Transient eye irritation was seen after instillation of liquid FC-21 chilled to the temperature of dry ice or of a 40% solution in propylene glycol into the eyes of rabbits (Brittelli, 1976; Hood, 1964b). Mild lacrimation, but no corneal or iritic effect, was seen after FC-21 was sprayed directly into the eyes of rabbits (Hood, 1964b).
A group of 10 rats exposed at 10,000 ppm, 6 h/d, 5 d/wk, for 2 wk all survived, but pathologic examination revealed liver damage (Trochimowicz et al., 1977b). In a later 90-d study, groups of 54 rats and 4 dogs were similarly exposed at 1,000 and 5,000 ppm (Trochimowicz et al., 1977a). Excessive mortality and bilateral hair loss were seen in both groups of rats. The dogs lost weight at both concentrations. Histopathologic examination revealed cirrhosis in all rats, but only minimal changes in the livers of dogs exposed at 5,000 ppm. No compound-related effects were seen in dogs exposed at 1,000 ppm. Another incomplete 90-d study reported gross pathologic changes in the livers of rats exposed at 500 ppm, probable changes at 200 ppm, but no gross effects at 50 ppm (Allied Chemical, unpublished report to TLV Committee, 1978).
FC-21, like other chlorofluorocarbons and hydrocarbons, is capable of sensitizing the beagle heart to exogenous epinephrine in 5-min cardiac-sensitization screening studies (Mullin, 1975). A concentration of 10,000 ppm produced a marked response in 2 of 12 exposed dogs. No response was seen at 5,000 ppm; at this concentration, FC-21 is considered slightly less cardiotoxic than FC-11, which produced sensitization at 5,000 ppm. In the monkey, respiratory depression and tachycardia were seen after 5 min at 25,000 ppm (Aviado and Smith, 1975).
Kelly et al. (1978) exposed 25 pregnant rats to FC-21 at 10,000 ppm 6 h/d on days 6–15 of gestation. There was an unspecified adverse effect on maternal weight and a preimplantation loss of fertilized ova in 15 of the 25 rats. No teratogenic effects were observed.
The ACGIH (1980, 1983) established a TLV-TWA for FC-21 of 10 ppm (40 mg/m3). This represented a downward revision from the previous TLV-TWA of 1,000 ppm and was recommended because data had suggested that FC-21 was considerably more hepatotoxic than closely related fluorinated compounds and was similar in that respect to chloroform (ACGIH, 1980). OSHA (1983) recommended a permissible exposure level (PEL) of 1,000 ppm.
On the basis of 5-min cardiac-sensitization screening findings in dogs, which were positive at 10,000 ppm and negative at 5,000 ppm; hepatotoxic effects in rats exposed at 10,000 ppm over a 2-wk period; and reproductive changes with exposure at 10,000 ppm at a critical period in gestation, the Committee recommends a 60-min EEL of 100 ppm.