Toxicity testing with animal viruses: I. Vaccinia virus growth as a model system for teratogens.

Abstract

A simple, rapid, inexpensive test for teratogens has been developed using vaccinia virus growth in primate cell cultures. Eighty-four percent of the test compounds that are known to produce teratogenesis in laboratory animals, prevented the formation of viable virus at dosages that did not cause any observable cytotoxicity to uninfected cells. The virus test had one false positive and 5 false negatives out of 74 test compounds. Moreover, the 50% inhibitory dose in vitro (RD50) was significantly correlated (p less than 0.001) with the in vivo, lowest reported teratogenic dose (LTD). The RD50 was not correlated with the in vivo lethal dose (LD50). Thus the virus test appears to be more sensitive to development than to general toxicity. A comparison of the in vitro RD50 with the in vivo, rodent LTD indicated that the two tests were equally predictive of human teratogenesis.