Design of developmental toxicity studies for assessing joint effects of dose and duration

Daniel O Scharfstein, P. L. Williams

Research output: Contribution to journalArticle

Abstract

In the assessment of developmental and reproductive effects, the timing and duration of exposures to chemical compounds or other environmental contaminants are of particular interest, as the gestational cycle is known to have periods of increased sensitivity. The goal of this research is to identify optimal experimental designs for conducting developmental toxicity studies when the effects of both exposure level and duration of exposure are of interest. The elements of the study design considered in this evaluation are the allocation of animals to dose-duration exposure groups and the determination of the most efficient intermediate exposure levels. The optimality of various designs is assessed via the accuracy of the estimated excess risk as well as testing criteria. Simulation studies are conducted to compare these criteria and determine optimal design strategies under various underlying dose-response patterns. Asymptotic results are also derived to lend support to the simulation studies.

Original languageEnglish (US)
Pages (from-to)1057-1072
Number of pages16
JournalRisk Analysis
Volume14
Issue number6
DOIs
StatePublished - Dec 1994
Externally publishedYes

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Toxicity
Research Design
Chemical compounds
Research
Design of experiments
Animals
simulation
Impurities
Testing
animal
evaluation
Group
Optimal design

ASJC Scopus subject areas

  • Social Sciences (miscellaneous)
  • Safety, Risk, Reliability and Quality

Cite this

Design of developmental toxicity studies for assessing joint effects of dose and duration. / Scharfstein, Daniel O; Williams, P. L.

In: Risk Analysis, Vol. 14, No. 6, 12.1994, p. 1057-1072.

Research output: Contribution to journalArticle

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