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Phenol RED Document Prepared for: Office of Pesticide Programs Antimicrobials Division U. S. Environmental Protection Agency 1801 South Bell Street Arlington, VA 22202 TABLE OF CONTENTS 1.0 EXECUTIVE SUMMARY . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1 2.0 PHYSICAL/ CHEMICAL PROPERTIES CHARACTERIZATION . . . . . . . . . . . . 8 2.1 Chemical Identification . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8 2.2 Physical/ Chemical Properties . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8 3.0 HAZARD CHARACTERIZATION . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10 3.1 Hazard Profile . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10 3.2 FQPA Considerations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 25 3.3 Dose Response Assessment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 27 3.4 Endocrine Disruption . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 28 4.0 EXPOSURE ASSESSMENT AND CHARACTERIZATION . . . . . . . . . . . . . . . . . 29 4.1 Summary of Registered Uses . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 29 4.2 Dietary Exposure/ Risk Pathway . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 29 4.2.1 Methodology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 30 4.2.2 Acute Dietary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 30 4.2.3 Chronic Dietary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 30 4.3 Water Exposure/ Risk Pathway . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 31 4.4 Residential Exposure/ Risk Pathway . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 33 4.4.1 Residential Handler Scenarios . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 33 <IP_ADDRESS> Paint Exposures and Risks . . . . . . . . . . . . . . . . . . . . . . . 33 <IP_ADDRESS> Disinfectant/ Deodorizing Spray and Towlette Exposures and Risks . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 34 4.4.2 Residential Postapplication Exposure . . . . . . . . . . . . . . . 37 5.0 AGGREGATE RISK ASSESSMENTS AND RISK CHARACTERIZATIONS . . 38 5.1 Acute and Chronic Oral Risk . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 38 5.2 Short, Intermediate, and Long Term Dermal Risk . . . . . . . . . . . . . . . . . . . . . 38 5.2 Short, Intermediate, and Long Term Inhalation Risk . . . . . . . . . . . . . . . . . . . 39 6.0 OCCUPATIONAL EXPOSURE . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 44 6.1Occupational Handlers.................................................................................................. 44 6.2 Occupational Postapplication................................................................................. 48 7.0 ENVIRONMENTAL FATE ASSESSMENT . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 48 8.0 ECOTOXICOLOGY ASSESSMENTS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 49 8.1 Terrestrial Animals . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 49 8.2 Freshwater Fish . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 49 8.3 Freshwater Invertebrates . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 51 8.4 Estuarine and Marine Organisms . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 53 8.5 Plants . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 53 9.0 REFERENCES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 54 LIST OF TABLES Table 2.1. Chemical Identification . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Table 2.2. Physical/ Chemical Properties . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Table 2.2 Physical/ Chemical . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Table 3.1. Acute Toxicity of Phenol and Phenol salts . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Table 3.2. Toxicity Profile of Phenol/ Sodium Phenate . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Table 3.3 Summary of Toxicological Doses and Endpoints for Phenol/ Sodium phenate for Use in Human Risk Assessment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Table 4.1. EPA Registration Numbers for Phenol Products . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Table 4.2. Summary of Dietary Exposure and Risk for Phenol . . . . . . . . . . . . . . . . . . . . . . . . . . Table 4.3. Calculation of Dermal and Inhalation MOE for Residential Handlers . . . . . . . . . . . . . Table 4.4. Short and Intermediate term Risks Associated with Postapplication Exposure to Disinfectant on Carpets . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Table 5.1 Short and/ or intermediate term aggregate oral/ dermal risk. . . . . . . . . . . . . . . . . . . . . . Table 5.2 Short and/ or intermediate term aggregate inhalation risk. . . . . . . . . . . . . . . . . . . . . . . Table 6.1. Calculation of Dermal and Inhalation MOE for Commercial/ Institutional Scenarios . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Table 8.1. Acute Toxicity of Phenol to Freshwater Fish . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Table 8.2. Acute Toxicity of Phenol to Freshwater Invertebrates . . . . . . . . . . . . . . . . . . . . . . . . . Table 8.3. Acute Toxicity of Phenol to Marine/ Estuarine Invertebrates . . . . . . . . . . . . . . . . . . . . Table 8.4. Chronic Toxicity of Phenol to Marine/ Estuarine Invertebrates . . . . . . . . . . . . . . . . . . Page 1 of 57 1.0 EXECUTIVE SUMMARY Phenol ( hydroxybenzene, carbolic acid, phenyl hydroxide) and sodium phenate, is registered with the Office of Pesticides Programs ( OPP) as an active ingredient and used as an intermediate in the production of epoxy resins and various other products, as a general disinfectant, and in medicinal preparations. It is used to control Animal Pathogenic Bacteria ( Gand G+ Vegetative), Pseudomonas SPP., Mycobacterium SPP. ( Tubercle Bacilli), Animal Pathogenic Fungi, Hydrophilic Viruses, Poliovirus Type 1, Parvovirus, Lipophilic Viruses, Vaccinia Virus, Influenza A2 ( Hong Kong, Japan, Japan 305/ 57 Asian Strain), HIV I ( Human Immunodeficiency Virus), and mold/ mildew.

Formulated as a pressurized and ready to use liquid, phenol is registered for use as a sanitizer, bacteriostat, fungicide/ fungistat, tuberculocide, disinfectant, and virucide ( EPA Reg. No. 707 159). Phenol has a number of use sites including indoor food uses in eating establishments on equipment and utensils, non food indoor uses in commercial transportation facilities, institutional/ industrial floors, industrial premises/ equipment, laundry equipment, paints, latex, and specialty industrial products. Indoor residential uses of phenol encompass the bathroom premises, hard surfaces, diaper pails, dogs/ canines, household/ domestic dwellings, and solid waste containers ( garbage cans). Phenol also has indoor, medical uses on surgical instruments and pacemakers ( critical items), catheters and inhalation equipment ( semi critical items), bedpans and furniture ( noncritical items), non conductive floors, critical premises ( burn wards), noncritical premises, patient premises, and institution premises ( human/ veterinary). Phenol is also found in over the counter drugs for the treatment of various conditions, including insect bites, poison ivy, diaper rash, antiseptics, and acne ( 21 CFR § 310.531 and § 310.545). Concentrations in these formulations range from 1.6 8.2%.

Phenol is produced through both natural and anthropogenic processes. It is naturally occurring in some foods, in human and animal wastes, and in decomposing organic material, and it is produced endogenously in the gut from the metabolism of aromatic amino acids. Phenol has been isolated from coal tar, but is now synthetically manufactured. Currently, the largest use of phenol is as an intermediate in the production of phenolic resins, which are used in the plywood, adhesive, construction, automotive, and appliance industries. Production and use of phenol and its products, especially phenolic resins and caprolactam, exhaust gases, residential wood burning and cigarette smoke are potential sources.

Hazard: Phenol has a moderate order of acute toxicity via the oral and dermal routes of exposure ( Toxicity Category II or III) and produces severe and marked irritation to the eyes and skin ( Toxicity Category I or II). Phenol concentrations used in acute inhalation studies failed to induce mortality in the study animals; therefore, toxicity endpoints and a toxicity category could not be established.

In the subchronic database, oral range finding studies in both the rat and the mouse were completed. Although the studies were non guideline ( due to the lack of subchronic parameters), Page 2 of 57 systemic toxicities were noted at 10,000 ppm in the rat and mouse, based on a decrease in mean body weight gain. In a two week inhalation study, rats had elevated plasma Mg2+ levels ( Hypermagnesaemia) and exhibited toxic effects in the central nervous system ( CNS).

Phenol was administered in two developmental guideline studies in the rat and mouse at concentrations of 30, 60, or 120 mg/ kg/ day and 70, 140, or 280 mg/ kg/ day, respectively. There was no evidence of toxicity in these animals at concentrations below the high dose. Fetal body weight was significantly reduced at 120 ( rat) and 280 ( mouse) mg/ kg/ day. Additionally, female mice experienced increased mortality and clinical signs of CNS toxicity ( tremors, ataxia, lethargy) at the high dose ( 280 mg/ kg/ day). The NOAEL was determined to be 60 mg/ kg/ day.

In a two generation reproductive study in rats exposed to 200, 1,000, or 5,000 ppm phenol in drinking water for 10 weeks/ generation, there were decreases in water and food consumption, body weight and body weight gain at the high dose ( potential reduced palatability). Offspring toxic effects including decreases in body weight and litter survival were observed at 5,000 ppm. This occurred concurrently with maternal toxicity ( decreased maternal body weight); believed to be secondary to the animals' aversion to the flavor of the phenol treated water and resulted in decreased maternal as well as offspring body weight. In a non guideline reproductive study ( Bishop, et al. 1997), phenol was administered to mice at a concentration of 350 mg/ kg. There were no treatment related clinical signs or mortality observed in maternal, reproductive, and developmental parameters and the lowest observable adverse effects level ( LOAEL) was not established ( highest dose tested, 350 mg/ kg).

Two carcinogenicity studies performed by the National Cancer Institute did not report an increased incidence of neoplasms in male and female mice or rats following administration of phenol, with the exception of a statistically significant increase in the occurrence of leukemia, lymphoma, or interstitial cell tumors in low dose male rats. Due to the lack of significant tumors in high dose males and the absence of significant neoplasms in mice and female rats, phenol was found to be non carcinogenic in the 2 year drinking water studies. Although phenol treated rats and mice experienced a decrease in mean body weight and body weight gain, the reduction was not significantly different from the respective controls and chronic toxicity was not observed at phenol concentrations up to 5,000 ppm. A 20 week dermal study exhibited effects of chronic irritation and hair growth inhibition with administration of 3 mg phenol ( in 200 uL acetone). A single papilloma was found 7 weeks into the study, but there was no evidence that it was significantly increased or treatment related. In a special, mechanistic study, there was no evidence of tumor initiation or hepatocyte GSH depletion following administration of 100 mg/ kg/ day phenol. Phenol is classified as a Group D carcinogen; there is inadequate or no human or animal evidence of carcinogenicity.

The results of the mutagenicity studies indicated that phenol was not mutagenic in Salmonella typhimurium or Drosophila melanogaster and did not induce micronuclei or bone marrow chromosomal aberrations in mice. However, mutagenic effects were observed in Chinese Hamster Ovary cells and spermatocytes in mice and HL60 cells. The genotoxic potential of Page 3 of 57 phenol appears to depend on the competing processes of activation to a genotoxic form and metabolic inactivation ( e. g., via conjugation). Phenol tended to be negative in bacterial gene mutation assays, but was positive or equivocal in mammalian cell gene mutation assays. Phenol tended to induce micronuclei in mice when administered intraperitoneally, but was negative ( or positive only at very high doses) when administered orally. This difference is likely due to the first pass conjugation and inactivation of orally administered phenol. Phenol was also positive in in vitro micronucleus tests with human lymphocytes and Chinese Hamster Ovary cells. Results from DNA damage assays are inconsistent, but they tend to show that phenol can cause sister chromatid exchanges or cell transformation if it is not metabolically inactivated. Overall, phenol did not exhibit strong mutagenic effects.

The Antimicrobial Division Toxicolgy Endpoint Selection Committee ( ADTC) committee noted neurotoxic signs from acute dermal toxicity studies ( Brown, et al., 1975  convulsions; OTS 0515567 tremors; Conning, et al., 1970  stimulation of motor nerve endings or spinal motor centers) and from a 15 day inhalation study ( tilting plane results showed an effect in treated rats). As noted in the Intergrated Risk Information System ( IRIS) Toxicological profile, numerous CNS effects have been observed following phenol dosing. Tremors were observed in one animal that later died ( apparently of dehydration) following dosing in drinking water ( ClinTrials BioResearch, 1998). Tremors have also been observed in several gavage studies in rats and mice ( 43735402; Dow Chemical Co., 1994; Moser et al., 1995). However, in a specialized 13 week neurotoxicity study in male and female rats that included a Functional Observational Battery Study ( FOB) and a detailed neurohistopathology evaluation ( ClinTrials BioResearch, 1998), the only observed nervous system effects were tremors in one animal and decreased motor activity in females. A short term gavage screening study ( Moser, et al., 1995) found that the only effect in an FOB was a marginal decrease in motor activity and increased rearing post exposure. Part of this could be attributed to the dehydration observed in the study.

Toxicity Endpoints: The toxicity endpoints used in this document to assess potential risks include the chronic dietary reference dose ( RfD), and short, intermediate and/ or long term incidental oral, dermal, and inhalation doses. The endpoints selected were reviewed by the ADTC in 2004.

Dietary Endpoints: On March 9, 2004, the ADTC reviewed the available toxicology data for phenol and discussed endpoint selection for use as appropriate in occupational/ residential exposure risk assessments. The ATDC determined that for acute dietary risk, there was no appropriate endpoint for assessment. The conclusion was based upon examination of the hazard data which might be used in support of such an endpoint. Body weight effects observed are not believed to be the result of a single exposure, and there were no other effects from the data that were considered reflective of an adverse effect from a single exposure. An acute RfD value was not selected.

For chronic dietary risk, the ATDC cited the published chronic RfD value in EPA's Integrated Risk Information System ( IRIS) database. This RFD value is based upon an Page 4 of 57 unpublished developmental toxicity study conducted according to GLP guidelines ( Argus Research Laboratories, 1977). The chronic RfD value was determined to be 0.6 mg/ kg/ day. The ATDC determined that a special hazard based safety factor was not required for phenol and could be reduced to 1x.

Based on Agency policy, a RfD modified by a FQPA safety factor is a population adjusted dose ( PAD). The chronic RfD value was calculated to be 0.6 mg/ kg/ day, based on a maternal No Obsevable Adverse Effects Level ( NOAEL) value of 60 mg/ kg/ day and an uncertainty factor of 100 ( 10x interspecies extrapolation, 10x intraspecies variation). The Agency calculated a chronic PAD to be 0.6 mg/ kg/ day.

Dermal Endpoints: The maternal toxicity NOAEL of 60 mg/ kg/ day was selected for shortand intermediate term dermal risk assessments from a developmental toxicity study in rats ( Argus, 1997) based on decreased body weight gain at the LOAEL of 120 mg/ kg/ day. A dermal absorption factor of 50% is used since an oral endpoint was selected. A target margin of exposure ( MOE) of 100 was selected for the dermal risk assessment, based on 10x for differences among humans ( intra species variability) and 10x for differences between the test animals and humans ( inter species extrapolation).

Inhalation Endpoints: The endpoint used for inhalation risk assessment is a LOAEL of 0.1 mg/ L ( 26 mg/ kg/ day) from a published inhalation toxicity study ( Dalin and Kristoffersson ( 1974) ) based on alterations in sliding angle from tilting plane test, and significant increases in liver enzymes. An uncertainty factor of 300 is applied to this risk assessment for short and intermediate term risk assessments ( 10x interspecies extrapolation, 10x intraspecies variation, 3x for use of a LOAEL). For long term risk assessments, an uncertainty factor of 1,000 is applied to the risk assessment ( 10x interspecies extrapolation, 10x intraspecies variation, 3x for use of a LOAEL, 3x for lack of a long term study).

