Thiram/07980 I Human Health Risk Assessment 

UNITED STATES ENVIRONMENTAL PROTECTION AGENCY 

WASHINGTON, D.C. 20460 

OFFICE OF CHEMICAL SAFETY AND POLLUTION PREVENTION 

MEMORANDUM 

Date: May 2 1, 20 15 

D427383 

SUBJECT: T hiram. Revised Human Health Risk Assessment for the Import Use ofThiram 

on Avocado, PP#4E8250 and Banana, PP#4E8268. 

PC Code: 07980 I DP No.: 0 427383 

Decision No.: 488085 Registration No.: NA 

Petition No.: PP#4E8250 Regulatory Action: Tolerance, no registration 

Risk Assessment Type: Single Chemical, Aggregate Case No.: 0122 

TXR No.: NA CAS No.: 137-26-8 

MRID No.: NA 40CFR: §180.132 d 

FROM: Thurston G. Morton, Chemist/Risk Assessor '.(;J.:;....-- Kelly O'Rourke, ORE )t.J~ IY/, V t-vt..,'--'-

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

THROUGH: Charles 

Risk Assessment 

Smith, Branch 

Branch 

Chief 

IV/Health Effects Division (7509P

C_ 

) -

~ 

TO: Driss Benmhenol 

Rachel Holloman, Branch Chief 

Fungicide Branch, Registration Division (7505P) 

1.0 Executive Summary 

Taminco, Inc., submitted petitions proposing tolerances for residues of thiram on banana at 0.8 

ppm and avocado at 8.0 ppm, both expressed as thiram. Currently, tolerances for residues of 

thiram are expressed as carbon disulfide. No U. S. registration is proposed. An earlier petition 

for residues ofthiram on avocado (PP#1E7823, D405132, G. Otakie, 9/ 19112) was withdrawn 

due to lack of storage stability data; which have been included in the current submission. An 

earlier petition for residues of thiram on banana (6E7 l 44, D365442, G. Kramer, 619109) resulted 

in a time-limited tolerance due to an inadequate number of field trials for thiram on banana, 

which was extended in PP#4E8243, D418114, W. Cutchin, 2118/2014). The required field trial 

data have been included in the current submission. The tolerances to be established are based on 

the use of the OECD Tolerance Calculation Procedures. A revised dietary exposure assessment 

has been conducted for the avocado and banana uses outside the U.S. (D427382, T. Morton, 

5/2 1/15) to correct language on what residues were used in the dietary exposure assessment. 

Page 1 of 20 
Thiram/07980 I Human Health Risk Assessment 0427383 

There are no residue chemistry issues which will preclude issuance of a tolerance for residues of 

thiram of 0.5 ppm (expressed as CS2) on banana, nor issuance of a tolerance for residues of 

thiram of 10 ppm (expressed as CS2) on avocado, with no U.S. registration. No additional data 

are needed. 

HED conducted an updated dietary risk assessment to support the requested uses. 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., < l 00% of the acute and chronic 

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

The acute dietary exposure at the 95th exposure percentile was 1.9% of the aPAD for the general 

U.S. population and 61 % of the aPAD for females 13-49 years old, the population subgroup with 

the highest percent aPAD. Chronic dietary exposure for the general U.S. population was 13% of 

the cPAD and 70% 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 previously assessed for 

children 6 to <I I years old, children l l to <16 years old, and adults. The dermal margins of 

exposure (MO Es) for the populations assessed ranged from 850 to I 000, which did not fall 

below the level of concern of I 00. 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 of thiram (food and drinking water). As referenced above, both the 

acute and chronic dietary risk estimates are not of concern to HED (<100% 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 

onl y, in the case of this assessment). The combined exposure may then be used to calculate an 

MOE for aggregate risk. Using the golfe r 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 570, 540, and 280, 

respectively. As these MO Es are greater than the target LOC of l 00, the short- and intermediateterm aggregate risks are not of concern. 

An updated occupational exposure and risk assessment is not required to support the 

requested import uses. 

Page 2 of 20 
Thiram/07980 I Human Health Risk Assessment 0427383 

2.0 HED Recommendations 

HED concludes that there are no risk issues that would preclude granting a tolerance for residues 

of thiram of 0.50 ppm (expressed as CS2) on banana, nor issuance of a tolerance for residues of 

thiram of 10 ppm (expressed as CS2) on avocado, with no U. S. registration. 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 (MRJD 48646401 ). The HASPOC determined 

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

Therefore, a 1 OX 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 CSi 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 0.50 ppm supports the banana use pattern and a tolerance of I 0 ppm supports the 

avocado import use. A summary of tolerance recommendations is presented in Table 2.2.2. The 

recommended tolerances were derived with the aid of the OECD tolerance calculation procedure. 

