### UNIT E D STATES ENVIRONMENTAL PROTECTION AGENCY

WASHINGTON, D.C. 20460



## MEMORANDUM

Date: August 8, 201 4 O FF ICE OF
C H E MICAL**FI TY**  ANI>
POLL U TION PREVE N TION



## SUBJECT: 

## Triallate. Human Heal th Ri sk Assessment Scoping Document in Support of Registration Review

PC Code: 078802
Decision No. : 489685
Petition No.: Not App l icable
Risk Assessment Type: Single Chemical

TXR No.: Not Applicabl e MRID No.: Non e



## FROM:

THRU:

TO: Katherine St. Clair DP Barcode: 0419239 Registration No.: Not Applicable Regula tory Action: Registration Review Scoping
Case No

. : Not Applicable
CAS No.: 2303-17-5
40 CFR: §180.314



## Pes t i c ide Re-e v aluation Division (7508P)
Offic e of Pesticide Programs

Attached is the Health Effects Division's (HED) human heal t h scoping document for triallate to support the registrat i on r eview process.

Page 1 

## o f 24

## Executive Summary



## The Health Effects Division (HED) has evaluated the status of the human health risk assessment for triallate to determine the scope of work necessary to support Registration Review. T he most recently completed human health risk assessment (2008; D351897) was cons id ered as part of this scoping exercise.

Triallate (S-(2

, 3

, 3-trichloro-2

- propen-1

- yl) .N,N -bis ( l-methylethy l )carbamothioate) is a preemergent selective herbicide used on barley

, lentils

, peas (dried and succulent)

, triticale, sugar beets, wheat, and grass grown for seed/hay. It is used for the pre-emergent control of weeds by inhibiting cell division and promoting the elongation of seedling shoots in targeted plants.
Triallate is an herbicide active ingredient in the c l ass of thiocarbamates. Triallate is so ld under
the trade name s Far-Go ®, Buckle®, and Avadex ® as either granular or emulsifiable concentrate end-use products. It is registered for use on Bermuda grass grown for seed with tolerances
established under 40 CFR § 180.314(a) for the hay raw agricultural commodity (RAC).
Tolerances for its regional use on barley (grain

, hay & 

## straw), sugar beets (dried pulp, roots & 

## tops)

, peas (dry

, hay

, vines & 

## succulent)

, and wheat (forage, grain

, hay & 

## straw) are also
established under 40 CFR §180.314(c). Applications to crops are typicall y made at rates of 1.0

- 1.5 lb ail A as pre-plant and post-plant soil incorporated treatments using ground or aerial equipment. It 

## is applied in either the fall or spring before targeted weed species germinate.

The tox icity database for triallate is complete and adequate for characterization of potential developmental, reproductive, carcinogenetic, mutagenic, and neurotoxic effects. No new toxicity studies have been received since the last risk assessment. During registration review of triallate, endpoint selection

, points of departure (PODs)

, and uncertainty factors (UFs) / safety
factors (SFs) for the risk assessments will be re-evaluated based upon updated policies and procedures.

The residue chemistry database is complete. The current tolerance expression should be updated

to comp ly with H ED ' s current policy on tolerance express ion s during reg i stration review.

There are no maximum residue limits (MRLs) established for the residues oftriallate by Codex

or Mexico. Canada has established MRLs on triallate for a nuinber of commodities which are harmonized with those tolerances set by the U.S. As such

, there are no international
harmonization issues. HED is not currently involved in any joint international review projects
that involve the active ingredient

, triallate.

Currently there are no acute or chronic dietary (food and drinking water) risk estimates which are of concern for triallate and its metabolites

. A cancer dietary risk assessment was performed
which determined a cancer risk est ima te of3.0 x 10· 7 

## for the general U.S. population. Updated dietary exposure assessments for triallate may be necessary under registration review if there are significant changes to the drinking water estimated concentrations which will be updated by EFED, or if there are significant changes to the PoDs or UFs / SFs.

There are no non-occupational (residential) uses registered for triallate.

Page 2 of24

## Page 3 of 24

Residential bystander exposures resulting from off

- site transport (i.e., spray drift or volatilization) may occur as a result of occupational applications of triallate . The need for a bystander risk assessment for trial late will be considered during registration review.

There are no current aggregate risks estimates of concern for triallate . During registration review, updated aggregate assessments may be conducted as required to include any significant change that mi ght occur for toxicological PODs, FQPA and uncertainty facto rs, dietary exposure estimates, or estimated drinking water concentrations ( EDWCs )

.

The exposure database for triallate is complete. Based on the previous occupational exposure
assessment, all of the handler (dermal and inhalation) exposure non

- cancer risk estimates were
not of concern with label required PPE

. Some occupational handler cancer risk estimates with label required PPE are within the 10

- 6 

## to 10

- 4 

## range; all risk estimates do not ex ceed 5 x 10

- 5



## . There are no post

- application worker exposure non

- cancer risk estimates of concern

. Based on the previous occupational handler exposure assessment, all post

- application cancer risk estimates
do not exceed 7 x 10

- 6 

## . No DFR or TTR data are required for triallate. The Worker Protection Standard ( WPS ) restricted entry interval ( REI ) for triallate is 12 hours. An updated occupational exposure and risk assessment may be required during registration review if warranted by any changes to policy or points of departure.

Introduction

HED has evaluated the most recent complete human health risk assessment for triallate to determine if sufficient data are available and if updates are needed to support registration review. HED has also considered updates to its toxicity, exposure and usage databases, and the latest Agency science policy and risk assessment methodologies.

Triallate is a selective, pre

- emergence herbicide in the class of thiocarbamates. The chemical structure, nomenclature, and the physical/chemical properties of triallate are presented in Appendix
A.



## Registered agricultural use sites of triallate incl ude barley, lentils, peas (d ried and succulent), triticale, sugar beets, wheat , and grass grown for seed/hay

. Formulations include granulars and
emulsifiable concentrates

.

Hazard Identification/Toxicology

The toxicology database for triallate is complete. No new animal toxicity studies have been submitted since the most recent HED risk assessment conducted in 2008 (D351897). It is
recommended that the immunotoxicity study be waived (see HASPOC report, TXR#0056861, January 28, 2014).

Following chronic exposure, systemic toxicity in dogs was limited to an increase in liver weight in both sexes, increases in serum alkaline phosphatase in both sexes and increases in hemosiderin in the spleen at dose levels higher than 4.25 mg/kg/day. In mice, toxicities observed at the

## Page 4 of 24

Lowest Observed Adverse Effect Level (LOAEL) of 60 ppm (9 mg/kg/day) included increased absolute liver weight, increased incidence of altered foci of the liver and hematopoiesis in the spleen . In rats, systemic toxicity was manifested as decreased survival in both sexes, decreased body weight and increased adrenal weight in males at approximately 12.5 mg/kg/day. In high dose males from the chronic toxicity/carcinogenicity study, the only treat ment

- related finding at interim sacrifice was linear papillary mineralization in 1/10 rats (uncommon finding in rats at one year and typical of alpha 2 μ

- globulin

- induced renal pathology). The only treatment

- related effect noted in male Syrian hamsters was decreased serum triglycerides at the mid

- and high

dose levels of 300 ppm (LOAEL) and 2000 ppm.

Triallate is neurotoxic in rats based on the acute and subchronic neurotoxicity studies, the rat
multi

- generation reproduction study and the developmental ne urotoxicity study. In the acute neurotoxicity screening study, neurotoxic signs include gait abnormalities, increased alertness, waddling, rocking lurching, circling movements, retropulsion, and head shaking, decreases followed by increases in motor activ ity and other symptoms at 300 or 600 mg/kg. The rat subchronic neurotoxicity study indicated pathological lesions in the nerve fibers of both central and peripheral origin, FOB changes and increased motor activity at dose levels of approximately 33 mg/kg/d ay and above. In addition, head bobbling and circling movements were noted in the
rat multi

- generation reproduction study in the parental groups at 600 ppm (30 mg/kg/day). A special supplementary neurotoxicity study indicated that both central and peripher al neuropathological lesions result from triallate exposure at a dose level of 6000 ppm (295 mg/kg/day). The developmental neurotoxicity study indicated the fetuses exposed in utero and during lactation displayed increased motor activity at a maternal dose of 60 mg/kg/day but there was no associated neuropathology. Triallate did not produce neuropathology in hens at doses up to 312.5 mg/kg in the acute delayed neurotoxicity study.

