Submarine Exposure Guidance Levels for Selected Hydrofluorocarbons: HFC-236fa, HFC-23,and HFC-404a (2000)
Chapter: Genotoxicity
the exposed groups and the control group in any of the litter indices evaluated (i.e., number of corpora lutea and implants, pre-implant loss, embryonic deaths, post-implant loss, number of live young, litter weights, and mean fetal weights) or in the incidences of fetal malformations, visceral abnormalities, or skeletal anomalies.
In the study with rabbits, groups of 16 pregnant rabbits were exposed (whole body) to HFC-125 at concentrations of 0, 5,000, 15,000, and 50,000 ppm for 6 hr per day on days 6-18 of gestation (Brooker et al. 1992, as cited in Kawano et al. 1995). The adult rabbits exposed to HFC-125 at 50,000 ppm exhibited transient lower weight gain and food consumption but no other adverse clinical signs. The litters were evaluated for the same litter indices evaluated in the rat study and for malformations and anomalies. No significant changes in those end points were found in any of the exposed groups compared with controls.
Genotoxicity
Ames bacterial reverse mutation assays were conducted in two independent laboratories using a modified experimental design for testing HFC-125 gas (Longstaff et al. 1984; May et al. 1992, as cited in ECETOC 1994). At concentrations ranging from 200,000 to 1,000,000 ppm, HFC-125 was not mutagenic in five Salmonella strains (TA98, TA100, TA1535, TA1537, and TA1538). It was also negative in an Escherichia coli strain (WP2uvrA) assay, which detects DNA damage and repair.
At concentrations ranging from 175,000 to 700,000 ppm, HFC-125 was not clastogenic in an in vitro cytogenic assay using human lymphocytes (Dance et al. 1992, as cited in ECETOC 1994). HFC-125 was also evaluated for chromosomal aberration using Chinese hamster ovary cells at concentrations up to 600,000 ppm (Dance and Hodson-Walker 1992, as cited in ECETOC 1994). There was no clear evidence of clastogenic activity at any of the test concentrations after 4 or 24 hr of exposure, but after 48 hr, an increase in both frequency of aberrant cells and incidence of polyploid cells was observed at 600,000 ppm.
There was no statistically significant increase in micronuclei in the bone-marrow erythrocytes of male and female mice exposed at concentrations of up to 600,000 ppm for 6 hr (Edwards et al. 1992, as cited in ECETOC 1994). Mice exposed to HFC-125 at a concentration of 600,000 ppm exhibited transient tremors, hunched posture, and weight loss at 24 hr post-exposure.
