfone has a pleiotropic expression of activity again 3t 

nematodes that includes weak inhibition of motility in adults, strong inhibition of motility : n 

larvae, feeding inhibition and egg-laying, hatching and developmental inhibition. Inhibitic>>1 of 

larval thrashing and feeding is irreversible after 24 hours of exposure and the cuticle does ilot 

appear to prevent access of fluensulfone. 

1'roducts: Fluensulfone is registered with the EPA Registration Number 11678-73 (Fluen.sulfone 

"I'echnical) and 66222- 243 (Fluensulfone 480EC Nematicide). Methods of application inc:lude 

broadcast, banded, and drip irrigation applications. Applications must be soil incorporated by 

water and/or mechanical means to a 6-8-inch depth. The maximum application rate is 2.5 ] ~ 

a.i./A. Aerial applications are prohibited. 

41< Human Health 12isk AssessnIlent 

A summary of the human health risks of fluensulfone is provided below. The database is 

complete and the occupational risks were deemed acceptable with the proposed mitigatiorl and 

labeling requirements. There were no other human health risks identified with the registracion of 

this chemical for the proposed uses. 

4.1. Hazau°d Chap-acterization 

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

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 e-ffects 

on the hematopoietic system observed at higher doses. Effects on the hematopoietic systc•rn 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 fluensulfone can 

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

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 Jays) 

compared to plasma (DT5o = 16-17 hours). 

Other effects commonly observed in mice, rats and dogs included changes in clinical chetnistry 

parameters and decreased body weights, both of which were often seen at the LOAELs in 

subchronic and chronic studies. Altered clinical chemistry parameters included decreasecl 

plasma alanine amino transferase (ALAT, rats and dogs), increased cholesterol (rats), increased 

triglycerides (rats), increased phospholipids (rats), increased (mice) or decreased (dogs) 

Page 3 of 23 
bilirubin, 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, th. ~ dog 

appeared to be slightly more sensitive than mice and rats. 

Fluensulfone also caused effects on the kidney in male rats; however, the effects are cons tent 

with accumulation of a-2-microglobulin in the kidneys which is a male rat specific proce: ,: that 

is not relevant for human health risk assessment. 

Effects on the lung were observed following chronic dietary exposure in mice and rats. T'hese 

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

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

to cubodial 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 ::1;-day 

dermal study. The dermal effects were considered adaptive due to the moderate degree o1' 

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, the toxicity studies do indicate that exposure to fluensulfone has the 

potential to result in fluoride exposure. However, residue data demonstrate that total fluor:de 

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

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

exposure. 

There was no evidence of immunotoxicity in the rat. Following a single oral administratican, rats 

exhibited decreased locomotor activity, decreased spontaneous activity, decreased rearing, and 

impaired righting response was observed only on Day 1 in the acute neurotoxicity study. Pdo 

evidence 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 very high dose (2000 

mg/kg/day which is twice the highest dose required by the guidelines for a dermal study). 

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 obse.rved in the presence of decreased body weight in maternal animals. In thc 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. In the two generation reproduction study, there was no evidence of 

quantitative susceptibility. Evidence for qualitative susceptibility was observed, manifestE:d as 

Page •4 of 23 
decreased pup weight, decreased spleen weight, and an increase in post-natal pup loss [post-natal 

days (PND) 1-4]. These effects were seen at the same dose that caused decreases in body weight 

in the parental 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) classitied 

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 

female mice in the carcinogenicity study. All genotoxicity studies that were conducted oil 

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 st:rain 

TA 100 in the absence of inetabolic activation during a bacterial reverse mutation assay. `:,"aere is 

little concern for the positive results as the strain was abolished by the presence of S9 and -xas 

not observed in other tester strains specific for base-pair changes. Based on the results of the 

genetic toxicology studies, it was concluded that there is no mutagenic concern for fluens ,111fone 

or the fluensulfone metabolites tested. 

4.1.1. Food Quality Protection Act (FQPA) Safety Factor 

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

1 Ox FQPA safety factor to 1 x based on the following considerations: the completeness of :he 

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 t 7xicity 

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 susceptibi L ity 

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 

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. 

4.1.2. Cumulative Effects 

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

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

to fluensulfone and any other substances. For the purposes of this action, therefore, EPA 

believes that fluensulfone does not have a common mechanism of toxicity with other substances. 

Page :5 of 23 
4.1.3. Toxicological Endpoints 

Table 1. Summary of Toxicological Doses and Endpoints 1'or use in IFluensulfone Dia: :rry 

and Non-®ccu ational Human Health Risk Assessments. 

Exposure/Scenario Point of Departure and RfD, PAD, Studv and Toxicologicai Eff ~ cts 

Uncertainty/Safety LOC for Risk 

Factors Assessment 

Acute dietary NOAEL = 16.2 Acute RfD = 2-generation reproduction-rat 

(AIl populations, including rng/kg/day 0.16 Offspring LOAEL = 122.0 rn ;~;.'kg/day 

infants and children and UFA = lOx mg/kg/day based on an increase in pup Ic*s 

females 13-49 years of UF,, = l Ox between PND 1 and 4 in the E" and F2 

age) FQPA SF = 1 x aPAD = 0.16 offspring with the rnajority of cleaths 

mg/kg/day occurring on day 2. 

Chronic dietary NOAEL= 3.1 mg/k;/day Chronic RfD = Co-critical 90-day dog and chr•anic dog 

(AII populations) UFA = l Ox 0.03 mg/kg/day 

UFfr = l Ox Chronic:NOAEL = 3.1 mg/k,-;'aay 

FQPA SF = 1 x cPAD = 0.03 LOAEL = 16 mg/kg/day based on 

mg/kg/day decreased body weight, increus•ed 

mean hemoglobin concentration 

distribution width, and increa>c:d 

relative and absolute reticulo<:vte 

counts in both sexes, decreasacl 

prothrombin time in males ancl 

increased platelets in females 

Subchronic:NOAEL = 1.6 m:; kg/dav 

LOAEL = 17.1 mglkg/day ba>1:d on 

decreased body weight in fen - ,: I,,s and 

increased relative and absolute 

reticulocyte counts, decreasecl 

bilirubin, decreased albumin, 

decreased A/G ratio, increase;i "fSH, 

and pigmented Kupffer cells ir; both 

sexes. 

Incidental oral (AIl A dose and endpoint for incidental oral exposure were not selected because there are 

durations) presently no residential uses for fluensulfone. 

Dermal (AII Durations) A dose and endpoint for dermal exposure were not selected because there arc: 

presently no residential uses for fluensulfone. 

Inhalation (All Durations) A dose and endpoint for inhalation exposure were not selected because there are 

presently no residential uses for fluensulfone. 

