TETRAHYDROFURAN

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: 109-99-9; Chemical Formula: (C₂H₄)₂O

OSHA’s former PEL for tetrahydrofuran was 200 ppm as an 8-hour TWA. The Agency proposed revising this limit to 200 ppm TWA with a 15-minute STEL of 250 ppm and is establishing these limits, which are consistent with those recommended by the ACGIH, in the final rule. NIOSH (Ex. 8-47, Table N1) concurred with OSHA’s proposal to add a STEL for this substance. Tetrahydrofuran is a colorless liquid with an odor like that of ether.

This proposed limit was selected on the basis of extensive data from experimental animal studies. Lehmann and Flury (1943c/Ex. 1-879) reported irritation of the upper respiratory tract as well as kidney and liver injury in a number of animals exposed by inhalation to more than 3000 ppm tetrahydrofuran for 20 days, eight hours daily. Aqueous solutions exceeding a concentration of 20 percent tetrahydrofuran proved irritating to the skin of rabbits. One study (Stoughton and Robbins 1936/Ex. 1-597) found that tetrahydrofuran concentrations in excess of 25,000 ppm were needed to anesthetize dogs. The anesthesia process in these animals showed a delayed induction period and poor recovery. In other studies with dogs (Zapp 1971, as cited in ACGIH 1986/Ex. 1-3, p. 564), 200 ppm tetrahydrofuran in daily six-hour inhalation exposures produced an observable effect on the pulse pressure of these animals within three to four weeks; despite an exposure of nine weeks at this dosage level followed by three weeks at nearly twice this concentration, no histopathologic changes were observed in the critical organs. Studies (Jochmann 1961/Ex. 1-1021) in which tetrahydrofuran was given orally and peritoneally to a variety of laboratory animals resulted in both liver and kidney damage; however, some of the effects observed by this author may have been caused by peroxide contamination of the tetrahydrofuran. Oettel (as cited in ACGIH 1986/Ex. 1-3, p. 564) observed no kidney or liver damage in cats, rabbits, rats, or mice exposed repeatedly by inhalation to tetrahydrofuran at concentrations of 3400 to 17,000 ppm for as long as six hours. Technicians involved in the experiment of Stoughton and Robbins (1936/Ex. 1-597, described above) experienced severe headaches when conducting these experiments.

Dr. Larry Hecker, Director of Corporate Industrial Hygiene and Toxicology for Abbott Laboratories, commented that there was no toxicological basis to justify a STEL for tetrahydrofuran (Ex. 3-678). However, OSHA believes that the severe headaches experienced by researchers conducting animal experiments (Stoughton and Robbins 1936/Ex. 1-597) are indicative of an acute effect that constitutes material impairment of health and is best avoided by establishing a short-term limit. OSHA also notes that the ACGIH (Threshold Limit Values and Biological Exposure Indicies for 1988-1989, ACGIH 1988b) has not proposed to delete its recommended STEL for this substance. Therefore, OSHA finds that both a 200-ppm 8-hour TWA and a 250-ppm STEL are necessary to reduce the risk of long-term systemic and acute effects associated with exposure to tetrahydrofuran and is establishing these limits in the final rule.