Basic Exploratory Research versus Guideline-Compliant Studies Used for Hazard Evaluation and Risk Assessment: Bisphenol A as a Case Study
Tyl, R. (2009). Basic Exploratory Research versus Guideline-Compliant Studies Used for Hazard Evaluation and Risk Assessment: Bisphenol A as a Case Study. Environmental Health Perspectives, 117(11), 1644-1651.
BACKGROUND: Myers et al. [Environ Health Perspect 117:309-315 (2009)] argued that Good Laboratory Practices (GLPs) cannot be used as a criterion for selecting data for risk assessment, using bisphenol A (BPA) as a case study. They did not discuss the role(s) of guideline-compliant studies versus basic/exploratory research studies, and they criticized both GLPs and guideline-compliant studies and their roles in formal hazard evaluation and risk assessment. They also specifically criticized our published guideline-compliant dietary studies on BPA in rats and mice and 17beta-estradiol (E(2)) in mice. OBJECTIVES: As the study director/first author of the criticized E(2) and BPA studies, I discuss the uses of basic research versus guideline-compliant studies, how testing guidelines are developed and revised, how new end points are validated, and the role of GLPs. I also provide an overview of the BPA guideline-compliant and exploratory research animal studies and describe BPA pharmacokinetics in rats and humans. I present responses to specific criticisms by Myers et al. DISCUSSION AND CONCLUSIONS: Weight-of-evidence evaluations have consistently concluded that low-level BPA oral exposures do not adversely affect human developmental or reproductive health, and I encourage increased validation efforts for 'new' end points for inclusion in guideline studies, as well as performance of robust long-term studies to follow early effects (observed in small exploratory studies) to any adverse consequences