Cancer Classitication: Suggestive evidence of carcinogenicity in humans based on lung 

tumors in female mice. 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 clata and 

used to mark the beginning of extrapolation to determine risk associated with lower environmentally relevant huinari 

exposures. NOAEL = no observed adverse effect level. LOAEL = lowest observed adverse effect level. [. I' = 

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 LOAEL to extrapolate a 

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

reference dose. MOE = margin of exposure. LOC = level of concern. 

Pagc 6 of 23 
'g'able 2. Summary o6 Toxieological Doses and Endnoints for use in Fluensulfone 

OccuPational Human Health 12isk Assessments. 

Fxposure/Scenario Point of 19eparture and RfD, PAD, Study and Toxicological E1'fects 

Uncertaintv/Safety Factors LOC for Risk 

Assessment 

Dermal short- and NOAEL= 3.1 mg/kg/day Occupational Co-critical 90-day dog and cltironic 

intertnediate-term dennal absorption factor: LOC for MOE dog 

( I to 30 days and I to 6 40.9% =100 

months) UFA = l Ox Chronic: NOAEL=3.1 mg/k;;-'day 

UFH = lOx LOAEL = 16 mg/kg/day based on 

decreased body weight, increased 

mean hetnoglobin concentraJon 

distribution width, and incre3:ied 

relative and absolute reticulocyte 

counts in both sexes, decreas , .I 

prothrotnbin time in males t{rta 

increased platelets in femalea. 

i

Subchronic: NOAEL = 1.6 in,;!kg/day 

LOAEL = 17.1 tng/kg/day ba 5ed on 

decreased body weight in females and 

increased relative and absoluK ~ 

reticulocyte counts, decreasec 

bilirubin, decreased albumin, 

decreased A/G ratio, increas.d TSH. 

and pigmented Kupffer cells in both 

sexes. 

Inhalation short- and NOAEL= not established Occupational 90-day inhalation toxicity — rat 

intermediate-term (<0.04 mg/L) LOC for MOE = LOAEL = 0.04 mg/L based c-n weight 

(1 to 30 days and I to 6 HEC = 0.00429 mg/L 300 loss in males, prolonged pro- :rirombin 

months) HED = 0.244 mg/kg/day (low time in fetnales, decreased thytnus 

breathing rate), = 0.491 weight in males, histopathobo;;ical 

mg/kg/day (medium changes in the epiglottis in hoth sexes. 

breathing rate), = 0.853 and histopathological chang(n in the 

mg/kg/day (high breathing nasal cavity of males. 

rate) 

UFA = 3x 

UFH = I Ox 

UFL 

Cancer Classification: Suggestive evidence ofcarcinogenicity in humans based on lunlz tumors 

in female mice. 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 usc.:i 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. UI - A = 

extrapolation from animal to human (interspecies). UFH = potential variation in sensitivity among members of the hum:111 

population (intraspecies). UFL = use of a LOAEL to extrapolate a NOAEL. MOE = margin ot'exposure. LOC =level ol' 

concern. DAF = dermal absorption factor 

HEC = rat NOAEL x(daily duration adjustment) x weekly daily duration adjustment x RDDR 

=0.04 mg/L x(6 hr/8 hr) x(1) x 0.143 = 0.00429 mg/L. 

1-IFD = hIEC 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: 'T of 23 
4.2. Exposure and Rislc Chau°acterization 

4.2.1. Dietary Exposure and Risk 

Studies depicting the metabolism of fluensulfone in lettuce, potato, and tomato as primar:, :;rops 

are adequate to delineate the residues of concern for the currently proposed uses. The stuc .cs 

were conducted at approximately a 1X application rate but with a shorter pre-plant interv4.i 1'0 

days) than specified on the label (7 days). Mature and immature lettuce and potatoes and r.latui -e 

tomatoes were harvested and analyzed for residues. The only major residues in the harvested 

matrices were the BSA and TSA metabolites and, with the exception of trace levels of 

fluensulfone in immature lettuce and mature potato, no parent compound was detected. Tlic short 

pre-plant interval is not expected to have significantly altered the residue profile in the harvested 

crops. 

Rotational crop studies were conducted with radish, lettuce, and wheat at plant-back inter;.ds of 

30, 120, and 360 or 390 days. As with primary crops, the major residues were the BSA a ~~~ :l "I'SA 

metabolites. The similarity in the results is not unexpected given that for both types of stticlies, 

application of the test compound was to the soil early in the planting season. In the rotatioiial 

crop studies, a low level of the parent compound was observed in lettuce, radish root, radish 

foliage, and wheat forage, hay, and straw (but not grain). Fluensulfone, when found, was 

typically 1 to 2 orders of magnitude less than the BSA or TSA residue levels. In all cases, 

residues of fluensulfone and BSA were not quantifiable after the 120-day plant-back interc-al 

whereas residues of TSA persisted at quantifiable levels for at least one year. 

1'Qants (Primary Crops): For dietary risk assessment of fluensulfone on primary crops, parent 

compound should be the only residue included as a residue of concern because at levels e ~ cpected 

in foods, the TSA and BSA metabolites are considered to be relatively non-toxic. No 

quantifiable residues of parent fluensulfone were observed in the crop field trials and only :race 

residues of parent fluensulfone were observed in potato tubers and immature lettuce from 

metabolism studies. The metabolites TSA and BSA are the primary residues observed in 

metabolism and field trials. 

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

compound alone is a poor indicator of adulteration due to the lack of quantifiable residues. "I'hc 

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 adulteratiori. 

Rotational Crops: Rotational crop data indicate that metabolites TSA and BSA are the primary 

anticipated residues, with minimal residues of fluensulfone observed. Although TSA was a 

primary residue in rotational crop studies, it may not be an adequate indicator of adulteratic>n 

given its persistence. For tolerance enforcement, residues of BSA, expressed as parent 

equivalents, are considered an adequate indicator of adulteration, as discussed above for primary 

crops. 

Livestoek: There are no livestock feed items associated with the current application tor tl ;: 

proposed uses. Therefore, EPA did not assess livestock feed. 

Pa ~,c : oi'23 
Water: The Agency's Residues of Concern Knowledgebase Subcommittee (ROCKS) 

recommended including parent fluensulfone as well as the two transformation products McS and 

deschloro-fluensulfone in the risk assessment concerning water. The deschloro-fluensulfcnie 

metabolite is considered to be substantially similar to the parent compound, and the MeS 

metabolite has acute toxicity data suggesting that it has similar toxicity to fluensulfone. 

