United States Prevention, Pesticides EPA739 R 05 003 Environmental Protection and Toxic Substances August 2006 Agency ( 7510P)

Reregistration Eligibility Decision for 2( Thiocyanomethylthio) benzothiazole ( TCMTB) UNITED STATES ENVIRONMENTAL PROTECTION AGENCY WASHINGTON, D. C. 20460 OFFICE OF PREVENTION, PESTICIDES AND TOXIC SUBSTANCES CERTIFIED MAIL Dear Registrant:

This is to inform you that the Environmental Protection Agency ( hereafter referred to as EPA or the Agency) has completed its review of the available data and public comments received related to the preliminary risk assessments for the antimicrobial 2 ( thiocyanomethylthio) benzothiazole ( TCMTB). The Reregistration Eligibility Decision ( RED) for TCMTB was approved on August 1, 2006. Public comments and additional data received were considered in this decision.

Based on its review, EPA is now publishing its Reregistration Eligibility Decision ( RED) and risk management decision for TCMTB and its associated human health and environmental risks. A Notice of Availability will be published in the Federal Register announcing the publication of the RED.

The RED and supporting risk assessments for TCMTB are available to the public in EPA's Pesticide Docket EPA HQ OPP 2006 0320 at: www. regulations. gov.

The TCMTB RED was developed through EPA's public participation process, published in the Federal Register on September 10, 2004, which provides opportunities for public involvement in the Agency's pesticide tolerance reassessment and reregistration programs. The public participation process encourages robust public involvement starting early and continuing throughout the pesticide risk assessment and risk mitigation decision making process. The public participation process encompasses full, modified, and streamlined versions that enable the Agency to tailor the level of review to the level of refinement of the risk assessments, as well as to the amount of use, risk, public concern, and complexity associated with each pesticide. Using the public participation process, EPA is attaining its strong commitment to both involve the public and meet statutory deadlines.

Please note that the TCMTB risk assessment and the attached RED document concern only this particular pesticide. This RED presents the Agency's conclusions on the dietary, drinking water, occupational and ecological risks posed by exposure to TCMTB alone. This document also contains both generic and product specific data that the Agency intends to require in Data Call Ins ( DCIs). Note that DCIs, with all pertinent instructions, will be sent to registrants at a later date. Additionally, for product specific DCIs, the first set of required responses will be due 90 days from the receipt of the DCI letter. The second set of required responses will be due eight months from the receipt of the DCI letter. As part of the RED, the Agency has determined that TCMTB will be eligible for reregistration provided that all the conditions identified in this document are satisfied, including implementation of the risk mitigation measure outlined in Section IV of the document. Sections IV and V of this RED document describe the labeling amendments for end use products and data requirements necessary to implement this mitigation measure. Instructions for registrants on submitting the revised labeling can be found in the set of instructions for product specific data that accompanies this document.

Should a registrant fail to implement any of the risk mitigation measures outlined in this document, the Agency will continue to have concerns about the risks posed by TCMTB. Where the Agency has identified any unreasonable adverse effect to human health and the environment, the Agency may at any time initiate appropriate regulatory action to address this concern. At that time, any affected person( s) may challenge the Agency's action.

If you have questions on this document or the label changes relevant to this reregistration decision, please contact the Chemical Review Manager, K. Avivah Jakob, at ( 703) 305 1328. For questions about product reregistration and/ or the Product DCI that will follow this document, please contact Marshall Swindell at ( 703) 308 6341.

Sincerely,

Frank T. Sanders Director, Antimicrobials Division REREGISTRATION ELIGIBILITY DECISION for 2( Thiocyanomethylthio) benzothiazole ( TCMTB) List B CASE 2625 Approved By:

Frank T. Sanders Director, Antimicrobials Division August 1, 2006 Attachment Table of Contents TCMTB Reregistration Team                   ....... i Glossary of Terms and Abbreviations              ...    ii Abstract    ...                      .  .... iv I. Introduction                           .. 1 II. Chemical Overview                       . ... 3 A. Regulatory History                    .. ... 3 B. Chemical Identification                   ... 3 C. Use Profile                        ... 4 III. Summary of TCMTB Risk Assessments               . 7 A. Human Health Risk Assessment               ... 7 1. Toxicity of TCMTB                  .... 7 2. Metabolite Assessment                 ... 12 3. FQPA Safety Factor                   13 4. Population Adjusted Dose ( PAD)            ... 14 a. Acute PAD                    14 b. Chronic PAD                   14 5. Dietary Exposure Assumptions              14 6. Dietary Risk Assessment                . 15 a. Dietary Risk from Food and Drinking Water    .. 15 b. Dietary Risk from Drinking Water         .. 17 7. Residential Risk Assessment ...              18 a. Residential Toxicity        ..   ..   . 18 b. Residential Handlers           ..  .. .. 20 i. Exposure Assessment .           . 20 ii. Risk Assessment       .  .    . 21 c. Residential Post Application ..           21 i. Exposure Assessment .           . 21 ii. Risk Assessment       .  .    . 22 8. Aggregate Risk                    . 23 a. Acute Aggregate Risk          .   ... 24 b. Chronic Aggregate Risk            ... .. 24 9. Occupational Risk                  ... 25 a. Occupational Toxicity              . 26 b. Occupational Handler Exposure           26 c. Occupational Handler Risk Summary       ... 30 d. Occupational Post application Risk Summary    . 34 9. Human Incident Data        ...        ... 37 B. Environmental Risk Assessment               .. 38 1. Environmental Fate and Transport           ... 38 a. Bioaccumulation in Aquatic Organisms        40 2. Ecological Risk                    . 40 a. Environmental Toxicity...            ... 40 b. Ecological Exposure and Risk      .     . 44 c. Risk to Listed Species       .       . 47 IV. Risk Management, Reregistration, and Tolerance Reassessment Decision  49 A. Determination of Reregistration Eligibility           . 49 B. Public Comments and Responses               .. 49 C. Regulatory Position                      50 1. Food Quality Protection Act Findings          ... 50 a. " Risk Cup" Determination            . 50 b. Determination of Safety to U. S. Population     .. 50 c. Determination of Safety to Infants and Children   . 50 d. Endocrine Disruptor Effects           .. 51 e. Cumulative Risks                . 52 2. Tolerance Summary                   52 a. Currently Established Tolerances Under 40 CFR 180.288 & Tolerance Reassessment of TCMTB   ... 52 b. Codex Harmonization              . 53 D. Regulatory Rationale                    .. 53 1. Human Health Risk Management            . 54 a. Dietary ( Food) Risk Mitigation          .. 54 b. Drinking Water Risk Mitigation           54 c. Residential Risk Mitigation             54 i. Handler Risk Mitigation           . 54 ii. Post Application Risk Mitigation  .    . 54 d. Occupational Risk Mitigation            55 i. Handler Risk Mitigation           . 55 ii. Post Application Risk Mitigation .     . 56 2. Environmental Risk Management          ... .. 56 3. Other Labeling Requirements               57 4. Listed Species Considerations          ..   .. 57 a. The Endangered Species Act  .         . 57 b. General Risk Mitigation    ...        .. 58 V. What Registrants Need to Do                     60 A. Manufacturing Use Products                  62 1. Additional Generic Data Requirements           62 2. Labeling for Technical and Manufacturing Use Products  .. 64 B. End Use Products                   ...   64 1. Additional Product Specific Data Requirements    ......... 64 2. Labeling for End Use Products             .. 64 a. Label Changes Summary Table          . 64 VI. Appendices                           . 66 A. Table of Use Patterns for TCMTB              . . 67 B. Table of Generic Data Requirements and Studies Used to Make the Reregistration Decision              ..................... 86 C. Technical Support Documents                .. 94 D. Bibliography Citations                   ... 96 E. Generic Data Call In                    .. 108 F. Product Specific Data Call In                  109 G. Batching of End Use Products                .. 110 H. List of All Registrants Sent the Data Call In          ... 111 I. List of Available Forms                   ... 112 i TCMTB Reregistration Team Health Effects Risk Assessment Deborah Smegal Robert Quick Siroos Mostaghimi Jonathan Chen Charles Smith Samuel Ary Timothy McMahon Chris Jiang Ecological Risk Assessment Kathryn Montague Environmental Fate Risk Assessment Srinivas Gowda James Lin Risk Management K. Avivah Jakob Diane Isbell ii GLOSSARY OF TERMS AND ABBREVIATIONS a. i. Active Ingredient aPAD Acute Population Adjusted Dose APHIS Animal and Plant Health Inspection Service ARTF Agricultural Re entry Task Force BCF Bioconcentration Factor CDC Centers for Disease Control CDPR California Department of Pesticide Regulation CFR Code of Federal Regulations ChEI Cholinesterase Inhibition CMBS Carbamate Market Basket Survey cPAD Chronic Population Adjusted Dose CSFII USDA Continuing Surveys for Food Intake by Individuals CWS Community Water System DCI Data Call In DEEM Dietary Exposure Evaluation Model DL Double layer clothing { i. e., coveralls over SL} DWLOC Drinking Water Level of Comparison EC Emulsifiable Concentrate Formulation EDSP Endocrine Disruptor Screening Program EDSTAC Endocrine Disruptor Screening and Testing Advisory Committee EEC Estimated Environmental Concentration. The estimated pesticide concentration in an environment, such as a terrestrial ecosystem. EP End Use Product EPA U. S. Environmental Protection Agency EXAMS Tier II Surface Water Computer Model FDA Food and Drug Administration FFDCA Federal Food, Drug, and Cosmetic Act FIFRA Federal Insecticide, Fungicide, and Rodenticide Act FOB Functional Observation Battery FQPA Food Quality Protection Act FR Federal Register GL With gloves GPS Global Positioning System HIARC Hazard Identification Assessment Review Committee IDFS Incident Data System IGR Insect Growth Regulator IPM Integrated Pest Management RED Reregistration Eligibility Decision LADD Lifetime Average Daily Dose LC50 Median Lethal Concentration. Statistically derived concentration of a substance expected to cause death in 50% of test animals, usually expressed as the weight of substance per weight or volume of water, air or feed, e. g., mg/ l, mg/ kg or ppm. LCO Lawn Care Operator LD50 Median Lethal Dose. Statistically derived single dose causing death in 50% of the test animals when administered by the route indicated ( oral, dermal, inhalation), expressed as a weight of substance per unit weight of animal, e. g., mg/ kg. LOAEC Lowest Observed Adverse Effect Concentration LOAEL Lowest Observed Adverse Effect Level LOC Level of Concern LOEC Lowest Observed Effect Concentration mg/ kg/ day Milligram Per Kilogram Per Day MOE Margin of Exposure MP Manufacturing Use Product MRID Master Record Identification ( number). EPA's system of recording and tracking studies submitted. MRL Maximum Residue Level iii N/ A Not Applicable NASS National Agricultural Statistical Service NAWQA USGS National Water Quality Assessment NG No Gloves NMFS National Marine Fisheries Service NOAEC No Observed Adverse Effect Concentration NOAEL No Observed Adverse Effect Level NPIC National Pesticide Information Center NR No respirator OP Organophosphorus OPP EPA Office of Pesticide Programs ORETF Outdoor Residential Exposure Task Force PAD Population Adjusted Dose PCA Percent Crop Area PDCI Product Specific Data Call In PDP USDA Pesticide Data Program PF10 Protection factor 10 respirator PF5 Protection factor 5 respirator PHED Pesticide Handler's Exposure Data PHI Pre harvest Interval ppb Parts Per Billion PPE Personal Protective Equipment PRZM Pesticide Root Zone Model RBC Red Blood Cell RED Reregistration Eligibility Decision REI Restricted Entry Interval RfD Reference Dose RPA Reasonable and Prudent Alternatives RPM Reasonable and Prudent Measures RQ Risk Quotient RTU ( Ready to use) RUP Restricted Use Pesticide SCI GROW Tier I Ground Water Computer Model SF Safety Factor SL Single layer clothing SLN Special Local Need ( Registrations Under Section 24C of FIFRA) STORET Storage and Retrieval TEP Typical End Use Product TGAI Technical Grade Active Ingredient TRAC Tolerance Reassessment Advisory Committee TTRS Transferable Turf Residues UF Uncertainty Factor USDA United States Department of Agriculture USFWS United States Fish and Wildlife Service USGS United States Geological Survey WPS Worker Protection Standard iv ABSTRACT The Environmental Protection Agency ( EPA or the Agency) has completed the human health and environmental risk assessments for 2( thiocyanomethylthio) benzothiazole ( TCMTB) and is issuing its risk management decision and tolerance reassessment. The risk assessments, which are summarized below, are based on the review of the required target database supporting the use patterns of currently registered products and additional information received through the public docket. After considering the risks identified in the revised risk assessments, comments received, and mitigation suggestions from interested parties, the Agency developed its risk management decision for uses of TCMTB that pose risks of concern. As a result of this review, EPA has determined that TCMTB containing products are eligible for reregistration, provided that risk mitigation measures are adopted and labels are amended accordingly. That decision is discussed fully in this document. 1 I. Introduction The Federal Insecticide, Fungicide, and Rodenticide Act ( FIFRA) was amended in 1988 to accelerate the reregistration of products with active ingredients registered prior to November 1, 1984 and amended again by the Pesticide Registration Improvement Act of 2003 to set time frames for the issuance of Reregistration Eligibility Decisions. The amended Act calls for the development and submission of data to support the reregistration of an active ingredient, as well as a review of all submitted data by the U. S. Environmental Protection Agency ( EPA or the Agency). Reregistration involves a thorough review of the scientific database underlying a pesticide's registration. The purpose of the Agency's review is to reassess the potential hazards arising from the currently registered uses of the pesticide; to determine the need for additional data on health and environmental effects; and to determine whether or not the pesticide meets the " no unreasonable adverse effects" criteria of FIFRA.

On August 3, 1996, the Food Quality Protection Act of 1996 ( FQPA) was signed into law. This Act amends FIFRA to require tolerance reassessment. The Agency has decided that, for those chemicals that have tolerances and are undergoing reregistration, the tolerance reassessment will be initiated through this reregistration process. The Act also requires that by 2006, EPA must review all tolerances in effect on the day before the date of the enactment of the FQPA. FQPA also amends the Federal Food, Drug, and Cosmetic Act ( FFDCA) to require a safety finding in tolerance reassessment based on factors including consideration of cumulative effects of chemicals with a common mechanism of toxicity. This document presents the Agency's revised human health and ecological risk assessments and the Reregistration Eligibility Decision ( RED) for 2( thiocyanomethylthio) benzothiazole ( TCMTB).

As an antimicrobial pesticide, TCMTB has several uses. TCMTB is used as a wood preservative for antisapstain control, a microbiocide/ microbiostat and bacteriocide/ bacteriostat in industrial processes and water systems ( e. g., pulp and paper mill systems, sewage systems) and in industrial/ residential materials preservatives ( e. g., pulp/ paper products, leather products and hides, paint, latex, carpet, textiles, wallpaper). TCMTB is also used as an agricultural pesticide for seed treatment ( e. g., barley, oats, rice, wheat, safflower, cotton and sugar beets).