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

Page 3 of 20 
Thiram/07980 I Human Health Risk Assessment 0427383 

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 are listed 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 2.2.2. Tolerance Summary for Thi ram. 

Proposed Tolerance Recommended Comments; 

Commodity 

(ppm thiram) Tolerance (ppm [Correct Commodity Definition] 

CS2) 

Banana 0.8 0.50 OECD Tolerance Calculation procedures 

recommend 0.7 ppm thiram. (The 

conversion factor is 0.63x, resulting in a 

recommendation of 0.5 ppm as CS2)* 

Avocado 8 10 OECD Tolerance Calculation procedures, 

using the residues found at a 3 day PHI 

recommend 15 ppm thiram. (The 

conversion factor is 0.63x, resulting in a 

recommendation of I 0 ppm as CS2) 

*A CODEX MRLof2 ppm as carbon disulfide has been established, based on mancozeb use on banana 

2.2.3 Revisions to Petitioned-For Tolerances 

Tolerance proposals for raw agricultural commodities were changed to be based on the OECD 

Tolerance Calculation Procedures, and to express the residue as carbon disulfide to harmonize 

with CODEX. A revised Section Fis needed with the changes in tolerance expression and 

tolerance levels. 

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 banana of 2 

mg/kg, from the use of mancozeb on banana. CODEX has not established any MR Ls for carbon 

disulfide from the use of thiram on avocado or banana. U.S. tolerances are curTently established 

and expressed as carbon disulfide. The tolerance expression is now compatible with CODEX. 

Page 4 of 20 
Thiram/07980 I Human Health Risk Assessment 0427383 

2.3 Label Recommendations 

No label revisions are required. 

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 Cll3 s I J N s c1-4 

H1C s N 

s CH. 

Common name Thiram 

IUPAC name tetramethylthiuram d isul!ide 

CJ\S name tetramethylthiopcroxydicarbonic diamide 

CAS registry number 137-26-8 

End-use products (EPs) used in Banguard 42 PLUS (37.0% ai SC) or Banguard 60 (52.6% ai SC) 

residue !ield study 

3.2 Physical/Chemical Characteristics 

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

Parameter Value Reference 

Melting range 142-150°C Revised Thiram Product and 

Density 0.32-0.35 g/mL Residue Chemistry Chapters 

Water solubility at 20-25°C 0.00165 g/100 mL 

for the RED Document, 

12/ 16/03. 

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

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

xylene (0.9 1 g/100 mL). and methanol 

(0.184 g/ 100 mL) 

Vapor pressure 1.6-1.8 x I 0·

5 Torr at 25°C 

Dissociation constant, pK. 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. 

Page 5 of 20 
Thiram/07980 I Human Health Risk Assessment 0427383 

Table3.3. Summa ry of Directions for Use ofThiram 

Max. No. Max. 

Applic. Timing; Formulation Applic. Applic. Seasonal PHI Use Directions and 

Type; a nd Eq uip. !EPA Reg. No.I Rate, 

per App lie. (days) Limitations kg a i/ha Season Rate 

(kg a i/ha) 

Avocado 

80% WDG Use a 6-7 day interval 

roliar broadcast [Thiram 80 2.4 3 7.2 0 between applications. 

WG) 

Banana 

42%SC 

Use a 5-7 day interval 

Foliar broadcast 1.26 10 12.6 0 between applications. [Banguard 42] 

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://epa.gov/compliance/ej/resources/policy/exec order 12898.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 conswnption 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, 0 365442, 

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. 

Page 6 of20 
Thiram/07980 I Human Health Risk Assessment D427383 

The Hazard and Science Policy Counci I (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 

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

required. Therefore, a 1 OX 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 ONT 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 Htimans" 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 ofrats following single or repeated oral 

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

radioactivity was eliminated as expired air (

14C02, 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 IX. The recommendation of 1 X 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 

Page 7 of20 
Thiram/07980 I Human Health Risk Assessment 0427383 

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 ONT study. However, there is low concern for the enhanced 

susceptibility seen in the ONT study because clear NOAELs/LOAELs were established for the 

offspring 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 susceptibi lity 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 1 OX 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 jn the database for thiram, there are no residual 

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

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

in a ONT 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 ONT 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 ONT 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 max imum 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 

Page 8of20 
Thiram/07980 I Human Health Risk Assessment 0427383 

support these petitions. 