FQPA Safety Factor: The ATDC determined that a special hazard based safety factor was not required for phenol and could be reduced to 1x.

Dietary Exposure: The Agency has conducted a dietary exposure and risk assessment for use of phenol in a ready to use disinfecting solution. A counter top that is treated with this product may come into contact with food, which in turn may be ingested. An acute RfD/ PAD value was not selected, thus the acute dietary risk was not evaluated. For chronic dietary exposure, children had the highest percentage of the chronic PAD, at 36%. For adult males and females, the dietary exposure is 9.0% and 7.5%, respectively, which is below the Agency's level of concern ( 100% of the cPAD).

Water Exposure and Risk: Phenol's use in the production of resins and other manufacturing industries and as a general disinfectant allows for the possibility of ground and surface water contamination. Despite phenol's high water solubility and poor sorption to soil, Page 5 of 57 biodegradation of phenol is sufficiently rapid so that the probability of groundwater contamination will be low. Because phenol absorbs light in the region of 290 330 nm, phenol might photodegrade directly in surface water. Phenol is not expected to absorb to sediment in the water column.

Residential Exposure and Risk: Phenols and salts are formulated as a soluble concentrate, towelette, ready to use solution an aerosol spray. Based on product labels, all formulations are liquid. The following scenarios were considered for residential handlers of phenol containing products: ( 1) application of paint treated with a material preservative using paintbrush/ roller and airless sprayer, ( 2) use of disinfectant/ deodorizing spray on hard non porous surfaces, and ( 3) use of disinfectant towelette on hard non porous surfaces. Inhalation and dermal exposures were addressed for residential populations using surrogate data from the Chemical Manufacturers Association ( CMA, 1992), and several studies which relate to the use patterns of phenol. Using surrogate unit exposure data, application rates from labels, and EPA estimates of daily amount handled, exposure and risks to handlers and postapplication scenarios were assessed. At this time, EPA does not have available chemical specific handler or postapplication exposure studies that meet Agency guidelines.

The calculated inhalation MOEs for the painting scenarios resulting from aerosol inhalation is above the target of 300 for roller/ brush ( 6500) and slightly below ( 290) for the airless sprayer. However, for inhalation exposure to vapors resulting from painting, the MOE exceeds the Agency's level of concern ( 27). This is considered to be conservative given that the exposure value used represents the highest 24 hour inhalation dose. Inhalation MOEs for the use of the disinfectant on hard surfaces do not exceed the Agency's level of concern.

The calculated dermal MOEs for the following scenarios were below the target MOE of 100, and are therefore of concern: painting using a paintbrush/ roller ( MOE = 31) and painting using an airless sprayer ( MOE = 12). The use of phenol for hard surface disinfection did not exceed the Agency's level of concern.

Residential postapplication exposures ( adults and children) are expected to be minimal because the majority of exposure is expected occur through contact with dry surfaces ( e. g. paints) and the end use products are expected to be diluted. The residential post application scenario considered in this assessment is exposure to residue from carpets that have been machine cleaned with a product containing phenol ( and phenol salts). The residential post application exposures result from the dermal and incidental oral routes of exposure to toddlers from residue on carpets that have been machine cleaned with a product containing phenol ( and phenol salts). While the label also indicates that the product may be sprayed directly onto carpets, this scenario was not evaluated due to lack of data regarding application rates. However, it is believed that the carpet shampoo represents the high end of the exposures to toddlers on carpets. Calculated dermal and incidental oral MOEs for toddlers crawling on carpet and incidental oral ingestion are above the level of concern ( MOEs of 21,000 and 86,000 respectively). Postapplication inhalation exposures were also evaluated for the paint and carpet scenarios and found not to exceed the Agency's level Page 6 of 57 of concern.

Aggregate Exposure and Risk: In order for a pesticide registration to continue, it must be shown that the use does not result in " unreasonable adverse effects on the environment". Section 2 ( bb) of FIFRA defines this term to include " a human dietary risk from residues that result from a use of a pesticide in or on any food inconsistent with standard under section 408..." of FFDCA. Consequently, even though no pesticide tolerances have been established for phenol, the standards of FQPA must still be met, including " 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). Aggregate risk assessments were conducted for acute ( 1 day), short term ( 1 30 days), intermediate term ( 1 6 months) and chronic ( several months to lifetime) exposures.

Acute/ Chronic Aggregate Risk: The acute and chronic aggregate risk assessments generally include both dietary and drinking water exposures. Drinking water exposure is not expected from the indoor uses of phenol and phenol salts; thus, drinking water exposure is not assessed in this document.

The ADTC determined that for acute dietary risk, there was no appropriate endpoint for assessment of acute dietary exposure. As a result, acute dietary risk estimates were not calculated.

Cumulative chronic dietary risk estimates from indirect food uses ( i. e., exposure to disinfectant solutions and room deodorizers) were calculated to be 36% for children, 9.0% for adult females, and 7.5% for adult males, indicating no risk of concern from dietary exposure For children, dietary exposure was aggregated with dermal exposure and incidental exposure from use of phenol cleaning products on carpet. The aggregate Margin of Exposure was found to be acceptable ( aggregate MOE of 273, acceptable MOE of 100).

Short and Intermediate Term Aggregate Risk: In accordance with the policy of the Office of Pesticide Programs, short, intermediate, and long term aggregate risk typically includes dietary exposures ( food and water) and residential exposures that can be thought of as occurring together. For homeowner residential scenarios, exposures are interpreted as only short or intermediate term; exposures are not felt to be long term.

Based on the above, for adults, chronic dietary exposure is aggregated with the dermal exposure from one cleaning scenario. ( The painting scenario was not chosen to aggregate since the dermal MOEs for both the airless sprayer and brush/ roller already exceed the Agency's level of concern for handlers ( i. e., Page 7 of 57 an individual who paints his/ her house). For toddlers, aggregate exposure would involve dietary exposure and dermal plus incidental oral exposures to treated carpets.

Occupational Exposure and Risk: Six commercial/ institutional premises scenarios have been considered in this assessment: ( 1) use as a material perservative as a liquid pour, ( 2) use of disinfectant solutions in hemodialysis machines, ( 3) application of paint treated with a material preservative using airless sprayer, ( 4) application of paint treated with a material preservative using paintbrush/ roller, ( 5) use of disinfectant/ deodorizing spray on hard non porous surfaces, and ( 6) use of disinfectant towelette on hard non porous surfaces.

The calculated dermal MOEs for the following scenarios are below the target MOE of 100, and are therefore of concern: ( 1) painting using an airless sprayer ( MOE= 21), and ( 2) wiping hard surfaces using a towelette ( MOE= 70).

The calculated inhalation MOE for use of an airless sprayer in painting ( MOE= 88) was below the target MOE for short and intermediate term exposure ( Target MOE = 300). The MOEs for inhalation exposure to vapors also exceed the Agency's level of concern.

Ecotoxicity: Phenol is not expected to bioaccumulate in plants, even though plants readily absorb phenol, because of the high respiratory decomposition rate of phenol to CO 2. Phenol does not pose concerns to aquatic organisms due to the low BCF and the rapid biodegradation in water. Page 8 of 57 2.0 PHYSICAL/ CHEMICAL PROPERTIES CHARACTERIZATION 2.1 Chemical Identification Chemical identification parameters, including chemical and common/ trade names, chemical family, CAS Number, and molecular formula are provided in Table 2.1.

Table 2.1. Chemical Identification Parameter Phenol Phenol salt ( Sodium phenate)

Synonyms Carbolic Acid; Hydroxybenzene Sodium Phenolate; Phenol, Sodium Salt Common/ Trade Names Phenol; Cabolic Acid Sodium Phenate; Permicide; Sporicidin Chemical Family Phenols Phenols CAS Number 108 95 2 139 02 6 Molecular Formula C6H6O C6H6ONa 2.2 Physical/ Chemical Properties The physical and chemical properties of the Technical Grade Active Ingredient ( TGAI) of phenol and phenol salts are shown in Table 2.2.

Table 2.2. Physical/ Chemical Properties Parameter Phenol Phenol Salt ( Sodium phenate)

Molecular Weight 94.11 116.10 Color Colorless to light pink White to reddish Physical State Crystalline solid Crystalline needles or rods Specific gravity 1.07 at 20oC Not Found Acid Dissociation Constant ( pKa) 9.9 at 25

C Not Found Dissociation Constant in water ( Ka) 1.28 x 10 10 Not Found pH Mildly acidic Alkaline in aqueous solutions Stability Stable at normal conditions Stable at normal conditions Melting point 43.0

C 40.9

C ( ultra pure material) Not Found Boiling point 181.8

C at 760 mm Hg Not Found Water Solubility 67 g/ L in water at 16

C Highly soluble in water Log KOW 1.46 at 25oC Not Found Table 2.2. Physical/ Chemical Properties Parameter Phenol Phenol Salt ( Sodium phenate)

Page 9 of 57 Vapor Pressure ° 0.341 mm Hg at 25

C ° 2.48 mm Hg at 50

C ° 41.3 mm Hg at 100

C Not Found Relative Vapor Density ( air = 1) 3.24 Not Found Saturation concentration in air 0.77 g/ m3 at 20

C Not Found Page 10 of 57 3.0 HAZARD CHARACTERIZATION A detailed hazard assessment for phenol and phenol salts is included in the appendix of this report. Generally, phenol and phenol salts are readily absorbed by the inhalation, oral, and dermal routes. The portal of entry metabolism for the inhalation and oral routes appears to be extensive and involves sulfate and glucuronide conjugation and, to a lesser extent, oxidation. Once absorbed, phenol is widely distributed in the body, although the levels in the lung, liver, and kidney are often reported as being higher than in other tissues ( on a per gram tissue basis). Elimination from the body is rapid, primarily as sulfate and glucuronide conjugates in the urine, regardless of the route of administration. Phenol does not appear to accumulate significantly in the body.

3.1 Hazard Profile Acute Toxicity. The acute toxicity database for phenol technical is considered complete. No additional studies are required at this time. Phenol has a moderate order of acute toxicity via the oral and dermal routes of exposure ( Toxicity Category II or III) and produces severe and marked irritation to the eyes and skin ( Toxicity Category I or II). Phenol concentrations used in acute inhalation studies failed to induce mortality in the study animals; therefore, toxicity endpoints and a toxicity category could not be established. The acute toxicity data for phenol are summarized in Table 3.1.

Subchronic Toxicity. In the subchronic database, oral range finding studies in both the rat and the mouse were completed. Although the studies were non guideline ( due to the lack of subchronic parameters), systemic toxicities were noted at 10,000 ppm in the rat and mouse, based on a decrease in mean body weight gain. In a two week inhalation study, rats had elevated plasma Mg2+ levels ( Hypermagnesaemia) and exhibited toxic effects in the central nervous system.

Developmental Toxicity. The toxicity profile for phenol presented several developmental and reproductive toxicity studies found in the open literature. These studies are also referred to in the IRIS update. In addition, the National Toxicology Program conducted developmental toxicity studies in both rats and mice. The ADTC considered the NTP studies to be acceptable for regulatory purposes. Published reports by Kavlock ( 1990) and Bishop ( 1997) were considered unacceptable for purposes of determining the developmental toxicity of phenol, based on study design.

In the NTP rat developmental toxicity study ( MRID # 43735402), phenol ( in distilled water) was administered to groups of 23 rats/ dose via gavage at dose levels of 0, 30, 60, or 120 mg/ kg/ day from gestation days ( GD) 6 to 15. No significant maternal toxicity was observed up to the high dose of 120 mg/ kg/ day tested in this study. In offspring, the only effect noted was a significant decrease in mean fetal body weight, but no teratogenic effects were observed. Therefore, the maternal toxicity LOAEL is greater than 120 mg/ kg/ day and the developmental toxicity LOAEL is 120 mg/ kg/ day. The maternal NOAEL is 60 mg/ kg/ day.

In the NTP mouse developmental toxicity study ( MRID # 43735401), phenol was administered in distilled water to groups of 31 36 mice/ dose by gavage at dose levels of 0, 70, 140, or 280 Page 11 of 57 mg/ kg/ day from gestation days ( GD) 6 to 15. Clinical signs of toxicity were observed in maternal animals at a dose of 280 mg/ kg/ day, which included signs of neurotoxicity ( tremors, ataxia, lethargy). In addition, maternal body weight was decreased during the treatment period ( 31% decrease) and entire gestation period ( 28% decrease). Offspring in the 280 mg/ kg/ day dose group experienced an increase in cleft palate in 8 of 214 fetuses ( 3 litters), but this increase was not statistically significant. The fetuses, male and female combined, exhibited reduced mean fetal weights. The high dose ( 280 mg/ kg/ day) was fetotoxic due to significant reductions ( 18%) from controls in mean fetal weight in treated animals. The maternal and developmental toxicity NOAEL was 140 mg/ kg/ day, and the maternal and developmental toxicity LOAEL was 280 mg/ kg/ day in this study.

Reproductive. In a two generation reproductive toxicity study conducted by Ryan et al ( 2001), phenol ( 100% purity) was administered to groups of 30 Sprague Dawley rats/ sex/ dose in drinking water at concentrations of 200, 1,000, or 5,000 ppm ( 14, 70, and 310 mg/ kg/ day for males and 20, 93, and 350 mg/ kg/ day for females, respectively) for both generations. There were treatment related decreases from control in body weight and body weight gain in P1 generation rats treated with phenol. These reductions were concomitant with decreases in food and water consumption and observed in the high dose rats. There were also treatment related decreases from controls in F1 body weight in the 5000 ppm phenol treated rats. The lower maternal body weight may have contributed to the lower birth weight of F1 generation as a result of the decreased food and water consumption during lactation and decreased palatability. The maternal toxicity NOAEL is 1,000 ppm in the P1 and F1 generations. The maternal toxicity LOAEL is 5,000 ppm based on decreases in water and food consumption, body weight ( average 11% decrease during pre mating weeks 1 and 10, gestation, and lactation) and body weight gain ( average 18% decrease during pre mating weeks 1 through 10) in the P1 and F1 generations. These effects are associated with flavor aversion to phenol in the drinking water.

There were no treatment related effects on reproductive performance in either the P1 or F1 generation. The estrus cycle, epididymal sperm count, motility, sperm morphology, testicular sperm count, and production rate were unaffected by phenol treatment in the P1 and F1 generations. However, the percent of offspring alive after PND 0 was significantly decreased in the 5,000 ppm groups with a 10% decrease on PND 4 for the P1 generation and decreases of 28 and 24% on PND 4 and 7 21, respectively, for the F1 generation. The reproductive toxicity NOAEL is greater than or equal to 5,000 ppm in the P1 and F1 generations ( highest dose tested). The Reproductive Toxicity LOAEL is greater than 5,000 ppm in the P1 and F1 generations ( not established).