The Agency has concluded that the FQPA Safety Factor for TCMTB should be removed ( equivalent to 1X) based on: ( 1) the toxicology data base is complete with respect to assessing the increased susceptibility to infants and children as required by FQPA for TCMTB; ( 2) there is no concern for developmental neurotoxicity resulting from exposure to TCMTB in the rat and rabbit prenatal developmental studies and 2 generation reproduction study; ( 3) there is no evidence of increased susceptibility to the fetus following in utero exposure in the prenatal developmental toxicity studies or to the offspring when adults are exposed in the two generation reproductive study; and ( 4) the risk assessment does not underestimate the potential exposure for infants and children.

Risks summarized in this document are those that result only from the use of the active ingredient, TCMTB. The Food Quality Protection Act ( FQPA) requires that the Agency consider available information concerning the cumulative effects of a particular pesticide's residues and other substances that have a common mechanism of toxicity. The reason for consideration of other substances is due to the possibility that low level exposures to multiple chemical substances that cause a common toxic effect by a common toxic mechanism could lead 2 to the same adverse health effect that would occur at a higher level of exposure to any of the substances individually. Unlike other pesticides for which EPA has followed a cumulative risk approach based on a common mechanism of toxicity, EPA has not made a common mechanism of toxicity finding for TCMTB and any other substances. TCMTB does not appear to produce a toxic metabolite produced by other substances. For the purposes of this action, therefore, EPA has not assumed that TCMTB has a common mechanism of toxicity with other substances. For information regarding EPA's efforts to determine which chemicals have a common mechanism of toxicity and to evaluate the cumulative effects of such chemicals, see the policy statements released by EPA's Office of Pesticide Programs concerning common mechanism determinations and procedures for cumulating effects from substances found to have a common mechanism on EPA's website at http:// www. epa. gov/ pesticides/ cumulative.

This document presents the Agency's decision regarding the reregistration eligibility of the registered uses of TCMTB. In an effort to simplify the RED, the information presented herein is summarized from more detailed information which can be found in the technical supporting documents for TCMTB referenced in this RED. The revised risk assessments and related addenda are not included in this document, but are available in the Public Docket at http:// www. regulations. gov ( Docket ID # EPA HQ OPP 2006 0320).

This document consists of six sections. Section I is the introduction. Section II provides a chemical overview, a profile of the use and usage of TCMTB and its regulatory history. Section III, Summary of TCMTB Risk Assessments, gives an overview of the human health and environmental assessments, based on the data available to the Agency. Section IV, Risk Management, Reregistration, and Tolerance Reassessment Decision, presents the reregistration eligibility and risk management decisions. Section V, What Registrants Need to Do, summarizes the necessary label changes based on the risk mitigation measures outlined in Section IV. Finally, the Appendices list all use patterns eligible for reregistration, bibliographic information, related documents and how to access them, and Data Call In ( DCI) information. 3 II. Chemical Overview A. Regulatory History TCMTB was first registered as an active ingredient by the United States Environmental Protection Agency ( EPA) on January 21, 1980. Currently, there are 27 products containing TCMTB. TCMTB products are used in commercial/ institutional premises and residential and public access areas. As an antimicrobial pesticide, TCMTB is used largely as a materials preservative ( e. g., leather products and hides, pulp/ paper products, latex, wallpaper, paints, carpets). TCMTB is a slimicide regulated by the FDA ( 21 CFR 176.300) for controlling bacteria, fungi and yeasts, which cause deterioration of paper and paperboard products.

TCMTB is also used as a fungicide for commercial and on farm seed treatment. TCMTB has 23 tolerances in the 40 CFR 180.288 for use as a fungicide on barley, sugar beets, cotton, oats, rice, safflower and wheat. Seed treatment use of TCMTB are not being supported by the technical registrant but are being supported by end users.

B. Chemical Identification Technical TCMTB N S S S N Figure 1. Molecular Structure of TCMTB Common name: TCMTB or TCMB Chemical name: 2( thiocyanomethylthio) benzothiazole Chemical family: Thiazole Empirical formula: C9H6N2S3 CAS Registry No.: 21564 17 0 Case number: 2625 OPP Chemical Code: 035603 Molecular weight: 238 g/ mol Other names: 2( Benzothiazolythio) methyl thiocyanate, TCMTB, TCMB, Busan 72 4 Basic manufacturers: Buckman Laboratories Chemical properties: TCMTB is a vivid orange liquid with a strong sour and pungent odor ( like mineral oil). TCMTB is a liquid and, therefore, has no melting point. It has a boiling point of 1910C, and decomposition begins at 741.9 mm Hg. TCMTB has a log Kow of 3.23 at 20oC.

C. Use Profile The following information is a description of the currently registered uses of TCMTB products and an overview of use sites and application methods. A detailed table of the uses of TCMTB eligible for reregistration is contained in Appendix A.

Type of Pesticide: Microbiocide/ microbiostat, bacteriocide/ bacteriostat, slimicide, fungicide, algecide.

Summary of Use: Materials Preservatives: For use in industrial premises and residential & public access areas as a materials preservative in leather processing liquors/ extracts ( preservative incorporation), leather products and hides ( preservative incorporation), textiles/ fibers/ cordage ( preservative/ additive incorporation), paints, sealants, emulsions/ slurries/ solutions, adhesives ( preservative incorporation), coatings ( preservative incorporation), , metalworking cutting fluids ( preservative incorporation), oil recovery drill muds/ packer fluids ( preservative incorporation), nonfood pulp/ paper and paper products ( preservative/ additive incorporation), wet end/ industrial process chemicals ( preservative incorporation), caulking compounds, vinyl wallpaper pastes, latex, dispersed colors, fuels ( additive incorporation) and paper/ paperboard surface treatments.

Wood Preservative: TCMTB is used to control sapstain and mold in commercial/ industrial premises and residential & public access areas on forest products ( seasoned, unseasoned, unpainted), lumber, poles/ posts, timbers, wood walls, wood ( particleboard), wood shingles ( roof), wood pressure treatment, wood millwork, wood products, wood sashes, wet lap/ sheet pulp, wood surfaces, wood porches/ decks, wood fences, wood homes/ houses, wood steps, window frames, wood doors, wood siding and wood barns.

Industrial Processes and Water Systems: For use in commercial and industrial water cooling tower systems, pulp and paper mill systems, secondary oil recovery injection water, sewage 5 systems, non potable water storage tanks, fuel and oil storage tanks bottom water, industrial disposal water, waste water systems, sewage effluent water, storage tanks, metalworking cutting fluids and water based cutting fluid mixes.

Agricultural: TCMTB is used as a fungicide for treating seeds ( barley, oats, rice, wheat, safflower, cotton and sugar beets) in commercial and on farm settings.

Target Pests: Bacteria ( unspecified); bacterial blight ( xanthomonas); bacterial slime ( of paper mills, water systems); basal rot ( fusarium); brown rot; bunt ( smut) ( tilletia); covered kernel smut ( sphacelotheca); covered smut ( ustilago kolleri/ ustilago); damping off ( fusarium/ pythium/ rhizoctonia/ thielviopsis), deterioration/ spoilage bacteria; dry rot; dry rot fungi; false loose smut ( ustilago avenae/ u. nigra); fungal decay/ rot; fungal slime ( of paper mills/ water systems); fungi ( coatings/ leather/ metal working coolants); fusarium blight; rot/ SPP; helminthosporium blight; mildew/ mold; rhizopus; rust ( puccinia); sapstain; scab ( head blight); seed and seedling diseases/ decay/ rot/ fungi; slime forming bacteria; sulfatereducing bacteria.

Formulation Types: Liquid ready to use, soluble concentrate, emulsifiable liquid, suspendedemulsion formulation intermediate, wettable powder.

Method and Rates of Application:

Equipment for Antimicrobial Use:

TCMTB end use products are added during the manufacturing process of treated articles and materials. Examples include: TCMTB being added directly to pulp slurry by chemical metering pump; dipping/ pressure impregnation or brush/ low pressure spraying of TCMTB for sapstain control; TCMTB directly mixed into solution for leather preservation.

Equipment for Agricultural Use: There are two primary methods for treating seeds: the batch system and the continuous flow system. There are various pieces of equipment used for on nursery seed treatment such as drum mixers, other devices using augers, cement mixers, hand cranked revolving drums, and gravity feed systems. TCMTB treated seed can be planted with a wide range of equipment. 6 Application Rates: For details about specific use sites for TCMTB, refer to Appendix A.

  Dosage rates of 0.025 0.2% ( 250 2,000 ppm) TCMTB solution can be used during various stages of leather processing.   Application rates can range from 0.026 lbs ai/ 100 lbs seed to 0.093 lbs ai/ 100 lbs of seed for seed treatment.   Application rates can range from 5.6 to 44.0 kg antisapstain product/ 100 L. of water for antisapstain treatment.

Use Classification: General use. 7 III. Summary of TCMTB Risk Assessments The purpose of this summary is to assist the reader by identifying the key features and findings of these risk assessments and to help the reader better understand the conclusions reached in the assessments. The human health and ecological risk assessment documents and supporting information listed in Appendix C were used to formulate the safety finding and regulatory decision for TCMTB. While the risk assessments and related addenda are not included in this document, they are available from the OPP Public Docket EPA HQ OPP 2006 0320, and may also be accessed from www. regulations. gov. Hard copies of these documents may be found in the OPP public docket. The OPP public docket is located in Room S 4900, One Potomac Yard, 2777 South Crystal Drive, Arlington, VA 22202, and is open Monday through Friday, excluding Federal holidays, from 8: 30 a. m. to 4: 00 p. m.

The Agency's use of human studies in the TCMTB risk assessment is in accordance with the Agency's Final Rule promulgated on January 26, 2006, related to Protections for Subjects in Human Research, which is codified in 40 CFR Part 26.

A. Human Health Risk Assessment 1. Toxicity of TCMTB A brief overview of the toxicity studies used for determining endpoints in the risk assessment is outlined below in Table 1. Further details on the toxicity of TCMTB can be found in the " Toxicology Disciplinary Chapter for the Reregistration Eligibility Decision ( RED) Risk Assessment," dated April 4, 2006; " 2( Thiocyanomethylthio) benzothiazole ( TCMTB) Risk Assessment for the Reregistration Eligibility Decision ( RED) Document," dated August 1, 2006; and " 2( Thiocyanomethylthio) benzothiazole ( TCMTB) Report of the Antimicrobials Division Toxicity Endpoint Selection Committee ( ADTC)," dated April 19, 2006. These documents are available on the Agency's website in the EPA Docket at: http:// www. regulations. gov ( Docket ID # EPA HQ OPP 2006 0320).

The Agency has reviewed all toxicity studies submitted for TCMTB and has determined that the toxicological database is sufficient for reregistration. The studies have been submitted to support guideline requirements.

Major features of the toxicology profile are presented below. TCMTB exhibits low acute oral and dermal toxicity ( toxicity category III). However, it is highly irritating to the eyes and skin ( toxicity category I and II, respectively) and is also considered to be highly toxic via the inhalation route of exposure ( toxicity category I). TCMTB is a dermal sensitizer. 8 Table 1. Summary of Acute Toxicity Data for TCMTB Guideline No. Study Type MRID #( s) Results Toxicity Category Acute Toxicity 870.1100 Acute oral toxicity 41583801 LD50 = 750 mg/ kg ( M+ F); 80% ai III 870.1200 Acute dermal toxicity 41515401 LD50 > 2000 mg/ kg ( M+ F); 80% ai III 870.1300 Acute inhalation toxicity 41640601 LC50= 0.07 mg/ L; 80% ai I 870.2400 Acute eye irritation Acc No. 111991 Diluted Busan 72 ( 60 % ai): Primary Irritation Score ( PIS)= 2/ 110 ( slight conjunctival redness, no corneal opacity); Undiluted Busan 72 ( 60% ai) PIS= 34/ 110 ( blanched conjunctivae, chemosis, corneal opacity not reversible by day 7) I 870.2500 Acute dermal irritation 41583701 Primary Irritation Index ( PIS)= 7.42 with severe erythema and edema observed at 72 hours; 80% ai II 870.2600 Skin sensitization MRID 42349201 Acc No. 259676 Busan 74 ( 80% ai) caused delayed contact hypersensitivity in guinea pigs when induced and challenged by a 40% w/ v aqueous concentration of active ingredient. Sensitizer.

Notes: LC = Lethal Concentration; LD = Lethal Dose; NA = Not Applicable 9 The doses and toxicological endpoints selected for the dietary exposure scenarios are summarized in Table 2 below:

Table 2. Dietary Toxicological Endpoints for TCMTB Exposure Scenario Dose Used in Risk Assessment, UF Special FQPA SF* and Level of Concern for Risk Assessment Study and Toxicological Effects Acute Dietary ( all populations, including infants and children) NOAEL= 25.1 mg/ kg/ day 83.55% ai purity UF = 100 ( 10x inter species extrapolation and intra species variation)

FQPA SF = 1x Acute PAD = 0.25 mg TCMTB/ kg/ day Developmental toxicity study in rats ( MRID 00154295, 92179009 ( 1985))

Maternal LOAEL = 76.5 mg TCMTB/ kg/ day, based on clinical signs of toxicity ( ventral alopecia, rough coat, dyspnea/ wheezing, oral discharge, diarrhea/ loose stool, urine staining, piloerection, and hunched gait).

Acute Dietary ( females 13 49) An endpoint specific for females 13 49 was not identified because the Acute Dietary endpoint for all populations is protective of developmental effects.

Chronic Dietary ( all populations) LOAEL = 3.8 mg/ kg/ day 81.6% ai purity UF = 300 ( 10x inter species extrapolation and intra species variation, 3x for use of a LOAEL)

FQPA SF = 1x Chronic PAD = 0.01 mg ai/ kg/ day Chronic toxicity study in dogs ( MRID 41342201, 92179008 ( 1989))

LOAEL = 3.8 mg/ kg/ day ( males), based on decreased body weight gain, decreased white cells, monocytes, and plasma ALT; decreased uterine weight in females.

Carcinogenicity The Agency concluded that TCMTB should be classified as Group C  possible human carcinogen  and recommended that for the purpose of risk characterization, the Reference Dose ( RfD) approach should be used for quantitation of human risk. This was based on statistically significant increases in tumors in both sexes of the Sprague Dawley rat: testicular interstitial cell adenomas in males and thyroid C cell adenomas in females. Notes: UF = uncertainty factor, FQPA SF = 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 ( a) Note: an additional UF of 10X is used for route extrapolation from an oral endpoint to determine if a confirmatory inhalation study is warranted. If results are below a MOE of 1,000, a confirmatory inhalation study may be required.

Developmental toxicity studies were available in both the rat and rabbit for TCMTB. Rabbits appear to be more sensitive to the toxicity of TCMTB than rats. In rabbits, the maternal NOAEL and LOAEL were significantly lower than those for rats. However, no developmental effects were noted in the rabbit at the highest dose tested ( 32 mg ai/ kg/ day). In the rat, adverse developmental effects including increased fetal and litter incidence of fused/ wavy ribs, 10 rudimentary cervical, thoracic and lumbar ribs and increased incidence of sternebrae and pelvic girdle anomalies were noted at doses of 105 mg ai/ kg/ day, which was maternally toxic.

