UNITED STATES ENVIRONMENTAL PROTECTION AGENCY 

WASHINGTON, D.C. 20460 

OFFICE OF CHEMICAL SAFETY AND POLLUTION PREVENTION 

MEMORANDUM 

Date: December 11, 2013 

SUBJECT: Thiram. Update to the Aggregate Risk Assessment to Support the Requested 

PHI Reduction and Increased Tolerance Request on Strawberry 

PC Code: 07980 I 

Decision No.: 471074 

Petition No.: 2F81 06 

Risk Assessment Type: Single Chemical, Aggregate 

TXRNo.: NA 

MRID No.: NA 

DP No.: D412465 

Registration No.: NA 

Regulatory Action: Section 3 

Case No.: NA 

CAS No.: 137-26-8 

40 CFR: §180.132 

FROM: Jessica Kidwell, Risk Assessor ~ . ~ ~ Thurston G. Morton, Chemist ~~ q' .,/\/ 

Sue 

Kelly 

Hummel, 

O'Rourke, 

Chemist 

ORE ~ 

'- J ~ ~ 

Marquea King, PhD, Toxicologi~~· 

Risk Assessment Branch IV, Health Effects ~ion (7509P)/ 

THROUGH: Elissa Reaves, Branch Chief 

Risk Assessment Branch IV /Health Effects Division ( 509P) 

TO: Shaunta Hill, RM21 

Cynthia Giles-Parker, Branch Chief 

Fungicide Branch, Registration Division (7505P) 

1.0 Executive Summary 

Taminco, Inc. submitted an amendment requesting a change in the preharvest interval (PHI) 

from 3 days to 1 day for strawberry on the label for Spotrete-F (EPA Reg. No. 45728-26), a 

Plowable (Soluble Concentrate or SC) formulation for thiram. Concurrently, the registrant 

submitted a petition proposing an increase in the current tolerance of 7 ppm to 20 ppm for 

residues ofthiram on strawberry. This risk assessment updates the dietary and residential 

postapplication dermal exposure assessments to support this petition. An updated worker 

exposure and risk assessment is not required to support the requested label amendment. 
Thiram/07980 1 Human Health Risk Assessment 0412465 

The toxicity database for thiram is considered adequate to support the current petition. 

Endpoints, points of departure, and uncertainty factors for this risk assessment remain unchanged 

from our previous reviews. The residue chemistry database for thiram is complete. Potential 

areas of environmental justice concerns, to the extent possible, were considered in this human 

health risk assessment. 

HED concludes that there are no risk issues that would preclude increasing the tolerance for the 

residues ofthiram on strawberry. The tolerance of20 ppm supports the amended strawberry use 

pattern of a reduction to a 1 day PHI. No additional data are needed. 

HED conducted an updated dietary risk assessment to support the requested label amendment 

and tolerance increase. No dietary risks of concern were identified. The acute and chronic dietary 

risk estimates for food and drinking water are below HED's level of concern (i.e., <100% of the 

acute and chronic population adjusted doses (PADs)) for the general U.S. population and all 

population subgroups. Acute dietary exposure at the 99.9th exposure percentile for the general 

U.S. population was 3.1% ofthe aPAD and 78% ofthe aPAD for females 13-49 years old, the 

population subgroup with the highest estimated acute dietary exposure to thiram. Chronic dietary 

exposure for the general U.S. population was 9.2% of the cPAD and 56% of the cPAD for 

children 1-2 years old, the population subgroup with the highest estimated chronic dietary 

exposure to thiram. Thiram is classified as "Not Likely to be Carcinogenic to Humans" based on 

lack of evidence for carcinogenicity in mice or rats; therefore, a quantitative cancer risk 

assessment is not required. 

Thiram is not available for sale or use by homeowner applicators; therefore, there are no 

residential handler exposure scenarios applicable to thiram. However, there is potential for 

residential post-application dermal exposure from treated golf course greens and tees. Residential 

exposures resulting from dermal contact with thiram-treated turf were assessed for children 6 to 

<11 years old, children 11 to <16 years old, and adults. The dermal margins of exposure (MOEs) 

for the populations assessed ranged from 850 to 1000 and all greatly exceeded the level of 

concern of 100. Inhalation post-application exposures for golf courses were not assessed since 

inhalation exposures are thought to be negligible in outdoor post-application scenarios. 

HED also conducted updated aggregate risk assessments, and no aggregate risks of concern were 

identified. Acute and chronic aggregate risk assessments take into account exposure estimates 

from dietary consumption ofthiram (food and drinking water). As referenced above, both the 

acute and chronic dietary risk estimates are not of concern to HED ( <1 00% aPAD and cPAD). In 

aggregating short/intermediate-term risk, the Agency routinely combines background chronic 

dietary exposure (food+ water) with short- and intermediate-term residential exposure (dermal 

only). The combined exposure may then be used to calculate an MOE for aggregate risk. Using 

the golfer scenario for adult males, adult females, and children >6 years old, combined with the 

applicable subpopulation with the greatest dietary exposure, the total short/intermediate-term 

food and residential aggregate MOEs are 600, 600, and 370, respectively. As these MOEs are 

greater than 100, the short- and intermediate-term aggregate risks do not exceed the HED's LOC. 

An updated worker exposure and risk assessment is not required to support the requested label 

amendment. Since the subject amendment is limited to a change in the PHI, approval of this use 

Page 2 of21 
Thiram/079801 Human Health Risk Assessment D412465 

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does not impact the application rates, number of applications, or seasonal application rate; 

therefore, there is no impact on the occupational exposure from the proposed label amendment. 

2.0 HED Recommendations 

HED concludes that there are no risk issues that would preclude increasing the tolerance for the 

residues of thiram on strawberry. The tolerance of 20 ppm supports the amended strawberry use 

pattern of a reduction to a 1 day PHI. No additional data are needed. Specific tolerance 

recommendations are discussed in section 2.2. 

2.1 Data Deficiencies 

Toxicology: No new toxicity data are required to support this petition. A previously identified 

toxicity data gap with respect to immunotoxicity (OPPTS 870.7800) has been resolved. An 

immunotoxicity study in mice has been submitted (MRID 48646401). The HASPOC determined 

that a 28-day inhalation toxicity study with neurotoxicity parameters in rats is required. 

Therefore, a 10X database uncertainty factor will be retained for the inhalation route. An 

inhalation study is required for any future registration action that involves an updated inhalation 

assessment. However, the cholinesterase activity screening assay was waived by the HASPOC 

and is not required at this time.

Chemistry: None

ORE: None

2.2 Tolerance Considerations

2.2.1 Enforcement Analytical Method

A colormetric analytical method is available to enforce the proposed tolerances. The Pesticide 

Analytical Manual (PAM) Vol. II lists Method I, II, III, IV, and A for the determination of 

dithiocarbamate residues in/on plant commodities. These methods are based on the 

decomposition of dithiocarbamates with release of CS2. Using these methods, the CS2 is swept 

through a trap to remove any H2S and into a reaction tube containing a solution of copper acetate 

and an amine. A colored copper dithiocarbamate complex is formed and its absorbance read as a 

measure of the original dithiocarbamate. The stated limit of detection (LOD) for Method I is 0.5-

4.0 ppm. 

