UNITED STATES ENVIRONMENTAL PROTECTION AGENCY WASHINGTON, D. C. 20460 OFFICE OF PREVENTION, PESTICIDES AND TOXIC SUBSTANCES MEMORANDUM SUBJECT: Zinc Pyrithione ( Zinc Omadine ® ) : Occupational and Residential Exposure Assessment for the RED Document. Chemical No. 088002. Case No. 2480. DP Barcode: D301370 DATE: April 20, 2004.

TO: Connie Welch, Chief Benjamin Chambliss, Team Leader, Reregistration Team 36 Regulatory Management Branch I Antimicrobials Division ( 7510C)

FROM: Doreen Aviado, Biologist, Team Two and Deborah Smegal, Toxicologist/ Risk Assessor Risk Assessment and Science Support Branch Antimicrobials Division ( 7510C)

THRU: Nader Elkassabany, Team Leader, Team Two Risk Assessment and Science Support Branch Antimicrobials Division ( 7510C)

Norm Cook, Chief Risk Assessment and Science Support Branch Antimicrobials Division ( 7510C)

Attached is the revised Human Exposure Chapter for AD/ RASSB's science assessment of zinc pyrithione ( zinc omadine ® ) for the purpose of issuing a Reregistration Eligibility Decision ( RED) document. Potential nondietary exposures to occupational and residential handlers are addressed in this document, along with postapplication exposure from contact with zinc pyrithione treated articles. i 1.0 EXECUTIVE SUMMARY . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1 2.0 OCCUPATIONAL AND RESIDENTIAL EXPOSURE AND RISK ASSESSMENT . . . . . . . . . . . . . . . . 8 A. Toxicological Considerations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8 ( 1) Criteria for Conducting Exposure Assessments . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8 ( 2) Summary of Toxicity Concerns Relating to Occupational and Residential Non Dietary Exposures . . 8 ( a) Acute Toxicology Categories . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8 ( b) Summary of Toxicological Endpoint Selection . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9 ( c) Dermal Absorption . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12 B. Occupational and Residential Exposures . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12 ( 1) Handler Exposures . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12 ( a) Antifoulant Use Pattern . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 13 ( b) Materials Preservation Use Pattern . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 14 ( 2) Handler Exposure Data and Assumptions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 17 ( a) Handler Exposure Data . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 18 ( b) Estimated Amount Handled . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 22 ( 3) Handler Risk Assessment and Characterization . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 26 ( a) Handler Exposure and Non Cancer Risk Calculations . . . . . . . . . . . . . . . . . . . . . . . . . . . . 26 ( b) Handler Non Cancer Risks from Exposure to Zinc Pyrithione . . . . . . . . . . . . . . . . . . . . . . 34 ( 4) Postapplication Exposures and Risks . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 36 ( a) Primary Occupational Postapplication Exposures . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 37 ( b) Secondary Occupational Postapplication Exposures . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 37 ( c) Residential Postapplication Exposures and Risks . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 38 ( 5) Aggregate Postapplication Residential Risks . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 43 ( 6) Data Gaps, Uncertainties, and Limitations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 44 3.0 REFERENCES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 45 1 1.0 EXECUTIVE SUMMARY Background Zinc pyrithione ( Zinc Omadine ® ) is used as an industrial preservative to prevent microbial deterioration and to maintain the integrity of manufacturing precursor materials and finished manufactured articles. Zinc pyrithione is a bacteriostat, fungicide, microbiocide/ microbiostat registered for incorporation into food packaging adhesives ( indoor food), incorporation into articles made from or coated with FDA approved food contact polymers such as food processing equipment, conveyor belts, utensils, and storage containers ( indoor food), antifoulant paint preservation ( indoor/ outdoor nonfood), control of bacterial growth on laundered products ( indoor nonfood), and preservation of adhesives, caulks, patching compounds, sealants, grouts, latex paints, coatings, dry wall, gypsum, pearlite, and plaster ( indoor nonfood). Zinc pyrithione is used for the control of mildew in nonfood contact polymers and control of mildew and bacteria in styrene butadiene rubber and thermoplastic resins ( e. g. carpets and other floor coverings, textiles, home furnishings, housewares, sports equipment, automotive/ public transport systems, mattress liners, air ducts, etc.). Materials preservation extends to in can preservation of clay, mineral, pigment and guar gum slurries, latex emulsions, and similar high solids aqueous media. Zinc pyrithione is also conditionally registered as an antifoulant for incorporation as an active ingredient into boat paints. An exposure/ risk assessment for occupational exposures associated with this use pattern is not included in the current Zinc Pyrithione RED. The registrant, Arch Chemicals is conducting a study to assess exposures of workers performing painting of commercial vessels with antifoulant paints containing zinc pyrithione. This study is expected to be completed and submitted in 2006, and will be used to assess the conditional registrations for the antifoulant paint use. However, the occupational use on commercial vessels will be evaluated at a later date. The registrant has submitted a protocol to AD that, when accepted,

will allow the registrant to gather experimental data on exposures of workers performing painting of commercial vessels with antifoulant paints containing zinc pyrithione. Residential exposures and risks from use of antifoulant paint containing zinc pyrithione are assessed in this chapter.

There are five registered industrial end use products containing zinc pyrithione that are eligible for reregistration under Case 2480 as materials preservatives. They range in active ingredient concentration from 5% a. i. to 95% a. i. and are sold as powder, liquid, and aqueous dispersion ( solids in liquid) formulations. The end use products are applied during the manufacturing process of the incorporated treated articles and treated article precursor materials. Zinc Pyrithione formulations are added at rates typically up to 5000 ppm using both open pouring and closed delivery systems. They are added at a point where thorough mixing takes place.

Variations in formulations, conditions of use, and desired degree of protection for the manufactured articles/ substrates determines the pesticide use rates. 2 The resulting manufactured zinc pyrithione treated end products which are sold or distributed are exempt from pesticide registration requirements under FIFRA if they qualify as treated articles under the " treated articles exemption" [ 40 CFR, Part 152.25( a)]. The " treated articles exemption" provides an exemption from FIFRA requirements for qualifying articles or substances treated with, or containing a registered pesticide if ( 1) the incorporated pesticide is registered for use in or on the article or substance itself, and ( 2) the sole purpose of the treatment is to protect the article or substance itself, not to provide additional pesticidal ( antimicrobial) benefits.

Occupational and Residential Exposures The Occupational and Residential Exposure Chapter of the Zinc Pyrithione Reregistration Eligibility Decision Document ( RED) addresses potential exposures and risks to humans who may be exposed to zinc pyrithione in both " occupational" and " residential" settings. Specifically, in support of the materials preservation use patterns, this RED Chapter estimates non dietary exposures and non cancer risks to: primary occupational handlers ( mixers, loaders, applicators) of registered zinc pyrithione pesticide product concentrates in industrial settings; and secondary occupational/ residential handlers of zinc pyrithione treated end products ( e. g., paints) in residential settings. In addition, the use of zinc pyrithione as an antifoulant paint applied to recreational crafts ( i. e., boats) was assessed for residential handlers.

Also addressed are postapplication exposures which can occur to individuals who are involved in industrial activities following application of zinc pyrithione pesticides, and those in contact with zinc pyrithione treated end products in residential sites. Estimates of postapplication exposure to the chemical compound from contact with zinc pyrithione treated articles are presented for residential adults and children,

including child incidental non dietary oral ingestion pathways. Potential dietary exposures from indirect food contact are not addressed in this chapter and are presented as part of the human health risk assessment document.

The exposure scenarios developed for this RED Chapter are representative of potential occupational and residential exposures to zinc pyrithione preservative over short term ( 1 day to 1 month ), intermediate term ( 1 6 months), and long term ( > 6 months) exposure durations. The target MOE is 100 for occupationally exposed workers, while the target MOE is 300 for residential exposures.

At present, there are no available chemical specific occupational exposure monitoring studies meeting Agency guidelines that can be relied upon to assess handler and postapplication exposures to zinc pyrithione.

Therefore, inhalation and dermal exposure dose estimates were developed for occupational handler populations using surrogate data from the Chemical Manufacturers Association ( CMA) Antimicrobial Exposure 3 Assessment Study ( CMA, 1992), the Pesticide Handlers Exposure Database ( PHED) Version 1.1 ( PHED,

1997), and a literature exposure study on antifoulant paints ( Garrod et al. 2000). CMA surrogate data and approaches derived from the EPA Residential Exposure Assessment Standard Operating Procedures ( SOPs)

( U. S. EPA, 1997a, 2001) were used for handler and postapplication assessments for residential populations.

In addition, several studies which relate to the use patterns of zinc pyrithione were used to estimate postapplication exposure. These studies, combined with guidance from EPA SOPs, were used to develop the postapplication section. Most notably, an exposure assessment submitted to EPA in support of the reregististration requirements of zinc pyrithione entitled " Health Assessment of the Use of Zinc Pyrithione Incorporated Into Polyurethane Sole Liners of Shoes" ( MRID 441086 01) ( Olin Corporation, 1996) was used in conjunction with leach rate data from an FDA Migration Study ( MRID 441086 02) ( U. S. EPA, 2000) as " surrogate" data to calculate dermal exposures to the preservative incorporated into polymeric materials.

Potential non dietary exposures via oral ingestion of residues from treated toy surfaces ( i. e., infant toyto mouth and hand to mouth contact) were addressed using " surrogate" exposure information from " Risk Analysis For Microban Additive " B" ( Triclosan or Irgasan DP300) Treated Toys For Infants ( Dang, 1997),

MRIDs 441086 01 and 441086 02 and the Residential SOPs ( 2001).

Using surrogate unit exposure data, use application rates from EPA registered product labels, and Agency derived estimates of daily amounts handled, a variety of handler and postapplication exposures and risks were assessed.

Handlers Based on the EPA registered use patterns, appropriate primary and secondary handler exposure scenarios were identified for zinc pyrithione. In general terms, EPA defines " primary" handler exposure as direct exposure to the pesticide formulation during mixing/ loading/ applying operations. " Secondary" handler exposure is defined as exposure to a pesticide active ingredient as a direct result of its incorporation into an end product.

Primary Occupational Handlers. The exposure and risk assessment for primary occupational handlers was conducted using product label maximum application rates, related use information from Arch Chemicals, Inc., Agency standard values for industrial practices, and CMA unit exposure data. For mixing/ loading liquids and powders in closed systems ( i. e., using a metered pump, or automatic dispensing techniques), the margin of exposure ( MOE) calculations indicate risks ( i. e., target MOEs

100) not exceeding the Agency's level of concern for the dermal and inhalation exposure scenarios assessed. The " dermal" 4 exposure risks are not of concern ( i. e., MOE

100) for potential short term, intermediate term, and long term exposures during open mixing/ loading of powders and liquids for all the scenarios assessed. Also, the dermal and inhalation MOEs for the laundered fabrics scenarios were not of concern. However, MOEs from inhalation exposures exceed the Agency's level of concern ( i. e., MOEs < 100) for short term, intermediate term, and longterm exposure scenarios during:

° mixing/ loading/ applying powders and liquids for general preservative use patterns using open pour methods ( MOE= 50 for liquid formulations; MOE= 15 for powder formulation); and ° mixing/ loading/ applying powders and liquids for paint preservation using open pour methods ( MOE= 50 for liquid formulations; MOE= 15 for powder formulation).

The Agency may consider requiring risk mitigation steps, such as closed delivery systems or use of a respirator during open pouring.

Secondary Occupational Handlers. Secondary occupational handler exposures could occur through the application of treated paints and coatings, and building materials such as caulks, adhesives, spackling,

groutings, sealants, stucco and joint cements. Based on end use product application methods and use amounts,

it is assumed that exposures while applying paints will be equal to or greater than exposures while applying building materials. Therefore, occupational handler exposures were assessed for the application of paint, as this scenario represents maximum possible exposure to the chemical. Under this scenario, dermal and inhalation exposures were assessed for brush, airless sprayer, and aerosol application methods using PHED Version 1.1 data.

Using product label maximum application rates, related use information, Agency standard values, and PHED unit exposure data, the secondary handler potential short term, intermediate term, and long term MOEs exceed the Agency's level of concern ( MOEs < 100) for:

$ handling zinc pyrithione containing paint products using an airless sprayer application method ( inhalation MOEs= 4.4 and 44 without and with the use of a respirator as PPE, respectively,

and dermal MOE= 74 without the use of gloves as PPE).

It is assumed that in real use situations for airless sprayer applications, the occupational handlers will have adequate respiratory protection by wearing either a dust/ mist or organic vapor respirator as PPE recommended by paint manufacturers for spray equipment applications. Although the dermal MOE for airless spray painting operations is of concern ( MOE= 74) without gloves, the MOE is not of concern ( MOE= 200)

when gloves are worn as protective equipment. It is assumed that in real use situations for airless sprayer applications, the occupational handlers will have adequate dermal protection by wearing gloves as may be 5 recommended by paint manufacturers during spray equipment applications. Dermal and inhalation MOEs obtained for the painting scenarios involving use of paint brush and aerosol spray can application methods were found to be of no risk concern.

Primary Residential Handlers. Zinc Pyrithione is an antifouling agent used to control slime and algae growth below the water line of recreational and commercial boat hulls in fresh, salt, or brackish water.

Recreational boat owners have several techniques they can use to paint their hulls including paint brush, roller,

and airless sprayer. There are no chemical specific exposure data to assess these techniques. However,

surrogate data are available for painting with a brush and an airless sprayer. The surrogate data are based on test subjects painting a bathroom with a paint brush and staining the outside of a house with an airless sprayer.

The dermal and inhalation exposures from these techniques have been normalized by the amount of active ingredient handled and reported as unit exposures ( UE) expressed as mg/ lb ai handled. Although the exposures while painting a boat hull may differ slightly, the data are judged to be representative of painting and are used in this assessment. In addition, Garrod et al ( 2000) measured both inhalation and dermal exposures during the painting of recreational boat hulls. However, the dermal portion of this study only measured a limited number of outside patches on the test subject's clothing. Therefore, only the air concentration measurements from Garrod et al ( 2000) are used to estimate MOEs.

Calculation of dermal and inhalation MOEs for residential use of antifoulant boat paint showed that dermal and inhalation MOEs were of concern ( i. e. < 300) for all boat sizes when using a paint brush. Dermal and inhalation MOEs were also of concern when using an airless sprayer for all boat sizes, except dermal MOEs were not of concern for the smallest boat size. It is important to note that the inhalation exposure risk estimates are conservative because the toxicity endpoint used in the assessment is based on a whole body rat 90 day inhalation study.