In a two generation rat reproduction study, there were no treatment related effects noted at the highest dose tested for parental toxicity or on reproductive parameters examined in this study.

General Toxicity Observations Following subchronic oral exposures to rodents, TCMTB caused increased incidence of mild to severe stomach lesions characterized by inflammation, hyperplasia, necrosis, and ulceration. TCMTB resulted in decreased body weight gains ( 78 to 84% of control), food consumption ( 87 95% of control) and food efficiency. In a 21 day rat dermal toxicity study, TCMTB produced dose dependant dermal irritation in all dose groups beginning on treatment days 3 4, which progressed to eschar formation. Rats in the mid and high dose group had ulcers, hemorrhages and chronic dermatitis. Decreased body weight gain, food consumption, and hematological ( changes in hemoglobin, hematocrit, and segmented neutrophils) and clinical chemistry changes ( blood urea nitrogen, glucose, globulins, and elevated serum aspartate aminotransferase ( AST) were also noted. However, the clinical chemistry changes did not correspond to any treatment related findings in the liver or kidney.

The available toxicity data do no indicate neurotoxicity in the experimental animals exposed to TCMTB by either oral or derma routes.

Dogs appear to be the most sensitive species to TCMTB toxicity following chronic exposure. In the chronic dog toxicity study, adverse effects were noted at the lowest dose tested of 3.8 mg/ kg/ day. Adverse effects included decreased body weight gain, hematological effects ( changes in white blood cells, monocytes), alterations in clinical chemistry parameters ( plasma ALT) and decreased uterine weight in females.

In the chronic rat toxicity/ carcinogenicity study, no adverse effects were noted at the highest dose tested of 20 mg/ kg/ day. However, there was a statistically significant increase in the incidence of testicular interstitial cell adenomas in males of mid and high dose levels that had a highly significant positive dose related trend. Treatment was also associated with a possible increased incidence of thyroid C cell adenomas in females of the mid and high dose levels, which had a highly significant positive dose related trend, but did not attain a statistically significant level in the pairwise comparison with concurrent controls.

In the chronic mouse toxicity/ carcinogenicity study, decreased body weight gain was noted in both sexes, while there was a statistically increased incidence of focal and diffuse hyperplasia of duodenal mucosa in males. There was no evidence of carcinogenicity.

Dietary The acute RfD of TCMTB is 0.25 mg/ kg/ day. The acute RfD was determined by using a no observed effect level ( NOAEL) of 25.1 mg/ kg/ day for all populations based on clinical signs 11 of toxicity in maternal rats in a rat developmental study ( ventral alopecia, rough coat, dyspnea/ wheezing, oral discharge, diarrhea/ loose stool, urine staining, piloerection, and hunched gait). An uncertainty factor of 100 ( 10X for inter species extrapolation, 10X for intra species variability) was applied to the NOAEL.

The chronic RfD is 0.013 mg/ kg/ day for all populations. The chronic RfD was established by using a LOAEL of 3.8 mg/ kg/ day, which is based on a chronic dog study that observed decreased body weight gain, decreased white cells, monocytes and plasma ALT and decreased uterine weight in females. An uncertainty factor of 300 was applied ( 10X for interspecies extrapolation and intra species variation, and 3X for subchronic to chronic extrapolation).

Incidental Oral The NOAEL for the short and intermediate term incidental oral endpoint is 16 mg/ kg/ day, based on a rabbit developmental study. The target margin of exposure ( MOE) is 100 ( 10X for inter species extrapolation and intra species variation).

Short, Intermediate and Long term Dermal The short, intermediate and long term dermal NOAEL is 25 mg/ kg/ day, which is based on a dermal toxicity study. The uncertainty factor, or " target" MOE, for TCMTB dermal exposure is 100 for short and intermediate term durations and 300 for long term durations ( 10X for inter species extrapolation and intra species variation, and 3X for subchronic to chronic extrapolation).

Short and Intermediate term Inhalation The short and intermediate term inhalation endpoint is based on an oral rabbit developmental toxicity study NOAEL of 16 mg/ kg/ day. The long term inhalation endpoint is LOAEL of 3.8 mg/ kg/ day, based on a chronic toxicity study in dogs. In the absence of routespecific data, it was conservatively assumed that inhalation absorption is equivalent to oral absorption ( 100%). The target MOE for TCMTB is 100 for short and intermediate term durations and 300 for long term durations ( 10X for inter species extrapolation and intra species variation, 3X for subchronic to chronic extrapolation).

Carcinogenicity Classification TCMTB has been classified as group C, possible human carcinogen. In the chronic toxicity/ carcinogenicity study in rats there was a statistically significant increase in the incidence of testicular interstitial cell adenomas in males of mid ( 8 mg/ kg/ day) and high dose ( 20 mg/ kg/ day) levels, that had a highly significant positive dose related trend. Treatment was also associated with a possible increased incidence of thyroid C cell adenomas in females of the midand high dose levels, which had a highly significant positive dose related trend, but did not attain a statistically significant level in the pairwise comparison with concurrent controls. No historical data were available for review. 12 The Agency recommended that for the purpose of risk characterization the Reference Dose ( RfD) approach be used for quantifying the TCMTB cancer risk. The RfD approach is considered to be protective of any carcinogenic effect ( the chronic dietary endpoint is .01 mg/ kg/ day compared to .08 mg/ kg/ day). Further, the RfD approach was recommended because there is no apparent compound related increase in tumors in the mouse carcinogenicity study and there is no apparent concern for mutagenicity.

Mutagenicity Potential TCMTB was found to be negative for mutagenicity in the gene mutation assay with bacteria and did not cause an increase in unscheduled DNA synthesis ( UDS) in the rat hepatocytes assay. TCMTB was also found to be negative for chromosomal aberrations in the in vivo micronucleus assay in mice. Therefore, TCMTB is not mutagenic or genotoxic.

Endocrine Disruption Potential EPA is required under the Federal Food Drug and Cosmetic Act ( FFDCA), as amended by FQPA, to develop a screening program to determine whether certain substances ( including all pesticide active and other ingredients) " may have an effect in humans that is similar to an effect produced by a naturally occurring estrogen, or other such endocrine effects as the Administrator may designate." Following recommendations of its Endocrine Disruptor and Testing Advisory Committee ( EDSTAC), EPA determined that there was a scientific basis for including, as part of the program, the androgen and thyroid hormone systems, in addition to the estrogen hormone system. EPA also adopted EDSTAC's recommendation that the Program include evaluations of potential effects in wildlife. For pesticide chemicals, EPA will use FIFRA and, to the extent that effects in wildlife may help determine whether a substance may have an effect in humans, FFDCA authority to require the wildlife evaluations. As the science develops and resources allow, screening of additional hormone systems may be added to the Endocrine Disruptor Screening Program ( EDSP). When the appropriate screening and/ or testing protocols being considered under the Agency's Endocrine Disrupting Screening Program ( EDSP) have been developed, TCMTB may be subjected to additional screening and/ or testing to better characterize effects related to endocrine disruption.

2. Metabolite Assessment TCMTB has several metabolites, including 2 mercaptobenzothiazole ( 2 MBT) and 2 benzothiazolesulfonic acid ( 2 BTSA). The Agency's Risk Assessment Review Committee ( RARC) met and determined that the residue of concern for tolerance expression and risk assessment is TCMTB in/ on plants. 2 MBT and other TCMTB metabolites were not found at significant levels to be considered residues of concern. The determination of the residues of concern in plant commodities was based on tomato and melon metabolism studies and available toxicity data. 2 BTSA was found at significant levels ( 62% in tomato fruit); however, it was determined that it should be excluded as a residue of concern because it is expected to be less toxic than the parent TCMTB. 2 BTSA does not contribute significantly to the chronic toxicity of the parent. This decision is considered preliminary pending the results of confirmatory metabolism data that are required to support the currently registered uses of TCMTB. 13 For drinking water, the residues of concern included TCMTB and 2 MBT, based on an available aerobic soil metabolism study ( MRID 43532201). Although 2 MBT is distinctly less toxic than the parent, it was conservatively included in the drinking water assessment because it is a toxic metabolite of concern. All other metabolites were not found at significant levels; and are not to be considered residues of concern.

A summary of the decisions concerning the residues of concern in plants and drinking water are presented below in Table 3. For further information regarding the metabolism assessment of TCMTB please refer to, 3.0 Metabolism Assessment in the " 2 ( Thiocyanomethylthio) benzothiazole ( TCMTB) Risk Assessment for the Reregistration Eligibility Decision ( RED) Document," dated August 1, 2006.

Table 3. Summary of TCMTB Residues to be Included in the Risk Assessment and Tolerance Expression Matrix Residues Included in Risk Assessment Residues Included in Tolerance Expression Primary crop  barley, cotton, oat, rice, safflower, sugar beet, and wheat TCMTB TCMTB Plants Rotational crop NA = not applicable NA Ruminant NA NA Livestock Poultry NA NA Drinking water TCMTB and 2 MBT NA NA= Not applicable 3. FQPA Safety Factor The FQPA Safety Factor ( as required by the Food Quality Protection Act of 1996) is intended to provide an additional 10 fold safety factor ( 10X), to protect for special sensitivity in infants and children to specific pesticide residues in food, drinking water, or residential exposures, or to compensate for an incomplete database. The Agency has concluded that the FQPA Safety Factor should be removed ( i. e., reduced to 1X) for TCMTB based on: ( 1) a complete toxicology data base with respect to assessing the increased susceptibility to infants and children as required by FQPA; ( 2) a lack of evidence that TCMTB will induce neurotoxic effects; ( 3) no evidence of increased susceptibility to the fetus following in utero exposure in the prenatal developmental toxicity studies; ( 4) no evidence of increased susceptibility to the offspring when adults are exposed in the two generation reproductive study; and ( 5) the risk assessment does not underestimate the potential exposure for infants and children. Based on the analysis of submitted developmental toxicity studies, the Agency determined that no special FQPA Safety Factor was needed since there were no residual uncertainties for pre and/ or postnatal toxicity. 14 4. Population Adjusted Dose ( PAD)

Dietary risk is characterized in terms of the Population Adjusted Dose ( PAD), which reflects the reference dose ( RfD), either acute or chronic, that has been adjusted to account for the FQPA Safety Factor ( SF). This calculation is performed for each population subgroup. A risk estimate that is less than 100% of the acute or chronic PAD is not of concern. The Agency has conducted a dietary exposure and risk assessment for the use of TCMTB as a fungicide for seed treatment as well as a slimicide and materials preservative in pulp and paper manufacturing.

a. Acute PAD Acute dietary risk for TCMTB is assessed by comparing acute dietary exposure estimates ( in mg/ kg/ day) to the acute Population Adjusted Dose ( aPAD). Acute dietary risk is expressed as a percent of the aPAD. The aPAD is the acute reference dose ( 0.25 mg/ kg/ day) modified by the FQPA safety factor. The TCMTB acute reference dose was derived from a developmental toxicity study in rats in which a NOAEL ( 25 mg/ kg/ day) was determined. Acute dietary exposure was estimated for all populations, including infants and children. The TCMTB aPAD is 0.25 mg/ kg/ day based on a reference dose of 0.25 mg/ kg/ day and an FQPA safety factor of 1X.

b. Chronic PAD Chronic dietary risk for TCMTB is assessed by comparing chronic dietary exposure estimates ( in mg/ kg/ day) to the chronic Population Adjusted Dose ( cPAD). Chronic dietary risk is expressed as a percent of the cPAD. The cPAD is the chronic reference dose ( 0.01 mg/ kg/ day) modified by the FQPA safety factor. The cPAD was derived from a chronic toxicity study in dogs in which the LOAEL ( 3.8 mg/ kg/ day) was determined. The TCMTB cPAD is 0.01 mg/ kg/ day based on a reference dose of 0.01 mg/ kg/ day, which incorporates the FQPA safety factor ( 1X) for the overall U. S. population and all population subgroups.

5. Dietary Exposure Assumptions Acute and chronic dietary exposure assessments were conducted for the use of TCMTB as a fungicide for seed treatment as well as an antimicrobial pesticide for pulp and paper products.

Seed Treatment Use For the seed treatment use of TCMTB, conservative acute and chronic dietary exposure assessments incorporated maximum theoretical concentration factors for all commodities, existing tolerance level residues, and 100% crop treatment. These exposure assessments were conducted using the Dietary Exposure Evaluation Model software with the Food Commodity Intake Database ( DEEM FCID   , Version 2.03), which uses food consumption data from the USDA's Continuing Surveys of Food Intakes by Individuals ( CSFII) from 1994 1996 and 1998. 15 Antimicrobial Use The dietary risk assessment conducted for the antimicrobial use of TCMTB considered only potential food exposures from the antimicrobial uses of TCMTB because this use is expected to have minimal impact on drinking water exposure. In the absence of residue data, the Agency estimated antimicrobial residue levels that may occur in food that contacts treated pulp and paper products from the maximum application rates on TCMTB product labels. When assessing the antimicrobial dietary risks of TCMTB the Agency used FDA's Center for Food Safety & Applied Nutrition's ( CFSAN) screening level approach as presented in the " Preparation of Food Contact Notifications and Food Additive Petitions for Food Contact Substances: Chemistry Recommendations" dated April 2002. Using the maximum application rates and US FDA's default assumptions, " worst case" dietary concentration values were calculated by the Agency. This model was used to determine the estimated daily intake ( EDI).

In addition, the Agency estimated a total cumulative dietary intake of TCMTB that could result from simultaneous exposure from the three antimicrobial uses that were assessed ( pulp/ paper slimicide use; paper coating use; and paper adhesive preservative use).

6. Dietary Risk Assessment The Agency conducted a dietary exposure/ risk assessment for the use of TCMTB as a fungicide for seed treatment as well as an antimicrobial pesticide in pulp and paper products. Generally, a dietary risk estimate that is less than 100% of the acute or chronic PAD ( aPAD or cPAD) does not exceed the Agency's risk concerns. A summary of acute and chronic risk estimates are shown in Tables 4 and 5.

a. Dietary Risk from Food and Drinking Water Seed Treatment Use The Agency has determined that the acute dietary risk estimates do not exceed the Agency's level of concern ( less then 100% of the aPAD) at the 95th exposure percentile for the United States population ( less than 1% of the aPAD) and all population subgroups. The highest exposed population subgroup was children 3 5 years old at 2% of the aPAD.

