Docket Number: EPA-HQ-OPP-2010-0003 

www.regulations.gov 

United States Chemical Safety September 2010 

Environmental Protection and Pollution Prevention 

Agency (7510P) 

Irgarol Final Work Plan 

Registration Review 

September 2010 

 

 

Docket Number: EPA-HQ-OPP-2010-0003 

www.regulations.gov 

TABLE OF CONTENTS

Irgarol Registration Review Team.................................................................................. 4 

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

II. SUMMARY OF COMMENTS RECEIVED ON PRELIMINARY WORK 

PLAN.......................................................................................................................... 5 

III. RISK ASSESSMENT AND DATA NEEDS........................................................... 7 

IV. TIMELINE.............................................................................................................. 12 

V. GLOSSARY of TERMS & ABBREVIATIONS.................................................. 13 

 
Docket Number: EPA-HQ-OPP-2010-0003 

www.regulations.gov 

Irgarol Registration Review Team

Human Health & Environmental Effects 

William Hazel 

Srinivas Gowda 

Risk Management

Eliza Blair 

Lance Wormell 

Office of General Counsel

Philip Ross 

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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 Irgarol (Case 5031). The FWP includes 

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

received concerning the Preliminary Work Plan in the Summary Document which was 

posted in the Irgarol 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 Irgarol Preliminary Work Plan was entered into the docket for this 

registration review on March 31, 2010. The 60-day comment period ended on June 1, 

2010. The Preliminary Work Plan document is available on www.regulations.gov, docket 

number EPA-HQ-OPP-2010-0003. 

II. SUMMARY OF COMMENTS RECEIVED ON PRELIMINARY WORK 

PLAN

The Agency received one comment document from BASF addressing both the 

human health and ecotoxicity/environmental fate sections of the summary and scoping 

documents. 

In the Preliminary Work Plan, the Agency solicited comments on three specific 

topics: environmental justice, water body impairment, and trade irritants. No comments 

or information were received during the comment period concerning these issues. This 

document makes final the work plan for the Irgarol registration review process. 

Human Health 

Comment: BASF summarized the available toxicity studies followed by their rationale to 

support a waiver from the requirement of a 90-day rat inhalation toxicity study:

Extensive mammalian toxicity testing is available including 90-day rat and dog oral 

toxicity studies, 2-generation reproduction studies and teratology testing. Considerable 

additional data including 2 year rat studies are available for related triazines such as 

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terbutryn. Additionally, kinetic testing demonstrates that Irgarol is rapidly absorbed, 

widely distributed and also rapidly eliminated. 

Furthermore, the use of personal protective equipment is standard in the use situations 

likely to result in inhalation exposure which will significantly reduce exposures. As a 

result, the existing oral studies, with appropriate safety factors, provide adequate 

information for human risk assessment. 

Response: The Agency believes that the hazard of Irgarol via the oral route cannot be 

assumed to be equivalent to the hazard associated with the inhalation route of exposure; 

therefore, the 90-day rat inhalation toxicity study will remain as an expected requirement 

in this final work plan. A compound may be more toxic or incite a different adverse 

effect via inhalation than orally (e.g., portal of entry effects for the inhalation route). The 

pharmacokinetics could also be different by the two routes of exposure. The EPA has 

presented the use of oral route-to-route extrapolations in inhalation risk assessments to 

the SAP (1997 and 2009). The SAP recommendations are for the EPA to obtain 

inhalation toxicity data to permit the conduct of route-specific risk assessments. 

Registered uses of Irgarol in paints, coatings, and antifoulants, for example, include 

application using brush, roller, conventional spray, or airless spray. These use scenarios 

are expected to result in significant inhalation exposure to both residential and 

occupational applicators. EPA requires an inhalation toxicity study when occupational 

inhalation exposures are expected in order to determine the type of respirator required to 

sufficiently reduce inhalation exposure. This is particularly the case for pesticides 

applied in a residential setting because the Agency assumes that these applicators may 

not follow labeling directions requiring use of PPE. 

Environmental Fate / Ecotoxicity 

Comment: The Summary of Product Chemistry, Environmental Fate and Ecotoxicity 

Data document describes Irgarol 1071 as a “ready-to-use solution” (p.5) whereas it is dry 

powder formulation identical in composition to Irgarol 1051. 

Response: The Agency will revise the Summary of Product Chemistry, Environmental 

Fate and Ecotoxicity Data document to read “dry powder” on page 5. 

Comment: Several required studies in the Preliminary Work Plan appear to be tied to the 

use of Irgarol as a wood preservative. BASF does not list this use on its labels and should 

not be responsible for wood preservative-related data requirements. 

