UNITED STATES ENVIRONMENTAL PROTECTION AGENCY WASHINGTON, D. C. 20460 OFFICE OF PREVENTION, PESTICIDES AND TOXIC SUBSTANCES December 16, 2003 MEMORANDUM SUBJECT: THIRAM  Revised HED Chapter of the Reregistration Eligibility Decision Document ( RED)

PC Code: 079801 Case # 819239 DP Barcode: D293295 FROM: Felecia A. Fort, Risk Assessor Reregistration Branch I/ HED ( 7509C)

THROUGH: Whang Phang, Ph. D., Branch Senior Scientist Reregistration Branch I/ HED ( 7509C)

TO: Craig Doty, Chemical Review Manager Special Review Branch/ SRRD The Health Effects Division ( HED) has conducted a revised risk assessment for thiram. This assessment supercedes the HED chapter of the Reregistration Eligibility Decision Document ( RED) dated June 24, 2003 ( F. Fort, D291237). This assessment has been revised to incorporate changes to the Environmental Fate and Ecological Effects Assessment and Characterization which included revised drinking water EECs. A cumulative risk assessment considering risks from other pesticides or chemical compounds having a common mechanism of toxicity is not included in this assessment. Supporting information for this risk assessment included the following documents:

Thiram  Use Closure Memo. K. Rothwell; 3/ 20/ 00 Thiram  Product and Residue Chemistry Chapter. F. Fort; 4/ 17/ 00 D264769 Thiram  Report of the Hazard Identification Assessment Review Committee. E. Méndez 4/ 14/ 03 Thiram  Cancer Considerations Memorandum. W. Burnam; 4/ 7/ 00 Thiram  Dermal Absorption Factor; Report of the Hazard Identification Assessment Review Committee. E. Méndez; 1/ 18/ 00 Thiram  Toxicology Disciplinary Chapter for the Reregistration Eligibility Decision; E. Mendez; 3/ 5/ 00; D263948 Thiram  Dietary Exposure Analysis for the HED Preliminary Human Health Risk Assessment. F. Fort; 4/ 30/ 03; D289657 Thiram  Environmental Fate and Ecological Effects Assessment and Characterization. J. Carleton and F. Jenkins; 12/ 11/ 03 Thiram  Revised Phase 5 Occupational and Residential Exposure Assessment and Recommendations for the Reregistration Eligibility Decision Document. J. Dawson; 4/ 24/ 03; D289601. Thiram  Review of Incident Reports. J. Blondell and M. Spann; 3/ 29/ 00; D264598 Thiram  OREDCI Waiver Memorandum. T. F. Moriarty; 3/ 24/ 97 THIRAM HED Human Health Risk Assessment December 16, 2003 TABLE OF CONTENTS INTRODUCTION . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3 1.0 EXECUTIVE SUMMARY . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4 2.0 PHYSICAL/ CHEMICAL PROPERTIES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8 3.0 HAZARD CHARACTERIZATION . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9 3.1 Hazard Profile . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9 3.2 FQPA Safety Factor . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12 3.3 Dose Response and Hazard Endpoint Selection . . . . . . . . . . . . . . . . . . . . . . . . . . . 14 Table 1. Acute Toxicity Data on Thiram . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 16 Table 2. Summary of Toxicological Dose and Endpoints for Thiram for Use in Human Risk Assessment. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 17 4.0 DIETARY EXPOSURE AND RISK ASSESSMENT . . . . . . . . . . . . . . . . . . . . . . . . . . 18 4.1 Summary of Registered Uses . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 18 4.2 Dietary Exposure . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 19 4.2.1 Acute Dietary Exposure Assessment. . . . . . . . . . . . . . . . . . . . . . . . . . . 21 Table 3. Summary of Thiram Acute Dietary Exposure and Risk Estimates. . . . 21 4.2.2 Chronic Dietary Exposure Assessment. . . . . . . . . . . . . . . . . . . . . . . . . . 22 Table 4. Summary of Thiram Chronic Dietary Exposure and Risk Estimates. . . 22 Table 5. Acute Dietary Exposure Sensitivity Analysis . . . . . . . . . . . . . . . . . . . 23 4.3 Drinking Water Sources of Dietary Exposure . . . . . . . . . . . . . . . . . . . . . . . . . . . . 24 Surface and Groundwater Monitoring Data . . . . . . . . . . . . . . . . . . . . . . . . . . . 24 Groundwater . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 24 Surface Water . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 25 Table 6. EECs for use in the human health risk assessment . . . . . . . . . . . . . . . . 25 5.0 OCCUPATIONAL/ RESIDENTIAL EXPOSURE AND RISK ASSESSMENT . . . . . . 25 5.1 Non Occupational ( Residential and Recreational) Risk Assessments . . . . . . . . . . . . 26 5.1.1 Residential Postapplication Risk Assessment . . . . . . . . . . . . . . . . . . . . . . 27 Table 7. Summary of Postapplication Residential Risks . . . . . . . . . . . . . 32 Table 8. Summary of Postapplication Residential Aggregate MOEs for Toddlers . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 32 5.1.2 Residential Risk Characterization . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 33 5.2 Occupational Risk Assessment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 34 5.2.1 Occupational Handler Risk Assessment . . . . . . . . . . . . . . . . . . . . . . . . . . 34 5.2.2 Occupational Handler Non Cancer Risks . . . . . . . . . . . . . . . . . . . . . . . . . 41 Table 11. Summary of Occupational Handler Risks . . . . . . . . . . . . . . . . 42 5.2.3 Postapplication Exposure Risk Assessment . . . . . . . . . . . . . . . . . . . . . . . 44 5.2.4 Occupational Postapplication Non Cancer Risks . . . . . . . . . . . . . . . . . . . 47 Table 12. Summary of Postapplication Worker Risks . . . . . . . . . . . . . . 47 5.2.5 Occupational Risk Characterization . . . . . . . . . . . . . . . . . . . . . . . . . . . . 48 <IP_ADDRESS> Occupational Handler Risk Characterization . . . . . . . . . . . . . . . 48 <IP_ADDRESS> Occupational Postapplication Risk Characterization . . . . . . . . . . 50 5.3 Incident Report . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 52 5.4 Additional Data Requested . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 53 6.0 AGGREGATE EXPOSURE AND RISK ASSESSMENT . . . . . . . . . . . . . . . . . . . . . . 54 6.1 Acute Aggregate Exposure and Risk . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 55 Table 13. Acute DWLOC Comparison . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 55 6.2 Short/ Intermediate Term Aggregate Exposure and Risk . . . . . . . . . . . . . . . . . . . . . 55 Table 14. Short/ Intermediate Term DWLOCs Comparison . . . . . . . . . . . . . . . 56 6.3 Chronic Aggregate Risk . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 56 Table 15. Chronic DWLOCs Comparison . . . . . . . . . . . . . . . . . . . . . . . . . . . . 56 7.0 CUMULATIVE EXPOSURE AND RISK ASSESSMENT . . . . . . . . . . . . . . . . . . . . . . 57 8.0 ENDOCRINE DISRUPTORS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 57 9.0 DATA NEEDS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 57 9.1 Toxicology Data Needs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 57 9.2 Product Chemistry Data Needs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 57 9.3 Residue Chemistry Data Needs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 59 9.4 Occupational/ Residential Exposure Data Needs . . . . . . . . . . . . . . . . . . . . . . . . . . . 59 10.0 BIBLIOGRAPHY . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 60 3 INTRODUCTION This revised human health risk assessment for thiram incorporates the most recent deliberations on the hazard components of risk including review of a new acute neurotoxicity study in rats, and endpoints for incidental oral exposure risk assessments. The potential for increased susceptibility of infants and children from exposure to Thiram was also evaluated as required by the Food Quality Protection Act ( FQPA) of 1996 taking into consideration the submission of a new Multigeneration Reproduction Toxicity study and the 2002 OPP 10X Guidance. This assessment also includes the incorporation of new percent crop treated information, the results of strawberry washing and apple processing studies, revised transfer coefficients, a strawberry dislodgeable foliar residue study, revised use/ usage information, and revised application rates. An acute dietary risk assessment has been conducted using a probabilistic approach and DEEM FCID   Software, up to date usage ( percent crop treated) data, and the hazard endpoint and dose derived from an Acute Neurotoxicity Study in the Rat. Chronic dietary risks were calculated using the dose and endpoints selected from a Combined Chronic Toxicity/ Carcinogenicity Study in rats and the Chronic Oral Toxicity Study in Dogs and a DEEM  FCID   Software, and percent crop treated data. Thiram has been classified as " Not Likely To Be Carcinogenic to Humans." Occupational risks were calculated to reflect potential human exposure via the dermal and inhalation routes. The endpoint and dose selected for short/ intermediate term dermal exposure were derived from a 21 Day Dermal Toxicity Study in Rabbits which reflects the most relevant route and duration of exposure. The endpoint and dose identified in the Multigeneration Reproduction Toxicity Study, the Combined Chronic Toxicity/ Carcinogenicity study in rats and the Chronic Oral Toxicity study in Dogs were used for short and intermediate term incidental oral exposures, while the endpoint and dose from the Chronic Oral Toxicity Study in Dogs and the Combined Chronic Toxicity/ Carcinogenicity study in rats were selected for use in the longterm dermal and all inhalation exposure assessments. Given the current use patterns for thiram, no long term occupational/ residential exposure risks are anticipated. Private homeowners will no longer be able to purchase and handle thiram products. It has been determined, however, that certain turf and animal repellency uses may result in residential/ recreational exposure thereby making it necessary to conduct a residential post application risk assessment. An assessment for the potential exposure to thiram via drinking water was also conducted. Aggregate chronic risks resulting from chronic exposure to thiram via the diet ( food and drinking water only) were assessed since the current use patterns indicate no chronic residential exposures scenarios. are anticipated. An aggregate risk assessment for acute dietary exposures was not conducted since the potential risks from food exposure alone are of concern. As a result, any aggregation of drinking water exposure levels would only serve to increase the reported risks. Short term aggregate exposure risk assessments were also conducted. 4 1.0 EXECUTIVE SUMMARY The database for thiram has been evaluated by the Health Effects Division ( HED) in the Office of Pesticide Programs ( OPP) and a human health risk assessment has been conducted. This assessment supersedes any previous assessments.

Thiram is a dimethyl dithiocarbamate compound used as a fungicide 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 to protect turf from fungal diseases. In addition, thiram is used as an animal repellent to protect crops from damage by rabbits, rodents, and deer. This chemical is registered as a General Use Pesticide ( GUP) by the U. S. Environmental Protection Agency ( EPA). Tolerances for residues in/ on food and feed commodities are currently expressed in terms of residues of thiram ( CFR § 180.132) per se and are established at 7 ppm for apples, peaches, and strawberries. Seed treatments are considered to be nonfood uses and therefore do not require a tolerance.

Thiram is available as dust, dry flowable, wettable powder, flowable concentrate, soluble concentrate, and liquid ( ready to use) formulations. It may be applied to peaches, strawberries, and apples using ground and aerial equipment. For other specialty uses ( i. e. animal repellent) as well as seed treatment, applications may be made using hand held equipment. Thiram may be applied 1  7 days before harvest depending on the crop, geographic location and pest. Recreational exposure to thiram is expected as a result of the use on golf course fairways, greens, and tees. The only registered residential use is as an animal repellent. ( Memorandum from Kylie Rothwell 3/ 20/ 00; Appendix II).

Thiram has a low to moderate acute toxicity profile ( generally Toxicity Category IV to II). The currently available toxicological database for thiram suggests that this chemical has the potential to be a significant neurotoxicant ( in adults and children) as well as a developmental and reproductive toxicant. A 1976 study in rats by Lee and Peters, supports the idea that thiram is a significant neurotoxicant. In that study, Charles River CD rats exposed to thiram in their diet, showed significant signs of neurotoxicity such as ataxia and paralysis of the hind legs along with histopathology changes in the nervous system ( demyelination, macrophage infiltration of the nerve bundle in the sciatic nerve, etc.). The neurotoxic effects of thiram reported in other studies submitted to the Agency by the registrant include lethargy, reduced tail pinch response, no tail pinch response, reduced brain weights, and reduced motor activity. Severe fetal malformations including CNS defects ( anophthalmia, microphthalmia, and hydrocephalus), as well as protruding tongues, unilateral renal agenesis, cleft palate, and reduced ossifications have been reported after in utero exposure to thiram at dose levels that did not cause maternal toxicity. Finally, the chronic toxicity profile indicates that hematology and clinical chemistry parameters as well as the liver, and kidneys are affected after prolonged exposure to this compound. However, after careful consideration and analysis of the currently available toxicity data, it has been determined that thiram can be classified as " Not Likely To Be Carcinogenic to Humans". 5 Based on the toxicity profile, the Health Effects Division ( HED) has selected an endpoint based on neurotoxicity obtained from the Acute Neurotoxicity Study in Rats for use in the acute risk assessment. The endpoint selected for chronic risk assessment is based on changes in hematology, clinical chemistry, incidences fo bile duct hyperplasia and reduction in body weight seen in a Combined Chronic Toxicity/ Carcinogenicity study in Rats in conjunction with elevated cholesterol levels and increased relative liver weight reported in the Chronic Oral Toxicity Study in Dogs. Since thiram has been classified as a chemical " not likely to be carcinogenic to humans", no cancer risk assessment has been conducted. In the case of short/ intermediate term dermal exposure, a 21 Day Dermal Toxicity Study was used to obtain the endpoint ( changes in clinical chemistry, decreased body weight gain, and decreased food consumption) and dose ( 300 mg/ kg/ day) to be used in the risk assessment. Given that the thiram database does not contain any inhalation studies, the endpoint selected for inhalation exposure ( all durations) is based on the same endpoints selected for the chronic risk assessment. These studies were also used in selecting the endpoint and dose for the long term dermal exposure. The current use pattern and registered uses for thiram do not indicate long term occupational/ residential exposure risks. Consequently, long term risk assessments via the dermal and/ or inhalation routes were not conducted. HED also selected endpoints for short and intermediate term incidental oral exposure. The endpoints were based on decreased pup weight and pup weight gain seen in a Multigeneration Reproduction Toxicity study that is supported by data from the Combined Chronic Toxicity/ Carcinogenicity study in Rats and the Chronic Oral Toxicity Study in Dogs Dietary analyses were done using the DEEM FCID   software reflecting the use of anticipated residues based on field trial data and percent crop treated information. Since field trial data were used, these assessment are considered to be somewhat conservative. These assessments could be further refined by using monitoring data if sufficient monitoring data were available. Washing, cooking, and other processing factors were incorporated into the dietary assessment and provide another level of refinement.

