Qualitative and quantitative assessment of the risk from the exposure to fetotoxic chemical compounds

✍ Scribed by S. Talwalker; G. P. Patil; C. Taillie

• Publisher: Springer
• Year: 1995
• Tongue: English
• Weight: 564 KB
• Volume: 2
• Category: Article
• ISSN: 1352-8505
• DOI: 10.1007/bf00452932

✦ Synopsis

A new mathematical dose-response model for the expected probability of toxic response and also for the expected measure of the overdispersion parameter for the reproductive and developmental risk assessment is proposed. The model for the expected probability of toxic response is an improvised Weibull dose-response model incorporating the litter-size effect while the model for the overdispersion parameter is a polynomial function of the dose level. A beta-binomial distribution for the number of offspring showing toxic responses in a litter satisfactorily accounts for the extra-binomial variation and the intralitter correlation of responses of these pups. Confidence limits for low-dose extrapolation are based on the asymptotic distribution of the likelihood ratio. The safe dose for human exposure is then calculated by simple linear extrapolation. The model for overdispersion allows us to obtain the estimates of the overdispersion parameter at these dosages. This was not possible in the earlier models. The proposed model is illustrated by an application to a study on the effect of exposure to diethylhexylphthalate in mice. The results are compared with those obtained by Chen and Kodell (1989) who have applied the simple Weibull dose-response model to the same data set.