Thiram may be detectable using PAM I multiresidue methods without Florisil cleanup, but is not 

detected when Florisil cleanup is used.

2.2.2 Recommended Tolerances

A tolerance of 20 ppm supports the amended strawberry use pattern of a reduction to a 1 day 

PHI. A summary of tolerance recommendations is presented in Table 2.2.3. The recommended 
Thiram/079801 Human Health Risk Assessment D412465 

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tolerance for strawberry was derived with the aid of the OECD tolerance calculation procedure. 

In 2009 HED issued guidance on tolerance expressions (S. Knizner, 2009). The current thiram 

tolerance expression is not in accord with this guidance. The tolerance expression should read:

Tolerances for residues of the fungicide thiram (tetramethyl thiuram disulfide), including 

its metabolites and degradates, in or on the commodities in the table below. Compliance 

with the tolerance levels specified is to be determined by measuring only thiram.

The above recommendation is an interim solution until tolerances for dithiocarbamates are 

converted to being expressed as carbon disulfide. When this occurs, the tolerance expression 

should read:

Tolerances are established for residues of fungicide thiram (tetramethyl thiuram 

disulfide), including its metabolites and degradates, in or on the commodities in the table 

below. Compliance with the tolerance levels specified below is to be determined by 

measuring only those thiram residues convertible to carbon disulfide, expressed as carbon 

disulfide, in or on the commodity.

Table 2.2.3. Tolerance Summary for Thiram

Commodity

Proposed Tolerance 

(ppm)

Recommended 

Tolerance (ppm)

Comments

Strawberry 20 20 When dithiocarbamate tolerances are 

changed to be expressed as carbon 

disulfide, the recommended tolerance 

level becomes 13 ppm. (The conversion 

factor is 0.63x)

2.2.3 Revisions to Petitioned-For Tolerances

Tolerance proposals for raw agricultural commodities were not changed. 

2.2.4 International Harmonization

The Codex Alimentarius has established maximum residue limits (MRL), for “total 

dithiocarbamates, determined and expressed as mg carbon disulfide per kg” in strawberry of 5

mg/kg. As U.S. tolerances are currently established on the individual dithiocarbamates, 

compatibility is not possible with the proposed tolerances. However, HED has recommended that 

all tolerances for dithiocarbamates, including thiram be converted to be expressed as carbon 

disulfide. At that time, the tolerance expression will be compatible with CODEX, however the 

tolerance level will not be compatible, since there are differences in Good Agricultural Practices 

(GAP) and the current CODEX MRL would not cover actual residues seen in the U.S. field trials 

submitted to support the proposed label amendment. 

2.3 Label Recommendations

No label revisions are required.
Thiram/079801 Human Health Risk Assessment D412465 

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3.0 Introduction

3.1 Chemical Identity

Thiram is a dimethyl dithiocarbamate fungicide used to prevent crop damage in the field and to 

protect harvested crops (apples, peaches, and strawberries) from deterioration in storage or 

transport. It is also used as a seed protectant (e.g., small-seeded vegetables, large-seeded 

vegetables, cereal grains, other seeds, coniferous seeds, cotton seed, ornamental seeds, and 

soybeans) and as a turf protectant from fungal diseases.

TABLE 3.1. Test Compound Nomenclature.

Compound

Common name Thiram

IUPAC name tetramethylthiuram disulfide

CAS name tetramethylthioperoxydicarbonic diamide

CAS registry number 137-26-8

End-use products (EPs) used in 

residue field study 

Banguard 42 PLUS (37.0% ai SC) or Banguard 60 (52.6% ai SC)

3.2 Physical/Chemical Characteristics

TABLE 3.2. Physicochemical Properties of the Technical Grade of Thiram.

Parameter Value Reference

Melting range 142-150oC Revised Thiram Product and 

Residue Chemistry Chapters 

for the RED Document,

12/16/03.

Density 0.32-0.35 g/mL

Water solubility at 20-25oC 0.00165 g/100 mL

Solvent solubility at 20-25oC petroleum ether (0.0005 g/100 mL), benzene 

(4.12 g/100 mL), acetone (6.97 g/100 mL), 

xylene (0.91 g/100 mL), and methanol

(0.184 g/100 mL)

Vapor pressure 1.6-1.8 x 10-5 Torr at 25°C

Dissociation constant, pKa Not applicable

Octanol/water partition coefficient, POW 39.5-54.1

3.3 Pesticide Use Pattern

A summary of the proposed end-use product is presented in Table 3.3. 

H C3

N

CH3

S

S N

CH3

CH3 S

S
Thiram/079801 Human Health Risk Assessment D412465 

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Table 3.3. Summary of Directions for Use of Thiram

Applic. Timing; 

Type; and Equip.

Formulation

[EPA Reg. 

No.]

Applic. 

Rate, 

lb ai/A

Max. No. 

Applic. 

per 

Season

Max. 

Seasonal 

Applic. 

Rate

(lb ai/A)

PHI

(days)

Use Directions and 

Limitations

Strawberry

Foliar Ground 

Boom 4 lb/gal SC

[45728-26]

2.6 13.0 1 1

Use a 10 day interval 

between applications.

3.4 Consideration of Environmental Justice

Potential areas of environmental justice concerns, to the extent possible, were considered in this 

human health risk assessment, in accordance with U.S. Executive Order 12898, "Federal Actions 

to Address Environmental Justice in Minority Populations and Low-Income Populations," 

(http://www.eh.doe.gov/oepa/guidance/justice/eo12898.pdf. As a part of every pesticide risk 

assessment, OPP considers a large variety of consumer subgroups according to well-established 

procedures. In line with OPP policy, HED estimates risks to population subgroups from pesticide 

exposures that are based on patterns of that subgroup’s food and water consumption, and 

activities in and around the home that involve pesticide use in a residential setting. Extensive 

data on food consumption patterns are compiled by the USDA under the National Health and 

Nutrition Survey/What We Eat in America (NHANES/WWEIA) and are used in pesticide risk 

assessments for all registered food uses of a pesticide. These data are analyzed and categorized 

by subgroups based on age and ethnic group. Additionally, OPP is able to assess dietary 

exposure to smaller, specialized subgroups and exposure assessments are performed when 

conditions or circumstances warrant. Whenever appropriate, non-dietary exposures based on 

home use of pesticide products and associated risks for adult applicators and for toddlers, youths, 

and adults entering or playing on treated areas postapplication are evaluated. Further 

considerations are currently in development as OPP has committed resources and expertise to the 

development of specialized software and models that consider exposure to bystanders and farm 

workers as well as lifestyle and traditional dietary patterns among specific subgroups.