The chronic dietary risk assessment concluded that for all supported agricultural uses of TCMTB, the chronic risk estimates are below the Agency's level of concern ( less than 100% of the cPAD) for the general U. S. population ( 7% of the cPAD) and all population subgroups. The highest exposed population subgroup was children 3 5 years old at 17% of the cPAD. 16 Table 4. Seed Treatment Use Summary of Dietary Exposure and Risk for TCMTB Using DEEM FCID ( Food and Water)

Acute Dietary ( 95th Percentile) Chronic Dietary Population Subgroup Dietary Exposure ( mg/ kg/ day) % aPAD b Dietary Exposure ( mg/ kg/ day) % cPAD b General U. S. Population 0.002430 < 1 0.000888 7 All Infants (< 1 year old) 0.003256 1 0.000994 8 Children 1 2 years old 0.004467 2 0.002054 16 Children 3 5 years old a 0.004581 2 0.002226 17 Children 6 12 years old 0.003370 1 0.001625 13 Youth 13 19 years old 0.002109 < 1 0.000936 7 Adults 20 49 years old 0.001547 < 1 0.000680 5 Adults 50+ years old 0.001192 < 1 0.000542 4 Females 13 49 years old 0.001529 < 1 0.000671 5 a The bolded values represent the highest exposed populations for each percentile. b % PAD = dietary exposure ( mg/ kg/ day) / aPAD or cPAD, where aPAD= 0.25 mg/ kg/ day ( for all populations) and cPAD= 0.013 mg/ kg/ day ( for all populations)

Antimicrobial Use TCMTB is used as a slimicide and paper coating preservative for controlling bacteria, fungi and yeasts that cause deterioration of paper and paperboard products and used to preserve paper adhesive formulations.

The results of the acute dietary risk estimates for the antimicrobial use of TCMTB are below the Agency's level of concern for all population subgroups (< 1% of the aPAD for all use sites). The highest dietary risk estimate was at 0.66% of the aPAD for infants and children. The chronic dietary analysis indicates that all risk estimates are below the Agency's level of concern for all population subgroups (< 13% of cPAD for all use sites). The highest dietary risk estimate was at 12.8% of the cPAD, for combined exposure to infants and children. 17 Table 5. Antimicrobial Use Summary of Dietary Exposure and Risk for TCMTB Acute Dietary Chronic Dietary Population Subgroup Dietary Exposure ( mg/ kg/ day) a % aPAD b Dietary Exposure ( mg/ kg/ day) a % cPAD b Pulp/ Paper Slimicide Adult Male 0.00024 0.096 0.00024 1.8 Adult Female ( 13 50 years old) 0.00028 0.11 0.00028 2.2 Infants/ Children 0.00056 0.22 0.00056 4.3 Paper Coating Preservative Adult Male 0.00017 0.07 0.00017 1.31 Adult Female ( 13 50 years old) 0.0002 0.08 0.0002 1.54 Infants/ Children 0.0004 0.16 0.0004 3.08 Paper Adhesive Preservative Adult Male 0.00030 0.12 0.00030 2.3 Adult Female ( 13 50 years old) 0.00035 0.14 0.00035 2.7 Infants/ Children 0.0007 0.28 0.0007 5.38 Cumulative Adult Male 0.00071 0.29 0.00071 5.41 Adult Female ( 13 50 years old) 0.00083 0.33 0.00083 6.44 Infants/ Children 0.0017 0.66 0.0017 12.8 a Acute and chronic exposure analysis based on body weights of 70kg, 60 kg, and 15 kg for adult males, females and children, respectively. b % PAD = dietary exposure ( mg/ kg/ day) / aPAD or cPAD, where aPAD= 0.25 mg/ kg/ day ( for all populations) and cPAD= 0.013 mg/ kg/ day ( for all populations)

b. Dietary Risk from Drinking Water The Agency estimated drinking water exposures for the seed treatment use of TCMTB, only. There are no antimicrobial uses associated with TCMTB that are expected to impact either surface or groundwater resources.

The seed treatment drinking water estimates were incorporated directly into the dietary risk assessment. Thus, the drinking water and food assessments are combined into the acute and chronic dietary risk estimates where risk is shown as % PAD. The drinking water analysis was 18 based on a derivation of estimated upper bound Tier I drinking water concentrations from TCMTB seed treatment uses, which were based on the FQPA Index Reservoir Screening Tool ( FIRST). Both TCMTB and its' degradate, 2 MBT, were included in the drinking water estimates. 2 MBT is distinctly less toxic than the parent; but was conservatively included in the drinking water assessment because it is considered a toxic metabolite of concern.

A number of conservative assumptions related to runoff and leaching were utilized as inputs including: a maximum application rate of 0.041 lb ai/ acre, no potential degradation and transformation reactions occur, no partitioning between the liquid phase and the solid phase occurs, and that TCMTB does not sorb to the seed coat ( only to the soil).

For surface drinking water, results from FIRST indicate that the peak ( acute) concentration of TCMTB and its' degradates is not likely to exceed 0.94 ug/ L ( ppb) and that the average annual ( chronic) concentration is not likely to exceed 0.67 ug/ L ( ppb). These drinking water concentrations were used in the acute and chronic dietary risk assessment for the agricultural uses of TCMTB as was discussed above.

For further details regarding the dietary risk assessment conducted for the seed treatment use of TCMTB, refer to the " Drinking Water Assessment for the Use of the Fungicide of 2 ( Thiocyanomethylthio) benzothiazole ( TCMTB) as a Seed Treatment on Cotton, Wheat, Barley, Oats, Rice, Sugar Beets, and Safflower," dated January 31, 2006.

It should be noted that the Agency estimated higher concentrations for exposure to aquatic animals resulting from the antisapstain use than were used in the drinking water assessment. These levels were not considered appropriate for use in the drinking water assessment due to the very conservative nature of the model used, that the model estimates runoff concentrations and not water body concentrations, and the fact that the model does not account for dilution.

7. Residential Risk Assessment Residential exposure from TCMTB can occur from the antimicrobial uses of TCMTB. The residential exposure assessment considers all potential pesticide exposure, other than exposure due to residues in food and drinking water. Exposure may occur during and after application methods including painting via brush/ roller and airless sprayer. Each route of exposure ( oral, dermal, inhalation) is assessed, where appropriate, and risk is expressed as a Margin of Exposure ( MOE), which is the ratio of estimated exposure to an appropriate No Observed Effect Level ( NOAEL) dose. Based on the application methods, TCMTB has been assessed for the residential mixing/ loading/ applicator ( or " handler") exposure.

a. Residential Toxicity The toxicological endpoints and associated uncertainty factors used for assessing the nondietary residential and occupational risks for TCMTB are listed in Table 6. 19 A MOE greater than or equal to 100 is considered adequately protective for the residential exposure assessment for the dermal and inhalation routes of exposure. The MOE of 100 includes 10x for inter species extrapolation, 10x for intra species variation.

Table 6. Residential and Occupational Toxicological Doses and Endpoints for TCMTB Exposure Scenario Dose Used in Risk Assessment ( mg/ kg/ day) Target MOEs/ UFs FQPA Safety Factor for Risk Assessment Study and Toxicological Effects Short Term and Intermediate Term Incidental Oral ( 1 30 days; 30 days 6months) NOAEL= 16.2 mg ai/ kg/ day 81% ai purity ( 20 mg TCMTB/ kg/ day) MOE = 100 ( ST and IT)

( 10X for interspecies extrapolation and intra species variation) Developmental toxicity study in rabbits ( MRID 40075101, 40075102, 92179011, ( 1986))

LOAEL = 32 mg ai/ kg/ day ( 40 mg TCMTB/ kg/ day) based on decreased body weight gain and food consumption in maternal animals.

Short Term, Intermediate Term and Long Term Dermal Exposure NOAEL= 25 mg/ kg/ day 82.33% ai purity ( 20.6 mg ai/ kg/ day) MOE = 100 ( ST and IT)

MOE = 300 ( LT) ( 10X for interspecies extrapolation and intra species variation, and 3X for duration of exposure) 21 Day dermal toxicity study in rats ( MRID 41655801)

LOAEL = 100 mg TCMTB/ kg/ day ( 82.3 mg ai/ kg/ day) based on decreased body weight gain, food consumption and hematological and clinical chemistry changes Short Term and Intermediate Term Inhalation Exposure NOAEL = 16.2 mg ai/ kg/ day 81% ai purity ( 20 mg TCMTB/ kg/ day)

Absorption = 100% ( inhalation and oral equivalent) MOE = 100 ( ST and IT)

( 10X for interspecies extrapolation and intra species variation) Developmental toxicity study in rabbits ( MRID 40075102)

LOAEL = 32 mg ai/ kg/ day ( 40 mg TCMTB/ kg/ day) based on decreased body weight gain and food consumption in maternal animals.

Long Term Inhalation Exposure LOAEL = 3.8 mg/ kg/ day 81.6% ai purity Absorption = 100% ( inhalation and oral equivalent) MOE = 300 ( a) ( LT)

( 10X for interspecies extrapolation and intra species variation and 3X for use of a LOAEL) Chronic toxicity study in dogs ( MRID 41342201, 92179008 ( 1989))

LOAEL = 3.8 mg/ kg/ day ( males) based on decreased body weight gain, decreased white cells, monocytes, and plasma ALT. Decreased uterine weight in females. 20 Exposure Scenario Dose Used in Risk Assessment ( mg/ kg/ day) Target MOEs/ UFs FQPA Safety Factor for Risk Assessment Study and Toxicological Effects Short and Intermediate Term Incidental Oral ( 1 30 days; 30 days 6 months) NOAEL= 16.2 mg ai/ kg/ day 81% ai purity ( 20 mg TCMTB/ kg/ day) MOE = 100 ( 10X for interspecies extrapolation and intra species variation) Developmental toxicity study in rabbits ( MRID 40075101, 40075102, 92179011 ( 1986))

LOAEL = 32 mg ai/ kg/ day ( 40 mg TCMTB/ kg/ day), based on decreased body weight gain and food consumption in maternal animals.

Cancer The Agency concluded that TCMTB should be classified as a " Group C Possible Human Carcinogen" and recommended that for the purpose of risk characterization, the Reference Dose ( RfD) approach should be used for quantitation of human risk. The chronic RfD is protective of any potential carcinogenic effect. This decision was based on statistically significant increases in tumors in both sexes of the Sprauge Dawley rat ( testicular interstitial cell adenomas in males and thyroid C cell adenomas in females).

Notes: UF = uncertainty factor, NOAEL = no observed adverse effect level, LOAEL = lowest observed adverse effect level, LOC = level of concern, MOE = margin of exposure ( a) Note: An additional uncertainty factor ( UF) of 10X is used for route extrapolation from an oral endpoint to determine if a confirmatory inhalation study is warranted. If results are below a MOE of 1,000 a confirmatory inhalation study may be required.

b. Residential Handlers i. Exposure Assessment Residential exposure can occur through the application of TCMTB preserved paint via airless sprayer or paintbrush. EPA selected high end scenarios for each use site for the residential handler exposure assessment. These scenarios are listed below:

° Painting with an airless sprayer ° Painting with a brush/ roller There was no chemical specific exposure data to assess paint application with a brush roller or airless sprayer. Therefore, dermal and inhalation exposures were assessed for these scenarios using the Pesticide Handler Exposure Database ( PHED, Version 1.1) and values were found in the Residential Exposure SOPs ( U. S. EPA, 1997a, 2001). The dermal and inhalation exposures from these techniques have been normalized by the amount of active ingredient handled and reported as unit exposures ( UE), which are expressed as mg/ lb of active ingredient handled.

Maximum application rates, related use information and Agency standard values were used to assess residential handler exposure. For example, it was conservatively assumed that a resident applies 15 gallons of paint per day using an airless sprayer and 2 gallons of paint per day using a brush/ roller. The residential handler scenarios were assumed to be of short term duration ( 1 30 days). 21 ii. Risk Assessment Based on toxicological criteria and potential for exposure, the Agency has conducted dermal and inhalation exposure assessments. A MOE greater than or equal to 100 is considered adequately protective for the residential exposure assessment for the dermal and inhalation routes of exposure. The MOE of 100 includes 10x for inter species extrapolation, 10x for intraspecies variation.

All of the inhalation MOEs for residential handlers are above the target MOE of 100 and, therefore, are not of concern. For the residential handler dermal risk assessment, dermal MOEs are below the target of 100 and, therefore, are of concern ( MOE of 10 for airless sprayer, MOE of 25 for paint brush). In addition, total dermal and inhalation risk estimates were of concern primarily because of the dermal route of exposure. A summary of the residential handler exposures and risks are presented on Table 7.

Table 7. Residential Handler Risk Summary ( Short Term Duration) Exposure Scenario Use site Dermal Dose ( mg/ kg/ day) a Inhalation Dose ( mg/ kg/ day) b Dermal MOEc Inhalation MOEd Total Dermal and Inhalation MOE Airless Sprayer Residential/ Household Premises 2.54 0.0267 10 600 9.8 Paintbrush/ Roller Residential/ Household Premises 0.986 0.00122 25 13,000 25 a Dermal Dose ( mg/ kg/ day) = [ Unit dermal exposure ( mg/ lb ai) * Use rate ( lb ai/ lb product or lb ai/ gal product) * Amount handled per day ( lb product/ day)] / Body weight ( kg) b Inhalation Dose ( mg/ kg/ day) = [ Unite inhalation exposure ( mg/ lb ai) * Use rate ( lb ai/ lb product or lb ai/ gal product) * Amount handled per day ( lb product/ day) * inhalation absorption ( 1.0)] / Body Weight ( kg)

c Dermal MOE = Dermal NOAEL ( mg/ kg/ day) / Dermal Dose ( mg/ kg/ day), where the NOAEL is 25 mg/ kg/ day from the sub chronic rat dermal toxicity study d Inhalation MOE = Inhalation NOAEL ( mg/ kg/ day) / Inhalation Dose ( mg/ kg/ day), where the inhalation NOAEL of 16 mg/ kg/ day is from an oral rabbit developmental study. In absence of data, inhalation absorption is assumed to be equivalent to oral absorptions.

c. Residential Post application i. Exposure Assessment Residential post application exposures result when adults and children come in contact with TCMTB in areas where pesticide end use products have recently been applied ( e. g., treated textiles/ carpeting), or when children incidentally ingest the pesticide residues through mouthing the treated end products/ treated articles ( i. e., hand to mouth or object to mouth contact). The residential post application scenarios considered in this assessment are from exposure to residues on carpets that have been treated with TCMTB and wearing clothing that was treated with TCMTB. 22 There is the potential for dermal exposure to toddlers crawling on carpets preserved with TCMTB. Short term dermal risks to children have been identified, as the preservative is applied only during the manufacturing of the carpet. In addition to dermal exposure, infants crawling on treated floors will also be exposed to TCMTB via incidental oral exposure through hand tomouth transfer. To calculate incidental ingestion exposure to TCMTB due to hand to mouth transfer, the scenarios established in EPA's " Standard Operating Procedures ( SOPs) for Residential Exposure Assessments" were used.

The Agency evaluated the following three post application scenarios, which are considered to be representative of all possible residential exposure scenarios:

° Contact with treated carpets by children ( incidental oral and dermal exposure to children); ° Wearing treated textiles/ leather products ( dermal exposure to children and adults); ° Mouthing treated textiles such as clothing/ blankets/ leather products ( incidental oral exposure to children).

For treated textiles/ leather products, the Agency believes exposures are primarily shortterm because residents are assumed to be exposed to treated textiles with varying active ingredients and that these textiles have not exclusively been treated with TCMTB. However, if the products are used on a routine basis ( i. e., once a week or impregnated into carpets as materials preservative) and the active ingredient has a long indoor half life, exposures may occur over an intermediate term ( 30 days 6 months). The Agency did not have residue dissipation data or reliable use pattern data, including the frequency and duration use of antimicrobial products in residential settings. Because of this lack of data, intermediate term exposure was assessed to provide an upper bound estimate of exposure to treated textiles.