Analysis of whole body elimination in male and female rats indicated that 8 5% of the radiolabeled triallate was excreted within 24 hours of dosing. Most radioactivity was excreted in approximately equal amounts (42%) in the urine and feces of male rats after 10 days. Females excreted 51% in urine and 32% in feces after 10 days. M ales and females retained about 0.4% of the dose in organs and tissues and approximately 2.0% in the remaining carcass. The distribution of radioactivity in both sexes indicated that the greatest amount of activity was found in the red
blood cells followed by whole blood, spleen, kidney, liver and lung. Seven metabolites, in concentrations of greater than one percent, were identified in rat urine: 2,3,3

- trichloro

- 2

- propenesulfinic acid (20

- 27%), N

- acetyl

- S

- (2,2

- dichloro

- 1

- [methyl

- sulfonyl) methyl]ethenyl)

- L

cysteine (6

- 11%), (E)

- S

- (2 carboxy

- 2

- chloroethenyl)

- L

- cysteine (4

- 5%), carbon dioxide (4%), 2,3,3

- trichloro

- 2

- propene sulfonic acid; TCPSA (3

- 5%), (E)

- 3

- ((carboxymethyl)thio)

- 2

- chloro

2

- propenoic acid (1

- 3%), and 1

- ((3, 3, 2

- trichloro

- 2

- propenyl)thio)

- b eta

- D

- glucuronic acid. The remaining metabolites were found at less than 1% of the administered dose.

In the rat developmental toxicity study, the dams were more sensitive than the pups; the maternal toxicity NOAEL was 10 mg/kg/day and the LOAEL was 30 mg /kg/day based on deceases in body weight and food consumption whereas the developmental toxicity NOAEL was 30 mg/kg/day and the LOAEL was 90 mg/kg/day based on decreased fetal weight, external
malformations and skeletal variations.

## Page 5 of 24

However, there is evide nce of increased susceptibility in the prenatal developmental toxicity study in rabbits since the developmental effects were observed at a dose lower than the dose which produced maternal toxicity. Maternal toxicity manifested as increased incidence of cli nical signs and decreased body weight gain during the dosing period at 45 mg/kg/day (LOAEL); the NOAEL was 15 mg/kg/day. The LOAEL for developmental toxicity was 15 mg/kg/day based on decreased fetal body weight and increased incidence of malaligned sterne brae; the NOAEL was 5 mg/kg/day.

In the two

- generation reproduction study, increased neonatal mortality during the F2b litter interval, reduced pup weights at birth during the F2b litter interval, reduced pup weights in late lactation for all litters, red uced pregnancy rate and shortened gestation length occurred at the same dose (30 mg/kg/day) which produced maternal toxicity (increased mortality, increased incidences of chronic nephritis, head bobbing, circling movements and reduced body weights). The ma ternal and offspring toxicity NOAELs were 7.5 mg/kg/day.

In the developmental neurotoxicity study, offspring toxicity occurred at the same dose which produced maternal toxicity. For maternal toxicity, the NOAEL was 30 mg/kg/day and the LOAEL was 60 mg/kg/ day based on reductions in body weight gains and food consumption. At 60 mg/kg/day (developmental neurotoxicity LOAEL), there were several parameters affected in the developing offspring; reductions in body weight in both sexes, increased motor activity in both sexes and decreases in passive avoidance latency in females. The developmental neurotoxicity NOAEL was 30 mg/kg/day.

Triallate is classified as a Group C, possible hu m an carcinogen based on hepatocellular
carcino m as in m ale m ice, with a positive tre nd and borderline significa n ce in fe m ale m i ce and
increased incidence of renal tub u lar cell adenomas in rats. The cancer unit risk Q 1 

## * is 7.17 x 1 0 - 2


## ( m g/kg/day ) - 1 

## based on hepatocellular carcino m as in m ale m i ce. Tri a llate induced genotoxic responses in several in vitro m utagenicity assays in bacteria and tumor cells (i.e. in Salmonella typhimurium , in the m ouse ly mpho m a forward m u tation assay in L5178Y cells and in the s i ster chro m atid exchange a s say). However, triallate was negative in two more definitive mutagenic assays in primary rat hepatocytes. Additionally, triallate was negative for in vivo mutagenic assays in mice and hamsters at doses up to 700 mg/kg/day, well above the highest POD of 60 mg/kg/day. Therefore, the mutagenic concern of tri allate in vivo is low.

Triallate is not acutely toxic via the dermal and inhalation routes. It is slightly toxic via the oral route and is a slight eye irritant, as well as a slight dermal irritant and a dermal sensitizer.

The FQPA factor can be reduced to 1X. A 1X FQPA Safety Factor is appropriate because (i) the toxicology database is adequate for assessing the sensitivity of infants and children to triallate exposure; (ii) no quantitative or qualitative increased susceptibility was demonstrated in the fetuses in the prenatal developmental toxicity study in rats following in utero exposure, in the offspring in the developmental neurotoxicity study in rats, as well as in the offspring in the two

generational reproduction study in rats following in utero and/or postnatal exposure to triallate; (iii) although there is some increased susceptibility in the rabbit developmental toxicity study (where the developmental NOAEL of 5 mg/kg/day was lower than the maternal NOAEL of 15 mg/kg/day), the dose

- response fo r this effect has been adequately characterized, and the fetal

## Page 6 of 24

NOAEL was selected as a point of departure for the acute dietary, dermal and inhalation risk

assessment and is protective of potential adverse fetal effects.

An immunotoxicity study (required in accordance with the 2007 revised 40CFR Part 158 Toxicology Data requirements) has not been submitted for triallate. The existing sub

- chronic and chronic studies did not indicate that the immune system will be affected by triallate based on hematology, lymphoid organ weights, and histopathology measurements. The HASPOC
recommended waiv ing the immunotoxicity study based on a weight of evidence approach (TXR# 0056861).

Two acute dietary endpoints were selected for triallate. For females of childbearing age (females
13

- 50 , the acute population adjusted dose (aPAD) is derived from a No Observed Adverse Effect Level (NOAEL) of 5 mg/kg/day for increased skeletal variations in the rabbit developmental study. For the general population, the aPAD is based on a NOAEL of 60 mg/kg/day for altered motor activity and changes in functional observation battery (FOB) in the rat acute ne urotoxicity study.

The chronic population adjusted dose (cPAD) for the chronic dietary assessment is derived from the NOAEL of 2.5 mg/kg/day with a LOAEL of 12.5 mg/kg/day based on decreased survival and mean body weights, and increased adrenal weights in the chronic rat study. A total uncertainty factor (UF) of 100 (10x for interspecies extrapolation and 10x for intraspecies variation) is applied to the NOAELs.

Endpoints for dermal and inhalation exposure were also based on increased fetal skeletal

var iations observed at the LOAEL of15 mg/kg/day with an oral NOAEL of 5 mg/kg/day for developmental effects in the rabbit study. A dermal absorption factor of 1% was used in this assessment and inhalation toxicity is assumed to be equivalent to oral toxicity. Since both dermal and inhalation endpoints were based on the same toxicological effects, these route

- specific margins of exposure (MOEs) were combined into a total MOE.

A n MOE of 100 (10x for interspecies extrapolation and 10x for intraspecies variation ) is adequate for short

- and intermediate

- term dermal and inhalation occupational risk assessments (there are no non

- occupational uses of triallate)

.

See Attachment s 2 and 3 for a summary of the most recent toxicological endpoints and points of departure (PODs) for use in triallate risk assessments, available toxicity studies, and the toxicity profile.

Conclusion : The toxicology database for triallate is complete. HED will re

- evaluate the toxicity endpoints, points of departure (PoDs) and uncertainty and other fact ors during registration
review.

Dietary Exposure

Food Exposure

## Page 7 of 24

Triallate is a n herbicide active ingredient in the class of thiocarbamates. The HED Metabolism
Assessment Review Committee has determined that triallate and the TCPSA metabolite should be regulated and assessed for dietary exposure (L. Cheng memo of 6/22/98). A tolerance of 0.3 ppm is established under 40 CFR §180.314(a) for resi dues of triallate and its metabolite TCPSA in/on Bermuda grass hay. Tolerances with regional registrations are also established under 40 CFR §180.314(c) for residues of triallate and its metabolite TCPSA in/on barley (grain, hay & straw), sugar beets (roo ts, tops & dried pulp), peas (dry, succulent, field hay & vines), and wheat (grain, forage, hay and straw). The tolerances on these RACs range from 0.05 ppm for barley and wheat grain to 1.0 ppm for barley, pea and wheat hay. There are no tolerances esta blished
for livestock commodities because there is no secondary transfer of triallate residues to livestock.