Secondary Residential Handlers. An assessment for primary residential handlers was not conducted in support of reregistration for the materials preservative use patterns because only industrial workers handle the EPA registered zinc pyrithione pesticides; rather, residential populations are secondary handlers of consumer end products for which zinc pyrithione has been incorporated during the manufacturing process ( i. e,

zinc pyrithione treated articles).

Secondary residential handler exposures could occur through the application of treated paints and coatings, and building materials such as caulks, adhesives, spackling, groutings, sealants, stucco and joint cements. Based on end use product application methods and use amounts, it is assumed that exposures while applying paints will be equal to or greater than exposures while applying building materials. Therefore,

residential handler exposures were assessed for the application of paint, as this scenario represents maximum possible exposure to the chemical. Under this scenario, dermal and inhalation exposures were assessed for 6 brush, airless sprayer, and aerosol application methods using PHED Version 1.1 values found in the Residential Exposure SOPs ( U. S. EPA, 1997a, 2001). The surrogate exposure data in PHED are based on test subjects painting a bathroom with a paint brush and staining the outside of a house with an airless sprayer.

The dermal and inhalation exposures from these techniques have been normalized by the amount of active ingredient handled and reported as unit exposures ( UE) expressed as mg/ lb ai handled. The residential scenarios are similar to those developed for secondary occupational handlers, only the use rates and residential PHED data are modified.

Using product label maximum application rates, related use information, Agency standard values, and PHED unit exposure data, the secondary handler short term, intermediate term, and long term MOEs exceed the Agency's level of concern ( MOEs < 300) for the following scenarios:

° handling zinc pyrithione containing paint products using an airless sprayer application method ( Dermal MOE= 118 inhalation MOE= 15); and ° handling zinc pyrithione containing paint products using an aerosol spray can application method ( inhalation MOE= 271).

It is assumed that in real use situations for airless sprayer/ aerosol spray can paint applications, the residential handlers will have adequate respiratory protection by wearing either a dust/ mist or organic vapor respirator as may be recommended by paint manufacturers for spray applications, and adequate dermal protection by wearing gloves while painting. Dermal MOEs were not of concern for the painting scenarios involving use of a paint brush and aerosol spray can.

Postapplication Exposures Postapplication exposures refer to those potential exposures which may occur to handlers while involved in postapplication or reentry activities following application of the pesticide concentrate or formulated end use product. Postapplication exposures also result from bystander contact with treated surfaces/ articles and while occupying areas where pesticide end use products have recently been applied ( e. g. treated duct work).

Zinc pyrithione has a low vapor pressure ( i. e.,< 1.87x10 9 torr @ 25  C) and is, therefore, not likely to generate sufficient vapor to cause an inhalation concern to occupational and residential populations performing postapplication tasks, or occupying recently treated areas, or from bystander contact with treated articles.

Therefore, postapplication inhalation exposures were not assessed.

Primary Occupational Postapplication. Primary occupational postapplication inhalation exposures are limited to mists, steams, or vapors resulting from manufacturing process operations. Occupational postapplication dermal and inhalation exposures to zinc pyrithione are likely to be minimal compared to handler 7 exposure because of the dilution of the biocide during processing. Since primary occupational postapplication exposures are likely to be brief and pesticide concentrations are expected to be more diluted, a risk assessment is not required.

Secondary Occupational Postapplication. Secondary occupational postapplication exposures result when bystanders come in contact with zinc pyrithione in areas where pesticide treated end use products have recently been applied ( e. g., freshly painted walls). Workers could have dermal and inhalation exposures to zinc pyrithione treated adhesives, caulks, sealants, and paints. However, since the paint, caulks and sealants are expected to dry within a day, potential dermal and inhalation exposures are expected to be minimal. In addition, the short term dermal endpoint is based on a 90 day dermal study, rather than a one day study, and would significantly overestimate the risks associated with this scenario. Exposures resulting from contact with treated fabrics/ textiles, polymeric materials and related treated substances are expected to be negligible because of limited transfer of product residues and product dilution. Consequently, postapplication dermal exposures were not quantitatively evaluated in this report.

Residential Postapplication. Residential postapplication exposures result when bystanders ( adults and children) come in contact with zinc pyrithione in areas where pesticide treated end use products have recently been applied ( e. g., freshly painted walls or boat hulls of recreational craft), or when children incidentally ingest the pesticide residues through mouthing the treated end products/ treated articles ( i. e.,

handto mouth or object to mouth contact). As noted previously for the occupational scenarios, postapplication dermal exposures are expected to be minimal because the paint is expected to dry within a day. Thus,

postapplication dermal exposures to paint were not quantitatively evaluated in this report. Dermal exposures to plastic treated with zinc pyrithione, such as shoe liners, were evaluated and determined not to be of concern ( MOEs = 4,500 7,700). In addition, non dietary incidental ingestion exposures of children via toy to mouth and hand to mouth activities did not exceed the Agency's level of concern ( MOE > 300). Aggregate postapplication residential exposures for a young child were also greater than the target MOE of 300, and are not of concern.

Occupational and Residential Risk Characterization The exposure and risk assessment conducted for occupational and residential populations and use patterns indicated the following:

° Primary occupational handlers of registered zinc pyrithione industrial pesticides are best protected under conditions where automated pesticide delivery systems are used; 8 ° Inhalation exposure to zinc pyrithione is of concern for primary occupational handlers using " open pour" methods ( assessed as wearing no respiratory PPE as typical work conditions).

The Agency may need to require product labeling statements for adequate respiratory protection in the form of respirator PPE;

° Dermal exposure to zinc pyrithione is not a concern for primary occupational handlers ( assessed as wearing gloves under typical work conditions);

° Secondary occupational and residential handlers of zinc pyrithione treated products ( e. g.,

paints, caulks) are best protected under conditions where adequate dermal and inhalation protection occur in the form of PPE ( especially respiratory protection during paint spraying applications). The Agency has no regulatory purview over consumer goods which meet the FIFRA " treated articles exemption";

° Postapplication inhalation and dermal exposures to occupational and residential adult populations are not a concern;

° Postapplication exposures to child populations handling and mouthing treated objects ( i. e.,

toys) are not a risk concern.

2.0 OCCUPATIONAL AND RESIDENTIAL EXPOSURE AND RISK ASSESSMENT A. Toxicological Considerations ( 1) Criteria for Conducting Exposure Assessments An occupational and/ or residential exposure and risk assessment is required for an active ingredient if ( 1) certain toxicological criteria are triggered and ( 2) there is potential exposure to handlers ( mixers, loaders,

applicators) during use or to persons entering treated sites after application is complete. For zinc pyrithione,

both criteria are met.

( 2) Summary of Toxicity Concerns Relating to Occupational and Residential Non Dietary Exposures ( a) Acute Toxicology Categories Acute toxicity categories for zinc pyrithione are shown in Table 1. 9 Table 1. Acute Toxicity Categories for Zinc Pyrithione Test Results Toxicity Category Acute Oral Toxicity LD50= 267 mg/ kg II Acute Dermal Toxicity LD50 > 2000 mg/ kg III Acute Inhalation Toxicity LC50 > 0.61 mg/ L III Primary Eye Irritation Severe Irritant I Primary Dermal Irritation Slight Erythema and Edema IV Dermal Sensitization No Dermal Sensitization Observed NA As indicated above, zinc pyrithione is moderately toxic by the oral route, but acute toxicity by the dermal route is not as significant. Acute toxicity by the inhalation route is also relatively low. Zinc pyrithione is a severe eye irritant ( Toxicity category I) but does not appear to demonstrate significant dermal irritation nor dermal sensitization potential. Non acute toxicity studies with zinc pyrithione demonstrate developmental toxicity as well as neurotoxicity.

( b) Summary of Toxicological Endpoint Selection OPP's Antimicrobial Division Toxicology Endpoint Selection Committee ( ADTC) ( 2004) has identified toxicological endpoints of concern ( EPA, 2004). Table 2 summarizes these endpoints. Dermal endpoints of concern have been identified for short, intermediate, and long term dermal exposures. The noobserved adverse effect level ( NOAEL) selected for short, intermediate, and long term dermal exposures was 100 mg/ kg/ day, based on a 90 day dermal toxicity study in which toxic effects were observed in rats causing decreased body weight gain and food consumption/ food efficiency ( MRID 428279 02).

In addition to the dermal endpoints of concern, inhalation endpoints of concern have also been identified for short, intermediate, and long term inhalation exposures. The NOAEL selected for short,

intermediate, and long term inhalation exposures was 0.0005 mg/ L/ day based on toxic effects including labored breathing, rales, increased salivation, decreased activity, dry red brown material around the nose,

increased absolute and relative lung weights, and death of undetermined cause ( MRID 428279 03). Since the NOAEL was presented in mg/ L/ day, it was necessary to convert the dose to mg/ kg/ day because exposure doses are presented in these units. A route to route extrapolation equation was used to convert human and animal values from " mg/ L/ day" concentrations to " mg/ kg/ day." Using the " Route to Route Extrapolation" presented by EPA, the dose of 0.0005 mg/ L/ day converts to 0.13 mg/ kg/ day ( U. S. EPA, 1998). 10 Equation 1 mg/ L/ day x A x RV x D x AF = mg/ kg/ day BW where:

A = Absorption. The ratio of deposition and absorption in the respiratory tract compared to absorption by the oral route. 100% absorption is assumed for inhalation. RV = Respiratory Volume ( RV) is 10.26 L/ hr/ kg for male and female Sprague Dawley rats. D = Duration ( D) of daily animal or human body weight in kg. Duration of the rat study was 6 hr/ day. AF = Activity Factor ( AF) for animals is 1. BW = Mean animal weight for Sprague Dawley rats is 0.236 kg.

Table 2. Toxicological Endpoints for Assessing Occupational and Residential Exposures/ Risks Exposure Scenario Dose ( mg/ kg/ day) Endpoint Study Acute Dietary Exposure ( females 13+) Developmental NOAEL = 0.5 Increased post implantation loss and decreased viable fetuses were observed at LOAEL = 1.5 mg/ kg/ day Developmental Toxicity Study in Rabbits for gestation days 6 18 UF = 100 FQPA= 1X DB= 3X Acute Dietary Exposure ( general population & infants/ children) Maternal NOAEL = 0.75 Maternal toxicity characterized as increased salivation observed at LOAEL = 3.0 mg/ kg/ day Developmental Toxicity Study in Rats for gestation days 6 15 UF = 100 FQPA= 1X DB= 3X Chronic Dietary Exposure  Reference Dose ( all populations) Developmental NOAEL = 0.5 Increased post implantation loss and decreased viable fetuses were observed at LOAEL = 1.5 mg/ kg/ day Development Toxicity Study in Rabbits for gestation days 6 18 UF = 100 FQPA= 1X DB= 3X Short, Intermediate Term Oral Exposure NOAEL = 0.75 Target MOE= 300 Residential Maternal toxicity characterized as increased salivation at were observed at LOAEL = 3.0 mg/ kg/ day Developmental Toxicity Study in Rats for gestation days 6 15 Short, Intermediate, and Long Term Dermal Exposure Dermal NOAEL= 100 Target MOEs= 100 Occupational; 300 Residential Decreased body weight gain and food consumption/ food efficiency at LOAEL = 1000 mg/ kg/ day 90 day Subchronic Dermal Toxicity Study in Rats Short, Intermediate, and Long Term Inhalation Exposure Inhalation NOAEL= 0.0005 mg/ L ( i. e., 0.13 mg/ kg/ day) Target MOEs= 100 Occupational; 300 Residential Clinical signs of toxicity, decreased activity, and increased lung weights at LOAEL = 0.0025 mg/ L 90 day Subchronic Inhalation Toxicity Study in Rats Oral Cancer Slope Factor No chronic or carcinogenicity studies are available to assess the carcinogenic potential of zinc pyrithione N/ A N/ A 11 UF = Uncertainty Factor NA = Not applicable Recommended MOEs of 100 for the occupational assessment are based on applied uncertainty factors of 10x to account for interspecies extrapolation, and 10x for intra species variability. FQPA SF = An additional 1x is applied as an FQPA safety factor for the non dietary oral ( incidental ingestion) residential MOEs calculated in this assessment. DB UF = An additional 3x is applied as a database uncertainty factor for all residential MOEs calculated in this assessment.

For the residential postapplication assessment, it was necessary to address potential exposures through both the dermal route ( adults and children) and oral route ( child incidental ingestion via hand to mouth and direct mouthing of treated articles). The NOAEL of 0.75 mg/ kg/ day was selected by the ADTC/ HIARC for the general population and infants based on evidence of increased salivation in dams at a LOAEL of 3.0 mg/ kg/ day ( MRID 428279 05). For the female population, a NOAEL of 0.5 mg/ kg/ day was selected based on increased post implantation loss and decreased number of viable fetuses at a LOAEL of 1.5 mg/ kg/ day ( U. S. EPA, 1999a).

The 1999 HIARC report also addressed the potential increased susceptibility of infants and children from exposure to zinc pyrithione as required by the Food Quality Protection Act ( FQPA) of 1996. However,

a subsequent evaluation of the hazard and exposure data for zinc pyrithione was conducted by the Health Effects Division's FQPA Safety Factor Committee on August 7, 2001 for the purpose of determining the appropriate safety factor under FQPA. They initially recommended that an additional safety factor of 10x be retained for zinc pyrithione and that this factor be applied to all population subgroups for assessing residential risks. Since that time, changes to the application of the FQPA safety factor have been published by the Agency. For zinc pyrithione, while the rat and rabbit developmental toxicity studies show qualitative evidence of increased susceptibility, there is an adequately characterized endpoint in both studies. Thus, the effects observed in offspring in the developmental toxicity studies can be used to select dietary endpoints for assessing incidental oral ingestion exposure, and are thus protective of infants and children. Therefore, the special FQPA safety factor is reduced to 1x. However, a database uncertainty factor of 3x is applied to all assessed residential exposure scenarios ( i. e., oral, dermal and inhalation routes) due to a lack of characterization of neurotoxic dose response relationships for zinc pyrithione ( U. S. EPA, ADTC 2004).

For assessing all potential occupational exposures, a margin of exposure ( MOE) of 100 was selected.

For the residential exposure assessment an FQPA safety factor ( 1x) and a database uncertainty factor ( 3x) were applied resulting in the selection of an MOE of 300 for the non dietary oral exposure scenarios. The database uncertainty factor ( 3x) was also applied to all assessed residential dermal and inhalation exposure scenarios for a selected MOE of 300.