A number of conservative assumptions were used in assessing post application risks including maximum application rates from TCMTB product labels. In addition, quantities handled/ treated were estimated based on information form various resources, including the Draft Standard Operating Procedures ( SOPs) for Residential Exposure Assessments ( USEPA 2000, 2001) and standard Agency residential SOP assumptions. Standard values were not available for the textile and treated leather product uses. For these scenarios, it was assumed that either 100% or 5% of TCMTB could transfer and be available for dermal contact.

ii. Risk Assessment Based on toxicological criteria and potential for exposure, the Agency has conducted dermal and incidental oral exposure assessments. A MOE greater than or equal to 100 is considered adequately protective for the residential exposure assessment for the dermal, incidental oral and inhalation routes of exposure. The MOE of 100 includes 10x for interspecies extrapolation and 10x for intra species variation.

The residential post application risk assessment identifies short term ( 1 30 days) and intermediate term ( 1 6 month) exposure doses based on the reported toxicology endpoints for TCMTB. Because the toxicological endpoints are identical for short and intermediate term 23 durations for both dermal and incidental oral exposures, the Agency calculated a total MOE for children.

The short term and intermediate term MOEs for dermal contact with treated clothing/ leather products are of concern for both young children and adults ( MOEs are less than 1, assuming a 100% transfer factor; MOEs are less than 10, assuming a 5% transfer factor). In addition, the dermal MOE is of concern for young children crawling on treated carpets ( MOE of 2). TCMTB is a dermal sensitizer and thus, there is a potential for adverse dermal allergic reactions from direct skin contact of treated textiles.

The short and intermediate term MOEs for incidental oral ingestion of treated carpets by children exceeds the Agency's level of concern ( MOE of 4). In addition, the short term oral MOE for children mouthing treated textiles/ leather products is also a risk of concern as the MOE ( MOE of 21) is below the target of 100.

As shown in Table 8, the total MOE for children who may contact TCMTB treated carpet and treated clothing/ leather products is less then 1 and, therefore, the total ( oral and dermal exposures combined) MOE for children is of concern.

Table 8 presents a summary of the short term and intermediate term residential postapplication exposures and risk estimates.

Table 8. Antimicrobial Short and Intermediate term Residential Post application Exposures and Risk Summary Dose a ( mg/ kg/ day) MOEb ( Target MOE> 100) Scenario Child Adult Child Adult Dermal Exposure Treated carpets 15.6 mg/ kg/ day NA 2 NA 4.3 mg/ kg/ day ( 5% transfer) 2.7mg/ kg/ day ( 5% transfer) 5.8 ( 5% transfer) 9.1 ( 5 % transfer) Treated clothing/ leather products 86 mg/ kg/ day ( 100% transfer) 55 mg/ kg/ day ( 100% transfer) < 1 ( 100% transfer) < 1 ( 100% transfer) Incidental Oral Exposure Treated carpets 3.81 mg/ kg/ day NA 4.2 NA Treated clothing/ leather products 0.758 mg/ kg/ day NA 21 NA TOTAL MOE RISK ESTIMATE NA < 1 c NA NA= Not applicable a Dose calculations for each scenario above are outlined in the attached Occupational/ Residential Assessment ( memo from S. Mostaghimi, February 2006). b MOE= NOAEL ( mg/ kg/ day) / PDR ( mg/ kg/ day). Oral NOAEL is 16 mg/ kg/ day; dermal NOAEL is 25 mg/ kg/ day. c Total MOE includes carpet ( dermal and oral) and clothing ( dermal and oral) exposures using the exposure estimates based on 5% residue transfer.

8. Aggregate Risk Assessment The Food Quality Protection Act amendments to the Federal Food, Drug, and Cosmetic Act ( FFDCA, Section 408( b)( 2)( A)( ii)) require " that there is a reasonable certainty that no harm will result from aggregate exposure to pesticide chemical residue, including all anticipated 24 dietary exposures and other exposures for which there are reliable information." Aggregate exposure typically includes exposures from food, drinking water, residential uses of a pesticide, and other non occupational sources of exposure.

The acute aggregate risk assessment is designed to provide estimates of risks likely to result from exposures to the pesticide or pesticide residues in food, water, and from residential ( or other non occupational) pesticide uses. As previously mentioned in section six of this document, " Residential Risk Assessment," the antimicrobial residential uses evaluated for TCMTB have risks of concern for residential handlers applying paint via airless sprayer or brush roller; children playing on, or mouthing treated carpets; and, adults and children wearing treated textiles/ leather products. An aggregate assessment for short and intermediate term residential exposures was not conducted, because risks of concern were previously identified for individual residential exposure scenarios. An aggregate assessment would only reflect the identified individual risks of concern and, therefore, was unnecessary. There are no long term residential exposure scenarios for TCMTB.

However, the Agency conducted both acute and chronic dietary aggregate assessments, which considered food ( antimicrobial and agricultural) and drinking water ( agricultural only) exposures, for the registered antimicrobial and agricultural uses.

In the case of TCMTB, a cancer aggregate assessment is not needed, as the chemical has been classified by the Agency as having " Possible Human Carcinogen." Because an RfD approach was used to evaluate chronic dietary risk and is considered protective of any cancer risk concern, only the results of the chronic analysis are given.

a. Acute Aggregate Risk The acute aggregate risk assessment considered the 95th percentile dietary exposure ( food and drinking water) from the agricultural seed treatment uses, as well as the acute dietary exposure ( food only) from the antimicrobial uses in pulp and paper. While it is standard to use the chronic drinking water exposure estimate for acute aggregate risk assessments this was not done in this case. Since the acute food and drinking water exposures were combined into a single exposure estimate for the acute dietary assessment, this value was used in the aggregate assessment. Using the acute drinking water estimate is a more conservative approach than the standard method of conducting such an assessment. As shown in Table 9, the acute dietary aggregate risk is 2.5% of the aPAD for children and less than 1.3% of the aPAD for adults. These risk estimates are below the Agency's level of concern. 25 Table 9. TCMTB Acute Aggregate Risk Estimates Dose a ( mg/ kg/ day) % aPADb Exposure Scenario Child ( 15 kg) Adult Child ( 15 kg) Adult Dietary Exposure Agricultural Seed Treatment ( Food and Water) 0.004581 0.00243 1.8% < 1%

Antimicrobial Uses Total Pulp/ Paper/ Adhesive ( Food) 0.0017 0.00083 0.66% 0.33 Total Aggregate Dose and Risk 0.00628 0.00328 2.5% < 1.3%

NA= Not applicable ( a) Acute dietary exposure for females 13 50 years for antimicrobials uses. ( b) % aPAD = dietary exposure ( mg/ kg/ day) / aPAD, where aPAD = 0.25 mg/ kg/ day for all populations.

b. Chronic Aggregate Risk The chronic aggregate risk assessment considered average dietary exposure ( food and drinking water) from the agricultural seed treatment uses of TCMTB, as well as dietary exposure ( food only) from the antimicrobial uses of TCMTB in pulp and paper. As shown in Table 10, the chronic dietary aggregate risk estimate of TCMTB is 30% of the cPAD for children and is 13.4% of the cPAD for adults. These risk estimates are below the Agency's level of concern.

Table 10. TCMTB Chronic Aggregate Risk Estimates Dose a ( mg/ kg/ day) % cPADb Exposure Scenario Child ( 15 kg) Adult Child ( 15 kg) Adult Dietary Exposure Agricultural Seed treatment ( Food and Water) 0.002226 0.000888 17% 7%

Antimicrobial Uses Total Pulp/ Paper/ Adhesive ( Food) 0.0017 0.00083 12.8% 6.44 Total Aggregate Dose and Risk 0.003926 0.001718 30% 13.4%

NA= Not applicable ( a) Chronic dietary exposure for females 13 50 years for antimicrobials uses. ( b) % cPAD = dietary exposure ( mg/ kg/ day) / cPAD, where cPAD = 0.013 mg/ kg/ day for all populations.

9. Occupational Risk Workers can be exposed to a pesticide through mixing, loading, and/ or applying a pesticide, or re entering treated sites. TCMTB is used as an antimicrobial pesticide ( e. g., materials preservative, industrial processes and water systems, wood preservative and paint application) and as a seed treatment. Potential occupational exposure can occur in various use sites, which include commercial/ industrial premises, industrial process and water systems, from wood preservation, and from metal working fluid uses. 26 Occupational handlers of TCMTB include handlers applying TCMTB treated paint via airless sprayer or paint brush/ roller; handlers pouring TCMTB liquid preservative for paint preservation, textile preservation, drilling fluids, metal working fluids and small process water systems; handlers pumping ( metering) liquid preservative for metal working fluid, pulp and paper and cooling water systems, paint and textiles preservation, and small process water systems; and wood preservative handlers.

For the seed treatment use of TCMTB, occupational handlers include workers in agricultural seed treatment settings ( commercial and on farm settings) and workers handling seed previously treated ( post application worker exposure).

a. Occupational Toxicity The toxicological endpoints used in the occupational handler assessment of TCMTB can be found in Table 6, " Residential and Occupational Toxicological Doses and Endpoints for TCMTB", of this document.

b. Occupational Handler Exposure Occupational risk for all potentially exposed populations is measured by a Margin of Exposure ( MOE), which determines how close the occupational exposure comes to a No Observed Adverse Effect Level ( NOAEL) from toxicological studies. Occupational risk is assessed for exposure at the time of application ( termed " handler" exposure). Application parameters are generally defined by the physical nature of the formulation ( e. g., formula and packaging), by the equipment required to deliver the chemical to the use site and by the application rate required to achieve an efficacious dose.

The Agency evaluated representative scenarios using maximum application rates as recommended on TCMTB product labels. To assess handler risk, the Agency used surrogate unit exposure data from both the proprietary Chemical Manufacturers Association ( CMA) Antimicrobial Exposure Study ( USEPA, 1999) and the Pesticide Handlers Exposure Database ( PHED), ( USEPA, 1998). The duration of exposure to TCMTB is expected to be short term or intermediate term ( 1 day to 6 months) for most occupational scenarios. Wood preservation and metal working fluid uses were assumed to be long term exposure durations.

For more information on the assumptions and calculations of potential agricultural and antimicrobial risks of TCMTB to workers, see the Occupational Exposure Assessment ( Sections 9.0 9.2) in the " 2( Thiocyanomethylthio) benzothiazole ( TCMTB) Risk Assessment for the Reregistration Eligibility Decision ( RED) Document," dated August 1, 2006, the antimicrobial " Occupational and Residential Exposure Assessment for 2( Thiocyanomethylthio) benzothiazole TCMTB," dated April 19, 2006 and the " TCMTB [ 2( Thiocyanomethylthio) benzothiazole]: Third Revision of the Occupational and Residential Exposure Assessment for the Reregistration Eligibility Decision Document" for the agricultural uses of TCMTB, dated July 27, 2006. 27 Antimicrobial Use Inhalation and dermal exposures to TCMTB ( as an antimicrobial pesticide) were addressed for occupational populations for both short and intermediate term durations. The Agency used surrogate unit exposure data from the proprietary Chemical Manufacturers Associated ( CMA) antimicrobial exposure study ( USEPA, 1999) and the Pesticide Handlers Exposure Database ( PHED) to assess handler risks ( USEPA, 1998). MOEs for material preservation of paints, textiles, adhesives and metalworking fluid were calculated using unit exposure values from the cooling tower CMA data set ( USEPA, 1999) because exposure data were not available for ungloved handlers. Handler exposures were assessed for the application of TCMTB preserved paint.

For the airless sprayer scenario, PHED dermal and inhalation unit exposure values for a residential handler applying a pesticide using an airless sprayer were used. These unit un gloved exposure values ( 79 mg/ lb a. i. for dermal and 0.83 mg/ lb a. i. for inhalation) represent a handler wearing short pants and a short sleeve shirt, with no gloves. It was assumed that 15 gallons ( or 150 lb/ day, assuming paint has a density of 10 lb/ gal) of treated paint were to be used per day.

For the brush/ roller scenario, PHED dermal and inhalation unit exposure values for a residential handler applying a pesticide using an airless sprayer were used. These unit exposure values ( 230 mg/ lb a. i. for dermal and 0.284 mg/ lb a. i. for inhalation) represent a handler wearing short pants and a short sleeve shirt, with no gloves. It was assumed that for the brush/ roller paint applications 2 gallons ( or 20 lb/ day, assuming paint has a density of 10 lb/ gal) of treated paint were to be used per day.

The duration of exposure for most homeowner applications of paint is believed to be best represented by the short term duration ( 1 to 30 days). The reason that short term duration was chosen to be assessed is because the different handler and post application scenarios are assumed to be episodic, not daily. In addition, homeowners are assumed to use different products with varying activities, not exclusively TCMTB treated products.

The dermal and inhalation wood unit exposure values for wood preservation were based on two replicates where the test subjects were wearing a single layer of clothing and chemical resistant gloves. Surrogate unit exposures were taken from the CMA study ( USEPA, 1999). The quantity of the wood being treated was derived from other wood preservative estimates ( USEPA, 2004) for the amount of wood slurry treated because no chemical specific data were available for TCMTB. It was assumed that batches of wood slurry are treated in 10,000 gallon tanks and that eight batches of wood slurry are treated per day ( one per hour for an 8 hr work shift). Additionally, it was assumed that each batch requires 3,000 gallons of preservatives and the remainder volume of the tank consists of wood slurry ( 7,000 gallons of wood slurry per batch). Wood chips have a density of approximately 380 kg/ m3 ( SIMetric, 2005) and, therefore, the total amount of wood slurry treated per day would be 178,000 lbs ( 8 batches/ day * 7,000 gallons/ batch * 0.003785 m3/ gallon * 380 kg/ m3 * 2.2 lb/ kg). The assumptions used for batch sizes and the quantity of preservative needed are consistent with an assessment performed previously by the EPA. For this assessment, an application rate of 0.003 TCMTB w/ w was used. 28 Based on the antimicrobial use patterns of TCMTB, the exposure scenarios in Table 11 were assessed:

Table 11. TCMTB Antimicrobial Occupational Handler Scenarios Category Scenario Commercial Institutional Premises Airless sprayer and paint brush/ roller may be used as methods of application for paint application of TCMTB treated paint.

Materials Preservative Pouring or pumping TCMTB preservative into vats or tanks for preservation of textiles/ leather products, paints, adhesives and metal working fluid.

Industrial Processes and Water Systems Occupational Handler Scenarios:

Metered pumping, pouring or liquid pumping TCMTB into vats or tanks for drilling fluids, pulp and paper, and small process water systems/ cooling towers.

Post application Occupational Handler Scenarios:

Exposure can occur after the chemical has been incorporated into the cutting fluid and a machinist is using/ handling this treated end product.