A Tier 3 probabilistic acute dietary risk assessment was conducted using an aPAD ( acute Population Adjusted Dose) of 0.005 mg/ kg/ day. For all supported registered commodities, the acute risk estimates are above the Agency's level of concern at the 99.9th exposure percentile for the general U. S. population ( 380% of the aPAD) and all population subgroups. The acute dietary exposure estimate for children 1 2 years old, the highest exposed population subgroup, is 1005% of the aPAD.

When chronic dietary risk assessments were performed, the risks for children 1 2 years of age ( the most highly exposed population subgroup) were 28% of the cPAD which is below the Agency's level of concern. Exposure to the U. S. General Population was 8% of the cPAD.

Thiram is not available for sale or use by homeowner applicators. As such, all residential risks were calculated related to the non residential turf uses that include golfing for adults and toddler exposures in areas that can be treated such as parks and playgrounds. In residential settings, the Agency does not use REIs or other mitigation approaches to limit exposures because they are viewed as impractical and not enforceable. Risk estimates on the day of application are, therefore, 6 the key concern. It should also be noted that for thiram, short term calculations are protective since the exposure and hazard inputs are the same for intermediate term exposures but these exposures would also involve an amortization step. For golfers, MOEs were < 1000, the level of concern, on the day of application but exceeded 1000 within 3 days after application depending upon the data used for the assessment. For toddlers, MOEs on the day of application were all < 10 regardless of the application rate considered or the source of the residue dissipation data.

The residential risk assessment for thiram was based on both Agency inputs that are typically used in lieu of data and also on the strawberry dislodgeable foliar residue study that was conducted in California and Florida. The Agency felt that the strawberry DFR data were appropriate to use for defining decay rates for residues over time and also to establish initial concentrations of residues for the toddler object to mouth assessment. In the strawberry study at both sites, the initial percent dislodgeability was very high ( i. e., ~ 35%) so these data were not used for anything except the object to mouth assessment where exposures are thought to be more similar to the aqueous wash technique than others. It is clear that additional data could be used to refine the residential risk assessment, especially for toddlers, and that these data could include a thiram specific turf transferable residue study and a study that could better define doses received from hand to mouth exposures.

In examining aggregate exposure, EPA takes into account the available and reliable information concerning exposures from pesticide residues in food and other exposures including drinking water and non occupational exposures, e. g., exposure to pesticides used in and around the home ( residential). Risk assessments for aggregate exposure consider short, intermediate and long term ( chronic) exposure scenarios considering the toxic effects which would likely be associated with each exposure duration. There are residential uses of thiram; therefore, the considerations for aggregate exposure are those from food, water, and residential uses. Since conservative modeling was done to estimate concentrations in drinking water, Drinking Water Levels of Comparison ( DWLOCs) were calculated. A DWLOC is a theoretical upper concentration limit for a pesticide in drinking water based on how much of the PAD remains once exposures in food and in the home have been estimated and subtracted.

Aggregate chronic risks resulting from chronic exposure to thiram via dietary ( food and drinking water) exposures were assessed ( given the current use patterns, no chronic residential exposure scenarios are anticipated). To determine the maximum contribution of thiram residues in the drinking water to the aggregate risk that would not exceed the Agency's level of concern, Drinking Water Levels of Comparison ( DWLOCs) are calculated. A comparison of the DWLOC and the EECs ( Estimated Environmental Concentration) obtained from the PRZM/ EXAMS ( surface water) and SCIGROW ( ground water) models indicate that the drinking water residue contribution to the chronic aggregate risk is not of concern.. A short/ intermediate term aggregate risk assessment was also conducted. Short term DWLOCs were calculated based upon average food residues and residential post application exposure to golfing adults who are exposed to thiram after application to turf. These calculations were done using the lower bound application rate of 16.3 lb ai/ A. The registrants have indicated the lower rate is the rate that will be supported. A short/ intermediate term aggregate risk assessment for children and for adults using 7 the highest application rate of 24.5 lbs ai/ A have not been calculated since the MOEs derived from the residential/ recreational risk assessment alone exceed the Agency's level of concern. Consequently any aggregation would only serve to increase the reported risk. Surface and ground water concentrations estimated using modeling are at or below the short term DWLOC for thiram. Consequently, there is no short term exposure concern for drinking water from groundwater or surface water sources.

An aggregate risk assessment for acute dietary exposure was not conducted at this time since the potential risks from food exposure alone are of concern. Any aggregation of drinking water exposure levels would only serve to increase the reported risks. However, an acute DWLOC was calculated assuming no food contribution to the exposure. The results indicated that water alone will not consume the entire risk cup and is not of concern.

Occupational exposure assessments were also conducted for thiram. Since chemical specific handler exposure data are not available, the majority of analyses for short/ intermediate term exposure were performed using the Pesticide Handlers Exposure Database ( PHED).

Generally, most scenarios have risks associated with them that meet or exceed the Agency's uncertainty factors for noncancer risk assessments at some level of personal protection. Current thiram labels typically require that handlers wear long pants, long sleeved shirts, and gloves. Respirators are generally not required. For approximately one half of the scenarios, risks for this personal protection ensemble do not meet Agency risk requirements and additional levels of personal protection are required to achieve Agency risk targets. In fact, in some cases engineering controls such as closed loading systems are needed. Risks can be reduced to target levels for most scenarios that do not meet risk targets with the use of a protection factor 5 respirator ( e. g., a disposable dust/ mist type device). As would be expected, the scenarios with the highest associated risk also have application rates, high acreages/ amounts treated, and/ or the exposures for the scenarios in question are relatively high. Generally, the areas that appear to be problematic include: some loading scenarios for aerial applications, aerial granular application, some handheld equipment use, and a few commercial and on farm seed treatment scenarios. Several data gaps were also identified in many different use areas that include: in furrow/ at plant applications; repellent paint on applications; powered backpack; engineering control data for seed treatment; on farm seed treatment data with different application methods ( e. g., admixture); sprinkler can; and bulb dip applications.

The Agency has determined that workers may be exposed to thiram upon entering occupational areas which have been previously treated with thiram to perform specific work activities in these areas ( e. g., scouting, staking/ tying, irrigating, harvesting); consequently, an occupational postapplication risk assessment was conducted. Current label requirements specify 24 hour REIs. For all but the highest exposure scenarios, risks are not of concern ( i. e., MOEs> 100) at the current REI. The high exposure tasks that are of concern include apple thinning ( MOEs > 100 at 6 7 days), peach thinning on the east coast ( MOE> 100 at 2 days), and high contact turf activities such as sod harvest or golf course maintenance ( MOEs> 100 at 12 21 days). The uncertainties associated with this assessment should also be considered including strawberry data were used for 8 all assessments, the repellency use pattern is not well defined, and no turf specific data were available.

2.0 PHYSICAL/ CHEMICAL PROPERTIES Thiram ( tetramethylthiuram disulfide) is a dimethyl dithiocarbamate used as a fungicide 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 and to protect turf from fungal diseases. In addition, thiram is used as an animal repellent to protect crops from damage by rabbits, rodents, and deer.

Empirical Formula: C 6 H 12 N 2 S 4 Molecular Weight: 240.44 CAS Number: 137 26 8 PC Code: 079801 Thiram is a crystalline solid with a melting point of 142 150

C, bulk density of 0.32 0.35 g/ mL, octanol/ water partition coefficient ( P ow) of 39.5 54.1, and vapor pressure of 1.6 1.8 x 10 5 Torr at 25

C. Thiram is slightly soluble in water ( 0.00165 g/ 100 mL), 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) at 20 25

C.

Most pertinent product chemistry data requirements have been satisfied for the UCB 98.5% T and the Gustafson 97.5% T; additional data are required for OPPTS 830.8314 and 7050 for the UCB 98.5% T, and for OPPTS 830.6314, 6317, 6320, and 7050 for the Gustafson 97.5% T. All data requirements for the Prochimie 98.5% T produced by an unidentified Spanish source remain unfulfilled. The Agency has determined that data for certain physical/ chemical data requirements ( OPPTS 830.7370, 7550, 7840, and 7950) may be shared among Thiram Task Force members; however, Prochimie must demonstrate that the new source product is substantially similar to thiram products registered by the other Task Force members. Provided that the registrants submit the data required in the attached data summary tables ( refer to the Product Chemistry Chapter) for the 98.5% and 97.5% MPs, and either certify that the suppliers of beginning materials and the manufacturing processes for the thiram MPs have not changed since the last comprehensive product chemistry reviews or submit complete updated product chemistry data packages, CBRS has no objections to the reregistration of thiram with respect to product chemistry data requirements.

For further details, refer to the Product and Residue Chemistry Chapters for the Thiram Reregistration Eligibility Decision Document ( Memorandum by F. Fort 4/ 17/ 00; Appendix III).

3.0 HAZARD CHARACTERIZATION 9 3.1 HAZARD PROFILE The toxicology data for thiram is considered to be adequate to support the current Reregistration Eligibility Decision ( RED) and has been evaluated by the Health Effects Division ( HED) in the Office of Pesticide Programs ( OPP). Thiram is a neurotoxicant which can also act as a developmental toxicant. The neurotoxic effects of thiram include lethargy, reduced tail pinch response, no tail pinch response, reduced brain weights, and reduced motor activity. Severe fetal malformations including CNS defects ( anophthalmia, microphthalmia, and hydrocephalus), as well as protruding tongues, unilateral renal agenesis, cleft palate, and reduced ossifications have been reported after in utero exposure to thiram at dose levels that did not cause maternal toxicity.

A Developmental Neuroxicity Study has been recommended by the Hazard Identification Assessment Review Committee ( HIARC) to provide further understanding of the impact thiram exposure may have on the developing nervous system ( Report of the Hazard Identification Assessment Review Committee; 3/ 4/ 99; and 4/ 14/ 03.) The HIARC has also recommended submission of a Cholinesterase Activity Assessment Screening Assay based on concerns for potential cholinesterase activity inhibition by thiram as was seen in a structurally related dithiocarbamate. Also, given the expected use patterns for this compound and the lack of inhalation studies appropriate for risk assessments, a 28 day inhalation Toxicity Study including appropriate assessments of neurotoxicity potential is required.

Thiram has a low to moderate acute toxicity profile; the acute oral LD 50 = 2.6 g/ kg b. w. and the acute dermal LD 50  2.0 g/ kg b. w ( Toxicity Category III). In an acute inhalation study, the LC 50 for thiram was established at  0.1 mg/ L ( the most concentrated suspension that could be nebulized). As a result, thiram is considered to be a Toxicity Category II chemical via the inhalation route ( i. e. moderately toxic). Thiram is a moderate eye irritant ( Toxicity Category II), a slight dermal irritant ( Toxicity Category IV), and a moderate skin sensitizer.

The subchronic toxicity profile for thiram indicates that hematology, clinical chemistry and body weight are the parameters affected after subchronic exposure to the compound for all species evaluated.

The chronic toxicity profile for thiram indicates that the liver, blood and urinary system are the target organs for this chemical. In a Combined Chronic/ Oncogenicity Study in Rats, effects were seen at a dose level of 7.3 and 8.9 mg/ kg/ day for males and females, respectively. The effects described at these dose levels included changes in hematology parameters, increased incidence of bile duct hyperplasia, and reduction in body weight gain. At higher doses in this study, the severity of the toxicity described above was increased and other signs of toxicity such as an increased incidence in extramedullary hematopoiesis of the liver, and changes in clinical chemistry parameters were reported. In 10 a Chronic Oral Toxicity Study in Dogs, effects were seen at doses > 2.61 mg/ kg/ day. Toxicity at this dose level was manifested as elevated cholesterol levels and increases in liver to body weight ratio. At higher dose levels, the signs of toxicity were more severe. Signs of toxicity in a carcinogenicity study in mice were first reported at a dose level of 24 mg/ kg/ day for males and included decreases in body weight gain, anemia, as well as nonneoplastic lesions in the eyes, non glandular stomach and urinary bladder. At higher doses, the severity of these signs of toxicity was greater. In addition, decreases in RBC counts, hemoglobin, and hematocrit levels as well as increased hemosiderin in the spleen were seen at the higher doses.

The severity of developmental toxicity in the Thiram database varied considerably. In one Developmental Toxicity Study using Wistar rats, severe fetal malformations including CNS defects ( anophthalmia, microphthalmia, and hydrocephalus) as well as protruding tongues, unilateral renal agenesis, cleft palate, and reduced ossification were reported at doses as low as 12.5 mg/ kg/ day which was the NOAEL for maternal toxicity. In a subsequent Developmental Toxicity Study using Sprague Dawley rats, the evidence of developmental toxicity was not as severe ( retarded growth, reduced ossification, and a rudimentary 13th rib). Furthermore, a developmental NOAEL of 7.5 mg/ kg/ day was established in this latter study. The potential impact of thiram exposure on development in rabbits was examined in three studies [ 1 Range Finding Study, 2 Definitive Studies]. Independently, none of these studies is acceptable for regulatory purposes. However, when considered as a group, they provide sufficient information to assess the potential developmental toxicity of the test substance in rabbits. The results of these studies showed no developmental toxicity in rabbits in the absence of maternal toxicity. While maternal weight loss and decreased fetal weights were reported at the 10 mg/ kg/ day dose in the range finding study, in the definitive study no maternal or developmental effects were noted at this dose level ( highest dose tested). However, at the highest dose tested in the range finding study ( 20 mg/ kg/ day), maternal death and complete litter loss were seen.

In addition to the studies submitted to the Agency, the IARC profile for thiram ( 1991) provides further evidence of thiram's potential to act as a developmental toxicant. This report cites embryolethality and embryotoxicity in rats and hamsters and malformations in mice and hamsters. Furthermore, in a developmental toxicity study by Robens ( 1969), treatment at a dose level of 100 mg/ kg resulted in CNS malformations ( exencephaly) thus providing additional evidence of thiram's potential for developmental toxicity.

