Basic exploratory research versus guideline-compliant studies used for hazard evaluation and risk assessment: bisphenol A as a case study.
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.


OBJECTIVE
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.


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.
Tyl
Rochelle W
RW
RTI International, Research Triangle Park, North Carolina 27709-2194, USA. rwt@rti.org
D000284:Administration, Oral; D000818:Animals; D001559:Benzhydryl Compounds; D019411:Clinical Laboratory Techniques / Q000592:standards; D023381:Endpoint Determination / Q000379:methods; D004958:Estradiol / Q000633:toxicity; D004968:Estrogens, Non-Steroidal / Q000493:pharmacokinetics / Q000633:toxicity*; D019983:Guideline Adherence; D017408:Guidelines as Topic; D006801:Humans; D051379:Mice; D010636:Phenols / Q000493:pharmacokinetics / Q000633:toxicity*; D051381:Rats; D012106:Research / Q000592:standards; D012107:Research Design; D018570:Risk Assessment / Q000379:methods; D054928:Validation Studies as Topic; D000098826:Bisphenol A Compounds
D001559:Benzhydryl Compounds; D004958:Estradiol; D004968:Estrogens, Non-Steroidal; D010636:Phenols; C006780:bisphenol A; D000098826:Bisphenol A Compounds