Wood Preservative Occupational Handler Scenarios:   Blender/ spray operators are workers that add the wood preservative into a blender/ sprayer system for composite wood via closed liquid pumping.   Diptank Operators can be in reference to wood being lowered into the treating solution through an automated process ( i. e., elevator diptank, forklift diptank). This scenario can also occur in a smaller scale treatment facility in which the worker can manually dip the wood into the treatment solution.   Chemical operators for a spray box system consist of chemical operators, chemical assistants, chemical supervisors, and chemical captains. These individuals maintain a chemical supply balance along with flushing and cleaning spray nozzles.

Post application Occupational Handler Scenarios:   Graders, positioned right after the spray box, grade dry lumber by hand ( i. e. detect faults). In the DDAC study, graders graded wet lumber; therefore, the exposures to graders using TCMTB are worst case scenarios.   Millwrights repair all conveyer chains and general up keep of the mill.   Clean up crews perform general cleaning duties at the mill.   Trim saw operators operate the hula trim saw and consist of operators and strappers. In the DDAC study, hula trim saw operators handled dry lumber.   Construction workers install treated plywood, oriented strand board, medium density fiberboard, and others.

Agricultural Seed Treatment Uses EPA has assessed the exposure to handlers' mixing/ loading/ applying products containing TCMTB. Inhalation and dermal exposure scenarios were addressed for occupational populations for both short and intermediate term exposure durations. Occupational handler exposure estimates were based on surrogate data from the " Health Effects Division Science Advisory Committee on Exposure ( HED ExpoSAC) SOP # 15: Amount of Seed Treated or Planted per 29 Day", which was completed on March 2, 2004. Generic protection factors ( PFs) were used to calculate exposures when data were not available. For example, an 80 percent protection factor was assumed for the use of a respirator equipped with a quarter face dust/ mist filter. It was assumed that on farm treaters and planters are expected to have short term exposure duration ( less than 30 days) for all seed crops. It was also assumed that personal protective equipment for on nursery and commercial mixer/ loader/ applicators and planter includes a single layer and gloves. Personal protective equipment for commercial baggers and sewers includes baseline attire only  no gloves. Personal protective equipment for performing multiple activities in a commercial operation includes a single layer of clothing and gloves.

Exposure data used for the TCMTB seed treatment assessment are taken primarily from the Agency's recently developed seed treatment standard operating procedure ( SOPs for Seed Treatment, 6/ 1/ 03). The seed treatment SOP contains representative scenarios for worker exposure associated with seed treatment facilities and planting treated seed. These scenarios were used to describe the various types of handler exposures that may occur from TCMTB. Information from the current labels, use and usage information, toxicology data, and exposure data were all key components in the development of the exposure scenarios. Exposure estimates were taken from actual seed treatment studies and were based on exposure factors associated with occupational handler scenarios ( commercial seed treatment, on nursery seed treatment, planting of treated seed). Assessed application rates range from 0.026 lbs active ingredient/ 100 lbs of seed to 0.13 lbs active ingredient/ 100 lbs of seed.

Four categories of commercial seed treatment activities and two categories for on nursery activities were assessed and are shown in Table 12.

Table12. TCMTB Seed Treatment Occupational Handler Scenarios Category Scenario Agricultural Seed Treatment Commercial Seed Treatment Scenarios: ( S 1) Loading and applying liquid formulations with commercial seed treatment equipment. ( S 2) Commercial sewer stitching bags of seed. ( S 3) Bagging and otherwise handling treated seeds with commercial equipment. ( S 4) Multiple commercial seed treatment activities.

On Nursery Seed Treatment and Planting Post Application Scenarios: ( S 5) On nursery loading/ applying seed treatment. ( S 6) On nursery loading/ planting previously treated seeds. 30 c. Occupational Handler Risk Summary Antimicrobial Use The occupational handler risk assessment, for the antimicrobial use of TCMTB, included both inhalation and dermal exposure scenarios. The target MOE for short and intermediate term inhalation and dermal exposures was 100. The target MOE for long term dermal and inhalation exposures was 300. All but two of the short and intermediate term dermal and inhalation scenarios assessed were not of concern ( MOEs greater than 100). The following two dermal exposure scenarios indicate risks of concern even with the addition of chemical resistant gloves:

  Paint Application: Airless Sprayer ( ST/ IT Dermal MOE = 6.1 ungloved, MOE = 17 gloved)

  Paint Application: Paintbrush ( ST/ IT Dermal MOE = 30 ungloved, MOE = 97 gloved)

Risks of concern were identified for six use scenarios ( paint preservation liquid pour, paint preservation liquid pump, textile preservation liquid pour, textile preservation liquid pump, cutting fluid preservation liquid pour, pulp and paper liquid pump) at the baseline level of evaluation ( no PPE gloves). However, the dermal MOEs are greater than 100 with the addition of PPE ( gloves). Therefore, the use of PPE gloves eliminates all risks of concern for these six use scenarios.

The total dermal and inhalation MOEs with added PPE ( gloves) are not of concern for all but two of the scenarios evaluated. The following scenarios have remaining total dermal and inhalation MOEs that are less than 100 and are of concern:

  Paint Application: Airless Sprayer ( Total Dermal and Inhalation MOE = 16)

  Paint Application: Paintbrush ( Total Dermal and Inhalation MOE = 95)

For further information regarding the short and intermediate term risks associated with occupational handlers, refer to Tables 13 and 14. 31 Table 13. Antimicrobial Use Short and Intermediate Term Risks Associated with Occupational Handlers ST/ IT MOE c ( Target MOE   100) Exposure Scenario Method of Application Application Rate (% a. i. by weight) Quantity Handled/ Treated per day Baseline Dermala PPE Glove Dermal b Inhalation TOTAL MOE ( dermal and inhalation)

Airless Sprayer 500 lb/ day 6.1 17 180 16 Paint Application Paintbrush 50 lb/ day 30 97 5,300 95 Liquid Pour 2,000 lb/ day 1.2 430 11,000 414 Paint Preservation Liquid Pump 0.015 a. i. weight fraction 10,000 lb/ day 26 1900 19,000 1,727 Liquid Pour < 1 220 5,400 211 Textiles/ Leather Products Liquid Pump 0.006 a. i. weight fraction 10,000 lb/ day 64 4,600 46,000 4,182 Liquid Pour 11 3,000 42,000 2,800 Cutting Fluid Liquid Pump 0.00125 a. i. weight fraction 2,502 lb/ day 1,200 1,800 1.00x105 1,768 ST = 45.9 lb/ day ST = 1000 ST = 380,000 ST = 9.40x10 6 365,235 Drilling Fluids Liquid Pour IT = 22.9 lb/ day IT = 2,000 IT = 7.60x105 IT = 1.90x107 730,769 Pulp and Paper Liquid Pump 0.00075 a. i. weight fraction 1,000,000 lb/ day 5 510 5,600 467 Liquid Pour 90 lb/ day 43,000 21,000 3.10x106 20.858 Small Process Water Systems/ Cooling Tower Liquid Pump 0.000009 a. i. weight fraction 180,000 lb/ day 2,400 13,000 1.60x105 12,023 ST = short term; IT = intermediate term a Baseline Dermal: Long sleeve shirt, long pants, no gloves. b PPE Dermal with gloves: baseline dermal plus chemical resistant gloves. c MOE = NOAEL ( mg/ kg/ day) / Absorbed Daily Dose [ Where ST/ IT NOAEL = 25 mg/ kg/ day for dermal and 16 mg/ kg/ day for inhalation].

Table 14 provides short and intermediate term doses and MOEs for workers adding TCMTB preservative to wood slurry. When wearing single layer clothing and chemical resistant gloves, all MOEs are above the target MOE of 100 for ST/ IT dermal and inhalation and above 300 for LT dermal and inhalation exposures and, therefore, are not of concern. 32 Table 14. Short, Intermediate and Long term Risks Associated with Wood Preservative Blender/ Spray Operators Absorbed Daily Dosee ( mg/ kg/ day) MOEf Dermal Inhalation Total MOE Dermal Unit Exposurea ( mg/ lb ai) Inhalation Unit Exposureb ( mg/ lb ai) App. Ratec ( fraction ai in solution/

day) Wood Slurry Treatedd ( lb/ day) Dermal Inhal. ST/ IT/ LT ST/ IT LT ST/ IT LT Occupational Handler 0.00629 4.03x10 4 0.00300 1.78x105 0.0480 0.00307 520 5200 1200 478 364 ST = Short term duration; IT = Intermediate term duration; and LT = long term. a. Dermal unit exposure: Single layer clothing with chemical resistant gloves. b. Inhalation unit exposure: Baseline. c. The maximum application rate for the " immersion" application method is a solution containing 0.3% a. i. d. Wood slurry treated = ( 8 batches/ day * 7,000 gallons/ batch * 0.003785 m3/ gallon * 380 kg/ m3 * 2.2 lb/ kg) e. Absorbed Daily Dose = unit exposure ( mg/ lb ai) x App Rate ( fraction ai/ day) x Quantity treated ( lb/ day) / BW ( 70 kg) f. MOE = NOAEL ( mg/ kg/ day)/ Daily dose [ Where dermal ST/ IT/ LT NOAEL = 25 mg/ kg/ day, ST/ IT inhalation NOAEL = 16 mg/ kg/ day, and LT inhalation NOAEL = 3.8 mg/ kg/ day]. Target MOE is 100 for ST/ IT dermal exposures and 300 for LT dermal and 100 for ST/ IT and 300 for LT inhalation exposures.

Agricultural Seed Treatment Uses The occupational handler assessments were conducted using increasing levels of protection. The Agency typically evaluates all exposures with minimal protection and then considers additional protective measures using a tiered approach ( going from minimal to maximum levels of protection) in an attempt to obtain an adequate MOE. The lowest tier is represented by the baseline clothing scenario ( i. e., single layer clothing, socks and shoes), followed by, if MOEs are of concern, increasing levels of risk mitigation such as personal protective equipment ( PPE) and engineering controls ( EC).

The occupational handler risk assessment for the agricultural seed treatment use of TCMTB included both inhalation and dermal exposures. The target MOE for both the inhalation and dermal exposures was 100. Scenarios with an MOE less than 100 indicate a risk of concern. The Agency evaluated occupational risks to workers that use TCMTB as a fungicide for treating seeds in commercial and on nursery/ on farm settings.

For commercial seed treatment, all individual dermal and inhalation MOEs met or exceeded the target MOE of at the baseline level of mitigation ( single layer of clothing with gloves and no respirator). MOEs were above the target of 100 for the combined inhalation and dermal exposure scenarios at the baseline level of mitigation ( single layer of clothing with gloves and no respirator). Please refer to Tables 15 and 16 for further details regarding the estimated worker exposures and risks from commercial and on nursery seed treatment. 33 Table 15. Estimated Worker Exposure and Risk from Commercial Seed Treatment Short and Intermediate term Risk Estimates Crop Exposure Scenario Application Rate ( lb ai/ 100 lb) a Amount Handled per Day ( lb ai/ day) b Dermal MOE ( Target MOE  100) Inhalation MOE ( Target MOE  100) Total MOE c ( Target MOE  100) Level of Mitigationc Loader/ Applicator 410 18,000 400 SL, G+ NR Sewer 1,500 26,000 1,400 SL + NR Bagger 1,000 37,000 970 SL + NR Barley, Oat, Rice, Wheat Seeds Multiple Activities 0.026 187 220 3,700 210 SL, G+ NR Loader/ Applicator 370 16,000 360 SL, G+ NR Sewer 1,400 23,000 1,300 SL + NR Bagger 920 34,000 900 SL + NR Cotton Seeds Multiple Activities 0.13 208 200 3,400 190 SL, G+ NR Loader/ Applicator 260 11,000 250 SL, G+ NR Sewer 960 17,000 910 SL + NR Bagger 650 24,000 630 SL + NR Safflower Seeds Multiple Activities 0.041 294 140 2,400 130 SL, G+ NR Loader/ Applicator 2,100 91,000 2,100 SL, G+ NR Sewer 7,800 130,000 7,400 SL + NR Bagger 5,300 190,000 5,200 SL + NR Sugar Beet Seeds Multiple Activities 0.041 36 1,200 19,000 1,100 SL, G+ NR ND = No Data; NF = Not Feasible; NR= No respirator a Application rates are the maximum application rates determined from EPA registered labels for TCMTB b Amount handled per day calculated from the maximum application rate and the lbs of seed treated or planted/ day and: for barley, rice, safflower, and wheat seed  718000 lb/ day; for cotton seed   160000 lb/ day; and sugar beet seed   88000 lb/ day. c Baseline Dermal: Long sleeve shirt, long pants, no gloves. Baseline Inhalation: no respirator. SL, G = Single layer w/ gloves is baseline attire plus chemical resistant gloves. DL, G = Double layer w/ gloves is coveralls worn over long sleeve shirt and long pants, plus Table 16. Estimated Worker Exposure and Risk from On nursery Seed Treatment Unit Exposures Short and Intermediate term MOEs Baseline Personal Protective Equipment Engineering Controls Baseline Personal Protective Equipment Dermal ( mg/ lb ai) Inhalation ( ug/ lb ai) Dermal Inhalation Crop Acres treated/ day App Rate ( lb ai/ 100 lb) a Amount Handled per dayb ( lb ai/ day) Dermalc ( mg/ lb ai) Inhalationd (

g/ lb ai) SL w/ glovese 80% Rf 90% Rg Dermalh ( mg/ lb ai) Inhalationi ( ug/ lb ai) Inhalation SL w/ gloves 80% R 90% R LOADING/ APPLYING LIQUID SEED TREATMENTS Cotton 125 0.051 0.64 NDj ND = No Data D On nursery seed treatment with liquid formulations is generally done with automated equipment, essentially miniature versions of commercial treaters. 34 d. Occupational Post application Risk Summary Occupational post application exposures may occur from both antimicrobial and agricultural use scenarios. Occupational handlers may be exposed to TCMTB by handling treated wood; handling metal working/ cutting fluids; and loading/ planting previously treated seeds.

Antimicrobial Use TCMTB is used in products that are intended to preserve wood through non pressure treatment methods. It can be applied as a sapstain control to freshly cut wood, incorporated into particle board, or used to treat wood chips. When used as a sapstain control, the product may be dipped, sprayed, or impregnated into the wood via pressure treatment ( up to 0.3% a. i. solution). When used in particle board, the pesticide is incorporated into the resin or binding agent ( 0.3% a. i., based on dry weight of wood). As very little chemical specific data were available regarding typical exposures to TCMTB as a wood preservative, surrogate data were used to estimate exposure risks. The blender/ spray operator position was assessed using CMA unit exposure data and the remaining handler and post application positions were assessed using data from a DDAC study ( Bestari et al., 1999).

Post application exposures to chemical operators, graders, millwrights, trim saw operators, and clean up crews were assessed using surrogate data from the DDAC study ( Bestari et al., 1999). The DDAC study examined individuals' exposure to DDAC while working with antisapstains and performing routine tasks at 11 sawmills/ planar mills in Canada. Dermal and inhalation exposure monitoring data were gathered for each job function of interest using dosimeters and personal sampling tubes. Dosimeters and personal air sampling tubes were analyzed for DDAC. Exposure data for individuals performing the same job functions were averaged together to determine job specific averages. Monitoring was conducted using 2 trim saw workers, 13 grader workers, 11 chemical operators, 3 millwrights, and 6 clean up staff.

