FORMAMIDE

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: 75-12-7; Chemical Formula: CH₃NO

Previously, OSHA had no limit for formamide. The ACGIH has a TLV-TWA of 20 ppm and a TLV-STEL of 30 ppm for this clear, viscous, odorless liquid. The proposed PELs were an 8-hour TWA of 20 ppm and a 15-minute STEL of 30 ppm, and the final rule establishes these limits.

Formamide has an LD(50) of approximately 6 g/kg for rats (Thiersh 1962/Ex. 1-690; Zaeva, Vinogradova, Savina, and Osipenko 1969/Ex. 1-1026). Dietary administration at 1.5 g/kg for two weeks resulted in fatalities in rats; pathologic examination revealed cumulative changes characteristic of gastritis and malnutrition (E.I. du Pont de Nemours and Company, Inc., as cited in ACGIH 1986/Ex. 1-3, p. 278). Czajkowska (1981, as cited in ACGIH 1986/Ex. 1-3, p. 278) reports the dermal LD(50) for skin absorption in rabbits as 6 g/kg. Mild and transient irritation, but no allergic skin sensitization, occurred when formamide was applied to the skin of guinea pigs ( Dangerous Properties of Industrial Materials, 6th ed., Sax 1984; E.I. du Pont de Nemours and Company, Inc., as cited in ACIGH 1986/Ex. 1-3, p. 278). Eye irritation tests in rabbits showed only slight, temporary irritation (Carpenter and Smyth 1946/Ex. 1-303). No signs of toxicity in rats were detected in single six-hour exposures at 3900 ppm formamide dispensed as a mist, or in six-hour daily exposures for 10 days at approximately 1500 ppm formamide vapor (equivalent to air saturated with formamide at room temperature); no indications of organ damage were seen in these animals on pathologic examination (E.I. du Pont de Nemours and Company, Inc., as cited in ACGIH 1986/Ex. 1-3, p. 278).

Gross fetal malformations were not noted following dermal applications of formamide to the skin of pregnant rats; the effects that were observed were weak and were produced at overwhelming concentrations (Stula and Krauss 1977/Ex. 1-1068). The no-observed-effect level in a rabbit developmental toxicity study was 22 mg/kg orally (Merkle and Zeller 1980/Ex. 1-683).

According to the ACGIH, there are no reports of industrial poisoning by formamide (E.I. du Pont de Nemours and Company, Inc., as cited in ACGIH 1986/Ex. 1-3, p. 278).

OSHA received comments on formamide from Grace Ziem (Ex. 46) and NIOSH (Ex. 8-47, Table N2). Dr. Ziem, an occupational physician on the staff of Johns Hopkins School of Hygiene and Public Health and the University of Maryland School of Medicine, believes that OSHA should revise the PEL for formamide to 10 ppm as an 8-hour TWA based on Grant’s (1986/Ex. 1-975) statement that this substance causes Grade 4 eye irritation rather than the “mild” irritation reported by du Pont (as cited in ACGIH 1986/Ex. 1-3, p. 278). Dr. Ziem also notes that the ACGIH has dropped its STEL for formamide, lowered its 8-hour TWA PEL to 10 ppm, and added a skin notation for this substance. In addition, consistent with the Agency’s policy on skin notations (discussed in Section VI.C.18 of the preamble), OSHA is not adopting the skin notation at the present time. The Agency concludes that the 30-ppm STEL should be retained to ensure that workplace exposures to formamide are not permitted to exceed the 8-hour TWA by any substantial margin. NIOSH (Ex. 8-47, Table N2) does not concur with the limits proposed and points out that formamide is a testicular toxin and has been identified in mice as a teratogen. OSHA is aware of the developing literature on both formamide and dimethyl formamide, and the Agency intends to monitor toxicological developments on these chemicals closely in the future to determine whether other action is necessary.

In the final rule, OSHA is establishing a PEL of 20 ppm TWA and a STEL of 30 ppm for formamide. The Agency concludes that this limit will not only protect workers against the significant risks of eye and skin irritation, but will substantially reduce the risks of other health effects that exist as a consequence of workplace exposure to formamide at levels above the new PELs. OSHA considers sensory irritation, testicular toxicity, and teratogenicity material impairments of health within the meaning of the Act.