While severe developmental effects were noted in a guideline, albeit unacceptable, study in rats and in the published literature, effects noted in the acceptable/ guideline studies were less severe ( reduced ossification and rudimentary 13th rib), occurred at doses where maternal toxicity was evident, or in the case of rabbits occurred at maternally lethal doses. 11 Consequently, no quantitative or qualitative susceptibility was noted in the acceptable/ guideline Developmental Toxicity Studies submitted to the Agency for review.

Similarly, the results of two Multigeneration Reproduction Toxicity Studies in rats did not reveal increased susceptibility of the young after in utero and perinatal exposure to Thiram. In both studies, the effects noted at the LOAEL in the offspring and parental animals were limited to decreases in body weight and/ or body weight gain. It is noteworthy, however, that although reproductive parameters were not affected in the two guideline Multigeneration Reproduction Toxicity Studies in rats, a 1996 study by Stoker et al. suggests that thiram may act as an endocrine disruptor by interfering with the proestrus surge of lutenizing hormone. Consequently, the possible impact of thiram in disturbing the lutenizing hormone surge has not been thoroughly explored, and the current design of the guideline studies could not detect this effect.

The mutagenicity database for thiram suggests that this chemical is a clastogen. It does not, however, induce unscheduled DNA synthesis nor does it increase the mutation frequency at the HPRT locus.

The thiram database contains two Acute Neurotoxicity Studies and one Subchronic Neurotoxicity Study. All three of these studies provide evidence that this chemical has the potential to be a significant neurotoxicant in adults. In the Acute Neurotoxicity Studies in Rats, Functional Observational Battery ( FOB) effects such as lethargy, lower temperature, reduced startle response and no tail pinch response were reported as well as reduced motor activity, and decreased brain weights. Reduced motor activity was observed at 3 ½ hours, and 7 and 14 days after treatment with the test article suggesting that thiram's effects on the nervous system were not readily reversed. In the Subchronic Neurotoxicity Study, rats exposed to thiram in their diet exhibited a statistically significant increase in the incidence of rearing events and hyperactivity in females and males; with the females being affected at a lower dose level than males. A statistically significant decrease in body weight in both males and females was also observed. Further evidence of the potential neurotoxicant properties of thiram is provided in the open literature. A 1976 study in rats by Lee and Peters supports the idea that thiram is a significant neurotoxicant. In that study, Charles River CD rats exposed to thiram in their diet, showed significant signs of neurotoxicity such as ataxia and paralysis of the hind legs along with histopathology changes in the nervous system ( demyelination, macrophage infiltration of the nerve bundle in the sciatic nerve etc.).

In a report dated June 10, 1997 the RfD Committee recommended that a Developmental Neurotoxicity Study be conducted and submitted for consideration by the Agency. That recommendation was based on the weight of the evidence including: 1) findings of CNS defects ( anophthalmia, microphthalmia, and hydrocephalus) in the Developmental Study in rats ( MRID 00259810); and 2) neurotoxic effects in the Acute and Subchronic Neurotoxicity Study ( MRID 42912401 and 43012701, respectively). This study has not 12 been submitted to the Agency for review and is, therefore, still outstanding. In addition, the Hazard Identification Assessment Review Committee ( HIARC) has recommended submission of a Cholinesterase Activity Assessment Screening Assay based on concerns for potential cholinesterase activity inhibition by thiram as was seen in ziram, a structurally related dithiocarbamate.

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 ( 14CO 2, carbamyl sulfide, and carbon disulfide). Identification of 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.

The dermal absorption factor was calculated to be 1% based on the LOAELs ( Lowest Observed Adverse Effect Levels) in a Range Finding Study for the Developmental Toxicity Study in rabbits and the 21 day Dermal Toxicity Study in rabbits. The Range Finding Study was used in conjunction with two definitive studies to establish the developmental rabbit LOAEL since no LOAEL could be established in either of the definitive studies. The LOAEL for the Range Finding Study was established at 10 mg/ kg/ day based on maternal weight loss coupled with a marked decrease in fetal weight. Thus, the LOAEL for the Developmental Range Finding Study in rabbits ( 10 mg/ kg/ day) and the LOAEL for the 21 Day Dermal Toxicity Study in Rabbits ( 1000 mg/ kg/ day) are based on decreased body weight gain ( common endpoint) ( Dermal Absorption Factor; Report of the Hazard Identification Assessment Review Committee; 1/ 18/ 00; Appendix VI).

It should be noted that intolerance to alcohol has been reported in workers exposed to thiram ( e. g. dizziness, hypotension, palpitations, etc.). This effect may be due to blocking of the oxidation of acetaldehyde ( caused by the inhibition of the enzyme acetaldehyde dehydrogenase). Interestingly, this is the mode of action of the drug Antabuse ( a diethyl homologue of thiram) which is used in aversion therapy to treat alcoholism.

For further details of the hazard component for the thiram risk assessment, refer to the Thiram Toxicology Disciplinary Chapter for the Reregistration Eligibility Decision Document by E. Mendez dated 3/ 5/ 00 ( Appendix VII).

3.2 FQPA SAFETY FACTOR Database Uncertainty Factor 13 In accordance with the 2002, OPP Guidance Document on Determination of the Appropriate FQPA Safety Factor( s) in Tolerance Assessment, the HIARC determined that a 10X database uncertainty factor ( UF DB) is required. After careful consideration of the thiram toxicological database, the HIARC concluded that there was insufficient evidence to support the reduction or removal of the default 10X factor. The following issues were considered by the committee during its deliberation:

° It is assumed that the DNT study will be conducted at dose levels similar to those used in the Reproduction Toxicity Study in rats ( 1.4, 4.2, and 12.2 mg/ kg/ day) in which the offspring NOAEL is 1.4 mg/ kg/ day and the LOAEL is 4.2 mg/ kg/ day based on decreases in pup weight and pup weight gain. ° It is possible that the results of the DNT study could impact the doses currently used for regulatory purposes since the NOAELs used for risk assessment ( 5 mg/ kg/ day for acute and 1.5 mg/ kg/ day for short, intermediate, and chronic assessments) are comparable to or higher than the offspring NOAEL in the rat reproduction study conducted with thiram ( 1.4 mg/ kg/ day). ° In light of the available information, HIARC does not have sufficient reliable data justifying selection of a safety factor for the protection of infants and children lower than the default value of 10X. Consequently, a UF DB of 10X will be applied to all dietary and residential exposure scenarios to account for the lack of a DNT study in the thiram database.

Degree of Concern Analysis and Residual Uncertainties Since there is quantitative evidence of increased susceptibility of the young following exposure to Thiram in the ( unacceptable) prenatal developmental study in rats and reported in the open literature, HIARC performed a Degree of Concern Analysis to: 1) determine the level of concern for the effects observed when considered in the context of all available toxicity data; and 2) identify any residual uncertainties after establishing toxicity endpoints and traditional uncertainty factors to be used in the risk assessment of this chemical. If residual uncertainties are identified, HIARC examines whether these residual uncertainties can be addressed by a special FQPA safety factor and, if so, the size of the factor needed. The results of the HIARC Degree of Concern analysis for Thiram follow.

Although there is a high degree of concern for the quantitative susceptibility seen in the unacceptable Developmental Toxicity Study in rats, there is no residual uncertainty since the results were not replicated in a subsequent acceptable developmental study in rats and when doses are used for regulatory purposes are taken into consideration. Concern for the potential developmental toxicity of thiram is also raised by reports in the published literature. However, the level of concern is low when the doses and endpoints selected for regulatory purposes are taken into consideration. This determination was based on a weight of the evidence analysis that takes into consideration the following factors: 14  No evidence of increased quantitative/ qualitative susceptibility in the available acceptable/ guideline studies .

 Clear NOAELs/ LOAELs have been identified for the effects of concern.

 Dose response relationships for the effects of concern are well characterized.

 The doses used for regulatory purposes are at least 10X lower than the doses where developmental and reproductive toxicity effects were reported in the published literature.

Special FQPA Safety Factor( s):

The HIARC concluded that the Special FQPA Factor could be reduced to 1X. This conclusion is based on the outcome of the degree of concern analysis that failed to identify any residual uncertainties.

The Special FQPA Safety Factor recommended by the HIARC assumes that the exposure databases ( dietary food, drinking water, and residential) are complete and that the risk assessment for each potential exposure scenario includes all metabolites and/ or degradates of concern and does not underestimate the potential risk for infants and children.

3.3 DOSE RESPONSE AND HAZARD ENDPOINT SELECTION The endpoints and doses selected to conduct various risk assessments are described below. The acute toxicity endpoints, utilized to establish the appropriate labeling parameters, are summarized in Table 1. Table 2 summarizes the doses and endpoints selected for use in this human health risk assessment.

 Acute Toxicity. Thiram has a low to moderate acute toxicity profile; the acute oral LD 50 = 2.6 g/ kg b. w. and the acute dermal LD 50  2.0 g/ kg b. w ( Toxicity Category III). The LC 50 for thiram was established at  0.1 mg/ L ( the most concentrated suspension that could be nebulized) ( Toxicity Category II). Thiram is a moderate eye irritant ( Toxicity Category II), a slight dermal irritant ( Toxicity Category IV), and a moderate skin sensitizer.

 A No Observed Adverse Effect Level ( NOAEL) of 5 mg/ kg b. w. from an Acute Neurotoxicity Study was selected for acute dietary risk assessment. Lethargy, reduced tail pinch response, reduced brain weights, and reduced motor activity were the effects seen at the Lowest Observed Adverse Effect Level ( LOAEL) of 150 mg/ kg b. w. Acute dietary risk assessments have been conducted using this study. The uncertainty factors ( UF) applied were 10x for intraspecies variation and 10x for interspecies extrapolation and 10X for database UF due to lack of a DNT study which result in a hazard based UF of 1000x. Consequently, the calculated acute RfD is 0.005 mg/ kg b. w.

Chronic Dietary. A Combined Chronic Toxicity/ Carcinogenicity Study in rats 15 and Chronic Oral Toxicity Study in dogs were used to conduct this risk assessment. These studies are considered to be co critical studies for this risk assessment. Although the Chronic Oral Toxicity Study in dogs has a lower NOAEL ( 0.84 mg/ kg/ day) than the Combined Chronic/ Carcinogenicity Study in rats ( 1.5 mg/ kg/ day), the use of the dose in the rat study would address the effects of concern seen in the dog study ( elevated cholesterol levels and increased liver weights) since they were noted at a higher dose ( 2.6 mg/ kg/ day) than the one selected for regulatory purposes ( 1.5 mg/ kg/ day).

Similarly, use of these studies to establish the cRfD would address the effects of concern noted in the developmental and reproduction toxicity studies. While the NOAELs for all acceptable/ guideline developmental studies are higher than the NOAEL selected for this risk assessment, the lowest NOAEL ( 1.4 mg/ kg/ day) for a Multigeneration Reproduction Toxicity Study in rats is equivalent to the 1.5 mg/ kg/ day in the Combined Chronic Toxicity/ Carcinogenicity Study ( the difference of 0.1 mg/ kg/ day in these studies is within the margin of error for the estimation of compound intake from dietary administration).

In addition to the 10X factor for interspecies extrapolation and 10X factor for intraspecies variation, a 10X UF DB factor is applied to this risk assessment to account for the lack of a DNT study as discussed earlier in this assessment.

Carcinogenicity. Thiram is not considered to be carcinogenic. The incidence of combined hepatocellular adenomas and/ or carcinomas revealed that there was no significant pairwise ( p= 0.05) increases in these tumors at any dose. In addition, although there were no historical control information from the laboratory on combined liver adenomas and carcinomas, the high dose males were at the high end of the adenoma historical controls, while the high dose females were slightly outside. Similarly, the thyroid c cell combined adenomas and/ or carcinomas showed no significant trends or pairwise increases ( p= 0.05) in either sex and the incidences for all doses were within the historical controls. Generally, for commonly occurring tumors such as these, pairwise significance between the controls and treated groups are necessary before a pesticide needs to go to the CARC. ( Cancer Assessment Review Committee). Consequently, it has been determined that thiram does not need to go to the CARC and that it can be classified as " Not Likely To Be Carcinogenic to Humans". Consequently, a cancer risk assessment was not conducted.

Incidental Oral Exposure: Short/ Intermediate Term. Three studies, Chronic Oral Toxicity/ Carcinogenicity in rats, Chronic Oral Toxicity Study in dogs, and the Multigeneration Reproduction Toxicity Study in rats were considered when determining the dose and endpoint for these risk assessments. The NOAEL of 1.5 mg/ kg/ day is based on changes in hematology, clinical chemistry , incidences of bile duct hyperplasia, and reduction in mean body weight gain seen at 7.9 mg/ kg/ day in conjunction with decreases in pup weight and pup weight gain noted 16 in the Multigeneration Reproduction Toxicity Study at 4.2 mg/ kg/ day. The dose and endpoint selected for this risk assessment are relevant since they evaluate potential effects of thiram exposure on the population of concern ( toddlers) during the appropriate time of exposure. Although the Combined Chronic Toxicity/ Carcinogenicity Study in rats and Chronic Oral Toxicity Study in dogs are of a longer duration than the duration of exposure in this risk assessment, the NOAEL in the Chronic Rat Study ( 1.5 mg/ kg/ day) is equivalent to the offspring NOAEL ( 1.4 mg/ kg/ day) which evaluates the population of concern ( toddlers) during the appropriate time of exposure. The NOAELs in these studies are equivalent since the difference of 0.1 mg/ kg/ day is within the margin of error for the estimation of compound intake after dietary administration. Use of the Combined Chronic Toxicity/ Carcinogenicity Study in rats addresses the effects of concern reported in the Chronic Oral Toxicity Study in dogs.

Short/ Intermediate Term Dermal. The rabbit 21 Day Dermal Toxicity Study NOAEL of 300 mg/ kg/ day has been selected for these risk assessments. In this study, changes in clinical chemistry and decreases in body weight gain and food consumption were reported at the LOAEL of 1000 mg/ kg/ day. MOEs less than 1000 are of concern for residential assessments based on intraspecies variability ( 10x), interspecies extrapolation ( 10x) and the database uncertainty factor ( 10x). No database uncetainty factor is applied for occupational assessment; therefore, the MOEs less than100 are of concern.