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, 0 365442, 6/9/2009). The endpoint summary table is included below. 

Table 4.3.1. Summary of Toxicological Doses a nd End points for Thiram for Use in Dietary a nd NonOccupationa l Huma n Healt h Risk Assessments. 

Expos ure/ Uncerta inty/FQPA RID, PAD, LOC for Study a nd Toxicological 

Scenario PoD SFs Risk Assessment Effects 

Acute Acute Neurotoxicity Study -

Dietary BMDL10= Rat 

(General 64.94 UFA= !Ox Acute RID = 0.6494 MRID 429 12401 

Population) mg/kg UFH = IOx mg/kg/day LOA EL = 150 mg/kg/day based 

FQPA SF = Ix on FOB effects (lethargy, lower 

aPAD = 0.6494 temperature, reduced startle 

mg/kg/day response, no tail-pinch 

response), reduced motor 

activity, and reduced brain 

weights. 

Acute NOAEL = UF" = !Ox Dev. Neurotoxicity Study - Rat 

Dietary 1.4 mg/kg UFH = I Ox Acute RID = 0.0 14 MRJD 46455201 

(Females FQPA SF = Ix mg/kg/day LOAEL = 3.7 mg/kg/day based 

13-49 years aPAO =0.0 14 on increases in motor activity 

old) seen in fema le offspring on mg/kg/day PND 17. 

Chronic UFA= !Ox Chronic RID = 0.015 Co-critical: I) Combined 

Dietary UF11 = !Ox mg/kg/day Chronic 

(All FQPA SF = Ix Toxicity/Carcinogenicity Study 

populations) cPAD =0.0 15 - Rat and 2) Chron ic Oral 

mg/kg/day Toxicity-Dog 

NOAEL = LOAEL = 7.3 mg/kg/day based 

1.5 mg/kg 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 

Intermediate 

-Tenn No incidental oral residential exposure. 

Incidenta l 

Oral 

Page 9of 20 
Thiram/07980 I Human Health Risk Assessment D427383 

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

Exposure/ Uncertainty/FQPA RID, PAD, LOC for Study and Toxicological 

Scenario PoD SFs Risk Assessment Effects 

Short-Tem1 

NOAEL = UFA= I Ox Residential LOC for Dev. Neurotoxicity Study - Rar 

Dermal (I- UF11 = IOx MOE = 100 MRJD 46455201 

30 days) 1.4 FQPA SF = Ix mg/kg/day (Dermal-absorption Occupational LOC for LOAEL = 3.7 mg/kg/day based 

factor= 1%) MOE = 100 on increases in motor activity 

seen in female offspring on 

PND 17. 

Intermediate NOA EL UFA = !Ox Residential LOC for Dev. Neurotoxicity Study - Rat 

-Term =1.4 UF11 = IOx MOE = 100 MRID 4645520 I 

Dermal (I to mg/kg/day FQPA SF = Ix LOAEL = 3.7 mg/kg/day based 

6 months) (Dermal-absorption Occupational LOC for on increases in motor activity 

factor = 1%) MOE = 100 seen in female offspring on 

PND 17. 

Short- and 

Intermediate Current assessment does not warrant an inhalation assessment. -Term 

Inhalation 

Cancer (oral, 

dermal, "Not Likely to be Carcinogenic to Humans" 

inhalation) 

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). UF H = potential variation in sensitivity 

among members of the human population (interspecies). FQPA SF = FQPA Safety Factor. PAD = populationadjustcd 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 

Avocado. Avocado data have been reviewed previously (48342 101 , 0 389505, G. Otakie, 

2/2/2012). Three field trials for thiram on avocado were conducted in Michoacan, Mexico. 

Initially the three trial locations were determined to be a single trial because the tri als were 

conducted close together with few distinguishing characteristics. This decision was later 

reconsidered. In the three trials, three foliar applications of the 80% WG formulation of thiram 

at a total rate of6.42-6.43 lb ai/A(?.20-7.2 1 kg ai/ha), residues ofthiram, determined as CS2.and 

expressed as thiram, were l.1 -3.4 ppm (per trial average residue of 2.3 ppm) in/on avocado 

whole fruit at a 0-day PHI. Residues of thiram were below the LOQ (<0.05 ppm) in/on avocado 

pulp harvested at a 0-day PHI. A decline study was conducted, but no discernible pattern of 

decline was seen. Adequate field trial data had already been submitted for avocado. However, 

the fi eld trials show higher residues at a 3 day PHI than at the 0 day PHI. The data from the 3 

day PHI have been entered into the OECD tolerance calculation spreadsheet, which is found in 

the appendix to this review. This results in a tolerance estimate of 15 ppm expressed as thiram. 

