DISULFIRAM

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: 97-77-8; Chemical Formula: C₁₀H₂₀N₂S₄

OSHA had no former limit for disulfiram. The ACGIH recommends a limit of 2 mg/m³ TWA for this crystalline solid. The proposed PEL was 2 mg/m³ as an 8-hour TWA; NIOSH concurs with this limit (Ex. 8-47, Table N1), which is established by the final rule.

Disulfiram’s LD(50) in rats is reported as 8.6 g/kg (Windholz 1983e, pp. 491-492, as cited in ACGIH 1986/Ex. 1-3, p. 225), and the oral LD(50) for rabbits is reported to be 2.05 g/kg (Brieger 1947/Ex. 1-717). The compound is highly toxic when injected intraperitoneally, with an LD(50) of 75 mg/kg for mice (National Technical Information Service, as cited in ACGIH 1986/Ex. 1-3, p. 225). The effects of high-dose ingestion include degenerative changes in the liver and kidneys. Very high doses can cause leukopenia and marked hypoplasia or aplasia of the bone marrow; in the most seriously afflicted animals, the blood urea nitrogen sometimes increased and the thymol turbidity test was positive (Brieger 1947/Ex. 1-717).

Adverse health effects occur in humans consuming alcohol and simultaneously exposed to disulfiram. This represents a significant concern since disulfiram, under the trade name Antabuse, is used as a medication in the treatment of chronic alcoholism. For individuals who drink alcohol and are exposed to disulfiram, the symptoms of exposure are facial vasodilation, tachycardia, tachypnea, nausea, vomiting, pallor, and hypotension. High doses of disulfiram can induce convulsions, cardiac arrhythmias, and myocardial infarction, and the compound has also been associated with polyneuropathy, peripheral neuritis, and skin eruptions (Compendium of Pharmaceuticals and Specialties 1968, as cited in ACGIH 1986/Ex. 1-3, p. 225). In industry, there have been reports of minimal skin irritation (Mastromatteo 1973, as cited in ACGIH 1986, p. 225) and of optic neuritis (Norton and Walsh 1972/Ex. 1-877). NIOSH submitted the only comment on this substance.

OSHA is establishing a PEL of 2 mg/m³ as an 8-hour TWA for disulfiram. The Agency concludes that this limit will protect workers against the significant risk of Antabuse-like effects associated with exposure to airborne concentrations of disulfiram in combination with alcohol consumption. OSHA has determined that this limit will substantially reduce this significant risk and that the symptoms of the Antabuse syndrome clearly constitute material impairment of health.