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 2010Docket Number: EPA-HQ-OPP-2010-0003 www.regulations.gov



### TABLE OF CONTENTS

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

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

II. SUMMARY OF COMMENTS RECE IVED ON PRELIMINARY WORK

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

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

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

V. GLOSSARY of TERMS & ABBREVIATIONS .................................................. 13Docket 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. Th e work plan also addresses public comments received concerning the Preliminary Work Plan in the Summary Document which was posted in the Irgarol registration review doc ket, and any other comments concerning the initial docket postings. The Summary Do cument 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 year s 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 registrati on 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 Irgarol Preliminary Work Plan was entered into the docket for this registration review on March 31, 2010. Th e 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 RE CEIVED 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 Agen cy solicited comments on three specific topics: environmental justice, water body impairment, and trade irritants. No comments or information were received during the co mment period concerning these issues. This document makes final the work plan for th e Irgarol registration review process.

Human Health

Comment : BASF summarized the available toxicity st udies followed by their rationale to support a waiver from the requirement of a 90-day rat inhalation toxicity study:

Extensive mammalian toxicity testing is av ailable 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 demons trates 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 whic h will significantly reduce exposures. As a result, the existing oral studies, with ap propriate 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 asso ciated 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 th e two routes of exposure. The EPA has presented the use of oral route-to-route extr apolations in inhalati on risk assessments to the SAP (1997 and 2009). The SAP recomm endations are for the EPA to obtain inhalation toxicity data to permit the conduct of route-sp ecific risk assessments.

Registered uses of Irgarol in paints, coa tings, and antifoulants, for example, include application using brush, roller , conventional spray, or airles s spray. These use scenarios are expected to result in significant inha lation exposure to both residential and occupational applicators. EPA requires an inhalation toxicity st udy 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, Envi ronmental Fate and Ecotoxicity Data document describes Irgarol 1071 as a “ready-to-use soluti on” (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 Prelimin ary Work Plan appear to be tied to the use of Irgarol as a wood preservative. BASF doe s not list this use on its labels and should not be responsible for wood preser vative-related data requirements.

Response: Each Irgarol technical registrant will receive a DC I 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 w ood preservative use:

o (GLN 850.3020) Honeybee acute contact LD 50

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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 requi rements. These submissions may be made voluntarily prior to the issuance of the DCI or in re sponse to the DCI once

it has been issued.

III. RISK ASSESSMEN T AND DATA NEEDS

Irgarol is registered for use as an an tifoulant and materials preservative with a variety of registered uses. It is registered for use as an an tifoulant to boat hulls, and as a preservative in paints, caulks, coatings, s ealants, grouts, vinyl r oofing, roof coatings, cements, stucco, wood stains, adhesives, plas ters, and incorporated into boat hulls

themselves.

A pesticide product containing Irgarol wa s first registered in September 1994. Because the Reregistration program applied on ly 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 Irgar ol is not expected to occu r. 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/coa tings/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 re sult in contamination of surface water and groundwater because the algaecide is expected to slowly leach fr om 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 out door surfaces cove red with Irgarol-

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treated materials may occur. Published lite rature indicates that abiotic hydrolysis, photolysis, and microbial metabolism will occur sl owly 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 potent ial 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 th e environmental fate data the Agency anticipates needing. These environmental fate data would be expected to be useful to determine if Irgarol can pass through wastewat er 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 a ssociated 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 assessment s 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 Reporti ng and Calculations

Further information is available in “1,3,5-Triazine-2,4-diamine, N-cyclopropylN'-(1,1-dimethylethyl)-6-(methylthio)- (Ir garol). Human Health Effects Scoping Document for the Registration Review Decision,” dated March 26, 2010.

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Anticipated Physical/ Chemic al 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 Da ta for the 1,3,5-Triazine-2,4-Diamine, NCyclopropyl-N'-(1,1-Dimethylethyl)-6-(Meth ylthio)-Registration Review Decision Document”, dated March 29, 2010.

Environmental Fate

The Agency has not conducted an envir onmental fate assessment for Irgarol use patterns described in this document. The Ag ency 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 eco toxicity study is needed to conduct this

assessment.

Anticipated Environmental Fate and Ecological Data Needs for Irgarol

The Agency anticipates needing the followi ng data in order to conduct a complete environmental fate and ecotoxicity asse ssment, 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 sl udge 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, elas tomeric 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 (sedim ent) 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 voluntar ily cancel the wood pres ervative 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 LD 50

o *(GLN 850.3030) Toxicity of resi dues to honeybees, “Honey Bee Toxicity of Residues on Foliage”

*The Agency has received a request to voluntar ily cancel the wood pres ervative 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 Da ta for the 1,3,5-Triazine-2,4-Diamine, NCyclopropyl-N'-(1,1-Dimethylethyl)-6-(Meth ylthio)-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 ex amined the some members of the triazine class of pesticides with respect to a po tential 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 identifie d as causing toxicity through a similar mechanism of action; specifically, they disrupt endoc rine 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 Pr ogram”, described below) the Agency does not anticipate that it will ask for endocrine-related data at th is time. However, if studies are received in response to an Endocrine Disr uptor 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 dete rmine whether certain substances (including pesticide active and other ingred ients) may have an effect in humans or wildlife similar to an effect produced by a “natur ally occurring estrogen, or othe r such endocrine effects as the Administrator may designate.” The ED SP 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 substa nce 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 inte ract with E, A, or T hormonal systems will proceed to the next stage of the EDSP wher e EPA will determine which, if any, of the Tier 2 tests are necessary based on the avai lable data. Tier 2 te sting is designed to identify any adverse endocrine related eff ects caused by the substance, and establish a dose-response relationship between th e 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 c ontains 58 pesticide ac tive ingredients and 9 inert ingredients. This list of chemicals was selected based on the potential for human exposure through pathways such as food and wa ter, residential activity, and certain postapplication agricultural s cenarios. This list should not be construed as a list of known or likely endocrine disruptors.

Irgarol is not among the group of 58 pesticid e 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

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 Dose PAIRA Pure Active Ingredient Radiolabelled PCA Percent Crop Area

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11 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 Q 1 * 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 (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