Acute and chronic dietary risk assessments were most recently performed for triallate and the
TCPSA metabolite using the Dietary Exposure E valuation Model (DEEM

- FCID  ) Version 2.03 (D351895, T. Goodlow, 12/09/2008). This model uses food consumption data from the U.S. Department of Agriculture’s Continuing Survey’s of Food Intakes by Individuals (CSFII) from
1994

- 1996 and 1998. It was perfor med to support the use of triallate on Bermuda grass grown for seed and hay. These acute and chronic analyses were conservative using field trial data, empirical processing factors, 100% crop treated values for all commodities, and estimated drinking wate r concentrations (EDWCs). The calculated acute exposure to food and water resulted in an estimated risk equivalent to <1% of the acute population adjusted dose (aPAD) at
the 95 th 

## percentile for all population subgroups. Chronic dietary risk calculated fr om exposures to food and water resulted in an estimated risk equivalent to <1% of the chronic population adjusted dose (cPAD) for all population subgroups as well.

Triallate is concluded to be a possible human carcinogen; therefore, a cancer dietary ris k assessment was performed which determined a cancer risk estimate of 3.0 x 10

- 7 

## for the general U.S. population.

Drinking Water Exposures

Drinking water exposures can potentially occur through run

- off resulting from the applications of
the herbicide triallate made to control weeds. To assess this potential exposure, the Environmental Fate and Effects Division (EFED) most recently modeled values for ground water
as well as surface water in support of its use on Bermuda grass grown for seed and hay (D3 58774, 11/20/2008, F.Khan)

. The EDWCs for the use on Bermuda grass did not exceed the values previously determined for wheat grown in North Dakota reported in the 2001 Triallate Reregistration Eligibility Decision (RED) document. Therefore, the EDWCs det ermined for the
wheat scenario were used for assessment. For the wheat scenario, ground water EDWCs were estimated using the SCI

- GROW (Tier I) computer model. Model simulations indicate that the maximum total triallate residue (triallate + TCPSA) concent rations in ground water are not likely to exceed 0.21 ppb. Surface drinking water concentrations were estimated using the PRZM/EXAMS (Tier II) computer model with the Index Reservoir and Percent Crop Area. Tier
II PRZM

- EXAMS modeling predicts that the ma ximum total triallate residue (triallate + TCPSA) concentration in surface water is not likely to exceed 9.45 ppb for peak (acute) concentration and 1.26 ppb for 36

- year annual mean (chronic: cancer and non

- cancer)
concentrations. The triallate label stat es that this product is to be incorporated into soil. Surface

## Page 8 of 24

water EDWCs were modeled with and without incorporation, and the highest value of the two were used for the dietary assessment.

Data Requirements

The 2001 RED for triallate required that a barley processing study and a field accumulation rotational crop study must be provided. T he barley processing study has since been waived and
the data from wheat processing studies may be translated to barley (D 278935, S. Knizner, 11/26/2001). A rotational crop study was submitted in 2004 ( MRID No. 46296301 ) and is undergoing review to determine if this fulfills the data requirement. As such, the residue chemistry database for triallate is otherwise complete an d there are no outstanding data requirements for this chemical.

Conclusions: Currently there are no acute or chronic (food and drinking water) dietary risk
estimates which are of concern for triallate and its metabolite. Updated dietary exposure

assess ments for triallate may be necessary under registration review if the toxicological PoDs or uncertainty f

actors/safety factors (UFs/SFs) change, or there are significant changes in the
EDWCs

.

Residential (Non

- Occupational) Exposure

There are no resident ial uses for triallate nor are there any occupational uses resulting in residential post

- application exposure, at this time.

Residential Bystander Exposures

Residential bystander exposures resulting from off

- site transport (e.g., spray drift or volatilization) may occur as a result of agricultural applications of triallate. The potential for spray drift will be quantitatively evaluated for each pesticide duri ng the Registration Review process which ensures that all uses for that pesticide will be considered concurrently. The approach is outlined in the revised (2012) Standard Operating Procedures for Residential Risk Assessment (SOPs)

– Residential Exposure A ssessment Standard Operating Procedures Addenda 1: Consideration of Spray Drift. This document outlines the quantification of indirect non

occupational exposure to drift. In terms of volatilization, the agency has developed a Volatilization Screening To ol and a subsequent Volatilization Screening Analysis ( http://www.regulations.gov/#!docketDetail;D=EPA

- HQ

- OPP

- 2014

- 0219 ). During Registration Review, the agency will uti lize this analysis to determine if data (i.e., flux studies, route

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

.

Aggregate Risk Assessment

In accordance with the Food Quality Protection Act (FQPA), HED must con sider and aggregate pesticide exposures and risks from three major sources: food, drinking water, and residential exposures. The acute and chronic aggregate risk assessments for triallate included food and drinking water only (there are no registered resi dential uses)

.

## Page 9 of 24

Acute

The 2008 acute aggregate risk assessment included exposure to triallate and TCPSA residues in
food and water. The analysis used field trial data, empirical processing factors and 100 percent crop treated (%CT) for all commodities. Estimated drinking water concentrations from the Environmental Fate and Effects Division were also included. Acute dietary risk estimates for food alone and food and drinking water at the 95th percentile of exposure are below HED’s level
of co ncern with exposures utilizing <1% of the aPAD.

Chronic

The 2008 chronic aggregate risk assessment (cancer and non

- cancer) included exposure to
triallate and TCPSA residues in food and water. Both the cancer and non

- cancer analyses
utilized field trial data, empirical processing factors, 100% CT, and incorporated EDWC values. The assessments resulted in dietary risk estimates for food alone and food and drinking water that are below the HED’s level of concern for chronic dietary exposure. For non

- cancer exposure, the highest exposure and risk estimates were for all infants (<1 year), with a cPAD of <1% including food and drinking water. For the cancer assessment, the estimated dietary exposure for the general U.S. population corresponded to a cancer risk of 3 x 10

- 7 

## for food and drinking water.

Conclusions : During registration review, updated aggregate assessments may be conducted as required to include any significant change that might occur for toxicological PODs, FQPA and uncertainty factors, dietary exposure estimates

, or EDWCs.

Occupational Exposure

Triallate is registered for agricultural use on Bermuda grass (grown for seed or hay), dry beans and peas, green peas, lentils, barley, triticale, wheat, and sugar beets. There is potential for

occup ational handler and post

- application exposure.

Occupational Handler Exposure

Triallate can be applied with a groundboom, tractor

- drawn spreader, or enclosed fixed wing aircraft, at a rate of up to 1.5 lbs active ingredient (a.i. ) per acre for liquids and granules. Based on the handler activity use pattern the duration of exposure is only short

- term and intermediate

term for occupational handlers. This is based on the fact that there are different planting periods of the registered cr ops for triallate. Based on the current use pattern (maximum application rate of 1.5 lb (a.i.) /A per year) and handler activities, long

- term dermal exposure is not anticipated.
The PPE on the emulsifiable concentrate product labels is baseline protection for all handlers; mixer/loaders are also required to wear chemical

- resistant gloves. The PPE on the granular product labels is baseline for all handlers; loaders must also wear dust/mist respirators

.

The RED assessed all occupational handler scenarios except for the use on Bermuda grass, which was assessed in 2008. For occupational handlers, MOE(s) above 100 do not exceed

## Page 10 of 24

HED's level of concern. All short

- and intermediate

- term combined dermal and inhalation occupational exposure risk estimates for g ranular and liquid formulations did not exceed HED's level of concern at the baseline protection and enclosed fixed wing

- aircraft scenarios except for two mixing/loading liquid scenarios. However with additional PPE (gloves) to minimize dermal exposures f

or these two scenarios, exposure risk estimates were not of concern.

An assessment was conducted for the carcinogenic risk estimates associated with triallate following exposures to occupational handlers (private and commercial; mi xers, loaders and applic ators). Based on the RED and 2008 risk assessments, all occupational handler c ancer risk
estimates with l abel required PPE do not exceed 5 x 10

- 5



## .

Recommended unit exposures for occupational handler assessments have generally been derived only from the Pesticide Handlers Exposure Database (PHED). However, recently both the Outdoor Residential Exposure Task Force (ORETF) and the Agricultural Handler Exposure Task Force (AHETF) have produced pesticide handler exposure monitoring data that the Agency i s using in place of PHED (http://www.epa.gov/pesticides/science/handler

- exposure

- data.html). As more reliable data become available, the Agency will continue to replace existing data. Reviewers should incorporate new exposure monitoring data, as necessary , during registration
review.