Although there are several other major metabolites, the Agency only included the two 

transformation products mentioned earlier in this section. The Agency made this determin,ition 

in particular, because acute and subchronic toxicity data for the sulfonic acid metabolites 

(deschloro thiazole sulfonic acid (TSA) and butene sulfinic acid (BSA)) indicate that they are 

significantly less toxic than the parent fluensulfone. Furthermore, concern for toxicity of the 

other acid metabolites (BSA and TSA) are diminished because in contrast to the parent chemical; 

the acid moiety in these metabolites significantly increases the likelihood of rapid body 

excretion. First, the acid moiety significantly decreases lipophilicity relative to the parent 

chemical and thus the likelihood for bioaccumulation. Second, the acid functional group i:; 

predicted to be charged in the body at physiological pH (predicted pKa =-7.11) and thus readily 

excreteable by renal anion transporters. In contrast, MeS and deschloro-fluensulfone are 

expected to be more similar to parent fluensulfone in terms of excretion by the body. Ther::fore, 

only fluensulfone, deschloro-fluensulfone, and MeS were included for risk assessment. 

4.1.1.1. Acute Dietary Risk 

For the acute assessment for fluensulfone, LOQ-level residues of fluensulfone (0.01 ppm;) ,tre 

assumed for all crops. EPA also assumed that 100% of the crops are treated with fluensulf ~ ne. 

Dietary exposure (food + drinking water) and risk estimates were developed for the follow .ng 

population subgroups: the general U.S. population, all infants (<1 year old), children 1-2, 

children 3-5, children 6-12, youth 13-19, adults 20-49, females 13-49, and adults 50+ years old. 

Generally, EPA is concerned when dietary risk estimates exceed 100% of the populationadjusted dose (PAD) for acute exposure scenarios. For fluensulfone, all dietary risk estimu.tes 

were well below 100% of the acute PAD. The maximum exposure and risk estimates occurred 

for the "all infants" population subgroup and occupied 7.4% of the aPAD. 

4.1.1.2. C7tronic Dletary Risk 

For the chronic assessment for fluensulfone, LOQ-level residues of fluensulfone (0.01 ppm) are 

assumed for all crops. EPA also assumed that 100% of the crops are treated with fluensulfone. 

Dietary exposure (food + drinking water) and risk estimates were developed for the follow ing 

population subgroups: the general U.S. population, all infants (<1 year old), children 1-2, 

children 3-5, children 6-12, youth 13-19, adults 20-49, females 13-49, and adults 50+ year.s old. 

Generally, EPA is concerned when dietary risk estimates exceed 100% of the populationadjusted dose (PAD) for chronic exposure scenarios. For fluensulfone, all dietary risk estimates 

were well below 100% of the chronic PAD. The maximum exposure and risk estimates oc:curred 

for the "all infants" population subgroup and occupied 9.5% of the cPAD. 

Page ') of 23 
4.1.1.3. C'ancer 1)iePary Risk 

Fluensulfone is classified as having "suggestive evidence of carcinogenic potential." Risk 

assessments based on the chronic RfD are considered to be protective of any cancer risks. 

4.2.2. Residential Exposure and Risk 

There are no proposed residential uses of fluensulfone and exposure via residential pathwavs is 

not expected. 

4.2.3. Aggregate Exposure and Risk 

In accordance with the FQPA, EPA must consider and aggregate (add) pesticide exposurf:s and 

risks from three major sources: food, drinking water, and residential exposures. In an aggr.-gate 

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. ~ 'rJhen 

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

of exposure. 

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

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

estimates are equivalent to the dietary risk estimates and are below EPA's level of concerri. 

4.2.4. Occupational Exposure and Risk 

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

loading, and applying). Based on the use pattenn and application timing (i.e., soil-incorpoi•ited 

application seven days before transplanting), no post-application exposure is expected for 

workers re-entering treated areas. Based on the use patterns (i.e., 1 application per seasot)) and 

resistance management practices, the duration of exposure for the proposed food uses is eypected 

to be short-term (1-30 days) and intermediate-term (1-6 months). Long-term exposures (l,reater 

than 6 months) are not anticipated. 

The short- and intermediate-PODs are the same for dermal and inhalation exposure. Thererore, 

the quantitative short-term handler assessment represents both exposure durations and is 

protective of intermediate-term exposure. All inhalation occupational handler exposure risk 

estimates were not of concern (MOE > 300) using some level of personal protective equipment 

(PPE; i.e. no respirator or PF5 respirator). Dermal risk estimates were also not of concern Nvhen 

using some level of PPE (e.g. chemical-resistant gloves, engineering controls (enclosed 

systems)) with one exception. The mixing/loading liquids for chemigation scenario result ,A in a 

potential dermal risk of concern using engineering controls. When engineering controls arc: used 

as mitigation of potential worker exposure risk the maximum single application rate to achieve 

an acceptable MOE for mixing/loading liquids for chemigation is 2.5 Ib a.i./acre. These 

Page .~ 0 of 23 
requirements have been required on the label and are discussed in the Mitigation and LabE:ling 

section of this document (see section 7.2.3). 

5. Ecologica0 Igisk Assessment 

A summary of the environmental fate and ecological effects data is provided below along vith a 

summary of the ecological risk assessment. 

4.1. lF;trnvironmental Fate 

Fluensulfone is not expected to volatize from water or moist soil based on its water solubil .ty 

(545.3 mg/L at 20 0C), vapor pressure (2.3 x 10 4torr at 25°C), and Henry's Law Constant 11.65 

x 10"7 atm-m3/mol), but may volatize in dry field conditions. It is moderately mobile in soil, 

persists in anaerobic soil, and does not undergo hydrolysis; aqueous photolysis is the fastt.!,t 

route of fluensulfone degradation. Fluensulfone does not undergo hydrolysis in water bodic;s 

over the range of pH 4 to 9. 

In aquatic systems fluensulfone is not persistent with aerobic metabolism half-lives ranging from 

39 to 42 days, and the anaerobic metabolism half-life ranged from 23 to 26 days. Terrestri,:.l field 

dissipation study results show that the chemical's dissipation half-lives range from 7.4 to 10.8 

days, which are relatively consistent with those of the laboratory studies (half-lives range(l from 

8 to 15 days). The partitioning coefficient from octanol to water (Kow) of 91.2 (log Kow =- 1.96) 

suggests low potential for bioaccumulation in aquatic organisms such as fish. Bioconcentr._:tion is 

not a concern due to its low Kow. 

4.2. Ecological Exposure 

Fluensulfone is applied pre-planting of seedlings/immature plants by broadcast or banded 

application or drip irrigation. The product is mechanically incorporated into the soil to de I iver 

the applied chemical into the root zone (6-8 inches below the soil surface) for the target pe: ~ts. 

Ecological receptors that may potentially be exposed to fluensulfone include terrestrial an<j semiaquatic wildlife (i.e., mammals, birds, ten:estrial-phase amphibians, terrestrial invertebrates, and 

reptiles) and plants. In addition, aquatic receptors, (i.e., freshwater and estuarine/marine fish and 

invertebrates, aquatic-phase amphibians, and plants) may also be exposed as a result of potential 

movement of fluensulfone to aquatic environments via spray drift, runoff, and/or base flow from 

ground water leachate originating at the site of application (no direct applications to water bodies 

are proposed). 

