NIEHS/FDA CLARITY-BPA research program update

Abstract

Bisphenol A (BPA) is a chemical used in the production of numerous consumer products resulting in potential daily human exposure to this chemical. The FDA previously evaluated the body of BPA toxicology data and determined that BPA is safe at current exposure levels. Although consistent with the assessment of some other regulatory agencies around the world, this determination of BPA safety continues to be debated in scientific and popular publications, resulting in conflicting messages to the public. Thus, the National Toxicology Program (NTP), National Institute of Environmental Health Sciences (NIEHS), and U.S. Food and Drug Administration (FDA) developed a consortium-based research program to link more effectively a variety of hypothesis-based research investigations and guideline-compliant safety testing with BPA. This collaboration is known as the Consortium Linking Academic and Regulatory Insights on BPA Toxicity (CLARITY-BPA). This paper provides a detailed description of the conduct of the study and a midterm update on progress of the CLARITY-BPA research program.

Keywords: Bisphenol A; CLARITY-BPA; Consortium; Endocrine disruptors; FDA; NIEHS; NTP.

Fig. 1

Schematic representation of the study design as described in the text. The planned animal assessment times for core chronic and specialty studies are indicated; continuous and stop dose arms are not depicted.

Fig. 2

Serum BPA-G measurements in vehicle, 2.5, and 25 μg BPA/kg bw/day animals from the BPA core chronic study. Vehicle (continuous and stop dose arms) and BPA-dosed (continuous arm only) males and females were evaluated. At a single time point within one week of termination at 12 months of age, rats from each of the 5 housing rooms of the core chronic study and representing all 5 study loads were sampled from the tail vein to provide approximately 0.5 ml of blood. The blood sample from animals in the continuous dosing arm was drawn 15–60 min after gavage, approximately C_max following gavage administration [8]. Rats from the vehicle control stop dose arm were sampled at approximately the same time of the day. Serum samples were analyzed by LC–MS/MS blinded to treatment group. The limit of detection (LOD) was established on each day of analysis and the range is indicated by the two horizontal lines on the graph. Red symbols indicate BPA-G measurements that were <LOD and are indicated as 1/2 LOD. X-axis labels, their definitions, and number of animals sampled are as follows: 0 Cont F and 0 Cont M represent continuous dose vehicle control females and males, respectively, n = 13/sex; 0 Stop F and 0 Stop M represent stop dose vehicle control females and males, respectively, n = 10/sex; 2.5 Cont F and 2.5 Cont M represent continuous dose 2.5 μg BPA/kg bw/day females and males, respectively, n = 15/sex; 25 Cont F and 25 Cont M represent continuous dose 25 μg BPA/kg bw/day females and males, respectively, n = 15/sex.