Docket Number; EPA–HQ–OPP–2010-0002 www.regulations.gov

United States Chemi cal Safety August 2010

Environmental Protection and Pollution Prevention Agency (7510P)



# Thymol Final Work Plan Registration Review August 2010Docket Number; EPA-HQ-OPP-2010-0002 www.regulations.gov

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### TABLE OF CONTENTS

THYMOL REGISTRATION REVIEW TEAM ........................................................................ 4

I. INTRODUCTION ................................................................................................................ ..... 5

II. COMMENTS RECEIVED ON THE PRELIMINARY WORK PLAN.............................. 5

III. RISK ASSESSMEN T AND DATA NEEDS......................................................................... 6

IV. TIMELINE ................................................................................................................... ......... 10

V. GLOSSARY of TERMS & ABBREVIATIONS.................................................................. 11Docket Number; EPA-HQ-OPP-2010-0002 www.regulations.gov

4 Thymol Registration Review Team

Human Health & Environmental Effects

Nathan Mottl

Jacob S. Moore

Srinivas Gowda

Risk Management

Monisha Harris

Lance Wormell Andrew Bryceland

Office of General Counsel Philip RossDocket Number; EPA-HQ-OPP-2010-0002 www.regulations.gov

5 I. INTRODUCTION

This is the Environmental Protection Ag ency’s (EPA or “the Agency”) Final Work Plan (FWP) for the registration review of Thymol. The work plan includes the expected registration review timeline. Th e work plan also addresses public comments received concerning the Preliminary Work Pl an (PWP) in the Summary Document which was posted in the thymol registration review docket, and any other comments concerning the initial docket postings. The Summary Document provided information on what EPA knows about the pesticide and what additional ri sk analyses and data or information the Agency believes are needed to make a registration review decision.

The Agency is implementing the registration review program pursuant to Section 3(g) of the Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA) and will review each registered pesticide every 15 years to de termine whether it continues to meet the FIFRA standard for registration. Changes in science, public policy and pesticide use practices will occur over time. The registra tion review program is intended to make sure that, as the ability to assess risk evolve s and as policies and practices change, all registered pesticides continue to meet th at statutory standard. The public phase of registration review begins when the initial docket is opened for each case. Information on this program is provided at: http://www.epa.gov/oppsrrd1/registration_review/

.

The thymol Preliminary Work Plan (PC Code 080402) was published March 31, 2010. The 90-day comment period ended on June 1, 2010. The Preliminary Work Plan

document is available on www.regulations.gov , docket number EPA-HQ-OPP-2010-

0002.

II. COMMENTS RECEIVED ON THE PRELIMINARY WORK PLAN

EPA received one comment during the public comment period on the initial docket, described below.

In the PWP, EPA also solicited comments on three specific topics: environmental justice; water body impairment; and trade irr itants. No comments or information were received during the public comment period concerning these issues.

During the public comment period, the EP A received one comment as described and discussed below. The comment received during the initial public comment period did not affect the data needs, work plan and timeline described in the PWP and they remain as they were presented initially in the PWP. Further, this document makes final the work plan for the thymol registration review process.

Comment : The Physicians Committee for Re sponsible Medici ne submitted a comment suggesting that the justification found in the summary document regarding the anticipated 90-day inhalation to xicity study is not sound fo r conducting this study. The Agency’s justification implies uncertainty whether the inhalation exposure occurs from the referenced use. Also, The Physic ians Committee for Responsible MedicineDocket Number; EPA-HQ-OPP-2010-0002 www.regulations.gov

6 recommend that the Agency gather the exposur e data first before conducting the 90-day inhalation study.

Response : Thymol could potentia lly irritate the lung and the Agency has no short- or intermediate-term inhalation toxicity studies that examine dose dependent inhalation irritation effects of thymol. As a result, the Agency anticipates the need for a 90-day inhalation study. The Agency will determine the need for occupational and/or residential inhalation risk assessments based on the results of an acceptable 90-day inhalati on toxicity study. The Agency will need additional exposure data only if an accep table 90-day inhalation toxicity study

results in the selection of an inhala tion toxicological e ndpoint of concern.