Long Term Dermal and Inhalation ( All Durations) The Chronic Oral Toxicity Study in Dogs and the Combined Chronic Toxicity/ Carcinogenicity Study in Rats were selected as co critical studies for use in this risk assessment. The LOAEL of 7.3 mg/ kg/ day was based changes in hematology, clinical chemistry , incidences of bile duct hyperplasia, and reduction in mean body weight gain seen at 7.9 mg/ kg/ day in conjunction with elevated cholesterol levels and increased liver weights reported in the Chronic Oral Toxicity Study in Dogs at 2.6 mg/ kg/ day. A default inhalation absorption factor of 100% was assumed.

Table 1. Acute Toxicity Data on Thiram Guideline No./ Study Type MRID No. Results Toxicity Category 870.1100 Acute oral toxicity 00163854 LD50 = 2.6 g/ kg/ day III 870.1200 Acute dermal toxicity 00259250 LD50

2.0 g/ kg/ day III 870.1300 Acute inhalation toxicity 00165855 LC50

0.1 mg/ L II 870.2400 Acute eye irritation 00259250 Moderate eye irritant II 870.2500 Acute dermal irritation 00259250 Very slight dermal irritant IV 870.2600 Skin sensitization 00153068 Moderate skin sensitizer 17 Table 2. Summary of Toxicological Dose and Endpoints for Thiram Exposure Scenario Dose Used in Risk Assessment, UF Special FQPA Safety Factor* and Level of Concern for Risk Assessment Study and Toxicological Effects Acute Dietary ( All Populations) NOAEL = 5 mg/ kg/ day UF = 1000* Acute RfD = 0.005 mg/ kg/ day FQPA SF = 1 aPAD = acute RfD FQPA SF = 0.005 mg/ kg/ day Acute Neurotoxicity Study  Rat 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 Chronic Dietary ( All populations) NOAEL= 1.5 mg/ kg/ day UF = 1000 Chronic RfD = 0.0015 mg/ kg/ day FQPA SF = 1 cPAD = chronic RfD FQPA SF = 0.0015 mg/ kg/ day Combined Chronic Toxicity/ Carcinogenicity Study  RAT & Chronic Oral Toxicity Study  DOG LOAEL = 7.3 based on changes in hematology, clinical chemistry , incidences of bile duct hyperplasia, and reduction in mean body weight gain seen at 7.9 mg/ kg/ day in conjunction with elevated cholesterol levels and increased liver weights reported in the Chronic Oral Toxicity Study in Dogs at 2.6 mg/ kg/ day Short Term Incidental Oral ( 1 30 days) NOAEL= 1.5 mg/ kg/ day Residential LOC for MOE = 1000 Occupational = NA Multigeneration Reproduction Toxicity Study and Combined Chronic Toxicity/ Carcinogenicity Study  RAT & Chronic Oral Toxicity Study  DOG LOAEL = 4.7 mg/ kg/ day based on decreased pup weight/ pup weight gain.

Intermediate Term Incidental Oral ( 1 6 months) NOAEL= 1.5 mg/ kg/ day Residential LOC for MOE = 1000 Occupational = NA Multigeneration Reproduction Toxicity Study and Combined Chronic Toxicity/ Carcinogenicity Study  RAT & Chronic Oral Toxicity Study  DOG LOAEL = 4.7 mg/ kg/ day based on decreased pup weight/ pup weight gain.

Short Term Dermal ( 1 to 30 days) Dermal ( or oral) study NOAEL= 300 mg/ kg/ day Residential LOC for MOE = 1000 Occupational LOC for MOE = 100 21 Day Dermal Toxicity/ Rabbit LOAEL = 1000 mg/ kg/ day based on decreases in body weight and food consumption as well as alterations in clinical chemistry. Exposure Scenario Dose Used in Risk Assessment, UF Special FQPA Safety Factor* and Level of Concern for Risk Assessment Study and Toxicological Effects 18 Intermediate Term Dermal ( 1 to 6 months) Dermal ( or oral) study NOAEL= 300 mg/ kg/ day Residential LOC for MOE = 1000 Occupational LOC for MOE = 100 21 Day Dermal Toxicity/ Rabbit LOAEL = 1000 mg/ kg/ day based on decreases in body weight and food consumption as well as alterations in clinical chemistry.

Long Term Dermal (> 6 months) Dermal ( or oral) study NOAEL= 1.5 mg/ kg/ day ( dermal absorption rate = 1% when appropriate) Residential LOC for MOE = 1000 Occupational LOC for MOE = 100 Combined Chronic Toxicity/ Carcinogenicity Study  RAT & Chronic Oral Toxicity Study  DOG LOAEL = 7.3 based on changes in hematology, clinical chemistry , incidences of bile duct hyperplasia, and reduction in mean body weight gain seen at 7.9 mg/ kg/ day in conjunction with elevated cholesterol levels and increased liver weights reported in the Chronic Oral Toxicity Study in Dogs at 2.6 mg/ kg/ day Inhalation ( All durations) Inhalation ( or oral) study NOAEL= 1.5 mg/ kg/ day ( inhalation absorption rate = 100%) Residential LOC for MOE = 1000 Occupational LOC for MOE = 100 Combined Chronic Toxicity/ Carcinogenicity Study  RAT & Chronic Oral Toxicity Study  DOG LOAEL = 7.3 based on changes in hematology, clinical chemistry , incidences of bile duct hyperplasia, and reduction in mean body weight gain seen at 7.9 mg/ kg/ day in conjunction with elevated cholesterol levels and increased liver weights reported in the Chronic Oral Toxicity Study in Dogs at 2.6 mg/ kg/ day.

Cancer ( oral, dermal, inhalation) NOT LIKELY TO BE CARCINOGENIC TO HUMANS * A database uncertainty factor of 10X was applied in addition to the usual inter and intraspecies safety factor. UF = uncertainty factor, FQPA SF = Special FQPA safety factor, NOAEL = no observed adverse effect level, LOAEL = lowest observed adverse effect level, PAD = population adjusted dose ( a = acute, c = chronic) RfD = reference dose, MOE = margin of exposure, LOC = level of concern, NA = Not Applicable 4.0 DIETARY EXPOSURE AND RISK ASSESSMENT 4.1 Summary of Registered Uses Thiram [ tetramethyl thiuram disulfide] is a fungicide registered for foliar treatments of apples, peaches, and strawberries and for seed treatment prior to planting of numerous vegetable and field crops. Foliar treatments with thiram on apples, peaches, and strawberries are the only food/ feed uses being supported for reregistration. Seed treatment uses of thiram have been determined to be a nonfood use based on metabolism 19 studies reflecting this type of treatment on three diverse crop groups.

The reregistration of thiram is being supported by the Thiram Task Force, with members consisting of Gustafson, Inc., Prochimie, and UCB Chemicals Corporation. The Task Force intends to support seed treatment uses only. UCB Chemical Corporation intends to support foliar uses on apples, peaches, and strawberries. Thiram formulations registered to UCB Chemicals for foliar treatments include the dry flowable ( DF) and wettable powder ( WP). Thiram formulations registered to the Thiram Task Force for seed treatments include dust ( D), wettable powder/ dust ( WP/ D), dry flowable ( DF), flowable concentrate ( FlC), soluble concentrate ( SC), and liquid ready to use ( RTU).

4.2 Dietary Exposure Tolerances for residues in/ on food and feed commodities are currently expressed in terms of residues of thiram ( tetramethyl thiuram disulfide) per se [ CFR § 180.132] and are established at 7 ppm for apples, strawberries, and peaches ( the only feed/ food crops being supported for reregistration). There are no established or proposed Codex MRLs for thiram residues; therefore, there are no issues of compatibility with respect to current U. S. tolerances and Codex MRLs. Tolerances have been reassessed for the HED Chapter of the RED. Adequate residue data have been submitted and evaluated to support the proposed uses of thiram on apples and strawberries, and no additional field trials are required for reregistration. The residue data suggest that a higher tolerance for residues of thiram in/ on apples and strawberries may be required for reregistration. The available data indicate that a tolerance of 9 ppm would be adequate.

For apples, the product label for the 65% WP formulation ( EPA Reg. No. 45728 24) must be modified to specify PHIs of 14 and 7 days for apples grown East and West of the Rockies, respectively. In the case of strawberries, there are discrepancies that must be clarified. The proposed 65% WP label shows a rate that is exclusive to Santa Maria and Fallbrook counties; however, our research has found that these are cities, not counties in California ( Santa Barbara and San Diego counties, respectively). Additionally, the registrant must submit additional data to support their claim that there is no accumulation of residues between crop cycles. Finally, the available residue data for peaches are inadequate to satisfy reregistration requirements because of insufficient geographic representation. Three additional field trials are required, and these trials must be conducted in Regions 2 ( 1 trials) and 10 ( 2 trials). The required trials should depict residues of thiram in/ on peaches according to the maximum use pattern being considered for reregistration.

Residue analytical methods for the determination of thiram residues of concern in animal commodities are not available because tolerances for animal commodities have not been established. If the requested ruminant feeding study suggests that tolerances in milk and edible tissues of ruminants are needed ( due to the feeding of apple pomace), the registrant will be required to develop enforcement and data collection methods capable of determining thiram residues of concern. 20 The Agency has issued several documents summarizing the status of available thiram residue chemistry data for the purpose of reregistration. They include the Reregistration Standard Guidance Document dated 6/ 29/ 84, the Residue Chemistry Science Chapter of the Guidance Document dated 3/ 2/ 84, and the Update to the Residue Chemistry Chapter 21 of the Thiram Reregistration Standard dated 7/ 25/ 91. These documents summarized the regulatory conclusions based on available residue chemistry data, and specified the additional data required for reregistration. Several data submissions have been received and evaluated since the Update; a few submissions are still under review by the Agency. Although the qualitative nature of the residue in plants and animals remains inadequately understood, HED has no objection to proceeding with the subject Thiram RED and with risk assessments given that the current common moiety plant method would likely include the residues of toxicological concern. Though the currently available methodology cannot detect thiram specific metabolites, it does detect CS 2,  a common metabolite for thiram and other dithiocarbamates. As a result, the dietary risk estimates are considered conservative since they may include CS 2 from chemicals or sources other than thiram.

The Pesticide Analytical Manual ( PAM) Vol. II lists a colorimetric method for plant commodities ( Method I) and additional methods ( Methods II IV and Method A for dithiocarbamates) based on the decomposition of dithiocarbamates with release of carbon disulfide and the corresponding amine. Consequently, there are no FDA or PDP monitoring data available for thiram. Field trial data are available on all crops. Therefore, field trial data were used to calculate the anticipated residue ( AR) values for refinement of dietary exposure scenarios. Still, the dietary analyses conducted for thiram are considered to be conservative. These assessments were conducted based solely on field trial data and could be substantially refined if monitoring data were available. Some refinement was accomplished by the submission of strawberry washing and apple processing/ washing studies.

OPP's Biological and Economic Analysis Division ( BEAD) provided information ( F. Hernandez memorandum, 10/ 15/ 02) on the percent of crop treated (% CT). For the chronic analysis, the weighted average % CT was incorporated; for the acute analysis, the estimated maximum % CT was used. In acute analyses the adjustment for % CT is incorporated in the residue distribution files ( RDFs) via addition of zero residue values corresponding to the % crop not treated. For blended commodities, the % CT is incorporated into an average residue value. For the chronic analyses, % CT is entered as adjustment factor # 2 in DEEM FCID   .

HED conducts dietary risk assessments using the Dietary Exposure Evaluation Model ( DEEM FCID   ) Software, which incorporates consumption data generated in USDA's Continuing Surveys of Food Intakes by Individuals ( CSFII), 1994 1996 and 1998. For acute dietary risk assessments, the entire distribution of consumption events for individuals is multiplied by a distribution of residues ( probabilistic analysis, referred to as " Monte Carlo" ) to obtain a distribution of exposures in mg/ kg/ day. For chronic dietary risk assessments, the three day average of consumption for each sub population is combined with average residues in commodities to determine average exposures in mg/ kg/ day. All commodities ( strawberries, peaches, apples) are considered high consumption food items for infants and children. There are no established or proposed Codex MRLs for thiram residues; therefore, there are no issues of compatibility with 22 respect to current U. S. tolerances and Codex MRLs.

For the probabilistic acute dietary exposure analysis, the entire distribution of field trial data was used to generate residue distribution files ( RDFs) for commodities that are considered to be not blended or partially blended. For blended commodities, the average field trial residues incorporating the likely maximum % CT were used as point estimates. Chronic anticipated residues ( ARs) were also calculated from field trial data. An average of the field trial residues was used.

Detailed information regarding how the ARs were calculated can be found in the F. Fort memorandum dated 4/ 17/ 00 ( Appendix III). The details of the DEEM FCIDTM analyses can be found in the F. Fort memorandum dated 4/ 30/ 03 ( IX).

4.2.1 Acute Dietary Exposure Assessment.

The refined ( Tier 3) acute probabilistic dietary exposure and risk estimates at the 99.9th percentile of exposure are of concern for the general U. S. population ( 380% of the aPAD) and all population subgroups. The acute dietary exposure estimate for children 1 2 years old, the highest exposed population subgroup, is 1005% of the aPAD at the 99.9th percentile. ( Table 3). Additional analyses were conducted to determine the contribution of each commodity to the dietary risk. These sensitivity analyses indicate that both strawberries ( uncooked) and apples ( uncooked) are significant contributors to the dietary risk for children 1  2 years old ( Table 5).

Table 3. Results of Acute Dietary Exposure Analysis 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 0.005 0.000339 7 0.004210 84 0.019022 380 All Infants (< 1 year old) 0.005 0.000060 1 0.004246 85 0.021088 420 Children 1 2 years old 0.005 0.001310 26 0.016274 330 0.050268 1000 Children 3 5 years old 0.005 0.001134 23 0.012079 240 0.043316 870 Children 6 12 years old 0.005 0.000584 12 0.007214 140 0.030360 610 Youth 13 19 years old 0.005 0.000173 3 0.003464 69 0.013902 280 Adults 20 49 years old 0.005 0.000150 3 0.003120 62 0.012330 250 Females 13 49 years old 0.005 0.000193 4 0.003776 76 0.014078 280 Adults 50+ years old 0.005 0.000415 8 0003583. 72 0.011278 230 4.2.2 Chronic Dietary Exposure Assessment 23 Estimated chronic dietary exposure and risk are below the Agency's level of concern, with  28% of the chronic Population Adjusted Dose ( cPAD) consumed for all population subgroups. The most highly exposed population subgroup was children 1 2 years old, with 28 % cPAD consumed. Exposure to the U. S. General Population was 8% cPAD ( Table 4).