Studies with zinc pyrithione were not available to address chronic toxicity and carcinogenicity for this chemical. [ Data on the carcinogenic potential of a related compound, sodium pyrithione, showed no evidence of carcinogenicity, and was classified as a Group D ( not classifiable as to carcinogenicity) carcinogen by the Health Effects Division Carcinogenicity Peer Review Committee.] Therefore, a cancer risk assessment was 12 not conducted since carcinogenic endpoints related to lifetime average absorbed doses of zinc pyrithione from occupational and residential exposures have not been identified.

( c) Dermal Absorption A dermal absorption factor is not required because a dermal NOAEL was selected for the dermal risk assessments. However, it should be noted that the 3% dermal absorption factor demonstrated in the swine study is supported by a literature study in mice which also showed a dermal absorption of 3% ( U. S. EPA,

1999a).

B. Occupational and Residential Exposures ( 1) Handler Exposures EPA has determined that there is a potential for exposures to mixers, loaders, applicators, or other handlers associated with the registered use patterns of zinc pyrithione pesticide products. There are potential exposures from use in commercial, industrial, and residential settings via the dermal and inhalation routes.

EPA has identified the following levels of handler exposures:

° Primary Handlers  Defined as persons having direct exposure to the pesticide formulations during mixing/ loading/ applying operations. For this RED, primary handlers are " occupational handlers" of EPA registered zinc pyrithione pesticide product concentrates used for industrial manufacturing purposes as dry film, in can, and general materials preservatives for incorporation into various substrates prone to fungal and bacterial degradation ( e. g., water based emulsions, coatings, slurries, thermoplastic resins, rubber, textiles, and polymeric systems). In addition, do it yourself ( D I Y) painters are considered primary handlers for antifoulant paints ( i. e. boat owner's painting hulls of recreational boats in residential settings).

° Secondary Handlers  Defined as persons having direct exposure to the pesticide active ingredient as a result of its incorporation into manufactured end products. Exposure occurs during normal use patterns of the end products. For this RED, secondary handlers are both " occupational handlers" and " residential handlers" of caulks, sealants, paints, and other end products to which zinc pyrithione has been added as a preservative.

EPA has identified the following exposure scenarios for primary occupational handlers, secondary occupational handlers, and primary and secondary residential handlers. These exposure scenarios are further developed in Table 4 for each of the major registered materials preservation use patterns. A separate section details the scenarios for residential handlers of antifoulant paints.

Primary Occupational Handlers 13 ° mixing/ loading/ applying liquid zinc pyrithione pesticide product concentrates using open pour methods.

° mixing/ loading/ applying liquid zinc pyrithione pesticide product concentrates using metering equipment ( pump liquid).

° mixing/ loading/ applying powder zinc pyrithione pesticide product concentrates using open pour methods.

° mixing/ loading/ applying powder zinc pyrithione pesticide product concentrates using metering equipment ( automatic dispensing techniques).

Secondary Occupational Handlers ° handling zinc pyrithione containing paint end products using paint brush, airless sprayer, and aerosol spray can application methods.

Primary Residential Handlers ( Antifoulants)

° handling zinc pyrithione containing antifoulant paints using a paint brush.

° handling zinc pyrithione containing antifoulant paints using an airless sprayer.

Secondary Residential Handlers ( Materials Preservatives)

° handling zinc pyrithione containing paint end products using paint brush, airless sprayer, and aerosol spray can application methods.

( a) Antifoulant Use Pattern Zinc Pyrithione is an antifouling agent used to control slime and algae growth below the water line of recreational and commercial boat hulls in fresh, salt, or brackish water. Zinc pyrithione is incorporated into various antifoulant paint formulations. The registered antifoulant paint end products bear labeling with specified use patterns, application methods and personal protective equipment ( PPE). Labeling for the following products ( EPA Reg. Nos.) shown in Table 3 have been reviewed and representative products selected for the residential handler assessment:

Table 3. Zinc Pyrithione Antifoulant Paint Use Pattern EPA Reg. No. Percent (%) Zinc Pyrithione in Formulation Use Pattern Table 3. Zinc Pyrithione Antifoulant Paint Use Pattern 14 2693 187 3.8 % Limited to commercial use only. No restrictions on application methods. Requires eyewear, long pants, long sleeved shirt, hat, gloves, and respirator. ( Accepted label 12/ 6/ 2001)

2693 188 3.18 % Limited to commercial use only. No restrictions on application methods. Requires eyewear, long pants, long sleeved shirt, hat, gloves, and respirator. ( Accepted label 9/ 7/ 2000)

2693 194 47.04 % No restrictions on use but does not specifically mention recreational boats. No restrictions on application methods. This is the Activator product portion of a twopart mixture. Requires eyewear only. ( Accepted label 5/ 2/ 2002)

2693 200 3.04 % No restrictions on use but does not specifically mention recreational boats. Application methods listed as brush or roller and that " spraying is not recommended". Requires eyewear, long pants, long sleeved shirt, hat, gloves, and respirator. Product can be thinned up to 10% and covers 320 ft2/ gallon at a 2 mil dry film thickness. ( Accepted label 10/ 3/ 2002)

2693 203 3.39 % Label specifically mentions small craft and car top boats. Application methods listed as brush or roller and that " spraying is not recommended". Requires eyewear, long pants, long sleeved shirt, hat, gloves, and respirator. Product can be thinned up to 10 to 25% and covers 400 ft2/ gallon and recommends a minimum of 3 coats. ( Accepted label 10/ 3/ 2002)

64684 4 4.8 % Label specifies commercial and recreational use. Application methods listed as brush or roller but does not prohibit spraying. Requires eye wear, long pants, longsleeved shirt, hat, and gloves while " spraying, sanding or blasting the paint" and respirator. Unclear if PPE is for the preparation of the hull or for the painting. Thinning is not recommended and recommends a minimum of 3 coats. ( Accepted label 3/ 17/ 2000)

64684 6 4.7 % No restrictions on use but does not specifically mention recreational boats. Application methods listed as brush, roller, and spraying. Requires eyewear, long pants, long sleeved shirt, hat, and gloves while " spraying, sanding or blasting the paint" and respirator. Unclear if the PPE is for the preparation of the hull or for the painting. Thinning is not recommended for brush and roller and up to 10 percent for spraying. A minimum of 3 coats is recommended and covers 300 ft2/ gallon. ( Accepted label 3/ 17/ 2000)

Note: Bold denotes products used for the residential handler assessment which were selected as representative of the range of registered antifoulant end products.

( b) Materials Preservation Use Pattern Zinc Pyrithione is used as an industrial preservative to prevent decay and maintain the integrity of manufacturing precursor materials and manufactured articles. Zinc pyrithione is a bacteriostat, fungicide, microbiocide/ microbiostat registered for use in food packaging adhesives ( indoor food), paint preservation ( indoor/ outdoor nonfood), control of bacterial growth on laundered products ( indoor nonfood), and preservation of adhesives, caulks, patching compounds, sealants, grouts, latex paints, coatings, dry wall, gypsum, pearlite, and plaster ( indoor nonfood). Zinc pyrithione is used for the control of mildew in nonfood contact polymers and control of mildew and bacteria in styrene butadiene rubber and thermoplastic resins. Materials preservation extends to in can preservation of clay, mineral, pigment and guar gum slurries, latex emulsions, and similar high solids aqueous media. 15 There are five registered industrial end use products containing zinc pyrithione that are eligible for reregistration under Case 2480 as materials preservatives. They range in active ingredient concentration from 5% a. i. to 95% a. i. and are sold as powder, liquid, and aqueous dispersion ( solids in liquid) formulations. The end use products are applied during the manufacturing process of the incorporated treated articles and treated article precursor materials. Zinc Pyrithione formulations are added at rates typically up to 5000 ppm using both open pouring and closed delivery systems. They are added at a point where thorough mixing takes place. Variations in formulations, conditions of use, and desired degree of protection for the manufactured articles/ substrates determines the pesticide use rates. Representative scenarios developed for the materials preservation use pattern are detailed in Table 4.

The resulting manufactured zinc pyrithione treated end products which are sold or distributed are exempt from pesticide registration requirements under FIFRA if they qualify as treated articles under the " treated articles exemption" [ 40 CFR, Part 152.25( a)]. The " treated articles exemption" provides an exemption from FIFRA requirements for qualifying articles or substances treated with, or containing a registered pesticide if ( 1) the incorporated pesticide is registered for use in or on the article or substance itself, and ( 2) the sole purpose of the treatment is to protect the article or substance itself, not to provide additional pesticidal ( antimicrobial) benefits.

Table 4. Exposure Scenarios for Occupational/ Residential Handlers Exposure Scenario Scenario Description Primary Occupational Handler General Preservative Uses: Dry Film, In Can, and Materials Preservation ( 1a) Mixing/ loading/ applying liquid pesticide concentrates using open pour methods Scenario encompasses a variety of general preservatives use patterns ( i. e., dry film, in can, and materials preservation) where the pesticide is incorporated into various substrates ( e. g., food/ non food contact adhesives, water based emulsions, coatings, slurries, thermoplastic resins ( e. g. air ducts), rubber, textiles, and food/ non food contact polymeric systems; including repeat use polymeric food contact materials such as manufactured food processing equipment and conveyor belts). The biocide is added using open pour methods. Potential exposures may occur during the open loading/ applying of the concentrate into bulk tanks/ mixing vats or other containers during manufacturing of the various substrates. The manufacturing of caulks/ sealants from slurries treated for dry film or in can preservation was selected as the representative scenario. Unit exposures from CMA database for pouring liquid preservatives are used to calculate exposure ( CMA, 1992).

( 1b) Mixing/ loading/ applying liquid pesticide concentrates using metering equipment ( pump liquid) Scenario encompasses a variety of general preservatives use patterns ( i. e., dry film, in can, and materials preservation) where the pesticide is incorporated into various substrates ( e. g., food/ non food contact adhesives, water based emulsions, coatings, slurries, thermoplastic resins ( e. g. air ducts), rubber, textiles, and food/ non food contact polymeric systems; including repeat use polymeric food contact materials such as manufactured food processing equipment and conveyor belts). The biocide is added using an automated metering system. Potential exposures may occur during the loading and setup/ maintenance of the automated metering system during manufacturing of the various substrates. Liquid concentrates are pumped into tanks or bins and diluted into a slurry. The manufacturing of caulks/ sealants from slurries treated for dry film or in can preservation was selected as the representative scenario. Unit exposures from CMA database for pumping liquid preservatives are used to calculate exposure ( CMA, 1992). Table 4. Exposure Scenarios for Occupational/ Residential Handlers Exposure Scenario Scenario Description 16 ( 1c) Mixing/ loading/ applying powder pesticide concentrates using open pour methods Scenario encompasses a variety of general preservatives use patterns ( i. e., dry film, in can, and materials preservation) where the pesticide is incorporated into various substrates ( e. g., food/ non food contact adhesives, water based emulsions, coatings, slurries, thermoplastic resins ( e. g. air ducts), rubber, textiles, and food/ non food contact polymeric systems; including repeat use polymeric food contact materials such as manufactured food processing equipment and conveyor belts). The powder biocide is added using open pour methods into liquid slurries. Potential exposures may occur during the open loading/ applying of the concentrate into bulk tanks/ mixing vats or other containers during manufacturing of the various substrates. The manufacturing of caulks/ sealants from slurries treated for dry film or in can preservation was selected as the representative scenario. Unit exposures from CMA database for solid pour are used to calculate exposure ( CMA, 1992).

( 1d) Mixing/ loading/ applying powder pesticide concentrates using metering equipment ( automatic dispensing techniques) Scenario encompasses a variety of general preservatives use patterns ( i. e., dry film, in can, and materials preservation) where the pesticide is incorporated into various substrates ( e. g., food/ non food contact adhesives, water based emulsions, coatings, slurries, thermoplastic resins ( e. g. air ducts), rubber, textiles, and food/ non food contact polymeric systems; including repeat use polymeric food contact materials such as manufactured food processing equipment and conveyor belts). The powder biocide is added using an automated metering system into liquid slurries. Potential exposures may occur during the loading and setup/ maintenance of the automated metering system during manufacturing of the various substrates. The manufacturing of caulks/ sealants from slurries treated for dry film or in can preservation was selected as the representative scenario. No unit exposure data were available to represent mixing/ loading/ applying of powder formulations in closed delivery systems. Therefore, CMA unit exposure data for general preservatives for pump liquid ( a closed delivery system) are used as a surrogate to calculate exposure ( CMA, 1992).

Paints: Dry Film Preservation ( 2a) Mixing/ loading/ applying liquid pesticide concentrates using open pour methods Scenario occurs when the pesticide is added at anytime during the paint manufacturing process for dry film preservation. The biocide is added using open pour methods. Potential exposures may occur during the loading/ applying of the concentrate into bulk tanks/ mixing vats for incorporation into paint formulations. CMA unit exposure data for general preservatives for pour liquid are used to calculate exposure ( CMA, 1992).

( 2b) Mixing/ loading/ applying liquid pesticide concentrates using metering equipment ( pump liquid) Scenario occurs when the pesticide is added at anytime during the paint manufacturing process for dry film preservation. The biocide is added using an automated metering system. Potential exposures may occur during loading and setup/ maintenance of the automated metering system. CMA unit exposure data for general preservatives for pump liquid are used to calculate exposure ( CMA, 1992).

( 2c) Mixing/ loading/ applying powder pesticide concentrates using open pour methods Scenario occurs when the pesticide is added at anytime during the paint manufacturing process for dry film preservation. The powder biocide is added using open pour methods. Potential exposures may occur during the loading/ applying of the concentrate into bulk tanks/ mixing vats for incorporation into paint formulations. CMA unit exposure data for general preservative for solid pour data are used to calculate exposure ( CMA, 1992).

( 2d) Mixing/ loading/ applying powder pesticide concentrates using metering equipment ( automatic dispensing techniques) Scenario occurs when the pesticide is added at anytime during the paint manufacturing process for dry film preservation. The powder biocide is added using an automated metering system. Potential exposures may occur during loading and setup/ maintenance of the automated metering system. No unit exposure data were available to represent mixing/ loading/ applying of powder formulations in closed delivery systems. Therefore, CMA unit exposure data for general preservatives for pump liquid ( a closed delivery system) are used as a surrogate to calculate exposure ( CMA, 1992).

