Sankhya: The Indian Journal of Statistics

1995, Volume 57, Series B, Pt. 2, pp. 223--236

ISSUES AND APPROACHES FOR ASSESSING RISKS FROM REPRODUCTIVE TOXICANTS : DBCP AS A CASE STUDY

By

SATI MAZUMDAR, DONALD R. MATTISON,  Graduate School of Public Health

and

C. V. DAMARAJU,  Schering-Plough Research Institute

SUMMARY.  This paper reviews several issues and statistical approaches for assessing risks from reproductive toxicants with emphasis on the study designs, data analysis techniques and most appropriate transformations for the response measures. Importance of time as a critical variable in this endeavor is also discussed. Selecting dibromochloropropane (DBCP) as a case study, the evidence of the reproductive risk of this toxicant from epidemiological studies are reviewed first. This is followed by a reanalysis of data from a rabbit inhalation fertility study where sperm concentration from individual rabbits exposed to one or four doses of DBCP vapor from pre-exposure, exposure and post-exposure phases constitute the response measure. The analyses use three transformations, logarithmic, cube root, and a transformation via additivity and variance stabilization and two longitudinal data analysis techniques using random-effects models and generalized estimating equations. Specific benchmark doses are calculated for alteration of spermatogenesis. Results show that the effects of DBCP on the sperm concentration varies within the period of experimentation, suggesting that chronic experiments must be continued until the estimate of the dose parameter stabilizes.

AMS (1991) subject classification.  62P10.

Key words and phrases. Dibromochloropropane(DBCP), sperm concentration, variance stabilizing transformations, longitudinal data analysis, reproductive risks, benchmark dose.

Full paper (PDF).