A selection of candidate compounds for in vitro teratogenesis test validation

Abstract

The Consensus Workshop on In Vitro Teratogenesis Testing recommended that test validation be facilitated by a listing of agents with defined teratogenicity; subsequently, a panel was convened to review and select such agents. This communication established a list of 47 compounds or conditions which demonstrate a wide range of teratogenicity in vivo. The agents were chosen primarily on the strength of the literature base denoting their in vivo effects. The tables note a number of general biological and toxicological characteristics for each agent, and the details of representative in vivo teratology studies are summarized and referenced. This list is intended to serve as a base for in vitro teratogenesis test validation and should prove useful in developing and identifying those systems which will contribute to a more effective testing program.

Differences in Sensitivity to Developmental Toxicants as Seen in Xenopus and Pimephales Embryos

“…At concentrations > 0.2 mg/mL severe curling of the tail and growth stunting occurred. Smith et al (1983) reported 5-FU as a strong teratogen in humans, mice, rats, and in chicks. In previous 4-d tests with FETAX, 5-FU exhibited strong teratogenic potential in Xenopus with a TI value of 11.8 (Dawson and Bantle 1987).…”

Pattern of Response of Intact Drosophila to Known Teratogens

“…For this reason, we plan to test up to 45 chemicals taken from a list generated by the ad hoc committee formed during the August 1981 "Consensus Workshop in In Vitro Teratogenesis Testing." (13) The test regimen is being revised to improve the range-finding studies, to provide better information on dose-response relationships, and to provide consistent group sizes for statistical analyses. In addition, concentrations causing abnormalities will be compared to concentrations causing toxicity (death of developing larvae or based upon an adult LD,, dose) to provide an index of the relative teratogenic potential of each chemical.…”

Alternative models in developmental toxicology

“…However, the lists of test compounds designed previously have been criticized. The first attempt was the 'Smith list' published in 1983 [Smith et al 1983]. This list contained 47 compounds; however, the criticism was that many of the negative compounds in the list would be non-toxic under all circumstances.…”