Docket Number; EPA–HQ–OPP–2010-0002 

www.regulations.gov 

 

United States Chemical Safety August 2010 

Environmental Protection and Pollution Prevention 

Agency (7510P)

Thymol Final Work Plan 

Registration Review August 2010 

Docket 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 ASSESSMENT AND DATA NEEDS......................................................................... 6

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

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

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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 Ross 
Docket Number; EPA-HQ-OPP-2010-0002 

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I. INTRODUCTION 

This is the Environmental Protection Agency’s (EPA or “the Agency”) Final 

Work Plan (FWP) for the registration review of Thymol. The work plan includes the 

expected registration review timeline. The work plan also addresses public comments 

received concerning the Preliminary Work Plan (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 risk 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 determine whether it continues to meet the 

FIFRA standard for registration. Changes in science, public policy and pesticide use 

practices will occur over time. The registration review program is intended to make sure 

that, as the ability to assess risk evolves and as policies and practices change, all 

registered pesticides continue to meet that 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 irritants. No comments or information were 

received during the public comment period concerning these issues. 

During the public comment period, the EPA 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 Responsible Medicine submitted a 

comment suggesting that the justification found in the summary document regarding the 

anticipated 90-day inhalation toxicity study is not sound for conducting this study. The 

Agency’s justification implies uncertainty whether the inhalation exposure occurs from 

the referenced use. Also, The Physicians Committee for Responsible Medicine 
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recommend that the Agency gather the exposure data first before conducting the 90-day 

inhalation study. 

Response: Thymol could potentially 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 inhalation toxicity study. The Agency will need 

additional exposure data only if an acceptable 90-day inhalation toxicity study 

results in the selection of an inhalation toxicological endpoint 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 Agency does not expect that data 

or risk assessments will be needed to assess dermal, dietary, drinking water or incidental 

oral exposures. However, inhalation exposure may result from the application/use of 

thymol via pressure sprayers, aerosols, airless sprayers; pump-up garden type sprayers, 

ULV (ultra low volume) and mist generating sprayers (foggers). Therefore, the Agency 

anticipates needing additional inhalation and mutagenicity toxicity studies; upon review 

of these data, EPA will revisit the need for exposure data and an inhalation exposure risk 

assessment. 

Dietary and Drinking Water Exposure and Risk

Dietary Food Exposure 

 Thymol is found naturally in food stuffs such as lime honey and cooking herbs 

and/or food stuffs derived from cranberry and mandarin and tangerine oils. Thymol is 

also added to food stuffs commonly consumed 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 source plant (thyme), from which thymol is 

extracted is acknowledged by FDA as generally 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; therefore, a dietary food assessment will not be 

performed. 
Docket Number; EPA-HQ-OPP-2010-0002 

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Dietary Drinking Water Exposure 

 Risks to thymol residues in drinking water are not expected since outdoor use is 

limited and thymol is GRAS therefore, release 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 tolerance 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 equipment, and/or food processing equipment and 

utensils (FRL-8404-4); and 2) an exemption from the requirement of a tolerance has been 

established for residues of thymol in or on honey and honeycomb when used in 

accordance with good agricultural practices (40 CFR 180.1240). 

Aggregate and Cumulative Exposure and Risk

 In examining aggregate exposure, EPA takes into account the available and 

reliable information concerning exposures to pesticide residues in food and drinking 

water, and non-occupational pesticide exposures. Dietary (food and drinking water) risks 

of concern are not anticipated for thymol. FDA considers thymol GRAS for use in foods 

and drinking water. Risks associated with thymol exposures are expected to be minimal 

through dermal and oral based on limited evidence 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 requires that, when considering whether to 

establish, modify, or revoke a tolerance, 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.” 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 Residential Assessment and Risk

The Agency reviewed all available data associated with thymol and has 

determined that the currently registered uses of thymol may result 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. 
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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 inhalation toxicity study 

Anticipated Occupational/Residential 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 justifications for studies that are expected to be 

needed are available in “Summary of Human Health Effects Data for the Thymol 

Registration Review Decision Document,” dated March 23, 2010.

Anticipated Physical/Chemical Property Data Needs 

All product chemistry data requirements have been fulfilled for thymol. 

Therefore, it is anticipated that additional product chemistry data will not be needed for 

thymol. 

Environmental Fate and Ecological Risk Assessment Status and Anticipated Data 

Needs

The Agency reviewed the environmental fate and ecological hazard databases for 

thymol. The Agency has waived all environmental 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 patterns, toxicity data, 

low/non-toxicity, very low environmental exposure, and the lack of reported adverse 

effects information, the Agency does not anticipate conducting an environmental fate or 

ecological risk assessment for thymol. In addition, no environmental fate or ecological 

data are anticipated as being needed 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-toxicity potential of thymol, the Agency 

anticipates concluding that the registered uses of thymol will have “no effect” (NE) on 
Docket Number; EPA-HQ-OPP-2010-0002 

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endangered or threatened terrestrial or aquatic species, or their designated critical 

habitats, as listed by the U.S. Fish and 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 environmental fate and ecological risk assessment is 

available in the document titled, Summary of Product Chemistry, Environmental Fate, 

and Ecotoxicity Data for the Thymol Registration Review Decision Document, dated 

March 23, 2010. 

Incidents:

A search of the OPP Incident Data System (IDS) revealed no reported incidents 

for thymol. 
Docket Number; EPA-HQ-OPP-2010-0002 

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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 Proposed 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 

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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 

LC50 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. 

LD50 Median Lethal Dose. A statistically derived 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 Identification (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 Dose 
Docket Number; EPA-HQ-OPP-2010-0002 

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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 

Q1* 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 (Registrations 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