Conclusions : An updated occupational handler assessment may be required under registration review if warranted by any significant changes in exposure assessment methodology, toxicological PODs or uncertainty factors.

Occupational Post

- application Exposure

No DFR (Dislodgeable Foliar Residue) data or exposure monitoring data were submitted for

t riallate. However, HED believes that the potential for post

- application worker exposure for all

uses except Bermuda grass is low, provided the 12 hour restricted entry interval is observed. There is low potential for exposure due to the timing of applications. Triallate is applied to the soil and/or soil incorporated pre

- emergence for wheat, barley, peas, lentils , and sugar beet s . This is well before the plants are mature, which likely mitigates the potential for post

- application exposure due to contact with treated foliage. Significant exposure to triallate during mechanical planting, harvesting, or any other late season activit ies, is not likely since triallate is applied pre

emergent (per Exposure Scientific Advisory Committee (SAC) policy #8). Also significant exposure to triallate during scouting, or while handling or coming in contact with treated soil is
minimal and would n ot exceed HED's level of concern. Therefore, HED does not require that any postapplication exposure data be generated to support the reregistration of triallate.

An exposure assessment was previously completed for exposure to triallate for workers entering treated Bermuda grass fields (D351897). O ccupational postapplication dermal exposure may occur after use of triallate on Bermuda grass grown for seed or hay as triallate ca n be applied to established stands, the REI is 12 hours, and irrigation is not required until 7 days after application to incorporate triallate. Based on the previous assessment, the MOE was 2,200 for post

- application activities associated with Bermuda gr ass. Cancer risk estimates were < 7 x 10

- 6 

## for post

- application workers. Based on a screen using updated exposure assessment policy using

## Page 11 of 24

forage crop assessment as surrogate for Bermuda grass, DFR data are not required as MOEs are greater than 2X the LOC

.

In accordance with 40CFR158, DFR data are required for all occupational (e.g., crop, nursery, greenhouse use sites) or residential (e.g., ornamental and vegetable gardens, pick your own farms, retail tree farms) uses that could result in post

- applicatio n exposure to foliage. In the
absence of chemical

- specific DFR data, EPA uses default values. The 2012 Standard Operating Procedures for Residential Pesticide Exposure Assessment includes an analysis of a number of DFR studies, which resulted in the sele ction of a revised default values for the fraction of the application rate available for transfer after a foliar application (F AR 

## ). These values are based on an analysis of 19 DFR studies. Since that time, the Agricultural Re

- entry Task Force has
submitt ed information (MRID 49299201) that corrects an application rate error made in the original submission of “ARF039

– Determination of Dermal and Inhalation Exposure to Reentry Workers During Chrysanthemum Pinching in a Greenhouse” (EPA MRID 45344501). As a result, the range of F AR 

## values was revised from 2%

- 89% to 2%

- 47%. In the data, a large range of transferability is observed and this variability can potentially be attributable to many factors such as active ingredient; formulation; field condition s in the studies; weather conditions (e.g., humidity); or many other difficult to quantify factors. Although witnessed across multiple chemicals, this range in F AR 

## values is not expected when considering DFR data for a single chemical. At this time, the ARTF submission did not alter the selection of 25% as the reasonable, high

- end default value. Because DFR data are not available for triallate , EPA is using the default value of 25%. Although there may be a small degree of uncertainty in the use
of the d efault DFR value for triallate (i.e., there is a small chance that the F AR 

## value may exceed the applicable default value), it is likely that the health

- protective aspects of EPA’s occupational post

- application assessment methodology will more than compensa te for this potential uncertainty. For example, when assessing residential and occupational post

- application exposure to gardens and ornamentals, EPA assumes the following: exposures occur to zero

- day (i.e., day of application ) residues every day of t he assessed exposure duration (i.e., EPA assumes that no dissipation or degradation occurs, it doesn’t rain, etc); individuals perform the same post

application activities performed in the transfer coefficient study day after day (e.g., weeding, harvesting , pruning, etc.); and individuals engage in these post

- application activities for a high

end amount of time every day (represented by data reflecting time spent gardening based on survey data).

Given the conservatisms discussed above and the potential com pounding nature of these conservatisms, EPA is able to rely upon the calculated exposure estimates with confidence that exposure is not being underestimated.

Since the highest estimated occupational post

- application exposure using default DFR values for
triallate is minimal in comparison to the level of concern (i.e., the calculated MOE is greater than 2 times higher than the level of concern, MOE = 540 compared to the LOC of 100 ); EPA is waiving the 40CFR DFR data requirement. In this instance, it is un likely that chemical

- specific DFR data would be needed to further refine exposure assessments or would add appreciably to our overall understanding of the availability of dislodgeable foliar pesticide residues for triallate

.

## Page 12 of 24

Recommended transfer coeffic ients for occupational post

- application assessments are derived from Agricultural Reentry Task Force (ARTF) exposure monitoring studies (http://www.epa.gov/pesticides/science/post

- app

- exposure

- data.html). These transfer coefficients have been updated in 2 012 based on a reanalysis and submission of new monitoring data. Reviewers should incorporate new exposure monitoring data, as necessary, during registration review.

The Worker Protection Standard (WPS) Restricted Entry Interval (REI) for triallate is 12 hours.

Conclusions : An updated occupational post

- application assessment may be required under registration review if warranted by any significant changes in exposure assessment methodology.
No chemical

- specific DFR or TTR data are required for triallate

.

Public Health and Pesticide Epidemiology Data

HED has evaluated the available incident data 1 

## and concludes that there does not appear to be a
concern at this time that would warrant furt her investigation, since t here were no incidents involving triallate reported to either IDS or SENSOR

- Pesticides. The Agency will continue to monitor the incident information and if a concern is triggered, additional analysis will be
included in the risk assessment.

Tolerance Assessment and International Harmonization

Permanent tolerances are established under 40 CFR §180.314 for the registered uses of triallate on raw agricultural commodities. A spreadsheet summarizing the international residue limits established for triallate and its metabolite TCPSA is presented in Attachment 4 . There are no MRLs established for the residues of triallate by Codex or Mexico. Canada has established
MRLs on triallate for a number of commodities which are harmonized with those tolerances set by the U.S. As such, there are no internati onal harmonization issues which are in difference with
the tolerances established for the herbicide triallate.

As per the HED memo on tolerance expressions (S. Knizner, 2009, Interim Guidance on Tolerance Expressions ) , the tolerance expressions for triallate should be revised as follows:

(a) General . Tolerance are established for residues of the herbicide triallate, including its metabolites and degradates, in or on the commodities in the table below. Compliance with the tolerance levels specified b elow is to be determined by measuring only the sum of triallate, S

- (2,3,3

- trichloro

- 2

- propen

- 1

- yl) N,N

- bis(1

- methylethyl)carbamothioate, and its metabolite 2,3,3

- trichloroprop

- 2

- enesulfonic acid (TCPSA), calculated as the stoichiometric equivalent of trial late, in or on the commodity.

(c) Tolerances with regional registrations . Tolerances with a regio nal registration, as
defined in 180.1(l) are established for residues of the herbicide triallate, including its metabolites and degradates, in or on the commodit ies in the table below. Compliance

1 

### Triallate: Tier I Review of Human Incidents. E. Evans, 5/8/14. D420141.

## Page 13 of 24

with the tolerance levels specified below is to be determined by measuring only the sum of triallate, S

- (2,3,3

- trichloro

- 2

- propen

- 1

- yl) N,N

- bis(1

- methylethyl)carbamothioate, and its metabolite 2,3,3

- trichloroprop

- 2

- enesu lfonic acid (TCPSA), calculated as the stoichiometric equivalent of triallate, in or on the commodity.

International or Intergovernmental Work Sharing

HED is not currently involved in any joint international review projects that involve the active ingre dient, triallate . Additionally, HED is unaware of any ongoing international assessments for
triallate

.

Cumulative

The FQPA requires the Agency to consider the cumulative risks of chemicals sharing a common mechanism of toxicity. Triallate is a membe r of the thiocarbamate class of pesticides. The Agency has determined that the thiocarbamate pesticides should not undergo cumulative assessments since chemicals in the group do not act the same way in the body. In late 2001 and early 2002, EPA provided an opportunity for the public to comment on the Agency’s common mechanism determinations for the thiocarbamates, which also belong to the carbamate group of pesticides. EPA determined that the thiocarbamates do not share a common mechanism of toxicity 2



## . Therefore, a cumulative risk assessment has not been performed

.