Page 10 of 20 
Thiram/07980 I Human Health Risk Assessment 0427383 

which requires a 10 ppm tolerance expressed as carbon disulfide. 

Banana. Previously submitted data. Banana data were submitted previously (MRID 4699230 I, 

D372408, G. Kramer, 9/13/2007). Banguard 42 (an SC formulation) was used in the trials. Nine 

trials were conducted in Columbia ( 1 ), Costa Rica (3), Ecuador (3), Honduras (I), and Mexico 

(I). Ten applications were made at a target rate of 1.26 kg ai/ha, for a total application rate of 

12.6 kg ai/ha. Spray oil was used as an adjuvant with the applications. Decline studies were 

included with some of the trials. Residues of thiram tended to increase and then decrease with 

time. 

Banana. New data. The locations for the additional banana field trials will be considered 

adequate, based on the explanation provided. The banana field trials are considered adequate and 

support a tolerance for residues of thiram on banana. Higher residues were reported in some, but 

not all of the field trials at PHis longer than the proposed PHI of 0 days. The data at the 0 day 

PHI should be reasonably representative of the residues expected for thiram on banana, so the 

data from the 0 day PHI were used in the OECD tolerance calculation procedure, which 

predicted a tolerance of 0. 7 ppm expressed as thiram. This tolerance was then converted to be 

expressed as ppm carbon disulfide with a 0.63x conversion factor, resulting in a tolerance needed 

of0.50 ppm. 

5.2 Water Residue Profile 

The Environmental Fate and Effects Division has previously assessed residues in drinking water 

from the existing uses of thiram. A new drinking water assessment is not required since 

requested uses are for import banana and avocado. 

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-FCIDrn 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. 

Annual 

App Rate SCI GROW PRZM/EXAMS* PRZM/EXAMS* PRZM/EXAMS* 

(lbs concentration Acute EEC non-cancer cancer chronic 

Crop ai/acre/vr) foob) foob) chronic EEC foob) EEC fnnb) 

Turf farm 146.6 0.84 47.8 2.5 2.2 

* Index Reservoir environment 

Page 11 of20 
Thiram/07980 I Human Health Risk Assessment 0427383 

5.3 Dietary Risk Assessment 

5.3.1 Description of Residue Data Used in Dietary Assessment 

A partially refined probabilistic acute dietary-exposure assessment was performed using l 00 

%CT, average residue of field-trial residue values for blended commodities, distribution of field 

trial residues, highest pulp residues, and empirical processing factors. Avocado and banana pulp 

residues, along with average field trial residues for apples, peaches and strawberries and 100% 

crop treated (CT) were used for the chronic dietary exposure analysis for all crops. Empirical 

processing factors were also used. 

5.3.2 Percent Crop Treated Used in Dietary Assessment 

Percent crop treated was set at 100% for the acute and chronic dietary exposure analyses. 

5.3.3 Acute Dietary Risk Assessment 

A partially refined probabilistic acute dietary-exposure assessment was performed using 100 

%CT, average residue of field-trial residue values for blended commodities, distribution of field 

trial residues, highest pulp residues, and empirical processing factors. Dietary risk estimates 

were determined considering exposures from food plus drinking water using EDWCs for surface 

water sources provided by EFED. 

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

concern (i.e., <100% of the aPAD of0.6494 mg/kg bw/day) for the general U.S. population and 

all population subgroups (including females 13-49 years old; aPAD of 0.014 mg/kg bw/day). 

Using DEEM-FCID, acute dietary exposure at the 95111 exposure percentile is estimated at 

0.012002 mg/kg bw/day for the general U.S. population (1.9% of the aPAD) and 0.008595 

mg/kg bw/day (6 1% of the aPAD) for females 13-49 years old, the population subgroup with the 

highest% aPAD dietary exposure to thiram. The estimated exposures/risks for food and 

drinking water are summarized in Table 5.3.3. 

Page 12 of 20 
Thiram/07980 I Human Health Risk Assessment D427383 

Table 5.3.3. Results of Acute Dietary Exposure a nd Risk 

Ana lysis for Thiram (Food + Water). 

95•h Per centile 

Population a PAD Exposure 

Subgroup (mg/kg/day) (mg/kg/day) %aPAD 

Genera l U.S. 

