Page 1 of 60 MEMORANDUM DATE: April 18, 2006 SUBJECT: Orthophenylphenol and orthophenylphenol salts: AD DRAFT Risk Assessment for the Reregistration Eligibility Decision ( RED) Document. Case No. 2575, PC Codes: 064103, 064104, 064108, 064116.

FROM: Tim McMahon, Ph. D., Senior Toxicologist Najm Shamim, Ph. D., Chemist Kathryn Montague, Biologist Talia Milano, Chemist Cassi Walls, Ph. D., Chemist Bob Quick, Chemist Antimicrobials Division ( 7510C)

TO: Rebecca Miller, Chemical Review Manager Regulatory Management Branch II Antimicrobials Division ( 7510C)

Attached is the Preliminary Risk Assessment for orthophenylphenol and orthophenylphenol salts ( OPP/ NA OPP) for the purpose of issuing a Reregistration Eligibility ( RED) Decision. The disciplinary science chapters and other supporting documents for the OPP/ NA OPP RED are also included as attachments as follows:

Toxicology Science Chapter for the Reregistration Eligibility Decision Document, T. McMahon, October 2005 Revised Occupational and Residential Exposure Chapter for Ortho phenylphenol & Ortho phenylphenol Salts. From T. Milano and C. Walls, Chemists, to Rebecca Miller, Chemical Review Manager. April 2006.

Inert Ingredient Dietary and Non dietary Risk Assessments for O Phenylphenol and Salts Reregistration Eligibility Document ( RED). From T. Milano and C. Walls, Chemists, to Rebecca Miller, Chemical Review Manager, February 2006.

Ortho Phenylphenol, and its Sodium and Potassium Salts. Dietary Exposure Assessments for the Reregistration Eligibility Decision Memorandum from Bob Quick, Chemist. to Michelle Centra, August 2005 Product Chemistry of Orthophenylphenol. From Najm Shamim, Ph. D. to T. McMahon, Ph. D. , April 2005 Science Chapter on: Environmental Fate Studies and Environmental Fate Assessment of Orthophenylphenol. From Najm Shamim, Ph. D. Chemist, to Michelle Centra, September 2005,

Ecological Hazard and Environmental Risk Assessment: 2 Phenylphenol and Salts From Kathryn V. Montague, M. S. , December, 2005. Page 2 of 60 Epidemiology Assessment based on Incident Reports. From J. Chen, Ph. D. Toxicologist, to Tim McMahon, Ph. D. Toxicologist, December 2005 Page 3 of 60 TABLE OF CONTENTS 1.0 EXECUTIVE SUMMARY 2.0 PHYSICAL/ CHEMICAL PROPERTIES 3.0 HAZARD CHARACTERIZATION 3.1 Hazard Profile 3.2 Dose Response Assessment 3.3 FQPA Considerations 3.4 Endocrine Disruption 4.0 EXPOSURE ASSESSMENT AND CHARACTERIZATION 4.1 Summary of Registered Antimicrobial Uses 4.1.1 Residential Exposure and Risk for antimicrobial uses 4.2 Dietary Exposure and Risk for Antimicrobial uses 4.2.1 Mushroom houses 4.2.2 Poultry uses 4.2.3 Greenhouse uses 4.2.4 Polymer and Plastic uses 4.2.5 Wood and wood products 4.2.6 Paper adhesive uses 4.3 Dietary Exposure and Risk from agricultural uses 5.0 AGGREGATE RISK ASSESSMENT AND RISK CHARACTERIZATION 5.1 Acute and Chronic Dietary Aggregate Risk 5.2 Short and Intermediate Term Aggregate Risk 6.0 CUMULATIVE RISK 7.0 OCCUPATIONAL EXPOSURE 7.1 Occupational Postapplication Exposure 7.1.1 Fogging Exposure 7.1.2 Metalworking fluid use 7.2 Wood Preservation 7.3 Summary of registered conventional ( agricultural) uses 7.3.1 Occupational Handler Exposure Scenarios 7.3.2 Occupational Postapplication exposure and risk 8.0 ENVIRONMENTAL RISK 8.1 Ecological Hazard 8.2 Environmental fate and transport 8.3 Environmental exposure and Risk 8.4 Endangered Species 8.0 INCIDENT REPORT ASSESSMENT 9.1 OPP Incident Data System 9.2 Poison Control Center 9.3 California Data 1982 2003 9.4 National Telecommunication Pesticide Network 9.5 Hazardous Substances Data Bank 9.6 Conclusions 10.0 REFERENCES 4 14 16 16 18 20 21 21 21 23 30 32 32 33 33 33 33 34 36 37 38 40 41 42 42 42 43 44 44 46 47 47 49 50 50 51 51 51 52 52 52 52 53 54 Page 4 of 60 Executive Summary Orthophenylphenol ( hence forth 2 phenylphenol or OPP) is a white flaky crystal and is sparingly soluble in water but soluble in alcohols and ethers. However, its sodium and potassium salts are highly water soluble. Due to the close chemical similarities between OPP and its sodium and potassium salts ( NA OPP and K OPP), the hazard characterization is a composite of the three chemicals. Currently, there are 124 active registrations for 2 phenylphenol and salts. Of these 124, seven are manufacturing use/ technical grade active ingredient ( MUP/ TGAI) products.

OPP is a bacteriostat, microbiostat, nematicide, fumigant, and bactericide chemical. As a fungicide, tolerances have been established ( 40 CFR 180.129) for the combined residues of OPP and Na OPP from postharvest application on apples, cantaloupes, carrots, cherries, citrus, cucumbers, grapefruits, kiwifruits, kumquats, lemons, limes, nectarines oranges, bell peppers, peaches, pears, pineapples, plums, and prunes, sweet potatoes, tangerines, and tomatoes. In addition, OPP is used in applications to hard surfaces, ( walls, floors, barns) agricultural premises and equipment, air deodorization, commercial and institutional premises, medical premises, residential and public access premises ( carpet, hard surfaces, crack and crevice treatment), and material preservatives ( stains, and paints, metal working fluids, textiles, paper slurries and cement mixtures, glues, and adhesives, and consumer, household and institutional cleaning products).

Sodium o phenylphenate ( Na OPP) is the only chemical in the RED case that is formulated as inert ingredient. Sodium o phenylphenate is formulated as inert ingredient in approximately 123 registered end use products. The types of products that contain sodium o phenylphenate as an inert ingredient include: turf insecticides and herbicides; garden and ornamental insecticides and herbicides; insect repellant for pets; and indoor/ outdoor crack and crevice insecticides. These products are formulated as soluble concentrates, gels, flowable concentrates, ready to use liquids, granular, and bait traps. The vast majority of these products contain sodium o phenylphenate as an inert ingredient in amounts less than 2% of the formulation. In these cases, the residues on food have an exemption from the requirement of a tolerance under the 40 CFR § 180.920 when used as an inert ingredient in pesticide formulations that are applied to growing crops.

Hazard Characterization The toxicology database for OPP is complete, with the exception of acute dermal toxicity ( 870.1200), acute inhalation toxicity ( 870.1300), and primary eye irritation ( 870.2400). Acceptable acute toxicity studies for these guidelines must be submitted. A complete toxicology profile for OPP can be found in the toxicology disciplinary chapter for OPP.

The Health Effects Division's Carcinogenicity Assessment Review Committee ( CARC) classified OPP and NA OPP as " Not Likely to be Carcinogenic to Humans" below a defined dose range, based on convincing evidence that carcinogenic effects are not likely below 200 mg/ kg/ day in experimental animal studies. This classification is based on Page 5 of 60 convincing evidence of a non linear mode of action for development of bladder tumors in carcinogenicity studies in rats. High doses of OPP (> 200 mg/ kg/ day) lead to saturation of phase II detoxification enzyme pathways, resulting in increased amounts of the oxidative metabolites phenylhydroquinone ( PHQ) and/ or phenylbenzoquinone ( PBQ). The generation of PBQ is considered dose dependent, appearing in increased quantity only at higher doses of OPP (> 200 mg/ kg/ day). The shift in biotransformation products with increased dose of OPP has been postulated to be associated with the non linear response observed in tumorigenicity of the urinary bladder, involving oxidative damage to cells and subsequent regenerative hyperplasia. With continued exposure, this process leads to development of tumors. Evidence suggests that a non genotoxic mode of action is operative.

OPP and NA OPP were also classified by the CARC as " Likely to be Carcinogenic to Humans," based on the presence of urinary bladder tumors in rats and the presence of liver tumors in mice at doses above 200 mg/ kg/ day. This classification is based on the fact that insufficient data were provided to support a mode of action for the mouse liver tumors. Although the tumors were benign and observed only in one sex at high doses, more data are required for any conclusion to be drawn regarding the mode of action for these tumors.

The CARC noted that although OPP and NA OPP are classified as " Likely to be Carcinogenic to Humans" above a defined dose range, quantification of cancer risk is not required since the NOAEL selected for the chronic Reference Dose ( 39 mg/ kg/ day, selected from the combined chronic toxicity/ carcinogenicity study in rats [ MRIDs 43954301, 44852701, 44832201] based on decreased body weight gains, decreased food consumption and reduced food efficiency, and increased clinical and gross pathological signs of toxicity at the LOAEL of 200 mg/ kg/ day) is sufficiently protective of the key events involved in the carcinogenic mode of action, which are not present at doses below 200 mg/ kg/ day in the rat and is also protective of liver adenomas occurring at 500 mg/ kg/ day in the mouse. Thus, the precursor events leading to development of bladder and liver tumors are not likely to occur using the NOAEL selected for the chronic RfD value and this value is thus protective against development of tumors.

Dose Response Assessment On October 20, 2004, the Antimicrobials Division Toxicology Endpoint Selection Committee ( ADTC) reviewed the available toxicology data for OPP and selected endpoints for use as appropriate in occupational/ residential exposure risk assessments. The potential for increased susceptibility of infants and children from exposure to OPP was also evaluated by the committee in order to meet the statutory requirements of the Food Quality Protection Act ( FQPA) of 1996. The committee concluded that: an acute dietary risk assessment is not required for OPP, because a single dose effect from OPP was not identified. For chronic dietary risk assessment, a NOAEL value of 39 mg/ kg/ day from the combined chronic toxicity/ carcinogenicity study in rats ( MRIDs 43954301, 44852701, 44832201) was identified, based on decreased body weight, body weight gain, food consumption and food efficiency, increased clinical and gross Page 6 of 60 pathological signs of toxicity at a dose of 200 mg/ kg/ day. For dietary risk assessments, an uncertainty factor of 100 is assigned ( 10x inter species extrapolation, 10x intra species variation). As the FQPA factor was reduced to 1x, the resulting chronic reference dose is 0.39 mg/ kg/ day.

For short term incidental oral risk assessments ( 1 30 days), a NOAEL value of 100 mg/ kg/ day was selected from the developmental toxicity study in rats ( MRIDs 00067616 and 92154037), based on clinical observations of toxicity, decreased weight gain, food consumption and food efficiency observed at the next higher dose of 300 mg/ kg/ day. An uncertainty factor of 100 was assigned to this endpoint ( 10x inter species extrapolation, 10x intra species variation). For intermediate term incidental oral risk assessments, a NOAEL value of 39 mg/ kg/ day was selected from the combined chronic toxicity/ carcinogenicity stud in rats. ( MRIDs 43954301, 44852701, 44832201), based on decreased body weight, body weight gain, food consumption and food efficiency, increased clinical and gross pathological signs of toxicity at a dose of 200 mg/ kg/ day. For risk assessments, an uncertainty factor of 100 was selected ( 10x inter species extrapolation, 10x intra species variation).

For short term dermal risk assessment ( 1 30 days), a NOAEL of 100 mg/ kg/ day was selected from the 21 day dermal toxicity study in rats ( MRID 42881901), based on dermal irritation ( erythema, scaling) at the site of test substance application at the next highest dose of 500 mg/ kg/ day. This is a route specific study and is also appropriate for the time frame of the risk assessment. For risk assessments, an uncertainty factor of 100 was assigned ( 10x inter species extrapolation, 10x intra species variation).

For intermediate term and long term dermal risk assessments, a NOAEL value of 39 mg/ kg/ day was selected from the combined chronic toxicity/ carcinogenicity stud in rats. ( MRIDs 43954301, 44852701, 44832201), based on decreased body weight, body weight gain, food consumption and food efficiency, increased clinical and gross pathological signs of toxicity at a dose of 200 mg/ kg/ day. For risk assessments, an uncertainty factor of 100 was assigned ( 10x inter species extrapolation, 10x intra species variation).

There are no repeated dose inhalation toxicity studies available for OPP. Thus, oral endpoints were used. For assessment of short term inhalation risk, a NOAEL value of 100 mg/ kg/ day was selected from the developmental toxicity study in rats ( MRIDs 00067616 and 92154037), based on clinical observations of toxicity, decreased weight gain, food consumption and food efficiency observed at the next higher dose of 300 mg/ kg/ day. An uncertainty factor of 100 was assigned ( 10x inter species extrapolation, 10x intra species variation). An additional database uncertainty factor of 10x was assigned in addition to determine the need for a confirmatory inhalation toxicity study.

For intermediate and long term inhalation risk assessments, a NOAEL value of 39 mg/ kg/ day was selected from the combined oral chronic toxicity/ carcinogenicity stud in rats. ( MRIDs 43954301, 44852701, 44832201), based on decreased body weight, body weight gain, food consumption and food efficiency, increased clinical and gross pathological signs of toxicity at a dose of 200 mg/ kg/ day. An uncertainty factor of 100 Page 7 of 60 was assigned ( 10x inter species extrapolation, 10x intra species variation). An additional database uncertainty factor of 10x was assigned in addition to determine the need for a confirmatory inhalation toxicity study. If estimated MOEs fall below 1000 for intermediate and long term inhalation risk, a confirmatory route specific inhalation toxicity study may be required.

FQPA Considerations The ADTC recommended that the special hazard based FQPA safety factor be reduced to 1x for OPP. There are available developmental toxicity and reproductive toxicity studies for OPP that are considered acceptable and that show no evidence of increased toxicity to offspring at the same or lower doses as those causing parental/ systemic toxicity or evidence of more severe toxicity relative to parental/ systemic toxicity.

Dietary Exposure and Risk Exposure from the direct and indirect food uses for OPP as well as the inert uses of OPP that result in dietary exposure have been assessed. Exposure estimates from direct food uses were developed using the Dietary Exposure Evaluation Model software with the Food Commodity Intake Database ( DEEM FCID), Version 2.00, which incorporates consumption data from USDA's Continuing Surveys of Food Intakes by Individuals ( CSFII), 1994 1996 and 1998. Exposure estimates from indirect food uses of OPP in counter top disinfectants, dishwashing disinfectants, paper slimicides, paper coatings, and paper adhesives were developed using FDA methodology. Exposure estimates from inert uses of Na OPP were developed using DEEM FCID.