Fabrics/ Textiles: Laundering Treatment for Materials Preservation Table 4. Exposure Scenarios for Occupational/ Residential Handlers Exposure Scenario Scenario Description 17 ( 3a) Mixing/ loading/ applying liquid pesticide concentrates using open pour methods Scenario occurs when the pesticide concentrate is added to the " acid sour" operation during industrial laundering treatments of manufactured fabrics/ textiles. The biocide is added in a recirculating water system using open pour methods. Potential exposures may occur via loading and filling bulk tanks, contact with wet laundered fabrics/ textiles or exposure to mists or vapors from the laundry machines. Unit exposures from CMA database for pouring liquid preservatives are used to calculate exposure ( CMA, 1992).

( 3b) Mixing/ loading/ applying liquid pesticide concentrates using metering equipment ( pump liquid) Scenario occurs when the pesticide concentrate is added to the " acid sour" operation during industrial laundering treatments of manufactured fabrics/ textiles. The biocide is added in a recirculating water system using an automated metering system. Potential exposures may occur via loading and setup/ maintenance of the automated metering system. Unit exposures from CMA database for pumping liquid preservatives are used to calculate exposure( CMA, 1992).

( 3c) Mixing/ loading/ applying powder pesticide concentrates using open pour methods Scenario occurs when the pesticide concentrate is added to the " acid sour" operation during industrial laundering treatments of manufactured fabrics/ textiles. The powder biocide is added in a recirculating water system using open pour methods. Potential exposures may occur via loading and filling bulk tanks, contact with wet laundered fabrics/ textiles or exposure to mists or vapors from the laundry machines. Unit exposures from CMA database for general preservatives for solid pour are used to calculate exposure ( CMA, 1992).

( 3d) Mixing/ loading/ applying powder pesticide concentrates using metering equipment ( automatic dispensing techniques) Scenario occurs when the pesticide concentrate is added to the " acid sour" operation during industrial laundering treatments of manufactured fabrics/ textiles. The powder biocide is added in a recirculating water system using an automated metering system. Potential exposures may occur via loading and setup/ maintenance of the automated metering system. No unit exposure data were available to represent mixing/ loading/ applying of powder formulations in closed delivery systems. Therefore, CMA unit exposure data for general preservatives for pump liquid ( a closed delivery system) are used as a surrogate to calculate exposure ( CMA, 1992).

Secondary Occupational Handler ( 4a Handling zinc pyrithione containing paint end products using a paint brush application method Scenario occurs when an occupational handler applies biocide treated paint using a paint brush. PHED unit exposure data for paint brush are used ( PHED, 1997).

( 4b) Handling zinc pyrithione containing paint end products using an airless sprayer application method Scenario occurs when an occupational handler applies biocide treated paint using an airless sprayer. PHED unit exposure data for airless sprayer are used ( PHED, 1997).

( 4c) Handling zinc pyrithione containing paint end products using an aerosol spray can application method Scenario occurs when an occupational handler applies biocide treated paint using an aerosol spray can. PHED unit exposure data for aerosol spray are used ( PHED, 1997).

Secondary Residential Handler ( 5a) Handling zinc pyrithione containing paint end products using a paint brush application method Scenario occurs when a residential handler applies biocide treated paint using a paint brush. PHED unit exposures from the Residential SOPs are used for paint brushing by a residential handler ( EPA 1997). Garrod et al ( 2000) is also used for determining inhalation exposure.

( 5b) Handling zinc pyrithione containing paint end products using an airless sprayer application method Scenario occurs when a residential handler applies biocide treated paint using an airless sprayer. PHED unit exposures from the Residential SOPs are used for airless spraying by a residential handler ( EPA 1997). Table 4. Exposure Scenarios for Occupational/ Residential Handlers Exposure Scenario Scenario Description 18 ( 5c) Handling zinc pyrithione containing paint end products using an aerosol spray can application method Scenario occurs when a residential handler applies biocide treated paint using an aerosol spray can. PHED unit exposures from the Residential SOPs are used for aerosol spraying by a residential handler ( EPA 1997).

( 2) Handler Exposure Data and Assumptions In the development of this Reregistration Eligibility Decision ( RED) Document, limited handler exposure data were available for use by the Agency. In the absence of chemical specific data for zinc pyrithione, surrogate data from the Pesticide Handlers Exposure Database ( PHED) Version 1.1, the Chemical Manufacturers Association ( CMA), and Garrod et al. ( 2000) were used to estimate unit exposures. Zinc pyrithione product labeling information along with EPA use estimates were relied on to calculate the approximate amount handled per day. These data were used to predict handler exposures for the various scenarios ( PHED, 1997; CMA, 1992; and U. S. EPA, 1997a).

( a) Handler Exposure Data Chemical specific handler exposure data were not submitted by the registrant for Zinc Pyrithione;

therefore, surrogate data from CMA, PHED, the residential SOPs, and Garrod et al. ( 2000) were used to estimate exposure.

( i) Chemical Manufacturers Association ( CMA) Data The CMA study data were used to estimate primary exposures for the following occupational handler scenarios ( Table 4).

Primary Occupational Handlers General Preservative Uses: Dry Film, In Can, and Materials Preservative ( 1a) Mixing/ loading/ applying liquid pesticide concentrates using open pour methods; ( 1b) Mixing/ loading/ applying liquid pesticide concentrates using metering pump equipment ( pump liquid); ( 1c) Mixing/ loading/ applying powder pesticide concentrates using open pour methods; and ( 1d) Mixing/ loading/ applying powder pesticide concentrates using metering equipment.

Paints: Dry Film Preservation ( 2a) Mixing/ loading/ applying liquid pesticide concentrates using open pour methods; 1 These guideline have been superceded by Series 875.1000 875.1600 of the Pesticide Assessment Guidelines.

19 ( 2b) Mixing/ loading/ applying liquid pesticide concentrates using metering pump equipment ( pump liquid); ( 2c) Mixing/ loading/ applying powder pesticide concentrates using open pour methods; and ( 2d) Mixing/ loading/ applying powder pesticide concentrates using metering equipment.

Fabrics/ Textiles: Laundering Treatment for Materials Preservation ( 3a) Mixing/ loading/ applying liquid pesticide concentrates using open pour methods; ( 3b) Mixing/ loading/ applying liquid pesticide concentrates using metering pump equipment ( pump liquid); ( 3c) Mixing/ loading/ applying powder pesticide concentrates using open pour methods; and ( 3d) Mixing/ loading/ applying powder pesticide concentrates using metering equipment.

The CMA ( 1992) " Antimicrobial Exposure Assessment Study" was conducted in order to meet the requirements of Subdivision U of the Pesticide Assessment Guidelines for " Applicator Exposure Monitoring" 1 and the " Occupational and Residential Exposure Test Guidelines" in Series 875 to support the registration of antimicrobial pesticide active ingredients. The purpose of this CMA study was to characterize exposure to antimicrobial chemicals in order to support certain antimicrobial pesticide reregistrations ( CMA, 1992). The unit exposures presented in the most recent EPA evaluation of the CMA database ( EPA, 1999b) were used in this assessment.

The Agency determined that the CMA study had fulfilled the basic requirements of Subdivision U

Applicator Exposure Monitoring. The advantages of CMA data over other " surrogate data sets" are that the chemicals and the job functions of mixer/ loader/ applicator were defined based on common application methods used for antimicrobial pesticides. Note that there were, however, a few deficiencies in this study particularly with respect to quality. [ Refer within to Section ( 9) Data Gaps, Uncertainties and Limitations.]

Exposure results from the CMA study seem to indicate that dermal exposure is the primary exposure route for the seven antimicrobial chemicals analyzed. Inhalation exposures in the CMA data were very low,

usually below the chemical limit of detection. Therefore, the data in the CMA study might not be a valid estimation of inhalation exposure for zinc pyrithione.

( ii) Pesticide Handlers Exposure Database ( PHED) Data 20 The Pesticide Handlers Exposure Database ( PHED) Version 1.1 was used to estimate exposures for the following primary residential handlers using antifoulant paints ( Tables 3 and 5), and secondary occupational/ secondary residential handler scenarios ( Table 4) for materials preservatives:

Primary Residential Handlers ( Table 5) Handling zinc pyrithione containing antifoulant paints using a paint brush; and ( Table 5) Handling zinc pyrithione containing antifoulant paints using an airless sprayer.

Secondary Occupational/ Residential Handlers ( 4a, 6a) Handling zinc pyrithione containing paint end products using a paint brush application method;

( 4b, 6b) Handling zinc pyrithione containing paint end products using an airless sprayer application method; and ( 4c, 6c) Handling zinc pyrithione containing paint end products using an aerosol spray can application method.

PHED Data PHED was designed by a task force consisting of representatives from the U. S. EPA, Health Canada,

the California Department of Pesticide Regulation, and member companies of the American Crop Protection Association ( PHED, 1997). PHED is a generic database containing measured exposure data for workers involved in the handling or application of pesticides under actual field conditions, in primarily agricultural settings. Currently, the database contains values for over 1,700 monitored exposure events ( i. e., replicates).

The basic assumption underlying the system is that exposure to pesticide handlers can be calculated using the monitored data because exposure is primarily a function of the physical parameters of the handling and application process ( i. e., the pesticide use scenario based on the packaging type, application method, and any protective clothing worn). PHED also contains algorithms that allow the user to complete surrogate,

taskbased exposure assessments beginning with one of the four main data files contained in the system ( i. e.,

mixer/ loader, applicator, flagger, and mixer/ loader/ applicator).

Users can select data from each major PHED file and construct exposure scenarios that are representative of the use of the chemical. The subsetting algorithms in PHED are based on the central assumption that one magnitude of handler exposures to pesticides are primarily a function of activity,

formulation type, application method, and clothing scenario. However, to add consistency to the risk assessment process, the EPA, in conjunction with the PHED Task Force, has evaluated all data within the system and developed surrogate exposure tables that contain a series of standard unit exposure values for 21 various exposure scenarios. These standard unit exposure values are based on the " best fit" values calculated by PHED. PHED calculates " best fit" exposure values by assessing the distributions of exposures for each body part included in data sets selected for the assessment ( i. e., chest or forearm) and then calculating a composite exposure value representing the entire body. PHED categorizes distributions as normal, lognormal,

or in any " other" category. Generally, most data contained in PHED are lognormally distributed or fall into the PHED " other" distribution category. If the distribution is lognormal, the geometric mean for the distribution is used as the " best fit" exposure value. If the data are an " other" distribution, the median value of the data set is used in the calculation of the " best fit" exposure value. As a result, the surrogate unit exposure values that serve as the basis for this assessment generally range from the geometric mean to the median of the selected data set. PHED unit exposure data used in this assessment represent the estimated level of exposure expected per unit amount of pesticide handled and are reported in units of mg exposure/ lbs ai handled ( PHED, 1998).

PHED has long been used as a surrogate for handler exposure assessment. The data for PHED may have some advantages to CMA data in that they are generally rated as grades A, B, C, so it tends to have better quality QA/ QC ( i. e., better field, lab and storage stability recoveries), more replicates ( i. e., over 15 replicates),

less variability ( i. e., lower CVs), and reportable inhalation unit exposure values. Data confidence refers to both the " quality" and the " amount" of data for each PHED run. Each study in PHED has been graded from " A"

to " E" according to certain Quality Assurance/ Quality Control ( QA/ QC) factors ( PHED, 1998).

The confidence levels for the unit exposures are Grade C for paintbrush, Grades B and C for airless spraying, and Grades A and B for aerosol can.

( iii) Residential Exposure Assessment Standard Operating Procedures ( SOPs)

The residential exposure assessment SOPs are designed for use in assessing exposure to pesticides in residential settings. The objective of these SOPs is to provide standard default methods for developing residential exposure assessments for both handler and postapplication exposures when chemical and/ or sitespecific field data are limited. These methods may be used in the absence of, or as a supplement to,

chemicaland or site specific data. The SOPs were prepared by EPA's Office of Pesticide Programs, Health Effects Division and Antimicrobials Division with input from EPA's Office of Pollution Prevention and Toxics, and Office of Research and Development ( U. S. EPA, 1997a).

For the residential handler exposure assessment, dermal and inhalation exposure data are from the residential SOPs developed using PHED Version 1.1. The values of the residential PHED data versus the occupational PHED data generally differ because the baseline attire is different. The baseline residential clothing attire is short pants, short sleeve shirt, socks, shoes, and no gloves. The occupational baseline scenario generally represents a handler wearing a long sleeved shirt, long pants, socks, and shoes with no respirator or chemical resistant gloves. The grading scheme for the residential PHED data is described in the 22 occupational section. The confidence levels of paintbrush, airless sprayer, and aerosol can are Grade C for paintbrush, Grades B and C for airless spraying, and Grades A and B for aerosol can.

( iv) Literature Study   Garrod et al. ( 2000)

The Garrod et al ( 2000) study was identified by the registrant during the 30 day error comment period of the Reregistration Eligibility Decision ( RED) process for Zinc Pyrithione ( i. e.,

zinc omadine ® ) . The Garrod et al ( 2000) study was reviewed by the Antimicrobials Division ( AD)

to provide dermal and inhalation unit exposures ( UEs) appropriate for use in developing antifoulant and wood preservative outdoor painting exposure scenarios for amateur ( consumer) applicators. The antifoulant paint in this study was applied using a paint brush and roller to boat hulls of recreational craft stored on sling/ cradle/ trailers. The scenario monitored in this study ( i. e., antifoulant applications via brush/ roller) is more representative for Do It Yourself ( DIY) painters than the surrogate data available in the Pesticide Handlers Exposure Database ( PHED). The surrogate data in PHED are based on an indoor painting scenario where latex paint containing a fungicide is applied to interior bathroom walls with a brush. However, only the air concentration data are available from Garrod et al ( 2000). The dermal portion of the study monitored mostly exposure on the outside of clothing and only one patch was used underneath clothing. New studies measuring both dermal and inhalation exposures are recommended. QA/ QC samples consisted of laboratory recoveries. The laboratory recovery results were mostly in the 90 percent range. No replicates were corrected for recovery. The article did not mention field fortifications or storage stability samples ( nor did it discuss shipment or storage of field samples).

( b) Estimated Amount Handled ( i) Antifoulants The estimated amounts handled per day were used in conjunction with data from PHED to calculate exposure dose estimates for residential handler scenarios. Based on review of the existing labels, the residential assessment for antifoulants is based on two products. EPA Reg. No. 64684 4 has been selected because it specifically lists recreational use, is formulated at 4.8 percent, and does not prohibit spraying. EPA Reg. No.

