has markedly different reproductive toxic effects in different mammalian species.
Having performed these chick embryo studies, what could these authors have done before becoming advocates for their data as a human teratogen? They could have examined the epidemiologic literature and found that there was not support for their advocacy position (Heinonen et al., '77; Aselton et al., '85). They could have called one of the many pharmaceutical companies that distribute cough medicines containing dextromethorpan and asked about their in-house animal studies which were submitted to the FDA as part of their new-drug application. I did call one company and this is what Andaloro et al. would have been able to learn:
''Pregnant rats were continuously administered two dosages of 1 mg kg Οͺ1 d Οͺ1 or 10 mg kg Οͺ1 d Οͺ1 for two generations. These dosages are equivalent to 2 and 20 times the human therapeutic dose on a mg/kg basis. After two generations of daily exposure to dextromethorpan, they were unable to demonstrate any difference between the controls and treated rats with regard to litter size, stillbirths, birth weight, maternal weight gain, viability of the young and incidence of congenital malformations.'' ''Pregnant rabbits were also administered dextromethorphan, at 0, 10, and 50 mg kg Οͺ1 d Οͺ1 from the 6th to 18th d of pregnancy. These dosages are equivalent to 20 and 100 times the human therapeutic dose, on a milligram/kg basis. Two hundred and thirty-five fetuses from treated dams were examined and there was no increased incidence of malformations. Litter size, fetal growth and fetal viability were also not affected.'' There are many other aspects of this article dealing with their interpretation of the literature with which I do not agree, but these differences of opinion are somewhat irrelevant to my basic criticisms of the article, which are that: 1) the model they selected for a teratology study is inappropriate, 2) the design of the study fails to consider the basic principles of teratology testing (Beckman and Brent, '92), 3) the authors have no basis for suggesting that dextromethorpan has teratogenic potential in the human when administered at 0.5 mg/kg or somewhat higher doses, and 4) the authors have become advocates for the importance of their work and its applicability to the problem of human teratogenicity, an unfortunate position of misguided scientific advocacy.