The EPA uses standard available models to evaluate potential exposures to aquatic and ten -estrial 

organisms as described athttp://www.epa .(,,~ov/pesticides/science/models db.htm . Estimat. ~d 

environmental concentrations (EECs) are the output of the models and represent the estimated 

exposure in ecological receptors. 

Page :I l of 23 
The identified degradates of fluensulfone from environmental fate studies include thiazole 

sulfonic acid (TSA), methyl sulfone (MS), butene sulfonic acid (BSA), deschloro-fluensultt}ne, 

butene sulfinic acid, deschloro thiazole sulfonic acid, and carbon dioxide. Available toxicity 

data for the major organic degradates indicate that, in general, degradates are orders of 

magnitude less toxic than fluensulfone to fish, aquatic invertebrates and algae. These less toxic 

degradates were, therefore, not included in the ecological exposure modeling even though i>ne 

TSA is persistent. However, MS had a somewhat similar toxicity profile compared to thai: of the 

parent compound and is considered persistent in the environment, therefore was included 

ecological exposure modeling. 

4.2.1. Exposure to Aquatic Organisms 

Exposure in surface water from the proposed fluensulfone uses due to runoff, erosion, and >.pray 

drift was assessed. The aquatic exposure assessed fluensulfone alone, MS alone, and the 

combined residues of fluensulfone + MS. Only parent fluensulfone was assessed for expasure via 

spray drift. 

Aquatic EECs for parent alone from use on fruiting vegetables and cucurbits were 1.49 and 

2.87 μg/L, respectively; aquatic EECs for MS alone from use on fruiting vegetables and 

cucurbits were 0.47 μg/L and 0.81 μg/L, respectively; and aquatie EECs for fluensulfone - MS 

for fruiting vegetables and cucurbits were 3.38 μg/L and 7.73 μg/L, respectively. 

Aquatic exposure via spray drift was assessed using the maximum application rate and no buffer 

zone, resulting in an EEC of 12.1 μg/L. However, using a larger droplet size and lower boc: m 

height in the assessment resulted in the EEC being reduced to 2.1 μg/L. 

Bioaccumulation is not a concern with fluensulfone as a result of its low Kow of 91. 

4.2.2. Exposure to Terrestrial Organisms 

The application methods of broadcast and band incorporation, and drip irrigation were inc:l. uded 

in the terrestrial exposure assessment. Terrestrial wildlife exposure estimates are calculate:c. for 

birds and mammals, focusing on a dietary exposure route for uptake of pesticide active 

ingredients. Pesticide residues on food items are estimated based on the assumption that 

organisms are exposed to pesticide residues in a given exposure use pattern. Birds are used as 

surrogates for terrestrial-phase amphibians and reptiles. 

Since neither fluensulfone nor MS are systemic, and application is to bare ground followed by 

incorporation to a depth of 6-8", dietary exposure to mammals, birds, reptiles and terrestri, ,tl.- 

phase amphibians is expected to be limited. This results in negligible exposure to animal<.c 

feeding on plants, fruits or pods. 

Arthropods and seeds, however, may be present during application or in the treated area aricl 

subsequently may be consumed by terrestrial organisms. Therefore, EECs were generated ..'or 

Page 1:> of 23 
these exposure routes. Estimated fluensulfone concentrations on arthropods and seeds were 329 

ppm (at application) and 52.50 ppm (in the treated field). Fluensulfone exposure to terrestrial 

wildlife was also evaluated by estimating residues on subterranean food items in the treated area. 

Exposure to earthworms and other subterranean invertebrates due to soil incorporation arn:l dripirrigation is likely, resulting in an EEC of 2.2 g/kg-soil. 

EECs were derived from combined exposure estimates of runoff and spray drift for terrest:rial 

plants- inhabiting dry and wetland treated areas. The following scenarios were assessed: Runoff 

to dry areas, runoff to semi-aquatic areas, spray drift, total for dry areas, and total for semi-. 

aquatic areas with EECs of 0.029, 0.29, 0.035, 0.064, and 0.33 lb a.i./A, respectively. With 

immediate soil incorporation and drip irrigation for all application, exposure will be limitE:d. 

4.3. Ecologica011:I'fects 

Measures of effect were obtained from a suite of registrant-submitted OCSPP guidelinecompliant studies that were conducted with a limited number of surrogate test species. Aca..te 

measures of effect used in the screening-level assessment are the LDso, LCso (median Lethal 

Dose or Concentration, respectively) or ECso (median Effects Concentration). These are 

measures of acute toxicity that result in 50% of the respective effect on tested organisms. "I'he 

endpoints used with sublethal effect measures, mainly from chronic or sub-chronic exposu:res, 

are the NOAEC and the NOAEL (No-Observed Adverse Effect Concentration or Level, 

respectively). Toxicity studies were submitted for freshwater fish and invertebrates, 

estuarine/marine fish and invertebrates, aquatic plants, birds, mammals, bees, and other 

terrestrial invertebrates. 

4.3.Il. Aquatic Organisms 

Freshwater Fish: Fluensulfone TGAI was found to be slightly toxic on an acute basis for 

freshwater fish. The 480EC formulation was found to be more toxic (moderately toxic) tlran 

fluensulfone alone with 96-hr LCso values of 3.2 and 2.5 mg a.i./L (compared to 38 and B mg 

a.i./L) for the rainbow trout and bluegill, respectively. Chronic toxicity was measured in x. 3-day 

early life-stage study using the fathead minnow under flow-through conditions; NOAEC and 

LOAEC values were 0.63 and 1.6 mg a.i./L, respectively. 

Freshwater Invertebrates: Fluensulfone TGAI was found to be slightly toxic on an acut;: basis 

to freshwater invertebrates. Freshwater invertebrates are more sensitive to the 480EC 

formulation than to the TGAI — EC50 of 0.38 mg a.i./L for the 480EC formulation compared to 

an EC50 22 mg a.i./L for TGAI. Chronic toxicity was measure in a daphnid life-cycle test 

establishing the NOAEC and LOAEC values of 0.20 and 0.39 mg a.i./L, respectively. 

Estuarine/Marine Fish: Fluensulfone TGAI was found to be slightly toxic to estuarine ar)d 

marine fish on an acute basis. Chronic toxicity data for estuarine/marine fish are not available. 

It was not feasible to derive an acute-to-chronic ratio (ACR) for estuarine/marine fish based on 

freshwater data since acute data was not available for the fathead minnow, the only species with 

Page :1.3 of 23 
chronic data. Fluensulfone 480EC was classified as moderately toxic on an acute level to 

estuarine and marine fish. The 96-hour LC50 was 5.9 mg a.i./L, with sublethal effects incliiding 

lethargy and surfacing. Based on the formulated product toxicity, fluensulfone is classifie(f as 

moderately toxic to saltwater fish on an acute basis. 