2693 194 is also included because of the high concentration ( 47.04 percent diluted as a two part mixture) and there are no label restrictions. Recreational boat owners have several techniques they can use to paint their hulls including paint brush, roller, and airless sprayer. There are no chemical specific exposure data to assess these techniques. However, surrogate data are available for painting with a brush and an airless sprayer. The surrogate data are based on PHED data for painters wearing long pants, long sleeve shirts, no gloves, and no respirator. The test subjects were painting a bathroom with a paint brush and staining the outside of a house 23 with an airless sprayer. The dermal and inhalation exposures from these techniques have been normalized by the amount of active ingredient handled and reported as PHED unit exposures ( UE) expressed as mg/ lb ai handled. Although the exposures while painting a boat hull may differ slightly, the data are judged to be representative of painting and are used in this assessment. The data from Garrod et al. ( 2000) were also used as a comparison to PHED because the Garrod ( 2000) study design is more representative of the use ( i. e.,

painting boat hulls using an antifoulant paint). The air concentration data from Garrod ( 2000) are used to present the inhalation route specific risks in normalized units of mg/ m3.

The amount of antifouling paint handled by a do it yourself ( DIY) boat hull painter is determined by the size of the hull painted. Based on label directions, one gallon of the antifouling paint covers roughly 300 ft2 with a minimum of 3 coats applied. The antifouling paint in label 64684 4 contains 4.8 percent ai and assuming one gallon of paint weighs ~ 10 lbs/ gallon this corresponds to 0.48 lb ai/ gallon. Label 2693 194 is a two part mixture with the Activator portion consisting of 47.04 percent ai. One pint of Activator is mixed with 7 pints of paint. Thus, the final paint mixture consists of 0.588 lb ai/ gallon ( 1.25 lb per pint/ gallon paint x 0.4704 ai = 0.588 lb ai/ gallon). Various size boats can be potentially painted and this assessment presents a range of boats. There are no label restrictions on the drying time between coats of paint, and therefore, it is assumed that the recommended number of coats of paint can be applied in one day. Refinements to the amount handled on a daily basis can be made if drying times are in the range of 24 hours. The range of boats and amounts of ai handled are listed below:

$ 14 ft Boat  The surface area of the hull of a 14 ft boat with a 5 ft beam is ~ 70 ft2 which corresponds to 0.336 lb ai handled for label 64684 4 ( i. e., (( 70 ft2 x 3 coats)/ 300 ft2 per gallon) x 0.48 lb ai/ gallon)

and 0.4116 lb ai for label 2693 194 ( i. e., (( 70 ft2 x 3 coats)/ 300 ft2 per gallon) x 0.588 lb ai/ gallon).

It is also estimated that it would require ~ 2 hours to paint 3 coats.

$ 20 ft Boat  The surface area of the hull of a 20 ft boat with a 8 ft beam is ~ 160 ft2 which corresponds to 0.768 lb ai handled for label 64684 4 ( i. e., (( 160 ft2 x 3 coats)/ 300 ft2 per gallon) x 0.48 lb ai/ gallon) and 0.9408 lb ai for label 2693 194 ( i. e., (( 160 ft2 x 3 coats)/ 300 ft2 per gallon) x 0.588 lb ai/ gallon). It is also estimated that it would require ~ 4 hours to paint 3 coats.

$ 30 ft Boat  The surface area of the hull of a 30 ft boat with a 10 ft beam is ~ 300 ft2 which corresponds to 1.44 lb ai handled for label 64684 4 ( i. e., (( 300 ft2 x 3 coats)/ 300 ft2 per gallon) x 0.48 lb ai/ gallon) and 1.764 lb ai for label 2693 194 ( i. e., (( 300 ft2 x 3 coats)/ 300 ft2 per gallon) x 0.588 lb ai/ gallon). It is also estimated that it would require ~ 6 hours to paint 3 coats.

( ii) Materials Preservatives 24 The estimated amounts handled per day were used in conjunction with data from PHED, the residential SOPs, or CMA to calculate exposure dose estimates for handlers in various scenarios. The estimates of amount handled during manufacturing are 10,000 pounds of slurry, 1,000 gallons of paint, and 1,000 gallons of water for laundry treatments. These estimates are based on Agency standard values for industrial practices and were used for all preservatives and paints ( density of 10 lb/ gal). An estimate of 1,000 gallons of " acid sour" was used for laundry treatments. According to the registrant, the " acid sour" is made in 1,000 gallon batches. This may, however, be an overestimate because the batch may last a few days or weeks depending on the volume of fabrics/ textiles treated.

Assumptions for secondary occupational handlers use of paint for brushing ( 5 gallons) and airless spraying ( 50 gallons) are also consistent with Agency standard values used in previous assessments. Assumed amounts for the secondary residential handlers use of paint for brushing ( 2 gallons), airless spraying ( 15 gallons), and aerosol can ( three 12 oz cans) are consistent with the Residential SOPs ( EPA, 1997a, 2001).

Table 5 provides the estimates used to calculate the amount of zinc pyrithione handled for each exposure scenario.

Note that the exposure scenarios developed for the secondary occupational handlers differ from the secondary residential handlers in terms of the amount of product handled per day and in the data used. The PHED data from the residential SOPs assumes that handlers may wear short pants, short sleeved shirt, socks,

and shoes. The occupational PHED data generally represents a handler wearing a long sleeved shirt, long pants, socks, and shoes.

Table 5. Exposure Estimates/ Assumptions for Amount of Zinc Pyrithione Handled Per Day Exposure Scenario Scenario Description Primary Occupational Handler General Preservative Uses: Dry Film, In Can, and Materials Preservation ( 1a) Mixing/ loading/ applying liquid pesticide concentrates using open pour methods Assumes treatment per day of 10,000 pounds of slurry used for various manufactured substrates ( e. g., food/ non food contact adhesives, caulks/ sealants, grouts/ patching compounds, processed rubber, textiles, thermoplastic resin based articles ( e. g. air ducts), and food/ non food contact polymeric systems; including repeat use polymeric food contact materials such as food processing equipment and conveyor belts). EPA Reg. 1258 841 ( 48 percent active ingredient ( a. i.)) indicates that the maximum application rate is 1000 ppm ( 10.4 lb/ 1000 lbs) to caulk/ sealants or 5 lb ai/ 1000 lbs.

( 1b) Mixing/ loading/ applying liquid pesticide concentrates using metering equipment ( pump liquid) Assumes treatment per day of 10,000 pounds of slurry used for various manufactured substrates ( e. g., food/ non food contact adhesives, caulks/ sealants, grouts/ patching compounds, processed rubber, textiles, thermoplastic resin based articles ( e. g. air ducts), and food/ non food contact polymeric systems; including repeat use polymeric food contact materials such as food processing equipment and conveyor belts). EPA Reg. 1258 841 ( 48 percent active ingredient ( a. i.)) indicates that the maximum application rate is 1000 ppm ( 10.4 lb/ 1000 lbs) to caulk/ sealants or 5 lb ai/ 1000 lbs. Table 5. Exposure Estimates/ Assumptions for Amount of Zinc Pyrithione Handled Per Day Exposure Scenario Scenario Description 25 ( 1c) Mixing/ loading/ applying powder pesticide concentrates using open pour methods Assumes treatment per day of 10,000 pounds of slurry used for various manufactured substrates ( e. g., food/ non food contact adhesives, caulks/ sealants, grouts/ patching compounds, processed rubber, textiles, thermoplastic resin based articles ( e. g. air ducts), and food/ non food contact polymeric systems; including repeat use polymeric food contact materials such as food processing equipment and conveyor belts). EPA Reg. 1258 840 ( 95 percent active ingredient ( a. i.)) indicates that the maximum application rate is 5000 ppm ( 5 lb/ 1000 lbs) to caulk/ sealants or 4.75 lb ai/ 1000 lbs. Maximum application rate of 5 lb ai/ 1000 lbs will be used for this assessment with an assumption of 10,000 pounds of slurry.

( 1d) Mixing/ loading/ applying powder pesticide concentrates using metering equipment ( automatic dispensing techniques) Assumes treatment per day of 10,000 pounds of slurry used for various manufactured substrates ( e. g., food/ non food contact adhesives, caulks/ sealants, grouts/ patching compounds, processed rubber, textiles, thermoplastic resin based articles ( e. g. air ducts), and food/ non food contact polymeric systems; including repeat use polymeric food contact materials such as food processing equipment and conveyor belts). EPA Reg. 1258 840 ( 95 percent active ingredient ( a. i.) indicates that the maximum application rate is 5000 ppm ( 5 lb/ 1000 lbs) to caulk/ sealants or 4.75 lb ai/ 1000 lbs. Maximum application rate of 5 lb ai/ 1000 lbs will be used for this assessment with an assumption of 10,000 pounds of slurry.

Paints: Dry Film Preservation ( 2a) Mixing/ loading/ applying liquid pesticide concentrates using open pour methods Assumes 1,000 gallons of paint are manufactured per day. EPA Reg. 1258 841 ( 48 percent active ingredient ( a. i.) indicates that the maximum application rate is 10000 ppm ( 10.83 lb/ 1000 lbs) to paints or 5.2 lb ai/ 1000 lbs (~ 5 lb ai/ 1000 lbs).

( 2b) Mixing/ loading/ applying liquid pesticide concentrates using metering equipment ( pump liquid) Assumes 1,000 gallons of paint are manufactured per day.. EPA Reg. 1258 841 ( 48 percent active ingredient ( a. i.) indicates that the maximum application rate is 10000 ppm ( 10.83 lb/ 1000 lbs) to paints or 5.2 lb ai/ 1000 lbs (~ 5 lb ai/ 1000 lbs).

( 2c) Mixing/ loading/ applying powder pesticide concentrates using open pour methods Assumes 1,000 gallons of paint are manufactured per day. EPA Reg. 1258 840 ( 95 percent active ingredient ( a. i.) indicates that the maximum application rate is 5000 ppm ( 5 lb/ 1000 lbs) to paints or 4.75 lb ai/ 1000 lbs (~ 5 lb ai/ 1000 lbs).

( 2d) Mixing/ loading/ applying powder pesticide concentrates using metering equipment ( automatic dispensing techniques) Assumes 1,000 gallons of paint are manufactured per day. EPA Reg. 1258 840 ( 95 percent active ingredient ( a. i.) indicates that the maximum application rate is 5000 ppm ( 5 lb/ 1000 lbs) to paints or 4.75 lb ai/ 1000 lbs (~ 5 lb ai/ 1000 lbs).

Fabrics/ Textiles: Laundering Treatment for Materials Preservation ( 3a) Mixing/ loading/ applying liquid pesticide concentrates using open pour methods Assumes 1,000 gallons water handled per day. EPA 1258 841 ( 48 percent active ingredient ( a. i.) indicates that the maximum application rate is 9 ounces of 48% per 1,000 gallons. EPA Reg 1258 841, the amount handled can be converted to 0.27 lb ai/ 1,000 gallons (~ 0.25 lb ai/ 1,000 gallons) as follows: 9 ounces x 1 lb / 16 oz ounces x 0.48 ( 48%)

( 3b) Mixing/ loading/ applying liquid pesticide concentrates using metering equipment ( pump liquid) Assumes 1,000 gallons water handled per day. EPA 1258 841 ( 48 percent active ingredient ( a. i.) indicates that the maximum application rate is 9 ounces of 48% per 1,000 gallons. EPA Reg 1258 841, the amount handled can be converted to 0.27 lb ai/ 1,000 gallons (~ 0.25 lb ai/ 1000 gallons) as follows: 9 ounces x 1 lb / 16 oz ounces x 0.48 ( 48%) Table 5. Exposure Estimates/ Assumptions for Amount of Zinc Pyrithione Handled Per Day Exposure Scenario Scenario Description 26 ( 3c) Mixing/ loading/ applying powder pesticide concentrates using open pour methods Assumes 1,000 gallons water handled per day. EPA 1258 840 ( 95 percent active ingredient ( a. i.) indicates that the maximum application rate is 18 ounces of 95% per 1,000 gallons. EPA Reg 1258 840 indicates an acid sour density of 8.3 lb/ gallon, the amount handled can be converted to 1.1 lb ai/ 1,000 gallons (~ 1lb ai/ 1000 gallons) as follows: 18 ounces x 1 gallon/ 128 ounces x 8.3 lb/ gallon x 0.95 ( 95%)

( 3d) Mixing/ loading/ applying powder pesticide concentrates using metering equipment ( automatic dispensing techniques) Assumes 1,000 gallons water handled per day. EPA 1258 840 ( 95 percent active ingredient ( a. i.) indicates that the maximum application rate is 18 ounces of 95% per 1,000 gallons. EPA Reg 1258 840 indicates an acid sour density of 8.3 lb/ gallon, the amount handled can be converted to 1.1 lb ai/ 1,000 gallons (~ 1lb ai/ 1000 gallons) as follows: 18 ounces x 1 gallon/ 128 ounces x 8.3 lb/ gallon x 0.95 ( 95%)

Secondary Occupational Handler ( 4a) Handling zinc pyrithione containing paint end products using a paint brush application method Assumes 5 gallons or 50 pounds of paint are used per day for occupational scenario. Approximately 5 lb ai are added per 1000 lbs ( 100 gallons) of paint.

( 4b) Handling zinc pyrithione containing paint end products using an airless sprayer application method Assumes 50 gallons or 500 pounds of paint are used per day for occupational scenario. Approximately 5 lb ai are added per 1000 lbs ( 100 gallons) of paint.

( 4c) Handling zinc pyrithione containing paint end products using an aerosol spray can application method Assumes 0.28 gal/ day ( three 12 oz cans) are used per day for occupational scenario. Approximately 5 lb ai are added per 1000 lbs ( 100 gallons) of paint.

Secondary Residential Handler ( 5a) Handling zinc pyrithione containing paint end products using a paint brush application method Assumes 2 gallons of paint are used per day for residential scenario. Approximately 5 lb ai are added per 1000 lbs ( 100 gallons) of paint.

( 5b) Handling zinc pyrithione containing paint end products using an airless sprayer application method Assumes 15 gallons of paint are used per day for residential scenario. Approximately 5 lb ai are added per 1000 lbs ( 100 gallons) of paint. ( SOEs 2001)

( 5c) Handling zinc pyrithione containing paint end products using an aerosol spray can application method Assumes 0.28 gal/ day ( three 12 oz cans) are used per day for residential scenario. Approximately 5 lb ai are added per 1000 lbs ( 100 gallons) of paint.

