Previously, OSHA had no limit for fenthion. The ACGIH has a TLV-TWA of 0.2 mg/m3, with a skin notation. The proposed PEL was 0.2 mg/m3, with a skin notation, and the final rule establishes this limit and a skin notation. Fenthion is an oily, yellow- to tan-colored liquid that smells slightly like garlic.
The primary health effect associated with exposure to fenthion is plasma cholinesterase inhibition. The oral LD(50) values for the rat and rabbit are 215 and 150 mg/kg, respectively, and the dermal LD(50) in rats is 330 mg/kg (Farm Chemicals Handbook 1976/Ex. 1-1147b; NIOSH 1977j, as cited in ACGIH 1986/Ex. 1-3, p. 268). Rats given single intramuscular injections of 5, 25, or 50 mg/kg of fenthion exhibited both enduring electroretinogram changes (ERG) and changes in cholinesterase activity; pseudocholinesterase activity in the plasma dropped to 50 percent of normal on the fourth day after injection. The retinal effects of fenthion persisted for as long as 50 days (Imai 1975/Ex. 1-910). Groups of Donryn rats fed 300 ppm fenthion daily showed symptoms of organophosphate intoxication, including nervousness, general spasms, diarrhea, salivation, and ophthalmologic effects (Kawai, Tojo, Miyazawa et al. 1976/Ex. 1-1157). The no-effect inhalation level for rats has been reported to be 1 mg/m3 for exposures to the aerosol of six hours/day, five days/week for three weeks; at a concentration of 3 mg/m3, cholinesterase inhibition was found (Thyssen 1979, as cited in ACGIH 1986/Ex. 1-3, p. 267). The four-hour inhalation LC(50) in the rat is between 800 and 1200 mg/m3 (Thyssen 1978, as cited in ACGIH 1986/Ex. 1-3, p. 267).
No mutagenic, carcinogenic, or reproductive effects have been reported (Shirasu, Moriya, Kato et al. 1976/Ex. 1-1097; Hanna and Dyer 1975/Ex. 1-485; and WHO 1976, Food and Agriculture Organization (FAO/WHO) 1979, Oesch 1977, Simmon, Mitchell, and Jergenson 1977, and Herbold 1980, all as cited in ACGIH 1986/Ex. 1-3, p. 268). Single and repeated applications of the compound produced no delayed neurotoxic effects in chickens (WHO 1972, as cited in ACGIH 1986/Ex. 1-3, p. 268). Two-year feeding studies of rhesus monkeys showed plasma cholinesterase inhibition at the highest oral dose given, i.e., 0.2 mg/kg daily (Rosenblum 1980, as cited in ACGIH 1986/Ex. 1-3, p. 268).
Griffin, Rosenblum, and Coulston (1979, as cited in ACGIH 1986/Ex. 1-3, p. 268) reported cholinesterase depression in humans at oral doses of 0.07 mg/kg daily for four weeks, but no effect was observed at 0.02 mg/kg. The lowest lethal dose for humans is 50 mg/kg (Farm Chemicals Handbook 1976/Ex. 1-1147b; NIOSH 1977j, as cited in ACGIH 1986/Ex. 1-3, p. 100).
NIOSH (Ex. 8-47, Table N2) does not concur with OSHA's limit for fenthion because a significantly increased incidence of tumors was seen in male mice exposed to fenthion (NCI 1979e, as cited in ACGIH 1986/Ex. 1-3, p. 268) and fenthion is also a mutagen, embryotoxin, and teratogen (Chen, Sirianni, and Huang 1985 and Budreau and Singh 1973, both as cited in NIOSH/Ex. 150, Comments on Fenthion). OSHA will monitor the toxicological literature on fenthion; however, the Agency believes that the new PEL will protect exposed workers from any of the adverse effects associated with exposure to this substance. No other comments on fenthion were received.
In the final rule, OSHA is establishing an 8-hour TWA limit of 0.2 mg/m3, with a skin notation, for fenthion. The Agency concludes that these limits will protect workers against the significant risk of cholinergic effects associated with exposures to this substance at the levels formerly permitted by the absence of any OSHA limit. A skin notation is established because of evidence that fenthion is toxic when absorbed through the skin. OSHA finds that cholinesterase inhibition constitutes a material impairment of health.