Population 0.6494 0.0 12002 1.9 

I - All lnfants I (< I year old) 0.6494 0.027109 4.2 

Children 1-2 

years old 0.6494 0.043503 6.7 

Children 3-5 

years old 0.6494 0.032302 5.0 

Children 6-

12 years old 0.6494 0.018667 2.9 

Youth 13-19 

years old 0.6494 ! 0.009851 1.5 

Adults 20-49 I years old 0.6494 0.007907 1.2 

Adults 50-99 

years old 0.6494 0.008705 1.3 

Females 13-

49 years old 0.0 14 0.008595 61 

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

5.3.4 Chronic Dietary Risk Assessment 

The partially refined chronic dietary risk estimates for food and water combined are below 

HEO's level of concern (i.e., <100% of the cPAO of0.015 mg/kg bw/day) for the general U.S. 

population and all population subgroups. Using the DEEM-FCID software, dietary exposure is 

estimated at 0.001999 mg/kg bw/day for the general U.S. population (13% of the cPAD) and 

0.010557 mg/kg bw/day (70% 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 

food and drinking water are summarized in Table 5.3.4. 

Table 5.3.4. Summa ry of Chronic Dietary Exposure a nd Risk for Thira m (Food + Wa ter). 

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

General U.S. Pooulation 0.015 0.001999 13 

All Infants (< l year old) 0.015 0.005387 36 

Children 1-2 years old 0.015 0.010557 70 

Children 3-5 years old 0.015 0.006870 46 

Children 6- 12 years old 0.015 0.003359 22 

Youth 13-19 years old 0.015 0.001413 9.4 

Adults 20-49 years old 0.015 0.001077 7.2 

Adults 50-99 years old 0.015 0.001421 9.5 

Females 13-49 years old 0.01 5 0.001186 7.9 

• The values for the highest exposed population is bolded. 

Page 13 of 20 
Thiram/07980 I Human Health Risk Assessment 0427383 

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 

(0 263948). 

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 previously 

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 I hour to reflect the anticipated time a 

player would be spending in contact with those areas. The dermal margins of exposure (MO Es) 

for the populations assessed ranged from 850 to I 000, which are above the target MOE of 100 

and, therefore, not of concern (Table 6.0). Inhalation post-application exposures for golf courses 

were not assessed since inhalation exposures are thought to be negligible in outdoor postapplication scenarios. 

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

Weight unit Transfer Hours of 

Formulation Lifestage 

T rR12 conversion Coefficicnt3 Exposure4 Exposures 

{ug./cm2) factor (cm21h r) (hr) {mg./day) 

(mg/ug) 

Liquids 1 Adult 1.81 0.001 5,300 I 9.6 

Liquids Children 11 to 1.81 0.001 4,400 I 7.8 

<16 years 

Liquids Children 6 to <11 1.81 0.001 2,900 I 5.3 

years old 

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

2. Tl'Rt = AR • F • ( 1-Fo)' • CF2 • CF3 where. ITRt = turf transferable residue on day "t" (μg/cm2): AR = 

application rate (16.3 lb ai/acrc); F= fraction ofai retained on turf(0.01): Fo= 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 I 08 μg/lb): and CF3= area unit conversion factor ( 2.4 7 x I o·

8 acrc/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 ru;sessmcnt 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 I hour exposure calculation is assumed. 

5. Exposure (mg/day) = ITRt •CF! •TC• ET where. ·rrnt = turf transferable residue on day "t" (μg/ cm2): 

CF! = weight unit conversion factor (0.00 I mg/μg); TC = transfer coefficient (cm2/hr): and ET = exposure 

time ( I hr/day). 

E*AF 

6. Absorbed Dose {mg/kg·day), D = where, E= exposure (mg./day): AF= absorption factor (0.0 I): BW 

and 13\.V = body weight (69. 57. and 32 kg for adults. children 11 to <16 yrs and children 6 to <I I yrs, 

respectively). 

7. MOE = POD ( 1.4 mg.lkg/day) I Absorbed Dose (mg/kg/day). The level of concern (LOC) is I 00. 

Page 14 of 20 

Absorbed 

Dosc6 

(mg/kg/day) 

0.0014 

0.0014 

0.0016 

Dermal 

MOE7 

1000 

1000 

850 
Thiram/079801 Human Health Risk Assessment 0427383 

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 951h 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 

short/ intermediate-term food and residential aggregate MOEs are 570, 540, and 280, 

respectively. As these MO Es are above the target MOE of 100, the short- and intermediate-tern1 

aggregate risks are not of concern. 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 

