OSHA comments from the January 19, 1989 Final Rule on Air Contaminants Project extracted from 54FR2332 et. seq. This rule was remanded by the U.S. Circuit Court of Appeals and the limits are not currently in force.
CAS: 79-46-9; Chemical Formula: CH3CHNO2CH3
OSHA’s former limit for 2-nitropropane (2-NP) was 25 ppm; OSHA proposed a limit of 10 ppm as an 8-hour TWA, and the final rule establishes this limit. The ACGIH classifies 2-nitropropane as a suspected human carcinogen (A2). NIOSH recommends that 2-nitropropane exposure be reduced to the lowest feasible limit. 2-Nitropropane is used as a chemical intermediate, a solvent, and a component in paint, ink, and varnishes (Fiala, Czenniak, Castonguay et al. 1987/Ex. 1-248). 2-Nitropropane is a colorless liquid.
In rats and chimpanzees, 2-NP is metabolized by microsomal enzymes in the liver to acetone, low levels of isopropanol, and nitrite (Mueller, Coulston, and Korte 1983/Ex. 1-247). Methemoglobin formation is associated with the metabolism of nitropropane and has been reported in cats exposed to 280 ppm of 2-NP for seven hours. Sensitivity to the toxic effects of 2-NP in animals varies by species (Dequidt, Vasseur, and Potencier 1972/Ex. 1-813; ACGIH 1986/Ex. 1-3, p. 441).
The mechanisms of carcinogenicity of 2-NP are thought to involve the release of nitrite and the formation of a reactive azoxy intermediate that can react with cellular macromolecules (Williams and Weisburger 1986/Ex. 1-65).
In mutagenicity tests, 2-NP increased the frequency of mutations in all strains of Salmonella typhimurium with and without metabolic activation. Positive mutagenicity results were reported in Salmonella typhimurium strains TA100, TA1535, and TA98 by Lofroth, Nilsson, and Anderson (1981, as cited in ACGIH 1986/Ex. 1-3, p. 441) and Speck, Meyer, Zeiger, and Rosenkranz (1982/Ex. 1-290). 2-NP was not shown to be mutagenic in the mouse micronucleus test (Hite and Skaggs 1979/Ex. 1-280).
Acute exposures to 2-NP from occupational accidents have been reported to cause severe liver toxicity and subsequent death in humans (ACGIH 1986/Ex. 1-3, p. 441). However, the available epidemiology data on the chronic health effects of occupational exposure to 2-NP do not contain sufficient dose-response data to use as a basis for quantitative risk estimation. An unpublished retrospective mortality study of 1,481 potentially exposed workers from a nitropropane production plant found no increase in liver cancer or liver disease mortality. However, lack of exposure data, the small number of workers with long exposures (greater than 15 years), and a short latency period make interpretation of the results of this study difficult (Miller and Temple 1979, and Bolender 1983, both as cited in ACGIH 1986/Ex. 1-3, p. 441).
There are two studies that report high incidences of liver tumors in male rats exposed to 2-NP by gavage and inhalation. Fiala et al. (1987/Ex. 1-248) administered, by gavage, 1 mmo1/kg body weight (approximately 27 mg per treatment per 300-gram rat) of 2-NP in a 10-percent aqueous Emulphor EL-620 vehicle to male Sprague-Dawley rats three times weekly for 16 weeks. Dosing was discontinued after 16 weeks because of excessive mortality in the treated rats. Seventy-seven weeks from the first treatment, the surviving rats were sacrificed and subjected to necropsy. All (100 percent) of the treated rats examined had developed hepatocarcinomas (Fiala, Czenniak, Castonguay et al. 1987/Ex. 1-248).
The results of the Fiala et al. (1987/Ex. 1-248) study support the earlier positive results reported by Lewis, Ulrich, and Busey (1979/Ex. 1-826). In the Lewis et al. (1979/ Ex. 1-826) study, male Sprague-Dawley rats and male New Zealand White rabbits were exposed via inhalation to 27 ppm or 207 ppm of 2-NP for seven hours/day, five days/week for six months. At the end of six months, all 10 rats in the high-dose group exhibited hepatocellular carcinomas and neoplastic nodules. No exposure-related lesions were seen in the rats exposed to 27 ppm, and no exposure-related lesions were observed in any of the rabbits.
One high-dose and two low-dose studies reported negative results for rats exposed to 2-NP vapors. Griffin, Benitz, Coulston, and Rosenblum (1978/Ex. 1-243) reported no hepatic carcinomas in male and female rats exposed to 200 ppm of 2-NP by inhalation using a protocol similar to that described by Lewis et al. (1979/Ex. 1-826). Although no hepatic carcinomas were observed, the following effects (generally occurring more extensively in males) were seen: increased liver weights (both sexes); hepatic nodules; hepatocellular necrosis; and peripheral compression.
Two low-dose studies (Griffin, Coulston, and Stein 1980/ Ex. 1-268; Griffin, Stein, and Coulston 1981/Ex. 1-279) also produced negative results. Male and female Sprague-Dawley rats were exposed by inhalation to 25 ppm of 2-NP for seven hours/day, five days/week for 22 months. No pathological changes associated with exposure to 2-NP were seen.
Although the results of both the Lewis et al. (1979/ Ex. 1-826) and the Fiala et al. (1987/Ex. 1-248) studies show statistically significant increases in liver carcinomas, neither study provides sufficient dose-response information to use as a basis to quantify the excess cancer risk to humans exposed to 2-NP. Both studies were terminated before the natural lifetime expectancy of the controls, so it is not possible to determine a background incidence of cancer risk. No historical information is provided on tumor incidence for these animals.
2-Nitropropane produced a high incidence of liver tumors in male rats by two routes of administration: inhalation and ingestion. Its ability to cause mutations in Salmonella typhimurium further supports the premise that 2-NP is a potential human carcinogen. OSHA considered whether to perform a quantitative risk assessment on 2-NP, and concludes that the studies described above do not contain sufficient dose-response data to use as the basis for quantitative risk estimation using standardized risk assessment models. However, two studies (Fiala, Czenniak, Castonguay et al. 1987/Ex. 1-248; Lewis, Ulrich, and Busey 1979/Ex. 1-826) demonstrate that exposure to 2-NP, either by gavage or inhalation, produced hepatocarcinomas in rats. In addition, this substance produced positive results in two mutagenic assays (Lofroth, Nilsson, and Andersson 1981, as cited in ACGIH 1986/Ex. 1-3, p. 441; Speck, Meyer, Zeiger, and Rosenkranz 1982/Ex. 1-290). NIOSH (Ex. 8-47, Table N6B) was of the opinion that this evidence warranted a separate 6(b) rulemaking.
OSHA is establishing an 8-hour PEL for 2-NP of 10 ppm. The Agency concludes that a reduction in the PEL is necessary to protect exposed workers from the significant risk of cancer potentially associated with exposure to 2-NP at the former PEL. The Agency has also concluded that the effects associated with exposure to 2-NP constitute material impairments of health.