( 3) Handler Risk Assessment and Characterization ( a) Handler Exposure and Non Cancer Risk Calculations Handler exposure assessments are completed by EPA using a baseline exposure scenario and,

if required, increasing levels of risk mitigation [ personal protective equipment ( PPE) and engineering controls] to achieve an appropriate margin of exposure ( MOE) or non cancer risk for occupationally exposed workers only. The baseline scenario generally represents a handler wearing a long sleeved shirt, long pants, socks, and shoes with no respirator or chemical resistant gloves. PPE scenarios generally represent handlers wearing one or more of the following PPE: double layer clothing,

chemical resistant gloves, and/ or a respirator. Engineering controls generally represent the use of closed systems for mixing/ loading/ applying. 27 ( i) Antifoulants Table 6 presents the estimated dermal and inhalation exposures and MOEs. The clothing scenarios presented are based on DIY wearing long pants, long sleeved shirts, no gloves, and no respirator.

Table 6. Exposure and MOEs for Do it yourself Boat Hull Painters Scenario Boat Size a Amount ( Lb ai) b Unit Exposure ( mg/ lbai) c Dermal Dosed ( mg/ kg/ day) Inhalation Dosee ( mg/ kg/ day) Dermal MOE f Target MOE

300 Inhalation MOE g Target MOE

300 Dermal Inhalation EPA Reg. No. 64684 4 ( 4.8 percent ai) All Estimates Based on 3 Coats of Paint in One Day Brush ( PHED) 14ft x 5 ft 0.336 180 0.28 0.86 0.0013 120 97 20ft x 8 ft 0.768 2.0 0.0031 51 42 30ft x 10ft 1.44 3.7 0.0058 27 23 Brush &

roller ( Garrod et al.

2000) 14ft x 5 ft 0.336 NA 0.00087 ( mg/ m3/%

ai) NA 2 hrs painting NA 140 20ft x 8 ft 0.768 4 hrs painting 72 30ft x 10ft 1.44 6 hrs painting 48 Airless 14ft x 5 ft 0.336 38 0.83 0.18 0.0040 550 33 20ft x 8 ft 0.768 0.42 0.0091 240 14 30ft x 10ft 1.44 0.78 0.017 130 8 EPA Reg. No. 2693 194 ( 47 percent ai) All Estimates Based on 3 Coats of Paint in One Day Brush 14ft x 5 ft 0.4116 180 0.28 1.1 0.0017 94 79 20ft x 8 ft 0.9408 2.4 0.0038 41 35 30ft x 10ft 1.764 4.5 0.0071 22 18 Brush &

roller ( Garrod et al.

2000) 14ft x 5 ft 0.4116 NA 0.00087 ( mg/ m3/%

ai) NA 2 hrs painting NA 15 20ft x 8 ft 0.9408 4 hrs painting 7 30ft x 10ft 1.764 6 hrs painting 5 Airless 14ft x 5 ft 0.4116 38 0.83 0.22 0.0049 450 27 20ft x 8 ft 0.9408 0.51 0.011 200 12 30ft x 10ft 1.764 0.96 0.021 100 6 Bold indicates MOE exceeds level of concern ( i. e., MOE less than target MOE of 300). 28 a Hull area for various size boats assumes that the dimension of the hull's painted surface area is roughly based on length and width.

b Amount handled based on the label ( 300ft2/ gallon, 3 coats, % ai, 10 lb/ gal density of paint).

c Unit exposures based on PHED data for painters wearing long pants, long sleeve shirt, no gloves, and no respirator. The inhalation UE from Garrod et al ( 2000) is normalized by the percent of ai in the paint.

d Dermal Dose ( mg/ kg/ day) = dermal UE ( mg/ lbai) x amount handled ( lb ai) x 1/ 70 kg BW.

e Inhalation Dose ( mg/ kg/ day) = inhalation UE ( mg/ lbai) x amount handled ( lb ai) x 1/ 70 kg BW.

f Dermal MOE = dermal NOAEL of 100 mg/ kg/ day / Dermal dose ( mg/ kg/ day).

g Inhalation MOE = NOAEL 0.13 mg/ kg/ day / Inhalation dose ( mkd) or the route specific inhalation MOE = ( 0.5 mg/ m3 x 6 hrs/ day animal) / [( paint air conc mg/ 3/% ai x % ai in paint x hrs painting) x ( 1 m3 work breathing rate / 0.4 m3 resting breathing rate)].

Note: The route specific inhalation MOEs do not coincide with the route extrapolation inhalation MOEs because of the differences in methodologies ( e. g., UE, dose vs air conc, estimates of hours painting versus amount of ai handled].

The estimated dermal and inhalation MOEs are of concern for most of boat sizes when using a paint brush. For the airless sprayers the dermal MOEs are not of concern ( i. e. are greater than 300) for a 14ft boat but are of concern for the larger boats. For all boat sizes, all of the inhalation MOEs are below the target MOE of 300. The majority of the painting exposure is attributed to the hands and all of the dermal MOEs would not be of concern if painters wore chemical resistant gloves.

( ii) Materials Preservatives Exposure estimates for primary occupational handlers are presented in Table 7. The CMA study data were considered more appropriate than PHED data for best characterizing the antimicrobial uses of zinc pyrithione in industrial manufacturing settings. The CMA study provides two risk mitigation methods ( open pouring of liquid/ solid using gloves and pump metering liquid using gloves). These two risk mitigation methods are both reported in Table 7. It should be noted that no adjustments were made to the baseline CMA exposure values to reflect use of additional PPE ( i. e., respirators). It is not standard Agency practice to apply protection factors to baseline CMA exposure values to estimate doses adjusted for use of additional PPE in scenarios where the actual CMA data were not generated using such PPE.

The CMA study does not assess paint application methods/ exposure doses. Therefore, the PHED database is used to assess dermal and inhalation exposures to secondary handlers applying paint end products containing zinc pyrithione, using a paint brush, airless sprayer, and aerosol can. Table 7 presents the exposure/ risk calculations at baseline for secondary occupational handlers. In addition to the baseline calculations for the airless spray painting scenario, MOEs are calculated for PPE protection using gloves and an organic vapor respirator. Table 9 presents the exposure/ risk calculations at baseline for secondary residential handlers using PHED data reported in the residential SOPs ( U. S. EPA, 1997) for the painting scenarios. It is not current Agency policy to evaluate PPE for residential uses. For the painting scenarios in Table 8 for occupational handlers, the PHED database allows for the calculation of unit exposures at both baseline and with the addition of PPE by applying a protection factor of 90% to baseline values for chemical 29 resistant gloves and/ or organic respirator in scenarios where the actual PHED data were not generated using such PPE.

Although the secondary occupational handler assessments include PPE considerations, the mandatory use of PPE by handlers for non spray applications of paint ( i. e., paint brush) is not considered a viable protective measure due to probable non compliance among paint handlers even if the zinc pyrithione treated paint end products have labeling requiring the use of PPE. However, the Agency assumes that PPE use compliance would be viable for the spray painting scenarios, specifically airless sprayer applications that would result in the greatest potential for inhaled particulate without the use of a dust/ mist or organic vapor respirator. 30 Table 7. Estimates of Exposures and Risks to Primary Occupational Handlers of Zinc Pyrithione Application Scenarioa Unit Exposureb ( mg/ lb ai) Use Rate ( lb ai/ 1000 lb, or lb ai/ 100 gal) c Amount Handled ( lb/ day or gal/ day) d Body Weight ( kg) Dermal Dose ( mg/ kg/ day) e Inhalation Dose ( mg/ kg/ day) f Dermal MOEg Target MOE

100 Inhalation MOEh Target MOE

100 Dermal Inhalation General Preservatives Uses: Dry Film, In Can, and Material Preservation ( 1a) Mixing/ loading/ applying liquid pesticide concentrates using open pour methods 0.135 0.00361 5 lb ai/ 1,000 lb 10,000 lb/ day 70 0.0964 2.58E 3 1037 50 ( 1b) Mixing/ loading/ applying liquid pesticide concentrates using metering equipment ( pump liquid) 0.00629 0.000403 5 lb ai/ 1,000 lb 10,000 lb/ day 70 0.0045 2.88E 4 2.23E+ 4 452 ( 1c) Mixing/ loading/ applying powder pesticide concentrates using open pour methods 0.466 0.0125 5 lb ai/ 1,000 lb 10,000 lb/ day 70 0.333 8.93E 3 300 15 ( 1d) Mixing/ loading/ applying powder pesticide concentrates using metering equipment ( automatic dispensing techniques) 0.00629 0.000403 5 lb ai/ 1,000 lb 10,000 lb/ day 70 0.0045 2.88E 4 2.23E+ 4 452 Paints: Dry Film Preservation ( 2a) Mixing/ loading/ applying liquid pesticide concentrates using open pour methods 0.135 0.00361 5 lb ai/ 100 gal 1,000 gal 70 0.0964 2.58E 3 1037 50 ( 2b) Mixing/ loading/ applying liquid pesticide concentrates using metering equipment ( pump liquid) 0.00629 0.000403 5 lb ai/ 100 gal 1,000 gal 70 0.0045 2.88E 4 2.23E+ 4 452 ( 2c) Mixing/ loading/ applying powder pesticide concentrates using open pour methods 0.466 0.0125 5 lb ai/ 100 gal 1,000 gal 70 0.333 8.93E 3 300 15 Table 7. Estimates of Exposures and Risks to Primary Occupational Handlers of Zinc Pyrithione Application Scenarioa Unit Exposureb ( mg/ lb ai) Use Rate ( lb ai/ 1000 lb, or lb ai/ 100 gal) c Amount Handled ( lb/ day or gal/ day) d Body Weight ( kg) Dermal Dose ( mg/ kg/ day) e Inhalation Dose ( mg/ kg/ day) f Dermal MOEg Target MOE

100 Inhalation MOEh Target MOE

100 Dermal Inhalation 31 ( 2d) Mixing/ loading/ applying powder pesticide concentrates using metering equipment ( automatic dispensing techniques) 0.00629 0.000403 5 lb ai/ 100 gal 1,000 gal 70 0.0045 2.88E 4 2.23E+ 4 452 Fabrics/ Textiles: Laundering Treatment for Material Preservation ( 3a) Mixing/ loading/ applying liquid pesticide concentrates using open pour methods 0.135 0.00361 0.25 lb ai/ 1,000 gal 1,000 gal 70 5.0E 4 1.29E 5 2.07E+ 5 1.01E+ 4 ( 3b) Mixing/ loading/ applying liquid pesticide concentrates using metering equipment ( pump liquid) 0.00629 0.000403 0.25 lb ai/ 1,000 gal 1,000 gal 70 2.2E 5 1.44E 6 4.45E+ 6 9.03E+ 4 ( 3c) Mixing/ loading/ applying powder pesticide concentrates using open pour methods 0.466 0.0125 1 lb ai/ 1,000 gal 1,000 gal 70 6.7E 3 1.79E 4 1.5E+ 4 728 ( 3d) Mixing/ loading/ applying powder pesticide concentrates using metering equipment ( automatic dispensing techniques) 0.00629 0.000403 1 lb ai/ 1,000 gal 1,000 gal 70 9.0E 5 5.76E 6 1.11E+ 6 2.26E+ 4 Footnotes:

a Scenarios based on use patterns described on labels and LUIS report. Primary occupational handlers include people who add zinc pyrithione as a general preservative to products such as food/ non food contact adhesives; floor tile adhesives; caulks and sealants; grout and patching compounds; food/ non food contact polymeric materials; rubber and thermoplastic resins;

preservatives in latex paint; architectural coatings; dry film preservative in products such as dry wall and building materials; and laundered fabrics.

b Unit exposures based on CMA data for inhalation and dermal exposure. Data represent single layer clothing and gloves.

c Represents the maximum use rates on the registered zinc pyrithione product labels; EPA Registration Nos.: 1258 840 and 1258 841. 32 d Standard EPA default assumptions: 10,000 for caulk; 1,000 for paint; and 1,000 for laundered fabric.

e 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).

f Inhalation Dose ( mg/ kg/ day) = [ Unit Inhalation 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).

g Dermal MOE = Dermal NOAEL ( mg/ kg/ day) / Dermal Dose ( mg/ kg/ day). Where the dermal NOAEL is 100 mg/ kg/ day.

h Inhalation MOE = Inhalation NOAEL ( mg/ kg/ day) / Inhalation Dose ( mg/ kg/ day). Where the inhalation NOAEL of 0.0005 mg/ L/ day is converted to 0.13 mg/ kg/ day.

Table 8. Estimates of Exposures and Risks to Secondary Occupational Handlers of Zinc Pyrithione Application Scenarioa Unit Exposure ( mg/ lb ai) b Use Rate ( Lb ai/ 1,000 lb or lb ai/ 100 gal) c Amount Handled ( lb/ day or gal/ day) d Body Weight ( kg) Dermal Dose ( mg/ kg/ day) e Inhalation Dose ( mg/ kg/ day) f Dermal MOEg Target MOE

100 Inhalation MOEh Target MOE

100 Dermal Inhalation Paints Containing Zinc Pyrithione ( 4a) Handling zinc pyrithionecontaining paint end products using a paint brush application method 180 0.28 5 lb ai/ 100 gal 5 gal/ day 70 0.64 1.0E 3 156 130 ( 4b) Handling zinc pyrithionecontaining paint end products using an airless sprayer application method 38 0.83 5 lb ai/ 100 gal 50 gal/ day 70 1.36 0.030 74 4.4 14*

( PPE) 0.083**

( PPE) 0.5*

( PPE) 0.003**

( PPE) 200 ( PPE) 44 ( PPE)

( 4c) Handling zinc pyrithionecontaining paint end products using an aerosol spray can application method 190 1.3 5 lb ai/ 100 gal 0.28 gal/ day ( 3 12 oz cans) 70 0.038 2.60E 4 2,632 500 Footnotes:

a Scenarios based on use patterns described on labels and LUIS report. Secondary occupational handlers include persons who apply products containing zinc pyrithione incorporated as a general preservative ( e. g., floor tile adhesives, caulks/ sealants, grout/ patching materials, and rubber/ thermoplastic resin/ polymeric based products), and persons who apply latex paint, architectural paints and coatings, or dry wall and building materials that contain zinc pyrithione.

b Dermal unit exposures based on data from PHED, Version 1.1 ( single layer clothing; long sleeved shirt, long pants; no gloves), except for scenario 4 which is based on CMA data. CMA data represent single layer clothing and no gloves. Unit exposure values for inhalation based on data from PHED, Version 1.1 and assumes no respirator worn.