Human Studies

There are no triallate

- specific human studies that require an ethics review at this time.

Data Requirements

The following data deficiencies were identified for triallate :

Toxicolog y : N one

Res idue Chemistry :

 Submittal of Analytical Reference Standards

2 

### http://www.epa.gov/oppsrrd1/cumulative/

## Page 14 of 24 o The current stock of TCPSA standards available in the EPA National Pesticide Standards Repository has expired (personal communication with Theresa Cole, BEAD, 03/28/2014). Analytical reference standards of TCPSA must be provided with an updated certificat e of analysis (COA) or new materials sent to the Repository as soon as possible. The reference standards should be sent to the Analytical Chemistry Lab, which is located at Fort Meade, to the attention of either Theresa Cole or Thuy Nguyen at the followin g address:

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

- 5350

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

Occupational and Residential Exposure : None

References

Triallate. PC Code 078802. Outcome of the Metabolism Assessment Review Committee Meeting Held on May 14, 1998. L. Cheng, June 22, 1998. No. 012656.

Triallate. Acute, Chronic, and Cancer Aggregate Dietary (Food and Drinking Water) Exposure and Risk Assessments for the Section 3 Registration Action on Bermuda Grass. T. Goodlow, December 09, 2008. D351895.

Triallate. Revised Drinking Water Exposure Assessment to establish tolerances of t riallate and its degradate 2,3,3

- trichloro

- 2

- propenesulfonic acid (TCPSA) on Bermud a grass grown for seed.
F. Khan, November 20, 2008. D358774.

Triallate. Wheat Hay/Barley Hay Data Waiver Request. Guideline 860.1500. Chemic al
Number 078802. S. Knizn er, November 26, 2001. D278935.

446296301 Moran, S. J. and Beasley, R. K. (2004) Residues of Triallate in Rotational Crop Raw Agricultural Commodities Following Application of Far

- GO ® 

## Herbicide . Report Number MSL

I7772 . Unpublished study prepared by Monsanto Company. 226 p.

Triallate: Risk Assessment for Proposed New Use of Triallate as Pre

- emergence Herbicide for Bermuda grass, Case #82 4883. A. LaMay, 12/8/08. D351897

Triallate. HED Reregistration Eligibility Document. PC Code: 0 78802. DP Barc ode D260034.
J. Morales.

Triallate: Tier I Review of Human Incidents. E. Evans, 5 /8 /14. D 420141

## Page 15 of 24

Attachment 1. Chemical Identity and Physicochemical Properties of Triallate

Physical and Chemical Properties of Triallate [ S

- (2,3,3

- trichloro

- 2

- propen
- 1

- yl) N,N

- bis(1

- methylethyl)carbamothioate]

Table 1. Triallate Nomenclature. Compound Chemical Structure

Common name Triallate Company experimental name N/A

IUPAC name 

### S

- 2,3,3

- Trichloroallyl diisopropyl

- thiocarbamate

CAS name S

- (2,3,3

- trichloro

- 2

- propen

- 1

- yl) N,N

- bis(1

- methylethyl)carbamothioate

CAS # 2303

- 17

- 5
End

- use product/(EP) Far

- GO® Granular Herbicide
Avadex® MicroActiv Herbicide


### TCPSA Metabolite Nomenclature. Compound Chemical Structure

Common name TCPSA Company experimental name N/A

IUPAC name 

### 2,3,3

- Trichloroprop

- 2

- enesulfonic acid

Table 2. Physicochemical Properties of Technical Grade Triallate.

Parameter Value Reference
Melting point/range 29

- 30°C

Triallate Product Chemistry Chapter, D078802, 7/29/99, J.
Morales. Density 1.2600

- 1.2624 at 35°C
Water solubility 4 ppm at 25°C
Solvent solubility Soluble in methylene chloride, n

- octanol, and toluene at >200 g/100 mL
Vapor pressure 1.1 x 10

- 4 mm Hg at 25 o C
Dissociation constant (pKa) Not Provided
Octanol/water partition coefficient log (K ow ) 4.54

UV/visible absorption spectrum Not Provided

## Page 16 of 24

Attachment 2. Acute, Subchronic, and Chronic Toxicity Profile

Acute Toxicity of Technical Triallate

Guide l ine Study T y pe (D a t e ) MRID Results Tox.
Cat.

870. 1 1 0 0 (§ 81

- 1) Acute Oral

- Rat

(6/29/98) 44 6 6 0 701 L D 50 (males) = 36 1 2 mg/kg (26 5

- 4 9 09 m g /kg)

L D 50 (females) = 3455 mg/kg (25 9 0

- 4 6 11 m g /kg)
L D 50 ( combined) = 3382 mg/ k g (27 5 5

- 4 151 mg/kg) III

870. 1 2 0 0 (§ 81

- 2) Acute Derm a l

- Ra b b it (1/11/ 9 1 ) 42 1 9 2 001 L D 50 > 5000 mg/kg IV

870. 1 3 0 0 (§ 81

- 3) Acute Inha l ati o n

- Rat

(9/9/82) 00 1 2 1 856 L C 50 > 5.3 mg/L IV

870. 2 4 0 0 (§ 81

- 4) Prima r y E y e Ir r itation

- Ra b b it

(1/22/98) 44 5 9 1 801 Sli g ht e y e irrit a nt III

870. 2 5 0 0 (§ 81

- 5) Prima r y Derm a l Irritation

Ra b bit (1/27/ 9 8) 44 5 8 1 601 Sli g ht dermal i r ritant IV

870. 2 6 0 0 (§ 81

- 6) Dermal S ensit i zation

- G u in e a

pig B u eh l er te s t (10/7/83) 00 1 3 2 879 Non s e nsitizer N/A

870. 2 6 0 0 (§ 81

- 6) Dermal S ensit i zation

- G u in e a pig

m a ximizat i on test (6/6/97) 44 3 0 8 301 Dermal s e nsit i zer N/A



## Sub

- chronic, Chronic, and Other Toxicity Profiles for Triallate

Guide l ine Study T y pe (D a t e ) MRID Results

Subchronic T oxicity

870. 3 1 0 0 (§ 82

- 1) 90

- Da y Fe ed in g

- Rat

(8/23/82) 00 1 1 5 639 S y stemic NO A EL=100 p p m (5/mg/kg/d a y )
S y stemic LO A EL=500 p p m (25 mg/kg/d a y) bas e d on
decr e ased bo d y w e i g ht in ma l es and fem a le s , slight

ane m ia in fe m ales ( d ecrea se d red b l o o d cel l s, hematoc r it and hemo g lo b in) and hist o pat h o l og y of the
kid ne y in ma le s (tubular e p it h e li a l re g e n e rat i on a n d

ne p hro p at h y )

870. 3 2 0 0 (§ 82

- 2) 21

- Day Dermal

- R at

(1/29/90) 41 4 8 7 001 S y stemic NO A EL = 500 mg/kg/d a y S y stemic LO A EL = 3000 mg/kg/d a y ba s ed o n bo d y w e i g ht

ga i n d e creases, re l a ti v e kid ne y a n d l i ver w ei ght incr e a ses, inc r eas e d pre s en c e of bas o ph i lic tubu l es of the ren a l cort e x ,
a n d al p h a μ

- gl o bu l in in c lu si ons in the pr o x im a l con vo luted

r e nal t ub u les.

Dermal NOA E L<1 0 0 mg/kg / d a y Dermal LOA EL =100 mg/kg/d a y b ased o n inc r eas e d inci d en c es of a canthotic e p i d e rmal thick e ni ng

.

## Page 17 of 24

(§ 82

- 2) Subch r onic I nh alat i on (6

hr/d a y 5 d a ys / w e e k for 7

w e eks)

- Rat (9/27/83) 40 0 7 2 105
00 1 3 2 878 NOAEL < 0.01 mg/L (2.62 m g / kg/d a y) not es t abli s h e d

LOAEL=0.01 mg/L (2.62 mg / kg/d a y) ba s ed on histo l ogi c a l c h an g es in the k i dn e y ( n e p hro p at h y and
tubu l ar epi t he li a l re g ene r ati on ).