Exposures to diptank operators were also assessed using surrogate data from the DDAC study ( Bestari et al., 1999). The diptank scenario assessment was conducted differently than for the other job functions because the concentration of DDAC in the diptank solution was provided. The exposure data for diptank operators wearing gloves were converted into unit exposures in terms of mg a. i. for each 1% of concentration of the product. Dermal and inhalation unit exposures were 2.99 and 0.046 mg/ 1% solution, respectively. The air concentrations presented in the DDAC study were converted to unit exposures using an inhalation rate of 1.0 m3/ hr ( light activity) and a sample duration of 8 hrs/ day.

There are no risks of concern for the short, intermediate or long term occupational handler dermal and inhalation wood preservative exposure scenarios ( ST/ IT dermal and inhalation MOEs > 100; LT dermal and inhalation MOEs > 300). The combined dermal and inhalation scenarios also met or exceeded the target MOE of 100 when handlers were wearing short sleeve shirts, cotton work trousers, and cotton glove dosimeter gloves under chemical resistant gloves and, therefore, are not of concern. 35 Table 17. Short, Intermediate and Long Term Exposures and Risk for Occupational Handlers for Wood Preservative Use MOEsc( Target MOE   100 for ST/ IT, 300 for LT)

Dermal Inhalation TOTAL MOE ( dermal and inhalation) Exposure Scenarioa ( number of volunteers)

ST/ IT/ LT ST/ IT LT ST/ IT LT Blender/ Spray Operator ( b) 520 5,200 1,200 478 364 Chemical Operator ( n= 11) 48,000 1.10x107 2.50x106 47,790 47,095 Grader ( n= 13) 1.50x105 1.00x107 2.40x106 147,783 141,176 Trim Saw ( n= 2) 3.40x105 4.90x106 1.20x106 317,940 264,935 Millwright ( n= 3) 36,000 5.20x106 1.20x106 35,752 34,951 Clean Up ( n= 6) 8,400 4.90x105 1.20x105 8,258 7,850 Diptank Operator 1,900 8.10x104 19,000 1,856 1,727 ST = Short term duration; IT = Intermediate term duration; and LT = long term a. Unless specified, the exposure scenario represents a worker wearing short sleeve shirts, cotton work trousers, and cotton glove dosimeter gloves under chemical resistant gloves. Volunteers were grouped according to tasks they conducted at the mill. b. Single layer clothing with chemical resistant c MOE = NOAEL ( mg/ kg/ day)/ Daily dose [ Where ST/ IT/ LT dermal NOAEL = 25 mg/ kg/ day, ST/ IT NOAEL for inhalation is 16 mg/ kg/ day and LT NOAEL for inhalation is 3.8 mg/ kg/ day]. Target MOE is 100 for ST/ IT dermal and inhalation exposures, 300 for LT dermal and inhalation exposure.

Not enough data exists to estimate the amount of exposure associated with construction workers who install treated wood. In particular, values for the transfer coefficient associated with a construction worker handling the wood could not be determined. It is believed that the construction worker using a trim saw will have larger dermal and inhalation exposures than the installer, due to the amount of sawdust generated and the greater amount of hand contact that would be necessary to handle the wood when using a saw compared to installing the wood. Because the dermal and inhalation MOE's are well above the target of 100 for trim saw operators and handler exposure is expected to be greater for trim saw operation, risks of concern are not anticipated for construction workers installing treated wood.

Occupational workers may also be exposed to TCMTB when handling previously treate metal working/ cutting fluids. For the metal working/ cutting fluids scenario, dermal exposure estimates were derived using the two hand immersion model from ChemSTEER. A screening level intermediate and long term inhalation exposure estimate for treated metal working fluids was developed using the OSHA Permissible Exposure Limit ( PEL) for oil mist. Post application dermal and inhalation exposure occurs after the chemical has been incorporated into the metal working fluid and a machinist is using/ handling this treated end product. It was assumed that a machinist is exposed to the metal working fluid 8 hours a day, for 5 days a week and that the body weight of an adult is 70 kg ( US EPA1997).

For the metal working fluid scenario, all combined dermal and inhalation scenarios met or exceeded the target MOE of 100 and, therefore, are not of concern. However, there are human incident data related to the occupational handler post application use of TCMTB as an antimicrobial product. This and other data indicate dermal irritation from exposure to TCMTB and that TCMTB is a dermal sensitizer ( toxicity category I for eye irritation and toxicity category II for dermal irritation). 36 Table 18. Short, Intermediate and Long Term Risks Associated with Post application Exposure to Metal Working Fluids Treated with TCMTB ( Machinist)

Dermal Inputs Inhalation Inputs MOE ( Target MOE   100 for ST/ IT, 300 for LT) c, d Dermal MOE Inhalation MOE TOTAL MOE ( dermal and inhalation) Weight Fraction a. i. in Fluid Hand Surface Area ( cm2) Film thickness ( mg/ cm2) Frequency ( event/ day) OSHA PEL ( mg/ m3) Inhal. rate ( m3/ hr) Exposure Duration ( hrs/ day)

ST/ IT/ LT ST/ IT LT ST/ IT LT 0.00125 840 1.75 1 5 1 8 950 22000 5300 910 806 a Absorbed Dermal Daily Dose ( mg/ kg/ day) = [ fraction a. i. in treated fluid * hand surface area* film thickness ( mg/ cm2)* Frequency ( event/ day)] / Body weight ( 70 kg). b Absorbed Inhalation Daily Dose ( mg/ kg/ day) = fraction a. i. in treated fluid * OSHA PEL ( mg/ m3) * Inhalation rate ( m3/ hr) * exposure duration ( hr/ day) / body weight ( 70 kg) c Dermal MOE = NOAEL ( mg/ kg/ day) / Absorbed Daily Dose ( mg/ kg/ day) [ Where: ST/ IT/ LT dermal NOAEL = 25 mg/ kg/ day]. d Inhalation MOE = NOAEL ( mg/ kg/ day) / Absorbed Daily Dose ( mg/ kg/ day) [ Where: ST/ IT inhalation NOAEL = 16 mg/ kg/ day and LT Inhalation NOAEL = 3.8 mg/ kg/ day].

Agricultural Seed Treatment Use For the agricultural seed treatment use, the post application occupational risk assessment considered exposure to TCMTB from entering nurseries after plants had been treated. Onnursery seed treatment scenarios were assessed for loading/ planting previously treated seeds.

Dermal and inhalation exposures were evaluated in the post application worker assessment. For the on nursery seed treatment scenarios, individual dermal and inhalation MOEs are all greater than the target of 100 without the use of PPE, and thus are not of concern. The combined dermal and inhalation on nursery seed treatment MOEs are also all above the target of 100 with PPE, single layer baseline attire and chemical resistant gloves. Table 19 list the worker risk estimates for the post application on nursery seed treatment. 37 Table 19. Estimated Worker Exposure and Risk from On Nursery Seed Treatment ( Postapplication

Short and Intermediate term Risk Estimates Crop Acres treated/ day App Rate ( lb ai/ 100 lb) a Amount Handled per dayb ( lb ai/ day) Inhalation MOE ( Target MOE  100) Dermal MOE SL w/ gloves ( Target MOE  100) Total MOE ( Target MOE  100) Level of Mitigation LOADING/ PLANTING PREVIOUSLY TREATED SEEDS Barley 35 0.026 0.64 360,000 7,700 7,500 SL, G + NR Beet; Sugar 80 0.041 0.26 1,300,000 27,000 26,000 SL, G + NR Cotton 200 0.13 4.68 70,000 1,500 1,500 SL, G + NR Oats 200 0.026 6.66 49,000 1,100 1,100 SL, G+ NR Rice 200 0.026 7.80 42,000 900 880 SL, G+ NR Safflower 80 0.041 3.28 100,000 2,100 2,100 SL, G + NR Wheat 200 0.026 7.80 42,000 900 880 SL, G+ NR ND = No Data; NF = Not Feasible; NR = no respirator SL, G = Single layer w/ gloves is baseline attire plus chemical resistant gloves.

a Application rates are the maximum application rates determined from EPA registered labels for TCMTB b Amount handled per day calculated from the acres treated/ day and the maximum lb of seed planted per acre. c On nursery seed treatment with liquid formulations is generally done with automated equipment, essentially miniature versions of commercial treaters. d Amount handled per day calculated from the maximum application rate and the lbs of seed treated or planted/ day for: barley, rice, safflower and wheat seed 718000 lb/ day; for cotton seed 160000 lb/ day; and for sugar beet seed 88000 lb/ day.

9. Human Incident Data The Agency reviewed available sources of human incident data for incidents relevant to TCMTB. EPA consulted the following sources of information for human poisoning incidents related to TCMTB use: ( 1) OPP Incident Data System ( IDS)  The Office of Pesticide Programs ( OPP) Incident Data System contains reports of incidents from various sources, including registrants, other federal and state health and environmental agencies and individual consumers, submitted to OPP since 1992; ( 2) California Department of Pesticide Regulation ( 1982 2004)   The California Department of Pesticide Regulation pesticide poisoning surveillance program consists of reports from physicians of illness suspected of being related to pesticide exposure since 1982; ( 3) National Pesticide Information Center ( NPIC)  NPIC is a toll free information service supported by OPP That provides a ranking of the top 200 active ingredients for which telephone calls were received during calendar years 1984 1991. 38 For TCMTB, dermal, inhalation, ocular and oral exposures were reported. Most of the incidents reported were irritation type reactions. The primary routes of exposure for these incidents were dermal and inhalation; though oral ingestion incidents were reported. The most common symptoms reported for each exposure route are as follows:

  Dermal exposure: skin irritation/ burning, rash, itching, skin discoloration/ redness and blistering.

  Inhalation exposure: respiratory irritation/ burning, irritation to mouth/ throat/ nose, coughing/ chocking, shortness of breath and sore throat.

  Ocular exposure: eye irritation/ burning, eye pain and swelling of eyes.

  Ingestion/ oral exposure: irritation to mouth/ throat/ nose, abdominal pain, kidney failure, hypothermia and loss of consciousness.

In addition, a cross sectional study was conducted to observe the health effects associated with the use of TCMTB in the British Columbia sawmill industry ( Teschke, 1992). Workers in five costal sawmills were asked to complete a self administered questionnaire about symptoms they experienced after fungicide exposure and about injuries commonly reported in sawmills. The reported symptoms related to TCMTB consistently included dry skin around the eyes, blood stained mucus from the nose, nose bleed, peeling skin, burning or itching skin, and skin redness or rash.

B. Environmental Risk Assessment A summary of the Agency's environmental risk assessment is presented below. TCMTB has several registered use sites that could result in environmental exposures. Indoor uses were not assessed as the Agency does not anticipate exposure, given the current use patterns of TCMTB. The following risk characterization is intended to describe the magnitude of the estimated environmental risks for TCMTB use sites and any associated uncertainties.

For a detailed discussion of all aspects of the environmental risk assessment, refer to the Environmental Risk Assessment ( Section 10.1) in the " 2( Thiocyanomethylthio) benzothiazole ( TCMTB) Risk Assessment for the Reregistration Eligibility Decision ( RED) Document," dated August 1, 2006; the " 2( Thiocyanomethylthio) benzothiazole ( TCMTB) Ecological Hazard and Environmental Risk Assessment Chapter Revised," dated August 1, 2006; and the " Environmental Fate Assessment of 2( Thiocyanomethylthio) benzothiazole ( TCMTB) for the Reregistration Eligibility Decision ( RED) Document," dated March 30, 2006.

1. Environmental Fate and Transport The environmental fate assessment for TCMTB was based on guideline data required by the Agency for an environmental fate assessment. These studies were submitted by the technical registrant. However, not all of these studies fulfill guideline requirements. For additional 39 information, please refer to the " Environmental Fate Assessment of 2( Thiocyanomethylthio) benzothiazole ( TCMTB) for the Reregistration Eligibility Decision ( RED) Document," dated March 30, 2006. Several metabolites are formed during the biotic degradation of TCMTB, including 2 benzothiazolesulfonic acid ( BTSA) and 2 mercaptobenzothiazole ( 2 MBT). BTSA is not of toxicological concern because it has negligible toxicity and is completely excreted. 2 MBT is generally less toxic than parent TCMTB; therefore, the environmental risk assessment was conducted for TCMTB only. Please note that although the environmental assessment does not include 2 MBT for the reasons stated above, 2 MBT was included in the drinking water assessment as a conservative approach to conducting the assessment.

An assessment of the submitted guideline studies indicates the hydrolysis of TCMTB to be pH dependent. TCMTB is hydrolytically stable under abiotic and buffered conditions at pH 5 and slowly degrades at pH 7. Under more alkaline conditions, hydrolysis proceeds more rapidly with a calculated half life ranging from 1.8 to 2.1 days. Photolytically, TCMTB degrades in pH 5 buffered aqueous solutions with a calculated half life of 1.5 hours. Based on its degradation in the environment, TCMTB is not likely to pose a concern for surface water run off.

Aquatic metabolism under aerobic and anaerobic conditions, as well as aerobic soil metabolism, are major routes of dissipation for TCMTB. TCMTB's calculated degradation halflife in flooded lake sediment is 6.9 days; however, the apparent half life occurs between 2 and 4 days. Similarly, TCMTB shows a tendency of degrading anaerobically in flooded sediment within 2.7 days. Under aerobic conditions in sandy loam soil, a representative agricultural soil, TCMTB degrades with a calculated half life of 1.4 days. Because of the biodegradation in water and soils, TCMTB is not likely to contaminate surface and ground waters.

TCMTB's tendency to bind with agricultural soils varies according to soil type. TCMTB is mobile very mobile in various soils; however, because of its tendency to biodegrade in water and soils, TCMTB is not likely to contaminate surface and ground waters. TCMTB is very mobile in clay loam, sand, and sandy loam soil, and mobile in clay and silt loam soil. Kds are 3.5 for clay loam soil, 0.99 for sand soil, 9.9 for sandy loam soil, 22.1 for clay soil, and 62.7 for silt loam soil. There may be a water/ sediment partitioning issue and an acute adverse impact on benthic organisms. However, TCMTB degrades fairly rapidly in freshwater and soils and the impacts may be short lived.

Additional information on the aqueous availability of TCMTB from treated wood, indicates that the use of TCMTB as a wood preservative may result in minimal releases to the environment. Nevertheless, the Agency conducted modeling to estimate TCMTB concentrations in surface water from the antisapstain use. Based on conservative assumptions, the Agency estimated runoff concentrations that range from 8.5 to 32.7 ppb. 40 a. Bioaccumulation in Aquatic Organisms Bioconcentration testing was conducted for TCMTB. Results from this study conducted with fish indicate that the bioaccumulation potential of TCMTB is minimal and, therefore, not of concern to the Agency.

2. Ecological Risk The Agency's ecological risk assessment compares toxicity endpoints from ecological toxicity studies to estimated environmental concentrations based on environmental fate characteristics and pesticide use data. A summary of the submitted data is provided below.

a. Environmental Toxicity Available data indicate that TCMTB is slightly toxicity to birds on an acute oral basis and subacute dietary basis. Because birds are not expected to come into contact with TCMTB on a chronic basis, avian reproduction studies were not required for TCMTB.

