Summary of dose-response modeling for developmental toxicity studies

Daniel L. Hunt, Shesh N. Rai, Chin-Shang Li

Research output: Contribution to journalArticle

4 Scopus citations

Abstract

Developmental toxicity studies are an important area in the field of toxicology. Endpoints measured on fetuses include weight and indicators of death and malformation. Binary indicator measures are typically summed over the litter and a discrete distribution is assumed to model the number of adversely affected fetuses. Additionally, there is noticeable variation in the litter responses within dose groups that should be taken into account when modeling. Finally, the dose-response pattern in these studies exhibits a threshold effect. The threshold dose-response model is the default model for non-carcinogenic risk assessment, according to the USEPA, and is encouraged by the agency for the use in the risk assessment process. Two statistical models are proposed to estimate dose-response pattern of data from the developmental toxicity study: the threshold model and the spline model. The models were applied to two data sets. The advantages and disadvantages of these models, potential other models, and future research possibilities will be summarized.

Original languageEnglish (US)
Pages (from-to)352-368
Number of pages17
JournalDose-Response
Volume6
Issue number4
DOIs
StatePublished - 2008

Keywords

  • Developmental toxicity study
  • Dose-group variation
  • Estimation
  • Spline
  • Threshold

ASJC Scopus subject areas

  • Toxicology
  • Health, Toxicology and Mutagenesis
  • Chemical Health and Safety
  • Public Health, Environmental and Occupational Health

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