2-HEXANONE

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: 591-78-6; Chemical Formula: CH₃CO – CH₂CH₂CH₂CH₃

OSHA’s former PEL for 2-hexanone was 100 ppm TWA; the NIOSH REL is a 1 ppm (10-hour) TWA; and the ACGIH recommends a TLV-TWA of 5 ppm. The Agency proposed, and the final rule establishes, a permissible exposure limit of 5 ppm as an 8-hour TWA for 2-hexanone. 2-Hexanone is a colorless, volatile liquid with a characteristic acetone-like odor that is more pungent than that of acetone.

Industrial exposure to 2-hexanone causes distal neuropathy manifesting as interference with motor and sensory function; even in cases characterized by minimal intensity, electrodiagnostic abnormalities were seen (ACGIH 1987/Ex. 1-16). In animals, exposure to 2-hexanone causes axonal swelling and thinning of the myelin sheath. A metabolite of 2-hexanone, 2,5-hexanedione, appears to be responsible for the neural damage; this same metabolite is formed when n-hexane (discussed above) is metabolized. Exposures of rats, cats, dogs, monkeys, hens, and guinea pigs to 2-hexanone have resulted in peripheral neuropathies (O’Donoghue 1985). Krasavage, O’Donoghue, and Terhaar (1978) reported that 2,5-hexanedione is 3.3 times more neurotoxic than 2-hexanone and 38 times more neurotoxic than n-hexane in rats. Thus, 2-hexanone would be approximately eleven times more neurotoxic than n-hexane in rats.

The limit of 5 ppm TWA for 2-hexanone recommended by the ACGIH is based on the results of several studies. These include studies showing evidence of peripheral neuropathy at levels of 50 ppm and above after exposures lasting six months or more (Johnson, Anger, Setzer et al. 1979/Ex. 1-984; Streletz, Duckett, and Chambers 1976/Ex. 1-1067). Another study identified 2,5-hexanedione (the metabolite believed responsible for neurotoxic effects) in the serum of humans after a one-day exposure to 50 ppm (DiVincenzo, Kaplan, and Dedinas 1976/Ex. 1-1049).

The NIOSH REL for 2-hexanone of 1 ppm (10-hour TWA) is based on an epidemiologic study describing an outbreak of neurologic disease among workers in a plant that manufactures printed fabrics (Allen, Mendall, Billmaier et al. 1975/ Ex. 1-80). This study reported that a screening of 1,157 exposed workers revealed 86 verified cases of distal neuropathy. 2-Hexanone was suspected of being the neurotoxicant because it had only recently been introduced into the process (Allen, Mendall, Billmaier et al. 1975/Ex. 1-80). When recommending its limit, NIOSH relied on an industrial hygiene survey of the plant conducted by Billmaier, Yee, Allen et al. (Ex. 1-76) in 1974, which showed that 2-hexanone concentrations near the textile printing machines ranged from 1 to 156 ppm (10-minute area samples). After reviewing this evidence, NIOSH concluded that 1 ppm could not be considered a no-effect level for 2-hexanone-induced neuropathy, and NIOSH (Ex. 8-47, Table N2; Tr. p. 3-86) continues to recommend a limit of 1 ppm TWA for 2-hexanone. The AFL-CIO (Ex. 194) also supports the adoption of the lower NIOSH REL. Dr. Franklin Mirer of the AFL-CIO (Ex. 197) described controls for use in workplaces where solvents present exposure problems.

The ACGIH (1987/Ex. 1-16) stated that interpretation of the results of the Billmaier, Yee, Allen et al. (1974/Ex, 1-76) study was complicated because the exposure measurements reported in the study had been taken after the outbreak of neuropathic effects had occurred. In addition, the ACGIH pointed out that Billmaier and colleagues (1974/Ex. 1-76) found poor work practices at the plant (gloves were rarely used, employees washed their hands with solvent, etc.); thus, dermal exposure may have contributed substantially to the outbreak.

Both human and animal studies show the development of disease at exposure levels well below the former 100-ppm PEL, clearly indicating the need to reduce this significant risk. In the final rule, OSHA is establishing a 5-ppm (8-hour TWA) PEL for 2-hexanone. The Agency concludes that this limit will substantially reduce the significant risk of distal neuropathy, which constitutes a material impairment of health and has been demonstrated to occur at concentrations above the new limit.