4.0 Hazard Characterization and Dose-Response Assessment

This assessment includes a summary of the prior assessment (Memo, G. Kramer, D365442, 

6/9/2009). The toxicity database for thiram is considered adequate to support the current petition 

which evaluates oral and dermal routes of exposure. HED also notes that an immunotoxicity 

study has been submitted and satisfies the data requirement. The toxicity database is inadequate,

however, for the inhalation route of exposure. At this time, however, there is no residential 

inhalation exposure from thiram. 

The Hazard and Science Policy Council (HASPOC) met on June 6, 2013 to discuss the need for 

a 28-day inhalation toxicity study with neurotoxicity measurements and a cholinesterase activity 

screening assay (TXR No. 0056685). Based on a Weight of Evidence approach, the HASPOC 
Thiram/079801 Human Health Risk Assessment D412465 

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concluded that a 28-day inhalation toxicity study with neurotoxicity parameters in rats is 

required. Therefore, a 10X database uncertainty factor is required for all inhalation exposure risk 

assessments. However, a cholinesterase activity screening assay is not required at this time.

4.1 Summary of Toxicological Effects

Thiram has been shown to cause neurotoxicity following acute and subchronic exposures. In the 

acute and subchronic neurotoxicity studies submitted, neurotoxicity is characterized as lethargy, 

reduced and/or tail pinch response, changes in the functional-observation battery (FOB) 

parameters, increased hyperactivity, changes in motor activity, and increased occurrences of 

rearing events. No treatment-related changes were observed in brain weights or in the 

histopathology of the nervous system. In a non-guideline study published in the open literature, 

chronic feeding of thiram to rats caused neurotoxicity, with onset of ataxia in some animals 5-19 

months after beginning of treatment. However, no evidence of neurotoxicity was seen following 

chronic exposures in mice or rats in guideline studies submitted to the Agency. In addition, no 

adverse effects on the developing fetal nervous system were seen in a DNT study. The chronic

toxicity profile for thiram indicates that the liver, blood, and urinary system are the target organs 

for this chemical in mice, rats, and dogs. There is no evidence for increased susceptibility 

following in utero exposures to rats or rabbits and following pre- and post-natal exposures to rats 

for two generations. There is low concern for the increased susceptibility seen in the 

developmental toxicity study since the dose response is well defined and this endpoint is used for 

assessing the acute dietary risk for the most sensitive population. Thiram is classified as “not 

likely to be carcinogenic to humans” based on lack of evidence for carcinogenicity in mice or 

rats. There are no mutagenic/genotoxic concerns with thiram. The available toxicological 

database for thiram suggests that this chemical has a low to moderate acute-toxicity profile. 

Thiram is readily absorbed (via the oral route), distributed, extensively metabolized and

eliminated primarily in the expired air and urine of rats following single or repeated oral 

administrations. Within 24 hours of administration of the compound, a high amount of 

radioactivity was eliminated as expired air (14CO2, carbamyl sulfide, and carbon disulfide). The 

parent compound was not detected in the urine. Fecal metabolites were not evaluated due to the 

low recovery of radioactivity in the feces. There is no apparent sex- or dose-related difference in 

the distribution, metabolism, or excretion of 14C-thiram. Bioaccumulation of 14C-thiram in 

tissues was low (1.54-4.24% of the administered dose). Therefore, an appreciable accumulation 

of thiram is not anticipated after repeated exposures.

4.2 Safety Factor for Infants and Children (FQPA Safety Factor)

For the current assessment which includes oral and dermal exposures, the FQPA safety factor for 

thiram is reduced to 1X. The recommendation of 1X is based on the following considerations. 

The toxicological database for thiram is complete with acceptable neurotoxicity, developmental, 

and reproductive toxicity studies. Thiram has been shown to cause neurotoxicity following acute 

and subchronic exposures. There was no evidence of increased susceptibility following in utero

exposure to rats or rabbits or following pre-and post natal exposures to rats. There is evidence of 

quantitative susceptibility in the DNT study. There is low concern for the enhanced susceptibility 

seen in the DNT study because clear NOAELs/LOAELs were established for the offspring 
Thiram/079801 Human Health Risk Assessment D412465 

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effects, the dose-response is well defined, and the dose/endpoint is used for acute dietary risk for 

the most sensitive population (females 13-49 years old. Consequently, there are no residual 

uncertainties for pre- and post-natal toxicity. There are no residual uncertainties in the thiram 

exposure database.

4.2.1 Completeness of the Toxicology Database

For this petition, the toxicology database for assessing sensitivity and susceptibility is complete. 

However, based on a Weight of Evidence approach, the HASPOC concluded that a 28-day 

inhalation toxicity study with neurotoxicity parameters in rats is required (TXR No. 0056685). 

Therefore, a 10X database uncertainty factor is required for all inhalation exposure risk 

assessments. A cholinesterase activity screening assay is not required at this time.

4.2.2 Evidence of Neurotoxicity

Although signs of neurotoxicity were observed in the database for thiram, there are no residual 

concerns since clear NOAELs were established and the PODs are protective of any 

neurotoxicity. In addition, no adverse effects on the developing fetal nervous system were seen 

in a DNT study. 

4.2.3 Evidence of Sensitivity/Susceptibility in the Developing or Young Animal

There was no evidence of increased susceptibility following in utero exposure to rats or rabbits 

or following pre-and post natal exposures to rats. There is evidence of quantitative susceptibility 

in the DNT study. Offspring effects (increased locomotor activity in females on PND 17) 

occurred at a lower dose than maternal effects (increased number of rearing events and elevated 

incidences of hyperactivity in females at weeks 8 and 13). There is low concern for the enhanced 

susceptibility seen in the DNT study because: 1) clear NOAELs/LOAELs were established for 

the offspring effects; 2) the dose-response is well defined; 3) behavioral effect of concern were

observed only in females on one evaluation time period; and 4) the NOAEL is used for acute 

dietary risk for the most sensitive population subgroup (females 13-49 years old). Consequently, 

there are no residual uncertainties for pre- and post-natal toxicity.

4.2.4 Residual Uncertainty in the Exposure Database

There are no residual uncertainties in the thiram database with regards to dietary exposure. A 

refined probabilistic acute dietary-exposure assessment was performed using maximum percent 

crop treated (%CT) provided by BEAD, tolerance, the highest residue found during field-trials, 

distribution of field trial residues, Federal Drug Administration (FDA) monitoring data for 

apples, and empirical processing factors. A refined chronic dietary-exposure assessment was 

performed using tolerances and average estimated %CT. Estimated drinking water 

concentrations were used. An updated worker exposure and risk assessment is not required to 

support the requested label amendment. 
Thiram/079801 Human Health Risk Assessment D412465 

Page 9 of 21

4.3 Toxicity Endpoint and Point of Departure Selections

A summary of the most updated toxicological endpoints and doses chosen for the relevant 

exposure scenarios for human risk assessment can be found in the 2009 risk assessment (Memo, 

G. Kramer, D365442, 6/9/2009). The endpoint summary table is included below.

Table 4.3.1. Summary of Toxicological Doses and Endpoints for Thiram for Use in Dietary and NonOccupational Human Health Risk Assessments.