Table 4. Results of Chronic Dietary Exposure Analysis Population Subgroup cPAD ( mg/ kg/ day) Exposure ( mg/ kg/ day) % cPAD General U. S. Population 0.0015 0.000121 8 All Infants (< 1 year old) 0.0015 0.000102 7 Children 1 2 years old 0.0015 0.000422 28 Children 3 5 years old 0.0015 0.000336 22 Children 6 12 years old 0.0015 0.000205 14 Youth 13 19 years old 0.0015 0.000087 6 Adults 20 49 years old 0.0015 0.000079 5 Females 13 49 years old 0.0015 0.000095 6 Adults 50+ years old 0.0015 0.000099 7 The dietary analyses conducted for thiram are considered to be conservative. These assessments were conducted based solely on field trial data and could be substantially refined if monitoring data were available. 24 Table 5. Acute Sensitivity Analyses ( 99.9% ile)

Population Subgroup All commodities Excluding Apple ( Strawberries and Peaches Only) Excluding Strawberry ( Apples and Peaches Only) Excluding Apple and Strawberries ( Peaches Only) Excluding Apples and Peaches ( Strawberries Only) Excluding Strawberries and Peaches ( Apples Only)

Dietary Exposure ( mg/ kg/ day) % aPAD Dietary Exposure ( mg/ kg/ day) % aPAD Dietary Exposure ( mg/ kg/ day) % aPAD Dietary Exposure ( mg/ kg/ day) % aPAD Dietary Exposure ( mg/ kg/ day) % aPAD Dietary Exposure ( mg/ kg/ day) % aPAD General U. S.

Population 0.019022 380 0.014792 296 0.011123 222 0.000063 1 0.014626 292 0.010841 217 All Infants (< 1 year old) 0.021088 422 0.008407 168 0.019577 392 0.001280 26 0.007302 146 0.019630 393 Children 1 2 years old 0.050268 1005 0.041105 822 0.036368 727 0.000621 12 0.040380 808 0.036228 725 Children 3 5 years old 0.043316 866 0.030811 616 0.033877 678 0.000238 5 0.030420 608 0.033545 671 Children 6 12 years old 0.030360 607 0.024356 487 0.018807 376 0.000129 3 0.024158 483 0.018479 370 Youth 13 19 years old 0.013902 278 0.011049 221 0.007772 155 0.000014 < 1 0.011196 224 0.007248 145 Adults 20 49 years old 0.012330 246 0.010700 214 0.007033 141 0.000014 < 1 0.010573 211 0.006827 137 Females 13 49 years old 0.014078 282 0.012392 248 0.007768 155 0.000035 < 1 0.012238 245 0.007520 150 Adults 50+ years old 0.011278 226 0.009207 184 0.007673 153 0.000118 2 0.009135 182 0.007470 149 25 26 4.3 Drinking Water Sources of Dietary Exposure The Environmental Fate and Ecological Effects Division ( EFED) has performed modeling to assess thiram estimated environmental concentrations ( EECs) in surface water and groundwater. Tier II surface water EECs for thiram were calculated using PRZM/ EXAMS ( surface water) and SCIGROW ( ground water) for apples, turf, golf courses, and cottonseed. PRZM/ EXAMS scenarios were run using the Index Reservoir ( IR) scenario and a Percent Crop Area ( PCA) adjustment to generate surface water EECs.

Hydrolysis, photodegradation, and aerobic soil metabolism are the main degradative processes for thiram. Observed half lives are generally less than 18 days under the nominal or expected use conditions, producing the volatile degradates COS and CS 2 ( carbon disulfide) from hydrolysis and photodegradation, and CO 2 ( carbon dioxide) from aerobic metabolism. Nonvolatile degradates are formed at less than 10% of the applied.

Based on supplemental information, the hydrolysis half life for thiram ( MRID 41840601) was 68.5 days in pH 5 buffer, 3.5 days in pH 7 buffer, and 6.9 hours in pH 9 buffer, and the aqueous photolysis half life ( MRID 41753801) was 10.4 hours in pH 5 buffer ( no degradation was observed in dark controls).

Thiram residues appear to have low mobility in the environment. In a supplemental laboratory study ( MRID 43787501), thiram, at concentrations of 0.01, 0.04, 0.20, and 1.07 mg/ L, was determined to be essentially immobile in sandy loam and silt loam soils, and to have low mobility in loam and loamy sand soils that were equilibrated for 4 hours at 20 oC ( a 4 hour equilibration period was first determined to be adequate). Freundlich K ads values were 54 for the sandy loam soil ( pH= 6.7), 150 for the loamy sand soil ( pH= 4.8), 67 for the silt loam soil ( pH= 6.7), and 263 for the loam soil ( pH= 7.3); corresponding K oc values were 2245, 24526, 6359, and 12899 mL/ g. Respective 1/ N values were 1.04, 1.15, 1.10, and 1.13 for adsorption. The degree of sorption of thiram to these soils was found not to be a function of the amount of organic matter present.

Surface and Groundwater Monitoring Data At this time, there are limited monitoring data available for thiram in either ground or surface water, with no reported detections. The Pesticides in Ground Water Database ( 1991) contains no records for thiram; STORET contains no detections of thiram. No detections of thiram have been reported to the Agency under 6( a) 2. The US Geological Survey National Water Quality Assessment program ( NAWQA) is not currently analyzing for thiram in their samples, and they do not have analytical methods in place for this chemical.

Groundwater Groundwater calculations for thiram were based on the SCI GROW model ( Screening Concentrations in Ground Water, version dated 11/ 12/ 97), which is a model for estimating concentrations of pesticides in groundwater under conditions of maximum exposure. 27 SCI GROW provides a screening concentration or an estimate of likely ground water concentration if the pesticide is used at the maximum allowed label rate in areas with ground water that is exceptionally vulnerable to contamination. In most cases, a majority of the use area will have ground water that is less vulnerable to contamination than the areas used to derive the SCI GROW estimate.

The SCI GROW model is based on normalized ground water concentrations from ground water monitoring studies, environmental fate properties ( aerobic soil half lives and organic carbon partitioning coefficients K oc's) and application rates. The model is based on permeable soils that are vulnerable to leaching and that overlie shallow ground water ( 10 30 feet). Based on the information provided by the groundwater monitoring studies, the model has a lower limit of reliability of 0.006

g/ mL. Refer to Table 6 for thiram EECs used for dietary risk assessment purposes.

Surface Water Tier II surface water EECs were generated using PRZM/ EXAMS. EECs are presented in Table 6. A Tier II EEC for a particular crop or use is based on a single site that represents a high exposure scenario for the crop or use. Weather and agricultural practices are simulated at the site for 36 years to estimate the probability of exceeding a given concentration ( maximum concentration or average concentration) in a single year. Maximum EECs are calculated so that there is a 10% probability that the maximum concentration in a given year will exceed the EEC at the site; peak and chronic EECs were calculated so that there is a 10% probability that the maximum average concentration for a given duration ( 4 day, 21 day, etc.) will equal or exceed the EEC at the site. This can also be expressed as an expectation that water concentrations will exceed EECs once every 10 years.

Table 6. EECs for use in the human health risk assessment Crop Annual App Rate ( lbs ai/ acre/ yr) SCIGROW concentration ( ppb) PRZM/ EXAM S* 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 Golf course 146.6 0.84 14.8 0.78 0.67 Apples 22.5 0.13 16.3 1.2 1.1 Cotton seed 0.01 0.00006 0.006 0.0002 0.00007 * Index Reservoir environment For further details, refer to the Environmental Fate and Ecological Effects Assessment and Characterization Chapter for the Thiram Reregistration Eligibility Decision Document ( J. Carleton and F. Jenkins memorandum; 12/ 11/ 03).

5.0 Occupational/ Residential Exposure and Risk The Occupational and Residential Exposure Assessment ( D289601) was prepared by Jeff Dawson. 28 The document D289601 contains detailed descriptions of the data used, methods, and risks calculated for each scenario. Please refer to that document for more specific information.

There are registered, supported products of thiram intended for both occupational and nonoccupational site applications. The major uses include thiram applications to seeds, terrestrial food and feed crops, terrestrial non food crops, nursery/ greenhouse crops, field grown/ residential grown ornamentals ( i. e., trees, shrubs, vines), and commercial turfgrass ( i. e., sod farms, golf courses, schools, parks, athletic fields, and rights of way). Thiram is registered for foliar application on the following crops: apples, peaches, and strawberries. According to the Thiram Use Closure Memo, thiram may be applied to residential ornamentals ( i. e., trees, shrubs, vines) by professional pesticide applicators only and will no longer be available as residential products for application by private homeowners. In addition, seeds treated with thiram will not be available for purchase by private homeowners.

Thiram is applied as a seed treatment to: small seeded vegetables ( e. g. broccoli, carrots, lettuce, peppers, etc.), large seeded vegetables ( e. g. beans, cantaloupe, corn, cucumbers, peas, etc.), cereal grains ( barley, oats, rice, rye, and wheat), other seeds ( including beets, peanuts, sesame, sorghum, sunflower, etc), coniferous seeds, cotton seed, ornamental seeds ( gladiolus bulbs, ornamental flowers, ornamental bulbs and tubers, etc.), and soybeans.

EPA estimates that the total annual domestic usage for foliar applications of thiram is approximately 200,000 pounds active ingredient ( ai) for about 50,000 acres treated. Thiram has its largest foliar markets, in terms of total pounds active ingredient, allocated to strawberries ( 65%), apples ( 20%), and peaches ( 3%). The Thiram Task Force II consortium reports that approximately 1.3 billion pounds of seed were treated with thiram in the U. S. in 1998 for both domestic and export use. Approximately 600,000 pounds active ingredient of thiram were used to treat the approximate 1.3 billion pounds of seed. It is estimated that approximately 29 million acres are planted annually in the U. S. with thiramtreated seed and that approximately 16% of overall acreage planted in the U. S. use seeds treated with thiram.

There are numerous methods for occupational applications of thiram products. Occupational applications to apples, peaches and/ or strawberries can be made by the following methods: aerial, airblast sprayer, groundboom ( only strawberries), high pressure handwand, and low pressure handwand. Commercial turfgrass ( e. g., sod farms, golf courses, parks and athletic fields) may be treated by the following methods: aerial, backpack sprayer, groundboom, high pressure handwand, low pressure handwand, push type granular spreader, and tractor drawn drop type spreader. Seeds may be treated by numerous methods which include: by hand, concrete tumbler ( conifer seeds), drill box, duster, in furrow application, mist type seed treater, paper bag, planter box, seed box, shaker can, and slurry type seed treater. Ornamental bulbs may be treated by dip tank application, drill box, duster, and paper bag. Finally, animal repellency treatment of golf courses, rights of way, residential sites, parks and athletic fields may be performed by backpack sprayer, low pressure handwand, high pressure handwand, handgun, rights of way sprayer, paintbrush, and sprinkler can.

5.1 Non Occupational ( Residential and Recreational) Risk Assessments As indicated in the Thiram Use Closure Memo ( K. Rothwell memorandum; 3/ 20/ 00), private 29 homeowners will no longer be permitted to purchase and apply thiram products in the residential environment. However, professional pesticide applicators may continue to make thiram applications in the residential environment for animal repellency and in recreational environments ( e. g., golf courses, parks, athletic fields) on turfgrass and for animal repellency. As a result, the public may still be exposed to thiram following application of thiram products in residential and recreational environments.

5.1.1 Residential Postapplication Risk Assessment Thiram uses that are believed to contribute to residential exposures are limited in nature. Products are not available for sale to or use by homeowners but there can be uses on turf in parks, golf courses, and athletic fields where exposures can occur. In order to complete a comprehensive assessment, the Agency considered individuals of varying ages and how they can potentially be exposed when they do activities in areas that have been previously treated. The residential postapplication risk assessment addresses these types of exposures.

The risks from postapplication exposure to thiram residues were determined for the following populations:

 Residential ( homeowner) Adults: these individuals are members of the general population that are exposed to chemicals by engaging in activities in areas previously treated with a pesticide ( e. g., golf courses or parks for thiram). These kinds of exposures are attributable to a variety of activities and usually addressed by the Agency in risk assessments by considering a representative activity as the basis for the exposure calculation. In this case, golfing is the predominant activity considered by the Agency.

 Residential Children: children are members of the general population that can also be exposed from their presence in areas previously treated with a pesticide ( e. g., playing on grass in parks). Toddlers have been selected as a sentinel ( or representative) population for evaluating the risks from the turf uses of thiram. Children are addressed by the Agency in risk assessments by considering a representative activity in an exposure calculation ( e. g., for toddlers on turf, an intense contact play activity is the basis for the assessment).

Data and Assumptions: A series of data, assumptions, and exposure factors served as the basis for completing the residential handler risk assessments, as described below. The assumptions and factors used in the risk calculations are consistent with current Agency policy for completing residential exposure assessments ( i. e., SOPs For Residential Exposure Assessment and related documents).

° The only thiram specific data that were used by the Agency in this assessment were the dislodgeable foliar residue data from strawberries contained in MRID 30 455603 01 that was conducted in California and Florida. These data have been used to complete the residential assessment which is based on exposures to turf. This extrapolation for using strawberry data for turf was completed because these data were the only available. These thiram DFR estimates had a very high percent transferability so use of the data would actually result in risks that are extraordinarily higher than would occur if the standard Agency method was used. As a result, the Agency only used the decay rates from the study and coupled this with initial concentration estimates calculated using the 5 percent of the application rate factor for the dermal and hand to mouth assessments. For the object to mouth calculations, the data were directly scaled based on application rate because the sampling method is believed to be similar to the types of extraction associated with mouthing.