Chronic Toxi c it y /Carcinogenicity

870. 4 1 0 0 (§ 83

- 1) Chronic T o x ici t y

- Dogs

(10/2/79) 00 0 2 9 455 S y stemic NO A EL=1.5 mg/kg/d a y (1.27 mg/ k g/d a y calcu l ated)
S y stemic LO A EL=5.0 mg/kg/d a y (4.25 mg/ k g/d a y calcu l ated) b a s ed on i n cr e a s e d hemo s ide r in
de p ositi o n in t h e spl e en, inc re ased se r um al k ali n e pho s p h atase a nd inc r eas e d l i ver w ei ght in f e males.

870. 4 1 0 0 (§ 83

- 1) Chronic T o x ici t y

- Dogs

(2/4/88) 40 7 3 0 604 S y stemic NO A EL=2.5 mg/kg/d a y S y stemic LO A EL=15.0 mg/k g /d a y bas e d on i n crea s ed
alka l i n e p h os p hatase l e v e ls a t all time inter v als in m a le and
fem a le do g s.

870. 4 2 0 0 (§ 83

- 2) Chronic T ox ici t y /
Carci n o g eni c ity

- Rat (7/10/87) 40 3 8 4 701
41 1 1 6 901 NOAEL= 50 p p m (2.5 mg/kg/d a y ).

LOAEL= 250 p pm (12.5 mg/ k g/d a y) ba s ed o n decr e ased

s u rvival (ma l e s a n d females), d e creas e d bo d y w e i g ht (males) a nd inc re a sed a d r e nal w e i g ht (males).

E v idence of carcinogenicity: Renal tu b u la r ad e nomas i n male rats.

870.4200 (§ 83

- 2) Chronic Toxicity/

Carcinogenicity

- Mice (10/83) 00132859 NOAEL(males) = 20 ppm (3 mg/kg/day)

LOAEL (males) = 60 ppm (9 mg/kg/day) based on increased absolute liver weight, increased incidence of altered foci of the liver and hematopoiesis in the spleen.

NOAEL(females) = 250 ppm (37.5 mg/kg/day) LOAEL(females) >250 ppm (37.5 mg/kg/day) not establ ished

Evidence of carcinogenicity: Increased incidence of hepatocellular carcinomas and hepatocellular adenomas (males). 870.4200 (§ 83

- 2) Chronic Toxicity/

Carcinogenicity

Hamster (10/18/84) 00151790

00159797 NOAEL=50 ppm

LOAEL=300 ppm based on decreased triglyceride levels (males and females).

No evidence of carcinogenicity

D e v elopmental/Reproduct i v e Toxicity

870. 3 7 0 0 (§ 83

- 3) Deve l op m ent a l T o xici t y

- R at

(5/10/82) 00 1 1 4 260
41 7 0 6 906 Matern a l NOAEL = 10 mg/kg/d a y

Matern a l LOAEL = 30 mg/kg/d a y ba s ed o n decr e ases in
b od y w ei ght ga i n a n d food consu m ption.

Deve l op m ent a l NOAEL = 30 mg/kg/d a y Deve l op m ent a l LOAEL = 90 mg/kg/d a y ba s ed on decr e ased fet a l bo d y

w e i g ht, ex t ern a l malfo r mations (protru d ing t on gue) a nd
sk e l e tal variat i ons.

## Page 18 of 24

870. 3 7 0 0 (§ 83

- 3) Deve l op m ent a l T o xici t y

Ra b b it (1/21/82) 00 1 1 4 261
43 3 1 5 001 Maternal NOAEL = 15 mg/kg/day

Matern a l LOAEL = 45 mg/kg/d a y ba s ed o n clini c al signs a nd d e c r eases i n b od y w e i g ht ga i n.

Deve l op m ent a l NOAEL = 5 mg/kg/d a y Deve l op m ent a l LOAEL = 15 mg/kg/d a y ba s ed on decr e ased fet a l bo d y

w e i g ht a nd inc r eas e d s kelet a l variat i ons.

870. 3 8 0 0 (§ 83

- 4) 2

- Gene r ati o n Rep r oduct i on

Stud y

- Rat (10/20/ 8 3 , 7/1 1 /84) 00 1 4 4 308
00 1 3 2 880 Parent a l/ S y st e mic NOAEL = 150 p pm (7.5 mg/kg/d a y)

Parent a l/ S y st e mic LOAEL = 600 ppm ( 3 0 m g /kg/d a y)
bas e d on mat e rnal mort a li t y , i n crea s ed in c i d ences of
chro n ic ne p hrit i s, head b ob b i n g, circli n g mo v e ments and

r e du c ed b o d y w e ights.

Rep r oducti v e/Deve l op m ent a l NOAEL = 150 ppm (7.5 mg/kg/d a y). Rep r oducti v e/Deve l op m ent a l LOAEL = 600 ppm (30 mg/kg/d a y) b a sed on i ncr e a s ed n e o n atal m ortali t y dur i ng the F 2b litter interval, r e duc e d p u p w e i ghts at
birth du r ing t h e F 2b litter interval, redu c ed pu p w ei ghts in
late l a ctati o n for all litters, redu c ed p r eg na n c y ra t e and

s h orte n ed gestati o n l e ng t h.

Mutagenicity

870. 5 1 0 0 (§84

- 2) Gene Mutati o n in Sa l m o ne l la

typh i mur iu m (7/1/77) 00 0 8 8 624 Posit i v e. T riallate i n du c ed a mutag e nic re s pon s e in
S a l m o ne l la typ h i mu r iu m stra i n s T A1535 and T A100 at

non c ytot o xic d o ses of 0.1 μg / plate a nd a bo v e

- S9 activati o n

a n d T A1535, T A98 and T A100 at 0.001 μg/p l ate a n d a bove + S9. In tester strains T A15 3 7 a n d
T A1538, there w e re n o a p pr e ciab l e inc r ea se s in revertant

co l o n ies or ev i den c e of c y t o t o xici t y at a n y dose.
Muta ge nesis w a s conf

i rmed in a r e p e at test w ith S a l m o ne l la
typ h i mu r iu m stra i n T A1535 at dose le v e ls
of 1, 5, and 10 μg/p l ate + /

- S9 activation.

870. 5 3 0 0 (§84

- 2) Gene Mutati on / In vitro

mammalian cell assay in

mouse l y m

ph o ma cells (8/1/77) 00 0 8 3 644 Negat i v e

. T riallate did not in d u ce fo r w a r d g e ne mutations at the th y midine kinase ( T K +/

- ) locus in L5 1 7 8 4 mouse l y m

p ho m a cel l s at concentrat i ons of
0.005 to 0. 0 4 μ l/mL in the ab s ence or p r es en ce of
metab o lic acti v a tion.

870. 5 3 0 0 (§84

- 2) Gene Mutati on / In vitro

mammalian cell assay in

mouse l y m

ph o ma cells (8/1/77) 41 0 9 1 007 Posit i v e

. T riallate i n du c ed f or w a rd g ene m

u tations at the

t h y m id i ne k ina s e ( T K +/

- ) l o cus in L 5 1 7 84 mouse l y m p h o ma

ce ll s. T he freque nc y of g e ne mu t a tions

w a s gr e a ter than or e q u a l to a t w o

- f o ld i n cr e a se a n d

occurr e d at n o n c y t ot o x ic co n centrati o n s of 60 μg/mL

- S9 activation and 2 1 a n d 24 μg/mL+S9 act i vation.

870. 5 3 8 5 (§84

- 2) C y t o g e netics/ In vivo

hamster micr o nuc l eus as sa y (5/7/82) 00 1 1 4 263 Negat i v e

. T here w a s no e v i de n ce of eit h er a clasto g enic or

an e u g enic eff

e ct in male a n d fema l e hamsters fed d ieta r y

c on c ent r ations of 0, 6 0 0, 2000 or 60 0 0 ppm T riallate at a n y sac r ifice time.

870. 5 3 9 5 (§84

- 2) C y t o g e netics/ In vivo mou s e

micronu c l e us a ss a y (1/15/91,
10/ 1 5/97; Amend m ent) 44 5 9 1 701 Negat i v e

. T here w a s no e v i d ence of ei t her a clasto g enic

or an e u g enic eff

e ct in male a n d fema l e mice adm i n ist e red 70, 3 5 0, or 700 mg/kg T riallate at any sacrifi c e time.

## Page 19 of 24

870. 5 5 5 0 (§84

- 2) Other Mutag en ic Mechanisms/

In vitro unsc h e d ul e d D NA

s y n t hesis in prima r y rat h epato c ytes (11/14/ 8 5 ) 40 7 3 0 601 Negat i v e

. T riallate did not induce a g e not o x i c effect in prima r y rat h ep a to c y t e s at c o n centrati o n s of 5, 10, 50, 100, 5 0 0 a n d 1 000 μ g /mL.