There were treatment related effects for both F1 and F2 generations with increases in litter mortality ( more so in the F2 generation) and reduced offspring body weights in the high dose group. This occurred concurrently with maternal toxicity ( decreased maternal body weight); believed to be secondary to the animals' aversion to the flavor of the phenol treated water and resulted in decreased maternal as well as offspring body weight. There were delays in vaginal patency of F1 females ( 38.3 days for treated females vs. 34.6 days for control females) and preputial separation of F1 males ( 47.8 days for treated males vs. 44 days for control males) observed with decreases in pre and post weaning body weights in the high dose group. Therefore, the onset of puberty was delayed and attributed to decreased food and water consumption and reduced body weight. The offspring toxicity NOAEL is Page 12 of 57 1000 ppm. The offspring toxicity LOAEL is 5,000 ppm based on decreases in body weight of F1 and F2 offspring ( 5 7% on PND 0; 15 30% on PND 4 21), decreases in litter survival of P1 and F1 offspring ( P1 generation: 90% treated vs. 99% control on PND 4; 96% treated vs. 100% control animals on PND 7 21 and F1 generation: 67% treated vs. 93% control on PND 4; 74% treated vs. 98% control on PND 7 21), delays in preputial separation in F1 males ( 47.8 days for treated males vs. 44 days for control males), and delays in vaginal patency in F1 females ( 38.3 days for treated females vs. 34.6 days for control females).

Carcinogenicity. Phenol is characterized as a Group D, not classifiable as to human carcinogenicity ( This group is used for agents with inadequate human and animal evidence of carcinogenicity or for which no data are available). The updated toxicological review in the EPA IRIS database ( USEPA, 2002a) provides a summary of the weight of the evidence with respect to the carcinogenic potential of phenol, and this is reproduced in part below.

Dermally administered phenol has been consistently observed to be a promoter. Several authors ( Salaman and Glendenning, 1957; Boutwell and Bosch, 1959; Wynder and Hoffmann, 1961) observed that dermally applied phenol promoted DMBA initiated skin tumors. These studies have generally reported significant skin ulceration at all phenol doses tested. The exception is Wynder and Hoffman ( 1961), who reported that 5% phenol promoted DMBA initiated tumors in mice in the absence of any toxic reactions. When the same phenol dose was administered in different volumes, higher promotion activity was exhibited by the more concentrated solution, which also produced severe skin ulceration, suggesting that some of the promotion activity may have been related to the rapid cell division of repair of skin damage ( Salaman and Glendenning, 1957).

A mechanistic study conducted by Stenius et al. ( 1989) was designed to assess the toxicity and carcinogenicity of phenol when administered to partially hepatectomized male SD rats. Phenol was administered by gavage 5 days/ week for 7 weeks at a concentration of 100 mg/ kg/ day. Animals were sacrificed, by decapitation, 1 week after last treatment. Sections of the rat liver were prepared and stained to measure for induction of   glutamyltranspeptidase ( GGT) positive enzyme altered foci as an indicator of tumor initiation. Additional studies involved single oral administrations of phenol to measure inductions of hepatic ornithine decarboxylase ( ODC), glutathione ( GSH) depletion, and in vivo lipid peroxidation.

Phenol did not increase the number or volume of foci and was found to have no tumor initiating properties within the confines of this study. Lipid peroxidation was not induced following administration of phenol as measured by malondialdehyde ( MDA) in the urine. There were small and inconsistent effects observed in hepatic ornithine decarboxylase ( ODC) in which there was an increase at the mid dose, but a decrease at the high dose. Observed measurements of hepatic ODC were 18.8, 32.3, and 11.4 pmol/ mg/ h for the phenol doses of 0, 50, and 100 mg/ kg/ day, respectively. Phenol did not induce GSH depletion in hepatocytes.

Mutagenicity. The results of the mutagenicity studies indicated that phenol was not mutagenic in Salmonella typhimurium or Drosophila melanogaster and did not induce micronuclei or bone marrow chromosomal aberrations in mice. However, mutagenic effects were observed in Chinese Page 13 of 57 Hamster ovary cells and spermatocytes in mice and HL60 cells. The genotoxic potential of phenol appears to depend on the competing processes of activation to a genotoxic form and metabolic inactivation ( e. g., via conjugation). Phenol tended to be negative in bacterial gene mutation assays but was positive or equivocal in mammalian cell gene mutation assays. Phenol tended to induce micronuclei in mice when administered intraperitoneally but was negative ( or positive only at very high doses) when administered orally. This difference is likely due to the first pass conjugation and inactivation of orally administered phenol. Phenol was also positive in in vitro micronucleus tests with human lymphocytes and Chinese Hamster ovary cells. Results from DNA damage assays are inconsistent, but they tend to show that phenol can cause sister chromatid exchanges or cell transformation if it is not metabolically inactivated. Overall, phenol did not exhibit strong mutagenic effects.

Metabolism. Phenol is essentially completely metabolized in 24 hours. Phenol was predominantly conjugated with sulfate and lower amounts of glucuronic acid and the metabolites were rapidly excreted in the urine. The major metabolites found were phenyl sulfate, quinol sulfate, phenyl glucuronide, and quinol glucuronide.

Neurotoxicity. The ADTC committee noted neurotoxic signs from acute dermal toxicity studies ( Brown et al., 1975  convulsions; OTS 0515567 tremors; Conning et al., 1970 stimulation of motor nerve endings or spinal motor centers) and a 15 day inhalation study ( tilting plane results showed an effect in treated rats). There were no neurotoxic signs of phenol noted from the oral studies using gavage or drinking water as the method of administration. As noted in the IRIS toxicological profile, numerous CNS effects have been observed following phenol dosing. Tremors were observed in one animal that later died ( apparently of dehydration) following dosing in drinking water ( ClinTrials BioResearch, 1998). Tremors have also been observed in several gavage studies in rats and mice ( 43735402; Dow Chemical Co., 1994; Moser et al., 1995). However, in a specialized 13 week neurotoxicity study in male and female rats that included an FOB and a detailed neurohistopathology evaluation ( ClinTrials BioResearch, 1998), the only observed nervous system effects were tremors in one animal and decreased motor activity in females. A short term gavage screening study ( Moser et al., 1995) found that the only effect in an FOB was a marginal decrease in motor activity and increased rearing post exposure. Part of this could be attributed to the dehydration observed in the study.

Table 3.1. Acute Toxicity of Phenol and Phenol salts Guideline Number Study Type/ Test substance (% a. i.) MRID Number/ Citation Results Toxicity Category 870.1100 ( § 81 1) Acute Oral Rat Phenol purity > 99% Berman, et al., 1994 LD50 = 400 ( 297 539) mg/ kg/ day II 870.110 ( § 81 1) Acute Oral  Rat Phenol purity 100% OTS #  0515567 86 870001405 LD50 = 1,030 ( 940 1120) mg/ kg/ day III 870.1100 ( § 81 1) Acute Oral Rat Phenol purity not reported Flickinger, 1976 LD50 = 650 ( 490 860) mg/ kg/ day III Table 3.1. Acute Toxicity of Phenol and Phenol salts Guideline Number Study Type/ Test substance (% a. i.) MRID Number/ Citation Results Toxicity Category Page 14 of 57 870.1200 ( § 81 2) Acute Dermal Rat Phenol purity not reported Brown, et al., 1975 LD50 ( Non occluded) = 0.68 ( 0.57 0.78) mL/ kg LD50 ( Occluded) = 0.50 mL/ kg II 870.1200 ( § 81 2) Acute Dermal Rabbit Sodium Phenate purity 57% OTS #  0515564 86 870001402 LD50 = 2,350 ( 1,880 2,940) mg/ kg/ day III 870.1200 ( § 81 2) Acute Dermal Rabbit Phenol purity 100% OTS #  0515567 86 870001405 LD50 = 0.63 ( 0.56 0.70) mL/ kg II 870.1200 ( § 81 2) Acute Dermal Rat Phenol purity laboratory reagent grade Conning et al., 1970 LD50 = 669.4 mg/ kg/ day II 870.1200 ( § 81 2) Acute Dermal Rabbit Phenol purity not reported Flickinger, 1976 LD50 = 850 ( 600 1,200) mg/ kg/ day II 870.1300 ( § 81 3) Acute Inhalation Rat Phenol purity 100% OTS #  0515567 86 870001405 No deaths occurred at 2.5 L/ min for 8 hours Not established 870.1300 ( § 81 3) Acute Inhalation Rat Phenol purity not reported Flickinger, 1976 No deaths occurred at 900 mg/ m3 for 8 hours Irritation and timerelated CNS effects Not established 870.2400 ( § 81 4) Acute Eye Irritation Rabbit Sodium Phenate purity 57% OTS #  0515564 86 870001402 15% solution caused corneal necrosis and conjunctiva lesions II 870.2400 ( § 81 4) Acute Eye Irritation Rabbit Phenol purity 100% OTS #  0515567 86 870001405 Severe damage to the cornea at 15% and lesser damage in 5% Not established 870.2400 ( § 81 4) Acute Eye Irritation Rabbit Phenol purity not reported Flickinger, 1976 Dose not provided. Severe conjunctiva, iritis, corneal opacities and ulcerations with no improvement after 14 day observation period. I 870.2500 ( § 81 5) Acute Dermal Irritation Rabbit Sodium Phenate purity 57% OTS #  0515564 86 870001402 Mild to marked erythema and marked capillary injection were observed in 50% of animals tested II Table 3.1. Acute Toxicity of Phenol and Phenol salts Guideline Number Study Type/ Test substance (% a. i.) MRID Number/ Citation Results Toxicity Category Page 15 of 57 870.2500 ( § 81 5) Acute Dermal Irritation Rabbit Phenol purity 100% OTS #  0515567 86 870001405 10% solution caused moderate to marked erythema Not established 870.2500 ( § 81 5) Acute Dermal Irritation Rabbit Phenol purity not reported Flickinger, 1976 Corrosive I Page 16 of 57 Table 3.2. Toxicity Profile of Phenol/ Sodium Phenate Guideline Number/ Study Type/ Test Substance (% a. i.) MRID Number ( Year)/ Citation/ Classification/ Doses Results Non guideline  Subchronic ( Oral) Range Finding Study ( Rat) Phenol purity not reported NIH PB#  80 1759 Acceptable  Non guideline 0, 100, 300, ,1000, 3,000, and 10,000 ppm NOAEL = 3,000 ppm LOAEL = 10,000 ppm, based on significant decreases in mean body weight gain.

Considering the test article was administered in the drinking water, palatability at the high dose may have affected water consumption.

Non guideline  Subchronic ( Oral) Range Finding Study ( Mouse) Phenol purity not reported NIH PB#  80 1759 Acceptable  Non guideline 0, 100, 300, 1,000, 3,000, and 10,000 ppm NOAEL = 3,000 ppm LOAEL = 10,000 ppm, based on significant decreases in mean body weight gain.

Considering the test article was administered in the drinking water, palatability at the high dose may have affected water consumption.

Special Study  Nonguideline Two Week Inhalation Study ( Rat) Phenol purity not reported Dalin and Kristoffersson, 1984 Acceptable  Non guideline 600 +/ 10 L/ hr in an inhalation chamber with a phenol concentration of 100 mg/ m3 CNS effects measured by the " tilting plane" method showed significant decreases in the value of the sliding angle after exposure to phenol. The mean sliding angle was 71.2 ± 2.4 degrees prior to phenol administration and following treatment there was a significant decrease ( 6%) to 66.8 ± 1.7 degrees. Rats had elevated plasma Mg2+ levels ( Hypermagnesaemia) and exhibited toxic effects in the central nervous system ( CNS).

870.3700a ( § 83 3) Developmental Rat Phenol purity 99.9% MRID# 43735402 Acceptable  Non guideline 0, 30, 60 or 120 mg/ kg/ day Maternal Toxicity NOAEL  120 mg/ kg/ day ( highest dose tested) LOAEL > 120 mg/ kg/ day ( not established) Reproductive Toxicity NOAEL  120 mg/ kg/ day ( highest dose tested) LOAEL > 120 mg/ kg/ day ( not established) Developmental Toxicity NOAEL = 60 mg/ kg/ day LOAEL = 120 mg/ kg/ day, based on reduced fetal weight Table 3.2. Toxicity Profile of Phenol/ Sodium Phenate Guideline Number/ Study Type/ Test Substance (% a. i.) MRID Number ( Year)/ Citation/ Classification/ Doses Results Page 17 of 57 870.3700a ( § 83 3) Developmental Rat Phenol purity 90% Argus, 1997 ( U. S. EPA IRIS database) Acceptable  Guideline 3 time daily with 0, 20, 40, or 120 mg/ kg/ dose ( 0, 60, 120, or 360 mg/ kg/ day) Maternal Toxicity NOAEL = 60 mg/ kg/ day LOAEL = 120 mg/ kg/ day, based on small decreases in maternal body weight Developmental Toxicity NOAEL = 120 mg/ kg/ day LOAEL = 360 mg/ kg/ day, based on decreased fetal body weight and delayed ossification 870.3700a ( § 83 3) Developmental Mouse Phenol purity 99.9% MRID # 34735401 Unacceptable ( Upgradable) 0, 70, 140, or 280 mg/ kg/ day Maternal Toxicity NOAEL = 140 mg/ kg/ day LOAEL = 280 mg/ kg/ day, based on increased mortality, significant reductions in body weight, and clinical signs of CNS toxicity ( tremors, lethargy, and ataxia) Reproductive Toxicity NOAEL  280 mg/ kg/ day ( highest dose tested) LOAEL > 280 mg/ kg/ day ( not established) Developmental Toxicity NOAEL = 140 mg/ kg/ day LOAEL = 280 mg/ kg/ day, based on reduced fetal weight and an apparent increase in the incidence of cleft palate Non guideline  Developmental Toxicity  Rat Phenol purity > 99% Narotsky and Kavlock, 1995 ( J. Toxicol. Env. Health 45( 2)) Acceptable  Non guideline 40, and 53.3 mg/ kg/ day Maternal Toxicity NOAEL < 40 mg/ kg/ day ( lowest dose tested) LOAEL = 40 mg/ kg/ day, based on reduced body weight gains and severe respiratory signs Reproductive Toxicity NOAEL = 40 mg/ kg/ day LOAEL = 53.3 mg/ kg/ day, based on significantly reduced litter sizes, full resorption, and prenatal loss Developmental Toxicity NOAEL  53.3 mg/ kg/ day ( highest dose tested) LOAEL > 53.3 mg/ kg/ day ( not established) Table 3.2. Toxicity Profile of Phenol/ Sodium Phenate Guideline Number/ Study Type/ Test Substance (% a. i.) MRID Number ( Year)/ Citation/ Classification/ Doses Results Page 18 of 57 870.3800 ( § 83 4) Reproduction  Rat Phenol purity 100% Ryan et al., 2001 ( Intl. J. of Tox. Vol. 20) Acceptable Guideline 0, 200, 1,000, and 5,000 ppm Males: 0, 14, 70, and 310 mg/ kg/ day Females: 0, 20, 93, and 350 mg/ kg/ day Maternal Toxicity NOAEL = 1,000 ppm in the P1 and F1 generations LOAEL = 5,000 ppm based on decreases in water and food consumption, body weight ( average 11% decrease during premating weeks 1 and 10, gestation and lactation) and body weight gain ( average 18% decrease during pre mating weeks 1 through 10) in the P1 and F1 generations. These effects are associated with flavor aversion to phenol in the drinking water Reproductive Toxicity NOAEL  5,000 ppm in the P1 and F1 generations ( highest dose tested) LOAEL > 5,000 ppm in the P1 and F1 generations ( not established) Offspring Toxicity NOAEL = 1,000 ppm LOAEL = 5,000 ppm based on decreases in body weight of F1 and F2 offspring ( 5 7% on PND 0; 15 30% on PND 4 21), decreases in litter survival of P1 and F1 offspring ( P1 generation: 90% in treated animals vs. 99% in control animals on PND 4; 96% in treated animals vs. 100% in control animals on PND 7 21. F1 generation: 67% in treated animals vs. 93% in control animals on PND 4; 74% in treated animals vs. 98% in control animals on PND 7 21) and delays in preputial separation in F1 males ( 47.8 days for treated males vs. 44 days for control males) and vaginal patency in F1 females ( 38.3 days for treated females vs. 34.6 days for control females) Table 3.2. Toxicity Profile of Phenol/ Sodium Phenate Guideline Number/ Study Type/ Test Substance (% a. i.) MRID Number ( Year)/ Citation/ Classification/ Doses Results Page 19 of 57 870.4200a ( § 83 2) Carcinogenicity  Rat Phenol purity 98.47% NIH PB# 80 1759 Acceptable  Non guideline 0, 2,500, or 5,000 ppm Male: 0, 322, or 645 mg/ kg/ day Female: 0, 360, or 721 mg/ kg/ day NOAEL  5,000 ppm ( highest dose tested) for both male and female rats LOAEL > 5,000 ppm ( not established)