Exposure/

Scenario PoD

Uncertainty/FQPA 

SFs

RfD, PAD, LOC for 

Risk Assessment Study and Toxicological Effects

Acute 

Dietary

(General 

Population)

BMDL10 =

64.94 mg/kg

UFA = 10x

UFH = 10x

FQPA SF = 1x

Acute RfD = 0.6494

mg/kg/day

aPAD = 0.6494

mg/kg/day

Acute Neurotoxicity Study – Rat

MRID 42912401

LOAEL = 150 mg/kg/day based 

on FOB effects (lethargy, lower 

temperature, reduced startle 

response, no tail-pinch response), 

reduced motor activity, and 

reduced brain weights.

Acute 

Dietary

(Females 13-

49 years old)

NOAEL = 

1.4 mg/kg

UFA = 10x

UFH = 10x

FQPA SF = 1x

Acute RfD = 0.014

mg/kg/day

aPAD =0.014 

mg/kg/day

Dev. Neurotoxicity Study – Rat

MRID 46455201

LOAEL = 3.7 mg/kg/day based 

on increases in motor activity 

seen in female offspring on PND 

17.

Chronic 

Dietary

(All 

populations)

NOAEL = 

1.5 mg/kg

UFA = 10x

UFH = 10x

FQPA SF = 1x

Chronic RfD = 0.015 

mg/kg/day

cPAD =0.015 

mg/kg/day

Co-critical: 1) Combined Chronic 

Toxicity/Carcinogenicity Study –

Rat and 2) Chronic Oral 

Toxicity-Dog

LOAEL = 7.3 mg/kg/day based 

on changes in hematology, 

clinical chemistry, incidences of 

bile duct hyperplasia, and 

reduction in mean body-weight 

gain from the chronic 

toxicity/carcinogenicity rat study 

in conjunction with elevated 

cholesterol levels and increased 

liver weights reported in the 

Chronic Oral Toxicity Study in 

Dogs at a LOAEL = 7.23 

mg/kg/day 

Short- and 

IntermediateTerm

Incidental 

Oral 

No incidental oral residential exposure. 
Thiram/079801 Human Health Risk Assessment D412465 

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Table 4.3.1. Summary of Toxicological Doses and Endpoints for Thiram for Use in Dietary and NonOccupational Human Health Risk Assessments.

Exposure/

Scenario PoD

Uncertainty/FQPA 

SFs

RfD, PAD, LOC for 

Risk Assessment Study and Toxicological Effects

Short-Term 

Dermal (1-

30 days)

NOAEL = 

1.4

mg/kg/day

UFA = 10x

UFH = 10x

FQPA SF = 1x

(Dermal-absorption 

factor = 1%)

Residential LOC for 

MOE = 100

Occupational LOC for 

MOE = 100

Dev. Neurotoxicity Study – Rat

MRID 46455201

LOAEL = 3.7 mg/kg/day based 

on increases in motor activity 

seen in female offspring on PND 

17.

IntermediateTerm

Dermal (1 to 

6 months)

NOAEL

=1.4 

mg/kg/day

UFA = 10x

UFH = 10x

FQPA SF = 1x

(Dermal-absorption 

factor = 1%)

Residential LOC for 

MOE = 100

Occupational LOC for 

MOE = 100

Dev. Neurotoxicity Study – Rat

MRID 46455201

LOAEL = 3.7 mg/kg/day based 

on increases in motor activity 

seen in female offspring on PND 

17.

Short- and 

IntermediateTerm

Inhalation

Current assessment does not warrant an inhalation assessment.

Cancer (oral, 

dermal, 

inhalation)

“Not Likely to be Carcinogenic to Humans”

Point of Departure (PoD) = A data point or an estimated point that is derived from observed dose-response data and 

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

exposures. NOAEL = no observed adverse effect level. LOAEL = lowest observed adverse effect level. UF = 

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

among members of the human population (interspecies). FQPA SF = FQPA Safety Factor. PAD = populationadjusted dose (a = acute, c = chronic). RfD = reference dose. MOE = margin of exposure. LOC = level of concern. 

5.0 Dietary Exposure and Risk Assessment

5.1 Food Residue Profile

The proposed new use is a reduction in PHI to 1 day. As a result of the shorter PHI, quantifiable 

surface residues of thiram are likely to be found. Field trial results are summarized in Table 5.1.

TABLE 5.1. Summary of Residue Data from Crop Field Trials with Thiram on Strawberries

Commodity Total Applic. 

Rate

(lb a.i./A)

(kg a.i./ha)

PHI 

(days)

Residue Levels

(ppm)

n Min. Max. LAFT* HAFT* Median Mean Std. 

Dev.

Data from the use of Spotrete F (SC formulation) Five Applications at 2.62 lb ai/A, 1 day PHI

Strawberry 13 1 10 <0.05 13 <0.05 11.4 4.25 4.89 2.99

* LAFT = Lowest Average Field Trial; HAFT = Highest Average Field Trial.

5.2 Water Residue Profile

The Environmental Fate and Effects Division has previously assessed residues in drinking water 
Thiram/079801 Human Health Risk Assessment D412465 

Page 11 of 21

from the existing uses of thiram, including the currently registered use on strawberries. A new 

drinking water assessment is not required since, not only is the label amendment limited only to 

a PHI change, and the use rate, timing, number of applications, and seasonal application remain 

the same, but the use that drives the current drinking water assessment is turf; therefore, this 

change in PHI has no impact on the drinking water assessment. 

EFED provided estimated drinking water concentrations (EDWCs) in their memo entitled

“Environmental Fate and Ecological Effects Assessment and Characterization Chapter for the 

Thiram Registration Eligibility Decision Document” (J. Carleton and F. Jenkins, 12/11/03). 

Because monitoring data are unavailable, estimates of thiram concentrations were made only 

with mathematical models. EDWC values were generated by the PRZM (Pesticide Root Zone 

Model)-EXAMS (Exposure Analysis Modeling System) for the turf application scenario, since 

this crop yielded the highest EDWC values. Ground water sources were not included, as the 

EDWCs for this water source are minimal in comparison to those for surface water. Water 

residues (surface water EDWC of 0.0478 ppm for acute and 0.0025 ppm for chronic) were 

incorporated in DEEM-FCIDTM into the food categories “water, direct, all sources” and “water, 

indirect, all sources” for the dietary assessments.

Table 5.2. EDWCs for Use in the Human-Health Risk Assessment.

Crop 

Annual 

App Rate 

(lbs 

ai/acre/yr) 

SCIGROW 

concentration 

(ppb) 

PRZM/EXAMS* 

Acute EEC 

(ppb) 

PRZM/EXAMS* 

non-cancer 

chronic EEC (ppb) 

PRZM/EXAMS* 

cancer chronic 

EEC (ppb) 

Turf farm 146.6 0.84 47.8 2.5 2.2 

* Index Reservoir environment 

5.3 Dietary Risk Assessment

5.3.1 Description of Residue Data Used in Dietary Assessment

For strawberry, banana, and peach, the highest residue from submitted field trials were used for 

the acute dietary exposure analysis. For apple, monitoring data from the Food and Drug 

Administration (FDA) pesticide monitoring study was used. In addition, washing factors and 

processing factors from submitted studies were used. Tolerance level residues were used in the 

chronic dietary exposure analysis for all commodities.