Response: Each Irgarol technical registrant will receive a DCI requiring the submission 

of all studies needed to support registration review. For studies required based on uses 

not listed on a registrant’s labels, the Agency intends to waive such data requirements for 

that registrant provided a waiver request with supporting rationale is submitted to EPA 

within 90 days of receipt of the DCI. The Agency anticipates requiring the following 

studies to support the wood preservative use: 

o (GLN 850.3020) Honeybee acute contact LD50

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o (GLN 850.3030) Toxicity of residues to honeybees, “Honey Bee Toxicity of 

Residues on Foliage” 

o (GLN 835.2410) Photodegradation in soil 

o (GLN 835.4200) Anaerobic soil metabolism 

o (Special study) Leachability of Wood Preservatives (AWPA E11-06) 

o (Special study) Soil leaching from wood study (AWPA E20-04) 

Comment: In Table 2, we discuss some of the key issues related to the anticipated testing 

needs indicated by EPA and we identify testing on file with the Agency that addresses 

these potential data requirements. 

Response: The Agency encourages BASF/Ciba to submit any available ecological 

effects/environmental fate studies (including MRID numbers, if available) that may be 

used to support anticipated registration review data requirements. These submissions 

may be made voluntarily prior to the issuance of the DCI or in response to the DCI once 

it has been issued. 

III. RISK ASSESSMENT AND DATA NEEDS

 Irgarol is registered for use as an antifoulant and materials preservative with a 

variety of registered uses. It is registered for use as an antifoulant to boat hulls, and as a 

preservative in paints, caulks, coatings, sealants, grouts, vinyl roofing, roof coatings, 

cements, stucco, wood stains, adhesives, plasters, and incorporated into boat hulls 

themselves. 

 A pesticide product containing Irgarol was first registered in September 1994. 

Because the Reregistration program applied only to chemicals registered prior to 1984, 

no Reregistration Eligibility Decision (RED) has been issued for this chemical. The 

Agency anticipates needing additional data to complete a risk assessment for the Irgarol 

registration review. 

Human Health Risk 

 

Dietary and Drinking Water Exposure

Dietary (food) exposure to Irgarol is not expected to occur. Many of the use sites 

are inherently non-food-contact such as boat bottoms, stucco, and building materials. 

Labels of products used in paints/stains/coatings/caulks clearly prohibit any use that may 

result in contact with food. These labels also prohibit use that may result in contact with 

animal feed, livestock, dairy animals, potable water, or living plants. 

The registered uses of Irgarol could result in contamination of surface water and 

groundwater because the algaecide is expected to slowly leach from antifoulant-painted 

boats. Also, wastewater containing residues may be discharged from facilities 

manufacturing paints, coatings, stucco, stains, caulks, and building materials formulated 

with Irgarol. Finally, leaching of residues from outdoor surfaces covered with Irgarol-

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treated materials may occur. Published literature indicates that abiotic hydrolysis, 

photolysis, and microbial metabolism will occur slowly in water. There is evidence that 

the degradates (see Table 1), which are closely related to Irgarol, are persistent in the 

aquatic environment. In fact, these degradates have been detected in a number of coastal 

waterways. Therefore, there is the potential for human exposure to Irgarol residues in 

drinking water to occur. The need for a drinking water exposure assessment will be 

revisited upon submission and review of the environmental fate data the Agency 

anticipates needing. These environmental fate data would be expected to be useful to 

determine if Irgarol can pass through wastewater treatment facilities into drinking water 

or migrate into residential groundwater wells as a result of its current use patterns. 

 

Occupational and Residential Exposure

 

 The Agency reviewed all available data associated with Irgarol and has determined 

that the currently registered uses of Irgarol may result in residential and occupational 

exposure. Therefore, the Agency will conduct residential (handler and post-application) 

and occupational (handler) risk assessments to assess possible dermal and inhalation 

exposure to Irgarol. 

Anticipated Human Health Data Needs 

Human Health Toxicity:

o (GLN 870.3465) 90-day rat inhalation toxicity 

Occupational and Residential Exposure:

o (GLN 875.1700) Product Use Information – Outdoor 

o (GLN 875.2700) Product Use Information – Indoor 

o (GLN 875.2800) Description of Human Activity 

o (GLN 875.1100) Dermal Exposure - Outdoor 

o (GLN 875.1200) Dermal Exposure - Indoor 

o (GLN 875.1300) Inhalation Exposure - Outdoor 

o (GLN 875.1400) Inhalation Exposure- Indoor 

o (GLN 875.1600) Applicator Exposure Monitoring Data Reporting for 

Dermal and Inhalation Data 

o (GLN 875.2900) Data Reporting and Calculations 

Further information is available in “1,3,5-Triazine-2,4-diamine, N-cyclopropylN'-(1,1-dimethylethyl)-6-(methylthio)- (Irgarol). Human Health Effects Scoping 

Document for the Registration Review Decision,” dated March 26, 2010. 