Various neoplasms were observed in both control and treated rats. The low dose male rats exhibited increased tumor occurrence over controls. Pheochromocytomas of the adrenal medulla were found in 44% of low dose males; significantly higher ( p= 0.046) than the 26% in controls and 18% in high dose males. The incidence of either leukemia or lymphomas in high dose and low dose males were higher than controls, but were only significantly higher ( p= 0.008) in low dose treated. The incidence of interstitial cell tumors in the testis of males is also significantly higher ( p= 0.05) in low dose males than control; found in 49 of the 50 animals. Results of histopathologic examinations suggest phenol may have increased the incidence of pheochromocytoma, leukemia or lymphoma in low dose male rats. Females did not exhibit increased incidences of tumors at any time in this study. Table 3.2. Toxicity Profile of Phenol/ Sodium Phenate Guideline Number/ Study Type/ Test Substance (% a. i.) MRID Number ( Year)/ Citation/ Classification/ Doses Results Page 20 of 57 870.4200b ( § 83 2) Carcinogenicity  Mouse Phenol purity 98.47% NIH PB# 80 1759 Acceptable  Non guideline 0, 2,500, or 5,000 ppm Male: 0, 590, or 1,180 mg/ kg/ day Female: 0, 602, or 1,204 mg/ kg/ day NOAEL  5,000 ppm ( highest dose tested) for male and female mice LOAEL > 5,000 ppm ( not established)

Neoplasms observed in treated animals were of the usual number and type found in mice. Uterine endometrial stromal polyps were increased in 5 of 48 high dose female mice, although this was not significantly different from similar historical control mice. Any other neoplasms noted were occurrences normally associated with aged B6C3F1 mice and were not treatment related.

Results of the histopathologic examinations suggest phenol was not toxic or carcinogenic to B6C3F1 mice under the conditions of this 2 year drinking water carcinogenic bioassay; no tumor at any site in the mice could be clearly associated with the administration of phenol in this study.

Non guideline  Mechanistic Study Phenol purity 99.5% Stenius et al., 1989 ( Carcinogenesis Vol. 10) Acceptable  Non guideline 0 or 100 mg/ kg/ day 5 days/ week for 7 weeks NOAEL  100 mg/ kg ( highest dose tested) LOAEL > 100 mg/ kg ( not established)

Phenol is not a potent stimulator of foci development and can be regarded at a negative control in this study because it should not be susceptible to oxidation reduction reactions.

870.5100 ( § 84 2) Bacterial reverse mutation test Phenol purity not reported Florin, et al. 1980 ( Toxicology Vol. 15) Acceptable  Non guideline 2.3  2343  g/ plate 3  mol/ plate Negative There was no evidence of induced mutant colonies over background. Positive controls produced the appropriate responses in the corresponding strains of the bacterial reverse mutagenesis test. S. typhimurium did not show mutagenic activity in the presence or absence of metabolic activation when phenol was administered at 3  mol/ plate. Table 3.2. Toxicity Profile of Phenol/ Sodium Phenate Guideline Number/ Study Type/ Test Substance (% a. i.) MRID Number ( Year)/ Citation/ Classification/ Doses Results Page 21 of 57 870.5100 ( § 84 2) Bacterial reverse mutation test Phenol purity 99.9% Haworth et al., 1983 ( Env. Mutagenesis Suppl. Vol. 1) Acceptable  Non guideline 0, 33, 100, 333, 1,000, 2,500, and 3,333  g/ plate Negative There was no evidence of induced mutant colonies over background. Positive controls produced appropriate responses in corresponding strains of the bacterial reverse mutagenesis test. S. typhimurium did not show mutagenic activity in the presence or absence of metabolic activation following administration of phenol.

870.5100 ( § 84 2) Bacterial reverse mutation test Phenol purity 98% Pool and Lin, 1982 ( Food Chem. Tox. Vol. 20) Acceptable  Non guideline 0.5, 5, 50, 500, and 5,000  g/ plate Negative The most abundant phenolic compounds found in smokehouse smoke condensates were not mutagenic in the Salmonella Typhimurium assay. There was no evidence of mutagenic activity following administration of phenol to 5 bacterial strains of S. typhimurium in the presence or absence of metabolic activation.

870.5100 ( § 84 2) Bacterial reverse mutation test Phenol purity not reported Gocke et al., 1981 ( Mutat. Res. Vol. 90) Acceptable  Non guideline 0  3,000  g/ plate Negative Phenol was not mutagenic in the bacterial strains in the absence of metabolic activation. Phenol showed mutagenic effects, in the presence of metabolic activation, predominantly in the Ames tester strains of S. typhimurium that are sensitive for frameshift mutagens ( ie., TA 98). Table 3.2. Toxicity Profile of Phenol/ Sodium Phenate Guideline Number/ Study Type/ Test Substance (% a. i.) MRID Number ( Year)/ Citation/ Classification/ Doses Results Page 22 of 57 870.5275 ( § 82 4) Sex linked recessive lethal test in Drosophila melanogaster Phenol purity not reported Gocke et al., 1981 ( Mutat. Res. Vol. 90) Acceptable  Non guideline 50 mM Negative Phenol was administered to D. melanogaster and 3543, 3458, and 2139 chromosomes were tested for sex linked recessive lethals in Broods 1, 2, and 3, respectively. There were no significant increases in recessive lethals observed following administration of phenol to Broods 1, 2, and 3 and only 17 ( 0.48%), 6 ( 0.17%), and 7 ( 0.33%) sex linked recessive lethals, respectively, were measured in the chromosomes tested.

After feeding phenol to adult flies, the frequency of recessive lethals was increased, but not to significant levels. Phenol was not mutagenic within the confines of this study.

870.5275 ( § 82 4) Sex linked recessive lethal test in Drosophila melanogaster Phenol purity 99.9% Woodruff et al., 1985 ( Env. Mutagenesis Vol. 7) Acceptable  Non guideline Feeding: 0 and 2,000 ppm Injection: 0 and 5,250 ppm Negative Phenol was tested up to cytotoxic concentrations 2,000 and 5,250 ppm in feeding and injection studies, respectively. The number of sex linked recessive lethal mutations in the feeding study were 7 and 11 at the 0 and 2,000 ppm doses, respectively. The injection assay resulted in 5 ( 0 ppm) and 6 ( 5,250 ppm) sex linked recessive lethal mutations, while the feeding study exhibited 0.12 ( 0 ppm) and 0.17 ( 2,000 ppm) lethals. These sex linked recessive lethal mutations were not significantly different from those found in controls. One cluster of 32 lethals and one cluster of 86 lethals were observed in the treated feeding experiment. Phenol was negative in inducing sex linked recessive lethal mutation in D. melanogaster. Table 3.2. Toxicity Profile of Phenol/ Sodium Phenate Guideline Number/ Study Type/ Test Substance (% a. i.) MRID Number ( Year)/ Citation/ Classification/ Doses Results Page 23 of 57 870.5300 ( § 84 2) In Vitro mammalian call gene mutation test Phenol purity not reported Pashin and Bahitova,. 1982 ( Mutation Res. Vol. 104) Acceptable  Non guideline Phenol: 0, 25, 50, 100, 250, and 500  g/ mL Benzo[ a] pyrene and Phenol mix: 100, 250, 500  g/ mL. The mixture includes the addition of sodium Phenobarbital metabolic activation. Positive At doses of 25, 50, 100, 250, and 500  g/ mL phenol, there was a dose dependent increase in the number of revertant colonies ( 1.2, 1.2, 1.7, 2.5, and 4.3 fold increases, respectively). Statistically significant increases were observed in the frequency of AGr ( selective agent, 8 azaguanine added to determine resistant mutants) mutants over spontaneous levels with 52 and 72% increases at 250 and 500  g/ mL, respectively. The combination of phenol with benzo[ a] pyrene at a concentration of 12  g/ mL, exhibited an increase in frequency of 8 azaguanine resistant colonies with increasing concentrations of phenol. The results were the same as the sum of the separate effects of phenol and benzo[ a] pyrene and the researchers concluded that phenol did not block or activate the mutagenicity of benzo[ a] pyrene.

870.5375 ( § 84 2) In Vitro mammalian chromosome aberration test Phenol purity not reported ( high commercial grade) Kolachana et al., 1993 ( Cancer Res. Vol. 53) Acceptable  Non guideline HL60 cells exposed for 30 minutes to 100  M phenol Positive Phenol increased the steady state level of 8 hydroxy 2' deoxyguanosine in DNA of human leukemia HL60 cells. The increase in this oxidative damage product was 3.5 fold and indicates genotoxic effects resulting from active oxygen following exposure to phenol.

870.5380 ( § 84 2) Mammalian spermatogonial chromosomal aberration test  Rat Phenol purity not reported Bulsiewicz, 1977 ( Folia Morphology Vol. 36) Acceptable  Non guideline 0.08, 0.8, or 8.0 mg/ L/ day for 30 days for 5 generations Positive There was evidence of a concentration related ( 0.08 8.0 mg/ L) positive response of spermatogonial chromosome aberrations in Porton strain male mice following 30 days of exposure to phenol in water. Table 3.2. Toxicity Profile of Phenol/ Sodium Phenate Guideline Number/ Study Type/ Test Substance (% a. i.) MRID Number ( Year)/ Citation/ Classification/ Doses Results Page 24 of 57 870.5385 ( § 84 2) Mammalian bone marrow chromosome aberration test  Mouse Phenol purity not reported ( high commercial grade) Kolachana et al., 1993 ( Cancer Res. Vol. 53) Acceptable  Non guideline 75 mg/ kg/ day Negative Individual treatment with phenol, hydroquinone, or catechol did not significantly increase 8 hydroxy 2' deoxyguanosine levels in mouse bone marrow cells compared to the control with only 11, 7, and 26% increases, respectively, in treated cells over control)

870.5395 ( § 84 2) Mammalian erythrocyte  Mouse Phenol purity not reported Barale et al., 1990 Acceptable  Non guideline 40, 80, and 160 mg/ kg/ day Negative There was no significant increase in the frequency of micronucleated polychromatic erythrocytes in bone marrow of Swiss CD 1 male mice after treatment with phenol ( 40 160 mg/ kg). However, when phenol is combined with hydroquinone ( 40 80 mg/ kg) a significant dose related increase was observed.

870.5395 ( § 84 2) Mammalian erythrocyte  Mouse Phenol purity 99% Chen and Eastmond, 1995 ( Carcinogenesis Vol. 16) Acceptable  Non guideline 50, 75, 100, or 160 mg/ kg/ day Negative There was no significant increase in the frequency of micronucleated polychromatic erythrocytes in bone marrow of CD 1 male mice following treatment with phenol ( 50 160 mg/ kg) alone. However, when phenol is combined with hydroquinone ( 60 mg/ kg), a significant increase in MNPCEs was observed. The data suggest that phenol genotoxic when combined with hydroquinone.

870.5395 ( § 84 2) Mammalian erythrocyte  Mouse Phenol purity not reported Gocke et al., 1981 ( Mutation Res. Vol. 90) Acceptable  Non guideline 47, 98, and 188 mg/ kg/ day Negative There were no significant increases in the frequency of micronucleated polychromatic erythrocytes in mouse bone marrow cells at the concentrations of phenol used in this study. Phenol was not mutagenic in NMRI mouse bone marrow cells. Table 3.2. Toxicity Profile of Phenol/ Sodium Phenate Guideline Number/ Study Type/ Test Substance (% a. i.) MRID Number ( Year)/ Citation/ Classification/ Doses Results Page 25 of 57 870.7485 ( § 85 1) Metabolism and pharmacokinetics  Rat Phenol purity not reported Capel et al., 1972 ( Xenobiotica Vol. 2) Acceptable  Non guideline 25 mg/ kg/ day An average of 95% of 14C dose of phenol ( 25 mg/ kg) was excreted in the urine in 24 hours. Four metabolites, the sulfates and glucuronides of phenol and quinol, were found in the urine of rats after an oral dose of phenol. The phenyl sulfate and quinol sulfate metabolites represented 54 and 1%, respectively of the metabolites recovered in the urine. The remaining phenol metabolites recovered from the urine were phenyl glucuronide ( 42%) and quinol glucuronide ( 2%).