* Use of gloves as PPE assumes a 90% protection factor. ** Use of organic vapor respirator as PPE assumes a 90% protection factor.

c Represents the maximum use rates on the registered zinc pyrithione product labels; EPA Registration Nos.: 1258 840, 1258 841, and 1258 1183.

d Standard EPA default assumptions.

e 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).

f Inhalation Dose ( mg/ kg/ day) = [ Unit Inhalation 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). 33 g Dermal MOE = Dermal NOAEL ( mg/ kg/ day) / Dermal Dose ( mg/ kg/ day). Where the dermal NOAEL is 100 mg/ kg/ day.

h Inhalation MOE = Inhalation NOAEL ( mg/ kg/ day) / Inhalation Dose ( mg/ kg/ day). Where the inhalation NOAEL of 0.0005 mg/ L/ day is converted to 0.13 mg/ kg/ day. 34 Table 9. Estimates of Exposures and Risks to Secondary Residential Handlers of Zinc Pyrithione Scenarioa Unit Exposure ( mg/ lb ai) b Use Rate ( Lb ai/ 1,000 lb or lb ai/ 100 gal) c Amount Handled ( lb/ day or gal/ day) d Body Weight ( kg) Dermal Dose ( mg/ kg/ day) e Inhalation Dose ( mg/ kg/ day) f Dermal MOEg Acceptable MOE

300 Inhalation MOEh Acceptable MOE

300 Dermal Inhalation Paints Containing Zinc Pyrithione ( 5a) Handling zinc pyrithionecontaining paint end products using a paint brush application method 230 0.28 5 lb ai/ 100 gal 2 gal/ day 70 0.328 4.0E 4 304 325 ( 5b) Handling zinc pyrithionecontaining paint end products using an airless sprayer application method 79 0.83 5 lb ai/ 100 gal 15 gal/ day 70 0.846 8.89E 3 118 15 ( 5c) Handling zinc pyrithionecontaining paint end products using an aerosol spray can application method 220 2.4 5 lb ai/ 100 gal 0.28 gal/ day ( 3 12 oz cans) 70 0.044 4.80E 4 2,273 271 Footnotes:

a Scenarios based on use patterns described on labels and LUIS report. Secondary residential handlers include homeowners who apply products containing zinc pyrithione incorporated as a general preservative ( e. g., floor tile adhesives, caulks/ sealants, grout/ patching materials, and rubber/ thermoplastic resin/ polymeric based products), and homeowners who apply latex paint, architectural coating, and dry wall and building materials that contain zinc pyrithione.

b Dermal unit exposures based on data from PHED, Version 1.1 ( single layer clothing; short sleeved shirt, short pants; no gloves), except for scenario 6 which is based on CMA data. CMA data represent single layer clothing and no gloves. Unit exposure values for inhalation based on data from PHED, Version 1.1 and assumes no respirator worn.

* Use of gloves as PPE assumes a 90% protection factor. ** Use of organic vapor respirator as PPE assumes a 90% protection factor.

c Represents the range of use rates in the zinc pyrithione labels; EPA registration Numbers 1258 840 and 1258 841.

d Standard EPA default assumptions.

e 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).

f Inhalation Dose ( mg/ kg/ day) = [ Unit Inhalation 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).

g Dermal MOE = Dermal NOAEL ( mg/ kg/ day) / Dermal Dose ( mg/ kg/ day). Where the dermal NOAEL is 100 mg/ kg/ day.

h Inhalation MOE = Inhalation NOAEL ( mg/ kg/ day) / Inhalation Dose ( mg/ kg/ day). Where the inhalation NOAEL of 0.0005 mg/ L/ day is converted to 0.13 mg/ kg/ day. 35 Daily Dermal Dose

Unit Exposure x Use Rate x Amount Handled x 1 Body Weight Daily Inhalation Dose

Unit Exposure x Use Rate x Amount Handled x 1 Body Weight ( i) Daily Dermal Dose The potential daily dermal doses in Tables 7, 8, and 9 were calculated using the following equation:

Equation 2:

where:

Unit Exposure ( mg ai/ lb ai) = Values obtained from CMA ( CMA, 1992), PHED ( PHED, 1997), or Residential SOPs ( U. S. EPA, 1997a)

Use Rate ( lb ai/ 1000 lb or 1 lb ai/ 100 gallons) = Values from Table 6 Amount Handled ( lb/ day or gal/ day) = Values from Table 6 Body weight ( kg) = 70 kg ( ii) Daily Inhalation Dose The potential daily inhalation doses shown in Tables 7, 8, and 9 were calculated using the following equation:

Equation 3:

where:

Unit Exposure ( mg ai/ lb ai) = Values obtained from CMA ( CMA, 1992), PHED ( PHED,

1997), or Residential SOPs ( U. S. EPA, 1997a).

Use Rate ( lb ai/ 1000 lb or 1 lb ai/ 100 gallons) = Values from Table 6 Amount Handled ( lb/ day or gal/ day) = Values from Table 6 Body weight ( kg) = 70 kg The calculations of both the daily dermal and inhalation doses of zinc pyrithione received by handlers were used to assess the potential dermal and inhalation risks to handlers. The MOEs were calculated using a dermal NOAEL of 100 mg/ kg/ day and an inhalation NOAEL of 0.13 mg/ kg/ day, respectively. The following formula describes the calculation of an MOE: 36 MOE

NOAEL ( mg/ m3) x D A Inhalation Exposure Concentration ( mg/ m3) x D H x Human MV ACTUAL Human MV REST Equation 4:

MOE = NOAEL mg kg / day Daily Dose ( mg / kg / day)

     The inhalation route specific MOEs for the antifoulant paint use were calculated using equation 4a. This equation was only used for the antifoulant paints because the inhalation exposure data were available as air concentrations ( mg/ m3) for this scenario.

Equation 4a:

Where:

NOAEL = Inhalation endpoint of concern for zinc pyrithione in ( mg/ m3)

DA = Duration of daily animal exposure in study ( hrs/ day)

Inhal Exp Con = Inhalation exposure concentration from Garrod et al ( 2000) ( mg/ m3)

DH = Duration of daily human exposure ( hrs/ day)

MVACTUAL = Minute Volume for exposure scenario ( L/ min)

MVREST = Minute Volume at rest ( L/ min)

This equation accounts for the differences in the duration of daily exposure for animals ( D A) and humans ( D H), and the increased respiration and exposure that results from the increased activity ( USEPA 1998).

( b) Handler Non Cancer Risks from Exposure to Zinc Pyrithione The target MOE is

100 for occupational handlers and the target MOE is

300 for residential handlers for short term, intermediate term, and long term exposures. The results presented in Tables 7, 8, and 9 are summarized as follows. 37 ( i) Primary Occupational Handler Scenarios with Non Cancer Dermal and Inhalation Risk Concerns ( Short Term, Intermediate Term, and Long Term Risks)

The calculations for dermal risk indicate that MOEs are greater than 100 for the all the primary occupational handler scenarios assessed. ( See Table 7.) However, a few scenarios have inhalation risks of concern ( MOEs < 100) at baseline ( no respirator). These scenarios are:

° ( 1a) and ( 2a) Mixing/ loading/ applying liquid pesticide concentrates using open pour methods ( MOEs = 50); and ° ( 1c) and ( 2c) Mixing/ loading/ applying powder pesticide concentrates using open pour methods ( MOEs = 15);

The MOEs for inhalation risks are not of concern ( MOE

100) for the remaining primary occupational handler scenarios. It should be noted that no adjustments were made to the baseline CMA exposure values to reflect use of additional PPE ( i. e., respirators). It is not standard Agency practice to apply protection factors to baseline CMA exposure values to estimate adjusted doses representing use of additional PPE in scenarios where the actual CMA data were not generated using such PPE. In addition, there are a number of data gaps for many of the scenarios identified.

Data Gaps Since CMA data are not available for closed loading of powders ( i. e., metering systems) CMA data for closed liquid delivery systems ( i. e., metered pump liquid) were used as " surrogate" data. There is some uncertainty regarding whether this approach may underestimate potential exposures/ risks. Therefore, data gaps exist for the following scenarios:

° ( 1d) Mixing/ loading/ applying powder pesticide concentrates using metering equipment (

automaticdispensing techniques);

° ( 2d) Mixing/ loading/ applying powder pesticide concentrates using metering equipment ( automatic dispensing techniques); and ° ( 3d) Mixing/ loading/ applying powder pesticide concentrates using metering equipment ( automatic dispensing techniques).

( ii) Secondary Occupational Handler Scenarios with Non Cancer Dermal and Inhalation Risk Concerns ( Short Term, Intermediate Term, and Long Term Risks)

The calculations of dermal risks indicate that MOEs are less than 100 at baseline for the following scenarios ( See Table 8): 38 ° ( 4b) Handling zinc pyrithione containing paint end products using an airless sprayer application method ( MOE = 74 without the use of gloves as PPE).

The use of adjusted PHED values to represent use of chemical resistant gloves in scenario ( 4b) yielded dermal risk MOE greater than 100 ( MOE = 200), which is not of concern.

The calculations of inhalation risks indicate that MOEs are less than 100 at baseline ( i. e., no respirator) for the following scenarios ( See Table 8):

° ( 4b) Handling zinc pyrithione containing paint end products using an airless sprayer application method ( MOE = 4).

The calculations of inhalation risks indicate that the MOE is less than 100 even with applied protection factors for organic vapor respirator PPE in the following scenario:

° ( 4b) Handling zinc pyrithione containing paint end products using an airless sprayer application method ( MOE = 44).

The MOEs for inhalation risks are not of concern ( MOE

100) for the remaining secondary occupational handler scenarios ( i. e., paint brush and aerosol spray can).

( iii) Secondary Residential Handler Scenarios with Non Cancer Dermal and Inhalation Risk Concerns ( Short Term, Intermediate Term, and Long Term Risks)

The calculations of dermal and inhalation risks indicate that MOEs are less than 300 at baseline for the following scenarios ( See Table 9):

° ( 5b) Handling zinc pyrithione containing paint end products using an airless sprayer application method ( dermal MOE = 118; and inhalation MOE= 15), and ° ( 5c) Handling zinc pyrithione containing paint end products using an aerosol spray can application method ( MOE = 271).

It is not current Agency policy to assume PPE for residential handlers.

( 4) Postapplication Exposures and Risks EPA has determined that there are potential exposure concerns relating to postapplication exposures to zinc pyrithione. There are potential exposures following applications of zinc pyrithione concentrates in industrial settings and zinc pyrithione treated end products manufactured for commercial, industrial, and residential use sites. EPA has identified two levels of postapplication exposures: primary and secondary 39 occupational, and secondary residential postapplication exposures. Zinc pyrithione has a low vapor pressure ( i. e.,< 1.87x10 9 torr @ 25  C) and is, therefore, not likely to generate sufficient vapor to cause an inhalation concern to occupational and residential populations performing postapplication tasks, or occupying recently treated areas, or from bystander contact with treated articles. Therefore, postapplication inhalation exposures were not assessed.

( a) Primary Occupational Postapplication Exposures EPA has identified zinc pyrithione exposure scenarios for primary occupational postapplication exposures in commercial and industrial settings as follows:

° Dermal and inhalation exposures to occupational workers in areas where polymeric materials have been treated with zinc pyrithione during the manufacturing process.

° Dermal and inhalation exposures to occupational workers in areas where paints have been treated with zinc pyrithione during the manufacturing process.

° Dermal and inhalation exposures to occupational workers in areas where adhesives, coatings, emulsions have been treated with zinc pyrithione during the manufacturing process.

° Dermal and inhalation exposures to occupational workers in areas where fabrics have been treated with zinc pyrithione in the manufacturing process.

Postapplication exposures are limited to mists and steams resulting from manufacturing process operations. However, occupational postapplication dermal and inhalation exposures to zinc pyrithione are likely to be minimal compared to handler situations because of dilution of the zinc pyrithione concentrates into manufactured end use product matrices. Since primary occupational postapplication dermal exposures are likely to be brief and concentrations are expected to be more diluted compared to handler exposures, a risk assessment is not required.

( b) Secondary Occupational Postapplication Exposures EPA has identified one secondary occupational postapplication exposures scenario in commercial and industrial settings, including both dermal and inhalation exposures. Workers could have dermal and inhalation exposures to zinc pyrithione treated adhesives, caulks, sealants, and paints. However, this exposure is expected to be minimal, since the paint, and caulks and sealants are likely to dry within one day. Therefore, these scenarios were not quantitatively evaluated. Exposures resulting from contact with treated fabrics/ textiles,

polymeric materials and related treated substrates are expected to be negligible because of limited transfer of product residues and product dilution. 40 ( c) Residential Postapplication Exposures and Risks Although EPA registered zinc pyrithione pesticide product concentrates are not used in residential areas, the manufactured consumer end products containing zinc pyrithione are used extensively in and around the home. Based on the use patterns, EPA has identified exposure scenarios for assessing residential postapplication exposures including:

° Dermal exposures to consumers from products made of polymeric materials containing zinc pyrithione, such as shoe sole liners;

° Non dietary ingestion exposures to children associated with object to mouth contact with zinc pyrithione treated polymeric products ( i. e., toys); and ° Non dietary ingestion exposures to children associated with hand to mouth contact with zinc pyrithione treated polymeric products ( i. e., toys).

Zinc pyrithione is used as a microbiostat and mildewcide to control bacterial and mildew growth in articles used as components of heating ventilation and air conditioning ( HVAC) systems. Zinc pyrithione ( EPA Reg. No. 1258 840 at 95 percent ai, 1258 841 at 48 percent ai, and 1258 1235 at 37.6 percent ai) is impregnated into thermoplastic resins at concentrations up to 4000 ppm. These thermoplastic resins can be incorporated into air filters, air filtration components, air filtration media, and duct work. These end use products are intended for industrial, hospital, residential and commercial HVAC systems.

Postapplication residential dermal exposures are expected to be of minimal concern for treated articles used in HVAC systems since these components are not readily available for dermal contact. Dermal contact with wet paint was not assessed because the paint is expected to dry within a day, so any potential exposure is expected to be negligible. The potential postapplication inhalation exposure from zinc pyrithione treated articles, such as air duct surfaces in HVAC systems, is expected to be minimal based on bounding estimates of saturation concentrations and/ or dry aerosols from particles degraded from air duct surfaces. Thus, there are no risk concerns and inhalation postapplication exposures were not quantitatively evaluated.