Short- or Intermediate-Term Scenario 

Max Aver age Aggr egate Food and Residentia l Total Population NOAEL Loe• Allowable Water Exposu re Exposure MOE (food, 

mg/kg/day Exposure2 

Exposure mg/kg/day3 mg/kg/day4 water, and 

mg/kg/day m1?/k1?/dav r esidentia l)5 

Adult6 Male 1.4 100 0.014 0.001071 0.0014 0.002471 570 

Adult6 Female 1.4 100 0.014 0.001179 0.0014 0.002579 540 

Children6 >6 1.4 100 0.014 0.003339 0.0016 0.004939 280 

years old 

1 The Level of Concern (LOC) is based on the I OX for interspecies extrapolation, I OX for intraspecies variations, 

and IX 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 Aggregate MOE = [NOAEL I (Avg Food & Water Exposure + Residential Exposure)] 

6 Relevant population subgroup with highest exposures (Tables 5.3.4 and 6.0). 

Page 15of20 
Thiram/07980 I Human Health Risk Assessment 0427383 

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% cPAD) 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 

imported uses. 

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'' 

Hummel, S. 12/1 8/2014. 041934 1. Thiram on Avocado, PP#4E8250 and Banana, PP#4E8268. Summary of 

Analytica l Methods and Residue Data. 

Kramer, G.and Greear. W. 06/09/2009. D365442. Thiram inion 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. 0 14 193. Thiram- Toxicology Disciplinary Chapter for the 

Reregistration Eligibil ity Decision Document. 

Morton. T. 5/2 1/20 15. 0427382. Thiram: Revised Acute and Chronic Dietary (Food and Drinking Water) Exposure 

and Risk Assessment to Support a Petition For Conversion of the Time-Limited Banana Tolerance to Permanent and 

Import use on Avocado. 

Rury, K. 6/30/20 13. 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. 

Page 16 of 20 
Thiram/079801 Human Health Risk Assessment D427383 

Appendix A. Toxicity Profiles 

Table A.2.1. Acute Toxicity Profile - Thiram. 

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

1100 Acute oral (rat) 00163854 LDso = 2.6 g/kg Ill 

1200 Acute dermal 00259250 LDso 2.0 g/kg 111 

1300 Acute inhalation (rat) 00165855 LCso 0.1 mg/L II 

2400 Primary eye irritation (rabbit) 00259250 Moderate eye II 

irritant 

2500 Primary dermal irritation (rabbit) 00259250 Very slight dermal IV 

irritant 

2600 Dermal sensitization 00153068 Moderate skin NIA 

sensitizer 

Table A.2.2. Subchronic and Chronic Toxicity and Genotoxicity Profile - Thi ram. 

G uideline MRID No. (year)/ 

No. Study Type Classification /Doses Results 

870.3100 90-Day oral 4077360 I ( 1988) NOAEL = could not be determined due to lack 

toxicity (rat) Unacceptable/guideline of information on stability. 

0, 50, 500, or I 000 ppm LOAEL = 25 mg/kg/day, based on decreases in 

(0, 2.5, 25, or 50 mg/kg body-weight gain, hematology and clinical 

bw/day) chemistrv oarameters. 

870.3150 90-Day oral 46 1503608 (1990) NOAEL = 1.9 mg/kg/day. 

toxicity (dog) Acceptable/guideline LOA EL = 6.3 mg/kg/day, based on adverse 

0, 75, 250, or 500 ppm changes in clinical chemistry, and decreases in 

(0, 1.94-2.58, 6.17-7.85, mean body weight and food consumption. 

or 10.55-14.69 mg/kg 

bw/dav) 

870.3200 21-Day dermal 4264250 I ( 1992) NOAEL = 300 mg/kg/day. 

toxicity (rabbit) Acceptable/guideline LOAEL = I 000 mg/kg/day, based on decreases 

0,250, 500, or 1000 in body-weight gain and food consumption as 

mg/kg bw/day well as alterations in clinical chemistry. 

870.3700a Prenatal 00151610 ( 1978) Maternal NOA EL = 12.5 mg/kg. 

developmental (rat) Unacceptable/guideline LOAEL = 25 mg/kg, based on reduced body0, 12.5 , 25, 50, or I 00 weight gains and food consumption. 

mg/kg bw Developmental NOAEL could not be 

detennined. 

LOAEL = 12.5 mg/kg, based on reduced 

ossification. 

