The acute, genetic, developmental and inhalation toxicology of trans-1-chloro,3,3,3-trifluoropropene (HCFO-1233zd(E))

Abstract

Trans-1-chloro,3,3,3-trifluoropropene (HCFO-1233zd(E)) is being developed as a foam blowing agent, refrigerant and solvent because it has a very low global warming potential (<10), as contrasted to the hydrofluorocarbons (>500). The toxicology profile is described. The acute 4-hour 50% lethal concentration value in rats receiving HCFO-1233zd(E) was 120 000 ppm. The no observed effect level (NOEL) in cardiac sensitization studies in dogs was 25 000 ppm. In a 2-week range-finding study, rats were exposed to HCFO-1233zd(E) at levels of 0, 2000, 7500 and 20 000 ppm 6 hours/day for 5 days/week. Histopathological changes in the heart described as multifocal mononuclear infiltrates were observed in males (mid- and high-exposure group) and females (high-exposure group), suggesting this organ was the target for HCFO-1233zd(E) toxicity. In a 4-week study, rats were exposed to 0, 2000, 4500, 7500 and 10 000 ppm. The only finding was an increase in potassium (mid- and high-exposure males). No increase was observed after a 2-week recovery period, nor in a subsequent 13-week toxicity study. In a 13-week study, rats were exposed to 4000, 10 000 and 15 000 ppm 6 hours/day for 5 days/week. Findings consisted of multifocal mononuclear cell infiltrates in the heart with a NOEL/lowest observed adverse effect level of 4000 ppm. No genetic toxicity was observed in a battery of genetic toxicity studies. In a rat prenatal developmental toxicity study, dilated bladders were observed in the high-exposure group fetuses (15 000 ppm), a finding of unclear significance. HCFO-1233zd(E) was not a developmental toxin in rabbits, even at exposure levels up to 15 000 ppm.