title: Critical evaluation of key evidence on the human health hazards of exposure to bisphenol A.
abstract: Despite the fact that more than 5000 safety-related studies have been published on bisphenol A (BPA), there seems to be no resolution of the apparently deadlocked controversy as to whether exposure of the general population to BPA causes adverse effects due to its estrogenicity. Therefore, the Advisory Committee of the German Society of Toxicology reviewed the background and cutting-edge topics of this BPA controversy. The current tolerable daily intake value (TDI) of 0.05 mg/kg body weight [bw]/day, derived by the European Food Safety Authority (EFSA), is mainly based on body weight changes in two- and three-generation studies in mice and rats. Recently, these studies and the derivation of the TDI have been criticized. After having carefully considered all arguments, the Committee had to conclude that the criticism was scientifically not justified; moreover, recently published additional data further support the reliability of the two- and three-generation studies demonstrating a lack of estrogen-dependent effects at and below doses on which the current TDI is based. A frequently discussed topic is whether doses below 5 mg/kg bw/day may cause adverse health effects in laboratory animals. Meanwhile, it has become clear that positive results from some explorative studies have not been confirmed in subsequent studies with higher numbers of animals or a priori defined hypotheses. Particularly relevant are some recent studies with negative outcomes that addressed effects of BPA on the brain, behavior, and the prostate in rodents for extrapolation to the human situation. The Committee came to the conclusion that rodent data can well be used as a basis for human risk evaluation. Currently published conjectures that rats are insensitive to estrogens compared to humans can be refuted. Data from toxicokinetics studies show that the half-life of BPA in adult human subjects is less than 2 hours and BPA is completely recovered in urine as BPA-conjugates. Tissue deconjugation of BPA-glucuronide and -sulfate may occur. Because of the extremely low quantities, it is only of minor relevance for BPA toxicity. Biomonitoring studies have been used to estimate human BPA exposure and show that the daily intake of BPA is far below the TDI for the general population. Further topics addressed in this article include reasons why some studies on BPA are not reproducible; the relevance of oral versus non-oral exposure routes; the degree to which newborns are at higher systemic BPA exposure; increased BPA exposure by infusions in intensive care units; mechanisms of action other than estrogen receptor activation; and the current regulatory status in Europe, as well as in the USA, Canada, Japan, New Zealand, and Australia. Overall, the Committee concluded that the current TDI for BPA is adequately justified and that the available evidence indicates that BPA exposure represents no noteworthy risk to the health of the human population, including newborns and babies.
authors: Leibniz Research Centre for Working Environment and Human Factors (IfADo), University of Dortmund, Dortmund, Germany. hengstler@ifado.de
authors: J G
authors: JG
authors: Hengstler
authors: H
authors: H
authors: Foth
authors: T
authors: T
authors: Gebel
authors: P-J
authors: PJ
authors: Kramer
authors: W
authors: W
authors: Lilienblum
authors: H
authors: H
authors: Schweinfurth
authors: W
authors: W
authors: Völkel
authors: K-M
authors: KM
authors: Wollin
authors: U
authors: U
authors: Gundert-Remy
mesh_terms: D000818:Animals; D001559:Benzhydryl Compounds; D004781:Environmental Exposure / Q000009:adverse effects / Q000706:statistics & numerical data; D004784:Environmental Monitoring; D004968:Estrogens, Non-Steroidal / Q000633:toxicity*; D006207:Half-Life; D015386:Hazardous Substances / Q000633:toxicity*; D006801:Humans; D051379:Mice; D010636:Phenols / Q000633:toxicity*; D051381:Rats; D018570:Risk Assessment; D018675:Toxicity Tests / Q000379:methods; D000098826:Bisphenol A Compounds
chemical_list: D001559:Benzhydryl Compounds; D004968:Estrogens, Non-Steroidal; D015386:Hazardous Substances; D010636:Phenols; C006780:bisphenol A; D000098826:Bisphenol A Compounds