The Food Quality Protection Act ( 1996) sets an explicit standard for assessing potential exposures and risks to children/ infants and other sensitive sub populations from contact with pesticide residues.

Specifically, FQPA requires EPA to give special consideration to exposure to " ensure that there is a reasonable certainty that no harm will result to infants and children from aggregate exposure to the pesticide chemical residue..." Because of the potential increased susceptibility of infants and children,

FQPA requires that EPA evaluate and characterize potential exposure/ risk scenarios specific to children/

infants and other sensitive sub populations in residential settings. 41 ( i) Dermal Exposure to Rubber/ Plastic Products Incorporated with Preservative To calculate dermal exposures to preservatives incorporated into polymeric materials, an exposure assessment entitled " Health Assessment of the Use of Zinc Pyrithione Incorporated Into Polyurethane Sole Liners of Shoes" MRID 441086 01 was used for " surrogate" exposure information ( Olin Corporation,

1996). In general, the study was not designed to satisfy any of the requirements ( i. e., laboratory, method,

and field recoveries, storage stability issues, field fortifications, sufficient replications) of EPA's Series 875.2400 Occupational and Residential Exposure Test Guidelines; therefore, the study does not comply with these guidelines. Review of this study was based solely on issues of technical merit and a discussion of uncertainties and limitations. Leach rate information provided in the FDA Migration Study ( MRID 441086 02) was used in conjunction with information in the Exposure Factors Handbook ( U. S. EPA,

1997a) to estimate dermal exposure to preservative incorporated in sole liners ( U. S. EPA, 2003).

The dermal assessment assumes that 0.4 percent ( 4,000 ppm) of zinc pyrithione is incorporated into polyurethane. The FDA Migration Study ( MRID 441086 02) indicates that 1.5 ppm ( 0.00015%) of zinc pyrithione leaches out of polyethylene after 10 days using corn oil as a solvent. For this assessment, it is assumed that 1.5 ppm of preservative will leach out from the sole liner and be available for contact. This assessment conservatively assumes that 100 percent of the residues available on the surface of the soles are transferred to the skin. Both feet will be assumed to be exposed.

The Exposure Factors Handbook indicates that the 50th percentile surface area of feet is 1,310 cm2 for adult males and 1,140 cm2 for adult females ( U. S. EPA, 1997b). Since only the soles of the feet are expected to contact the liners, one half of the surface area of the feet is assumed. The sole liners are expected to be 1 cm thick. The density of polyurethane is close to 1 g/ cm3. Thus, the mass of the sole liners ( SL) are expected to be 655 gm for male feet and 570 gm for female feet. A body weight of 70 kg was assumed.

For children, the surface area of the feet is 7.1 percent of the total surface area ( U. S. EPA, 1997b).

The total mean surface area for male and female children ages 3 to 4 is 6,565 cm2 ( U. S. EPA, 1997a).

Therefore, the surface area of the feet is 466 cm2. Since only the soles of the feet are expected to contact the sole liner, one half of the surface area of the feet is assumed to contact the sole liner. The sole liners are expected to be 1 cm thick. The density of polyurethane is close to 1 gm/ cm3. Thus, the mass of the sole liners ( SL) is expected to be 233 gm. The body weight used for children ( ages 1 to 6) is 15 kg. This scenario was considered to be short, intermediate and long term in duration.

The calculation of PDR is as follows: 42 Equation 5: PDR = [ SL x AR x LR x CF] / [ BW]

where: PDR = Potential dose rate from dermal contact ( mg/ kg day) SL = Mass of sole liner ( gm) LR = Leach rate. Fraction of preservative leaching out ( i. e., 1.5 ppm/ 4,000 ppm) AR = Application rate is 4,000 ppm. 3.8 mg ai/ 1,000 mg polymer incorporated into sole liners CF = Conversion factor is 1,000 mg/ gm BW = The body weight is 70 kg for adults and 15 kg for children.

 EXPOSURES PREDICTED

PDR = 1.33E 2 mg/ kg day adults 2.2E 2 mg/ kg day children The dermal NOAEL of 100 mg/ kg/ day is divided by the PDR to calculate MOE. The results of this assessment are presented in Table 10.

( ii) Impregnated Toys Incidental ingestion exposures were assessed for a toddler exposed to a zinc pyrithione treated plastic toy. Incidental ingestion exposures were assessed for both hand to mouth and toy to mouth scenarios. These exposure scenarios were assumed to be of short and intermediate term duration ( up to 6 months), since many of the other toys children could play with during childhood are not likely to contain zinc pyrithione. A detailed analysis of the exposures is presented below. The calculations of the exposure estimates for each scenario are based on a risk analysis conducted for Microban Additive " B" ( Triclosan or Irgasan DP 300) ( Dang, 1997) which assessed risks to a 12 month old children playing with treated toys,

and updated exposure assumptions from the Residential SOPs ( 2001). Data from chemical specific studies were also used in this analysis. The analysis was conducted using registrant submitted migration studies ( MRIDs 44108601 and 44108602) and research on child behavior ( holding and mouthing toys). For this assessment, incidental ingestion exposures were assessed for a 12 month old child playing with a " Create

A Song" toy treated with the antimicrobial. Dermal exposure to impregnated toys was considered to be negligible, since most dermal contact will occur only through the hands, and thus was not quantitatively evaluated.

Non Dietary Incidental Ingestion of Preservative from Hand to Mouth Contact ( 1) Exposure Algorithims Equations 6 and 7 were used to calculate the daily dose for hand to mouth incidental ingestion exposure to children playing with a treated toy. An MOE was calculated using Equation 4. 43 Equation 6 SR = % A. I. x W x CF x F SA where:

SR = Surface residue ( mg a. i./ cm2) ( 0.0075 mg ai/ cm2)

% A. I. = Percent a. i. in toy by total weight (%) ( 0.4%)

W = Weight of toy ( g) ( 50 g)

CF = Conversion factor ( 1,000 mg/ g)

F = Percent additive available at the surface of the toy (%) ( 0.00375% based on MRID 44108602)

SA = Surface area of toy ( cm2) ( 500 cm2)

Equation 7 PDD = SR x F1 x F2 x SA x FQ x ED BW where:

PDD = Potential daily dose ( mg/ kg/ day) ( 0.0036 mg/ kg/ day)

SR = Surface residue ( mg a. i./ cm2) ( 0.0075 mg ai/ cm2)

F1 = Fraction residue transferred from toy to hand (%) ( 50%)

F2 = Fraction residue transferred from hand to mouth (%) ( 50%)

SA = Surface area of hands contacting the toy ( cm2) ( 20 cm2)

FQ = Frequency of mouthing a toy ( events per hour) ( 20 times/ hr)

ED = Exposure Duration ( hr/ day) ( 2 hr)

BW = Body weight of a 12 month old child ( kg) ( 10 kg)

( 2) Surrogate Exposure Data and Assumptions The non dietary ingestion of preservative from Hand to Mouth contact uses " surrogate" exposure estimates from Dang, 1997 and data from MRID 441086 01. Chemical specific leaching data were used to estimate the amount of active ingredient at the surface of the toy which is available for each holding event using Equation 7. MRID 441086 02 indicates that 1.5 ppm of active ingredient out of 4,000 ppm of zinc pyrithione incorporated into polyethylene, leached out under conditions of elevated temperatures and 10 days of extraction ( i. e., 0.00375% per day). This exposure estimate is based on the assumption that for each holding event, diffusion of the active ingredient available at the surface to the child's hands is allowed to reach equilibrium ( Dang, 1997). Other inputs used in the calculation are as follows: 44 ° The percent zinc pyrithione in the toy by total weight is 0.4% ( based on same assumptions used for polyurethane sole liners);

° The total surface area of the impregnated material was assumed to be 500 cm2 ( i. e., the surface area of an impregnated toy) ( Dang, 1997);

° The weight of the toy is 50 grams, based on data that show a polyethylene highchair sample with a surface area of 12.7 cm2 weighs 1.3072 g ( i. e., 0.1 g/ cm2, or 0.1 g/ cm2 * 500 cm2 = 50 g) ( Dang,

1997).

Using the above data and assumptions, the residue available at the surface at any one time is 0.000015 mg/ cm2.

The potential daily dose ( Equation 7) was calculated using the surface residue obtained from Equation 6. The daily dose equation assumes that 50% of the available residue will be transferred from the toy to the child's hands and then 50% of that residue will then be transferred to the child's mouth ( i. e.,

saliva extraction factor). The surface area of the child's hand is assumed to be 20 cm2, which represents the surface area of three fingers for a young child. Other inputs from Dang, 1997 which were used in the calculation are as follows:

° An exposure duration of 2 hours;

° A body weight of 10 kg for a 12 month old; and ° A mouthing frequency of 20 events per hour, which represents the 90th percentile value for preschool aged children ( ages 2 5 yrs) based on observations of video tapes.

This method is conservative because it does not account for washing of the toy or depletion of the residue after each toy to mouth episode.

( 3) Results The oral potential daily dose through hand to mouth contact with treated plastic toys was calculated to be 0.0003 mg/ kg/ day. Using 0.75 mg/ kg/ day for children as the NOAEL, the calculated MOE is 2500, which is greater than the target MOE of 300, and does not exceed the Agency's level of concern. These results are shown on Table 10.

Non Dietary Incidental Ingestion of Preservative from Toy to Mouth Contact ( 1) Exposure Algorithims Equation 8 was used to calculate the daily dose for toy to mouth exposure to children playing with a treated toy. An MOE was calculated using Equation 4. 45 Equation 8 PDD = Total SR x F BW where:

PDD = Potential dermal dose ( mg/ kg/ day)

Total SR = Total surface residue ( mg) ( 0.0075 mg for a 500 cm2 toy)

F = Fraction Ingested (%) ( 50%, saliva extraction factor)

BW = Body weight of a 12 month old child ( kg) ( 10 kg)

( 2) Surrogate Exposure Data and Assumptions The potential daily dose for toy to mouth exposure is based on similar assumptions as the potential daily dose for hand to mouth exposures. The non dietary ingestion of preservative from Toy to Mouth contact uses " surrogate" exposure estimates from Dang ( 1997) and data from MRID 441086 02. The following assumptions were used in this assessment:

° A polyethylene highchair sample with a surface area of 12.7 cm2 weighs 1.3072 grams ( i. e., 0.1 gm/ cm2) ( Dang, 1997). ° The total surface area of the impregnated material was assumed to be 500 cm2 ( i. e., the surface area of an impregnated toy) ( Dang, 1997). ° MRID 441086 02 estimates that out of 4,000 ppm of zinc pyrithione incorporated into polyethylene, only 1.5 ppm leached out under conditions of elevated temperatures and 10 days of extraction ( 0.00375% per day). ° 50% of the surface residue from the toy is ingested ( i. e., saliva extraction factor); ° The body weight is 10 kg ( 12 month old); and ° A child mouths 500 cm2 of treated toy surface per day.

Using these assumptions, a polyethylene sample with a surface area of 500 cm2 weighs 50 grams ( 0.1 gm/ cm2 x 500 cm2) and contains 0.4% ai of active ingredient. This assessment is conservative because it ( 1) does not account for washing of the toy or depletion of the residue after each toy to mouth episode, ( 2) assumes that 50% of the available residue is transferred and ingested ( Dang, 1997), and ( 3)

assumes that the amount accumulated under elevated temperatures is the amount available for contact for the each event per day.

( 3) Results The oral potential daily dose through toy to mouth contact with treated plastic toys was calculated to be 0.0004 mg/ kg/ day. Using 0.75 mg/ kg/ day as the NOAEL for children, the calculated MOE is 2000,

which is greater than the target MOE of 300, and does not exceed the level of concern. This method is conservative because it does not account for washing of the toy or depletion of the residue after each toy

tomouth episode and it assumes that 50% of the total available residue on the toy surface is transferred and ingested. The MOE is presented in Table 10. 46 ( 5) Aggregate Postapplication Residential Risks As shown in Table 10, the combined potential dose of exposure to plastic toys ( incidental ingestion) is 0.0007 mg/ kg/ day. Using 0.75 mg/ kg/ day as the NOAEL, the MOE for total exposure is 1,100, which is greater than the target MOE of 300. Therefore, risk resulting from contact with treated plastic toys does not exceed the level of concern. Dermal exposures were not aggregated with oral exposures, since the toxicological effects of concern are different. The total dermal MOEs are also greater than 300, and do not exceed the Agency's level of concern.

Table 10: Summary of Short, and Intermediate Term Residential Postapplication Exposure and Risks ( c)

Scenario Receptor Use PDRa ( mg/ kg/ day) Dermal MOEb Target MOE

300 Oral MOEb Target MOE

300 Dermal Contact to Rubber/ Plastic Incorporated with Preservative Adult Rubber/ Plastic 1.3E 2 7,700 NA Toddlers 2.2E 2 4,500 NA Non Dietary Ingestion Toy to Mouth Infants Rubber/ Plastic 0.0004 NA 2,000 Non Dietary Ingestion Hand to Mouth Infants Rubber/ Plastic 0.0003 NA 2,500 Total Exposure and Risk Infant Rubber/ Plastic 0.0007 ( total oral) NA 1,100 Toddler 2.2E 2 ( dermal) 4,500 NA Adult 1.3E 2 ( dermal) 7,700 NA NA = Not applicable. a PDR calculations for each scenario above are outlined in the text.. b MOE= NOAEL ( mg/ kg/ day) / PDR ( mg/ kg/ day). Dermal NOAEL is 100 mg/ kg/ day; oral NOAEL general population and children is 0.75 mg/ kg/ day. c Dermal risks are also for long term exposures.

( 6) Data Gaps, Uncertainties, and Limitations Currently, zinc pyrithione chemical specific handler or postapplication exposure studies that meet Agency guidelines have not been identified for use in assessing both occupational and residential exposures.

Surrogate dermal and inhalation data primarily from the Pesticide Handlers Exposure Database ( PHED)

Version 1.1, the Chemical Manufacturers Association ( CMA) database, and draft Standard Operating Procedures ( SOPs) for Residential Exposure Assessments were used to assess handler exposure.

Surrogate data were not available for the following scenario: 47 ° Mixing/ loading/ applying " powder" pesticide concentrates using metering In order to characterize exposures for this scenario CMA unit exposure data for metering equipment for " liquids" was used as a surrogate for " powders". There is a possibility that this scenario may underestimate actual exposures.