III. RISK ASSESSMENT AND DATA NEEDS

Human Health Risk Assessment Status and Anticipated Data Needs

The Agency has reviewed the hazard and exposure databases for the thymol registration review case. As a result of this review, the Agen cy does not expect that data or risk assessments will be needed to assess dermal, dietary, drinking water or incidental oral exposures. However, inhalation exposur e may result from the application/use of thymol via pressure sprayers, aerosols, airl ess sprayers; pump-up ga rden type sprayers, ULV (ultra low volume) and mist generating sprayers (foggers). Therefore, the Agency anticipates needing additional inhalation and mutagenicity to xicity studies; upon review of these data, EPA will revisit the need for exposure data and an inhalation exposure risk

assessment.

Dietary and Drinking Wa ter Exposure and Risk

Dietary Food Exposure

Thymol is found naturally in food stu ffs such as lime honey and cooking herbs and/or food stuffs derived from cranberry a nd mandarin and tangerine oils. Thymol is also added to food stuffs commonly consum ed by humans such as ice cream, nonalcoholic beverages, candy, baked goods, and chewing gum. It is FDA-approved when used as a synthetic flavoring (21 CFR 172.515) , a preservative and indirect food additive of adhesives (21 CFR 172.105) and the sour ce plant (thyme), from which thymol is extracted is acknowledged by FDA as gene rally recognized as safe (GRAS)(21 CFR 182.10, 21 CFR 182.20).

Dietary food risks of concern are not anticipated for the use of thymol as a pesticide for all registered uses; theref ore, a dietary food assessment will not be performed.Docket Number; EPA-HQ-OPP-2010-0002 www.regulations.gov

7 Dietary Drinking Water Exposure

Risks to thymol residues in drinking wa ter are not expected since outdoor use is limited and thymol is GRAS therefore, rel ease to drinking water sources is unlikely. Therefore, a dietary drinking water assessment will not be performed.

Tolerances

The following exemptions have been established for the use of thymol: 1) an exemption from the requirement of a tolera nce has been established for residues of thymol (as present in thyme oil) in or on food commodities when applied/used in/on public eating places, dairy processing equipmen t, and/or food processing equipment and utensils (FRL-8404-4); and 2) an exemption fr om the requirement of a tolerance has been established for residues of thymol in or on honey and honeycomb when used in accordance with good agricultura l practices (40 CFR 180.1240).

Aggregate and Cumulative Exposure and Risk

In examining aggregate exposure, EP A takes into account the available and reliable information concerning exposures to pesticide residues in food and drinking water, and non-occupational pe sticide exposures. Dietary (f ood and drinking water) risks of concern are not anticipated for thymol. F DA considers thymol GRAS for use in foods and drinking water. Risks asso ciated with thymol exposures are expected to be minimal through dermal and oral based on limited eviden ce of any subchronic or chronic systemic effects through the oral routes of exposure. Therefore, an aggregate assessment will not

be needed.

Section 408(b)(2)(D)(v) of FFDCA requi res that, when considering whether to establish, modify, or revoke a tolerance, th e Agency consider "available information” concerning the cumulative effects of a part icular pesticide's residues and "other

substances that have a common mechanism of toxicity.” EPA has not yet determined whether thymol has a common mechanism with other compounds, consequently a cumulative assessment will not be performed at this time.

Occupational and Residen tial Assessment and Risk

The Agency reviewed all available data associated with thymol and has determined that the currently registered us es of thymol may resu lt in residential and occupational exposure. EPA expects dermal occupational and/or residential exposures will likely be minimized based on the label use directions, PPE (e.g. gloves), dilution, and lack of systemic toxicity. Therefore, no additional dermal risk assessments are anticipated as being needed for registration review. The Agency will determine the need for occupational and/or residential inhalation risk assessments based on the results of the inhalation toxicity study which the Agency anticipates needing as part of registration

review.Docket Number; EPA-HQ-OPP-2010-0002 www.regulations.gov

8 Anticipated Human Health Data Needs

The Agency anticipates requiring the following data for thymol.

