Prenatal developmental toxicity evaluation of higher olefins in Sprague-Dawley rats

Summary

Higher olefins (HO) are used primarily as intermediates in the production of other chemicals, such as polymers, fatty acids, plasticizer alcohols, surfactants, lubricants, amine oxides and detergent alcohols. The potential prenatal developmental toxicity of five HO (i.e. Hex-1-ene, Nonene, branched, Octadec-1-ene, and Hydrocarbons, C12–30, olefin-rich, ethylene polymn. by product) were evaluated in prenatal development toxicity studies (OECD TG 414 (2001)) in Sprague-Dawley rats as part of the regulatory requirements for REACH registration. In each study, the HO were administered by gavage at dose levels of 0, 100, 300 and 1000 mg/kg bw/day from Day 3 to Day 19 of gestation. Maternal food consumption, body weights, and clinical signs were monitored throughout gestation. The rats were sacrificed on Day 20 of gestation and examined for standard parameters of reproductive performance (number of corpora lutea, number of implantations, pre- and post-implantation loss, number of live- and dead fetuses, sex-ratio and the weight of the reproductive organs). The fetuses were weighed and examined for external, visceral, and skeletal variations and malformations. The results from these studies showed that none of the HO treated groups showed maternal or embryo–fetal toxicity. Although occasionally incidental skeletal and visceral malformations were observed with Hex-1-ene and Octadec-1-ene, these findings were found to be spontaneous, unrelated to treatment and not indicative for any disturbance of fetal development. In conclusion, the No-Observed-Adverse-Effect Level (NOAEL) for all tested HO was determined to be 1000 mg/kg bw/day, which is the highest dose level administered, for both maternal and developmental toxicity.