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Anticipated Physical/ Chemical Property Data Needs 

 All product chemistry data requirements have been fulfilled for the active 

ingredient Irgarol. Therefore, the Agency does not anticipate needing additional product 

chemistry data at this time. 

Further information is available in “Summary of Product Chemistry, 

Environmental Fate, and Ecotoxicity Data for the 1,3,5-Triazine-2,4-Diamine, NCyclopropyl-N'-(1,1-Dimethylethyl)-6-(Methylthio)-Registration Review Decision 

Document”, dated March 29, 2010. 

Environmental Fate 

The Agency has not conducted an environmental fate assessment for Irgarol use 

patterns described in this document. The Agency needs to conduct an environmental fate 

assessment for material preservatives that potentially pass through waste water treatment 

plants (WWTPs) and may be discharged into terrestrial and aquatic environments. For 

this assessment, the Agency anticipates needing those data outlined below. 

Ecological Risk 

No risk assessment has been performed for Irgarol. An ecological assessment will 

be needed for materials preservatives uses and paper mill discharges that potentially pass 

through waste water treatment plants (WWTPs) and may be discharged into terrestrial 

and aquatic environments. One additional ecotoxicity study is needed to conduct this 

assessment. 

Anticipated Environmental Fate and Ecological Data Needs for Irgarol 

The Agency anticipates needing the following data in order to conduct a complete 

environmental fate and ecotoxicity assessment, including an endangered species 

assessment for all uses: 

Environmental Fate Risk Assessment Data Needs: 

o (GLN 850.6800) modified activated sludge respiration inhibition 

o (GLN 835.1110) activated sludge sorption isotherm 

o (GLN 835.3110) ready biodegradability 

o (GLN None) Leachability of Irgarol used in coating systems for outdoor 

materials such as vinyl roofing, elastomeric roof and wall coatings and 

mastics, caulks, sealants, joint cements, spackling, stucco, and 

grouting. A special leaching study is anticipated as being needed 

which would be conducted with various typical end-use products that 

have been treated with Irgarol. 

o (GLN 835.6200) Aquatic (sediment) Field Dissipation 

o (Non-Guideline Special Study) Monitoring of representative U. S. waters 

(residue of concern). 

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o *(GLN 835.2410) Photodegradation in soil 

o *(GLN 835.4200) Anaerobic soil metabolism 

o *(Special study) Leachability of Wood Preservatives (AWPA E11-06) 

o *(Special study) Soil leaching from wood study (AWPA E20-04) 

*The Agency has received a request to voluntarily cancel the wood preservative uses. Should 

the voluntary cancellation process be completed and amended labels received prior to 

issuance of the DCI, these data requirements will not be included in the DCI. 

Ecological Risk Assessment Data Needs: 

o (GLN 850.1045) Acute Penaeid 

o (GLN 850.4225) Seedling emergence - dose response using rice (Oryza 

sativa) 

o (GLN 850.4250) Vegetative vigor - dose response using rice (Oryza 

sativa) 

o (GLN 850.1500) Fish (freshwater and/or estuarine/marine species) life cycle 

o (GLN 850.1710) Oyster BCF 

o (GLN 850.1850) Aquatic organism bioavailability/biomagnifications, 

toxicity 

o (GLN 850.2300) Avian reproductive studies with bobwhite quail and/or 

mallard duck 

o (Non-Guideline Special Study) Whole sediment - chronic invertebrates 

(freshwater and/or estuarine/marine) 

o (GLN 850.4300) Terrestrial Plants Field Study 

o (GLN 850.4450) Aquatic Plants Field Study 

o *(GLN 850.3020) Honeybee acute contact LD50

o *(GLN 850.3030) Toxicity of residues to honeybees, “Honey Bee 

Toxicity of Residues on Foliage” 

*The Agency has received a request to voluntarily cancel the wood preservative uses. Should 

the voluntary cancellation process be completed and amended labels received prior to 

issuance of the DCI, these data requirements will not be included in the DCI. 

