OSHA previously had an 8-hour limit of 50 ppm TWA for diisobutyl ketone. The Agency proposed to reduce this limit to 25 ppm TWA, based on both the ACGIH and NIOSH recommendations. NIOSH (Ex. 8-47, Table N1) concurred with this proposal, and the final rule revises OSHA's limit for diisobutyl ketone to 25 ppm as an 8-hour time-weighted average.
The primary health effects associated with exposure to diisobutyl ketone are eye, nose, and throat irritation, although experimental animals have shown some systemic effects. Diisobutyl ketone has a uniformly low acute toxicity by all routes of exposure. Rats and guinea pigs survived single exposures of from 7.5 to 16 hours to essentially saturated vapor (McOmie and Anderson 1949/Ex. 1-918). Smyth, Carpenter, and Weil (1949/Ex. 1-528) reported that five of six rats died after exposure to 2000 ppm for eight hours; these investigators also reported a percutaneous LD(50) for rabbits of greater than 20 ml/kg. Direct application of diisobutyl ketone to rabbit skin was only mildly irritating, and no eye irritation was reported after instillation of this substance into the rabbit eye. The oral toxicity for the rat was reported as 5.8 g/kg (Smyth, Carpenter, and Weil 1949/ Ex. 1-528). Carpenter and Smyth (1946/Ex. 1-859) reported a no-effect level for diisobutyl ketone of 125 ppm in rats and guinea pigs given 30 seven-hour exposures. At 250 ppm, the liver and kidney weights of female rats increased, and the liver weights of male guinea pigs decreased; at levels of 530 and 920 ppm, rats showed increased liver and kidney weights; and at 1650 ppm, increased mortality was noted (Carpenter and Smyth 1946/Ex. 1-859).
Silverman, Schulte, and First (1946/Ex. 1-142) reported eye irritation and complaints of objectionable odor in volunteer human exposures to concentrations above 25 ppm. No worker illnesses have been linked to diisobutyl ketone exposure (ACGIH 1986/Ex. 1-3, p. 203).
NIOSH (Ex. 150, Comments on Diisobutyl Ketone) concurred with OSHA's proposal to reduce the limit for diisobutyl ketone and reported that there are no new toxicological data beyond those described above; no other comments on this substance were received. The Agency concludes that the previous 50-ppm TWA limit is inadequate to protect workers against the significant risk of irritation associated with workplace exposures to diisobutyl ketone levels greater than 25 ppm. The Agency has determined that the irritation associated with exposure to diiso- butyl ketone constitutes a material impairment of health and functional capacity. Therefore, OSHA is revising its limit for diisobutyl ketone to 25 ppm as an 8-hour TWA.