5.3.2 Percent Crop Treated Used in Dietary Assessment 

The following maximum percent crop treated estimates for thiram from the Screening Level 

Usage Analysis (SLUA), dated January 12, 2012, were used in the acute dietary risk assessment 

for the following crops that are currently registered for thiram: apples: 10%; peaches: 2.5%; and 

strawberry: 30%. The following average percent crop treated estimates were used in the chronic 

dietary risk assessments for the following crops that are currently registered for thiram: apples: 

5%; peaches: 1.0%; and strawberry: 20%.

Table 5.3.2 presents percent crop treated (%CT) estimates that were used in the acute and 

chronic dietary exposure analysis. 
Thiram/079801 Human Health Risk Assessment D412465 

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Table 5.3.2. Summary of Percent Crop Treated Used in the Dietary Exposure Analyses

Commodity Average % CT Maximum %CT

Apple 5 10

Banana 100 100

Peach 1 2.5

Strawberry 20 30

Avocado 100 100

5.3.3 Acute Dietary Risk Assessment

A refined probabilistic acute dietary exposure assessment was performed using maximum 

percent crop treated (%CT) provided by BEAD, tolerance, the highest residue found during 

field-trials, distribution of field trial residues, Federal Drug Administration (FDA) monitoring 

data for apples, and empirical processing factors. Dietary risk estimates were determined 

considering exposures from food and drinking water using estimated drinking water 

concentrations (EDWCs) for surface water sources provided by the Environmental Fate and 

Effects Division (EFED). 

The resulting acute dietary risk estimates for food and drinking water are below HED’s level of 

concern (i.e., <100% of the acute population adjusted dose; aPAD of 0.6494 mg/kg bw/day) for 

the general U.S. population and all population subgroups. Using DEEM-FCIDTM, acute dietary 

exposure at the 99.9th exposure percentile is estimated at 0.020104 mg/kg bw/day for the general 

U.S. population (3.1% of the aPAD) and 0.010887 mg/kg bw/day (78% of the aPAD) for 

females 13-49 years old, the population subgroup with the highest estimated acute dietary 

exposure to thiram. 
Thiram/079801 Human Health Risk Assessment D412465 

Page 13 of 21

Table 5.3.3 Results of Acute Dietary Exposure and Risk Analysis for Thiram (Food + Water)

Population 

Subgroup

aPAD 

(mg/kg/day)

95th Percentile 99th Percentile 99.9th Percentile

Exposure 

(mg/kg/day)

% 

aPAD

Exposure 

(mg/kg/day)

% 

aPAD

Exposure 

(mg/kg/day)

% 

aPAD

General U.S. 

Population 0.6494 0.003419 <1 0.007029 1.1 0.020104 3.1

All Infants (<1 

year old) 0.6494 0.010016 1.5 0.016352 2.5 0.040956 6.3

Children 1-2 years 

old 0.6494 0.008983 1.4 0.024980 3.9 0.064254 9.9

Children 3-5 years 

old 0.6494 0.005982 <1 0.014708 2.3 0.039745 6.1

Children 6-12 

years old 0.6494 0.003733 <1 0.008783 1.4 0.021715 3.3

Youth 13-19 years 

old 0.6494 0.002718 <1 0.004989 <1 0.011129 1.7

Adults 20-49 

years old 0.6494 0.003017 <1 0.004806 <1 0.010891 1.7

Adults 50-99 

years old 0.6494 0.002807 <1 0.005012 <1 0.011093 1.7

Females 13-49 

years old 0.014 0.003074 22 0.005024 36 0.010887 78

The values for the highest risk population for each percentile are bolded.

5.3.4 Chronic Dietary Risk Assessment

A refined chronic dietary-exposure assessment was performed using tolerance level residues and 

average estimated %CT. Dietary risk estimates were determined considering exposures from 

food and drinking water using EDWCs for surface water sources provided by EFED. The 

resulting chronic dietary risk estimates for food and water combined are below HED’s level of 

concern (i.e., <100% of the chronic population adjusted dose; cPAD of 0.015 mg/kg bw/day) for 

the general U.S. population and all population subgroups. Using DEEM-FCIDTM, dietary 

exposure is estimated at 0.001384 mg/kg bw/day for the general U.S. population (9.2% of the 

cPAD) and 0.008369 mg/kg bw/day (56% of the cPAD) for children 1-2 years old, the 

population subgroup with the highest estimated chronic dietary exposure to thiram. The 

estimated exposures/risks for combined food and water are summarized in Table 5.3.4.

Additional refinements (i.e. monitoring data for commodities other than apple) could be done but 

were not needed at this time.
Thiram/079801 Human Health Risk Assessment D412465 

Page 14 of 21

Table 5.3.4. Summary of Chronic Dietary Exposure and Risk for Thiram (Food + Water).

Age Group cPAD (mg/kg/day) Exposure (mg/kg/day) % cPAD

General U.S. Population 0.015 0.001384 9.2

All Infants (<1 year old) 0.015 0.004443 30

Children 1-2 years old 0.015 0.008369 56

Children 3-5 years old 0.015 0.004947 33

Children 6-12 years old 0.015 0.002172 15

Youth 13-19 years old 0.015 0.000877 5.8

Adults 20-49 years old 0.015 0.000716 4.8

Adults 50-99 years old 0.015 0.000947 6.3

Females 13-49 years old 0.015 0.000823 5.5

* The values for the highest exposed population is bolded.

5.3.5 Cancer Dietary Risk Assessment

Thiram is classified as “Not Likely to be Carcinogenic to Humans” based on lack of evidence for 

carcinogenicity in mice or rats; therefore, a quantitative cancer risk assessment is not required

(D263948). 

6.0 Residential (Non-Occupational) Exposure/Risk Characterization

Thiram is not available for sale or use by homeowner applicators; therefore, there are no 

residential handler exposure scenarios applicable to thiram. However, there is potential for 

residential post-application dermal exposure from treated golf course greens and tees. 

Residential exposures resulting from dermal contact with thiram-treated turf were assessed for 

children 6 to <11 years old, children 11 to <16 years old, and adults. When use is restricted to 

greens and tees, the duration of exposure is 1 hour to reflect the anticipated time a player would 

be spending in contact with those areas. The dermal margins of exposure (MOEs) for the 

populations assessed ranged from 850 to 1000 and all greatly exceeded the level of concern of 

100 (Table 6.0). Inhalation post-application exposures for golf courses were not assessed since 

inhalation exposures are thought to be negligible in outdoor post-application scenarios.
Thiram/079801 Human Health Risk Assessment D412465 

Page 15 of 21

Table 6.0. Residential Post-Application Dermal Exposure from Treated Golf Course Greens and Tees.