Estuarine/Marine Invertebrates: Submitted mysid (Americamysis bahia) data resulted i n a 

classification of highly toxic for estuarine/marine invertebrates. A mysid life-cycle test subrnitted 

to determine chronic toxicity resulted in a NOAEC of 0.37 mg a.i./L and LOAEC of 0.75 rig 

a.i./L were established. Effects seen were reduction in total length of males, and reduced juvenile 

and adult survival. 

Aquatic Plants: Submitted aquatic plant toxicity data with fluensulfone TGAI included si:udies 

with five algal species and one vascular plant. Results of acute non-vascular plant data show that 

aquatic plants are sensitive to fluensulfone and the freshwater green algae is the most sensative 

species tested followed by (in descending order of sensitivity) marine diatom, freshwater l-iluegreen algae, and freshwater diatom. The formulated product had similar toxicity to parent vvith 

96-hr EC50 and NOAEC values of 0.015 and 0.0034 mg a.i./L for the formulation compa:. ~-c:d to 

0.022-0.025 and <0.003600-0.0089 mg a.i./L for TGAI. For vascular aquatic plants, the 7.-<Iay 

EC50 and NOAEC values for duckweed were 2.4 and 0.49 mg a.i./L, respectively, based on 

biomass yield (no data were available for the formulated product). 

4.3.2. TerrestrialOrganisms 

Birds: The bobwhite oral LD50 for TGAI was 1510 mg/kg-bw (body weight) classifying 

fluensulfone as slightly toxic to avian species on an acute oral exposure basis; the NOAEI., was > 

1506 mg ai/kg-bw. Due to regurgitation in the canary acute oral toxicity study, no useable 

endpoints for calculating risk were determined apart from the regurgitation NOAEL of <1 45 mg 

ai/kg-bw. An additional passerine dietary study using zebra finches (Taeniopygia guttata) tivas 

reviewed which did not yield an LD50, and therefore this study was only used to qualitatively 

describe risk. Note, that while not required for this registration, the one outstanding data 

requirement for the ecological database is the Acute Avian Oral Toxicity Study using a p ~~-.serine 

species (OCSPP guideline # 850.2100). The submitted studies were not sufficient to defirne a 

quantitative endpoint for risk assessment due to regurgitation issues therefore the studies were 

used qualitatively for describing risk to passerine species. Fluensulfone is applied to bare pround 

and is incorporated into the soil limiting exposure to avian species, therefore an additiona :>tudy 

is not required at this time. 

Subacute dietary toxicity studies using the Northern bobwhite quail (C. virginianus) and r.riallard 

duck (Ana platyrhynchos) resulted in LC50 values of >5930 mg a.i./kg-diet and >5760 m;: 

a.i./kg-diet, respectively, thus classifying fluensulfone TGAI as practically nontoxic to upland 

game and waterfowl species. 

No overt signs of reproductive toxicity were observed in any of the treatments. The NnA:E_C for 

parental toxicity and reproduction endpoints was 1,010 mg a.i./kg diet. 

Page lA of 23 
An avian acute oral toxicity study using the formulated 480EC product showed that there 13 no 

increased toxicity to avian species exposed to the formulated product compared to the TGrtl on 

an acute oral basis. 

Mammals: Five mammalian acute oral toxicity studies using the TGAI, 480EC formulatir)n and 

three metabolites (TSA, MS and BSA) were submitted to establish the toxicity of fluensulione to 

mammals. The results of the acute mammalian oral toxicity studies indicate that fluensul; ~one 

TGAI has an oral LD50 of 671 mg a.i./kg-bw, the 480EC fonmulation has an LD50 of > 947 mg 

a.i./kg-bw, and the metabolites TSA and BSA had LD50 values > 2,000 mg/kg-bw, while 'viS 

had an LD50 value 500 mg ms/kg-bw. These results classify fluensulfone and its metabolites as 

having low to moderate toxicity to mammals on an acute oral exposure basis. 

A 2-generation Wistar rat reproduction study was reviewed to establish chronic toxicity ot' 

fluensulfone to mammals. The NOAEL for Wistar rats was 250 ppm based on decreased I ~-ody 

weight, decreased body weight gain, decreased food consumption and increased liver and l:idney 

weights and histopathology changes in the liver and kidney as well as decreased pup weih.;lits and 

spleen weights, and an increase in post-natal pup loss between days 0 and 4 in the F1 and l- 1 

offspring. The reproductive LOAEL was not determined as no treatment-related effects on. 

reproductive performance were observed. 

Terrestrial Invertebrates (honeybee): Based on the results of the submitted studies, 

fluensulfone is classified as practically non-toxic to the honeybee. Two 48-hr acute contaci 

toxicity studies were submitted using the fluensulfone TGAI and the 480EC formulation t 

establish the toxicity of fluensulfone to young adult honeybees (Apis mellifera). The 48-hr LU50 

values for the honeybee acute contact TGAI and 480EC formulations were 167 ug a.i./bee and 

>200 ug a.i./bee, respectively. 

Terrestrial Invertebrates (Earthworms): The 14-day earthworm acute soil exposure to;c .city 

test with fluensulfone TGAI and the 480EC formulation resulted in an LC50 value of 148 -ng 

a.i./kg soil dw and 57.4 mg a.i.;kg soil dw, respectively. The NOAEC for fluensulfone TGAI was 

48.3 mg a.i./kg soil dw and the NOAEC for the 480EC formulation was 10.5 mg a.i./kg swil dw. 

The effects measured were mortality and weight, though the NOAEC was based on weiglit. 

Terrestrial Plants: The most sensitive monocots were onion (NOAEC = 1.21 lbs a.i./A) Eind 

w•heat (NOAEC = 0.0415 lbs a.i./A). The most sensitive dicots were cabbage (NOAEC =0.419 

lbs a.i./A) and soybean (0.141 lbs a.i./A). 

4.4. IEcological Risk 

The exposure and toxicity effects data are integrated in order to evaluate the risks of adver3e 

ecological effects on non-target species. For risk assessment, the risk quotient (RQ) methi) I is 

used to compare estimated exposure and measured toxicity values. For this method, RQs are 

calculated by dividing exposure estimates by ecotoxicity values, both acute and chronic (RQ = 

Exposure/Toxicity). RQs are then compared to EPA's levels of concern (LOCs). The LOd:'s are 

criteria used by the Agency to indicate potential risk to non-target organisms. The criteri;t 

Page 15 of 23 
indicate whether a pesticide, when used as directed on the label, has the potential to cause 

adverse effects to non-target organisms. 