 The Agency combines or aggregates risks resulting from exposures to individual chemicals when it is likely they can occur simultaneously based on the use pattern and the behavior associated with the exposed population. Within a residential assessment, this can take two forms. The first is to add together risks for individual exposure scenarios from all likely sources of exposure such as after an application to turf. For thiram, the Agency has added together risk values ( i. e., MOEs) for different kinds of toddler exposures from treated turf ( dermal, hand to mouth, object to mouth, and soil ingestion). These represent the standard set of exposures that are typically added together when chemicals are used on turf because it is logical they can co occur. For adults, only dermal exposures were considered from golfing. The second would be to potentially add handler and postapplication risks together but the Agency typically does not do this because of low likelihoods of co occurrence. Additionally, for thiram it would be inappropriate because there are no labeled homeowner handler uses.

 Exposures to children playing on treated turf as well as adults on turf ( lawncare and golfing) have been addressed using the latest Agency approaches for this scenario including:

$ 5 percent of the application rate has been used to calculate the 0 day TTR ( turf transferable residue) levels which were used for calculating dermal and hand tomouth exposures, this approach was taken rather than extrapolating directly from the strawberry DFR data because the DFR sampling technique is thought to lead to a gross overestimate of exposure when coupled with the transfer coefficient; the decay rate from the strawberry DFR study ( i. e., the slope of the dissipation curve) was used to estimate residue decline over time rather than the Agency standard value of 10 percent/ day which would be used in lieu of data because it provides a chemical specific basis for this factor;

$ 20 percent of the application rate is normally used to calculate the 0 day residue levels for assessing object to mouth behaviors, however, the percent dislodgability of thiram observed in the strawberry DFR study was much higher ( i. e., ~ 35%) so the Agency used the day 0 DFR concentrations from the DFR 31 study instead and extrapolated the value based on application rate differences to define 0 day residue concentrations;

$ the transfer coefficients used, except golfing, are those presented at the 1999 Agency presentation before the FIFRA Science Advisory Panel that have been adopted in routine practice by the Agency;

$ adult golfers have been assessed using a transfer coefficient of 500 cm2/ hour [ Note: The Agency is currently developing a policy on golfer exposures and has used this value in other assessments];

$ 3 year old toddlers are expected to weigh 15 kg;

$ hand to mouth exposures are based on a frequency of 20 events/ hour and a surface area per event of 20 cm2 representing the palmar surfaces of three fingers;

$ saliva extraction efficiency is 50 percent meaning that every time the hand goes in the mouth approximately ½ of the residues on the hand are removed;

$ object to mouth exposures are based on a 25 cm2 surface area;

$ exposure durations are expected to be 2 hours based on information in the Agency's Exposure Factors Handbook except for golfers where the exposure duration for an 18 hole round of golf is 4 hours based on a 1992 report ( Golf Course Operations, Cost of Doing Business/ Profitability by the Center For Golf Course Management);

$ soil residues are contained in the top centimeter and soil density is 0.67 mL/ gram;

$ dermal, hand and object to mouth, and soil ingestion are added together to represent an overall risk from exposure to turf while granular ingestion is considered to be a much more episodic behavior and is considered separately by the Agency; and $ children of various ages down to the very young ( e. g., 4 or 5 years old) are currently playing golf, the Agency recognizes that age may impact exposures because of changes in behavior and skin surface area to body weight ratios but has not yet developed a quantitative approach for calculating their risks.

 The hazard inputs are identical for both short and intermediate term exposures but intermediate term exposures, in comparison, would be lower than the 32  corresponding short term estimates because they would be amortized over time, hence the Agency has completed only short term calculations for the scenarios included in this assessment as they are protective for that duration as well as extended periods of exposure.

The Agency calculated short term risk estimates for thiram and did not calculate intermediate term risks because that would involve an additional amortization step which would reduce the exposures and provide lower risk estimates which is counter intuitive. In effect, short term estimates for thiram are protective for all durations of exposure that would be anticipated for thiram. Noncancer risks were calculated using the MOE approach which is essentially a ratio of the NOAEL compared to a dose estimate for a particular exposure pattern. MOEs are then added together if appropriate, for example, for children playing on treated turf ( i. e., dermal and mouthing behaviors would be added). Risks from dermal exposures were assessed based on a NOAEL of 300 mg/ kg/ day from a 21 day dermal rabbit study where the effects seen were decreases in body weight and food consumption as well as alterations in clinical chemistry. Risks from the mouthing behaviors of children were also assessed based on similar endpoints which were defined based on a number of studies ( i. e., chronic dog, rat repro., and chronic rat studies were predominant) with a NOAEL of 1.5 mg/ kg/ day. The Agency establishes the level of concern for these calculations through uncertainty factors which account for intra species sensitivity and inter species variability ( i. e., 10x10 = 100). The FQPA statute also requires that the Agency consider special sensitivities of various populations ( e. g., infants and children) through the application of an additional factor which was retained ( i. e., FQPA SF = 10) because of the lack of a developmental neurotoxicity study making the overall safety factor 1000 for residential risks. As such, MOEs ( or the ratio of a NOAEL to a dose for a particular activity) must exceed 1000 for the Agency not to have a risk concern for the particular activity.

Several different types of calculations were used in this assessment to reflect the varying age groups, behaviors, data, and activities that were considered. In essence, all can be summarized by saying that a source of some sort ( e. g., turf residues) comes in contact with a person as they are doing an activity ( e. g., kids playing or golfers). Exposures were then calculated by multiplying the source concentration by some factor ( e. g., transfer coefficient for golfing) and the duration of time people are engaged in that activity. All of the calculations are explained in detail in the Occupational and Residential Exposure Chapter ( D289601). Two of the key algorithms are presented below for informational purposes. These represent the predominant types of exposures considered in the postapplication assessment ( i. e., dermal and hand to mouth).

Dermal exposures were calculated by considering the potential sources of exposure in the environment ( i. e., TTRs on turf) using the following equation. It should also be noted that there are distinct transfer coefficients for different activities ( e. g., kids at play versus golfing). 33 D

( TR  ( SE/ 100)  SA  Freq  Hr  ( 1mg/ 1000

g)) DE( t) ( mg/ day) = ( TR( t) (

g/ cm2) x TC ( cm2/ hr) x Hr/ Day)/ 1000 (

g/ mg)

Where:

DE( t) = Daily exposure or amount deposited on the surface of the skin at time ( t) attributable for activity in a previously treated area, also referred to as potential dose ( mg ai/ day); TR( t) = Transferable residues, in this case turf transferable residues at time ( t) where the longest duration is dictated by the decay time observed in the studies (

g/ cm2); TC = Transfer Coefficient ( cm2/ hour); and Hr/ day = Exposure duration meant to represent a typical workday ( hours).

Likewise, nondietary ingestion from hand to mouth behaviors also consider the environmental concentrations and the mouthing behaviors of children. The following equation describes how these exposures have been calculated.

Where:

D = Dose from hand to mouth activity ( mg/ day); TR = Transferable residues, in this case turf transferable residues at time ( t) where the longest duration is dictated by the decay time observed in the studies (

g/ cm2); SE = Saliva extraction factor (%); SA = Surface area of the hands ( cm2); Freq = Frequency of hand to mouth events ( events/ hour); and Hr = Exposure duration ( hours).

Adult MOEs for golfing exceed the Agency's level of concern on the day of application ( i. e., 764) at the highest application rate of 24.5 lb ai/ A. Risks are not of concern 3 days after the application ( i. e., MOE = 1043) using California data and 2 days after the application ( MOE = 1029) using Florida data. If the application rate is 16.3 lb ai/ A, then MOEs exceed the Agency's target of 1000 on the day of application ( MOE = 1148). These results should be put in context in that the approach used by the Agency is based on an entire course being treated and an individual being exposed on the day of application. It should also be pointed out that a turf specific residue dissipation study was not available and that the Agency used strawberry DFR estimates and standard inputs to complete the assessment. Regional impacts where small but did allow for 1 day quicker exceedence of the Agency's target risk level based on Florida data. Table 7 presents the postapplication MOE values calculated for adults while golfing after applications of thiram. 34 Table 7: Summary of Thiram Noncancer Postapplication Residential MOEs For Adults Scenario Descriptor Results MOE on Day 0 Days MOE

UF Golfing 16.3 lb ai/ A  California Data 1148 0 24.5 lb ai/ A  California Data 764 3 16.3 lb ai/ A  Florida Data 1148 0 24.5 lb ai/ A  Florida Data 764 2 Toddler ( 3 year old) MOEs were calculated for toddlers after exposure to treated turf. Table 8 presents a summary of these risk estimates based using both California and Florida data. MOEs from exposure to treated turf were < 1000 on the day of application for both rates considered ( i. e., 16.3 and 24.5 lb ai/ acre) regardless of the data used for the assessment ( i. e., California or Florida). In fact, MOEs from individual pathways were not  1000 for any turf scenario considered on the day of application except for the soil ingestion component of the turf assessment which is a very minor contributor to overall exposures. As a reminder, dermal, hand to mouth, and object to mouth exposure pathways were also considered. Finally, it should be pointed out that MOEs ( all pathways) were never  1000 even at 30 days after application. The highest MOEs achieved were based on the Florida data where, 30 days after application, they were 337 ( 16.3 lb ai/ A) and 224 ( 24.5 lb ai/ A). In contrast, the highest MOEs achieved based on the California data, also at 30 days after application, were 89 ( 16.3 lb ai/ A) and 59 ( 24.5 lb ai/ A). Dermal and hand to mouth exposures were the key contributors while soil ingestion was a minor contributor to the total MOE estimates.

Table 8: Summary of Thiram Noncancer Postapplication Residential Aggregate MOEs For Toddlers Scenario Descriptor Results MOE on Day 0 Days For MOE

UF Residential Turf ( High Activity) 16.3 lb ai/ A  California Data 4.0 > 30 24.5 lb ai/ A  California Data 2.6 > 30 16.3 lb ai/ A  Florida Data 3.9 > 30 24.5 lb ai/ A  Florida Data 2.6 > 30 Ingestion of thiram granules is also a potential source of exposure because children can eat them if they are found in treated lawns or gardens. This scenario is considered an episodic scenario by the Agency ( i. e., acute dietary endpoints are always used). The concentration in granular products ranges generally from 1 to 10 percent. If this information is coupled with the body weight of a toddler ( 15 kg), the endpoint of 5 mg/ kg/ day which is the same value used for the APAD, and the uncertainty factor of 1000 the amount of formulation that can be consumed at the uncertainty factor MOE 35 level can be calculated. The Agency generally presents these results based on the number of granules that can be ingested. However, this is difficult without specific information pertaining to the formulations that are available. If a 1 percent formulation is ingested, 7.5 mg represents exposure at an MOE of 1000 ( i. e., 1.6 x 10 5 lb). For illustrative purposes, if one considers a 1 percent formulation and the density of soil ( 0.67 mL/ gram, many granulars are clay based), only 0.005 mL of formulation would need to be ingested to have a risk concern ( i. e., 7.5 mg * 1g/ 1000mg * 0.67 mL/ gram). Note that this volume is orders of magnitude less than a teaspoon of granular formulation ( i. e., 0.1% of a teaspoon where a tsp. = 5 mL).

5.1.2 Residential Risk Characterization The Agency considered exposure scenarios that were appropriate to address the potential for nonoccupational exposures to thiram from treated turf. These assessments considered toddlers and adults playing on treated lawns or golfing. In residential settings, the Agency does not use REIs or other mitigation approaches to limit exposures because they are viewed as impractical and not enforceable. As such, risk estimates on the day of application are the key concern. It should also be noted that for thiram that short term calculations are protective for thiram since the exposure and hazard inputs are the same for intermediate term exposures but these exposures would also involve an amortization step.

Characterization of the residential risks included in this document must consider the approaches used to calculate risks as well as the data that were available. The general population can be exposed essentially from uses on turf which are probably sporadic for thiram given that a majority of it is used in the seed treatment market and by all accounts the turf/ repellency market is very small. For turf uses, the Agency considered adults and toddlers ( 3 year olds) in the assessments which is the standard practice. For thiram, this meant addressing exposures to adult golfers and for toddlers playing on turf which included dermal exposures ( using exposure data from the Jazzercize model) and exposures from nondietary ingestion ( hand/ object to mouth and soil ingestion).

The data that were used in the thiram residential postapplication assessment are minimal but represent the best data and approaches that are currently available. To the extent possible, the Agency has attempted to use thiram specific strawberry dislodgeable foliar residue ( DFR) data for the turf scenarios. However, due to the high percent transferability and the extrapolation from strawberry to turf, it is recommended that this approach be considered as a rangefinder by nature. When chemical specific data were unavailable, the Agency used the current approaches for residential assessment, many of which include recent upgrades to the SOPs. There are also many embedded uncertainties that should be considered in the interpretation of this assessment such as those associated with the use of Jazzercize and with the nondietary ingestion calculations. Readers should consider these in the interpretation of the overall 36 risk estimates. Readers should also consider the screening nature of the SOPs For Residential Exposure Assessment and how additional data could refine the results.

Finally, the Agency believes that the values presented in this assessment represent the highest quality results that could be produced based on the currently available data. Readers of this document should consider the quality of individual inputs when interpreting the results and make decisions accordingly. It is difficult to ascertain where, on a distribution, the calculated values fall because the distributional data for exposure, residue dissipation and many other parameters are unrefined. The Agency does believe, however, that the risks represent conservative estimates of exposure because maximum application rates are used to define residue levels upon which the calculations are based. Additionally, estimates are thought to be conservative even when measures of central tendency ( e. g., most transfer coefficients are thought to be central tendency) are used because values that would be considered to be in the lower percentile aspect of any input parameter have not been used in the calculations.

5.2 Occupational Risk Assessment This section of the risk assessment addresses exposures to individuals who are exposed as part of their employment. These exposures can occur because people have contact with thiram residues while using commercial products containing thiram ( i. e., handlers) or by being in areas that have been previously treated ( postapplication workers).

5.2.1 Occupational Handler Risk Assessment The Agency completes occupational handler risk assessments using scenarios as the basis for the calculations as described in the U. S. EPA Guidelines For Exposure Assessment. For commercial pesticide products, the Agency categorizes handler exposures based on the kinds of formulations ( e. g., liquids or various solids), the kinds of equipment used to make applications ( e. g., groundboom, aerial, or airblast), the nature of the task ( e. g., mixing/ loading, applying, or both combined), and the level of personal protection used. Identifying the duration of exposure is also a critical element in the development of a risk assessment to ensure that the proper hazard component is used.