Formulation Lifestage TTRt

2

(ug/cm2)

Weight unit 

conversion 

factor 

(mg/ug)

Transfer 

Coefficient3

(cm2/hr) 

Hours of

Exposure4

(hr)

Exposure5

(mg/day)

Absorbed 

Dose

6

(mg/kg/day) 

Dermal 

MOE7

Liquids1 Adult 1.81 0.001 5,300 1 9.6 0.0014 1000

Liquids Children 11 to 

<16 years 1.81 0.001 4,400 1 7.8 0.0014 1000

Liquids Children 6 to <11 

years old 1.81 0.001 2,900 1 5.3 0.0016 850

1. Liquids is the representative formulation for flowable concentrate formulation.

2. TTRt = AR * F * (1-FD)

t

* CF2 * CF3 where, TTRt = turf transferable residue on day "t" (μg/cm2); AR = 

application rate (16.3 lb ai/acre); F= fraction of ai retained on turf (0.01); FD= fraction of residue that 

dissipates daily (0.1); t= post-application day on which exposure is being assessed (0); CF2= weight unit 

conversion factor (4.54 x 108μg/lb); and CF3= area unit conversion factor ( 2.47 x 10-8acre/cm2).

3. The transfer coefficients used for the “golfer” dermal scenarios were derived using the best available data. In 

this case, data collected during a golf course maintenance study (Klonne and Bruce, 2005) was considered to

provide the best representation of the exposures that might be experienced by golfers. The recommended 

point estimates for use in post-application adult, children 11<16 years old, and children 6<11 years old 

dermal exposure assessment are 5,300; 4,400; and 2,900 cm2/hr, respectively

4. For a chemical that has a label restriction for greens and tees, a 1 hour exposure calculation is assumed. 

5. Exposure (mg/day) = TTRt * CF1 * TC * ET where, TTRt = turf transferable residue on day "t" (μg/cm2); 

CF1 = weight unit conversion factor (0.001 mg/μg); TC = transfer coefficient (cm2/hr); and ET = exposure 

time ( 1hr/day).

6. Absorbed Dose (mg/kg-day),

BW

E AF D*

where, E= exposure (mg/day); AF= absorption factor (0.01); 

and BW = body weight (69, 57, and 32 kg for adults, children 11 to <16 yrs and children 6 to <11 yrs, 

respectively).

7. MOE = POD (1.4 mg/kg/day) / Absorbed Dose (mg/kg/day). The level of concern (LOC) is 100.

7.0 Aggregate Exposure/Risk Characterization 

7.1 Acute Aggregate Risk

The acute aggregate risk assessment takes into account exposure estimates from dietary 

consumption of thiram (food and drinking water). The acute dietary risk estimates are not of 

concern to HED (<100% aPAD) at the 99.9th exposure percentile for the general U.S. population 

and all other population subgroups. Therefore, the acute aggregate risk associated with the 

proposed uses of thiram is not of concern to HED for the general U.S. population or any 

population subgroups.

7.2 Short- and Intermediate-Term Aggregate Risk

In aggregating short- and intermediate-term risk, the Agency routinely combines background 

chronic dietary exposure (food + water) with short/intermediate-term residential exposure

(dermal only). The combined exposure may then be used to calculate an MOE for aggregate risk. 

Using the golfer scenario for adult males, adult females, and children >6 years old, combined 

with the applicable subpopulation with the greatest dietary exposure, the total 
Thiram/079801 Human Health Risk Assessment D412465 

Page 16 of 21

short/ intermediate-term food and residential aggregate MOEs are 600, 600, and 370, 

respectively. As these MOEs are greater than 100, the short- and intermediate-term aggregate 

risks do not exceed the HED’s LOC. For children <6 years old, there is no residential exposure, 

therefore, a short/intermediate term aggregate risk assessment is not required for this population. 

Table 7.2 summarizes the short/intermediate-term aggregate exposures to thiram.

Table 7.2 Short-Term and/or Intermediate Term Aggregate Risk Calculations

Population

Short- or Intermediate-Term Scenario

NOAEL 

mg/kg/day LOC1

Max 

Allowable 

Exposure2

mg/kg/day

Average 

Food and 

Water 

Exposure 

mg/kg/day

Residential 

Exposure 

mg/kg/day3

Total 

Exposure 

mg/kg/day4

Aggregate 

MOE (food, 

water, and 

residential)5

Adult6 Male 1.4 100 0.014 0.000947 0.0014 0.002347 600

Adult6Female 1.4 100 0.014 0.000947 0.0014 0.002347 600

Children6>6 

years old 1.4 100 0.014 0.002172 0.0016 0.003772 370

1

The Level of Concern (LOC) is based on the 10X for interspecies extrapolation, 10X for intraspecies variations, 

and 1X FQPA SF, totaling 100.

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

3 Residential Exposure = [Oral exposure + Dermal exposure + Inhalation Exposure]. In this case, only dermal 

exposure is applicable. Source of residential exposure values used in aggregate assessment (Table 6.0).

4 Total Exposure = Avg Food & Water Exposure + Residential Exposure

5

6 Relevant population subgroup with highest exposures (Tables 5.2.4 and 6.0).

7.3 Chronic Aggregate Risk

The chronic aggregate risk assessment takes into account exposure estimates from dietary 

consumption of thiram (food and drinking water). The chronic dietary risk estimates are not of 

concern to HED (<100% aPAD) at the 99.9th exposure percentile for the general U.S. population 

and all other population subgroups. Therefore, the chronic aggregate risk associated with the 

proposed uses of thiram is not of concern to HED for the general U.S. population or any 

population subgroups.

8.0 Occupational Exposure/Risk Characterization

An updated worker exposure and risk assessment is not required to support the requested label 

amendment. Since the subject amendment is limited to a change in the PHI, approval of this use 

does not impact the application rates, number of applications, or seasonal application rate; 

therefore, there is no impact on the occupational exposure from the proposed label amendment.

9.0 References

Carleton, J. and Jenkins,F. 12/11/03. “Environmental Fate and Ecological Effects Assessment 

and Characterization Chapter for the Thiram Registration Eligibility Decision Document” 
Thiram/079801 Human Health Risk Assessment D412465 

Page 17 of 21

Hummel, S. 6/6/2013. D407356, D407357, D407358, D302803. Thiram on Strawberry, 

PP#2F8106. Summary of Analytical Methods and Residue Data. 

Kramer, G.and Greear, W. 06/09/2009. D365442. Thiram in/on Imported Bananas. Revised 

Human Health Risk Assessment.

Knizner, S. 05/27/2009. “Interim Guidance on Tolerance Expressions,” EPA Memorandum.

Mendez, E. 5/30/2000. D263948. HED DOC No. 014193. Thiram- Toxicology Disciplinary 

Chapter for the Reregistration Eligibility Decision Document.

Morton, T. 06/26/2013. D405397. Thiram: Acute and Chronic Dietary (Food and Drinking 

Water) Exposure and Risk Assessment to Support a Petition for an Increased Tolerance on 

Strawberry..