870.3700a Prenatal 40534 101 ;41498301 Maternal NOAEL could not be determined. 

developmental (rat) (1988) LOAEL = 7.5 mg/kg, based on decreases in 

Acceptable/guide! ine body-weight gain, alopecia, scars, damaged 

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

Page 17 of 20 
Thiram/07980 I Human Health Risk Assessment 0427383 

Table A.2.2. Subchronic and Chronic Toxicity and Genotoxicity Profile - T hiram. 

Guideline 

No. Study Type 

870.3700b Prenatal 

developmental 

(rabbit) 

-

870.3700b Prenatal 

developmental 

(rabbit) 

870.3700b Prenatal 

developmental 

(rabbit) 

870.3800 2-Gen. 

reproduction and 

fertility effects 

(rat) 

>----

870.3800 2-Gen. 

reproduction and 

fertility effects 

(rat) 

>------

870.4 100 Chronic toxicity ( I 

year; dog) 

MRLD No. (year)/ 

Classification /Doses Results 

40444702( 1987) Maternal NOAEL = 3 mg/kg bw/day. 

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

0, I , 3, 5, 7.5, 10, 20, 40, maternal body-weight gains. 

or 80 mg/kg bw Developmental NOAEL was not determined. 

(range-finding) LOAEL was not determined. 

4057730 I ( 1988) Maternal NOAEL = 5 mg/kg bw/day. 

Acceptable LOAEL was not determined. 

0, I, 2.5, or 5mg/kg bw Developmental NOAEL = 5 mg/kg. 

ranoe-finding)~ ___ ,_LOAEL was not determtned. 

4222360 I ( 1992) Materna l NOA EL = I 0 mg/kg bw/day 

Acceptable LOA EL was not determined 

0, I , 5, or I 0 mg/kg bw Developmental NOAEL = I 0 mg/kg 

LOAEL was not determined. 

42095901 ( 1991) 

Acceptable/guideline 

0, 30, 60, or 180 ppm 

(FO: 010, 1.2/1.9, 2.4/3.9, 

or 8.5111 .8 mg/ kg bw/day 

[M/F]) 

(Fl: 010, 1.5/2.0, 3.24.3, 

or 9.2/ 13.4 mg/kg bw/day 

[M/F) 

4544 1203 ( 1997) 

Acceptable/guideline 

0, 20, 60, or 180 ppm 

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

bw/day) 

4196790 I ( 199 1) 

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 ~ 

Page 18 of20 

Parental/Systemic NOAEL = 30 ppm (1.9 

I ng/kg/day [M!F]). 

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

ased on decreases in body-weight gain and 

ood consumption. 

L 

b 

fi 

Reproductive NOA EL was not determined. 

L OAEL > 180 ppm (8.9 mg/kg/day). 

Offspring NOA EL = 180 ppm (I 1.8 

I ng/kg/day). 

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

d ecreased mean body weight. 

p a r ental/Systemic NOA EL = 20 ppm ( 1.4 

mg/kg/day). 

L 

r 

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

educed body-weight gains during gestation. 

Reproductive NOA EL ~ 180 ppm ( 12.2 

I ng/kg/day). 

L OAEL was not determined. 

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

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

d ecreases in pup body weight and body-weight 

g ain. ----

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

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

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

0 n increased mean cholesterol levels. 

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

b ased on increased mean cholesterol levels and 

II 1crcased liver-to-bod weight ratios. _J 
Thiram/07980 I Human Health Risk Assessment 0427383 

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

Guideline MRID No. (year)/ 

No. Study Type Classification /Doses Results 

870.4200 Carcinogenicity 4231340 I ( 1992) NOAEL = 15 ppm (M/F: 2.5/3.1 mg/kg 

(mouse) Acceptable/guideline bw/day). 

M: 0, 15, 150, or 300 ppm LOAEL (M) = 150 ppm (24 mg/kg bw/day. 

F: 0, 15, 300, or 600 ppm LOAEL (F) = 300 ppm (57 mg/kg/day), based 

M: 0, 2.5, 24, and 57 on decreases in mean body weight and mean 

mg/kg bw/day body-weight gain, anemia, and non-neoplastic 

F: 0, 3. 1, 57, and 11 2 lesions in the eyes, non-glandular stomach and 

mg/kg bw/day urinary bladder. 

No evidence of carcinogenicity. 

870.4300 Combined chronic 42157601 (1991) NOAEL = 30 ppm (M/F: 1.5/ 1.8 mg/kg/day). 

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

carcinogenicity 0, 30, 150, or 300 ppm (0, based on changes in hematology, clinical 

(rat) M: 0, 1.5, 7.3, and 14.7 chemistry, incidences of bile duct hyperplasia 

mg/kg bw/day and reduction in mean body-weight gain. 

