Health and Environmental Effects Profile for Isobutanol

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Health and Environmental Effects Profile for Isobutanol EPA/600/X-86/149 May 1986 PB89-12.3376 HEALTH AND ENVIRONMENTAL EFFECTS PROFILE FOR ISOBUTANOL ENVIRONMENTAL CRITERIA AND ASSESSMENT OFFICE OFFICE OF HEALTH AND ENVIRONMENTAL ASSESSMENT OFFICE OF RESEARCH AND DEVELOPMENT U.S. ENVIRONMENTAL PROTECTION AGENCY CINCINNATI, OH 45268 \ DISCLAIMER This document has been reviewed in accordance with U.S. Environmental Protection Agency policy and approved for publication. Mention of trade names or commercial products does not constitute endorsement or recommendation for use. i i PREFACE Health and Environmental Effects Profiles (HEEPs} are prepared for the Office of Solid Waste by the Office of Health and Environmental Assessment. The HEEPs are intended to support listings of hazardous constituents of a wide range of waste streams under Section 3001 of the Resource Conservation and Recovery Act (RCRA). Both published literature and information obtained from Agency program office files are evaluated as they pertain to potential human health, aquatic life and environmental effects of hazardous waste constit­ uents. The literature searched and the dates of the searches are included in the section titled "Appendix: Literature Searched." Quantitative estimates are presented provided sufficient data are available. For systemic toxicants, these include, Acceptable Daily Intakes (ADis} for chronic exposures. An ADI is defined as the amount of a chemical to which humans can be exposed on a daily basis over an extended period of time (usually a lifetime} without suffering a deleterious effect. In the case of suspected ca-rcinogens, ADis are not estimated in this document series. Instead, a carcinogenic potency factor or ql* is provided. These potency estimates are derived for both oral and inhalation exposures where pos·sible. In addition, unit risk estimates for air and drinking water are presented based on inhalation and oral data, respectively. The first draft of this document was prepared by Syracuse Research Corporation under EPA Contract No. 68-03-3112. The document was subsequently revised after reviews by staff within the Office of Health and Environmental Assessment: Carcinogen Assessment Group, Reproductive Effects Assessment Group, Exposure Assessment Group, and the Environmental Criteria and Assessment Office in Cincinnati. The HEEPs will become part of the EPA RCRA docket. 1 i i ACKNOWLEDGEMENTS The initial draft of this report was prepared by Syracuse Research Corporation under Contract No. 68-03-3228 for U.S. EPA's Office of Health and Environmental Assessment, Environmental Criteria and Assessment Office, Cincinnati, OH. Dr. Christopher DeRosa was the Technical Project Monitor and Helen Ball was the Project Officer. The final documents in this series were prepared for the Office of Solid Waste, Washington, DC. Scientists from the following U.S. EPA offices provided review comments for this document series: Environmental Criteria and Assessment Office, Cincinnati, OH Carcinogen Assessment Group Exposure Assessment Group Reproductive Effects Assessment Group Editorial review for the document series was provided by: Judith Olsen and Erma Durden Environmental Criteria and Assessment Office, Cincinnati, OH Technical support services for this document series were provided by: Bette Zwayer, Pat Daunt, Karen Mann, and Jacky Bohanon Environmental Criteria and Assessment Office, Cincinnati, OH. iv EXECUTIVE SUMMARY Isobutanol (CAS number 78-83-1} is a colorless liquid with a sweet musty odor. It is miscible· with ethanol and ether, but is partially soluble in water (Verschueren, 1983; Rowe and McCollister, 1982). In 1984, five U.S. companies at seven locations manufactured isobutanol (SRI, 1985). About 163.15 million pounds of isobutanol were produced in the United States in 1984 (USITC, 1985) and in 1981, 14 million pounds were imported (TSCA-ITC, 1980). Isobutanol is made commercially as a by-product of the oxo process (SRI, 1985) and is used primarily as a solvent and intermediate (TSCA-ITC, 1980; Lawler, 1977; Windholz, 1983). In ambient water, . hydrolysis and oxidation of isobutanol by hydroxyl radicals are not expected to be important reaction processes. In activated sludge systems, isobutanol has been significantly biodegraded. Although no data on the biodegradability of isobutanol in natural waters are available, the results of biodegradation in activated sludge are used to indicate that significant biodegradation will occur in natural waters. Volatilization of isobutanol may be significant in aquatic media (Lyman et al., 1982). The relatively low octanol/water partition coefficient (K w) and high water solubility (WS) suggest adsorption to sediments and 0 bioconcentration in aquatic organisms are unlikely. In