870. 5 5 5 0 (§84

- 2) Other Mutag en ic Mechanisms/

In viv o / In vitro unsc h e d ul e d
D NA s y n t hesis in prima r y rat h epato c ytes (9/20/89, 9/ 2 5/89;
Amend m ent) 44 7 0 1 001 Negat i v e

. T here w a s no e v i de n ce that T riall a te in d u ced
either a c y tot o xic or g enot o xic res po n se at a n y do s e (50,
250 or 5 00 mg / kg) or sacrifice time (92 or 16 h o urs).

870. 5 9 0 0 (§84

- 2) Other Mutag en ic Mechanisms/

In vitro sister chromat i d

e x c h an g e in Chi n ese h a mster

ova r y c e l ls (9/3/82) 00 1 2 1 859 Posit i v e

. T rial l ate in d u c e d si g n ific a n t increa s es in the

num b e r of sister chromat i d e x c h a n ges p e r cell at

conc e n trati o ns of 1.6 x 1 0 - 5 M to 8.1 x 1 0 - 5 M

- S9 activati o n a n d 0.8 x 1 0 - 5 M to 4.0 x 1 0 - 5 M +S9
activati o n after either a t w o or four hour e xp o sure per i od,

res p ective l y . R e peat a ss a y s c o n d ucted for 30 hours at

con ce n trations u p to 40.4 x 1 0 - 5 M

- S9
activati o n a n d for 2 hours at c onc e n trati o ns up to 12.1 x 1 0 - 5

M + S9 activation c o nfi r med these fi n d i ngs.

N e uroto x i c ity

870. 6 1 0 0 (§ 81

- 7) Acute De la y e d Neu r ot o x ici t y

Hen

(8/10/83) 00 1 3 2 874

40 0 7 2 104 S y stemic NO A E L ≺ 3 12.5 mg / kg (not estab l ish e d)

S y stemic LO A EL=312.5 mg/ k g bas e d on acute, revers i b l e clini c al s i gns (muscle w e a k ness/ p a r al y s is, salivat i o n and
invo l unta r y n e c k movement) Trial l ate d i d not in d u ce d e l a y e d peri p her a l n eu ropat h y

870. 6 2 0 0 (§ 81

- 8) Acute Neu r ot o x i c i t y

- Rat

(7/8/93) 42 9 0 8 101 S y stemic NO A EL = 60 mg/kg
S y stemic LO A EL=300 mg/kg bas e d on d e c r eas e d bo d y

w e i g ht g a in a n d alte r a ti o n s in motor act i vi t y

870. 6 2 0 0 (§ 82

- 7) Subch r onic Ne urot o x i c i t y

- R at

(11/17/ 9 3 ) 43 0 2 1 601 S y stemic/ N eu r ot o x ici t y NOA E L=100 p p m (6.38/8.14 mg/kg/day for males/females) S y stemic/ N eu r ot o x ici t y LOA E L=500 p pm (3 2 .9/38.9 mg/kg/d a y for
males/fem a les) based o n dec r eas e d bo d y, b od y w ei ght

ga i ns , food consu m

pti o n and lesi o n s (ner v e fiber
d eg e ne r at i on) in the c e nt r a l a n d per i phe r al n e r v ous

s y stems.

870. 6 2 0 0 (§ 82

- 7) Subch r onic Ne urot o x i c i t y

- R at

(11/3/98) 44 6 9 4 501 Neu r ot o x ic N O AEL= 2000 p p m (achie v ed d o se 1 3 4.32 mg/kg/d a y)
Neu r ot o x ic L O AEL = 4000 pp m (achie v ed d ose 2 2 3.79 mg/kg/d a y) b a sed on b e h a vi o ral effects (histo p atho l o g y for ax o nal d e g ene r ation w a s not

con d ucted at this do s e le v el)
At 6000 p p m (295 mg/kg/ da y) neur o h ist o pa t ho l ogi c a l
lesi o n s in b o th the central a n d peri p her a l ne r ves. S y stemic NO A EL = 500 ppm (34.64 mg/kg / da y ) S y stemic
LO A EL = 2000 p pm (achie v ed d o s e 134. 3 2 mg/kg/d a y) w a s based o n de c reas e d b od y wei g ht and food

con s umpt i on a n d food ef

f icien c y.

## Page 20 of 24

870. 6 3 0 0 (§ 83

- 6) Deve l op m ent a l Neurot o xici t y

Rat (12/2/98) 44 7 1 0 501 Matern a l NOAEL = 30 mg/kg/d a y Matern a l LOAEL = 60 mg/kg/d a y ba s ed o n reduct i ons in
b od y w ei ght ga i ns a n d food consumpt i on

Deve l op m ent a l Neurot o xici t y NOAEL = 30 mg/kg/d a y Deve l op m ent a l Neurot o xici t y LOAEL = 60 mg/kg/d a y bas e d on i n cr e a sed motor ac t ivi t y

.

Metabolism

870. 7 4 8 5 (§ 85

- 1) Gener a l Meta b olism

- R at

(10/6/83, Part I) 00 1 3 8 159 Ana l y s is of w h ole b o d y e lim in ation i n male a nd fema l e rats indi c a ted that 85% of the rad i ol a be l ed tr i a lla t e w a s exc r eted

w i t h in 24 hours of do sing. Most rad i oactivi t y w a s e x cret e d
i n app ro x imat el y e qu a l am o u n ts (42%) in the uri n e a n d feces
of male r a ts after 10 d a ys. F e males e x c re ted 51% i n ur in e and 3 2 % i n feces after
10 d a ys. Mal e s and fema l e s retai n ed a bout 0.4% of the
dose i n or g ans a n d tissu e s and a p pr o x i mate l y 2.0% in the re main i ng carca s s. T he distribut i on of
rad i oactivi t y in both s e xes i n di cated that the greatest amo u nt of activi t y w a s f

o und i n the red b l o o d cells foll o w e d b y

w h ole b lo o d, spl e en, kid ne y , l iv e r and l u ng.

## Page 21 of 24

Toxicology Data Requirements

The toxicology data requirements (40 CFR 158.340) for the food uses of triallate are presented below. Use of the new guideline numbers does not imply that the new (1998) guideline protocols were used.

Test Technical

Required Sati s fied

870

. 1100 A c u t e O ral T oxic i ty

....................................................... 870

. 1200 A c ute D e r m al Toxicity

.................................................. 870

. 1300 A c ute In halation T o xicity

.............................................. 870

. 2400 Pr i m ary Eye I r ritation

.................................................... 870

. 2500 Pr i m ary Der m al Irritation

.............................................. 870

. 2600 D e r m al Sensitization...................................................... yes
yes
yes
yes
yes
yes yes

yes
yes
yes
yes
yes

870

. 3100 Or al Sub

- ch r onic ( r od e n t)

............................................... 870

. 3150 Or al S u b

- ch r onic ( n on r od e n t)

......................................... 870

. 3200 21

- Day D e r m al

.............................................................. 870

. 3250 90

- Day D e r m al

.............................................................. 870

. 3465 90

- Day In halation

.......................................................... yes
yes
yes CR

yes yes

yes
yes
yes yes*

870

. 3700a D e velop m

ent a l Toxicity ( r od e n t )

................................... 870

. 3700b D e velop m

ental Toxicity ( n on ro den t )

............................. 870

. 3800 R e p r oduction

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

yes
yes

870

. 4100a Chronic T oxicity ( r od e nt)

.............................................. 870

. 4100b C h ronic T ox i city (non

- r od e nt)

........................................ 870

. 4200a On cog e nicity (rat)

.......................................................... 870

. 4200b On cog e nicity ( m ouse)....................................................
870

. 4300 C h r o nic/ O n cog e nicit y

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

no
yes
yes
yes yes

yes
yes
yes
yes

870

. 5100 M u tagenicity

— Re v erse Mutation

- bacteria l

................. 8 7 0 .5 3 7 5 M u tagenicit y

— C h ro m oso m al A b errati o ns

- m a mm alian
870

. 5395 M u tagenicit y

— Ma m m a lian Micronucleus

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

yes
yes

870

. 6100a A c ute Delayed N eu r otox. ( h en)

..................................... 870

. 6100b 90

- Day N e uro t ox i city (hen )

........................................... 870

. 6200a A c ute N e uro t ox. Scre e n ing Batt e ry ( rat)

....................... 870

. 6200b 90

- Day N e uro. S c reen i n g Battery (rat )

.......................... 870

. 6300 D e velop. N e u r o

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

no
yes
yes
yes yes

no
yes
yes
yes

870

. 7485 G e n e ral Metab o l i sm

...................................................... 870

. 7600 D e r m al Penetration

........................................................ 8 7 0 .7 8 0 0 I m m

unotoxicity

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

no
yes yes

no yes**
* 7 week i n halation s t

udy is a v ailable, ** Waived by HASPOC (TXR# 0056861)

## Page 22 of 24

Attachment 3. Triallate Toxicological Doses and Endpoints for Risk Assessment

T ox i c o lo g i c a l D o ses a nd Endp o ints f o r Tri a ll a te Hum a n He a l th Risk Assessments.