Anticipated Human Health Toxicity Data Needs

• (GLN 870.5915) In vivo sister chromosome exchange assay

• (GLN 870.5900) In vitro sister chromosome exchange assay

• (GLN 870.5375) In vitro mammalian chromosomal aberration test; and

• (GLN 870.5550) Unscheduled DNA synthesis, and

• (GLN 870.3465) 90-day inha lation toxicity study

Anticipated Occupational/Resid ential Exposure Data Needs

• (GLN 875.1400) Inhalation Exposure Indoor

• (GLN 875.1600) Application Exposure Monitoring Data Reporting; and

• (GLN 875.1700) Product Use Data

Further information and detailed justificati ons for studies that are expected to be needed are available in “Summary of Hu man Health Effects Data for the Thymol Registration Review Decision Do cument,” dated March 23, 2010.

Anticipated Physical/Chemical Property Data Needs

All product chemistry data requirement s have been fulfilled for thymol. Therefore, it is anticipated that additional pr oduct chemistry data will not be needed for thymol.

Environmental Fate and Ecological Risk A ssessment Status and Anticipated Data

Needs

The Agency reviewed the environmental fate and ecological hazard databases for thymol. The Agency has waived all envir onmental fate data requirements for thymol because of the relatively non-toxic nature of thymol, and its limited uses around

residential areas. All of the ecotoxicity data requirements for thymol have been waived by the Agency because the ecotoxicity status is so well known for this active ingredient.

Available data from literature reviews show that thymol is not toxic to aquatic organisms.

Based on thymol’s natural occurrence, current use pa tterns, toxicity data, low/non-toxicity, very low environmental e xposure, and the lack of reported adverse effects information, the Agency does not anti cipate conducting an environmental fate or ecological risk assessment for thymol. In addition, no environmental fate or ecological data are anticipated as being need ed for this registration review.

Based on the limited use patterns, very low exposure levels, the chemical's natural occurrence in the environment, common use as a food item, lack of reported adverse effects information, and very low/non-toxi city potential of thymol, the Agency anticipates concluding that the registered us es of thymol will have “no effect” (NE) onDocket Number; EPA-HQ-OPP-2010-0002 www.regulations.gov

9 endangered or threatened terr estrial or aquatic species, or their designated critical habitats, as listed by the U.S. Fish a nd Wildlife Service (USFWS) and the National Oceanic and Atmospheric Administration's (NOAA) National Marine Fisheries Service (NMFS). EPA anticipates conducting no further analysis of potential risks to endangered or threatened species unless public comments provide additional information that would alter the Agency's current position that thymol will have "no effect" on such species or their designated critical habitat.

Further information on the en vironmental fate and ecological risk assessment is available in the document titled, Summary of Product Chemistry, Environmental Fate, and Ecotoxicity Data for the Thymol Regi stration Review Decision Document, dated March 23, 2010.

Incidents:

A search of the OPP Incident Data Syst em (IDS) revealed no reported incidents for thymol.Docket Number; EPA-HQ-OPP-2010-0002 www.regulations.gov

10 IV. TIMELINE

The EPA has created the following estimated timeline for the completion of the thymol registration review case. The Agency anticipates requiring additional data and residential, occupational and ecological exposure assessments for this registration review

case.