Rury, K. 6/30/2013. TXR No. 0056685. Thiram: Summary of Hazard and Science Policy 

Council (HASPOC) Meeting of June 6, 2013: Recommendations on the Need for a 28-day 

Inhalation Study and Cholinesterase Assessment Screening Assay.
Thiram/079801 Human Health Risk Assessment D412465 

Page 18 of 21

Appendix A. Toxicity Profiles

Table A.2.1. Acute Toxicity Profile – Thiram.

Guideline No. Study Type MRID(s) Results Toxicity Category

870.1100 Acute oral (rat) 00163854 LD50 = 2.6 g/kg III

870.1200 Acute dermal 00259250 LD50 ≥2.0 g/kg III

870.1300 Acute inhalation (rat) 00165855 LC50 ≥0.1 mg/L II

870.2400 Primary eye irritation (rabbit) 00259250 Moderate eye 

irritant

II

870.2500 Primary dermal irritation (rabbit) 00259250 Very slight dermal 

irritant

IV

870.2600 Dermal sensitization 00153068 Moderate skin 

sensitizer

N/A

Table A.2.2. Subchronic and Chronic Toxicity and Genotoxicity Profile – Thiram.

Guideline 

No. Study Type

MRID No. (year)/ 

Classification /Doses Results

870.3100 90-Day oral 

toxicity (rat)

40773601 (1988)

Unacceptable/guideline

0, 50, 500, or 1000 ppm

(0, 2.5, 25, or 50 mg/kg 

bw/day)

NOAEL = could not be determined due to lack 

of information on stability.

LOAEL = 25 mg/kg/day, based on decreases in 

body-weight gain, hematology and clinical 

chemistry parameters.

870.3150 90-Day oral 

toxicity (dog)

461503608 (1990) 

Acceptable/guideline

0, 75, 250, or 500 ppm 

(0, 1.94-2.58, 6.17-7.85,

or 10.55-14.69 mg/kg 

bw/day) 

NOAEL = 1.9 mg/kg/day. 

LOAEL = 6.3 mg/kg/day, based on adverse 

changes in clinical chemistry, and decreases in 

mean body weight and food consumption.

870.3200 21-Day dermal 

toxicity (rabbit)

42642501 (1992)

Acceptable/guideline

0, 250, 500, or 1000 

mg/kg bw/day

NOAEL = 300 mg/kg/day.

LOAEL = 1000 mg/kg/day, based on decreases 

in body-weight gain and food consumption as 

well as alterations in clinical chemistry.

870.3700a Prenatal 

developmental (rat)

00151610 (1978)

Unacceptable/guideline

0, 12.5, 25, 50, or 100 

mg/kg bw

Maternal NOAEL = 12.5 mg/kg.

LOAEL = 25 mg/kg, based on reduced bodyweight gains and food consumption.

Developmental NOAEL could not be 

determined.

LOAEL = 12.5 mg/kg, based on reduced 

ossification.

870.3700a Prenatal 

developmental (rat)

40534101; 41498301

(1988)

Acceptable/guideline

0, 7.5, 15, or 30 mg/kg bw

Maternal NOAEL could not be determined. 

LOAEL = 7.5 mg/kg, based on decreases in 

body-weight gain, alopecia, scars, damaged 

digits, red-stained paws and excessive 

salivation.

Developmental NOAEL = 7.5 mg/kg. 

LOAEL = 15 mg/kg based on retarded growth 

and rudimentary 13th rib, and reduced 

ossification.
Thiram/079801 Human Health Risk Assessment D412465 

Page 19 of 21

Table A.2.2. Subchronic and Chronic Toxicity and Genotoxicity Profile – Thiram.

Guideline 

No. Study Type

MRID No. (year)/ 

Classification /Doses Results

870.3700b Prenatal 

developmental 

(rabbit)

40444702(1987)

Acceptable

0, 1, 3, 5, 7.5, 10, 20, 40,

or 80 mg/kg bw

(range-finding)

Maternal NOAEL = 3 mg/kg bw/day.

LOAEL = 5 mg/kg/day, based on decreased 

maternal body-weight gains. 

Developmental NOAEL was not determined.

LOAEL was not determined. 

870.3700b Prenatal 

developmental 

(rabbit)

40577301 (1988)

Acceptable

0, 1, 2.5, or 5mg/kg bw

(range-finding)

Maternal NOAEL = 5 mg/kg bw/day.

LOAEL was not determined. 

Developmental NOAEL = 5 mg/kg.

LOAEL was not determined.

870.3700b Prenatal 

developmental 

(rabbit)

42223601 (1992)

Acceptable

0, 1, 5, or 10 mg/kg bw

Maternal NOAEL = 10 mg/kg bw/day

LOAEL was not determined 

Developmental NOAEL = 10 mg/kg

LOAEL was not determined.

870.3800 2-Gen. 

reproduction and 

fertility effects

(rat)

42095901 (1991)

Acceptable/guideline

0, 30, 60, or 180 ppm

(F0: 0/0, 1.2/1.9, 2.4/3.9, 

or 8.5/11.8 mg/ kg bw/day 

[M/F])

(F1: 0/0, 1.5/2.0, 3.24.3,

or 9.2/13.4 mg/kg bw/day 

[M/F]

Parental/Systemic NOAEL = 30 ppm (1.9 

mg/kg/day [M/F]).

LOAEL = 60 ppm (2.6/3.1.7 mg/kg/day [M/F]) 

based on decreases in body-weight gain and 

food consumption.

Reproductive NOAEL was not determined.

LOAEL >180 ppm (8.9 mg/kg/day).

Offspring NOAEL = 180 ppm (11.8 

mg/kg/day).

LOAEL = 60 ppm (3.9 mg/kg/day), based on 

decreased mean body weight.

870.3800 2-Gen. 

reproduction and 

fertility effects

(rat)

45441203 (1997)

Acceptable/guideline

0, 20, 60, or 180 ppm

(0, 1.4, 4.2, or 12.2 mg/kg 

bw/day)

Parental/Systemic NOAEL = 20 ppm (1.4 

mg/kg/day).

LOAEL = 60 ppm (4.7 mg/kg/day) based on 

reduced body-weight gains during gestation.

Reproductive NOAEL ≥ 180 ppm (12.2 

mg/kg/day).

LOAEL was not determined.

Offspring NOAEL = 20 ppm (1.4 mg/kg/day).

LOAEL = 60 ppm (4.2 mg/kg/day), based on 

decreases in pup body weight and body-weight 

gain.

870.4100 Chronic toxicity (1 

year; dog)

41967901 (1991)

Acceptable/guideline

0, 30, 90, or 250 ppm

M; 0, 0.84, 2.61, or 7.35 

mg/kg bw/day

F: 0, 0.90, 2.54, or 7.23 

mg/kg bw/day

NOAEL (M) = 30 ppm (0.84 mg/kg/day).

NOAEL (F) = 90 ppm (2.54 mg/kg/day).

LOAEL (M) = 90 ppm (2.61 mg/kg/day, based 

on increased mean cholesterol levels.