Results of direct food exposure showed that for the adult U. S. population, 7.1% of the chronic Population Adjusted Dose ( cPAD) was occupied from this exposure, while for children, 19.9% of the cPAD was occupied for children ages 1 6, the highest exposed subpopulation. From indirect food exposure, aggregate dietary exposure occupied 20% and 29% of the cPAD for adults and children respectively. From the inert uses of Na OPP, 1.5% of the cPAD was occupied from adult exposure, while 5.4% was occupied from the highest exposed subpopulation of children ( ages 1 2). These percentages are all below 100% of the cPAD and are thus do not pose a risk of concern.

Drinking Water Exposure and Risk Residues of OPP are not expected to significantly impact surface or ground water, as OPP and its salts are known to breakdown in soils, under aerobic as well as anaerobic conditions within a few hours to weeks and therefore a drinking water assessment is not needed.

Residential Handler Exposure and Risk Page 8 of 60 Several residential handler exposure scenarios were assessed for OPP, including use on indoor and outdoor hard surfaces, air deodorization, fogging, treated plastics, and treated paint. Exposures were assessed using either CMA ( Chemical Manufacturers Association, now the American Chemistry Council) data, PHED data presented in HED's Residential SOPs, or ( for inhalation) EPA's Wall Paint Exposure Model. The duration of exposure assessed was primarily short term exposures, because the residential uses are expected to be episodic in nature and not daily. The resulting short term exposures and MOEs for the representative residential handler scenarios were above the target dermal and inhalation MOE of 100 for all scenarios. Furthermore, all short term inhalation MOEs for exposure to aerosolized paint are above the target MOE of 100. Results of exposure to chemical vapor exposure from treated paint using the Wall Paint Exposure Model showed that the inhalation ( vapor) MOE for the short term exposure for the homeowner painter is above the target MOE of 100.

For residential post application assessment, scenarios were developed that encompass multiple products, but still represent a high end exposure scenario for all products represented for purposes of a screening level assessment. Representative postapplication scenarios assessed include contacting treated hard surfaces/ floors ( dermal and incidental oral exposure to children), wearing treated clothing ( dermal exposure to adults and children), wearing treated diapers ( dermal exposure to infants), mouthing treated textiles such as clothing and blankets ( incidental oral exposure to children), and mouthing treated plastic toys ( incidental oral exposure to infants). Additionally, postapplication/ bystander inhalation exposures were assessed for use of the disinfecting/ deodorizing products ( vapor exposure to adults and children) and paints ( vapor exposure to adults and children). As with residential handler scenarios, most exposures were assessed for shortterm duration only. However, it is believed that intermediate term exposure to children may occur in day care centers where disinfecting products are used more frequently. Additionally, it is believed that exposures will occur on a continuous basis for infants wearing treated diapers. Therefore, short, intermediate and long term (> 6 months) exposures were necessary to assess this scenario.

Results of the post application residential assessment showed that for short and intermediate term dermal exposures of children contacting treated floors, dermal MOEs for short term ( 150) and intermediate term ( 930) were above the target level of 100 and thus not of concern. Short and intermediate term incidental oral exposures of children contacting treated floors were also above the target MOE of 100 ( 1,200 and 6,900 respectively) and thus are not of concern.

For short term dermal exposure of adults and children wearing treated clothing, the dermal MOEs for children were below the target MOE of 100 using the 100% transfer factor ( MOE < 1) and using the 5% transfer factor ( MOE = 16). For adults, the dermal MOEs were also below the target MOE of 100 using both the 100% transfer factor ( MOE = 1) and the 5% transfer factor ( MOE = 25) and thus present risks of concern for this scenario. In addition to treated clothing, there is the potential for dermal exposure to infants wearing cloth diapers treated with a trigger pump spray product containing OPP. Page 9 of 60 Though it is likely that the diapers treated with this product would be washed prior to use, the label does not provide specific use instructions pertaining to washing. Therefore, a post application assessment assuming no laundering was conducted as a conservative measure. Calculation of short, intermediate, and long term dermal doses and MOE for infants wearing treated cloth diapers showed all MOEs below the target of 100 using a transfer factor of either 100% or 5%.

For incidental oral exposures of children mouthing treated textiles or treated toys, calculation of incidental oral MOEs showed no risks of concern from these exposures ( MOEs of 300 and 2,400 respectively).

Inhalation exposures of adults and children from exposure to air deodorizers containing OPP were assessed using the Multi Chamber Concentration and Exposure Model ( MCCEM v1.2) to present a screening level estimate of the potential inhalation risk. For both adults and children, the calculated inhalation MOEs are greater than the target MOE of 100. Furthermore, these MOEs are also greater than 1,000 therefore; an additional inhalation toxicity study is not warranted based on the results of this scenario. The MCCEM model was also used to assess post application inhalation exposures for entry into a room after a fogging application. All of the adult and child inhalation MOEs were above the target MOE of 100. All of the MOEs for children were below 1,000. However, the ST vapor inhalation exposures to adults for a 0 hr REI and a 4 and 24 hour exposure duration along with the ST vapor inhalation exposure to adults for a 4 hr REI and 24 hour exposure duration were below 1,000. Therefore, the based on the results of these scenarios for which the calculated MOEs are below 1,000, the Agency may request that a confirmatory inhalation toxicity study be conducted.

Post application inhalation exposure to OPP from use in paint was estimated using the Wall Paint Exposure Model ( WPEM) version 3.2. Both the child and adult inhalation MOEs are above the target MOE of 100, but below a value of 1,000. Since the MOEs are below 1,000, the Agency may request that a confirmatory inhalation toxicity study be conducted.

Aggregate Exposure and Risk Acute and Chronic Dietary Aggregate Risk: Aggregate dietary risk includes exposure from direct food uses, indirect food uses, inert uses, and exposure from drinking water. As an acute dietary endpoint of concern was not identified for OPP, and as there are no concerns for surface or ground water residues of OPP, the aggregate dietary risk can be addressed from the direct and indirect food uses of OPP. Dietary exposure from conventional uses of OPP is detailed in a separate memorandum from the Health Effects Division of the Office of Pesticide Programs ( D319639), while dietary exposure from the indirect food uses of OPP have been detailed in a separate memorandum ( A Memo from Bob Quick, to Najm Shamim, 2006). Dietary exposure from the inert uses of NA OPP is detailed in a separate memorandum as well ( Talia Milano and Cassi Walls, Ph. D., February 2006). Aggregate dietary risk from these sources occupy 31.5% of the cPAD Page 10 of 60 for adults and 68.7% of the cPAD for children. These aggregate risk estimates are all below 100% of the cPAD for OPP and thus there is no risk of concern.

Short and Intermediate term aggregate risk: Short and intermediate term aggregate exposures and risks include food and/ or water exposures in conjunction with relevant residential exposures from both the active and inert uses of OPP and NA OPP. In the case of OPP, short and intermediate term aggregate risks were assessed for adults and children that could be exposed to OPP and OPP salt residues from the use of products in non occupational environments. Since the short term dermal toxicity endpoint ( NOAEL of 100 mg/ kg/ day from a 21 day dermal toxicity study) was based on skin irritation, in comparison to a different effect from the short term oral and inhalation end points ( NOAEL of 100 mg/ kg/ day from developmental toxicity studies), short term dermal exposures were not aggregated with the short term inhalation and oral exposures. Intermediate term toxicity endpoints for all of the routes of exposure ( oral, dermal and inhalation) are based on the same study and same toxic effect ( NOAEL of 39 mg/ kg/ day from a chronic/ carcinogenicity study); therefore, all intermediate term routes were aggregated together. The Total MOE method was employed to assess aggregate risk. This method is found at http:// www. epa. gov/ pesticides/ trac/ science/ aggregate. pdf. When dietary exposures were aggregated with oral and inhalation residential exposure scenarios, the aggregate short term Margin of Exposure ( MOE) for adults was 333, and the aggregate short term MOE for children was 355. Intermediate term aggregate risk ( children only) was calculated to be 247. Aggregate dermal risk ( MOE) for adults was calculated to be 141, and the aggregate MOE for children was 111. These values are above the target MOE of 100 and are thus not of concern.

Occupational Exposure Occupational handler exposures were assessed for numerous scenarios under the Use Site Categories ( USC) of agricultural premises, food handling premises, commercial/ institutional/ industrial premises, and medical premises. Additionally, occupational exposure can occur during the preservation of materials that are used for household, institutional, and industrial uses, along with the preservation of wood. A detailed analysis is presented in the occupational and residential exposure chapter for OPP ( D320537). In summary, the results of occupational handler analysis indicated no risks of concern with the exception of the following MOEs are slightly below the target MOE of 100:

  Agricultural premises, fogging: intermediate term PPE Total MOE = 98. The IT inhalation MOE = 880, and is below 1,000 so that the Agency may request a confirmatory inhalation toxicity study.   Commercial/ Institutional premises, wiping: short term baseline dermal MOE= 74, intermediate term baseline dermal MOE = 68, and intermediate term baseline Total MOE = 64.   Medical premises, mopping: short term baseline dermal MOE= 93, intermediate term baseline dermal MOE = 84, and intermediate term baseline Total MOE = 78. Page 11 of 60   Materials Preservatives, liquid pour preservation of textiles: short term PPE dermal MOE= 92, intermediate term PPE dermal MOE = 83, and intermediate term Total MOE = 78.   Materials Preservatives, painter ( applying paint post preservation), airless sprayer: baseline dermal short term MOE = 66.   Professional Painters: short term inhalation exposure MOE = 43, which is below the target MOE of 100.

An occupational post application assessment was only conducted for inhalation exposures as a result of entry into a building after a fogging application, because dermal post application is presumed to be negligible. The inhalation exposure assessment was conducted using the Multi Chamber Concentration and Exposure Model ( MCCEM v1.2). Both the short term MOE ( 690) and the intermediate term MOE ( 270) were above the target MOE of 100 but below 1,000. Therefore, the Agency may request that a confirmatory inhalation toxicity study be submitted since the current inhalation endpoint is based on an oral toxicity study.

In addition, there are also occupational exposure risks as a result of using materials that have been already treated with OPP and OPP Salt products. These include metalworking fluids and wood.

There is a potential for dermal and inhalation exposure when a worker handles treated metalworking fluids. This route of exposure occurs after the chemical has been incorporated into the metalworking fluid and a machinist is using/ handling this treated end product. The short term dermal MOE = 54 shows a risk of concern for exposure to metalworking fluid treated with OPP, and there is no concern with the inhalation risks associated with exposure to already treated fluids.

OPP and OPP salts are used in products that are intended to preserve wood ( non pressure treatment). There is the worker function of incorporating the wood preservative into the slurry. For this liquid pump treatment when workers add the preservative to the wood slurry, the MOEs are above the target MOE of 100 and therefore do not pose a concern. However, the IT inhalation MOE ( 840) for the blender/ spray operators adding the chemical via closed liquid pumping is less than 1,000 and therefore a confirmatory inhalation toxicity study is warranted based on these results.

There are also several other job functions that pose a risk for handlers to come into contact with OPP or OPP Salt preserved wood. For all worker functions, which include, chemical operators, graders, millwrights, clean up crews, trim saw operators and dip tank operators, the dermal, inhalation and total MOEs are not of concern.

Environmental Fate Assessment Orthophenylphenol is stable and persistent in abiotic aqueous medium at pHs 5, 7 and 9. It degrades completely in 14 days when exposed to sunlight and is therefore, photolytically unstable in neutral aqueous medium. When exposed to UV light ( 253.7 Page 12 of 60 nm), it degrades into phenylbenzoquinone, pehnylhydroquinone, and 2 hydroxy benzofuran. Its half life is ( measured against hydroxyl radical) 14 hours and is unstable in the atmosphere. It has a high KOC value of 10,000 and is immobile in soils and is likely to remain on the soil surfaces. It is not likely to migrate into ground water. Its major degradation pathway appears to be through biodegradation under aerobic and anaerobic conditions. The observed half lives vary from a few hours to three weeks. Hence even though it is likely to stay on soil surfaces, it biodegrades under aerobic and aerobic soil conditions. Thus it is not likely to contaminate surface water ( drinking water). The sodium salt of OPP ( applied as an antisapstain wood treatment) has been shown to leach out up to 58% within first day after treatment highest leach rate: 71 µ g/ cm2 / day on day one) and up to 82 % within 14 days after treatment ( maximum application rate is 4% of NA OPP). The exposure from the leaching of OPP/ NA OPP from wood treated for antisapstain purposes cannot be addressed at this time due to a lack of leaching information. The registrants have completed an antisapstain leaching study from the treated wood. The wooden blocks were treated with 1% and 4% DOWICIDE A. Since the DOWICIDE A contains 71.1% actives, actual dosings of SOPP were 0.71 and 2.84%, respectively). The study showed that under experimental conditions, 1% and 4 % solutions of SOPP leached 52 to 58% from the treated wooden blocks within the first day; after 14 days, 78 82 % of SOPP leached out from the treated wooden blocks.

Leach rates were: 1% solution 71 µ g SOPP/ cm2 / day and for 4% solution: 192 µ g/ SOPP/ cm2 / day for the first day; after 14 days, leach rates were: 0.5 to 2.0 µ g/ cm2 / day for both solutions. Maximum leaching occurred within the first day and attained pseudo equilibrium after 14 days. At the end of the experiment 20 24% SOPP was extracted from the wooden blocks. ( Orthophenylphenol: Determination of the leaching rate from Wood following a simulated Sapstain Treatment, The Dow Chemical Company, Study ID#: 051089, 2005, DP Barcode: 319656)

Ecological/ Environmental Risk Assessment 2 phenylphenol and its salts demonstrate low toxicity to birds, and moderate toxicity to mammals, freshwater fish, freshwater invertebrates, and algae.

The low exposure potential from the indoor uses of 2 phenylphenol and salts, coupled with the tendency for the compounds to degrade under environmental conditions, result in low likelihood of adverse acute effects to wildlife and aquatic organisms from the indoor uses. Based on the results of the antisapstain modeling, runoff from antisapstain treating facilities will exceed acute high risk, restricted use, and endangered species LOCs for freshwater fish, freshwater invertebrates, and aquatic plants. Chronic risks cannot be assessed at this time due to a lack of chronic toxicity data.

The model used to estimate exposure from antisapstain uses is intended as a Tier I screening model, and, as such, has inherent assumptions and uncertainties that may result in over or under estimation of exposure levels. Since the model is only intended as a screening level model, further refinement of the model is recommended to more accurately assess risks from the antisapstain uses of 2 phenylphenol. Page 13 of 60 Methods to reduce the amount of 2 phenylphenol potentially released from antisapstaintreated wood could potentially mitigate the risks. Possible mitigation methods might include, but are not limited to, lowering the application rate or requiring specific storage conditions to prevent exposure of recently treated wood to weather ( e. g., full covering) and/ or prevent the release of any associated runoff into aquatic habitats ( e. g., drip pads). 2 phenylphenol is not very mobile in soils, so any 2 phenylphenol leached outdoors will likely bind to soils and not reach aquatic habitats as free 2 phenylphenol. An environmental monitoring study of runoff from antisapstain facilities is needed to address the potential risks of concern and provide estimated environmental concentrations ( EEC) to use in a refined risk assessment. In the interim, precautions to limit leaching and runoff from antisapstain treatment facilities areas ( see Label Hazard Statements and Use Recommendations section, below) should prevent exposure to aquatic organisms.