870.7485 ( § 85 1) Metabolism and pharmacokinetics  Rat Phenol purity not reported Hughes and Hall, 1995 Acceptable  Non guideline 350 nmol/ kg Absorption of phenol was extensive following iv, oral, and it administration while dermal absorption was slightly lower by comparison. Phenol was predominantly conjugated with sulfate and lower amounts of glucuronic acid. These metabolites were rapidly excreted in the urine. Phenol was distributed throughout the body in low amounts and appeared to concentrate in liver, lung, and kidney. The data suggest that the exposure of phenol to rats by oral, dermal, intratracheal, and intravenous routes resulted in rapid absorption, conjugation, and elimination in urine.

870.7485 ( § 85 1) Metabolism and pharmacokinetics  Mouse Phenol purity not reported Capel et al., 1972 ( Xenobiotica Vol. 2) Acceptable  Non guideline 25 mg/ kg/ day Intestinal conjugation of phenol prior to absorption was significant only at low dose, the first pass intestinal conjugation alone does not explain lack of carcinogenicity of phenol at much higher doses. The data suggest that a combination of first pass conjugation and zonal segregation of hepatic enzymes may contribute to the greater production of hydroquinone after oral administration of benzene than phenol. Hydroquinone and other metabolites may be the metabolic basis for carcinogenic and genotoxic effects observed with benzene but not phenol. Table 3.2. Toxicity Profile of Phenol/ Sodium Phenate Guideline Number/ Study Type/ Test Substance (% a. i.) MRID Number ( Year)/ Citation/ Classification/ Doses Results Page 26 of 57 870.7600 ( § 85 3) Dermal Penetration Phenol purity not reported Behl and Linn, 1983 ( J Pharm. Sci. Vol. 72) Acceptable  Non guideline 0.5, 1.0, 2.0, 4.0, and 6.0% ( w/ v) in saline solution Age and hydration have little effect on the permeability of phenol through human and mouse skin and the effects on the skin were a result of destroyed barrier integrity. Permeation of and chemical denaturation by phenol were found to be similar between mouse and human skin tissue; indicating that the hairless mouse is an adequate model for chemical permeability in humans. The results suggest that the stratum corneum is proportionally impaired as the phenol concentration is increased.

3.2 FPQA Considerations Under the Food Quality Protection Act ( FQPA), P. L. 104 170, promulgated in 1996 as an amendment to the Federal Insecticide, Fungicide, and Rodenticide Act ( FIFRA) and the Federal Food, Drug and Cosmetic Act ( FFDCA), the Agency was directed to " ensure that there is a reasonable certainty that no harm will result to infants and children" from aggregate exposure to a pesticide chemical residue. The law further states that in the case of threshold effects, for purposes of providing this reasonable certainty of no harm, " an additional tenfold margin of safety for the pesticide chemical residue and other sources of exposure shall be applied for infants and children to take into account potential pre and post natal toxicity and completeness of the data with respect to exposure and toxicity to infants and children. Notwithstanding such requirement for an additional margin of safety, the Administrator may use a different margin of safety for the pesticide residue only if, on the basis of reliable data, such margin will be safe for infants and children."

On March 9, 2004, the Antimicrobials Division's Toxicity Endpoint Selection Committee ( ADTC) reviewed the available toxicology data for phenol. The ATDC concluded that there are low concerns and no residual uncertainties for pre and/ or postnatal toxicity with phenol for any of the available studies. Conservative NOAELs were established for all developmental and offspring effects. The developmental and reproductive toxicity studies conducted with phenol provide adequate information on the dose response relationships for developmental and reproductive toxicity and are considered adequate studies for regulatory purposes. The ATDC concluded that there is no evidence for susceptibility of phenol from the available data on developmental and reproductive toxicity. The hazard based default special FQPA safety factor ( 1x) can be reduced when assessing dietary and nonoccupational risks from the uses of phenol. Page 27 of 57 3.3 Dose Response Assessment The doses and toxicologic endpoints selected by ADTC for various exposure scenarios are summarized in Table 3.3 below.

Table 3.3 Summary of Toxicological Doses and Endpoints for Phenol/ Sodium phenate for Use in Human Risk Assessment Exposure Scenario Dose ( mg/ kg/ day) used in risk assessment UF Special FQPA SF( 1x) and Level of Concern for Risk Assessment Study and Toxicological Effects Acute Dietary ( gen population) This risk assessment is not required.

Acute Dietary ( females 13 49) This risk assessment is not required.

Chronic Dietary ( all populations) NOAEL= 60 UF = 100 Chronic RfD = 0.6 mg/ kg/ day Chronic PAD = 0,6 mg/ kg/ day FQPA SF = 1x Developmental toxicity study in rats ( Argus, 1997) NOAEL based on decreases in maternal body weight gain at 120 mg/ kg/ day ( LOAEL).

Incidental Oral Short Term ( 1  30 Days)

Residential Only NOAEL= 60 mg/ kg/ day MOE = 100 Developmental toxicity study in rats ( Argus, 1997) NOAEL based on decreases in maternal body weight gain at 120 mg/ kg/ day ( LOAEL).

Incidental Oral Intermediate Term ( 1  6 Months)

Residential Only NOAEL= 60 mg/ kg/ day MOE = 100 Developmental toxicity study in rats ( Argus, 1997) NOAEL based on decreases in maternal body weight gain at 120 mg/ kg/ day ( LOAEL).

Dermal1 Short and intermediateterm NOAEL = 60 mg/ kg/ day MOE = 100 Developmental toxicity study in rats ( Argus, 1997) NOAEL based on decreases in maternal body weight gain at 120 mg/ kg/ day ( LOAEL). Table 3.3 Summary of Toxicological Doses and Endpoints for Phenol/ Sodium phenate for Use in Human Risk Assessment Exposure Scenario Dose ( mg/ kg/ day) used in risk assessment UF Special FQPA SF( 1x) and Level of Concern for Risk Assessment Study and Toxicological Effects Page 28 of 57 Inhalation ( All durations) LOAEL = 0.1 mg/ L ( 26 mg/ kg/ day) MOE = 300 ( ST, IT)

MOE = 1,000 ( LT) Dalin and Kristofferson: Physiological Effects of a Sub lethal Concentration of Inhaled Phenol on the Rat. Ann. Zool. Fennici 11: 193 199, 1974 LOAEL of 0.1 mg/ L, based on alterations in sliding angle from tilting plane test, and significant increases in liver enzymes Cancer Data inadequate for assessment of human carcinogenic potential ( USEPA, 2002a)

1a dermal absorption factor of 50% should be used since an oral endpoint was selected. Dermal absorption data were available from the IRIS Toxicological profile for phenol. From the available data, dermal absorption percentages of 20 50% have been observed from in vivo and in vitro studies. The ADTC selected the 50% dermal absorption value for phenol for use in risk assessments as a conservative value. This value also takes into account the irritant properties of phenol which may increase its dermal absorption.

3.4 Endocrine Disruption The Food Quality Protection Act ( FQPA; 1996) requires that EPA develop a screening program to determine whether certain substances ( including all pesticides and inerts) " may have an effect in humans that is similar to an effect produced by a naturally occurring estrogen, or such other endocrine effect...." Following the recommendations of its Endocrine Disruptor Screening and Testing Advisory Committee ( EDSTAC), EPA determined that there was a 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 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, phenol and sodium phenate may be subjected to additional screening and/ or testing to better characterize effects related to endocrine disruption. Page 29 of 57 4.0 EXPOSURE ASSESSMENT AND CHARACTERIZATION Phenol and phenol salts are active ingredients in disinfectant, deodorizer and cleaner formulations. Exposure to phenol and phenol salts can occur on commercial, institutional and industrial premises and equipment, medical premises and equipment, residential and public access premises, and at food handling establishments.

4.1 Summary of Registered Uses Concentrations of phenol and phenol salts in products range from 1.6 % to 8.2% ( 1.6% being the most common concentration). These formulations have bactericidal, virucidal, fungicidal and tuberculocidal properties, kill mold and mildew and eliminate odors. All formulations are in liquid form and include ready to use solutions, pressurized liquids and impregnated materials ( towelettes). At least one product reviewed is an industrial additive used as a preservative for polishes, cleansers, paints, and protectants.

Use site categories for these formulations include commercial, institutional and industrial premises and equipment, medical premises and equipment, food handling establishments and residential and public access premises.

Table 4.1 lists the active EPA registration numbers of the products containing phenol and phenol salts evaluated in this document.

Table 4.1. EPA Registration Numbers for Phenol Products Use Category Formulation EPA Registration Numbers Disinfectant/ Deodorizer Aerosol Spray 8383 4, 69658 3, 75480 1, 8383 3 Concentrate 8383 6 Towelette 8383 7 Material Preservative Ready to Use 8383 1 4.2 Dietary Exposure/ Risk Pathway The Agency has carried out the dietary exposure and risk assessment for use of phenol and phenol salts as an active ingredient in that may result in dietary exposure. A detailed dietary exposure assessment is presented in the appendix.

Two products currently registered can be used to disinfect counter tops in kitchens, among other areas. One product is a ready to use solution, while the other is a wettable disposable cloth that is impregnated with phenol and sodium phenate. A counter top that has been treated with either of Page 30 of 57 these products may come into contact with food prepared on the counter top, which in turn may be ingested. Although neither product label states that it should be used on food preparation equipment, it is possible that food could be prepared or placed on treated kitchen counter tops before being eaten.

No residue chemistry data were submitted by registrants, nor were any data requested by the Agency, as these uses do not fall under the guidelines associated with residue chemistry ( OPPTS GLN 860.1300, OPPTS GLN 860.1340, OPPTS GLN 860.1500). The Agency has used available methods to estimate phenol residues on food due to migration of these products.

4.2.1Methodology As noted in the dietary exposure chapter of the phenol RED, the Agency used the following approach to calculation of dietary exposure for phenol as a disinfectant solution ( end use).

EDI = ( wash solution, mg/ cm2) x ( AR) ( wt. fraction of wash solution ) x MF( fraction of pesticide migrating to food) x SA( surface area of exposure)/ BW( 1)

Where EDI = Estimated Daily Intake, mg/ kg/ day) AR = Application Rate SA = Surface area to containing the pesticide to which food is exposed MF = Fraction of pesticide migrating to food, assuming 10% BW = Body weight, adult male = 70 kg, adult female = 60 kg and a child = 15 kg A value of 10% was used for the migration of residues to food due to the high vapor pressure of phenol. Confirmatory data will be needed to support this value.

4.2.2Acute Dietary Exposure and Risk The ADTC determined that for acute dietary risk, there was no appropriate endpoint for assessment of acute dietary exposure. This conclusion was based on examination of the hazard data which might be used in support of such an endpoint. Body weight effects observed were not felt to be the result of a single exposure, and there were no other adverse effects from the data that were considered reflective of a single exposure. An Acute RfD/ PAD value was not selected. As a result, evaluation of acute dietary risk was not necessary.

4.2.3Chronic Dietary Exposure and Risk For chronic dietary risk, the ADTC cited the published chronic RfD value in EPA's Integrated Risk Information System ( IRIS) database. This Reference Dose value is based upon an unpublished developmental toxicity study conducted according to GLP guidelines ( Argus Research Laboratories, 1997). In this study, pregnant Crl: CDRBR VAF/ Plus Sprague Dawley rats ( 25 per group) received Page 31 of 57 phenol by oral gavage on GDs 6 through 15. Dosing was three times daily with 0, 20, 40, or 120 mg phenol/ kg/ dosage using a dosing volume of 10 mL/ kg. The authors noted that the test material was 90% phenol United States Pharmacopeia ( USP); the authors adjusted the dosage calculations for test material purity.

The chronic PAD value was calculated to be 0.6 mg/ kg/ day, using the maternal NOAEL value of 60 mg/ kg/ day and an uncertainty factor of 100 ( 10x interspecies extraploation, 10x intraspecies variation). The ADTC determined that a special FQPA hazard based safety factor was not required for phenol, and could be reduced to 1x.

Chronic dietary risks for adult male, adult female, and children exposure to disinfectant solutions use is shown in Table 4.2. The disinfectant use assumed a transfer efficiency to food of 10%. On the basis of this and other assumptions used, cumulative chronic dietary risk estimates from the indirect food uses were calculated to be 36% for children, 9.0% for adult females, and 7.5% for adult males. Thus, from the indirect food uses of phenol, no risk of concern was identified for chronic dietary exposure.

Table 4.2. Summary of Dietary Exposure and Risk for Phenola Population Subgroup EDI ( mg/ person/ day) Chronic Dietary Dietary Exposure % cPAD b Disinfectant Solutions Adult male 3.2400 4.50e 02 7.50 Adult female 3.2400 5.40e 02 9.0 Child 3.2400 2.16e 01 36.0 a For adults males, chronic exposure analysis is based on a body weight of 70 kg. For adults females, chronic exposure analysis is based on a body weight of 60 kg. For children, exposure is based on a body weight of 15 kg.

b% cPAD = dietary exposure ( mg/ kg/ day) * 100 / cPAD, where cPAD for adults and children = 0.6 mg/ kg/ day.

4.3 Water Exposure/ Risk Pathway Phenol appears to have degradation pathways in air ( calculated half life less than a day) water ( measured half life less than a day), aerobic and anaerobic soils ( degradation half lives less than 5 days). It is not likely to bioaccumalate in aquatic organisms. ( Measured BCF in goldfish is 0.28 and 1.3 in golden orfe). Data on plants show that due to a high respiratory decomposition of phenol into carbon dioxide ( mineralization); it is also not likely to accumulate in plants. Due to multimedia degradation pathways, phenol is not likely to be an environmental concern. Page 32 of 57 Phenol's use in the production of resins and other manufacturing industries and as a general disinfectant allows for the possibility of ground and surface water contamination. Despite phenol's high water solubility and poor sorption to soil, biodegradation of phenol is sufficiently rapid so that the probability of groundwater contamination will be low. Because phenol absorbs light in the region 290 330 nm, phenol might photodegrade directly in surface water. Phenol is not expected to absorb to sediment in the water column. Page 33 of 57 4.4 Residential Exposure/ Risk Pathway A detailed human exposure risk assessment for phenol and phenol salts is provided in the attached Appendix. The summary of the exposures and risks to the residential population are presented below.

4.4.1 Residential Handler Scenarios The following scenarios were considered for residential handlers of phenol containing products:

° Application of paint treated with a material preservative using an airless sprayer and a paintbrush/ roller, ° Use of disinfectant/ deodorizing spray on hard non porous surfaces, and ° Use of disinfectant towelette on hard non porous surfaces.

Using surrogate unit exposure data, application rates from labels, EPA estimates of daily amount handled, and two exposure models, exposure and risks to handlers were assessed.