4.4.1. Fish and Aquatic Invertebrates 

The proposed uses of fluensulfone for nematode control generally resulted in no LOC 

exceedances for aquatic invertebrates or fish (RQs were less than 0.01). However, a formi_tlated 

product was more toxic than technical grade material, and exposure from spray drift to the 

formulated product resulted in an LOC exceedance for listed marine invertebrates. Exposuu•e is 

reduced within a short distance off-field where deposition quickly drops below the Agenc;;, 's 

LOC. 

4.4.2. Aquatic Plants 

For aquatic vascular and non-vascular plants, RQ values based on refined EECs, and the 

incorporation of low boom and larger droplet sprays, are below Agency LOCs (1.0) for no;1- 

listed and listed species. For aquatic non-vascular plants, RQ values for non-listed and 

species were below the LOC for crop groups 8 and 9. 

4.4.3. "1'ccrestrialOrganisms 

The proposed use of fluensulfone for nematode control results in LOC exceedances for birds and 

mammals. 

Birds: Acute LOCs (based on dose-based toxicity estimates) are exceeded for non-listed small 

and medium birds feeding on arthropods. Listed species acute LOCs are also exceeded fc ,z small 

granivores, small and medium seed eaters and large birds feeding on arthropods. Chronic LOCs 

are exceeded (based on dietary toxicity) for birds feeding on arthropods. The chronic LO(; is also 

exceeded for birds consuming arthropods (RQ of 1.3), however, minimizing spray drift arui using 

coarser droplets reduces the distance off field where LOC exceedances are predicted for l:i:rds 

feeding on arthropods. Further, exceedances are based on conservative assumptions including 

high-end exposure values and 100% of the bird's diet is from the treated site, where avera3e or 

more typical exposure values resulting from a variable diet would not likely result in LOC 

exceedances. 

Mammals: Dose-based toxicity estimates indicate acute LOC estimates are exceeded for 1:sted 

small, medium and large mammals (RQs of 0.21, 0.18, and 0.10, respectively) feeding on 

arthropods. Chronic LOCs are exceeded based on both dose-based and dietary toxicity foimammals feeding on arthropods (RQ 1.3) up to an estimated 3 feet from the application site. 

Calculations indicate that only a small forage area is needed (2-23 ft2, depending on feedirig 

efiiciency) for consumption to cause exposure that exceeds the LOC. However these 

conservative assumptions are based on mammals foraging in the treated site and 100% of' their 

dietary requirements are from the treated site; therefore, since exposures were based on hi;:;h-end 

estimates, average or more typical exposure values would not likely result in LOC exceeclances. 

Page 1115 of 23 
Terrestrial Plants: RQ values for listed semi-aquatic dicots exceed the Agency's LOC of' 1.0 

based on fluensulfone exposure from the proposed use (RQ of 2.3). No other LOCs were 

exceeded for terrestrial plants. However, spray-drift exposure does not pose a significant 1-isk 

because the directions for use require mechanical soil incorporation or irrigation to a depth of 6- 

8". Therefore, exposure to non-target terrestrial plants is unlikely. Label statements ensirring 

incorporation following application reduces this risk. 

Terrestrial invertebrates: Based on the results of the submitted studies, fluensulfone is 

classified as practically non-toxic to honeybees. A refined screening-level assessment for 

terrestrial invertebrates (using the honeybee as a surrogate) showed that Agency LOCs were not 

exceeded resulting from the proposed use pattenns. 

Earthworms: Risk to subterranean invertebrates was assessed finding that exposure throu ;h 

incorporation or drip-in igation from 1-15 cm down into the soil does not exceed Agency L,OC 

for listed invertebrates. 

6. Benefits and Alteu°natives 

Fluensulfone is being registered for control of nematodes in transplanted crops; Crop Grorips 8 

and 9, including cucumbers, melons (cantaloupes, watermelon, honeydew), squash, tomalcles, 

okra, eggplant, and peppers (bell and non-bell). Root-knot nematodes (Meloidogyne spp. ). sting 

(Belonolaimus spp.), and lesion nematodes (Pratylenchus spp.) are the target pests specified on 

the label. 

Fluensulfone is a non-fumigant nematicide. Usage data indicates that the only other non-• 

fumigant nematicide used on Crop Groups 8 and 9 in the past 5 years is oxamyl, an n-metl - .vl 

carbamate. All other nematicides used on these crops in the past 5 years are fumigants. '1'Iiese 

fumigants are chloropicrin, methyl bromide, telone, metam-sodium, metam-potassium arn:l 

dimethyl disulfide. 

Nematodes are an agricultural pest that attack a wide range of plants including common 

vegetables, fruit trees, and ornamentals. These pests are difficult to control and can be easi.ly 

spread from garden to garden in soil, on tools, or on infested plants. They can cause signi:Eicant 

economic damage by reducing crop yield and quality through the formation of galls (swel l ings 

on the roots which damage water- and nutrient-conducting abilities of the roots), or througi 

infeetion from soil-borne, disease-causing microorganisms that gain access when the galls split 

or crack open.' 

The available chemical tools to eontrol nematodes are limited. EPA has not received an 

application for or registered a new conventional nematicide for over 10 years. Fluensulfor-.e 

presents a new modc of action that will be useful in resistance management and IPM programs. 

l. http::'N%wtiv.etahr.hawaii.edu/oc/fr •eepubs/pdVPD-35.{)dl' 

Page 17 of 23 
The seven main alternatives to fluensulfone used in the last five years include six soil furriigants 

(chloropicrin, methyl bromide, telone, metam-sodium, metam-potassium and dimethyl dis«Ifide) 

and one n-methyl carbamate (oxamyl). All seven pose a greater risk to human health thari 

fluensulfone. The labels for the six fumigants contain text identifying significant risks to h.iman 

health. All are in Toxicity Category 1(Danger signal word, skull and crossbones image) ~ xcept 

Dimethyl Disulfide (Toxicity Category 2, Warning Signal Word). All are classified as Ro=.tricted 

Use Pesticides, as follows: 

Chloropicrin: Restricted Use Due to Acute Toxicity 

"Danger. Extremely hazardous liquid and vapor under pressure. Do not breathe vapors. 

Inhalation may be fatal or cause serious acute illness or delayed lung or nervous s:;:>tem 

injury which may have a delayed onset. This product contains chloropicrin which i:> very 

irritating to the upper respiratory tract, and even at low levels can cause painful irri :ation 

to the nose, throat, and eyes, producing tearing. If these symptoms occur, leave thf: 

fumigation area immediately. Continued exposure after irritation, or higher 

concentrations, may cause painful irritation to the eyes or temporary blindness whi{;h 

may cause panic that may in turn lead to further accidents." 