the atmosphere, reactions with OH· radicals and NO are likely to X be the significant fate processes for isobutanol. Its half-life resulting from OH· reaction is expected to be -1 day. Removal of atmospheric isobutanol through dry deposition and adsorption onto particulate matters and subsequent deposition are likely to be insignificant. Because of its reasonably high WS, wet deposition may be somewhat significant in removing atmospheric isobutanol. v Based on its behavior in aquatic media, both volatilization and bio­ degradation processes are expected to play important roles in the loss of isobutanol from soil. The estimated Koc data also indicate that isobuta­ nol should be highly mobile in soil. If the biodegradation of isobutanol in soil becomes less competitive compared with its leachability in soil, substantial leaching of the compound into groundwater will occur. The general population is almost continuously exposed to low levels of "natural" isobutanol (U.S. EPA, 1983), which is produced by the fermentation of carbohydrates (Windholz, 1983). Thus, isobutanol can enter air, water and food from a variety of sources; however~ considerably higher concentra­ tions of isobutanol are expected to evolve from sites where isobutanol is produced, processed or used, rather than from nature (U.S. EPA, 1983). Isobutanol has been monitored in river water and one groundwater sampling area (Yasuhara et al., 1981; Botta et al., 1984). Several sources of emissions into air have been reported, including volatilization from palm mill effluent (Hwang et al., 1978), petrochemical processes and storage, solvent use and animal wastes (Graedel, 1978; Yasuhara et al., 1984). Isobutanol has been found in various edible items 1ncluding some fruit (SRC, 1980}, fried chicken (Tang et al., 1983) and most alcoholic beverages (TSCA-ITC, 1980). Dermal exposure may result primarily from the use of products containing isobutanol as a solvent or during its direct use as a solvent (Luedersdorf et al., 1985; U.S. EPA, 1983). Concentrations of isobutanol acutely toxic to the aquatic species studied are measured in g/1, indicating that isobutanol is relatively nontoxic and not likely to cause ecological effects in the environment (TSCA-ITC, 1980}. Sublethal effects have been reported at lower concentra­ tions, the most sensitive of which was the threshold for cell multiplication vi inhibition of the bacterium Pseudomonas outida at 280 mg/!L The limited information available indicates that isobutanol is not highly toxic to aquatic organisms. I sobutano 1 is readi 1y absorbed through gas troi ntes tina 1 and pulmonary mucosa (Browning, 1965; Saito, 1975; Bonte et al., 1981). It is metabolized to isobutyraldehyde, then to isobutyric acid, which may enter the tricar­ boxylic acid cycle by a Coenzyme A-mediated pathway (Saito, 1975). While Saito (1975) detected unchanged isobutanol, acetaldehyde, acetic acid, isobutyraldehyde and isovaleric acid in the urine of rabbits dosed orally with isobutanol, Kamil et al. {1953) failed to detect aldehydes in the urine or breath of orally dosed rabbits. Kamil et al. (1953) administered -618 mg/kg isobutanol by gavage to rabbits. After 24 hours, 4.4% of the dose was excreted as a glucuronic acid conjugate in the urine. Analysis of urinary or breath data suggested that a negligible fraction of orally administered isobutanol was excreted as unchanged isobutanol within 40 hours after administration to rabbits (Saito, 1975}. In lifetime studies, rats given isobutanol by gavage at 0.2 mt/kg (160 mg/kg} 2 days/week or subcutaneous 1y at 0. 05 ml/kg ( 40 mg/kg) 2 days/week had increased incidences of total tumors, relative to controls; however, no significant increase of any particular tumor type was observed (Gibel et al., 1974, 1975}. Therefore the data are inadequate to assess the carcino­ genicity of isobutanol. Hilscher et al. (1969) showed that isobutanol could induce reverse mutation in Escherichia coli without metabolic activation. Although no studies regarding the effects of isobutanol on mammalian repro­ duction were located in the available literature, Clegg (1964) observed embryolethality in chicken eggs treated with the alcohol. vii \ ' In the carcinogenicity study by Gibel et al. (1974, 1975), rats treated orally with 0.2 mil/kg (160 mg/kg) 2 days/week until they died had a mark­ edly lower mean survival time than did controls. Non-neoplastic lesions, including necrosis and fatty degeneration of the liver, cirrhosis and hepatitis, appeared to be treatment-related. Rats exposed to a 2 M concentration of isobutanol in drinking water for 2 months had gastric and intestinal hemorrhage, decreased liver-to-body weight ratios, decreases in fat, glycogen and RNA content of the liver and smaller hepatocytes (Hillbom et al., 1974a,b). Mallory's alcoholic hyaline bodies
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