<IP_ADDRESS> Paint Exposures and Risks One phenol product is listed for use as an industrial additive, and lists paint as a possible use. The label recommends that between 2% 5% by weight of active ingredients be added. As a conservative measure, it is assumed that the treated paint is comprised of 5% active ingredient, by weight. Assuming that paint has a density of 10 lbs per gallon, the concentration of phenols in paint is 0.5 lbs a. i./ gallon. Two painting scenarios were considered in this assessment for homeowners: use of an airless sprayer and use of a paintbrush/ roller to paint the exterior of a house. It is assumed ( Residential SOPs) that a homeowner will paint up to 15 gallons per day with an airless sprayer and up to 2 gallons per day with a brush/ roller, that the exposures will be short term in duration, and that a painter will be exposed through both the dermal and inhalation routes. Due to the fact that the shortterm toxicological endpoints for the dermal and inhalation routes of exposure are derived from different studies and produce different effects, it is not appropriate to combine these routes of exposure. Consequently, separate MOEs are presented in the risk assessment. The results of the assessment are presented in Table 4.3. Based on these assumptions and unit exposure data from the Pesticide Handlers Exposure Database ( PHED), the dermal MOEs for both the airless sprayer and brush/ roller are of concern ( MOEs = 12 and 31, respectively, target MOE = 100). The aerosol portion of the inhalation route slightly exceeds the level of concern ( MOE = 290, target MOE of 300) for the airless sprayer use only.

In addition to the aerosol inhalation risks presented in Table 4.3 for painters, phenol has a relatively high vapor pressure ( 0.341 mmHg @ 25 C), and therefore, EPA is also the concern for potential vapor inhalation exposure. To determine the potential inhalation exposure resulting from the vapor of phenol, the WPEM ( Wall Paint Exposure Assessment Model) was used to estimate the air concentration. Page 34 of 57 OPPT/ EETD has developed the model, WPEM, to estimate air concentrations from painting. More information and access to WPEM is available at http:// epa. gov/ opptintr/ exposure/ docs/ wpem. htm. In summary, WPEM bases its air concentration estimates on models developed from small chamber data on paints.

WPEM is a user friendly, flexible software product that uses mathematical models developed from small chamber data to estimate the emissions of chemicals from oil based ( alkyd) and latex wall paint. This is then combined with detailed use, workload and occupancy data ( e. g., amount of time spent in the painted room, etc,) to estimate exposure. The output of WPEM was evaluated in a home used by EPA for testing purposes and, in general, the results were within a factor of 2. The WPEM provides exposure estimates such as Lifetime and Average Daily Doses, Lifetime and Average Daily Concentrations, and peak concentrations. 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. ( WPEM website).

Phenol was assessed using WPEM for latex paints indoors. The following were used in estimating the short term vapor inhalation exposure from phenol in paints using the WPEM: a vapor pressure of 0.341 mmHg @ 25C, a mw of 94.11, a paint weight fraction of 0.05, and default model parameters. WPEM estimated a peak instantaneous concentration of 22.2 mg/ m3 and a acute potential dose rate ( representing the highest 24 hour exposure) of 0.98 mg/ kg/ day. Although the peak instantaneous concentration is available, it is not representative of the short term inhalation toxicological endpoint. The highest 24 hour inhalation dose estimate of 0.98 mg/ kg/ day corresponds to a short term inhalation MOE of 27 ( i. e., LOAEL 26 mg/ kg/ day / 0.98 mg/ kg/ day).

<IP_ADDRESS> Disinfectant/ Deodorizing Spray and Towlette Exposures and Risks The ready to use sprays and the solution used to treat the towelette contain 1.62% phenol/ sodium phenate ( i. e., no further dilution). It was assumed that the density of this solution is the same as the density of water. The label for the towelette product did not describe the quantity of product to be used; rather, the directions state that the towelette is to be used to wipe the surface, and then the surface should be wiped dry. In the absence of more specific use information, it was assumed that a homeowner uses up to 0.5 liter of the solution in wet towelettes in a single day. This is a screeninglevel assumption that does not trigger a risk of concern. However, refinements to this input may be necessary for the aggregate risks. Similarly, the aerosol spray directions state that the product can be sprayed 2 4 seconds to deodorize a room, but no data were available describing the quantity of product that is emitted by spraying for this time. Therefore, 0.5 liter of solution was also assumed for use of the aerosol spray ( i. e., 1 can). Both the wipe and sprays are assumed to be represented by the short term exposure duration and both dermal and aerosol inhalation exposures are estimated from the CMA data and PHED.

In addition to the aerosol inhalation exposures, there is the concern for potential vapor inhalation exposure because phenol has a relatively high vapor pressure ( 0.341 mmHg @ 25 C). To determine the potential inhalation exposure resulting from the vapor of phenol, the model EFAST ( Exposure and Fate Page 35 of 57 Assessment Screening Tool) was used to estimate the air concentration. OPPT/ EETD has developed the model, EFAST, to estimate air concentrations. More information and access to the EFAST model is available at http:// www. epa. gov/ opptintr/ exposure/. In summary, EFAST Version 1.0 bases its air concentration estimates on physical/ chemical properties. The air concentration estimates for the phenols are based on the model's standard input parameters. The following information is presented in the EFAST model:

".... it is assumed to contact the target surface, and to subsequently volatilize at a rate that depends upon the chemical's molecular weight and vapor pressure."

EFAST presents a peak air concentration as well as a daily air concentration. The peak air concentration estimate "... is the highest instantaneous air concentration that is modeled during the exposure event." This peak air concentration is not expected for any appreciable length of time.

EFAST was used to model the air concentration from general purpose cleaners using a weight fraction of 0.0162. EFAST indicates a peak instantaneous concentration of 7.29 mg/ m3 from this activity. Because the peak concentration does not represent a daily inhalation exposure, the daily dose rather than the peak estimate from EFAST is used to compare to the short term inhalation toxicological endpoint. If a short term toxicological endpoint of less than one day were to be generated it should be compared to the peak air concentration estimate. However, because the toxicological endpoint of concern is based on greater than one day of exposure, the daily dose rate of 0.065 mg/ kg/ day from EFAST is used in this assessment. The daily dose rate is based on the average daily concentration of 0.35 mg/ m3.

The results of the MOE analysis using the CMA data for these scenarios are presented in Table 4.3. The calculated short term dermal MOEs are not of concern for any of the scenarios ( MOE = 140 and 1,800, for wiping and mopping, respectively). The calculated short term ( aerosol) inhalation MOEs from the CMA data for the wiping and mopping are not of concern ( MOE = 1,500 and 79,000, for wiping and mopping, respectively). The results of the EFAST model indicate a short term inhalation MOE from the vapor of phenol to be 400. Therefore, the short term vapor inhalation portion of phenol is also not of concern ( i. e., above the target MOE of 300). Page 36 of 57 Table 4.3. Calculation of Dermal and Inhalation MOE for Residential Handlers a Exposure Scenario Method of Applicatio n Dermal Unit Exposure ( mg/ lb ai) b Inhalation Unit Exposure ( mg/ lb ai) c Appl. Rate d ( lb a. i./ gal) Amount Treated Absorbed Dermal Dose ( mg/ kg/ day) f Dermal MOE g Inhalation Dose ( mg/ kg/ day) h Inhalatio n MOE i Painting Airless Sprayer 79 ( Res SOP PHED) 0.83 ( Res SOP PHED) 0.5 15 gal/ day 4.94 12 0.089 290 Paintbrus h/ Roller 230 ( Res SOP PHED) 0.28 ( Res SOP PHED) 0.5 2 gal/ day 1.92 31 0.0040 6500 Hard Surface Disinfection Towelette 2870 ( CMA no glove) 67.3 ( CMA) 0.0357 lbs a. i./ liter used 0.5 liter of product 0.427 140 0.017 1500 Aerosol Spray 220 ( Res SOP PHED) 1.3 ( PHED) 0.0357 lbs a. i./ liter used 0.5 liter of product 0.033 1800 0.00033 79,000 a MOEs rounded to 2 significant figures. b Dermal unit exposures are from CMA and PHED ( short pants and short sleeves for residential uses   Residential SOPs). c Inhalation unit exposures are from CMA and PHED study. d Application rates are based on the phenol labels. It is assumed that both the phenol and sodium phenate present in products are active ingredients. f Abs. dermal dose ( mg/ kg/ day) = [ unit exposure ( mg/ lb ai) * Dermal Absorption Factor ( 0.5) * Appl. rate ( lb ai/ gallon) * gallons handled / Body weight ( 60 kg). g Dermal MOE = NOAEL ( mg/ kg/ day) / Daily Dose [ Where short term dermal NOAEL = 60 mg/ kg/ day]. Target MOE is 100. h Inhalation dose ( mg/ kg/ day) = [ unit exposure (  g/ lb ai) * 0.001 mg/  g unit conversion * max appl rate ( lb ai/ gal) * gallons handled * 1 inhalation absorption] / Body weight ( 70 kg). i Inhalation MOE = LOAEL ( mg/ kg/ day) / Daily Dose [ LOAEL for all durations = 0.1 mg/ L ( which equals 0.1 mg/ L * 10.26 L/ hr/ kg * 6 hrs/ day / 0.236 kg = 26.08 mg/ kg/ day]. Target MOE is 300 for short term. Page 37 of 57 4.4.2Residential Postapplication Exposure ( Dermal and Incidental Ingestion)

Post application exposures can occur to toddlers from the dermal, oral ( incidental), and inhalation ( high vapor pressure) routes from carpets that have been machine cleaned with a product containing phenol ( and phenol salts). Additionally, adults may be exposed to inhalation exposures after this use. It is believed that the carpet shampoo use represents the high end of the exposures to toddlers from the use of phenol products. The carpets have been assessed rather than hard surface floors because the products appear not to be used to mop floors. Residential carpets are believed to be machine washed on an intermittent basis ( perhaps a few times per year), facilities such as day care centers may clean the carpets more often but are still believed to be of a short term duration ( i. e., carpets machine washed no more than weekly). Therefore, only the short term risks have been presented. There is also the potential of inhalation exposure from vapors resulting from painting indoors with a paint containing phenol. Exposure estimates and the resulting MOEs are also presented for that scenario. Due to the fact that the short term toxicological endpoints for the dermal and oral routes of exposure are derived from the same study and produce the same effect, it is appropriate to combine these exposure estimates. These estimates are combined in the aggregate exposure section.

Dermal Exposure There is the potential dermal exposure to toddlers crawling on treated carpets. To determine toddler exposure to residues in treated carpet, the following equation was used:

PDD FR x SA BW =

where:

PDD= Potential daily dose FR = Flux rate of chemical from material ( mg/ m2/ day) SA = Surface area of the body which is in contact with carpet ( m2) BW = Body weight ( kg)

The following conservative assumptions were made in calculating the exposures/ risks due to limited data:

° Toddlers ( 3 years old) are used to represent the 1 to 6 year old age group and are assumed to weigh 15 kg, the median for male and female toddlers ( USEPA, 2000). A body surface area of 0.657 m2 has been assumed, which is the median value. ° The label did not provide information on the volume of disinfectant to be used for carpet cleaning. Based on information about other carpet sanitizing solutions, it was assumed that 2 ounces of disinfectant are mixed with a gallon of water ( for rotary floor machines), and that the resulting solution is applied at a rate of 1,000 sq. ft. per gallon. ° No data could be found regarding the quantity of solution residue left in the carpet after treatment. As a conservative measure, it has been assumed that 25% of the shampoo remains after the final vacuuming process. ° No leaching data were available that could be used to estimate a flux rate of the chemical from the Page 38 of 57 carpet. Therefore, Residential SOPs estimate of 5% of the amount on the carpet is available for dermal transfer.

The estimated dermal dose and the dermal MOE is presented in Table 4.4. The calculated dermal MOE is greater than the target MOE of 100 and therefore does not present a risk of concern for dermal exposure from treated carpets. Page 39 of 57 Table 4.4. Short term Risks Associated with Postapplication Exposure to Disinfectant on Carpets.

Parameter Value Rationale Application Rate 1000 ft2/ gallon of solution USEPA Assumption % a. i. in Formulated Product 1.62% Maximum rate listed on label (# 8383 3)

Formulated Product in solution 2 oz/ gallon Assumption Density of cleaning solution 1.0 g/ mL Assumed to be similar to density of water Flux Rate of Chemical from Carpet 0.13 mg/ m2/ day ( Density) * (% a. i.) * ( Formulated Product in Sol.) * ( 25% remaining)* ( 5% transfer) / ( App. Rate) * ( Conversion Factors)

Surface Area of Body in Contact with Carpet 0.657 m2 Median surface area of toddler Dermal Absorption 50%

Body Weight 15 kg Median body weight of toddler Potential Dermal Exposure 0.0028 mg/ kg/ day FR * SA * DA/ BW Dermal NOAEL 60 mg/ kg/ day Dermal MOE 21,000 ( Derm. NOAEL) / ( Daily Derm. Dose). Target MOE = 100.

Incidental Ingestion In addition to dermal exposure, infants crawling on treated carpets will also be exposed to phenol via incidental oral exposure during hand to mouth activities. To calculate incidental ingestion exposure to phenols due to hand to mouth transfer, the scenarios established in the Standard Operating Procedures ( SOPs) for Residential Exposure Assessments were used. These scenarios use assumptions that are similar to those used in calculating exposures due to dermal contact of phenols from toddlers crawling on treated carpets. The assumptions above in the dermal assessment ( Table 4.4) estimates the transferable residues as 0.013 µ g/ cm2 . The estimated potential ingestion dose rate immediately after application would be calculated as follows:

PDR norm= ISR t x SA x FQ x SE x ET x 0.001 mg/ µ g BW where:

PDR norm = Potential dose rate ( mg/ kg/ day); ISR t = Indoor Surface Residue ( µ g/ cm2) at time 0; SA = Surface area of the hands that contact both the treated area, and the individuals mouth ( cm2/ event); FQ = Frequency of hand to mouth events ( events/ hr); Page 40 of 57 SE = Saliva extraction efficiency; and, ET = Exposure Time ( 4 hrs/ day) BW = Body weight ( 15 kg)

The surface area used for each hand to mouth event is 20 cm2 . It is assumed that there are 20 handto mouth exposure events per hour ( 90th percentile). The short term incidental oral NOAEL of 60 mg/ kg/ day should be used as the toxicity endpoint for this scenario because of the intermittent nature of carpet shampoos at both residents and day care centers. The potential dose rate ( PDR) using this equation is 0.0007 mg/ kg/ day resulting in a hand to mouth short term MOE for toddlers of 86,000. Inhalation Exposure Carpet Treatments: Post application inhalation exposure to adults and toddlers after phenol use ( as a carpet cleaner) is concern because of the relatively high vapor pressure of phenol ( i. e., 0.341 mm Hg @ 25C). No postapplication air concentration data have been submitted to determine potential inhalation risk to the vapor phase. Therefore, EFAST was used to present a screening level estimate of the potential shortterm inhalation risk. The post application estimates are based on the EFAST results for the air concentration and inhalation dose from the adult handlers. The toddler risk estimates are corrected for the lower body weight ( i. e., 15 kg).