Endocrine Disruption Laboratory studies indicate that 2 phenylphenol ( aka 2 hydroxybiphenol) demonstrates some potential to act as an endocrine disruptor. When the appropriate screening and/ or testing protocols being considered under the Agency's Endocrine Disruptor Screening and Testing Advisory Committee ( EDSTAC)' s Endocrine Disruptor Screening Program ( EDSP) have been developed, 2 phenylphenol may be subjected to additional screening and/ or testing to better characterize effects related to endocrine disruption.

Endangered Species For certain use categories, the Agency assumes there will be minimal environmental exposure, and only a minimal toxicity data set is required ( Overview of the Ecological Risk Assessment Process in the Office of Pesticide Programs U. S. Environmental Protection Agency  Endangered and Threatened Species Effects Determinations, 1/ 23/ 04, Appendix A, Section IIB, pg. 81). Chemicals in these categories therefore do not undergo a full screening level risk assessment, and are considered to fall under a A no effect @

determination. The active ingredient uses of 2 phenylphenol, with the exception of the antisapstain wood preservation use, fall into this category. Using Tier I screening modeling to assess potential exposure from antisapstain wood preservation uses of 2 phenylphenol, risks to Listed Species are indicated. Since the model is only intended as a screening level model, and, as such, has inherent uncertainties and limitations which may result in inaccurate exposure estimations, further refinement of the model is recommended before any regulatory action is taken regarding the antisapstain uses of 2 phenylphenol . Additionally, impacts from the antisapstain use could potentially be mitigated with precautions to prevent leaching and runoff when wood is stored outdoors ( see Label Hazard Statements/ Use Recommendations, below). Due to these circumstances, the Agency defers making a determination for the antisapstain uses of 2 phenylphenol until additional data and modeling refinements are available. At that time, the environmental exposure assessment of the antisapstain use of 2 phenylphenol will be revised, and the risks to Listed Species will be reconsidered. Page 14 of 60 Data Gaps:

The following ecological effects data gaps exist for the registered uses of 2 phenylphenol and salts:

Marine/ estuarine organism acute testing ( 72 3/ 850.1075, 850.1035/ 1045, and 850.1025/ 1055) ( These studies have recently been submitted to the Agency and are currently undergoing review).

Aquatic organism chronic toxicity testing ( 72 4a/ 850.1300 and 72 4b/ 850.1400)

Terrestrial plant toxicity testing using rice ( 123 1/ 850.4225 and 850.4250) ( These studies have recently been submitted to the Agency and are currently undergoing review).

Aquatic plant toxicity testing on four species ( 123 2/ 850.4400 and 850.5400) ( These studies have recently been submitted to the Agency and are currently undergoing review).

Monitoring study of runoff from antisapstain facilities to establish EEC's for risk assessment Label Hazard Statements/ Use Recommendations 2 phenylphenol and salts labels must state:

" Do not discharge effluent containing this product into lakes, streams, ponds, estuaries, oceans, or other waters unless in accordance with the requirements of a National Pollutant Discharge Elimination System ( NPDES) permit and the permitting authority has been notified in writing prior to discharge. Do not discharge effluent containing this product to sewer systems without previously notifying the local sewage treatment plant authority. For guidance contact your State Water Board or Regional Office of the EPA."

Antisapstain labels must state: " Treated lumber must not be stored outdoors without precautions to prevent to prevent leaching by rainfall to the environment. Suitable precautions include: covering wood with plastic or other impervious covering, installation of berms and placement of plastic under the wood to prevent surface water runoff away from the storage area."

Incident Reports For assessment of human incidents, several databases were searched for available information, including the Office of Pesticides Programs ( OPP) Incident Data System ( IDS), Poison Control Centers, the California Department of Pesticide Regulation, the National Pesticide Telecommunications Network ( NPTN), and the published scientific peer reviewed literature. From examination of these databases, OPP and salts appear to cause dermal effects which are perhaps due to irritation. Inhalation is another route which Page 15 of 60 shows some symptoms. However, it is clear that all the databases and published literature show that specific chemical toxic effects can not be attributed specifically to OPP or NA OPP or K OPP only, as most of the symptoms appear in a mixture of active ingredients, one of them OPP or its salts.

2.0 PHYSICAL/ CHEMICAL PROPERTIES AND CHARACTERIZATION Chemical Identity:

Chemical Name: Orthophenylphenol ( or 2 phenylphenol) Chemical Family: Phenol Common/ Trade Name: Dowcide1, Preventol O extra CAS Number: 90 43 7 Molecular Formula: C12H20O Chemical Structure:

OH Orthophenylphenol Table 2 1 Chemical Characteristics for Technical Grade Active OPP Molecular Weight 170.2 Color Colorless Physical State Solid ( flakes) Specific Gravity 1.2 Dissociation Constant 9.9 at 25 o C pH 6.1 in aqueous solution at 22.7 o C Stability Stable at normal conditions Melting Point 56 58 o C Boiling Point 286 o C Water Solubility 700 mg/ L at 25 o C Octanol Water Partition constant ( LogKOW) 3.3 Vapor Pressure 2 x 10 3 mm Hg at 25 o C Chemical Identity Chemical Name: Sodium orthophenylphenol ( NA OPP) Chemical Family: Phenol Common/ Trade Names: Dowcide A, Preventol ON Extra CAS Number: 132 27 4 Molecular Formula: C12H19NaO Page 16 of 60 Molecular Structure:

Na OPP ( Sodium orthophenylphenate)

Table 2 2 Chemical Characteristics for Technical Grade NA OPP Molecular Weight 192.19 Color White to light buff Physical State Solid ( flakes) Specific Gravity 1.36 Dissociation Constant 10 at 20 o C pH 12. 13.5 Stability Stable under controlled conditions Melting Point 298.5 o C Boiling Point N/ A Octanol Water Partition Coefficient ( Log KOW) 0.59 Water Solubility 60.6 g/ 100 mL, 53.37 % ( w/ w) Vapor Pressure 1.8 x 10 9 mm Hg at 25 o C Chemical Identity Chemical Name: Potassium Orthophenylphenate ( K OPP) Chemical Family: Phenol Common/ Trade Name: Potassium salt CAS Number: 13707 65 8 Molecular Formula: C12H19KO Chemical Structure:

K OPP ( Potassium Orthophenylphenate) Page 17 of 60 Table 2 3 Chemical Characteristics for Technical Grade Active Potassium o Phenylphenate ( K OPP) Molecular Weight 208.30 Color White Physical State Solid Specific Gravity n/ a Dissociation Constant n/ a PH n/ a Stability n/ a Melting Point 230.7 C Boiling Point n/ a Octanol Water Partition Coefficient ( Log KOW) 0.59 Water Solubility Highly water soluble Vapor Pressure 1.91 x 10 11 mm Hg at 25 C 3.0 HAZARD CHARACTERIZATION 3.1 Hazard Profile Acute Toxicity The acute toxicity database for 2 phenylphenol and salts is incomplete. Acute dermal toxicity ( 870.1200), acute inhalation toxicity ( 870.1300), and primary eye irritation ( 870.2400) studies must be submitted. 2 phenylphenol has a moderate order of acute toxicity via the oral route of exposure ( Toxicity Category III). For dermal irritation, 2 phenylphenol and its sodium salt are severe ( Toxicity Category I) and moderate to severe ( Toxicity Category II) irritants, respectively. 2 phenylphenol and its sodium salt are not dermal sensitizers. The acute toxicity profile is presented in Table 3 1.

Table 3 1 Acute Toxicity Profile for 2 Phenylphenol and Salts Guideline Number Study Type/ Test substance (% a. i.) MRID Number/ Citation Results Toxicity Category 870.1100 ( § 81 1) Acute Oral Rat 2 phenylphenol purity 99.9% 43334201 LD50 = 2733 mg/ kg III 870.1100 ( § 81 1) Acute Oral Rat 2 phenylphenol, sodium salt purity 99.1% 43334204 LD50 = 846 mg/ kg ( male) LD50 = 591 mg/ kg ( female) III 870.1200 ( § 81 2) Acute Dermal Rat OPP 99.73% a. i. 00078779 LD50 > 5000 mg/ kg IV 870.1300 ( § 81 3) Acute Inhalation Rat OPP 99.75% a. i. 42333101 Unacceptable Study NA Page 18 of 60 Table 3 1 Acute Toxicity Profile for 2 Phenylphenol and Salts Guideline Number Study Type/ Test substance (% a. i.) MRID Number/ Citation Results Toxicity Category 870.2400 ( § 81 4) Primary Eye Irritation Rabbit Dowicide ® 1 00139884 Unacceptable Study NA 870.2500 ( § 81 5) Primary Dermal Irritation Rabbit 2 phenylphenol purity 99.9% 43334202 Primary Irritant I 870.2600 ( § 81 6) Dermal Sensitization  Guinea pig 2 phenylphenol purity 99.9% 43334203 Not a sensitizer. No 870.2600 ( § 81 6) Dermal Sensitization  Guinea pig 2 phenylphenol, sodium salt purity 99.1% 43334205 Not a sensitizer. No In accordance with the EPA Final Guidelines for Carcinogen Risk Assessment ( March 29, 2005), the Health Effects Division's Carcinogenicity Assessment Review Committee ( CARC) used multiple descriptors for the classification of orthophenylphenol and sodium orthophenylphenol in its meeting of June 8, 2005.

OPP and NA OPP were classified as " Not Likely to be Carcinogenic to Humans" based on convincing evidence that carcinogenic effects are not likely below a defined dose range ( i. e, below 200 mg/ kg/ day). This classification is based on the following: convincing evidence that a non linear mode of action for bladder tumors was established in rats. High doses of OPP lead to saturation of phase II detoxification enzyme pathways, resulting in increased amounts of the oxidative metabolites PHQ and/ or PBQ. The generation of PBQ is considered dose dependent, appearing in increased quantity only at higher doses of OPP (> 200 mg/ kg/ day). The shift in biotransformation products with increased dose of OPP has been postulated to be associated with the non linear response observed in tumorigenicity of the urinary bladder, involving oxidative damage to cells and subsequent regenerative hyperplasia. With continued exposure, this process leads to development of tumors. Evidence suggests that a non genotoxic mode of action is operative.

OPP and NA OPP were also classified as " Likely to be Carcinogenic to Humans," based on the presence of urinary bladder tumors in rats and the presence of liver tumors in mice at doses above 200 mg/ kg/ day. This classification is based on the fact that insufficient data were provided to support a mode of action for the mouse liver tumors. Although the tumors were benign and observed only in one sex at high doses, more data are required for any conclusion to be drawn regarding the mode of action for these tumors. Page 19 of 60 The CARC noted that although both chemicals are classified as " Likely to be Carcinogenic to Humans" above a defined dose range, quantification of cancer risk is not required since the NOAEL selected for the chronic Reference Dose ( 39 mg/ kg/ day) is protective of the precursor events leading to development of bladder tumors that occur at doses above 200 mg/ kg/ day and liver tumors that occur above 500 mg/ kg/ day.

3.2 Dose Response Assessment On October 20, 2004, the Antimicrobials Division Toxicology Endpoint Selection Committee ( ADTC) reviewed the available toxicology data for OPP and selected endpoints for use as appropriate in occupational/ residential exposure risk assessments. The potential for increased susceptibility of infants and children from exposure to OPP was also evaluated by the committee in order to meet the statutory requirements of the Food Quality Protection Act ( FQPA) of 1996. A summary of the results are presented in Table 3 2.

Table 3 2 Summary of Toxicological Doses and Endpoints for Orthophenylphenol for Use in Human Risk Assessments Exposure Scenario Dose Used in Risk Assessment ( mg/ kg/ day) Target MOE, UF, Special FQPA SF, for Risk Assessment Study and Toxicological Effects Dietary Risk Assessments Acute Dietary ( general population and females 13 49) No appropriate endpoints were identified that represent a single dose effect. Therefore, this risk assessment is not required.

Chronic Dietary ( all populations) NOAEL = 39 mg/ kg/ day ( 43% dermal absorption) FQPA SF = 1 UF = 100 ( 10x inter species extrapolation, 10x intra species variation)

Chronic RfD = 0.39 mg/ kg/ day Chronic PAD = 0.39 mg/ kg/ day Combined oral toxicity/ carcinogenicity study in rats ( MRID 43954301, 44852701, 44832201)

LOAEL of 200 mg/ kg/ day based upon decreased body weight, body weight gain, food consumption and food efficiency, increased clinical and gross pathological signs of toxicity.

Non Dietary Risk Assessments Incidental Oral Short Term ( 1  30 days) NOAEL ( maternal) = 100 mg/ kg/ day Target MOE = 100 FQPA SF = 1 UF = 100 ( 10x inter species extrapolation, 10x intra species Developmental ( gavage) toxicity studies in rats ( MRID 00067616, 92154037) and rabbits ( MRID 41925003; co critical developmental toxicity study)

Maternal LOAEL of 300 mg/ kg/ day Page 20 of 60 Table 3 2 Summary of Toxicological Doses and Endpoints for Orthophenylphenol for Use in Human Risk Assessments Exposure Scenario Dose Used in Risk Assessment ( mg/ kg/ day) Target MOE, UF, Special FQPA SF, for Risk Assessment Study and Toxicological Effects variation) based upon clinical observations of toxicity, decreased weight gain, food consumption and food efficiency observed in the rat developmental toxicity study.

Incidental Oral Intermediate Term ( 1  6 months) NOAEL = 39 mg/ kg/ day Target MOE = 100 FQPA SF = 1 UF = 100 ( 10x inter species extrapolation, 10x intra species variation) Combined oral toxicity/ carcinogenicity study in rats ( MRID 43954301, 44852701, 44832201)

LOAEL of 200 mg/ kg/ day based upon decreased body weight, body weight gain, food consumption and food efficiency, increased clinical and gross pathological signs of toxicity.

Dermal Short Term ( 1  30 days)

( residential and occupational) NOAEL ( dermal) = 100 mg/ kg/ day ( 200 µ g/ cm2) a Target MOE = 100 FQPA SF = 1 UF = 100 ( 10x inter species extrapolation, 10x intra species variation) 21 Day Dermal toxicity study in rats ( MRID 42881901)

LOAEL ( dermal) of 500 mg/ kg/ day based upon dermal irritation ( erythema, scaling) at the site of test substance application.