Anticipated Schedule

Activities Estimated

Month/Year Phase 1: Opening the docket
Open Public Comment Period for Thymol Docket Completed March 2010
Close Public Comment Period Completed June 2010
Phase 2: Case Development

Develop Final Work Plan (FWP) August 2010
Issue DCI September 2011
Data Submission September 2015
Open Public Comment Period for Preliminary Risk Assessments March 2016

Close Public Comment Period June 2016

Phase 3: Registration Review Decision
Open Public Comment Period for Propos ed Reg. Review Decision September 2016

Close Public Comment Period December 2016 Final Decision and Begin Post-Decision Follow-up 2017 Total (years) 7

Next Steps

The Agency plans to develop a Data Call-In for this pesticide and expects to issue it in September 2011.Docket Number; EPA-HQ-OPP-2010-0002 www.regulations.gov

11 V. GLOSSARY of TERMS & ABBREVIATIONS

ai Active Ingredient AR Anticipated Residue ASTM American Society for Testing and Materials

AWPA American Wood Preserver’s Association

CBI Confidential Business Information CFR Code of Federal Regulations cPAD Chronic Population Adjusted Dose

CSF Confidential Statement of Formula CSFII USDA Continuing Surveys for Food Intake by Individuals

DCI Data Call-In DEEM Dietary Exposure Evaluation Model DFR Dislodgeable Foliar Residue DNT Developmental Neurotoxicity DWLOC Drinking Water Level of Comparison

EC Emulsifiable Concentrate Formulation EDWC Estimated Drinking Water Concentration

EEC Estimated Environmental Concentration

EP End use Product EPA Environmental Protection Agency

EUP End-Use Product FDA Food and Drug Administration FIFRA Federal Insecticide, Fungicide, and Rodenticide Act FFDCA Federal Food, Drug, and Cosmetic Act FQPA Food Quality Protection Act FOB Functional Observation Battery GENEEC Tier I Surface Water Computer Model

IR Index Reservoir

LC 50 Median Lethal Concentration. A statistically derived concentration of a substance that can be expected to cause death in 50% of test animals. It is usually expressed as the weight of substance per weight or volume of water, air or feed, e.g., mg/l, mg/kg or ppm.

LD 50 Median Lethal Dose. A statistically deri ved single dose that can be expected to

cause death in 50% of the test animals when administered by the route indicated (oral, dermal, inhalation). It is expressed as a weight of substance per unit weight of animal, e.g., mg/kg.

LOC Level of Concern

LOAEL Lowest Observed Adverse Effect Level μg/g Micrograms Per Gram μg/L Micrograms Per Liter mg/kg/day Milligram Per Kilogram Per Day mg/L Milligrams Per Liter MOE Margin of Exposure

MRID Master Record Identifi cation (number). EPA's system of recording and tracking

submitted studies. MUP Manufacturing-Use Product NA Not Applicable NAWQA USGS National Ambient Water Quality Assessment NPDES National Pollutant Discharge Elimination System NR Not Required

NOAEL No Observed Adverse Effect Level OPP EPA Office of Pesticide Programs OPPTS EPA Office of Prevention, Pesticides and Toxic Substances PAD Population Adjusted DoseDocket Number; EPA-HQ-OPP-2010-0002 www.regulations.gov

12 PAIRA Pure Active Ingredient Radiolabelled PCA Percent Crop Area PDP USDA Pesticide Data Program PHED Pesticide Handler's Exposure Data

PHI Preharvest Interval phr Pounds Per Hundred ppb Parts Per Billion PPE Personal Protective Equipment ppm Parts Per Million PRZM/EXAMS Tier II Surface Water Computer Model Q 1 * The Carcinogenic Potential of a Compound, Quantified by the EPA's Cancer

Risk Model RAC Raw Agriculture Commodity RED Reregistration Eligibility Decision REI Restricted Entry Interval

RfD Reference Dose RQ Risk Quotient RTU Ready to Use SCI-GROW Tier I Ground Water Computer Model SAP Science Advisory Panel SF Safety Factor SLN Special Local Need (Registrati ons Under Section 24©) of FIFRA) TGAI Technical Grade Active Ingredient TEP Typical End-Use Product USDA United States Department of Agriculture UF Uncertainty Factor

WPS Worker Protection Standard