EFAST was used to model the air concentration from carpet cleaning using the general purpose cleaner portion of the model ( i. e., specific assessment of carpet cleaners are not available). The weight fraction is 0.002 ( 1.62% ai x 2 fl oz/ 128 oz per gallon conc x 8 lb per gallon density of carpet wash/ water = weight fraction of 0.002 or 0.2 percent). EFAST indicates a peak concentration of 0.90 mg/ m3. Because the peak instantaneous concentration does not represent a daily inhalation exposure, the daily dose rather than the peak estimate from EFAST is used to compare to the short term inhalation toxicological endpoint. If a short term toxicological endpoint of less than one day were to be generated it should be compared to the peak air concentration estimate. However, because the toxicological endpoint of concern is based on greater than one day of exposure, the daily dose rate of 0.008 mg/ kg/ day from EFAST is used in this assessment for adults based on an average daily air concentration of 0.044 mg/ m3. The toddler's dose is extrapolated from the adult value presented in EFAST and is estimated as 0.038 mg/ kg/ day for toddlers ( i. e., 0.008 mg/ kg/ day x 71.8 kg adult BW x ( 1/ 15 kg toddler BW)). The inhalation MOE for adults is not of concern ( i. e., MOE = LOAEL of 26 mg/ kg/ day / 0.008 mg/ kg/ day = 3,300, target MOE of 300). Based on the same scenario, the toddler inhalation risk, scaled to the weight of the toddler is not of concern ( i. e., MOE = LOAEL of 26 mg/ kg/ day / 0.038 mg/ kg/ day = 680, target MOE of 300). The risks for the toddlers were scaled by body weight but not breathing rate. The breathing rate of a toddler is lower than that of an adult and therefore the MOEs would be slightly higher. Page 41 of 57 Painting:

In addition to the estimates provided above for post application inhalation exposure, estimates are provided for post application inhalation exposure to paints because of the high vapor pressure of phenol. The WPEM used in the painting scenario above was also used for the post application assessment. The toddler post application assessment from WPEM uses a body weight of 20.3 kg, a slight deviation from EPA's estimate of 15 kg. WPEM estimated a peak instantaneous concentration of 5.28 mg/ m3 after painting and a acute potential dose rate ( representing the highest 24 hour exposure) of 1.3 mg/ kg/ day. Although the peak instantaneous concentration is available, it is not representative of the short term inhalation toxicological endpoint. WPEM also estimates an average daily dose with a daily air concentration of 0.022 mg/ m3 and a dose of 0.011 mg/ kg/ day which corresponds to a MOE of 2,400 ( i. e., LOAEL 26 mg/ kg/ day / 0.011 mg/ kg/ day). The short term target MOE is 300, and therefore, the risk is not of concern. Page 42 of 57 5.0 AGGREGATE RISK ASSESSMENTS AND RISK CHARACTERIZATION In order for a pesticide registration to continue, it must be shown that the use does not result in " unreasonable adverse effects on the environment". Section 2 ( bb) of FIFRA defines this term to include " a human dietary risk from residues that result from a use of a pesticide in or on any food inconsistent with standard under section 408..." of FFDCA. Consequently, even though no pesticide tolerances have been established for phenol and phenol salts, the standards of FQPA must still be met, including " 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 nonoccupational sources, for all known or plausible exposure routes ( oral, dermal, and inhalation).

5.1 Acute and Chronic Dietary Aggregate Risk The acute and chronic aggregate risk assessments generally include both dietary and drinking water exposures. Drinking water exposure is not expected from the indoor uses of phenol and phenol salts; thus, drinking water exposure is not assessed in this document.

The ADTC determined that for acute dietary risk, there was no appropriate endpoint for assessment of acute dietary exposure. As a result, acute dietary risk estimates were not calculated.

Cumulative chronic dietary risk estimates from indirect food uses ( i. e., exposure to disinfectant solutions and room deodorizers) were calculated to be 36% for children, 9.0% for adult females, and 7.5% for adult males, indicating no risk of concern from dietary exposure.

5.2 Short, Intermediate, and Long Term Aggregate Risk In accordance with the policy of the Office of Pesticide Programs, short, intermediate, and long term aggregate risk typically includes dietary exposures ( food and water) and residential exposures that can be thought of as occurring together. For homeowner residential scenarios, exposures are interpreted as only short or intermediate term; exposures are not felt to be long term.

The study and endpoint defining toxicity by the oral and dermal routes was the same as determined by the ADTC committee. Therefore, dietary, incidental oral, and dermal exposure scenarios are aggregated as appropriate. Inhalation exposures are considered separately as there was a route specific study and different toxic effects by this route of exposure.

Based on the above, for adults, chronic dietary exposure is aggregated with the dermal exposure from one cleaning scenario. ( The painting scenario was not chosen to aggregate since the dermal MOEs for both the airless sprayer and brush/ roller already exceed the Agency's level of concern for handlers ( i. e., an individual who paints his/ her house.) For toddlers, aggregate exposure would involve dietary exposure and dermal plus incidental oral exposures to treated carpets.

Inhalation aggregate exposures were not considered necessary, as the exposures arising from adult activities ( vapor from painting, cleaning products, and application of phenol products to carpet) and toddlers ( exposure to vapor from paint and from carpet cleaning products) were felt not to co occur. Page 43 of 57 Thus individual Margins of Exposure define any risks of concern from these exposures. Individual Margins of Exposure for inhalation exposure scenarios for phenol which included painting ( roller or airless sprayer) and hard surface disinfection ( towelette and spray) were found to be acceptable for these scenarios ( 6500/ 290 for roller and airless spraying paint scenarios; 1500 and 79,000 for disinfection towelette and spray respectively).

As the study and endpoint selected for phenol describing effects from dermal and oral exposure was the same for all durations of exposure, exposure scenarios can be aggregated according to the guidance set forth in HED SOP 2000.2, Risk Assessment Guidance. This approach is similar to that using the Total MOE method as described in the Office of Pesticide Programs' guidance " General Principles for Performing Aggregate Exposure and Risk Assessments" ( USEPA, 2001).

The results of this approach are summarized in the following table:

Table 5.1 Short Term and/ or Intermediate Term Aggregate Oral/ Dermal Risk Calculations ( Oral and Dermal Endpoints and NOAELs are the Same)

Population Short or Intermediate Term Scenario NOAEL mg/ kg/ day Target MOE1 Max Exposure2 mg/ kg/ day Average Food Exposure mg/ kg/ day Residential Exposure3 mg/ kg/ day Aggregate MOE ( food and residential) 4 Adult Male 60 100 0.6 0.045 0.46 119 Adult Female 60 100 0.6 0.054 0.46 117 Toddlers 60 100 0.6 0.216 0.0035 273 110x intraspecies, 10x interspecies uncertainty factors applied. 2 Maximum Exposure ( mg/ kg/ day) = NOAEL/ Target MOE 3 Residential Exposure = Dermal exposure from cleaning ( adults); dermal + incidental oral exposure from carpets ( toddlers)

4 Aggregate MOE = [ NOAEL ÷ ( Avg Food Exposure + Residential Exposure)] Target MOE of 100.

As noted in the above table, aggregate MOEs are not of concern for adults or children based on the scenarios aggregated. Page 44 of 57 6.0 Occupational Exposure A detailed human exposure risk assessment for phenol and phenol salts is provided in the Appendix. The summary of the occupational exposures and risks are presented below.

6.1 Occupational Handlers Inhalation and dermal handler exposures were addressed for occupational populations using surrogate data from the Chemical Manufacturers Association ( CMA, 1992) and PHED. Using surrogate unit exposure data, application rates from labels, and EPA estimates of daily amount handled, exposure and risks to handlers and postapplication workers were assessed. At this time, EPA has not identified postapplication scnearios for commercial uses that are not addressed by the residential postapplication exposure assessment ( e. g., the contacting treated surfaces are represented by children's incidental oral and dermal exposures while crawling on treated surfaces such as carpets).

The following commercial/ institutional scenarios have been considered in this assessment:

11. Liquid pour of the formulated product as a material preservative ( paint), 12. Use of disinfectant solutions in hemodialysis machines, 13. Application of paint treated with a material preservative using airless sprayer, 14. Application of paint treated with a material preservative using paintbrush/ roller, 15. Use of disinfectant/ deodorizing spray on hard non porous surfaces, and 16. Use of disinfectant towelette on hard non porous surfaces For hemodialysis machines, the label indicates that the product can be used in single patient and multiple patient delivery systems. The use of this product in multi patient delivery systems was chosen for evaluation since it involves a greater volume of product ( 1.0 L vs. 0.150 mL) than the single patient delivery system. It was assumed that the machines are disinfected daily and on average, a worker handles 3 machines per day. Page 45 of 57 One phenol product is listed for use as an industrial additive, and lists paint as a possible use. The label recommends that between 2% 5% by active ingredients be added. As a conservative measure, it is assumed that the treated paint is comprised of 5% active ingredient, by weight. Assuming that paint has a density of 10 lbs per gallon, the concentration of phenols in paint is 0.5 lbs a. i./ gallon. For the material preservative use of phenol, primary handlers adding the product during the manufacturing of paint has been selected to represent the high end of exposure for the primary handlers. It is assumed that paint is produced in 1,000 gallon batches ( i. e., 10,000 lbs). In addition, painting has also been selected to represent the high end of the exposures for the painters using the preserved paint. Two painting scenarios were considered in this assessment: use of an airless sprayer ( 50 gallons per day) and use of a paintbrush/ roller ( 5 gallons per day) to paint the exterior and/ or interior of houses.

The sprays and the solution used to treat the towelette contain 1.62% phenol/ sodium phenate. It was assumed that the density of this solution is the same as the density of water. The label for the towelette product did not describe the quantity of product to be used; rather, the directions state that the towelette is to be used to wipe the surface, and then the surface should be wiped dry. In the absence of more specific use information, it was assumed that 1 liter of the solution used to wet the towelette is used by the exposed individual per day. Similarly, the aerosol spray directions state that the product can be sprayed 2 4 seconds to deodorize a room, but no data were available describing the quantity of product that is emitted by spraying for this time. Therefore, 1 liter of solution was also assumed for use of the aerosol spray.

The results of the MOE analysis for these scenarios are presented in Table 6.1. The estimated short and intermediate term dermal MOEs for the following scenarios were below the target MOE of 100, and are therefore of concern:

° Painting using an airless sprayer, with chemical resistant gloves ( MOE = 21); and ° Wiping hard surfaces using a towelette ( MOE = 70).

The estimated short and intermediate term inhalation MOEs for the following scenarios were below the target MOE of 300, and are therefore of concern:

° Painting using an airless sprayer ( MOE = 88).

The aerosol inhalation exposure and risk estimates from CMA and PHED discussed above do not account for the potential vapor inhalation exposure to phenol ( phenol has a relatively high vapor pressure). Therefore, the potential vapor inhalation exposure to handlers are addressed by modeling of the air concentrations. Because the occupational handlers for the cleaning products use the same weight fraction of phenol as the residential handlers, the same type of application techniques ( i. e., wipes, sprays), and will clean in various rooms to accommodate the additional amount handled ( e. g., moving room to room in a hotel), the air concentrations and vapor inhalation risk estimates will be similar to those experienced by the residents from the EFAST assessment presented above. Based on these assumptions, the short and intermediate term vapor derived inhalation risks are not of concern ( i. e., MOEs greater than the target MOE of 300 for the average daily dose). For commercial painters, the WPEM estimated a peak instantaneous concentration of 23 mg/ m3 while painting. WPEM also estimates an average daily dose for professional painters of 0.36 mg/ kg/ day which corresponds to a MOE of 72 ( i. e., LOAEL 26 mg/ 0.36 mg/ kg/ day). This risk estimate is of concern ( ST/ IT target MOE is 300 and long term target target MOE is 1,000). Table 6.1. Calculation of Dermal and Inhalation MOE for Commercial/ Institutional Scenariosa Page 46 of 57 Exposure Scenario Method of Applicati on Dermal Unit Exposure ( mg/ lb ai) b Inhalatio n Unit Exposur e ( mg/ lb ai) c Appl. Rate d ( lb a. i./ gal) Amount Treated Absorbed Dermal Dose ( mg/ kg/ day ) f Dermal MOE g Inhalation Dose ( mg/ kg/ day) h Inhalatio n MOE i Material Preservative ( Paint) Liquid Pour 0.135 ( CMA gloves) 0.00361 ( CMA) 5% by weight 10,000 lbs of paint 0.56 110 0.030 870 Hemodialysis Liquid Pour 36.5 ( CMA gloves) 1.89 ( CMA) 0.187 lbs a. i./ delivery system 3 delivery systems/ d ay 0.171 350 0.015 1700 Painting Airless Sprayer 14 ( PHED gloves) 0.83 ( PHED) 0.5 50 gal/ day 2.9 21 0.296 88 Paintbrus h/ Roller 24 ( PHED gloves) 0.28 ( PHED) 0.5 5 gal/ day 0.50 120 0.010 2600 Hard Surface Disinfection Towelette 2870 ( CMA no gloves) 67.3 ( CMA) 0.0357 lbs a. i./ liter used 1 liter of product 0.854 70 0.0343 760 Aerosol Spray 81 ( PHED gloves) 1.3 ( PHED) 0.0357 lbs a. i./ liter used 1 liter of product 0.024 290 0.00066 39,000 a MOEs rounded to 2 significant figures. b Dermal unit exposures are from CMA and PHED, gloves worn as indicated. c Inhalation unit exposures are from CMA and PHED. d Application rates are based on the phenol labels. It is assumed that both the phenol and sodium phenate present in products are active ingredients. f Abs. dermal dose ( mg/ kg/ day) = [ unit exposure ( mg/ lb ai) * Dermal Absorption Factor ( 0.5) * Appl. rate ( lb ai/ gallon) * gallons handled / Body weight ( 60 kg). g MOE = NOAEL ( mg/ kg/ day) / Daily Dose [ Where short and intermediate term dermal NOAEL = 60 mg/ kg/ day]. Target MOE is 100. h Inhalation dose ( mg/ kg/ day) = [ unit exposure (  g/ lb ai) * 0.001 mg/  g unit conversion * max appl rate ( lb ai/ gal) * gallons handled * 1 inhalation absorption] / Body weight ( 70 kg). i MOE = LOAEL ( mg/ kg/ day) / Daily Dose [ LOAEL for all durations = 0.1 mg/ L ( which equals 0.1 mg/ L * 10.26 L/ hr/ kg * 6 hrs/ day / 0.236 kg = 26.08 mg/ kg/ day]. Target MOE is 300 for short and intermediate term. Page 47 of 57 6.2 Occupational Postapplication The potential short and intermediate term occupational postapplication exposures to phenol are based on the relatively high vapor pressure. Postapplication inhalation exposure is expected for workers remaining in areas of treatment ( e. g., medical personnel, janitors, etc). At this time, air concentration measurements taken after phenol treatments are not available. In addition, modeled results for inhalation exposure are not specific for occupational postapplication uses. Therefore, the air concentration for the 1.62% product in the EFAST model estimate listed in the residential handler section above was used. The average daily air concentration is 0.352 mg/ m3. Using an 8 hour workday, the dose is estimated to be 0.050 mg/ kg/ day ( i. e., 0.352 mg/ m3 x 1.25 m3/ hr breathing rate x 8 hr/ day x ( 1/ 70 kg BW)). The short and intermediate term inhalation MOE is 520, and therefore, not of concern ( i. e., LOAEL of 26 mg/ kg/ day / 0.05 mg/ kg/ day, target MOE = 300).