Dermal Intermediate and Long Term ( 1  6 months and > 6 months)

( residential and occupational) NOAEL = 39 mg/ kg/ dayb Target MOE = 100 FQPA SF = 1 UF = 100 ( 10x inter species extrapolation, 10x intra species variation) Combined oral toxicity/ carcinogenicity study in rats ( MRID 43954301, 44852701, 44832201)

LOAEL of 200 mg/ kg/ day based upon decreased body weight, body weight gain, food consumption and food efficiency ( effects observed as early as 13 weeks in this study), increased clinical and gross pathological signs of toxicity.

Inhalation Short Term ( 1  30 days)

( residential and occupational) NOAEL ( maternal) = 100 mg/ kg/ dayc Target MOE = 100 FQPA SF = 1 UF = 100 ( 10x inter species extrapolation, 10x intra species variation) Note: an additional 10x is necessary for route extrapolation. If results are below a MOE of 1,000, a Developmental ( gavage) toxicity studies in rats ( MRID 00067616, 92154037) and rabbits ( MRID 41925003; co critical developmental toxicity study)

Maternal LOAEL of 300 mg/ kg/ day based upon clinical observations of toxicity, decreased weight gain, food consumption and food efficiency observed in the rat developmental toxicity study. Page 21 of 60 Table 3 2 Summary of Toxicological Doses and Endpoints for Orthophenylphenol for Use in Human Risk Assessments Exposure Scenario Dose Used in Risk Assessment ( mg/ kg/ day) Target MOE, UF, Special FQPA SF, for Risk Assessment Study and Toxicological Effects confirmatory inhalation study may be required Inhalation Intermediate and Long Term ( 1  6 months and > 6 months)

( residential and occupational) NOAEL = 39 mg/ kg/ dayc Target MOE = 100 FQPA SF = 1 UF = 100 ( 10x inter species extrapolation, 10x intra species variation) Note: an additional 10x is necessary for route extrapolation. If results are below a MOE of 1,000, a confirmatory inhalation study may be required Combined oral toxicity/ carcinogenicity study in rats ( MRID 43954301, 44852701, 44832201)

LOAEL of 200 mg/ kg/ day based upon decreased body weight, body weight gain, food consumption and food efficiency ( effects observed as early as 13 weeks in this study), increased clinical and gross pathological signs of toxicity.

Cancer ( oral, dermal, inhalation) Classification: Orthophenylphenol is classified as A Not likely to be carcinogenic below a specific dose range @, without quantification of risk.

UF = uncertainty factor, DB UF = data base uncertainty factor, FQPA SF = special FQPA safety factor, NOAEL = no observed adverse effect level, LOAEL = lowest observed adverse effect level, PAD = population adjusted dose ( a = acute, c = chronic), RfD = reference dose, MOE = margin of exposure a ( 100mg x 0.200 kg rat x 1000 µ g ) / 100 cm2 area of rat dose = 200 µ g/ cm2 Kg rat mg b A dermal absorption factor of 43% was chosen based on the results of a submitted study ( Timchalk et al., 1996) in humans. c The inhalation absorption factor of 100% ( default value, assuming oral and inhalation absorption are equivalent) is used as an assumption since an oral endpoint was selected for the inhalation exposure scenarios.

3.3 FQPA Considerations Developmental toxicity studies for orthophenylphenol are available in both the rat and rabbit, as summarized in this toxicology chapter. Both studies were well conducted and considered acceptable by the Agency. The examination of these studies shows that adverse effects in offspring occurred at doses higher than those producing maternal toxicity. In addition, the effects on offspring were not considered more severe than those occurring in maternal animals. Therefore, there is no increased concern for developmental toxicity of orthophenylphenol when comparing effects in adult animals with those in offspring. This conclusion is similar to that reached by the Department for Page 22 of 60 Environment, Food and Rural Affairs of the Pesticides Safety Directorate in their 1993 publication on the evaluation of 2 phenylphenol.

An acceptable two generation reproduction toxicity study conducted according to Agency guidelines is available for orthophenylphenol. There were no toxicologically significant effects on reproductive parameters in this study. Therefore, there is no increased concern for potential reproductive toxicity of orthophenylphenol.

Based on the above, the ADTC recommended that the special hazard based FQPA safety factor be reduced to 1x for OPP. There are available developmental toxicity and reproductive toxicity studies for OPP that are considered acceptable and that show no evidence of increased toxicity to offspring at the same or lower doses as those causing parental/ systemic toxicity or evidence of more severe toxicity relative to parental/ systemic toxicity.

3.4 Endocrine Disruption EPA is required under the Federal Food Drug and Cosmetic Act ( FFDCA), as amended by FQPA, to develop a screening program to determine whether certain substances ( including all pesticide active and other ingredients) " may have an effect in humans that is similar to an effect produced by a naturally occurring estrogen, or other such endocrine effects as the Administrator may designate." Following the recommendations of its Endocrine Disruptor Screening and Testing Advisory Committee ( EDSTAC), EPA determined that there was scientific basis for including, as part of the program, the androgen and thyroid hormone systems, in addition to the estrogen hormone system. EPA also adopted EDSTAC's recommendation that the Program include evaluations of potential effects in wildlife. For pesticide chemicals, EPA will use FIFRA and, to the extent that effects in wildlife may help determine whether a substance may have an effect in humans, FFDCA has authority to require the wildlife evaluations. As the science develops and resources allow, screening of additional hormone systems may be added to the Endocrine Disruptor Screening Program ( EDSP).

When the appropriate screening and/ or testing protocols being considered under the Agency's EDSP have been developed, OPP may be subjected to additional screening and/ or testing to better characterize effects related to endocrine disruption.

4.0 EXPOSURE ASSESSMENT AND CHARACTERIZATION 4.1 Summary of Registered Antimicrobial Uses Table 4 1 presents the uses of OPP and OPP salts that represent the high end exposures and risks associated with the labeled uses. Some OPP and OPP salts are registered for residential uses such as disinfectants and deodorizers. The use patterns for these include indoor and outdoor hard surfaces ( e. g., floors, bathroom fixtures, trash cans, household contents), textiles ( e. g., clothing, diapers, and bedding) and carpets. Additional uses include fogging and air deodorizing and also as material preservative for homeowner Page 23 of 60 type products ( e. g., plastics and paints, metalworking fluids, sapstain, glues, paper, polymers, and paper). The percentage of OPP and OPP salts in various products range from 0.0137% to 99.5%.

The routes of exposure evaluated in the present assessment are: short term ( ST), intermediate term ( IT), and long term ( LT) dermal and inhalation exposures, and shortterm ( ST) and intermediate term ( IT) oral exposures. Specific routes and durations are also presented in Table 4 1.

Table 4 1 Representative Uses Associated with Residential Exposure Representative Use Exposure Scenario Application Method Registration # Application Rate ST Handler: Dermal and Inhalation;

ST and IT Post app1,9: child incidental ingestion and dermal Mopping ST Handler: Dermal and Inhalation Wiping 40510 5 ( OPP Salt) 0.126 lb a. i./ diluted gal ( 8 oz. product / 4 gal water x 97% a. i. x 8.34 lb/ gal x 1 gal/ 128 oz) Indoor Hard Surfaces ST Handler: Dermal and Inhalation Aerosol foam spray3 777 27 ( OPP) 0.42% a. i. by weight Outdoor Hard Surfaces ( i. e. exterior house cleaner) ST Loader and Handler: Dermal and Inhalation Tank type garden sprayer ( i. e. low pressure sprayer) 71240 1 ( OPP Salt) 0.00104 lb a. i./ gal ( 0.25 gal product / 5 gal water x 0.25% a. i. x 8.34 lb/ gal: assuming product has the density of water)

Textiles ( i. e., clothing and cloth diapers) ST Handler: Dermal and Inhalation ST Post app: adult dermal; child incidental ingestion and dermal IT/ LT Post app: child dermal ( diaper) Trigger pump spray3 10088 105 ( OPP) 0.0208 lb ai/ gal ( 0.249% ai x 8.34 lb/ gal)

Air Deodorization ST Handler: Dermal and Inhalation Post app: adult ( ST) and child ( ST and IT) 1 inhalation 2 Aerosol spray 44446 67 ( OPP) 0.199% a. i. by weight Page 24 of 60 Table 4 1 Representative Uses Associated with Residential Exposure Representative Use Exposure Scenario Application Method Registration # Application Rate Fogging ST Post app: adult and child inhalation ( vapor) 8 Fogger 70263 3 5 ( OPP) 0.019 lb a. i./ 6000 ft2 ( 0.22% a. i. x 1 gal product/ 6000 ft2 x 8.34 lb/ gal)

Using Treated Plastic/ polymer products ( i. e., toys) ST Post app: child incidental ingestion NA 67869 24 ( OPP salt) 0.34% a. i. by weight of material to be preserved Using Treated Paint ST Handler: Dermal and Inhalation ( aerosol and vapor) 6 ST Post app: adult and child inhalation ( vapor) 7 Paint brush, rollers, airless sprayer 67869 24 ( OPP salt)

and 464 126 ( OPP) 0.56% a. i. by weight of material to be preserved 0.5% a. i. by weight of material to be preserved ST = Short term exposure, IT = Intermediate term exposure 1IT post application exposures for children were assessed because that this product could be used in a commercial day care facility. 2 Since this application rate is for OPP, which has a relatively high vapor pressure, it was necessary to assess post application inhalation exposure to the vapor. OPP salts have a much lower vapor pressure and will not readily volatilize. 3 The aerosol spray was chosen to represent the aerosol foam product and trigger pump spray product because it is expected that they have similar unit exposures. 4 The post app exposure is represented by the post app exposure scenario for air deodorization. 5 Label Reg # 70263 3 can be used in household settings by commercial applicators; therefore, a postapplication scenario was assessed using the % ai from this product. However, the application rate from another label (# 65020 7) for lack of better data. Note: Reg # 65020 7 also can be used in schools. 6 Handler dermal and inhalation ( to the particulates) exposure were assessed for OPP salts using PHED unit exposures. WPEM ( Wall Paint Exposure Model) was also used to assess the vapors of OPP for residential handlers because of the high vapor pressure of OPP. 7 Post application inhalation exposures to the vapor were assessed for only the OPP product because of its high vapor pressure. 8 For the fogging scenario, child post application incidental ingestion or dermal exposures were not assessed because they were assessed for the mopping application. The mopping application has a much higher application rate ( in terms of lb ai/ ft2) than the fogging application. It should also be noted that although the fogging application can occur in child care facilities, the intermediate term duration was not assessed because it was assumed that the fogging application would be used primarily in areas damaged by smoke, fire, floods, or sewage backups and these incidents do not occur on a continuous basis. 9This label, # 40510 5 states that the product can be used for " housekeeping santization" and to " sanitize latrine: buckets, urinals, toilet bowls, walls, shower stalls, garbage cans, and garbage platforms." This is why it is assumed to not be used in daycares. It does not specifically say " commercial and institutional premises."

4.1.1 Residential Exposure/ Risk The residential handler scenarios shown in Table 4 2 were assessed to determine dermal and inhalation exposures. The majority of the scenarios were assessed using CMA data. However, for handlers using paint, two approaches were used to determine inhalation Page 25 of 60 exposure. First, the Pesticides Handler Exposure Database ( PHED) was used to determine inhalation exposure to aerosolized particles of paint ( assessed below). Secondly, to assess the inhalation exposure to OPP vapor, EPA's Wall Paint Exposure Model ( WPEM) was used. For specific assumptions used in this analysis, consult the Occupational and Residential Exposure chapter for OPP.

Handlers The resulting short term dermal and aerosol portion of the inhalation exposures and MOEs for the representative residential handler scenarios are presented in Table 4 2. The calculated MOEs were above the target dermal and inhalation MOE of 100 for all scenarios. Furthermore, all short term inhalation MOEs exceeded 1,000 therefore, a confirmatory inhalation toxicity study is not warranted based on the results of these exposure scenarios.

Table 4 2 Short Term OPP & Salts Residential Handlers Exposures and MOEs Unit Exposure ( mg/ lb ai) Absorbed Daily Dose ( mg/ kg/ day) MOE ( ST)

Exposure Scenario Method of Application Dermala Inhalation Application Rate Quantity Handled/ Treated per day Dermalb Inhalationc Dermal ( Target = 100) d Inhalation ( Target = 100) e Mopping 71.6 2.38 0.126 lb ai/ gallon 1 gallons 0.1289 0.0043 780 23,000 Wiping 2870 67.3 0.126 lb ai/ gallon 0.13 gallons 0.6716 0.0157 150 6,300 Application to indoor hard surfaces Aerosol Foam Spray 220 2.4 0.42 % ai by weight 0.875 lbs 0.0116 0.0001 8,700 7.90x105 Application to outdoor hard surfaces ( i. e. exterior of homes) Tank Type Low Pressure Garden Sprayer 100 0.03 0.00104 lb ai/ gallon 5 gallons 0.01 0.00016 13,000 4.5x107 Application to textiles Trigger Pump Spray 220 2.4 0.0208 lb ai/ gallon 0.13 gallons 0.085 0.0065 12,000 1.10x106 Air deodorization Aerosol Spray 220 2.4 0.199% ai by weight 1.03 lbs 0.0064 7.5 x 10 5 16,000 1.4 x106 Brush/ roller 230 0.284 0.56% ai by weight 20 lb s ( 2 gal) 0.368 0.0005 270 220,000 Painting Airless sprayer 79 0.83 0.56% ai by weight 150 lbs ( 15 gal) 0.948 0.01 110 10,000 a All dermal unit exposures represent ungloved replicates. The aerosol spray, tank type garden sprayer ( i. e., low pressure sprayer), trigger pump sprayer, brush/ roller, and airless sprayer unit exposures represent short sleeve and short pant replicates. The mopping, wiping, and liquid pour represent long pant and long shirt replicates. b Dermal Daily Dose ( mg/ kg/ day) = [ dermal unit exposure ( mg/ lb ai) * application rate * quantity handled / body weight ( 70 kg). Page 26 of 60 c Inhalation Daily Dose ( mg/ kg/ day) = [ inhalation unit exposure ( mg/ lb ai) * application rate * quantity handled / body weight ( 70 kg). d Dermal MOE = NOAEL ( 100 mg/ kg/ day) / Daily Dose. Target dermal MOE is 100. e Inhalation MOE = NOAEL ( 100 mg/ kg/ day) / Daily Dose. Target inhalation MOE is 100.

Residential Painter Inhalation Exposure and Risk For assessment of the vapor portion of the inhalation exposure of residential painters, AD utilized EPA's Wall Paint Exposure Model ( WPEM) version 3.2 to estimate air concentrations resulting from the use of paint preserved with OPP. WPEM was developed under a contract by Geomet Technologies for EPA OPPT to provide estimates of potential air concentrations and consumer/ worker exposures to chemicals emitted from wall paint which is applied using a roller or a brush. WPEM uses mathematical models developed from small chamber data to estimate the emissions of chemicals from oilbased ( alkyd) and latex wall paint. The emission data can then be combined with detailed use, workload and occupancy data ( e. g., amount of time spent in the painted room, etc,) to estimate exposure. Specific input parameters include: the type of paint ( latex or alkyd) being assessed, density of the paint ( default values available), and the chemical weight fraction, molecular weight, and vapor pressure. Detailed information and the executable model can be downloaded from http:// www. epa. gov/ opptintr/ exposure/ docs/ wpem. htm.

