Developmental Toxicity of Cumene Vapor in Cd Rats and New Zealand White Rabbits

Abstract

The potential developmental toxicity of cumene vapor (99.9% pure) was assessed in pregnant CD (Sprague-Dawley) rats and New Zealand White rabbits exposed for 6 h per day by inhalation, the most relevant route of potential human exposure. Groups of 25 rats were exposed on gestational days (GD) 6–15 to concentrations of 0 (filtered air), 100, 500, or 1200 ppm, and groups of 15 rabbits were exposed on GD 6–18 to 0, 500, 1200, and 2300 ppm cumene vapor. In rats, reduced maternal body weight gain and increased relative liver weight was observed at 1200 ppm cumene. In rats and rabbits, reduced food consumption was observed at concentrations of 500 and 1200 ppm. A t 2300 ppm, 2 rabbits died, body weight gain and food consumption were reduced during the exposure period, and relative liver weights were increased. None of the gestational parameters, including numbers of viable implantations per litter, sex ratio, and fetal body weights, were affected at any exposure level in rats or rabbits. There were no treatment-related increases in incidences of external, visceral, or skeletal malformations or in the incidences of variations at any level. Thus, in rats, the no observable adverse effect level (NO A EL) for maternal toxicity was 100 ppm and the NO A EL for developmental toxicity was 1200 ppm, the highest concentration of cumene vapor tested. In rabbits, there was no NO A EL for maternal toxicity, but the NO A EL for developmental toxicity was 2300 ppm for cumene, the highest concentration tested. Therefore, even at exposure levels associated with maternal toxicity, cumene was not a developmental toxicant by inhalation exposure in either rats or rabbits.