Methyl Bromide: Restricted Use Due to Acute Toxicity 

"Danger. Extremely hazardous liquid and vapor under pressure. Do not breathe va1-'c>rs. 

Inhalation may be fatal or cause serious acute illness or delayed lung or nervous sv:>tem 

injury which may have a delayed onset. This product contains chloropicrin which k very 

irritating to the upper respiratory tract, and even at low levels can cause painful irri :ation 

to the nose, throat, and eyes, producing tearing. If these symptoms occur, leave thE; 

fumigation area immediately. Continued exposure after irritation, or higher 

concentrations, may cause painful irritation to the eyes or temporary blindness whil;h 

may cause panic that may in turn lead to further accidents." 

Telone (1,3-Dichloropropene): Restricted Use Due to Acute Toxicity and 

Carcinogenicity 

"DANGER. Hazardous liquid and vapor. May cause lung, liver, and kidney damap l--I and 

respiratory system irritation upon prolonged contact. The use of this product may 

.

",)e 

hazardous to your health. This product contains 1,3-dichloropropene, which has be-,-n 

determined to cause tumors in laboratory animals. Risks can be reduced by exactly 

following directions for use, precautionary statements, and by wearing the personal 

protective equipment specified in this labeling. Fatal if inhaled or swallowed. Poisanous 

liquid and vapor. Corrosive. Liquid causes skin burns and irreversible eye damage, Do 

not breathe vapor or gas. Do not get in eyes, on skin or on clothing. Chloropicrin i:> 

readily identifiable by smell. Exposures to very low concentrations of vapor will cu.use 

irritation of eyes, nose and throat. Continued exposure after irritation occurs, or ex:posure 

to higher concentration may cause painful irritation or temporary blindness." 

Metam-Sodium: Restricted Use Pesticide Due to Acute Inhalation Toxicity to Hurilans 

"DANGER. Con:osive - Causes skin damage. May be fatal if absorbed through the skin. 

Do not get on skin or clothing. Prolonged or frequently repeated skin contact may cause 

Page :I 3 of 23 
allergic reactions in some individuals. Harmful if swallowed or inhaled. Irritating t<) eyes, 

nose and throat. Avoid breathing vapor or spray mist. Do not get in eyes." 

Metam-Potassium: Restricted Use Pesticide Due to Acute Inhalation Toxicity to I-lumans 

"DANGER. Fatal if absorbed through skin. Corrosive. Causes skin burns and irrev,,-rsible 

eye damage. Do not get in eyes, on skin or on clothing. May be fatal if swallowed or 

inhaled. Do not breathe vapor or spray mist. Prolonged or frequently repeated skiri 

contact may cause allergic reactions in some individuals." 

Dimethyl disulfide: Restricted Use Pesticide Due to Inhalation Exposure to Hum<<iis 

"Warning. May be fatal if swallowed. Harmful if inhaled or absorbed through ski: ~ i. Do 

not breathe vapor. Causes slight eye irritation. Avoid contact with skin, eyes or 

clothing." 

Due to the risk to workers performing these soil fumigations, EPA has implemented new safety 

measures to address the risks posed by soil fumigants to workers and bystanders as discus:,ed in 

the following website: 

http://www2.epa.gov/soil-fumigants/implementing-safety-measures 

Additionally, it is noteworthy that soil fumigants are extremely labor intensive, i -equii- ing tarping 

and posting of fields, which also presents a financial burden to growers. 

The one non-fumigant alternative is oxamyl. It is an n-methyl carbamate group and is 

undergoing a cumulative risk assessment with related compounds that have a common 

mechanism of toxicity. Like the soil fumigants, it is more toxic to humans than fluensulfo le. It 

is in Toxicity Category 1 and is also classified as Restricted Use: 

Oxamyl: Restricted Use Pesticide Due to Acute Toxicity to Birds and Mammals 

"DANGER-POISON! Fatal if swallowed. May be fatal if inhaled. Do not breathe spray 

mist. Causes moderate eye in itation. Avoid contact with eyes or clothing. Contain.; 

methanol which may cause blindness." 

As noted above, all of the alternatives to fluensulfone are classified as Restricted Use Pes - ticides. 

This means that they are limited "For retail sale to and use by Certified Applicators or per::ons 

under their direct supervision, and only for those uses covered by the Certified Applicatoi - 's 

certification." Besides the need to receive special training to use them, and the requireme:nt to 

maintain an active certification from their state lead agency, the sale and use of these altertiatives 

are subject to reporting requirements and records maintenance. This presents an additional 

burden to applicators, growers and state personnel. 

By contrast, fluensulfone poses much lower risk to applicators. It is in Toxicity Category :3 with 

"Caution" as the signal word. It is not a Restricted Use Pesticide and so has no mandated 

applicator training and certification. The application methods of ground boom and chemi;=;ation 

are much less burdensome. 

Page 19 of 23 
For ecological effects, Table 3 below illustrates from the available data that fluensulfone i ~ . less 

toxic to birds and tnaminals compared to the identified alternatives, altliough acute avian mudies 

«ere not available for several ofthe alternatives, and is also less toaic to aquatic invertebrates 

relative to the alternatives except metltyl broniide. The toxicitv profiles for fisli are simila.- lor 

lluensull'one, 1, 3-dichloropropene, inetliyl bromide. and oxamyl (LC50s are within a fact ,:rr of 2 

of eacli other), but tnetam sodiutn and chloropicrin are considerably nlore toaic to fish tlian 

fluensulfone atld the other pesticides in the analYsis. Fluensulfbne is considerably niore toxic to 

algae tllan all ofthe alternatives. lt has siinilar toxicity to honey bees than 13-Dichloropn>penc 

and chloropicrin. and is eonsiderably less toxic to honey bees than oxaniyl. Coniparable noney 

bee toxicity studies were not available for the other alternatives. 

Table 3. Fcological I-Iazard ('omparison for Fluensulfone and Current Alternatives 

Chemical 

Vascular T Mammals Birds 

Fish I Daphnids Algae I Plants (LD50) (LD50 

Fluensulfone 

2500 u 1 380 ugZL 1 15 u L 2700 u L 1 671 

(Formulation) I (Formulation) (Formulation) (Formulation) m k -bw 

Chloropicrin ND I ND 

1,3- 

Dichloropropene 

Methyl bromide ND 

Oxamyl 

1510 

rng/kp,- 

_ bw 

ND 

ND 

Bees 

167 

u bee 

ND 

Metam Sodium ,, ~ ~ " " ND ND 

Green: Fluensulfone is less toxic than alternative 

Yellow: Fluensulfone is of similar toxicity compared with alternative (<factor of 2 difference) 

Red: Fluensulfone is more toxic than alternative 

ND = no data located for this analysis 

Growers are constantly seeking nematicides that are safer for workers and the public but a: -e also 

efficacious. Fluensulfone represents a safer alternative for nematode control with a new n- ode of 

action and a much simpler and straight forward product label. 