Based on the results of mammalian studies conducted to meet human toxicity data requirements, TCMTB exhibits low acute oral and dermal toxicity ( toxicity category III); however, it is highly irritating to the eyes and skin ( toxicity category I and II, respectively). TCMTB is also considered to be highly toxic via the inhalation route of exposure ( toxicity category I). TCMTB is a dermal sensitizer.

On an acute basis, TCMTB is very highly toxic to freshwater fish, freshwater invertebrates, estuarine/ marine fish, and estuarine/ marine invertebrates. TCMTB is generally more toxic then its' degradate, 2 MBT, and therefore, only TCMTB was evaluated in the risk assessment. Published literature reports ( MRID# 424053 01) indicate that TCMTB may cause sublethal effects in fish, which could result in an increase in predation and a decreased ability to survive. These studies demonstrate that exposure to TCMTB at levels of 8 10 ppb cause gill damage and behavioral changes, which can severely reduce the ability of fish to survive in the wild ( Chew., Proceedings of the Seventeenth Annual Aquatic Toxicity Workshop Vol. 1). The toxicity values used in the TCMTB ecological risk assessment ( 8.7 Mg/ L) are comparable to the levels described in the published literature where sublethal effects occur. Therefore, the TCMTB risk assessment is protective of these sublethal effects.

A summary of submitted acute ecological toxicity data for TCMTB and 2 MBT along with, avian sub acute dietary toxicity data, chronic freshwater fish toxicity data and aquatic plant toxicity data for TCMTB are provided in Tables 20, 21, 22 and 23, respectively. 41 Table 20. Acute Ecological Toxicity for TCMTB and 2 MBT Species Chemical % active ingredient ( ai) Endpoint Toxicity Category ( TGAI) Other Effects Noted Reference/ Status Birds TCMTB 80.4% LD50 = 660 mg/ kg NOEL < 292 mg/ kg Slightly toxic Signs of toxicity and reduction of body weight and feed consumption at 292 mg/ kg MRID: 41780901 ( Campbell 1991)/ Acceptable Northern bobwhite ( Colinus virginianus)

2 MBT 98.2% LD50 > 2150 mg/ kg NOEL < 1000 mg/ kg Practically non toxic Some evidence of dose related abnormalities upon gross necropsy ( friable livers, resorbed eggs, fluid filled sacs in abdomen) MRID:

42267101 ( Pedersen end Helsten 1992a)/

Acceptable Mammals Laboratory rat ( Rattus norvegicus) TCMTB 80% ai LD50= 750 mg/ kg Moderately toxic 41583801/ Acceptable Freshwater Fish TCMTB 90% 96hr static LC50 =

55.2 ug/ L ( ppb) Very highly toxic None reported TN 2437 ( USEPA 1980)/ Supplemental TCMTB 80.4% 96hr flow through LC50 = 20.91 ug/ L ( ppb) Very highly toxic NOEC = 8.7 µ g/ L ( ppb) due to mortality and lethargy and loss of equilibrium in surviving fish at higher levels 41818101 ( Machado 1991b)/ Acceptable Rainbow trout Oncorhynchusmykiss)

TCMTB 75% 96hr static LC50 =

29 ug/ L ( ppb) Very highly toxic Loss of equilibrium and lying on sides observed ACC+ 0916 24 ( Knott and Woodard 1968b)/ Supplemental TCMTB 90% 96hr static LC50 =

32 ug/ L ( ppb) Very highly toxic None reported TN 2432 ( USEPA 1979)/ Supplemental Bluegill sunfish ( Lepomis macrochirus)

TCMTB 80.4% 96hr flow through LC50 = 8.7 ug/ L Very highly toxic NOEC = 5.1 µ g/ L ( ppb) due to signs of toxicity at 41804201 ( Machado 1991a)/ Acceptable 42 Species Chemical % active ingredient ( ai) Endpoint Toxicity Category ( TGAI) Other Effects Noted Reference/ Status ( ppb) higher levels TCMTB 75% 96hr static LC50 =

47 ug/ L ( ppb) Very highly toxic Loss of equilibrium and lying on sides observed ACC# 091624 ( Knott and Woodard 1968b)/

Supplemental Rainbow trout Oncorhynchus mykiss) 2 MBT 98.2% 96 hr static LC50 = 730 ug/ L ( ppb) Very highly toxic NOEC = 310 µ g/ L ( ppb) due to mortality at higher treatment levels 42232201 ( Collins 1992)/ Acceptable Freshwater Invertebrates TCMTB 90%. 48 hr. static EC50 = 23 ug/ L ( ppb) Very highly toxic TN 2427 ( USEPA 1979)/

Supplemental TCMTB 80.4% 48 hr. flow through EC50 = 22 ug/ L ( ppb); NOEC = 8.7 ug/ L ( ppb) Very highly toxic 41838201 ( McNamara 1991)/ Acceptable Waterflea ( Daphnia magna)

2 MBT 100% 48 hr. static EC50 = 2,900 ug/ L ( ppb) Moderately toxic 42226001 ( Collins 1992b)/ Acceptable Estuarine/ Marine Fish Sheepshead minnow ( Cyprinodon variegates) TCMTB 80% 96 hr. static LC50 = 60 ug/ L ( ppb) Very highly toxic 40363601 ( Suprenant 1986a)/ Acceptable Estuarine/ Marine Invertebrates Quahog clam ( Mercenaria mercenaria) TCMTB 80% 48 hr. static EC50 = 13.9 ug/ L ( ppb); NOEC < 13 ug/ L ( ppb) Very highly toxic 40363603 ( Suprenant 1986) / Acceptable Mysid ( Americamysis bahia, formerly Mysidopsis bahia) TCMTB 80% 96 hour static LC50= 20.3 ug/ L ( ppb); NOEC < 7.8 ug/ L ( ppb) Very highly toxic 40363602 ( Suprenant 1987) / Acceptable 43 Table 21. Avian Sub acute Dietary Toxicity of TCMTB and 2 MBT Test Type ( Chemical and % a. i.) Chemical (% a. i.) Species Endpoint Results Other Effects Noted Reference/ Status TCMTB ( 80 83% a. i.) Mallard duck ( Anas platyrhynchos) Mortality 8 day LC50 > 10000 ppm " practically non toxic" Feed consumption and 10% mortality at 5,000 and 10,000 ppm Accession # 009869 ( Booden, 1974)/ Acceptable TCMTB ( 75 % a. i.) Bobwhite quail ( Colinus virginianus) Mortality LC50 > 10000 ppm " Practically non toxic" Huddling and depression at levels > 1000 ppm Accession # 091624 ( Knott and Woodard, 1968a)/ Supplemental TCMTB ( 80% a. i.) Mallard duck ( Anas platyrhynchos) Mortality 8 day LC50 > 4496 ppm " Slightly toxic" NOEC < 450 ppm based on reduction in body weight gain and food consumption 415956 01 ( Long et al., 1990/ Acceptable TCMTB ( 80% a. i.) Bobwhite quail ( Colinus virginianus) Mortality 8 day LC50 > 4496 ppm " Slightly toxic" NOEC = 450 ppm, based on reduction of average body weight gain at higher levels 415956 02 ( Long et al., 1990/ Acceptable Avian acute dietary, 850.2200/ 71 2 2 MBT ( 98.22% a. i.) Bobwhite quail ( Colinus virginianus Mortality 8 day LC50 > 3387 ppm " Slightly toxic" NOEC = 3387 ppm   no signs of toxicity at any level 424285 01( Pedersen and Helsten, 1992b)/ Acceptable Table 22. Freshwater Fish Chronic Toxicity of TCMTB Study Type Species Endpoint NOEC

g a. i./ l LOEC

g a. i./ l MRID# ( reference)/ Status Freshwater fish Early life stage toxicity ( 72 4a/ 850.1300) ( 83.78% a. i.) Rainbow trout ( Oncorhynchus mykiss) Reproduction, post hatch survival, growth 0.34 ppb based on growth and egg hatchability 0.56 ppb based on growth 425959 01 ( Rhodes, 1992)/ Acceptable 44 Table 23. TCMTB Aquatic Plant Toxicity Test Species/% a. i. Endpoint Toxicity NOEC/ other effects noted MRID ( reference) Status Aquatic Vascular Plant Acute Toxicity, Tier II ( doseresponse 123 2/ 850.4400 Duckweed ( Lemna gibba)/ 83.5% a. i. Frond growth 14 day static renewal EC50 = 0.43 ( 0.29   0.65) mg/ L ( ppm) 0.15 mg/ L ( ppm) 442009 01 ( Thompson and Swigert, 1996) Acceptable b. Ecological Exposure and Risk The Agency has evaluated the outdoor uses of TCMTB being considered for reregistration. Environmental exposure modeling was conducted for both the agricultural and antimicrobial uses of TCMTB.

Terrestrial Organisms Modeling was performed to address the exposure and risk to birds and mammals consuming seeds treated with TCMTB using the Terrestrial Residue Exposure Model ( TREX) ( http:// www. epa. gov/ oppefed1/ models/ terrestrial) for the treatment on safflower, which has the highest application rate of 0.041 lb ai/ A. The Agency determined that acute risk to birds and mammals from consuming TCMTB treated seeds are below the Agency's level of concern ( LOC). The following Risk Quotients ( RQs) for acute and chronic avian exposure to TCMTB treated seeds were calculated:

Avian Acute: 0.02 as ( mg ai/ kg/ day)/ LD50 Avian Chronic: Not required The avian RQ was calculated with no toxicity scaling factor. Scaling factors are used when it is likely that a pesticide will be proportionally more toxic to smaller organisms than larger ones. TREX recommended a default scaling factor of 1.15, based on Mineaue et al. ( 1996). This scaling factor was developed based on 37 conventional pesticides, most of which are cholinesterase inhibitors. There is no information available indicating that such an adjustment is necessary or appropriate for TCMTB. The following Risk Quotients ( RQs) for acute and chronic mammalian exposure to TCMTB treated seeds were calculated:

Mammalian Acute: 0.05 as ( mg ai/ kg/ day)/ LD50, 0.02 as ( mg ai/ ft2)/( LD50* BW) Mammalian Chronic: 0.53 as ( mg/ kg seed)/ reproduction NOAEC All of the agricultural use RQs are below any LOCs for avian and mammalian acute risk and mammalian chronic risk. Avian chronic data are not available or required for the currently registered uses of TCMTB, therefore chronic avian risk was not assessed.

Terrestrial risks from the wood preservative uses of TCMTB were not addressed due to a lack of available models to estimate terrestrial exposure from antisapstain treatments. The 45 Agency conducted environmental exposure modeling for the antisapstain wood preservation use. Runoff concentrations of TCMTB were estimated for facilities that treat wood with antisapstain chemicals. The concentrations were estimated using an approach developed to determine runoff concentrations of pesticides from antisapstain facilities in British Columbia, Canada ( Krahn and Strub, 1990).

Predictions of leaching behavior ( as would be observed in a study following the Krahn and Strub ( 1990) protocol) were made based on the chemical properties of TCMTB and a number of assumptions.

Krahn and Strub ( 1990) assume that leachate entering the storm drain is diluted with extra runoff water at a 1: 15 ratio. This is based on measurements of runoff in storm drains at facilities using antisapstain chemicals in British Columbia. Use of the ratios 1: 6 and 1: 23 were also suggested by Krahn and Strub ( 1990) to determine a " general industry wide" predicted runoff concentration. These values were used in this assessment. The estimated leachate concentration ( 0.196 ppm) was used in conjunction with these dilution factors to estimate runoff concentrations.

Table 24. Estimated Runoff Concentrations for TCMTB from Antisapstain Use Parameter Dilution Factor Estimated Runoff Concentration ( ppm) a High end dilution 23.0 0.00852 Typical dilution 15.0 0.0131 Low end dilution 6.00 0.0327 aEstimated Runoff Concentration = Estimated Leachate Concentration ( 0.196 ppm) / Dilution Factor.

Aquatic Organisms To develop risk quotients ( RQs), the estimated environmental concentrations ( EECs) determined by modeling were compared to the most sensitive endpoint for each taxa. For seed treatment, no levels of concern ( LOCs) were exceeded. The seed treatment use of TCMTB poses minimal risk to aquatic organisms and, therefore, is below the Agency's level of concern.

The Agency has also conducted environmental exposure modeling for the antisapstain wood preservative use. Based on the Tier I screening model used for the antisapstain use, there are risks of concern to aquatic organisms. Acute LOCs were exceeded for all taxa except aquatic plants. Chronic LOCs for fish were also exceeded. However, chronic risk to invertebrates could not be addressed due to lack of chronic invertebrate toxicity data. Additional information regarding the TCMTB ecological assessment can be found in the " 2( Thiocyanomethylthio) benzothiazole ( TCMTB) Risk Assessment for the Reregistration Eligibility Decision ( RED) Document," dated August 1, 2006; and the " 2( Thiocyanomethylthio) benzothiazole ( TCMTB) Ecological Hazard and Environmental Risk Assessment Chapter Revised," dated August 1, 2006. Please refer to Table 25 for a comprehensive list of the identified aquatic organism risk quotients for the seed treatment and antimicrobial uses of TCMTB. 46 Table 25. Aquatic Organism Risk Quotients for Seed Treatment and Antisapstain Uses of TCMTB Taxa/ Endpoint Seed treatment EEC Seed Treatment RQ Antisapstain EEC Low dilution High dilution Antisapstain RQ Freshwater fish Acute 8.7 µ g/ L 0.28 ppb 0.03 32.7 ppb 8.5 ppb 3.76 0.98 Freshwater Invertebrates Acute 22 µ g/ L 0.28 ppb 0.01 32.7 ppb 8.5 ppb 1.49 0.39 Marine/ Estuarine Fish Acute 60 µ g/ L 0.28 ppb 0.00 32.7 ppb 8.5 ppb 0.54 0.14 Marine/ Estuarine Bivalve Acute 13.9 µ g/ L 0.28 ppb 0.02 32.7 ppb 8.5 ppb 2.35 0.61 Marine/ Estuarine Invertebrate Acute 20.3 µ g/ L 0.28 ppb 0.01 32.7 ppb 8.5 ppb 1.61 0.42 Green Algae Acute EC50 430 µ g/ L 0.28 ppb 0.00 32.7 ppb 8.5 ppb 0.08 0.02 Green Algae NOEC 150 µ g/ L 0.28 ppb 0.00 32.7 ppb 8.5 ppb 0.22 0.06 Fish Chronic 0.34 µ g/ L 0.12 ppb 0.35 13.1 ppb 8.5 ppb 38.53 25.00 Invertebrate Chronic   DATA GAP 0.20 ppb  13.1 ppb

Plants A single aquatic plant study was submitted for TCMTB, the results of which are summarized in Table 23. Results indicate that TCMTB exposure impairs growth of aquatic vascular plants at levels greater than 0.15 ppm ( 150 ppb). Further data are required to support the antimicrobial and agricultural uses of TCMTB.

Non target Insects ( Honeybee)