For thiram uses, the Agency identified 28 major occupational exposure scenarios based on the types of equipment and techniques that potentially can be used for thiram applications. Most of the scenarios were classified as having short term and intermediate term exposures ( up to 30 days and 30 days to several months, respectively). For handlers the exposures and hazard components are identical so the calculated results reflect the risks associated with all appropriate durations of exposure.

The quantitative exposure/ risk assessment developed for occupational handlers was based on the following scenarios. [ Note: The numbers correspond to the tracking system included in D289601.] 37 Mixing/ Loading: ( 1a) Dry Flowable for Aerial; ( 1b) Dry Flowable for Airblast; ( 1c) Dry Flowable for Groundboom ( including in furrow uses at plant); ( 1d) Dry Flowable for High Pressure Handwand; ( 1e) Dry Flowable for Right of Way; ( 1f) Dry Flowable for Paint on Applications; ( 2) Granular for Turf Uses ( sod farm and golf courses); ( 3a) Wettable Powder for Aerial; ( 3b) Wettable Powder for Airblast; ( 3c) Wettable Powder for Groundboom ( including in furrow uses at plant); ( 3d) Wettable Powder for High Pressure Handwand; ( 3e) Wettable Powder for Right of Way; ( 3f) Wettable Powder for Paint on Applications; ( 4a) Liquid for Aerial; ( 4b) Liquid for Airblast; ( 4c) Liquid for Groundboom ( including in furrow uses at plant); ( 4d) Liquid for High Pressure Handwand; ( 4e) Liquid for Right of Way; ( 4f) Liquid for Paint on Applications; ( 4g) Liquid for Bulb Dip Tank Applications;

Applicator: ( 5a) Liquid Spray Aerial Application; ( 5b) Granular Aerial Application; ( 6) Airblast Application; ( 7) Groundboom Application ( includes in furrow application); ( 8) Solid Broadcast Spreader Application; ( 9) Right of Way Sprayer Application; ( 10) High Pressure Handwand Application; ( 11) Repellent Use Paint Brush Applications ( both liquids & slurries); ( 12) Dip Tank Application; ( 13) Granular Application By Hand; ( 14) Granular Application By Spoon;

Mixer/ Loader/ Applicator: ( 15) High Volume/ Low Pressure Turfgun; ( 16a) Low pressure handwand  Liquid Formulation; ( 16b) Low pressure handwand  Wettable Powder Formulation; ( 17) Liquid Backpack; ( 18) Push type Granular Spreader; ( 19) Powered Backpack; ( 20) Sprinkler Can; 38 Flaggers: ( 21) Flagging For Liquid Sprays; ( 22) Flagging For Granular Applications;

Seed Treatment Scenarios: ( 23) Mixing/ Loading For Seed Treatment In A Commercial Facility; ( 24) Bagging Treated Seed In A Commercial Facility; ( 25) Sewing Bags of Treated Seed In A Commercial Facility; ( 26) Combined Tasks Required To Operate A Commercial Seed Treatment Facility; ( 27) Loading/ Planting Treated Seed; and ( 28) On farm Seed Treatment.

For each of these scenarios, risk calculations were completed based on eight levels of personal protection, as appropriate, that were defined based on different combinations of the following:

1) Baseline Protection ( typical work clothing or a long sleeved shirt and long pants, no respiratory protection and no chemical resistant gloves);

2) Minimum Personal Protective Equipment ( baseline scenario with the use of chemical resistant gloves and a dust/ mist respirator with a protection factor of 5);

3) Maximum Personal Protective Equipment ( baseline scenario with the use of an additional layer of clothing ( e. g., a pair of coveralls), chemical resistant gloves, and an air purifying respirator with a protection factor of 10);

4) Engineering Controls ( use of an appropriate engineering control such as a closed tractor cab or closed loading system for granulars or liquids).

[ Note: Current labels mostly require single layer clothing, chemical resistant gloves, and no respirator.]

Data and Assumptions: A series of assumptions and exposure factors served as the basis for completing the occupational handler risk assessments. The inputs are consistent with current Agency policy for completing occupational exposure assessments ( e. g., PHED Surrogate Exposure Guide and Exposac Policy 9: Standard Values For Daily Acres Treated In Agriculture). [ Note: PHED is a database that contains monitored field data used for assessments. See the occupational and residential exposure assessment document for further information ( D289601).]

The assumptions and factors used in the risk calculations include:

 Average body weight of an adult handler is 70 kg because the toxicity endpoint values used for the assessments are appropriate for average adult body weight representing the general population. This is the case because none of the effects 39  identified in the selected toxicity studies were sex specific ( i. e., NOAELs selected by HIARC were the same for males and females).

 All analyses were completed using scenario specific exposure data or data that were deemed to be a source of acceptable surrogate exposure data for the scenario in question. Most scenarios were addressed using exposure estimates based on the Pesticide Handler Exposure Database ( PHED). Several handler assessments were completed using " low quality" PHED data due to the lack of a more acceptable dataset. The PHED unit exposure values range between the geometric mean and the median of the available exposure data. When data from other studies were used, the appropriate statistical measure of central tendency was used ( see each study summary below for data descriptor).

 Several generic protection factors were used to calculate handler exposures. The protection factors used for clothing layers ( i. e., 50%) and gloves ( 90%) have not been completely evaluated by the Agency. Additionally, the Agency uses a 98% reduction factor to estimate exposures that involve the use of engineering controls. There is an ongoing project through NAFTA to address the issue of protection factors ( a draft document assessing protection factors using PHED has been completed). The results of this effort show that the protection factors being currently used by the Agency are within those predicted in the analysis. The values used for respiratory protection ( i. e., PF 5 or PF 10) are based on the NIOSH Respirator Decision Logic.

 Exposure factors used to calculate daily exposures to handlers are based on applicable data if available. For lack of appropriate data, values from a scenario deemed similar enough by the assessor might be used. As a example, mixer/ loader/ applicator data for hose end sprayers were used to assess sprinkler can applications. The nature of these application methods are believed to be similar enough to bridge the data. There are other instances where the Agency has bridged specific data to represent other scenarios.

 In many scenarios it is likely that a grower would mix, load, and apply chemicals all in one day because of limited labor, efficiency, or many other reasons. In most cases, however, the Agency considers mixing/ loading, and application as separate job functions. This is done primarily due to a lack of data that allows additivity between tasks to be appropriately assessed. Also, this approach allows for more flexibility in the risk management process. For example, if a closed loading system might be required for mixer/ loaders but engineering controls might not be required to reduce applicator exposures. If combined exposure estimates were considered, engineering controls might have been required for both tasks.

 The Agency has evaluated scenarios that may be limited in nature such as flagging during aerial applications because engineering controls ( i. e., Global Positioning Satellite technology) are now predominantly used as indicated by the 40 1998 National Agricultural Aviation Association ( NAAA) survey of their membership. It appears, however, flaggers are still used in approximately 10 to 15 percent of aerial application operations. In cases like these, the Agency strongly encourages the use of the engineering control system but will continue to evaluate risks for flaggers and any other population where a clear exposure pathway exists until the potential for exposure is eliminated. The Agency is aware that NAAA is conducting another survey of its membership on exposure issues and will consider those results as is timely and appropriate.

 The Agency always considers the maximum application rates allowed by labels in its risk assessments in order to be able to consider what is legally possible based on the label. If additional information such as average or typical rates are available, these values were used as well in order to allow risk managers to make a more informed risk management decision.

 The average occupational workday is assumed to be 8 hours. The daily areas to be treated were defined for each handler scenario ( in appropriate units) by determining the amount that can be reasonably treated in a single day. The factors used for the thiram assessment are the same as those detailed in the Health Effects Division Science Advisory Committee on Exposure Policy 9: Standard Values for Daily Acres Treated in Agriculture which was completed on July 5, 2000. The following daily volumes handled and acres, excerpted from the policy, to be treated in each occupational scenario include:

 Aerial applications: 350 acres for agricultural crops and 80 acres for sod farms;

 Groundboom: 80 acres treated for strawberries and sod farm turf, and 40 acres on golf course turf;

 Airblast: 40 acres treated for agricultural applications;

° 1000 gallons of spray solution prepared when mixing/ loading liquids for high pressure handwand application or making the application with a right of way sprayer;

° 40 gallons when mixing/ loading/ applying liquids with a backpack sprayer or a low pressure handwand sprayer;

° Low pressure/ high volume turfgun: 5 acres for golf course and other ( nonresidential) turf;

° Paint brush repellent uses: 1 gallon of liquid or slurry for use as a repellent;

° Dip tank applications: ( no data to complete the assessment); 41 ° Solid broadcast spreader applications: 80 acres on sod farm turf and 40 acres on golf course turf;

° Low pressure handwand and backpack liquid sprayers: 40 gallons of spray solution; ° Push type spreaders and granular backpack applicators: 5 acres of treated turf; and ° Sprinkler can application: 10 gallons of spray for repellent uses.

 The Agency received information on the amount of seed treated in a day from a variety of sources. These included information from Gustafson ( email from Dave Vossen to Jeff Dawson dated 6/ 24/ 01) that pertained to the amount of seed that could be treated in a day, the thiram task force also provided information concerning the daily amounts that could be treated in a day, and information concerning how much seed is treated in a day from the survey conducted of thiram seed treaters was summarized and considered. The Agency used values of 330,000 and 800,000 lb seed treated per day in the previous assessment. To allow for a more informed risk management decision, the Agency has considered these estimates ( which are supported by the data from Gustafson as shown in Table 9 as well as the additional information provided from the thiram task force and the survey of seed treaters ( Table 8). This information is presented below:

Table 9: Small Grain Capacity For Various Gustafson Seed Treatment Equipment Model Minimum Rate Needed For Operation Maximum Throughput of Equipment ( metric tons/ hr) ( lb / hour) ( metric tons/ hr) ( lb / hour)

SS 1 3.4 7480 7.5 16500 SS 6 6.8 14960 12.3 27060 S 100SS 3.4 7480 7.5 16500 S 600SS 6.8 14960 12.3 27060 S 800SS 16.0 35200 27.0 59400 S 1000SS 19.0 41800 40.8 89760 Accu Treat 6x10 19.0 41800 40.8 89760 Accu Treat 8x12 16.0 35200 27.0 59400 Average NA 24860 NA 78555 Values over an 8 hour workday are: Lowest production model ( SS 1): 59840 lb seed/ day Highest production model ( S 1000SS): 718080 lb seed/ day Minimum average: 198880 lb seed/ day Maximum Average: 628440 lb seed/ day ( Source: Dave Vossen, Gustafson Inc.) 42 The information provided by the thiram task force in their comments on the Phase 3 risk assessment is provided below ( i. e., seed types and lb seed treated/ day are presented):

° Corn 193,600 ° Cottonseed. 160,160 ° Small grains 718,080 ° Peanuts 119,680 ° Soybeans 211,200 ° Vegetables ( small seed) 88,000 ° Vegetables ( large seed) 193,600 ° Sweet corn 193,600 Table 10: Amount Of Seed Treated Per Day For Thiram Applicator Crews Seed Type Avg. # in Crew Seed Treated/ Day ( lb/ day) Average Hours/ Crew N Per day Per Year Small Vegetable 2.7 16250 5 192 15 Large Vegetable 3.1 84140 7 364 20 Cereal Grains ( slurry  major method) 1.8 78962 7 241 82 Cotton 2.2 81192 8 834 14 Soybeans 2.5 61065 6 78 51 ( Source: Survey of Thiram using seed treaters)

 The Agency received information on the amount of seed treated in a day from a variety of sources. It was decided, however, to base the inputs used in the assessment on information provided by Drs. B. Schneider and Yuen Shaung, NG ( 4/ 3/ 03 memo). This includes the following:

° Small Seeded Vegetables: Tomato  1 Lb/ a; Broccoli  1 to 2 lb/ a; Cabbage  0.15 to 1 lb/ a; Cauliflower  1 to 2 lb/ a; Carrot  2 to 4 lb/ a; Dry Bulb Onions  1 to 4 lb/ a; Green Onions  5 to 15 lb/ a; and Lettuce  1 to 3 lb/ a.

° Large Seeded Vegetables: Lima Beans  40 to 60 lb/ a; Snapbeans  60 to 100 lb/ a; Field Corn  4 to 18 lb/ a; Sweetcorn  10 to 15 lb/ a; English Pea  80 to 120 lb/ a; and Watermelon 1 to 3 lb/ a.

° Cereals: Winter Barley  60 to 90 lb/ a; Spring Barley  30 to 50 lb/ a; Oats  50 to 90 lb/ a; Rice  100 to 150 lb/ a; Wheat  60 to 120 lb/ a.

° Other Crops: Alfalfa & Fescue  15 to 20 lb/ A; Red Clover  8 to 10 lb/ A; 43 ° Peanut  60 to 140 lb/ A; Cotton  10 to 15 lb/ A; Soybeans  45 to 60 lb/ A; Sunflower  3 to 7 lb/ A; and Bluegrass  10 to 15 lb/ A.

[ Note: Selected crops from this list were used to complete assessments for the planting of treated seed.]

The Pesticide Handler Exposure Database ( PHED) Version 1.1 August 1998, was used to address most non seed treatment exposure scenarios. For seed treatment and other scenarios ( e. g., some lawncare applications), unit exposure values were from studies not using thiram but that were pertinent to specific exposure scenarios associated with thiram. There are may be data compensation issues under FIFRA associated with the use of data contained in the non PHED. Please refer to the description of each contained in the occupational and residential exposure assessment chapter ( D289601) in order to ascertain if the registrants of thiram maintain ownership of any of these data.

5.2.2 Occupational Handler Non Cancer Risks Noncancer risks were calculated using the MOE approach, as described above in the residential assessment ( see 5.1). Risk estimates for short and intermediate term exposures are similar because all numerical inputs for both durations and the target MOEs were identical. A NOAEL from the 21 day dermal toxicity study in rabbits using technical grade thiram was used to calculate results for both durations ( i. e., 300 mg/ kg/ day). A NOAEL based on a reproduction study in rats, a chronic study in rats, and a chronic study in dogs ( i. e., 1.5 mg/ kg/ day), was used to calculate inhalation risks. The target MOE was 100 for all assessments.

