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n-HEXANE								Related Pages
										*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:** 110-54-3; **Chemical Formula:** CH3(CH2)4CH3
OSHA’s former PEL for n-hexane was 500 ppm. The ACGIH has a 50-ppm TWA limit for this substance, and the NIOSH REL is 100 ppm as a 10-hour TWA. OSHA proposed a limit of 50 ppm TWA for n-hexane, and the final rule establishes this limit. NIOSH (Ex. 8-47, Table N1) concurs that a PEL of 50 ppm is appropriate for n-hexane. Normal hexane is a clear, volatile liquid.
n-Hexane has been shown to produce distal axonopathy in both experimental animals and humans; it is metabolized to 2,5-hexanedione (2,5-HD), which is thought to be the causative agent of most of the adverse neurological effects observed after exposure to hexane (Schaumburg, Spencer, and Thomas 1983/ Ex. 1-228).
In the preamble to the proposed rule, OSHA asked:
Does the most current scientific information generally support acceptance of the hypothesis that the C(5-8) alkanes are not equally toxic because a metabolite of n-hexane exhibits unique neurotoxic properties?Several commenters (Exs. 3-593, 3-1246, and 124; Tr. III, pp. 109-110) responded to this question, and their detailed responses are discussed in Section V of this preamble, Summary of Commenters’ Responses to NPRM Questions.
The C(5)-(8) alkanes include pentane, n-hexane, the hexane isomers, n-heptane, octane, and the refined petroleum solvents. Whether all of these alkanes exhibit the same degree of toxicity or whether one (or more) is uniquely toxic has a direct bearing on the appropriate exposure limits for these substances. Based on a thorough review of the chemical and toxicological literature and the responses of these commenters, OSHA has determined that n-hexane is uniquely toxic to the peripheral nervous system. The Agency finds that 2,5-hexanedione (2,5-HD), a metabolite of n-hexane, is likely to be responsible for this unique toxicity, and the American Petroleum Insitute (Ex. 124) agrees with this finding. NIOSH (Tr. III, pp. 109-110), on the other hand, is of the opinion that any ketone or related chemical that can be metabolized to a gamma diketone has the potential to cause peripheral neuropathy. However, representatives of the Texaco Company (Ex. 3-1246) agree with OSHA that n-hexane is uniquely toxic because its toxicity is mediated by 2,5-HD.
The ACGIH established a TLV of 50 ppm for this substance, based primarily on studies (Miyagaki 1967/Ex. 1-198; Inoue, Takeuchi, Takeuchi et al. 1970/Ex. 1-75) showing peripheral neuropathies at exposure levels as low as 210 ppm. NIOSH based its 100-ppm REL on the same studies as those cited by the ACGIH (Miyagaki 1967/Ex. 1-198; Inoue, Takeuchi, Takeuchi et al. 1970/Ex. 1-75). NIOSH reasoned as follows:
The absence of definitive epidemiologic or toxicologic evidence makes it difficult to determine how much lower the environmental limit should be. Professional judgment suggests [that] a TWA concentration of 350 mg/m3 (100 ppm) offers a sufficient margin of safety to protect against the development of chronic nerve disorders in workers (NIOSH 1977a/ Ex. 1-233, p. 74).The adverse neurological effects of hexane exposure are manifested as both sensory and motor dysfunctions. Initially, there is a symmetric sensory numbness of the hands and feet, with loss of pain, touch, and heat sensation. Motor weakness of the toes and fingers is often present; as the neuropathy becomes more severe, weakness of the muscles of the arms and legs may also be observed (Schaumburg, Spencer, and Thomas 1983/Ex. 1-228). There are no known conditions that predispose an individual to hexane neurotoxicity (Schaumburg, Spencer, and Thomas 1983/Ex. 1-228). The onset of neurological symptoms may not be evident for several months to a year after the beginning of exposure. Recovery may be complete, but severely exposed individuals often retain some degree of sensorimotor deficit.
OSHA received comments on n-hexane from several participants, including NIOSH, the National Cotton Council, the American Petroleum Institute, the Corn Refiners Association, the AFL-CIO, and the United Auto Workers. Two commenters, the National Cotton Council (Tr. pp. 9-45 to 9-47) and the Corn Refiners Association (Ex. 177), stated that the revised PEL for n-hexane would impact their members, but did not provide further detail.
Some commenters (Exs. 194 and 197: Tr. pp. 3-290 to 3-293) urged OSHA to regulate all of the refined petroleum solvents on the basis of neurotoxicity. For example, the AFL-CIO recommended a 10-ppm PEL for all such solvents, and Dr. Franklin Mirer of the United Auto Workers described feasible controls that could be used, in his opinion, to achieve this level. Dr. Philip Landrigan (Tr. pp. 3-290 to 3-293) described the neurotoxic effects of exposure to any of the refined petroleum solvents. In response to these commenters, OSHA notes that it is reducing the limits for a number of these solvents in this rulemaking; however, the scale of this undertaking is such that OSHA was unable to perform the detailed analysis necessary to evaluate the health effects, risks, and feasibility for all of the solvents in this large group of substances.
The dose-response relationship for n-hexane exposure in humans is not well defined, although it is clear that the severity of the resulting neuropathy increases as the exposure level of n-hexane increases. A number of studies have shown a consistent relationship between exposure levels of 500 ppm (OSHA’s former exposure limit) to 2000 ppm and the development of characteristic peripheral neuropathies (Yamamura 1969, as cited in ACGIH 1986/Ex. 1-3, p. 305; Yamada 1967/Ex. 1-192). Neuropathic effects have also been shown to occur at levels between 210 and 500 ppm (Takeuchi, Maluchi, and Takagi 1975/Ex. 1-217).
Reports of effects occurring at levels of 210 to 500 ppm indicate that the former OSHA PEL of 500 ppm was not adequate to protect exposed workers from adverse sensorimotor neuropathic effects, and exposure at this level thus represents a significant risk to workers. The decreased sensitivity to pain, touch, and temperature associated with n-hexane exposure can also make a worker more susceptible to injuries and accidents. Further, the delayed onset of a clinical response, which is typical of hexane exposure, increases the probability that exposure will continue until irreversible effects occur.
Both the presence of peripheral neuropathies at 210 ppm and the delay in onset of neurological symptoms indicate that workers exposed at levels above the new limit are at significant risk of developing these symptoms. OSHA therefore establishes a PEL of 50 ppm TWA for n-hexane. The Agency concludes that this PEL will substantially reduce the significant risk of peripheral neurophathies and other adverse neuropathic effects, which constitute material impairments of health and are associated with the exposures permitted at levels above the new limit.
										
							
								Page last reviewed:  September 28, 2011						Content source:  	National Institute for Occupational Safety and Health NIOSH
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