Results of the WPEM model calculated the short term vapor inhalation MOE as 2,000, which does not present a risk of concern for inhalation exposure of residential painters.

Residential Post Application For the purposes of this screening level assessment, post application scenarios have been developed that encompass multiple products, but still represent a high end exposure scenario for all products represented. As shown in Table 4 1, representative postapplication scenarios assessed include contacting treated hard surfaces/ floors ( dermal and incidental oral exposure to children), wearing treated clothing ( dermal exposure to adults and children), wearing treated diapers ( dermal exposure to infants), mouthing treated textiles such as clothing and blankets ( incidental oral exposure to children), and mouthing treated plastic toys ( incidental oral exposure to infants). Additionally, postapplication bystander inhalation exposures were assessed for use of the disinfecting/ deodorizing products ( vapor exposure to adults and children) and paints ( vapor exposure to adults and children). Typically, most products used in a residential setting result in exposures occurring over a short term time duration ( 1 to 30 days).

There is the potential for dermal exposure to toddlers crawling on hard floors after mopping with OPP and OPP salts products. Exposures and MOEs were calculated for children contacting treated hard surface floors in residential homes ( short term exposure) and in commercial daycare centers ( intermediate term exposure). The dermal MOEs for the residential settings ( short term MOE) and institutional settings ( intermediate term MOE) are above the target MOE of 100. In addition to the dermal exposure, toddlers crawling on treated hard floors will also be exposed to OPP and OPP salts residues via Page 27 of 60 incidental oral exposure through hand to mouth activity. To calculate incidental ingestion exposure to these chemicals due to hand to mouth transfer, the methodologies established in the Standard Operating Procedures ( SOPs) for Residential Exposure Assessments ( USEPA 2000 and, 2001) were used. These use assumptions that are similar to those used in calculating dermal exposures for toddlers crawling on treated hard floors. Exposures were calculated for children contacting treated floors in residential homes and in commercial day care centers. The oral MOEs are above the target MOE of 100 for residential settings and institutional settings, and thus do not present a risk.

The calculation of the short and intermediate term dermal and oral doses and the dermal and oral MOEs are shown in Table 4 3 and 4 4 respectively.

Table 4 3. Short and Intermediate term Post application Dermal Exposures and MOEs for Children Contacting Treated Floors Exposure Scenario Application Rate ( lb ai/ sq ft) Product remaining after mopping Percent Trans. Residue Body Area in contact with floor ( m2) Absorbed potential daily dosea ( mg/ kg/ day) Dermal MOEb Hard surfaces  residential setting 1.26x10 4 25% 10% 0.657 0.674 150 ( ST)

Hard surfaces  daycare center 1.83x10 5 25% 10% 0.657 0.0421 930 ( IT)

a Absorbed Potential Daily Dose( mg/ kg/ day) = [( Application rate, lb ai/ ft2)*( conversion factor, 454 g/ lb)* ( conversion factor, 1,000 mg/ g) * ( conversion factor, 1 ft2/ 0.093 m2) * ( product remaining after mopping, 25%) * ( dermal transfer factor, 10%) * ( body surface area in contact with floor, 0.657 m2) * ( dermal absorption , 0.43 for IT exposure and not applicable for ST exposures) ] / ( body weight, 15 kg) b Dermal MOE = NOAEL ( mg/ kg/ day) / Absorbed Potential Daily Dose ( mg/ kg/ day) [ Where short term dermal NOAEL = 100 mg/ kg/ day and intermediate term dermal NOAEL = 39 mg/ kg/ day]. Target MOE = 100 Table 4 4. Short and Intermediate term Incidental Oral Post application Exposures and MOEs for Children Contacting Treated Floors Exposure Scenario Appl. Rate ( lb ai/ sq ft) Product remaining after mopping Surface Residuea ( µ g/ cm2) Percent transferable residue Surface area mouthed ( cm2/ event) Exposure Frequency ( events/ hr) Saliva Extraction Factor Exp. Time ( hrs/ day) Absorbed Potential Daily Doseb ( mg/ kg/ day) Oral MOEc Hard surfaces  residential setting 1.26x10 4 25% 15.45 10% 20 20 50% 4 0.0824 1,200 ( ST)

Hard surfaces  daycare center 1.83x10 5 25% 2.24 10% 20 9.5 50% 4 0.0057 6,900 ( IT)

a Surface residue ( µ g/ cm2) = ( application rate, lb ai/ ft2)*( Disinfectant fraction remaining on floor, 0.25)*( conversion factor to convert lb to µ g, 4.54E+ 08 µ g/ lb)*( conversion factor to convert ft2 to cm2, 1.08E 03 ft2/ cm2) b Absorbed Potential Daily Dose ( mg/ kg/ day) = [( Surface residue, µ g/ cm2)*( transferable residue, 0.10)*( exposure time, 4 hrs/ day)*( surface area of hands, 20 cm2/ event)*( frequency of hand to mouth Page 28 of 60 activity, 20 events/ hr, and 9.5 event for intermediate term)*( extraction by saliva, 50 %)*( conversion factor to convert µ g to mg, 0.001 mg/ µ g)]/( body weight, 15 kg) c MOE = NOAEL ( mg/ kg/ day) / absorbed potential daily dose( mg/ kg/ day) [ Where short term oral NOAEL = 100 mg/ kg/ day and intermediate term NOAEL = 39 mg/ kg/ day]. Target MOE = 100.

For the intermediate term exposures to the treated floors, it was necessary to determine Total MOEs since the toxicity effects are the same for the dermal and oral routes. The intermediate term Total MOE for children contacting treated floors in day care facilities was 820 and is greater than the target MOE of 100.

Dermal exposure from treated clothing There is the potential for dermal exposure to adults and children from wearing clothing treated with a trigger pump spray product containing OPP or treatment via factory impregnation of the chemical as a preservative. Even as there is anticipated exposure to result from an already preserved textile, the trigger pump use was identified to be the high end, and ultimately was the one assessed. ( See Table 4 5)

Table 4 5. Dermal Post application Exposures and MOEs for Children and Adults Contacting Treated Textiles % a. i. Product absorption rate ( mg/ cm2) Conc. on clothinga ( mg ai/ cm2) Surface area covered by textile ( cm2/ day) Percent transferred Exposure time Potential daily doseb ( mg/ kg/ day) Dermal MOEc Short Term Wearing Treated Clothing  Children 100% 16 ( hours/ day) 124.24 < 1 0.249 198 0.493 5,670 5% 16 ( hours/ day) 6.21 16 Short Term Wearing Treated Clothing   Adults 100% 16 ( hours/ day) 79.34 1 0.249 198 0.493 16,900 5% 16 ( hours/ day) 3.97 25 Wearing Treated Diapers  < 1 year old 100% 8 diapers/ day 182.2 ( ST) 78.35 ( IT/ LT) < 1 ( ST) < 1 ( IT/ LT) 0.249 198 0.493 462 5% 8 diapers/ day 9.11 ( ST) 3.92 ( IT/ LT) 11 ( ST) 10 ( IT/ LT)

a Concentration on clothing ( mg/ cm2) = % active ingredient / 100 * Product absorption rate ( 198 mg/ cm2) b Potential Daily Dose for clothing ( mg/ kg/ day) = [( concentration on clothing, mg/ cm2) * ( surface area of skin covered by clothing, cm2/ day) * ( percent transferable residue from textile) * ( exposure time, hrs/ day) * ( conversion factor, 1 day/ 24 hours)] / ( body weight, kg). Potential Daily Dose for diapers ( mg/ kg/ day) = [( concentration on diapers, mg/ cm2) * ( surface area covered by diaper, cm2/ diaper) * ( exposure frequency, diapers/ day) * ( dermal absorption Page 29 of 60 factor, 0.43 for IT, not applicable for ST) * ( percent transferable residue from diapers)] / ( body weight, kg) c MOE = NOAEL ( mg/ kg/ day) / absorbed potential daily dose [ Where short term dermal NOAEL = 100 mg/ kg/ day and IT/ LT dermal NOAEL = 39 mg/ kg/ day]. Target MOEs = 100.

The dermal MOEs for children are below the target MOE of 100 using the 100% transfer factor ( MOE < 1) and using the 5% transfer factor ( MOE = 16). For adults, the dermal MOEs are also below the target MOE of 100 using both the 100% transfer factor ( MOE = 1) and the 5% transfer factor ( MOE = 25).

For infants wearing treated cloth diapers, all MOEs were below the target MOE of 100 when using a transfer factor of either 100% or 5%, and therefore, are of concern.

Incidental Oral Exposure to Children Mouthing Treated Textiles There is the potential for incidental oral exposure to children from mouthing textiles treated with a trigger pump spray product containing OPP. The calculation of the oral dose and oral MOE for children mouthing treated textiles shows that the MOE value is above the target MOE of 100 ( MOE = 300). The results are presented in Table 4 6.

Table 4 6. Short term Post application Incidental Oral Exposures and MOEs for Children Contacting Treated Textiles % a. i. Product absorption rate ( mg/ cm2) Concentration on clothinga ( mg/ cm2) Area mouthed ( cm2/ day) Saliva Extraction Factor Potential daily dose ( mg/ kg/ day) Incidental Oral MOEc 0.249 198 0.493 20 50% 0.329 300 a Concentration on clothing ( mg ai/ cm2) = % active ingredient * Product absorption rate ( 198 mg/ cm2) b Potential Daily Dose ( mg/ kg/ day) = ( Concentration on clothing, mg/ cm2) * ( area mouthed, cm2/ day) * ( saliva extraction factor, unitless fraction) / ( body weight, kg). c MOE = NOAEL ( mg/ kg/ day) / absorbed potential daily dose [ Where short term oral NOAEL = 100 mg/ kg/ day]. Target MOE = 100.

Incidental Oral Exposure to Children from Mouthing Treated Plastic Toys The exposure estimates for children mouthing treated toys are based on the methodology used for Microban Additive " B" assessment ( USEPA 1997b), which assessed risks to 12 month old infants playing with treated toys, and exposure assumptions from HED's Residential SOPs ( USEPA, 2000 and 2001). The calculations of the oral dose and MOE for children mouthing treated toys are presented in Table 4 7. The MOE is above the target MOE of 100 ( MOE = 2400) and thus present no risk of concern. Page 30 of 60 Table 4 7 Short term Incidental Oral Exposures and MOEs for Infants Mouthing Treated Toys % ai Weight of toy ( g) Percent additive available at surface of the toy (%) Surface area of toy ( cm2) Surface Residue a ( mg ai/ cm2) Saliva Extraction Factor Surface area of toy mouthed ( cm2/ day) Absorbed potential Daily Dose b ( mg/ kg/ day) Incidental Oral MOE c 0.34% 50 0.5% 500 0.0017 50% 500 0.0425 2400 a Surface Reside ( mg ai for a 500 cm2 toy) = (% ai) * ( Weight of toy, 50 g) * ( Conversion factor, 1000 mg/ g) * ( Additive available at surface of toy, 0.5%) / ( Surface area of toy, 500 cm2) b Potential Daily Dose ( mg/ kg/ day) = Surface residue ( 0.0017 mg ai/ cm2) * ( toy area mouthed, 500 cm2/ day) * ( saliva extraction) /( body weight, 15 kg) c MOE = NOAEL ( mg/ kg/ day) / potential daily dose ( mg/ kg/ day) [ Where short term oral NOAEL = 100 mg/ kg/ day]. Target MOE = 100.

Air Deodorizers No post application air concentration data have been submitted for OPP products to determine potential vapor inhalation risk. Therefore, the Multi Chamber Concentration and Exposure Model ( MCCEM v1.2) was used to present a screening level estimate of the potential inhalation risk to adults and children. Results of the MCCEM calculation are shown in Table 4 8. For both adults and children, the calculated inhalation MOEs are greater than 100 and thus present no risk of concern. Furthermore, these MOEs are also greater than 1,000 therefore; an additional inhalation toxicity study is not warranted based on the results of this scenario.

Table 4 8 Short and Intermediate term Post application Inhalation Exposures and MOEs for Adults and Children in Areas Treated With Air Deodorizers Value Parameter Adult Child Rationale House* Generic House ( 2 chambers: 35 m3 bedroom, 373 m3 other rooms) MCCEM default Activity Schedule* In bedroom at start of modeling, out after 8 hours EPA Assumption Concentration of product 0.199% OPP by weight Product label # 44446 67 Quantity in Can 168 g product Product label # 44446 67 Quantity Used per Day 1.15 g product ( 2.54x10 3 lb product) Based on rate of 1 can per 6,000 m3 for 30 days, and a bedroom size of 35 m3 Quantity ai Used per Day 5.06x10 6 lb ai/ day ( 2.30x10 3 g/ day) ( Quantity per day) * ( Concentration)

Concentration in Bedroom after spraying ( Initial Concentration in 6.56x10 5 g a. i./ m3 ( 65.6 µ g a. i./ m3) ( Quantity ai per day) / ( Bedroom volume) Page 31 of 60 Bedroom)*

Body Weight* 70 kg 15 kg Average body weights for adults and young children Inhalation Rate* 11.6 m3/ day 8.88 m3/ day Average resting rate for adults and young children ( USEPA, 1997)

MCCEM Outputs Dose 2.67x10 4 mg/ kg/ day 9.53x10 4 mg/ kg/ day MCCEM Output Inhalation short term MOE 370,000 100,000 NOAEL ( 100 mg/ kg/ day)/ Dose Inhalation intermediate term MOE ( day care facilities) NA 41,000 NOAEL ( 39 mg/ kg/ day)/ Dose Paints AD utilized EPA's Wall Paint Exposure Model ( WPEM) version 3.2 to estimate air concentrations resulting from the use of paint preserved with OPP. For this exposure assessment, WPEM default scenarios were used to determine exposure to adults ( RESADULT) and children ( RESCHILD). In these scenarios, an adult and child are located in a non painted part of the house while a bedroom is being painted by a professional painter. For a detailed description of the RESADULT and RESCHILD scenarios, see the WPEM User's Guide. Both the child and adult inhalation MOEs are above the target MOE of 100, but below a value of 1,000. Since the MOEs are below 1,000, the Agency may request that a confirmatory inhalation toxicity study be conducted.