Further information is available in “Summary of Product Chemistry, 

Environmental Fate, and Ecotoxicity Data for the 1,3,5-Triazine-2,4-Diamine, NCyclopropyl-N'-(1,1-Dimethylethyl)-6-(Methylthio)-Registration Review Decision 

Document”, dated March 29, 2010. 

Cumulative Effects

 Unlike other pesticides for which EPA has followed a cumulative risk approach 

based on a common mechanism of toxicity, EPA has not yet examined Irgarol for a 

possible common mechanism of toxicity with other chemicals. Irgarol is a member of a 

class of pesticides collectively referred to as “triazine” pesticides, and is structurally 

similar to some of them. The Agency has examined the some members of the triazine 

class of pesticides with respect to a potential common mechanism of toxicity; this 

examination may be found at 

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http://www.epa.gov/oppsrrd1/REDs/triazine_cumulative_risk.pdf. Several members of 

this class have been identified as causing toxicity through a similar mechanism of action; 

specifically, they disrupt endocrine hormone production and have been shown to cause 

mammary gland tumors in rats. 

 Because a data call-in program already exists to specifically address endocrine 

concerns (“Endocrine Disruptor Screening Program”, described below) the Agency does 

not anticipate that it will ask for endocrine-related data at this time. However, if studies 

are received in response to an Endocrine Disruptor Screening Program data call-in, such 

data will be considered as part of a future risk assessment. 

 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/.

 

Endocrine Disruptor Screening Program

As required under FFDCA section 408(p), EPA has developed the Endocrine 

Disruptor Screening Program (EDSP) to determine whether certain substances (including 

pesticide active and other ingredients) may have an effect in humans or wildlife similar to 

an effect produced by a “naturally occurring estrogen, or other such endocrine effects as 

the Administrator may designate.” The EDSP employs a two-tiered approach to making 

the statutorily required determinations. Tier 1 consists of a battery of 11 screening assays 

to identify the potential of a chemical substance to interact with the estrogen, androgen, 

or thyroid (E, A, or T) hormonal systems. Chemicals that go through Tier 1 screening 

and are found to have the potential to interact with E, A, or T hormonal systems will 

proceed to the next stage of the EDSP where EPA will determine which, if any, of the 

Tier 2 tests are necessary based on the available data. Tier 2 testing is designed to 

identify any adverse endocrine related effects caused by the substance, and establish a 

dose-response relationship between the dose and the E, A, or T effect. 

Between October 2009 and February 2010, EPA issued test orders/data call-ins 

for the first group of 67 chemicals, which contains 58 pesticide active ingredients and 9 

inert ingredients. This list of chemicals was selected based on the potential for human 

exposure through pathways such as food and water, residential activity, and certain postapplication agricultural scenarios. This list should not be construed as a list of known or 

likely endocrine disruptors. 

Irgarol is not among the group of 58 pesticide active ingredients on the initial list 

to be screened under the EDSP. Under FFDCA sec. 408(p) the Agency must screen all 

pesticide chemicals. Accordingly, EPA anticipates issuing future EDSP test orders/data 

call-ins for all pesticide active ingredients. 

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For further information on the status of the EDSP, the policies and procedures, the 

list of 67 chemicals, the test guidelines and the Tier 1 screening battery, please visit our 

website: http://www.epa.gov/endo/. 

IV. TIMELINE

EPA has created the following estimated timeline for the completion of the Irgarol 

registration review. 

Registration Review for Irgarol 

Projected Registration Review Timeline

Activities Time 

Opening Docket 

Open Docket Completed March 2009 

Close Public Comment Period Completed May 2010 

Case Development 

Final Work Plan Completed September 2010 

Issue DCI September 2011 

Data Submission September 2012 

Preliminary Risk Assessment September 2014 

Close Public Comment Period December 2014 

Registration Review Decision 

Proposed Registration Review Decision March 2015 

Public Comment Period June 2015 

Final Registration Review Decision & 

Begin Post-Decision Follow-up 2015 

Total (years) 5 

Next Steps:

A Data Call-In (DCI) will be developed regarding the data gaps listed under the 

“Risk Assessment and Data Needs” section. Also, human health and ecological risk 

assessments will be conducted for all uses. 

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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 

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 

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 

PAIRA Pure Active Ingredient Radiolabelled 

PCA Percent Crop Area 

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PDP USDA Pesticide Data Program 

PHED Pesticide Handler's Exposure Data 

PHI Preharvest Interval 

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 

RASSB Risk Assessment and Science Support Branch 

RED Reregistration Eligibility Decision 

REI Restricted Entry Interval 

RfD Reference Dose 

RQ Risk Quotient 

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