Finally, because methyl bromide depletes the stratospheric ozone layer, it is being phased out 

under the Montreal Protocol and the Clean Air Act. Growers of cucurbits and fruiting ve _;etables 

have essentially lost methyl bromide as an efficacious nematicide and clearly are in need o f' new 

and safer tools. 

7, IEgegulatory Decision 

Under Section 3(c)(5) of the Federal Insecticide, Fungicide and Rodenticide Act (FIFRA; , the 

Agency is unconditionally registering the new active ingredient fluensulfone, formulated as a 

technical product and one end use product; Fluensulfone Technical and Fluensulfone 48U 13C. 

Fluensulfone is being registered to control nematodes on cucurbits, Crop Group 9; and fria ting 

vegetables, Crop Group 8. 

Page :2:0 of 23 
7.1. Public Comments 

As required by FIFRA, the Agency published a Notice of Receipt (NOR) of applications in the 

Federal Register on September 28, 2012, 77 FR 59611, announcing Makhteshim's (now 

ADAMA) request to register fluensulfone. A 30-day public comment period was held in M"liich 

no public comments were received. 

EPA announced a proposed decision for an unconditional registration of fluensulfone on July 25, 

2014, and held a public comment period for 30 days, closing August 25, 2014 at 11:59 pm. Six 

comments were received; five comments were in support of the registration, submitted by 1=acific 

Ag Research, University of California, Southeast Ag Research, Inc., and the Inter-Regiona l 

Research Project Number 4(IR-4). These five comments expressed support for the registnil ion 

of fluensulfone, noting that growers welcome a"safe and effective nematicide" product wi.lh 

lower toxicity to applicators that would "increase the options for conventional nematode 

management by growers" that could be used against "pests as serious and costly as nematocles." 

The sixth comment, an objection to the registration of fluensulfone, was submitted citing tlle 

failure of the EPA to consult with the U.S. Fish and Wildlife Service and the National Marine 

Fisheries Service under the Endangered Species Act. EPA discussed this issue on page 21 

(section 7.2.1) in the July 25, 2014 proposed decision. As noted in the proposed decision, 'f: PA is 

focusing most of its resources for assessing impacts to listed species on its registration revic:w 

program for currently registered pesticides. EPA believes that, as a general matter, currently 

registered pesticides present a greater degree of risk to listed species-than most new chemistries 

coming to market, including fluensulfone, and that it is therefore environmentally preferable in 

most circumstances for EPA to assess the impacts of existing pesticides sooner in the procf:ss 

than newer pesticides that are designed to compete with more risky alternatives. As a resi;.lt, 

EPA does not believe the environment or the public would be best served by delaying the 

registration of fluensulfone to complete consultation. Focusing EPA's and the Services' lii-nited 

resources on completing a eonsultation on the effects of fluensulfone would by necessity come at 

the expense of putting more resources into evaluating — and consequently regulating, wheri:: 

appropriate — what EPA believes to be more toxic compounds, that, among other things, pose 

greater risk to endangered species than does fluensulfone. With respect to the evaluation o .' 

fluensulfone specifically, it is important to understand that under any internal or interagency 

review, the ecological risk evaluation will continue to rely on the body of information used: in the 

current EPA ecological assessment. 

For the reasons explained above, EPA is not consulting with the Services on the issuance oFthe 

fluensulfone registration. However, EPA is currently working to prioritize its consultatioai 

activities with the Services and will evaluate the appropriate timing and scope of consultat.i:;}n on 

fluensulfone in connection with those efforts. In addition, to the extent EPA receives new 

information indicating that fluensulfone may pose a greater risk to listed species than indirated 

by the existing scientific database for this pesticide, EPA will re-evaluate the terms of 

registration and deter,mine whether additional use restrictions to protect listed species are 

necessary 

Page 2:1. of 23 
Ecological Risk Assessments were conducted based on draft labels which include a higl;.,::r single 

maximum application rate (3.5 lbs a.i./A). 

Fluensulfone is a non-fumigant nematicide presenting a safer alternative chemical contrc ~ l for 

nematodes and has a much simpler label to follow, thus presenting a lower risk for human health 

and environmental exposure. With the new mode of action and lower risk profile compared to 

the alternatives, EPA believes the benefits of the use of this chemical outweigh the poteri .ial 

risks. 

7.2.1. Data Requirements 

There are no outstanding data requirements for this registration of fluensulfone. 

7.2.2. Mitigation and Labeling Requirements 

Worker Exposure Risk 

The proposed label specifies PPE (i.e., long-sleeved shirt, long pants, socks, shoes, and 

chemical-resistant gloves) results in potential handler dermal and inhalation risks of cortc;ern 

from worker exposures from mixing/loading liquids for chemigation applications. To rrtitigate 

this risk for mixing/loading liquids for chemigation, EPA is requiring engineering contro.<; 

(closed systems) on the label. Good descriptions of enclosed system types can be foun(l n the 

report prepared by California Department of Pesticide Regulation (Fong, 2003) 2 , which explains 

the three essential elements of closed systems for liquids. 

Additional mitigation has been imposed on the label reducing the maximum single appl:. ~ ::ation 

rate to 2.5 lbs a.i./A (80 fl oz of product) for all application methods thus eliminating thc ~ rteed 

for closed cabs and respirators for applicators for ground broadcast and banded applicati.ons. 

Engineering controls (i.e., closed systems) are required for mixing/loading activities for 

chemigation (drip irrigation) due to the potential dermal and inhalation risks of concern i rom the 

chemigation application method at the reduced rate of 2.5 lbs a.i./A. 

EcoloQical Risk 

Risk was identified for aquatic organisms resulting from spray drift from ground spray 

application methods. The Agency investigated refinements of spray drift estimates (incr: ~ ,tsing 

the droplet spectra to medium, and lowering the boom height) which reduces exposure an 

order of magnitude such that the Agency's LOC exceedances for aquatic organisms are 

mitigated. Coarser droplets also reduce the distance off field where there are LOC exce:: ~ :lances 

for birds feeding on arthropods. Therefore, the Agency is proposing to require boom hei s_ ht and 

droplet spectra specifications on the label of 20 inches and medium spray droplet size. 

'- Fong et al. 2003. An Overview of Closed System Use in California 2001-2012. Health and Safety Repori: (HS1849. California Department of Pesticide Regulation, Sacramento, California. Available at: 

http://www.cdpr.ca.gov/docs/whs/pdf/hs 1849.pdf 

Pag< ~ 22 of 23 
Potential volatilization from dry soil applications is addressed by the labeling requiremc:irt that 

all applications must be incorporated by water and/or mechanical means to a depth of 6-8 inches. 

Page . ~ 3 of 23