Table 4 9 Short term Post application Inhalation ( vapor) Exposures and MOEs for Adult and Children in Areas Painted with Preserved Paint Exposed Individual 24 hr TWA ( mg/ m3) a Exposure Duration ( hrs/ day) Inhal. Rate ( m3/ hr) b Inhalation Dose ( mg/ kg/ day) c ST Inhal. MOEd Adult 0.98 24 0.5 0.168 600 Child 1.35 24 0.4 0.867 120 Foggers Post application inhalation exposures were assessed for entry into a room after a fogging application was conducted using MCCEM v1.2. Results are shown in the following Table 4 10. This table represents results for various exposure durations immediately after the fogging ( 0 hours) and 4 hours after starting treatment. All of the adult and child inhalation MOEs were above the target MOE of 100. All of the inhalation MOEs for children were below 1,000. In addition, ST vapor inhalation exposures to adults for a 0 hr REI and a 4 and 24 hour exposure duration along with the ST vapor inhalation exposure to adults for a 4 hr REI and 24 hour exposure duration were below 1,000. Therefore, the based on the results of these scenarios for which the calculated MOEs are Page 32 of 60 below 1,000, the Agency may request that a confirmatory inhalation toxicity study be conducted.

Table 4 10. Short term Post application Inhalation Exposures and MOEs for Adults and Children in Fogged Houses Re Entry Interval ( hrs) Exposure Duration ( hrs/ day) TWA Air Conc. ( mg/ m3) a Inhalation Rate ( m3/ hr) b Inhalation Dose ( mg/ kg/ day) c ST Inhal. MOEd Adults 2 5.25 0.5 0.075 1,300 4 4.45 0.5 0.127 790 0 24 1.43 0.5 0.245 410 2 2.56 0.5 0.037 2,700 4 2.17 0.5 0.062 1,600 4 24 0.695 0.5 0.119 840 Child 2 5.25 0.4 0.280 360 4 4.45 0.4 0.475 210 0 24 1.43 0.4 0.914 110 2 2.56 0.4 0.136 730 4 2.17 0.4 0.231 430 4 24 0.695 0.4 0.445 230 a Air concentrations calculated by MCCEM using inputs described in Table 4.11 of the Occupational and Residential Exposure chapter of this RED. Model provided air concentrations at 15 minute intervals. Starting after the REI, the TWA was calculated for each exposure time duration ( See Appendix B). b Inhalation rate is based on sedentary activity of adults and young children ( USEPA, 1997a) c Inhalation Dose = Exposure Duration x TWA x Inhalation Rate / Body Weight ( 70 kg for adults, 15 kg for children) d Short Term Inhalation MOE = Short Term Inhalation NOAEL ( 100 mg/ kg/ day) / Inhal. Dose 4.2 Dietary Exposure/ Risk for Antimicrobial Uses Dietary risk assessment incorporates both exposure and toxicity of a pesticide. A maximum acceptable dose at which there is no unreasonable adverse health effects is used for risk assessment. This dose is expressed as percent of the population adjusted dose ( PAD). The PAD is equivalent to Reference Dose ( RfD) divided by the special FQPA Safety Factor. Agency is concerned when the estimated dietary risks exceed 100% of PAD ( aPAD or cPAD). For OPP, an acute toxicological endpoint was not selected. Page 33 of 60 The Agency has addressed out the dietary exposure and risk assessment for OPP and its salts ( sodium and potassium). OPP and its sodium and potassium salts are used as disinfectants and sanitizers in the following scenarios:

  Counter tops   Tables   Refrigerators   Preservative in papermaking   Preservative in adhesive   Mushroom premises   Plastics, polymers The uses of these chemicals as antimicrobials in the scenarios shown above may result in pesticide residues in human food. These uses are considered indirect food uses.

The maximum rate of application for OPP in sanitizer end use solutions is 400 ppm as indicated in 40CFR 180.940. Label searches indicate at the end use level application rates are much higher than the limit Agency has set in the 40 CFR. Hence we have carried out the dietary assessment for all the scenarios listed above, except plastics and polymers. Table 4 11 summarizes the quantitative risks evaluated by AD for: disinfectant uses for counter tops, disinfectant use for dish washing, slimidice use for pulp and paper, paper coatings, and paper adhesives. For the remaining uses, either a quantitative assessment was not required or there is data gap as indicated in each subsection. ( For detailed calculations see Bob Quick's Memo on Indirect Food Contact Dietary Risk Assessment, 2006)

4.2.1 Mushroom Houses There are no EPA pesticide tolerances for residues of OPP and/ or NA OPP/ K OPP in mushrooms ( 40CFR 180.129). Mushrooms have not been classified into any crop groupings under 40 CFR 180.41. Search of USDA Pesticide Data Program ( PDP) for the monitoring data of years 2001, 2002 and 2003 showed residues of OPP on mushrooms up to 0.75 ppm level. 2001 data showed the presence of OPP residues in 63/ 184 samples ( 33%); 2003 data showed the presence of residues in 35/ 552 samples ( 6%). There is a definite decline in the presence of OPP. However, the highest residues were still at 0.75 ppm.

The presence of OPP/ NA OPP/ K OPP in mushrooms may be due to disinfection of non food contact surfaces in mushroom houses, or potentially from absorption of OPP by wood in the mushroom houses. The Agency recommends that a tolerance for indirect residues of OPP and its Salts in mushrooms under 40 CFR 180.129 subsection should be established.

4.2.2 Poultry Hatcheries, Poultry Laying Facilities, Greenhouse and Hydroponic Uses. Page 34 of 60 Label searches indicate that use of OPP products in poultry hatcheries appear to be non food use. No residues are expected. EPA Reg# 11725 7 indicates a registered use for poultry laying operation but it does not appear a sanitizer use. Measurable residues would not be expected to occur in the egg from this type of use.

4.2.3 Greenhouse and Hydroponic Uses For greenhouse and hydropnic uses there are label restrictions against applying to crop, soil or growing media in which a crop is grown. A potable rinse is recommended before treated surface contact crop or a substrate which is likely to contact crop. The Agency recommends a confirmatory data to show whether OPP residues are absorbed into treated surfaces and whether the potable water rinses eliminate the residues.

4.2.4 Polymers and Plastics Uses OPP is registered for use into polymers and plastics which are likely to contact food ( EPA Reg #: 464 126), applied at a rate of 0.1 to 0.5%. The Agency in its database does not have any information about a migration study on OPP migration into plastics and polymers. The Agency recommends a migration study should be conducted on migration of OPP to food from plastics and polymers.

4.2.5 Wood and Wood Product Use.

From the language of the label ( EPA Reg#: 464 126, at an application rate 1 3%) it is not clear if OPP migrates from pallets ( used to transfer fruits and vegetables) made of OPP treated wood migrates into fruits and vegetables. The Agency recommends that industry provide residue data to show how much OPP migrates from wood products into food.

4.2.6 Paper Adhesive Use FDA has provided a pre estimated residue value of 7 ppb for OPP when it is used as a paper adhesive in food packaging materials.

There is no acute dietary NOAEL, and hence the Agency has estimated the chronic dietary risks for use scenarios discussed above Estimated EDIs, DDD and % cPAD are provided in the Table 4 11.

Table 4 11 Cumulative Estimated Dietary Intake ( EDI)/ Daily Dietary Dose ( DDD) and % cPADs for OPP from INDIRECT Food uses Use Dietary Concentration ( ppb) Estimated Daily Intake ( µ g/ person/ day Daily Dietary Dose( mg/ kg/ day) % cPAD Counter top/ disinfectant 280 840 ( adult) 420 ( child) 0.012 ( adult) 0.056 ( child) 3.0 14 Page 35 of 60 Dishwashing/ disinfectant 91.5 274 ( adult) 137.5 ( child) 0.004 ( adult) 0.0092 ( child) 1.0 2.0 Paper slimicide use 1120 3360 ( adult) 1680 ( child) 0.048 ( adult) 0.017 ( child) 12.0 4.0 Paper Coating/ preservative 3200 9600 ( adult) 480 ( child) 0.014 ( adult) 0.032 ( child) 3.6 8.0 Paper Adhesive preservative 7 21 ( adult) 10.5 ( child) 0.0003 ( adult) 0.0007( child) 0.08 0.17 Cumulative 4978 14935 9adult) 3148 ( child) 0.090 ( adult) 0.17 ( child) 20 29 4.3 DIETARY EXPOSURE ASSESSMENT FOR CONVENTIONAL ( AGRICULTURAL) PESTICIDES.

Tolerances ( 40 CFR Part 180.129) were established for the residues of orthophenylphenol and its sodium salt ( FR Notice 27938, 1981 and its amendment FR Notice 32015, 1983). The tolerances were established for the fungicidal post harvest application of these chemicals: Raw agricultural commodities ( RAC) including: apple, cantaloupe, carrot, cherry, citrus, citron, cucumber, grapefruit, kiwifruit, kumquat, lemon, lime, nectarine, orange, bell pepper, peach, pear, pineapple, plum, prune, sweet potato, tangerine, tomato. The established tolerances vary from 125 ppm ( high end) on cantaloupe to 5 ppm ( cherry, nectarine) levels.

This part of the non cancer dietary risk assessment was carried out by OPP's Health Effects Division ( DP Barcode: D319639). It was conducted using the Dietary Exposure Evaluation Model ( DEEM FDIC   ) , Version 2.03 as well as Lifeline Model Version 3.0 which uses food consumption data from the USDA's Continuing Surveys of Food Intake by Individuals ( CSFII) from 1994 1996 and 1998. This assessment is tier 1, conservative ( assumes 100% crop treatment) and uses the deterministic approach. As input parameters for modeling analyses, residue level tolerances ( indicated above) were used as point estimates. The chronic analyses were below Agency's level of concern for the general US Population ( 7.1% of cPAD) and all other populations subgroups ( the most highly exposed being children 1 2 years old with a 24.6% of the cPAD)

Table 4 12 summarizes the Dietary Exposure and Risk for OPP/ NA OPP/ K OPP based on DEEM FCID   and Lifeline Model results.

Assumptions: 1) To the established pears and citrus tolerances ( 40 CFR 180.29), 1 ppm contribution by residues of OPP on mushrooms was added and DEEM FCID was run. 2) Reference dose RfD, Chronic = 0.39 mg/ kg/ day. There are no dietary concerns due to this additional exposure scenario. Page 36 of 60 Table 4 12 ===============================================================================

Total Exposure by Population Subgroup

Total Exposure   Population mg/ kg Percent of Subgroup body wt/ day Rfd    U. S. Population ( total) 0.027769 7.1%

U. S. Population ( spring season) 0.027756 7.1%

U. S. Population ( summer season) 0.025804 6.6%

U. S. Population ( autumn season) 0.027836 7.1%

U. S. Population ( winter season) 0.029815 7.6%

Northeast region 0.036468 9.4%

Midwest region 0.025900 6.6%

Southern region 0.023917 6.1%

Western region 0.028107 7.2%

Hispanics 0.036660 9.4%

Non hispanic whites 0.025299 6.5%

Non hispanic blacks 0.031023 8.0%

Non hisp/ non white/ non black 0.037770 9.7%

All infants (< 1 year) 0.037606 9.6%

Nursing infants 0.020614 5.3%

Non nursing infants 0.044057 11.3%

Children 1 6 yrs 0.077565 19.9%

Children 7 12 yrs 0.041654 10.7%

Females 13 19 ( not preg or nursing) 0.026256 6.7%

Females 20+ ( not preg or nursing) 0.019846 5.1%

Females 13 50 yrs 0.022823 5.9%

Females 13+ ( preg/ not nursing) 0.025276 6.5%

Females 13+ ( nursing) 0.025877 6.6%

Males 13 19 yrs 0.028211 7.2% Page 37 of 60 Table 4 13 Estimated Chronic Dietary Exposure and Risk from use of Na OPP as an inert ingredient.

Population Subgroup2 Generic Estimated Exposure1 ( mg/ kg/ day) OPP/ salts Estimated Exposure3 ( mg/ kg/ day) % cPAD U. S. Population ( total) 0.120 0.0012  0.006 0.31%  1.5% All infants (< 1 year) 0.245 0.0025  0.012 0.63%  3.1% Children ( 1 2 years) 0.422 0.0042  0.021 1.1%  5.4% Children ( 3 5 years) 0.310 0.0031  0.016 0.79%  4.0% Children ( 6 12 years) 0.174 0.0017  0.009 0.45%  2.2% Youth ( 13 19 years) 0.100 0.0010  0.005 0.26%  1.3%

Adults ( 20 49 years) 0.087 0.0008 7  0.004 0.22%  1.1%

Adults ( 50+ years) 0.086 0.0008 6  0.004 0.22%  1.1%

Females ( 13 49 years) 0.087 0.0008 7  0.004 0.22%  1.1% 1Exposure estimates are based on highest tolerance level residues of high use active ingredients for all food forms, including meat, milk, poultry, and eggs 2 Only representative population subgroups are shown 3 Generic exposures based on application rates of 1  5 lb ai/ acre were adjusted for the tolerance exemption limitation of 0.1% maximum formulation and maximum application rates ( 0.05 lb inert/ acre); the generic exposures were divided by a factor of 20 ( 1/ 0.05) and 100 ( 5/ 0.05) cPAD = 0.39 mg/ kg/ day 5.0 AGGREGATE RISK ASSESSMENT In order for a pesticide registration to continue, it must be shown " that there is reasonable certainty that no harm will result from aggregate exposure to pesticide chemical residue, including all anticipated dietary exposures and other exposures for which there are reliable information." Aggregate exposure is the total exposure to a single chemical ( or its residues) that may occur from dietary ( i. e., food and drinking water), residential, and other non occupational sources, and from all known or plausible exposure routes ( oral, dermal, and inhalation).

In performing aggregate exposure and risk assessments, the Office of Pesticide Programs has published guidance outlining the necessary steps to perform such assessments ( General Principles for Performing Aggregate Exposure and Risk Assessments, November 28, 2001; available at http:// www. epa. gov/ pesticides/ trac/ science/ aggregate. pdf). Steps for deciding whether to perform aggregate exposure and risk assessments are listed, which include: identification Page 38 of 60 of toxicological endpoints for each exposure route and duration; identification of potential exposures for each pathway ( food, water, and/ or residential); reconciliation of durations and pathways of exposure with durations and pathways of health effects; determination of which possible residential exposure scenarios are likely to occur together within a given time frame; determination of magnitude and duration of exposure for all exposure combinations; determination of the appropriate technique ( deterministic or probabilistic) for exposure assessment; and determination of the appropriate risk metric to estimate aggregate risk The short term dermal toxicity endpoint for OPP was based on skin irritation observed in a 21 day dermal toxicity study in rats. In comparison, the oral and inhalation endpoints are based on systemic effects from a developmental toxicity study in rats. Therefore, the short term dermal exposures were aggregated in a separate analysis from the shortterm inhalation and oral exposures. However, for intermediate term oral, dermal, and inhalation exposures, the same study and endpoint was used. Therefore, all intermediateterm exposures were aggregated together as appropriate.

The toxicological endpoints for OPP and OPP salts are assumed to be identical. The target MOEs for all routes of exposures for all durations is set at 100 for occupational and residential scenarios. Examination of product labels, showed that exposure to handlers can occur in a number of and residential environments. Post application exposures also occur in these settings.

