Does Bisphenol A (BPA) Exposure Cause Human Diseases?

Abstract

Background: Autism spectrum disorders (ASDs), attention-deficit disorder (ADHD), Parkinson's disease (PD), polycystic ovary disease (PCOS), and Alzheimer's disease (AD) have all been linked to exposure to bisphenol A (BPA).

Methods: This paper is a review and discussion of the published literature.

Results: Animal studies have shown BPA to be a broad-spectrum endocrine disruptor. BPA is metabolized via the glucuronidation pathway, which involves the addition of glucose to the target molecule, and is catalyzed by uridine 5'-diphospho-glucuronosyltransferases (UGTs). Evidence of compromised glucuronidation has been found for ASD, DHD, PD, and PCOS. Genetic polymorphisms that alter the catalytic activity of the UGTs and efflux transporters involved are common. There are two ways to interpret the findings of associations between BPA glucuronidation efficiency and disease, a 'direct' pathway and an 'indirect' pathway. With the 'direct' pathway, free BPA is the actual causative agent. Compromised BPA detoxification leads to higher concentrations of free BPA in vulnerable tissues. Decreased BPA detoxification leads to increased exposure of vulnerable tissues to free BPA, where it can function as an endocrine disruptor. With the 'indirect' pathway, BPA is not the causative agent. BPA serves as a marker for the decreased glucuronidation efficiency of another unknown compound of endogenous origin detoxified by a similar combination of UGTs and efflux transporters as BPA. It is this compound(s), acting as an endocrine disruptor, that leads to a metabolic environment that favors disease development over an extended time period.

Conclusion: A review of the existing literature supports the indirect 'marker' hypothesis over the 'direct' hypothesis.

Keywords: ADHD; Alzheimer’s; BPA; DEHP (diethyl hexyl phthalate); PCOS; Parkinson’s; autism; bisphenol A; glucuronidation.

Figure 1

Percentage of total number of Spearman’s rank-order correlations between glucuronidation efficiency, either +v or −ve, by glucuronidation pathway vs. individual metabolome compounds. Abbreviations: 5OX, 5-OXO MEHP; 5CX, 5-CX MEHP; 5OH, 5-OH MEHP; CRT, Cortisol; GDA, Glycocholate; GCA, Glycodeoxycholate; NAR, Naringenin; SAL, Salicylate.

Figure 2

Percent of total number of Spearman’s rank-order correlations from Figure 1, either positive or negative, by glucuronidation pathway for total metabolome. Abbreviations are the same as in Figure 1.