Short term and Intermediate term Risk Summary: Short term and intermediate term risks were calculated for different exposure scenarios at different levels of personal protection as illustrated in Table 11. The results represent both short and intermediateterm risks because the exposure factors used to calculate each are identical as are the hazard inputs ( e. g., NOAELs).

In most scenarios, MOEs meet or exceed the required uncertainty factor of 100 at some level of personal protection. For the most part, current label requirements ( for personal protection single layer clothing, gloves, and no respirator) appear to be generally inadequate for most scenarios except for operations where exposures and/ or the amount of chemical used is low. Scenarios where MOEs do not exceed 100 at any level of personal protection include some loading scenarios for aerial applications, aerial granular application, some handheld equipment use, and a few commercial and on farm seed treatment scenarios. [ Note: Scenarios of concern ( i. e., MOEs< 100) and the required PPE is also highlighted where risks exceed current label requirements.] Several data gaps were also identified in many different use areas that include: in furrow/ at plant applications; repellent paint on applications; powered backpack; engineering control data for seed treatment; on farm seed treatment data with different application methods ( e. g., admixture); sprinkler can; and bulb dip applications. 44 Table 11: Summary of Short/ Intermediate Term Occupational Handler Noncancer Risks Scenario Rate ( lb ai/ acre)

[ unless noted] Area Treated ( acres/ day)

[ unless noted] Risk Summary MOEs Min. Req. PPE Mixer/ Loaders 1a Dry Flowable: Aerial 2.6 ( peaches) 3.3 4.5 ( apples/ strawberries) 16.3 24.5 ( turf  sodfarm) 350 350 80 105 138 188 111 166 Baseline SL/ GL/ PF5 SL/ GL/ PF5 1b Dry Flowable: Airblast 2.6 4.5 ( apples/ peaches) 40 530 917 Baseline 1c Dry Flowable: Groundboom ( incl. In furrow) 3.3 ( strawberries) 16.3 24.5 ( sodfarm turf) 16.3 ( golf course turf) 24.5 ( golf course turf) 0.0025 0.35 ( SSV/ LSV/ cereals/ others) 80 80 40 40 80 362 111 166 221 146 3409 477273 Baseline SL/ GL/ PF5 SL/ GL/ PF5 Baseline Baseline 1d Dry Flowable: High Press HW Sprayer 1.3 lb ai/ gal ( repellency) 1000 gal. 167 SL/ GL/ PF5 1e Dry Flowable: Right of Way Sprayer 1.3 lb ai/ gal ( repellency) 1000 gal. 167 SL/ GL/ PF5 1f Dry Flowable: Paint on 1.3 lb ai/ gal ( repellency) 1 gal. 73427 Baseline 2 Granular: Aerial & Ground Applications 16.3 24.5 ( sodfarm) 16.3 24.5 ( golf course) 80 40 143 215 286 430 SL/ GL/ PF5 SL/ GL/ PF5 3a Wettable Powder: Aerial 2.6 4.5 ( apples/ peaches/ strawberries) 16.3 24.5 ( sodfarms/ golf courses) 350 80 231 399 185 279 EC EC 3b Wettable Powder: Airblast 2.6 ( peaches) 4.5 ( apples) 40 40 107 113 SL/ GL/ PF5 SL/ GL/ PF10 3c Wettable Powder: Groundboom ( Incl. In furrow) 3.3 ( strawberry) 16.3 24.5 ( sodfarm & golf course turf) 0.0025 0.21 ( SSV/ LSV/ cereals/ others) 0.35 ( others peanuts) 80 40 80 80 80 1376 185 557 102 8537 397 EC EC Baseline SL/ GL/ PF5 3d Wettable Powder: High pressure handwand sprayer 1.3 lb ai/ gal. ( repellency) 1000 gal. 280 EC 3e Wettable Powder: Right of way sprayer 1.3 lb ai/ gal. ( repellency) 1000 gal. 280 EC 3f Wettable Powder: Paint On 1.3 lb ai/ gal. ( repellency) 1 gal. 1313 Baseline 4a Liquids: Aerial 2.6 4.5 ( apples/ peaches/ strawberries) 16.3 24.5 ( sodfarm turf) 350 80 188 325 151 227 SL/ GL/ PF5 SL/ GL/ PF5 4b Liquids: Airblast 2.6 4.5 ( apples/ peaches) 40 444 768 SL/ GL/ NR 4c Liquids: Groundboom ( incl. In furrow) 3.3 ( strawberries) 16.3 24.5 ( sodfarm turf) 16.3 ( golf course turf) 24.5 ( golf course turf) 0.0025 0.35 ( SSV/ LSV/ cereals/ others) 80 80 40 40 80 303 151 227 123 302 239 33440 SL/ GL/ NR SL/ GL/ PF5 SL/ GL/ NR SL/ GL/ PF5 Baseline 4d Liquids: High pressure handwand sprayer 1.3 lb ai/ gal. ( repellency) 1000 gal. 228 SL/ GL/ PF5 4e Liquids: Right of way sprayer 1.3 lb ai/ gal. ( repellency) 1000 gal. 228 SL/ GL/ PF5 4f Liquids: Paint On 1.3 lb ai/ gal. ( repellency) 1 gal. 5145 Baseline 4g Liquids: Bulb dip No Data No Data No Data No Data Table 11: Summary of Short/ Intermediate Term Occupational Handler Noncancer Risks Scenario Rate ( lb ai/ acre)

[ unless noted] Area Treated ( acres/ day)

[ unless noted] Risk Summary MOEs Min. Req. PPE 45 Applicators 5a Aerial: liquid sprays 2.6 4.5 ( apples/ peaches/ strawberries) 16.3 24.5 ( turf  sodfarm) 350 80 698 1208 561 843 EC EC 5b Aerial: granular applications 16.3 24.5 ( turf  sodfarm) 80 41 62 MOE< 100 6 Airblast: Agricultural uses 2.6 ( peaches) 4.5 ( apples) 40 40 160 102 Baseline SL/ GL/ NR 7 Groundboom 3.3 ( strawberries) 16.3 24.5 ( sodfarm turf) 16.3 24.5 ( golf course turf) 0.0025 0.35 ( SSV/ LSV/ cereals/ others) 80 80 40 80 491 248 369 132 199 4930 648148 Baseline SL/ GL/ PF5 Baseline Baseline 8 Solid broadcast spreader ( granular) 16.3 24.5 ( sodfarm turf) 16.3 ( golf course turf) 24.5 ( golf course turf) 80 40 40 194 292 129 388 SL/ GL/ PF5 Baseline SL/ GL/ PF5 9 Right of way sprayer 1.3 lb ai/ gal. ( repellency) 1000 gal. 44 MOE< 100 10 High pressure handwand 1.3 lb ai/ gal. ( repellency) 1000 gal. 8 MOE< 100 11 Paint on 1.3 lb ai/ gal. ( repellency) 1 gal. 202 SL/ GL/ NR 12 Dip tank No Data No Data No Data No Data 13 Granulars & baits applied by hand 16.3 ( golf course turf) 24.5 ( golf course turf) 1 1 26 17 MOE< 100 MOE< 100 14 Granulars & baits applied by spoon 16.3 ( golf course turf) 24.5 ( golf course turf) 1 1 117 227 SL/ GL/ NR SL/ GL/ PF5 Mixer/ Loader/ Applicators 15 Low pressure, high volume turfgun ( ORETF Data) 16.3 ( golf course turf) 24.5 ( golf course turf) 5 5 131 188 SL/ GL/ NR SL/ GL/ PF5 16a Wettable powder, low pressure handwand 1.3 lb ai/ gallon ( repellency) 40 14.3 MOE< 100 16b Liquids, low pressure handwand 1.3 lb ai/ gallon ( repellency) 40 248 SL/ GL/ PF5 17 Backpack sprayer 1.3 lb ai/ gallon ( repellency) 40 109 SL/ GL/ PF5 18 Granular, push type spreader 16.3 ( golf course turf) 24.5 ( golf course turf) 5 5 139 330 Baseline SL/ GL/ PF5 19 Power backpack No Data No Data No Data No Data 20 Sprinkler can 1.3 lb ai/ gallon ( repellency) 10 204 SL/ GL/ NR Flaggers 21 Flagger: liquid sprays 2.6 4.5 ( apples/ peaches/ strawberries) 16.3 24.5 ( turf  sodfarm) 350 80 165 285 132 199 Baseline Baseline 22 Flagger: granular applications 16.3 24.5 ( turf  sodfarm) 80 327 491 Baseline Seed Treatment 23 Mixing/ loading for commercial seed treatment 0.031 0.25 lb ai/ cwt ( various) 1.5 lb ai/ cwt ( onions) 1.5 lb ai/ cwt ( onions) 0.094 0.25 lb ai/ cwt ( corn / cereals/ LSV/ SSV/ cotton/ peanuts) 0.10 0.25 lb ai/ cwt ( cotton/ cereals/ soybean/ SSV/ LSV) 330000 800000 ( Agency) 330000 ( Agency) 800000 ( Agency) 88000 718080 ( Thiram Task Force) 16250 81192 ( Doane Survey) 105 167164 111 69 291 1247 993 5144 SL/ GL/ NR SL/ GL/ PF5 MOE< 100 SL/ GL/ NR SL/ GL/ NR Table 11: Summary of Short/ Intermediate Term Occupational Handler Noncancer Risks Scenario Rate ( lb ai/ acre)

[ unless noted] Area Treated ( acres/ day)

[ unless noted] Risk Summary MOEs Min. Req. PPE 46 24 Bagging commercially treated seed 0.031 1.5 lb ai/ cwt ( various) 1.5 lb ai/ cwt ( onions) 0.094 0.25 lb ai/ cwt ( corn / cereals/ LSV/ SSV/ cotton/ peanuts) 0.10 0.25 lb ai/ cwt ( cotton/ cereals/ soybeans/ SSV/ LSV) 330000 800000 ( Agency) 800000 ( Agency) 88000 718080 ( Thiram Task Force) 16250 81192 ( Doane Survey) 103 408759 43 711 2419 2429 12577 Baseline MOE< 100 Baseline Baseline 25 Sewing bags of commercially treated seed 0.031 0.25 lb ai/ cwt ( various) 1.5 lb ai/ cwt ( onions) 0.094 0.25 lb ai/ cwt ( corn / cereals/ LSV/ SSV/ cotton/ peanuts) 0.10 0.25 lb ai/ cwt ( cotton/ cereals/ soybeans/ SSV/ LSV) 330000 800000 ( Agency) 330000 800000 ( Agency) 88000 718080 ( Thiram Task Force) 16250 81192 ( Doane Survey) 201 321839 34 81 560 2401 1913 9903 Baseline MOE< 100 Baseline Baseline 26 Commercially treated seed: combined tasks 0.031 0.25 lb ai/ cwt ( various) 0.12 0.25 lb ai/ cwt ( various) 1.5 2.0 lb ai/ cwt ( onions & conifers) 0.094 0.25 lb ai/ cwt ( corn / LSV/ SSV/ cotton/ peanuts) 0.10 lb ai/ cwt ( cereals) 0.10 0.25 lb ai/ cwt ( cotton/ cereals/ soybeans/ SSV/ LSV) 330000 800000 ( Agency) 330000 800000 ( Agency) 1769 800000 ( Agency) 88000 193600 ( Thiram Task Force) 718080 ( TTF) 16250 81192 ( Doane Survey) 126 567 177 240 24 80 120 346 276 276 1428 SL/ GL/ NR SL/ GL/ PF5 MOE< 100 SL/ GL/ NR SL/ GL/ PF5 SL/ GL/ NR 27 Loading/ planting treated seed 0.0025 1.22 lb ai/ A ( SSV/ LSV/ cereals/ others/ conifers/ ornam.) 80 638 112903 SL/ GL/ NR 28 On farm seed treatment 0.0025 0.168 lb ai/ A ( SSV/ LSV/ cereals/ others/ ornam.) 0.21lb ai/ A ( cereals rice) 0.35 1.22 lb ai/ A ( peanuts & conifers) 80 80 80 122 8179 103 50 63 Baseline SL/ GL/ NR MOE< 100 Baseline = Long pants, long sleeved shirts, no gloves SL = Single layer clothing with or without gloves ( GL or NG) DL = Double layer clothing ( i. e., coveralls over SL) with or without gloves ( GL or NG) EC = Engineering controls NR = No respirator PF5 = Protection factor 5 respirator PF10 = Protection factor 10 respirator Current label = SL/ GL/ NR Min. Req. PPE = level of PPE where MOEs > 100, where current label is exceeded or no adequate PPE is found, results are bold. MOEs which never exceed 100 are for highest feasible type of mitigation ( e. g., engineering control in most cases).

5.2.3 Postapplication Exposure Risks Assessment Workers can be exposed to thiram residues by entering previously treated areas to perform activities. Exposure varies with the specific tasks ( i. e., transfer coefficient), the level of thiram residue in the environment ( i. e., DFR or TTR depending upon crop), and the duration of the activity. Calculations were completed using the same approaches as already outlined above for the residential postapplication risk assessments.

An administrative approach, the Restricted Entry Interval ( REI), is used by the Agency to manage risks for postapplication workers doing hand labor activities that require direct contact with treated plants. The REI is the amount of time required between application of a pesticide and engaging in a task or activity in a treated field that it takes for residues to dissipate to an appropriate level. Current labels for thiram specify REIs of 24 hours after application for all crop/ cultural practice combinations. In other cases ( e. g., use of a combine or other mechanical harvesting) such as those specified in the 47 Agency's Worker Protection Standard ( 40CFR170) where no contact will occur, the Agency does not rely on the REI approach but adheres to the guidance included in § 170.110.( c)( 3) that allows for entry if the criteria are met. The Agency also considers short term excursions for people for such activities as unclogging machinery as stipulated in the guidance included in § 170.112.( c). The Agency encourages the use of viable engineering controls and other means to reduce exposures provided they are not overly burdensome for actual workers. Generally, it should also be noted that the use of personal protective equipment or other types of equipment to reduce exposures for postapplication workers is not considered a viable alternative for the regulatory process except in specialized situations ( e. g., a rice scout will wear rubber boots in flooded paddies).