Exposure
Scenar i o Point of

Departure Unce r tai n ty/ F QPA

S a fet y F a ct o rs R f D, P A D, Level
of Conce r n for
Risk Asses sm ent Stu d y a n d T o xicol o gical E f f ects

Acute Dietary (Fe m ales 13

- 49) N O AEL = 5

m g / kg / day U F H 

### = 10X

U F A 

### = 10X

T o tal UF = 10 0 X FQ P A = 1X acute R f D= 0

. 05

m g / kg / day

aPAD = Acute R fD FQPA Factor



### aPAD = 0.05

m g / kg / day Rabbit Develo pm ental Stu d y

LOAEL= 15 m g/kg/d a y ba s e d on inc r ea s ed s ke l e t al

v ari a tions in t

h e f etus. T h e sk e le t al variations a re
presu m ed to o ccur af

t er a s ing l e exposure (dose) and
thus are ap p ropriate for this ( acute) risk assess m ent. In
ad d itio n , s k e l et a l variations ( m alalig n e d s t e r nebrae)

were a lso seen in r a t fet u s e s following in utero exposure
to triallate.



### Acute Dietary (G e n eral US Pop.) N O AEL =6 0

m g / kg / day U F H 

### = 10X

U F A 

### = 10X

T o tal UF = 10 0 X FQ P A = 1X acute R f D= 0

. 6

m g / kg / day

aPAD = Acute RfD FQP A f a ctor



### aP A D = 0

. 6

m g / kg / day Rat Ac u te Neur o toxicity Stu d y

LOAEL=300 m g/kg/day based o n altered motor activity
and c h anges in F OB in t

h e r at acute n eurotoxicity stu d y

. Because of the n eurotox i c c h ar ac terist i cs of tr i al la te (altered

motor activity obser v ed in both sexes 7 h ours after

treatment at the mid

- and hig h

- d oses that persisted up to
14 da y s in high

- dose females), t h is endpoi n t is c o nsidered

a ppropriate for assessing risk in t h e gene r a l population.



### Chronic Dietary (all p o p u lati o ns) N O AEL =

2

. 5

m g / kg / day U F H 

### = 10X

U F A 

### = 10X

T o tal UF = 10 0 X FQ P A SF = 1X C h r onic R fD=
0

. 0 2 5 m g / kg / d ay

cPAD = C. RfD FQP A S F



### cPAD = 0

. 0 2 5

m g / kg / day 2

- y e ar chron i c t oxici t y /c arcino g eni c i t y in r a ts

LOAEL=12.5 mg/kg/day based o n dec r eased s ur v ival in

m a l e s a nd f

e m a l e s , de c r e a s e d mean bo d y w e ights in males
and inc r eased a drenal weights i n m a les.



### Der m al
Short

- Term (1

- 3 0 da y s)

I n ter m e d iate

Term ( 1

- 6 m on t h s) Oral

N O AEL = 5

m g / kg / day U F H 

### = 10X

U F A 

### = 10X

T o tal UF = 10 0 X

Der m al Ab s o r p tion = 1% ( o f oral a b s o r p ti o n) Occu p atio n al
LOC = 1 00 Rabbit Develo pm ental Stu d y

LOAEL= 15 m g/kg/d a y ba s e d on inc r ea s ed s ke l e t al
vari a tions in t

h e fetus. T h e 21

- da

y dermal toxicity stu d y
was not se l e c ted because de v elo pm ental eff e cts w ere n o t eval u a ted in th a t stu d y.

## Page 23 of 24 T ox i c o lo g i c a l D o ses a nd Endp o ints f o r Tri a ll a te Hum a n He a l th Risk Assessments.

Exposure Scenar i o Point of

Departure Unce r tai n ty/ F QPA

S a fet y F a ct o rs R f D, P A D, Level of Conce r n for
Risk Asses sm ent Stu d y a n d T o xicol o gical E f f ects

In h alati o n Short

- Term (1

- 3 0 da y s)

I n ter m e d iate

Term ( 1

- 6 m on t h s) Oral

N O AEL = 5

m g / kg / day U F H 

### = 10X

U F A 

### = 10X
U F DB 

### = 1X

T o tal UF = 10 0 X

In h alati o n to x i city is

assu m ed to be

equ i valent t o o ral

t ox icity Occu p atio n al
LOC = 1 00 Rabbit Develo pm ental Stu d y

LOAEL= 15 m g/kg/d a y ba s e d on inc r ea s ed s ke l e t al
vari a tions in t

h e fetus. T h e 7

- w e ek in h a l a tion st ud y was
not used b ecause the stu d y w a s classified supplementa r y due to t echn i cal diffic u lt i e s

.

Long

- Term (Der m al & Inhalation) A dose and end p oint we r e n o t selected because o f the cur r ent u s e pat t ern, hand l er ac t ivit i es and r e

- ent r y work e r a c t ivit i es. Since

long

- term dermal exposu r e (continuous ex p osure of g r eater than 180 da y s) is not a n ticipated, a qua n titati v e assessment is not

req u ire d

. 

### Cancer (oral,
der m a l

, i nh alatio n ) Group C chemical

– possible human carcinogen

- Q 1 * = 7.17 x 10
– 2 (mg/kg/day) - 1 in human eq u ivalents [con v erted from

ani m als to hu ma ns b y use of t h e (mg/kg bo d y weight ) 3⁄4 c ross sp e c i e s s c aling f a ctor] 

### b ased on hepatocellular carcinomas from a c h r on i c/carc i n o g e n i ci t y s t udy i n mi ce.

## Page 24 of 24

Attachment 4. International Residue Limits for Triallate



# International Residue Limits Triallate (078802; 03/27/14 )

Summary of US and International Tolerances and Maximum Residue Limits Residue Definition : US Canada Mexico 1 

### Codex §180.314 (a) General. Tolerances are established for residues of triallate, S

- (2,3,3

- trichloro

- 2

- propen

- 1

- yl) N,N

- bis(1

- methylethyl)carbamothioate and its metabolite 2,3,3

- trichloroprop

- 2

- enesulfonic acid (TCPSA) carbamothioic acid, N

, N

bis(1

- methylethyl)

- , S

- (2,3,3

- trichloro

- 2

- propen

- 1

- yl) ester, including the
metabolite 2

- propene

- 1

- sulfonic acid, 2,3,3

- trichloro

None

Commodity Tolerance (ppm) /Maximum Residue Limit (mg/kg)
US Canada Mexico 1 

### Codex Bermudagrass, hay 0.3

US 40 CFR §180.314 Canada Mexico 1 

### Codex 

### Plants: (c) Tolerances with regional registrations. Tolerances with a regional registration, as defined in 180.1(l),are
established for residues of the herbicide S

- (2,3,3

- trichloro

- 2

- propen

- 1

- yl) N,N

- bis(1

- methylethyl)carbamothioate and its metabolite 2, 3, 3

- trichloroprop

- 2

- enesulfonic acid (TCPSA) 

## Same as above None

Commodity Tolerance (ppm) /Maximum Residue Limit (mg/kg)
US Canada Mexico 1 

### Codex Barley, grain 0.05 0.05 Barley, hay 1.0 Barley, straw 0.3 Beet, sugar, dried pulp 0.2 Beet, sugar, roots 0.1 0.1 Beet, sugar, tops 0.5 Pea, dry 0.2 Pea, field, hay 1.0 Pea, field, vines 0.5 Pea, succulent 0.2 Wheat, forage 0.5 Wheat, grain 0.05 0.05 Wheat, hay 1.0 Wheat, straw 1.0

Completed: M. Negussie; 04/01/14

1 

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