Dose-dependent number of implants and implications in developmental toxicity.
Journal Article (Journal Article)
This paper proposes a method for assessing risk in developmental toxicity studies with exposure prior to implantation. The method proposed in this paper was developed to account for a dose-dependent trend in the number of implantation sites per dam, which is a common problem in studies with exposure prior to implantation. Toxins may have the effect of interfering with the early reproductive process, which can prevent implantation in the uterine wall. An imputation procedure is presented for estimating the number of potential fetuses by sampling from the empirical distribution of the number of implants per litter in the control group. The marginal death outcomes and the joint malformation and survival outcomes for each potential fetus can be estimated using multiple imputation or the chained data augmentation algorithm. Logit models can then be fit and used to estimate the effect of dose on reducing the probability of a normal birth. These models accommodate multiple covariate effects and can be applied to low-dose extrapolation. A simulation study is done to evaluate the properties of model-based estimators of the mean response and the virtually safe dose level (VSD). It was found that both estimates were good approximations of the underlying dose effect. A dominant lethal assay data set (Luning et al., 1966, Mutation Research 3, 444-451) is analyzed, and the results are compared with those of Rai and Van Ryzin.
Full Text
Duke Authors
Cited Authors
- Dunson, DB
Published Date
- June 1998
Published In
Volume / Issue
- 54 / 2
Start / End Page
- 558 - 569
PubMed ID
- 9629644
Pubmed Central ID
- 9629644
Electronic International Standard Serial Number (EISSN)
- 1541-0420
International Standard Serial Number (ISSN)
- 0006-341X
Digital Object Identifier (DOI)
- 10.2307/3109763
Language
- eng