5.1 Acute and Chronic Dietary Aggregate Risk In general, acute and chronic dietary aggregate risks are represented by dietary ( direct, indirect, and inert exposures) and drinking water exposures. As there is no acute dietary endpoint selected for OPP and drinking water exposure is not of concern, an acute aggregate dietary assessment is not performed for OPP. Exposure from direct food, indirect food, and inert uses for OPP have been assessed. Exposure from direct food and inert uses was conducted using the Dietary Exposure Evaluation Model software with the Food Commodity Intake Database ( DEEM FCIDJ), Version 2.00, which incorporates consumption data from USDA= s Continuing Surveys of Food Intakes by Individuals ( CSFII), 1994 1996 and 1998. Exposures from indirect food uses of OPP from counter top disinfectants, dishwashing disinfectants, paper slimicides, paper coatings, and paper adhesives were derived from FDA's methodology.

Results of indirect food use exposure are presented in Table 4 11 while results of direct food use exposure are presented in Table 4 12. Results of dietary exposure from the inert use of OPP are presented in Table 4 13. Total aggregate dietary exposure and risk is shown below in Table 5 1 for direct, indirect, and inert uses of OPP. The results indicate that for adults, 31.5% of the cPAD is occupied from all dietary exposure sources, while for children, 68.7% of the cPAd is occupied from all dietary sources. These percentages are below 100% of the cPAD and are thus not of concern to the Agency. Page 39 of 60 Table 5 1 Aggregate Dietary Exposures and Risks ( direct, indirect, and inert uses)

Direct Dietary Exposure ( mg/ kg/ day) Indirect Dietary Exposure ( mg/ kg/ day) Population Active Active Inert cumulative % cPAD Dose ( mg/ kg/ day) U. S. Population 0.027 0.090 0.006 31.5 Children 0.077 0.17 0.021 68.7 5.2 Short and Intermediate Term Aggregate Risk Short term aggregate exposures and risks were assessed for adults and children that could be exposed to OPP and OPP salt residues from the use of products in nonoccupational environments. The short term dermal toxicity endpoint ( NOAEL of 100 mg/ kg/ day from a 21 day dermal toxicity study) was based on skin irritation. In comparison, the short term oral and inhalation endpoints were based on systemic effects from the same study and toxic effect ( NOAEL of 100 mg/ kg/ day from developmental toxicity studies). Therefore, short term dermal exposures were aggregated in a separate analysis from the short term inhalation and oral exposures.

For OPP, the short term aggregate assessment includes average ( chronic) dietary exposure and estimated exposures from incidental oral and inhalation exposure that are believed to co occur. For short term aggregate risk to adults, the average dietary exposure was aggregated with short term oral and inhalation exposures that occur from mopping, wiping, and air deodorizer uses the short term incidental oral and inhalation residential exposures. Dermal aggregate risk is assessed separately as the study and endpoint used for risk assessment was different for this route of exposure.

Results of the short term dermal aggregate assessment are presented in Tables 5 2a and 5 2b. The results showed no aggregate risks of concern to adults applying OPP through wiping, mopping, or air deodorizing activities ( total MOE = 333) or to children from post application exposures ( MOE = 355).

Table 5 2a Short term Aggregate Exposure and Risk Assessment for Adults Exposure Routes Exposure ( mg/ kg/ day) Margin of Exposure Total MOE Dietary aggregate 0.123 317 Inhalation exposure  wiping  mopping  air deodorizer 0.0157 0.0043 0.0001 6,300 23,000 670,000 333 Page 40 of 60 Inhalation post app Air deodorozer 0.00026 370,000 a: Aggregate MOE = 1/( 1/ MOEdiet) + ( 1/ MOEwipe, app inhal) + ( 1/ MOEmop, app inhal) + ( 1/ MOEair deodorizer, app inhal) + ( 1/ MOEair deodorizer, post inhal))

Table 5 2b Short term Aggregate Exposure and Risk Assessment for Children Exposure Routes Exposure ( mg/ kg/ day) Margin of Exposure Total MOE Dietary aggregate 0.115 339 Oral exposure  mopping 0.0824 1200 Inhalation post app Air deodorozer 0.00095 105,000 355 a: Aggregate MOE = 1/( 1/ MOEdiet) + ( 1/ MOEmop, post app: oral) + ( 1/ MOEair deodorizer, post app: inhal))

Table 5 3 presents the results of short term dermal aggregate exposure and risk. For dermal aggregate exposures, there were no risks of concern to either adults or children.

Table 5 3 Short term Aggregate Dermal Exposures and Risks Exposure Routes Adults Children Exposure ( mg/ kg/ day) Margin of Exposure Exposure ( mg/ kg/ day) Margin of Exposure Wiping 0.672 150 0.674 150 mopping 0.129 780 N/ A Air deodorizer 0.0064 16,000 N/ A Pet product ( inert use) 0.00052 190,000 0.32 310 TOTAL MOE 0.807 141 0.99 111 a: Aggregate MOE = 1/(( 1/ MOEwipe) + ( 1/ MOEmop) + ( 1/ MOEair deodorizer))

Intermediate term aggregate risks ( children only) are presented in Table 5 4. The intermediate term toxicity endpoints for all of the routes of exposure ( oral, dermal and inhalation) are based on the same study and same toxic effect ( NOAEL of 39 mg/ kg/ day from a chronic/ carcinogenicity study); therefore, all intermediate term routes were aggregated together as appropriate. There are no intermediate term residential scenarios identified for adults. For children, intermediate term scenarios were identified for postapplication oral, inhalation, and dermal exposures from household cleaning. Page 41 of 60 Intermediate term aggregate risk ( children only) was calculated to be 247. This value are above the target MOE of 100 and is thus not of concern.

Table 5 4 Intermediate term Aggregate Exposure and Risks for Children Exposure Routes Exposure Margin of Exposure Dietary aggregate 0.115 339 Post app incidental oral from mopping 0.0057 6800 Post app dermal from mopping 0.0421 930 Incidental Oral pet product inert use 0.0039 10,000 Inhalation air deodorizer post app 0.00095 41,000 Total 0.167 247 a: Aggregate MOE = 1/( 1/ MOEdiet) + ( 1/ MOEinc. oral post app) + ( 1/ MOEdermal post app) + ( 1/ MOE inc. oral pet product) + ( 1/ MOE inhalation air deodorizer)

The exception to the above is for adult and child dermal post application exposures to textile OPP residues ( which alone are of concern to the Agency), and which were not included into the aggregate assessment as this would make aggregate risk of concern. This exposure scenario needs to be addressed in order to make exposure from this use of OPP not of concern.

6.0 CUMULATIVE RISK FQPA ( 1996) stipulates that when determining the safety of a pesticide chemical, EPA shall base its assessment of the risk posed by the chemical on, among other things, available information concerning the cumulative effects to human health that may result from dietary, residential, or other non occupational exposure to other substances that have a common mechanism of toxicity. The reason for consideration of other substances is due to the possibility that low level exposures to multiple chemical substances that cause a common toxic effect by a common mechanism could lead to the same adverse health effect as would a higher level of exposure to any of the other substances individually. A person exposed to a pesticide at a level that is considered safe may in fact experience harm if that person is also exposed to other substances that cause a common toxic effect by a mechanism common with that of the subject pesticide, even if the individual exposure levels to the other substances are also considered safe.

AD did not perform a cumulative risk assessment as part of this RED for OPP because AD has not yet initiated a review to determine if there are any other chemical substances that have a mechanism of toxicity common with that of OPP. For purposes of this RED, EPA has assumed that OPP does not have a common mechanism of toxicity with other substances. Page 42 of 60 On this basis, the Registrant must submit, upon EPA's request and according to a schedule determined by the Agency, such information as the Agency directs to be submitted in order to evaluate issues related to whether orthophenylphenol shares a common mechanism of toxicity with any other substance and, if so, whether any tolerances for OPP need to be modified or revoked. If AD identifies other substances that share a common mechanism of toxicity with OPP, AD will perform aggregate exposure assessments on each chemical, and will begin to conduct a cumulative risk assessment.

The Health Effects Division, Office of Pesticide Programs, has recently developed a framework proposed for conducting cumulative risk assessments on substances that have a common mechanism of toxicity. This guidance was issued for public comment on January 16, 2002 ( 67 FR 2210 2214) and is available from the OPP Website at: http:// www. epa. gov/ pesticides/ trac/ science/ cumulative_ guidance. pdf. In the guidance, it is stated that a cumulative risk assessment of substances that cause a common toxic effect by a common mechanism will not be conducted until an aggregate exposure assessment of each substance has been completed.

Before undertaking a cumulative risk assessment, AD will follow procedures for identifying chemicals that have a common mechanism of toxicity as set forth in the AGuidance for Identifying Pesticide Chemicals and Other Substances that Have a Common Mechanism of Toxicity@ ( 64 FR 5795 5796, February 5, 1999).

7.0 OCCUPATIONAL EXPOSURE AND RISK A complete explanation of the occupational exposure and risk assessment can be found in the supporting disciplinary chapter entitled Occupational and Residential Exposure Chapter for Orthophenylphenol & Orthophenylphenol Salts ( D320537). Summary information is provided in this section.

The occupational handler scenarios were assessed to determine dermal and inhalation exposures. The general assumptions and equations that were used to calculate occupational handler risks are provided in the section of the occupational and residential exposure chapter entitled Criteria for Conducting the Risk Assessment. The majority of the scenarios were assessed using CMA data and Equations. However, for the occupational scenarios in which CMA data were insufficient, other data and methods were applied.

For the majority of the occupational handler scenarios assessed, MOEs in the occupational setting were above the target MOE of 100 for dermal, inhalation and total exposures, except for the following scenarios:

  Agricultural premises, fogging: intermediate term PPE Total MOE = 98   Commercial/ Institutional premises, wiping: short term baseline dermal MOE= 74, intermediate term baseline dermal MOE = 68, and intermediate term baseline Total MOE = 64. Page 43 of 60   Medical premises, mopping: short term baseline dermal MOE= 93, intermediate term baseline dermal MOE = 84, and intermediate term baseline Total MOE = 78.   Materials Preservatives, liquid pour preservation of textiles: short term PPE dermal MOE= 92, intermediate term PPE dermal MOE = 83, and intermediate term Total MOE = 78.   Materials Preservatives, painter ( applying paint post preservation), airless sprayer: baseline dermal short term MOE = 66.   Using EPA's Wall Paint Exposure Model ( WPEM), an inhalation MOE of 43 was calculated for professional painters breathing the vapor of OPP.

All of the occupational inhalation MOEs were above the target MOE of 100, except for the following scenario:

Agricultural equipment, fogger IT inhalation MOE = 880 7.1 Occupational Post application Exposures Occupational post application exposures were assessed for inhalation from fogging use and dermal and inhalation from metalworking fluid use. In addition, the potential for inhalation exposures to the vapor of OPP may occur to bystanders as a result of material preservative applications in industrial settings. Currently, no data are available to assess these bystander exposures and therefore, monitoring data are needed.

7.1.1 Fogging Inhalation exposures were assessed for entry into a building which has gone through a fogging application; it is assumed that dermal post application exposure is negligible. The inhalation exposure assessment was conducted using the Multi Chamber Concentration and Exposure Model ( MCCEM v1.2). Based on the MCCEM . csv output, MOE values were calculated. Both the short term MOE ( 690) and the intermediate term MOE ( 270) were above the target MOE of 100 but below 1,000. Therefore, the Agency may request that a confirmatory inhalation toxicity study be submitted since the current inhalation endpoint is based on an oral toxicity study.

7.1.2 Metalworking Fluids: Machinist There is a potential for dermal and inhalation exposure when a worker handles treated metalworking fluids. This route of exposure occurs after the chemical has been incorporated into the metalworking fluid and a machinist is using/ handling this treated end product.

For dermal exposures, a short, intermediate, and long term exposure estimate were derived using the 2 hand immersion model from ChemSTEER. The dermal MOE value calculated is above the target MOE of 100 for intermediate and long term dermal exposures ( MOE = 290). However, there is concern with short term dermal exposure Page 44 of 60 because the calculated MOE of 54 is below the target MOE of 100. It should be noted that the short term end point is based on the dermal irritation and therefore, a higher film thickness value was used in comparison to the intermediate term and long term exposures.

For inhalation exposures, a screening level intermediate and long term inhalation exposure estimate for treated metalworking fluids has been developed using the OSHA PEL for oil mist. The inhalation MOE values for IT/ LT and ST exposures to OPP and OPP salts are all above the target MOE of 100 ( IT/ LT MOE = 3,600 and ST MOE = 9,300).

7.2 Wood Preservation OPP and OPP salts are used in products that are intended to preserve wood ( non pressure treated wood). As noted on label Reg # 67869 24, OPP Salt for wood preservation serves the purpose, " for the temporary protection of freshly sawn lumber against staining and molding. [ The product] are applied to the freshly sawn lumber by either dipping or spraying."

Handler and post application scenarios that have been identified for wood preservation were extracted from MRID 455243 04, " Measurement and Assessment of Dermal and Inhalation Exposures to Didecyl Dimethyl Ammonium Chloride ( DDAC) Used in the Protection of Cut Lumber ( Phase III)" ( Bestari et al., 1999). This proprietary study includes the potential ways that an individual can come into contact with preserved wood.

CMA unit exposure data were used to assess exposure to the composite wood blender/ spray operators. The liquid pump preservative unit exposures for gloved workers were used in this assessment. The dermal UE was 0.00629 mg/ lb ai and the inhalation UE was 0.000403 mg/ lb ai. These values are based on two replicates where the test subjects were wearing a single layer of clothing and chemical resistant gloves. The quantity of the wood being treated was derived from other wood preservative estimates for the amount of wood slurry treated because no chemical specific data were available for OPP.

Calculation of short, and intermediate term and IT total MOEs for the workers adding the preservative to the wood slurry showed that all of the MOEs were above the target MOE of 100 and therefore do not pose a concern. However, the IT inhalation MOE ( 840) for the blender/ spray operators adding the chemical via closed liquid pumping is less than 1,000 and therefore a confirmatory inhalation toxicity study is warranted based on these results.

For dip tank operators, the exposure assessment was conducted differently than for the other job functions. This was because concentrations of DDAC in the diptanks were known. Calculation of dermal and inhalation MOEs as well as total intermediate term MOEs showed that all were above the target MOE of 100. Page 45 of 60 CMA data were inadequate to represent the other job functions associated with preservation on non pressure treated wood ( e. g., chemical operators, trim saw operators, millwrights, cleanup crews, and construction workers). As very little chemical specific data were available regarding typical exposures to OPP as a wood preservative, surrogate data were used to estimate exposure and risks. Inhalation and dermal exposures associated with wood preservation were assessed using surrogate data from a study review Measurement and Assessment of Dermal and Inhalation Exposures to Didecyl Dimethyl Ammonium Chloride ( DDAC) Used in the Protection of Cut Lumber ( Phase III) ( Bestari et al., 1999). This study is proprietary; therefore, data compensation needs to be paid for use of the data in this exposure assessment. It was assumed that the workers at facilities using OPP and OPP salt preservatives are performing similar tasks as those monitored in the DDAC study.