7.0 ENVIRONMENTAL FATE ASSESSMENT Phenol is registered with OPP as an active product and is used as an intermediate in the production of epoxy resins, the production of various other products, as a general disinfectant and in medicinal preparations. For the reregistration eligibility decision ( RED) process the Agency has relied on open literature and fate properties of Phenol obtained from open literature. The following fate properties were obtained from an open literature search.

1. Vapor Pressure: 0.341 mm Hg 2. Henry law Constant ( air/ water partition coefficent): 4.0 x 10 7 m3/ mole 3. Log K OC ( organic carbon ratio in soil): 1.21 1.96 4. Log K OW ( octanol/ water partition coefficient): 1.46 5. Absorbs light in the region of 290 330 nm, may photodegrade directly in surface water. 6. Half life in freshwater < 1 day. 7. Biodegrades completely in soil within 5 days. 8. Estimated half life for gas phase reaction of phenol with photochemically produced hydroxyl radicals is 0.61 days ( Overall half life < 1 day). 9. Log bioconcentration factor ( BCF) is 0.28 in goldfish and 1.3 for golden orfe.

Phenol is not expected to bioaccumulate in plants, even though plants readily absorb phenol, because of the high respiratory decomposition rate of phenol to CO 2. Phenol does not pose concerns to aquatic organisms due to the low BCF and the rapid biodegradation in water. Page 48 of 57 8.0 ECOTOXICOLOGY ASSESSMENT Phenol and sodium phenate are used as sanitizers, primarily for hard surfaces and as materials preservatives. Outdoor uses, such as swimming pool waters and intermittently flooded areas, were once registered uses for phenol and sodium phenate, but are apparently no longer supported by any registrants. The following assessment of ecological and environmental risk is therefore based only on indoor uses for these chemicals.

8.1 Terrestrial Animals For indoor uses, an acute oral toxicity study using the technical grade of the active ingredient ( TGAI) is required to establish the toxicity of phenol to birds. The preferred test species is either mallard duck ( a waterfowl) or northern bobwhite quail ( an upland game bird). No avian acute toxicity studies were identified in the reviewed literature for phenol or its salts. Avian acute oral toxicity testing ( 850.2100/ 71 1) is required to support the currently registered uses of phenol/ sodium phenate.

Avian dietary toxicity studies using the TGAI of phenol and its salts are not required for the indoor uses of phenol/ sodium phenate.

8.2 Freshwater Fish Freshwater fish toxicity studies using the TGAI are required to establish the toxicity of phenol to fish. Data are generally required for only one species. Testing in two fish species is required for stable chemicals with high volume effluents ( e. g., including, but not limited to, egg washing, fruit and vegetable rinses, swimming pools or materials preservatives) and if the LC 50 in the first species is greater than (>) 1 ppm. The preferred test species are rainbow trout ( a coldwater fish) and bluegill sunfish ( a warmwater fish), although other test species identified in the OPPTS Guideline ( i. e., OPPTS 850.1075 ( e)( 4)( i)( A)) may also be used. Many freshwater fish acute toxicity studies were identified from peer reviewed literature, but no studies have been submitted to support registration of phenol/ sodium phenate. Freshwater fish acute toxicity testing ( 850.1075/ 72 1) on one species is required to support the currently registered uses of phenol/ sodium phenate.

The results from freshwater fish acute toxicity studies obtained from peer reviewed literature are summarized in the table below ( Table 8.1).

Table 8.1. Acute Toxicity of Phenol to Freshwater Fish Organism Results  LC50 ( mg/ L) ( 95% Confidence Limit) Toxicity Category Comments Reference Rainbow trout ( Oncorhynchus mykiss) 5.02 ( 4.23  7.49) moderately toxic  96h test duration;  juvenile organisms;  renewal system EPA AWQC, 1980; and U. S. EPA, 2002b Rainbow trout ( Oncorhynchus mykiss) 11.6 slightly toxic  96h test duration;  flow through system  used active ingredient concentration EPA AWQC, 1980; and U. S. EPA, 2002b Organism Results  LC50 ( mg/ L) ( 95% Confidence Limit) Toxicity Category Comments Reference Page 49 of 57 Rainbow trout ( Oncorhynchus mykiss) 13.1 ( 11.9 14.1) slightly toxic  48h test duration;  system type not reported;  used active ingredient concentration Tisler and Zagorc Koncan, 1995 Rainbow trout ( Oncorhynchus mykiss) 6.1 ( 5.5 6.8) moderately toxic  96h test duration;  flow through system;  used active ingredient concentration U. S. EPA, 2002b Rainbow trout ( Oncorhynchus mykiss) 8.9 moderately toxic  96h test duration;  flow through system U. S. EPA, 2002b Rainbow trout ( Oncorhynchus mykiss) 9.7 moderately toxic  96h test duration;  flow through system;  used active ingredient concentration Hodson et al., 1984; U. S. EPA, 2002b Rainbow trout ( Oncorhynchus mykiss) 10.5 ( 9.1  12.2) slightly toxic  96h test duration;  flow through system;  used active ingredient concentration U. S. EPA, 2002b Rainbow trout ( Oncorhynchus mykiss) 7.7 moderately toxic  96h duration;  flow through system U. S. EPA, 2002b Rainbow trout ( Oncorhynchus mykiss) 8.9 moderately toxic  96h duration;  flow through system U. S. EPA, 2002b Bluegill ( Lepomis macrochirus) 17.4 ( 11.9  25.3) slightly toxic  96h test duration;  flow through system  used active ingredient concentration. U. S. EPA, 2002b Bluegill ( Lepomis macrochirus) 13.5 slightly toxic  96h test duration;  static system EPA AWQC, 1980; and U. S. EPA, 2002 Bluegill ( Lepomis macrochirus) 19.3 slightly toxic  96h test duration;  juvenile organisms;  renewal system EPA AWQC, 1980; and U. S. EPA, 2002 Bluegill ( Lepomis macrochirus) 11.5 slightly toxic  96h test duration;  renewal system;  used active ingredient concentration. EPA AWQC, 1980; and U. S. EPA, 2002 Bluegill ( Lepomis macrochirus) 23.9 ( 20.2  31.5) slightly toxic  96h test duration;  static system EPA AWQC, 1980; and U. S. EPA, 2002 As shown in Table 8.1, acute toxicity for freshwater fish ranged from 5 mg/ L ( rainbow trout) to 23.9 mg/ L ( bluegill), with average values of 9.1 mg/ L for rainbow trout and 17.1 mg/ L for bluegill. These data indicate that phenol is moderately toxic to coldwater species, such as the rainbow trout, and Page 50 of 57 slightly toxic to warmwater species, such as the bluegill.

Fish early life stage testing is not required for the currently registered indoor uses of phenol/ sodium phenate.

8.3 Freshwater Invertebrates A freshwater aquatic invertebrate toxicity test using the TGAI is required to establish the toxicity of a pesticide to aquatic invertebrates. The preferred test species is Daphnia magna or Daphnia pulex. Many acute toxicity studies were identified for these species in peer reviewed literature, but no studies have been submitted by registrants to support the registered uses of phenol or sodium phenate. Freshwater invertebrate acute toxicity testing ( 850.1010/ 72 2) is required for the currently registered uses of phenol/ sodium phenate. The results of the studies obtained from peerreviewed literature are summarized in Table 7.2.

Table 8.2. Acute Toxicity of Phenol to Freshwater Invertebrates Organism Results  EC50 ( mg/ L) ( 95% Confidence Limit) Toxicity Category Comments Reference Water flea ( Daphnia magna) 9.6 moderately toxic  48h test duration;  static system EPA AWQC, 1980; and U. S. EPA, 2002b Water flea ( Daphnia magna) 7 moderately toxic  50h test duration;  juvenile organisms;  static system EPA AWQC, 1980; and U. S. EPA, 2002b Water flea ( Daphnia magna) 88 slightly toxic  48h test duration;  static system EPA AWQC, 1980; and U. S. EPA, 2002b Water flea ( Daphnia magna St.) 0.102 ( mmol/ L) (= 9.6 mg/ L) moderately toxic  48h test duration;  renewal system Arambasic et al., 1995 Water flea ( Daphnia magna Strauss) 33.9 ( 30  39.2) slightly toxic  24h test duration;  system type not reported  used active ingredient concentration Tisler and Zagorc Koncan, 1995 Water flea ( Daphnia magna) 23.5 ( 21  26.3) slightly toxic  48h test duration;  static system U. S. EPA, 2002b Water flea ( Daphnia magna) 6.6 moderately toxic  48h test duration;  static system;  used active ingredient concentration U. S. EPA, 2002b Water flea ( Daphnia magna Strauss) 4.2 moderately toxic  48h test duration;  static system;  used active ingredient concentration U. S. EPA, 2002b Water flea ( Daphnia magna) 30 slightly toxic  48h test duration;  static system; U. S. EPA, 2002b Organism Results  EC50 ( mg/ L) ( 95% Confidence Limit) Toxicity Category Comments Reference Page 51 of 57 Water flea ( Daphnia magna) 12.6 ( 10.2  15.5) slightly toxic  48h test duration;  flow through system;  used active ingredient concentration U. S. EPA, 2002b Water flea ( Daphnia magna) 10 ( 8.8  12) moderately to slightly toxic  48h test duration;  static system; U. S. EPA, 2002b Water flea ( Daphnia magna) 15 slightly toxic  48h test duration;  static system; U. S. EPA, 2002b Water flea ( Daphnia magna) 5.5 ( 4.9  6.3) moderately toxic  48h test duration;  system type not reported;  used active ingredient concentration U. S. EPA, 2002b Water flea ( Daphnia magna) 12* ( 7.3  20) slightly toxic  48h test duration;  static system U. S. EPA, 2002b Water flea ( Daphnia magna) 30.1* slightly toxic  48h test duration;  system type not reported U. S. EPA, 2002b Water flea ( Daphnia magna) 32* ( 24  43) slightly toxic  48h test duration;  static system U. S. EPA, 2002b Water flea ( Daphnia magna) 8.6* ( 7.2  10.2) moderately toxic  48h test duration;  static system U. S. EPA, 2002b Water flea ( Daphnia magna) 19.8* ( 18  22) slightly toxic  48h test duration;  static system;  used active ingredient concentration U. S. EPA, 2002b Water flea ( Daphnia magna) 23* slightly toxic  48h test duration;  static system;  used active ingredient concentration U. S. EPA, 2002b Water flea ( Daphnia magna) 13* ( 10 17) slightly toxic  48h test duration;  static system U. S. EPA, 2002b Water flea ( Daphnia magna) 11.2* ( 9.8  12.6) slightly toxic  48h test duration;  static system;  used active ingredient concentration U. S. EPA, 2002b Water flea ( Daphnia magna) 8.3* ( 5.8  12.5) moderately toxic  48h test duration;  system type not reported U. S. EPA, 2002b * Endpoint in study is identified as LC 50 Page 52 of 57 As shown in Table 8.2, acute toxicity for aquatic invertebrates ( Daphnia magna) ranged from 4.2 mg/ L to 88 mg/ L. The endpoint for these studies is the EC 50 for immobilization or the LC 50. The average value for the endpoint concentrations shown in Table 8.2 is 18.8 mg/ L. Notably, when considering only the studies where the endpoint is reported to be based on the active ingredient concentration ( Table 8.2), the average concentration is relatively lower at 14.6 mg/ L. These data results indicate that phenol is moderately to slightly toxic to aquatic invertebrates.

8.4 Estuarine and Marine Organisms Acute toxicity testing with estuarine and marine organisms using the TGAI is not required for the indoor uses of phenol/ sodium phenate. Several studies on marine/ estuarine invertebrates were found in the ECOTOX database ( EPA, 2002b). The endpoints from these studies are summarized in the table below:

Table 8.3. Acute Toxicity of Phenol to Marine/ Estuarine Invertebrates Organism Results  LC50 or EC (

g/ L) ( 95% Confidence Limit) Toxicity Category Comments Reference Mysid ( Archaeomysis kokuboi) 96 hr LC50 = 260  4530 ( formulation) highly to moderately toxic  96h test duration;  static system U. S. EPA, 2002b Opossum shrimp ( Americamysis bahia) 96 h LC50 = 12,500 ( 10,700  15,600) ( formulation) slightly toxic  96h test duration;  static system U. S. EPA, 2002b Daggerblade grass shrimp ( Palaemonetes pugio) 96 hr LC50 = 5,800 ( 4330  7,770) moderately toxic  96h test duration;  static system U. S. EPA, 2002b Table 8.4. Chronic Toxicity of Phenol to Marine/ Estuarine Invertebrates Organism Results  LOEC, NOEC, MATC (

g/ L) Comments Reference Opossum shrimp ( Americamysis bahia) mortality 27 d NOEC= 2,410 LOEC = 6,880 MATC = 4,080  27 day test duration;  flow through system U. S. EPA, 2002b 8.5 Plants Terrestrial and aquatic plant testing is not required for the registered indoor uses of phenol/ sodium phenate. There were aquatic phytotoxicity endpoints reported in the ECOTOX database Page 53 of 57 ( EPA, 2002). While these data were reported in summary form, they indicate that phenol demonstrates low toxicity to various aquatic plant species, with 4 day EC 50 values ranging from 12,000 ppb ( duckweed, Lemna minor) to 370,000 ppb ( green alga, Chlorella vulgaris). 9.0 REFERENCES 34735401 ( MRID #): Jones Price, C and T. A. Ledoux. ( 1983). Teratologic Evaluation of Phenol ( CAS No. 108 95 2) in CD1 Mice. RTI.

43735402 ( MRID #): Jones Price, C and TA Ledoux. ( 1983). Teratologic Evaluation of Phenol ( CAS No. 108 95 2) in CD Rats. RTI.

Arambasic, M. B., Bjelic, S., and G. Subakov. 1995. Acute Toxicity of Heavy Metals ( Copper, Lead, Zinc), Phenol and Sodium on Allium cepa L., Lepidium sativum L. and Daphnia magna Strauss. Water Res. 29( 2): 497 503.

Argus Research Laboratories, Inc. ( 1997). Oral ( gavage) developmental toxicity study of phenol in rats. Horsham, Pennsylvania. Protocol number: 916 011.