LOAEL (F) = 250 ppm (7.23 mg/kg/day), 

based on increased mean cholesterol levels and 

increased liver-to-body weight ratios. 
Thiram/079801 Human Health Risk Assessment D412465 

Page 20 of 21

Table A.2.2. Subchronic and Chronic Toxicity and Genotoxicity Profile – Thiram.

Guideline 

No. Study Type

MRID No. (year)/ 

Classification /Doses Results

870.4200 Carcinogenicity

(mouse)

42313401 (1992)

Acceptable/guideline

M: 0, 15, 150, or 300 ppm 

F: 0, 15, 300, or 600 ppm

M: 0, 2.5, 24, and 57 

mg/kg bw/day

F: 0, 3.1, 57, and 112 

mg/kg bw/day

NOAEL = 15 ppm (M/F: 2.5/3.1 mg/kg 

bw/day).

LOAEL (M) = 150 ppm (24 mg/kg bw/day.

LOAEL (F) = 300 ppm (57 mg/kg/day), based 

on decreases in mean body weight and mean 

body-weight gain, anemia, and non-neoplastic 

lesions in the eyes, non-glandular stomach and 

urinary bladder.

No evidence of carcinogenicity.

870.4300 Combined chronic 

toxicity/

carcinogenicity

(rat)

42157601 (1991)

Acceptable/guideline

0, 30, 150, or 300 ppm (0, 

M: 0, 1.5, 7.3, and 14.7 

mg/kg bw/day

F: 0, 1.8, 8.9, and 18.6 

mg/kg bw day 

NOAEL = 30 ppm (M/F: 1.5/1.8 mg/kg/day).

LOAEL = 150 ppm (M/F: 7.3/8.9 mg/kg/day), 

based on changes in hematology, clinical 

chemistry, incidences of bile duct hyperplasia 

and reduction in mean body-weight gain. 

No evidence of carcinogenicity.

870.5300 In Vitro

Mammalian Gene 

Mutation Assay in 

V79 Chinese 

Hamster Cells at 

the HPRT Locus)

00160621 (1986)

Acceptable/guideline

0.001-56.0 μg/mL (±S9)

No evidence of mutagenicity with or without 

metabolic activation.

870.5375 In Vitro

Mammalian 

Cytogenetics 

(Chromosomal 

Aberration Assay 

in Chinese Hamster 

Ovary Cells) 

40510901 ( 1987)

Acceptable/guideline

0.56, 1.0, or 2.4 μg/mL 

(-S9)

1.8, 5.6, or 18.0 μg/mL 

(+S9)

Significant dose-related increases in 

chromosomal aberrations with and without 

metabolic activation. Classified as a clastogen.

870.5395 Mammalian 

erythrocyte 

micronucleus test

40510902 (1987)

Acceptable/guideline

38, 189, or 377 mg/kg

Administration of 38, 189, or 377 mg/kg thiram 

did not cause a significant increase in the 

frequency of micronucleated polychromatic 

erythrocytes (MPEs) harvested from male and 

female mice.

870.5550 UDS in Primary 

Rat 

Hepatocytes/Mam

malian Cell 

00156064 (1985)

0.03, 0.1, 0.3, 1.0, 3.0, or 

10.0 μg/mL

Did not induce DNA repair.

870.6200a Acute neurotoxicity 

screening battery

45589101 ( 1993)

Unacceptable/nonguideline

0, 10, 25, 60, or 150 

mg/kg bw

NOAEL = 10 mg/kg.

LOAEL = 25 mg/kg, based on decreases in 

food consumption in males and females.

870.6200a Acute neurotoxicity 

screening battery

42912401 ( 1993)

Acceptable/guideline

0, 5, 150, or 600 mg/kg 

bw

BMDL10 = 64.94 mg/kg.

LOAEL = 150 mg/kg, based on FOB effects at 

21/2 hours post-dosing; reduced motor activity 

at 31/2 hours, and at 7 and 14 days posttreatment. 
Thiram/079801 Human Health Risk Assessment D412465 

Page 21 of 21

Table A.2.2. Subchronic and Chronic Toxicity and Genotoxicity Profile – Thiram.

Guideline 

No. Study Type

MRID No. (year)/ 

Classification /Doses Results

870.6200b Subchronic 

neurotoxicity –

feeding study in 

rats

43012701 (1993)

Acceptable/guideline

0, 30, 125 or 500 ppm 

(0/0, 1.74/2.04, 7.26/8.07, 

and 28.63/31.82 mg/kg 

bw/day [M/F])

NOAEL = 30 ppm (1.74/2.04 mg/kg/day 

[M/F]).

LOAEL = 125 ppm (7.26/8.07 mg/kg/day 

[M/F]), based on increased numbers of rearing 

events and elevated incidences of hyperactivity 

in females at weeks 8 and 13. 

870.6300 DNT 46455201 (2004)

Acceptable/guideline

0, 20, 45, or 90 ppm

0, 1.4, 3.7, or 7.2 mg/kg 

bw/day

Maternal NOAEL = 45 ppm (3.7 mg/kg/day).

LOAEL = 90 ppm (7.2 mg/kg/day), based on 

decreased body weight, body-weight gain, and 

food consumption, clinical signs of toxicity, 

and FOB findings.

Offspring NOAEL = 20 ppm (1.4 mg/kg/day.

LOAEL = 45 ppm (3.7 mg/kg/day) based on 

increased locomotor activity in females on 

PND17.

870.7485 Metabolism and 

pharmacokinetics

(rat)

No DERs or MRIDs could 

be located 

Rats (6 male + 6 female) were dosed orally for 

14 days with unlabelled thiram at 2 mg/kg bw 

then with [14C]thiram at 2 mg/kg bw on day 15 

(Nomeir and Markham, 1990). Expired air and 

excreta were collected for a further 96 hours 

and then the animals were slaughtered for 

tissue collection. Approximately 33-35% of 

the administered 14C was eliminated in the 

urine, 2.6-5.3% in the feces and 47-48% in the 

expired air. The nature of the volatile 14C was 

not investigated in detail, but 75-85% of it was 

collected in a KOH trap suggesting CO2, or 

COS, with the remainder collected in a reagent 

for CS2. Norris (1991) identified by HPLC the 

metabolites in the urine of the rats from the 

single dose study of Gay (1987) and the 

multiple dose study of Nomeir and Markham 

(1990). There were no sex differences in the 

metabolism but the proportions of some of the 

metabolites depended on the dosage level and 

the time after dosing. 

[www.fao.org/docrep/W5897E/w5897e5a.htm]

870.7800 Immunotoxicity 

(mouse)

48646401

Acceptable/guideline

0, 15/17.5, 150, or 450 

ppm

(0, 3, 25, 74 mg/kg/day)

Systemic NOAEL = 450 ppm (74 mg/kg/day, 

the highest dose tested).

Systemic LOAEL was not established.

Under conditions of this study, the 

Immunotoxicity NOAEL = 150 ppm (25 ppm)

Immunotoxicity LOAEL= 450 ppm (74 

mg/kg/day) based on treatment related 

decreases in anti-SRBC antibody response.