F: 0, 1.8, 8.9, and 18.6 

mg/kg bw day No evidence of carcinogenicity. 

870.5300 Jn Vitro 00160621 (1986) No evidence ofmutagenicity with or without 

Mammalian Gene Acceptable/guideline metabolic activation. 

Mutation Assay in 0.001-56.0 μg/mL (±S9) 

V79 Chinese 

Hamster Cells at 

the HPRT Locus) 

870.5375 Jn Vitro 40510901 ( 1987) Significant dose-related increases in 

Mammalian Acceptable/guideline chromosoma l aberrations with and without 

Cytogenetics 0.56, 1.0, or 2.4 ~1g/mL metabolic activation. Classified as a clastogen. 

(Chromosomal (-S9) 

Aberration Assay 1.8, 5.6, or 18.0 μg/mL 

in Chinese Hamster (+S9) 

Ovary Cells) 

870.5395 Mammalian 40510902 ( 1987) Administration of38, 189, or 377 mg/kg thiram 

erythrocyte Acceptable/guideline did not cause a significant increase in the 

micronucleus test 38, 189, or 377 mg/kg frequency of micronucleated polychromatic 

erythrocytes (MPEs) harvested from male and 

female mice. 

870.5550 UDS in Primary 00156064 (1985) Did not induce DNA repair. 

Rat 0.03, 0.1, 0.3, 1.0, 3.0, or 

Hepatocytes/Mam 10.0 μg/mL 

malian Cell 

870.6200a Acute neurotoxicity 45589 101 ( 1993) NOA EL = I 0 mg/kg. 

screening battery Unacceptable/non- LOA EL = 25 mg/kg, based on decreases in 

guideline food consumption in males and females. 

0, 10, 25, 60, or 150 

mg/k~ bw 

870.6200a Acute neurotoxicity 4291240 1 ( 1993) BMDL10 = 64.94 mg/kg. 

screening battery Acceptable/guide! ine LOAEL = 150 mg/kg, based on FOB effects at 

0, 5. 150, or600 1ng/kg 21 /2 hours post-dosing; reduced motor activity 

bw at 3 I /2 hours, and at 7 and 14 days posttreatment. 

Page 19 of 20 
Thiram/07980 I Human Health Risk Assessment 0427383 

Table A.2.2. Subchronic and C hronic Toxicity and Genotoxicity Profile - Thiram. 

Guideline MRID No. (year)/ 

No. Study Type Classification /Doses Results 

870.6200b Subchronic 430 12701 (1993) NOA EL = 30 ppm (1.74/2.04 mg/kg/day 

neurotoxicity - Acceptable/guideline [M/F]). 

feeding study in 0, 30, 125 or 500 ppm LOAEL = 125 ppm (7.26/8.07 mg/kg/day 

rats (010, 1.74/2.04, 7.26/8.07, [M/F]), based on increased numbers of rearing 

and 28.63/3 1.82 mg/kg events and elevated incidences of hyperactivity 

bw/day rM/Fl) in fema les at weeks 8 and 13. -

870.6300 ONT 4645520 I (2004) Maternal NOAEL = 45 ppm (3.7 mg/kg/day). Acceptable/guideline LOA EL = 90 ppm (7.2 mg/kg/day), based on 0, 20, 45, or 90 ppm decreased body weight, body-weight gain, and 

0, 1.4, 3.7, or 7.2 mg/kg food consumption, clinical signs of toxicity, bw/day and FOB findings. 

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

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

increased locomotor activity in females on 

PNDl7. - 870.7485 Metabolism and No DERs or MRIDs could Rats (6 male + 6 female) were dosed orally for 

pharmacokinetics be located 14 days with unlabelled thiram at 2 mg/kg bw 

(rat) 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 e liminated 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 C02, 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 

mu ltiple dose study ofNomeir 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.or&docree/W5897E/w5897e5a.htmJ_ 

870.7800 lmmunotoxic ity 48646401 Systemic NOAEL = 450 ppm (74 mg/kg/day, 

the highest dose tested). 

(mouse) Acceptable/guideline Systemic LOAEL was not established. 

0, 15/ 17.5, 150. or 450 

Under conditions of this study, the ppm 

L lmmunotoxicity NOA EL = 150 ppm (25 ppm) 

(0, 3, 25, 74 mg/kg/day) lmmunotoxicity LOA EL= 450 ppm (74 

mg/kg/day) based on treatment related 

decreases in anti-SRBC antibody reseonse. 

Page 20 of 20