Calculation of short and intermediate term dermal and inhalation MOEs for these other job functions ( chemical operators, trim saw operators, millwrights, cleanup crews, and construction workers) showed all MOEs above the target level of 100. In addition, the total intermediate term MOEs were also above the target level of 100 for the entire list of job functions.

7.3 Summary of Registered Conventional ( Agricultural) Uses 7.3.1 Occupational Handler Exposure Scenarios OPP and NA OPP are used as a conventional post harvest fungicide for citrus and pears. Application rates range from 0.0066 to 0.19 lb ai/ gallon solution ( 0.05 to 2%). Treatment rates range from 3,000 10,000 lbs fruit/ gallon of solution depending on the concentration of ai. For example, the RTU thermo fogging product has an application rate of 0.0633 lb ai/ 2200 lbs fruit. It is to be noted that in the absence of actual chemical specific data, the Agency utilizes data from the Pesticide Handler Exposure Database ( PHED), Version 1.1 to assess handler exposures. The potential exists for dermal and/ or inhalation exposure during the following occupational handler scenarios:

  M/ L liquid concentrate solutions for post harvest foaming, dipping, drenching, brushing, spraying treatments;   Loading RTU solutions for post harvest foaming, dipping, drenching, brushing, spraying treatments;   Loading RTU solution for thermo fogging post harvest treatment using an XEDA ® Electrofogger; significant dermal and inhalation exposures are not expected for thermo fogging applications   workers are not present within the storage rooms during the application process;   Application of solutions by foaming, dipping, drenching, brushing, spraying. Note: this scenario is not a typical " applicator" scenario. The assessment for automated application estimates exposures and risks ( inhalation exposure only   automated application process results in negligible dermal exposure) for workers in the vicinity of the application process. Page 46 of 60 A study designed to evaluate potential postapplication exposures of workers to NAOPP OPP during post harvest pear and citrus fruit handling activities was conducted by Dow Chemical to fulfill a portion of the data requirements requested by the Agency in a Data Call In ( DCI) in 1992. A protocol of the study was reviewed and comments and recommendations were made by HED ( Morris, 1993 . The submitted study ( MRID 43432901), completed in 1994, is titled " Evaluation of Postapplication Exposures to Sodium o Phenlyphenate Tetrahydrate/ o Phenylphenol to Workers During Post Harvest Activities at Pear and Citrus Fruit Packaging Facilities."

The study, mainly designed to evaluate postapplication activities ( i. e., sorters and packers), included area ( i. e., background) air monitoring data. It is assumed that this data captured NA OPP/ OPP air concentrations during the automated application process and will be used to quantitatively assess inhalation risk for process area workers during this process ( dermal exposure during the automated application process is considered negligible). It should be noted that the stated intention of the area monitoring was not for quantitative assessment of inhalation exposures during application. It was determined, however, that this data, although mostly collected in the sorting/ packing areas, provided a reasonable representation of inhalation exposure for workers in the vicinity of the operation during the application process.

With the use of chemical resistant gloves ( i. e., baseline/ gloves PPE), short term dermal risks are not of concern for handlers. Short term inhalation risks are not of concern at baseline PPE ( i. e., no respiratory protection). Intermediate/ long term dermal risks are not of concern when chemical resistant gloves are used and intermediate/ long term inhalation risks are not of concern at baseline PPE. Tables 7 1 and 7 2 below summarize the handler risk estimates.

Table 7 1 Short term Dermal and Inhalation Risks for OPP, and salts Handler Activities Short term Risk Dermal MOE ( Target MOE = 100) Inhalation MOE ( Target MOE = 100*) Exposure Scenario Crop Application Rate ( lb ai/ lb fruit) Baseline Baseline/ Gloves Baseline Mixing/ Loading & Loading Mixing/ loading EC/ SC for Automated Post harvest Applications Citrus & Pears 0.0000633 26 3300 64000 Loading RTU for Automated Postharvest Applications Citrus only 0.0000133 130 16000 300000 Loading RTU for Thermofogging applications Pears only 0.0000288 58 7300 140000 Automated Application Process Page 47 of 60 Citrus & Pears Activities during automated application ( i. e., operations monitoring) Citrus only NA Negligible 6100 Table 7 2 Intermediate/ Long term Dermal and Inhalation Risks for OPP, and salts Handler Activities Intermediate/ Long term Risk Dermal MOE ( Target MOE = 100) Inhalation MOE ( Target MOE = 100*) Exposure Scenario Crop Application Rate ( lb ai/ lb fruit) Baseline Baseline/ Gloves Baseline Mixing/ Loading & Loading Mixing/ loading EC/ SC for Automated Post harvest Applications Citrus & Pears 0.0000633 24 3000 25000 Loading RTU for Automated Postharvest Applications Citrus only 0.0000133 110 14000 120000 Loading RTU for Thermofogging applications Pears only 0.0000288 53 6700 55000 Automated Application Process Citrus & Pears Activities during automated application ( i. e., operations monitoring) Citrus only NA Negligible 2400 7.3.2 Occupational Postapplication Exposure and Risk Assessment In the case of NA OPP/ OPP post harvest commodity applications, workers performing sorting and packing activities are potentially exposed to NA OPP/ OPP following application. Additionally, potential dermal and inhalation exposures exist for storage room re entry workers following thermo fogging applications performing post treatment residue sampling and for workers transporting treated pears from the storage room to be processed and/ or distributed.

Although the label specifying use with the XEDA ® Electrofogger requires users to follow the machine's operator instructions, which, in turn, directs re entry workers to wear SCBA when oxygen levels are low, it is recommended that this provision be directly referenced on the label for workers re entering the storage room to collect residue samples or perform other early re entry activities. Page 48 of 60 It is recommended that sorters ( including pre sorters) and packers of citrus fruits and pears wear chemical resistant gloves with baseline PPE ( i. e., long sleeve shirt and pants). It was noted in the study that sorters/ packers typically wear short sleeve shirts, so chemical resistant gloves with arm extensions ( instead of a long sleeve shirt) may be more appropriate. The incident reports, OPP/ NA OPP's classifications as Category I and II acute dermal irritants, respectively, and the absence of acute toxicity data warrant use of this additional PPE. Currently, some labels require handlers to wear baseline PPE with chemical resistant gloves and goggles or a faceshield.

Table 7 3 below summarizes the postapplication risk estimates for citrus and pear facilities. Short term risk calculations are shown using both the arithmetic mean and maximum reported exposures; intermediate/ long term risks are calculated using the arithmetic mean only. Additionally, all dermal risk estimates are calculated with exposures adjusted for the maximum labeled application rate ( 2% solution).

Table 7 3 Postapplication Risk Estimates for Sorters and Packers in Citrus Fruit and Pear Facilities Short term Risk ( Target MOE = 100) Intermediate/ Long term Risk ( Target MOE = 100*)

Dermal MOE Inhalation MOE Dermal MOE Inhalation MOE Postapplication Activity Crop ( State)

Mean Max Mean Max Mean Mean Citrus ( FL) 240 150 20000 11000 220 7900 Pre sorting Citrus ( CA) 870 580 5900 2800 790 2300 Pears ( WA) 120 51 5800 3600 110 2200 Citrus ( FL) 770 550 28000 18000 700 11000 Sorting Citrus ( CA) 2200 880 72000 20000 2000 28000 Pears ( WA) 190 130 7300 5700 170 2800 Citrus ( FL) 1300 620 120000 100000 1100 47000 Packing Citrus ( CA) 5500 2400 81000 33000 5000 32000 8.0 ENVIRONMENTAL RISK 8.1 Ecological Hazard Page 49 of 60 2 phenylphenol and its salts demonstrate low toxicity to birds, and moderate toxicity to mammals, freshwater fish, freshwater invertebrates, and algae.

The low exposure potential from the indoor uses of 2 phenylphenol and salts, coupled with the tendency for the compounds to degrade under environmental conditions, result in low likelihood of adverse acute effects to wildlife and aquatic organisms from the indoor uses. Risk from the antisapstain used has been assessed on a screening level.

Laboratory studies indicate that 2 phenylphenol demonstrates some potential to act as an endocrine disruptor. When the appropriate screening and/ or testing protocols being considered under the Agency's Endocrine Disruptor Screening and Testing Advisory Committee ( EDSTAC)' s Endocrine Disruptor Screening Program ( EDSP) have been developed, 2 phenylphenol may be subjected to additional screening and/ or testing to better characterize effects related to endocrine disruption.

8.2 Environmental fate and Transport Orthophenylphenol is stable and persistent in abiotic aqueous medium at pHs 5, 7 and 9. When exposed to sunlight in neutral aqueous medium, it degrades with a half life of 14 days. Photolytically, therefore, it is not stable. Exposure to uv light ( at 253.7 nm), results in the degradation products: phenyl benzoquinone, phenylhydroquinone, and 2 hydroxy benzofuran. Its half life in air is 14 hours ( measured against the reaction with hydroxyl radical). OPP in its vapor form in the air is unstable and not persistent. It is immobile in soils with a KOC value of 10,000. Ground water contamination does not seem likely. The major degradation route appears to be through biodegradation in aerobic and anaerobic environments. The observed half life values vary from three hours to three week, depending on the exposure sites ( holding pond to open river etc.) When wood is treated for antisapstain use, NA OPP leaches up to 58% the first day after application ( highest application rate for NA OPP is 4%). After day 14, 86% of NA OPP leaches out from the treated wood.

8.3 Environmental Exposure and Risk Most uses of 2 phenylphenol are considered to be indoor uses. The discharge of any effluents which might contain 2 phenylphenol residues is regulated by the NPDES program; facilities discharging any such effluents are required to have an NPDES permit prior to discharging effluents into receiving waters. EPA/ ORD/ NRML's Treatability Database shows that wastewater treatment technologies have 95% removal efficiency for phenolic compounds. This, coupled with 2 phenylphenol's tendency to degrade under aerobic and anaerobic conditions in the environment, indicates that environmental exposure from the indoor uses of 2 phenylphenol is likely to be low.

Based on the results of the antisapstain modeling, runoff from antisapstain treating facilities will exceed acute high risk, restricted use, and endangered species LOCs for freshwater fish, freshwater invertebrates, and aquatic plants. Chronic risks cannot be assessed at this time due to a lack of chronic toxicity data. Page 50 of 60 The model used to estimate exposure from antisapstain uses is intended as a Tier I screening model, and, as such, has inherent assumptions and uncertainties that may result in over or under estimation of exposure levels. Since the model is only intended as a screening level model, further refinement of the model is recommended to more accurately assess risks from the antisapstain uses of 2 phenylphenol.

Methods to reduce the amount of 2 phenylphenol potentially released from antisapstaintreated wood could potentially mitigate the risks. Possible mitigation methods might include, but are not limited to, lowering the application rate or requiring specific storage conditions to prevent exposure of recently treated wood to weather ( e. g., full covering) and/ or prevent the release of any associated runoff into aquatic habitats ( e. g., drip pads). 2 phenylphenol is not very mobile in soils, so any 2 phenylphenol leached outdoors will likely bind to soils and not reach aquatic habitats as free 2 phenylphenol.

8.4 Endangered Species Consideration Section 7 of the Endangered Species Act, 16 U. S. C. Section 1536( a)( 2), requires all federal agencies to consult with the National Marine Fisheries Service ( NMFS) for marine and anadromous listed species, or the United States Fish and Wildlife Services ( FWS) for listed wildlife and freshwater organisms, if they are proposing an " action" that may affect listed species or their designated habitat. Each federal agency is required under the Act to insure that any action they authorize, fund, or carry out is not likely to jeopardize the continued existence of a listed species or result in the destruction or adverse modification of designated critical habitat. To jeopardize the continued existence of a listed species means " to engage in an action that reasonably would be expected, directly or indirectly, to reduce appreciably the likelihood of both the survival and recovery of a listed species in the wild by reducing the reproduction, numbers, or distribution of the species." 50 CFR. ' 402.02.

To facilitate compliance with the requirements of the Endangered Species Act subsection ( a)( 2) the Environmental Protection Agency, Office of Pesticide Programs has established procedures to evaluate whether a proposed registration action may directly or indirectly reduce appreciably the likelihood of both the survival and recovery of a listed species in the wild by reducing the reproduction, numbers, or distribution of any listed species ( U. S. EPA 2004). After the Agency= s screening level risk assessment is performed, if any of the Agency= s Listed Species LOC Criteria are exceeded for either direct or indirect effects, a determination is made to identify if any listed or candidate species may co occur in the area of the proposed pesticide use. If determined that listed or candidate species may be present in the proposed use areas, further biological assessment is undertaken. The extent to which listed species may be at risk then determines the need for the development of a more comprehensive consultation package as required by the Endangered Species Act.

For certain use categories, the Agency assumes there will be minimal environmental exposure, and only a minimal toxicity data set is required ( Overview of the Ecological Page 51 of 60 Risk Assessment Process in the Office of Pesticide Programs U. S. Environmental Protection Agency  Endangered and Threatened Species Effects Determinations, 1/ 23/ 04, Appendix A, Section IIB, pg. 81). Chemicals in these categories therefore do not undergo a full screening level risk assessment, and are considered to fall under a Ano effect@ determination. The active ingredient uses of 2 phenylphenol, with the exception of the antisapstain wood preservation use, fall into this category. Using Tier I screening modeling to assess potential exposure from antisapstain wood preservation uses of 2 phenylphenol, risks to Listed Species are indicated. Since the model is only intended as a screening level model, and, as such, has inherent uncertainties and limitations which may result in inaccurate exposure estimations, further refinement of the model is recommended before any regulatory action is taken regarding the antisapstain uses of 2 phenylphenol. Additionally, impacts from the antisapstain use could potentially be mitigated with precautions to prevent leaching and runoff when wood is stored outdoors ( see Label Hazard Statements/ Use Recommendations, below). Due to these circumstances, the Agency defers making a determination for the antisapstain uses of 2 phenylphenol until additional data and modeling refinements are available. At that time, the environmental exposure assessment of the antisapstain use of 2 phenylphenol will be revised, and the risks to Listed Species will be reconsidered.

9.0 INCIDENT REPORT ASSESSMENT OPP and its sodium and potassium salts are used fungicides and disinfectants. OPP is known to be a skin and mucous membrane irritant. NA OPP and K OPP are known for their corrosivity. We have used two approaches to determine the potential health effects of incidences on humans by OPP, NA OPP and K OPP. 1) Gather and analyze the incidence reports obtained from different sources; 2) A Literature search of chronic health effects associated with OPP/ NA OPP/ K OPP exposure, including results from epidemiological studies, if any.

The Following databases were consulted for poisoning incidence data on OPP: 1) Office of Pesticides Programs ( OPP) Incident Data System ( IDS) 2) Poison Control Centers 3) California Department of Pesticide Regulations 4) National Pesticide Telecommunications Network ( NTPT) 5) Published Scientific Literature on Incidences 9.1 OPP's Incident Data System ( IDS)