In Utero Phase Carcinogenicity Testing

Abstract

Early experimentation with transplacental exposure (1940s) demonstrated that expression of lung tumors in mice was enhanced when urethane was given during development in utero. In 1970, a U. S. Food and Drug Administration (FDA) expert panel on the safety evaluation of food additives and pesticides met and recommended that an in utero exposure phase be added to carcinogenicity testing (U.S. FDA, 1 971). An analysis was conducted of studies in the open scientific literature, in food additive studies available in FDA files and in studies performed by the National Institute of Environmental Health Sciences (NIEHS). While exposure to rodents during only the adult phase provided qualitatively similar results, early neonatal exposure typically provided slightly higher incidences of turnors, and decreased latency to turn or onset in certain scientific studies. In a series of studies recently performed by the NIEHS with three known animal carcinogens, neonatal or adult exposure produced similar tumors in similar tissues. The food additive saccharin, which shows bladder tumors, and eugenol reliably produced tumors only with neonatal exposure. Implieations for carcinogenicity testing of food additives are discussed in light of these experi-mental findings.