The scientific controversy about BPA currently is focused on the issue of metabolism: People are widely exposed to bisphenol A (BPA), but the estrogenic compound is thought to be rapidly inactivated by the body’s detoxifying mechanisms, and excreted as inactive, conjugated BPA-glucuronide. On the other hand, several human biomonitoring studies have found the free, estrogenic form of BPA to be present in blood samples. These findings have recently been validated (FPF article). One possible explanation, why free BPA is found in biomonitoring studies, despite its rapid detoxification, has been given now.
On June 12, 2013 French scientists from Toulouse University and the INRA Toulouse (Institute National de la Recherche Agronomique) published new findings of BPA uptake in the scientific peer-reviewed journal Environmental Health Perspectives (Gayrard et al. 2013). In their study, the researchers investigated the difference in free BPA blood levels in dogs, depending on the route of administration. In particular, they dosed test animals with the common method of gavage, where a tube is inserted into the animal’s throat, and BPA is placed directly in the stomach. They also studied free BPA blood levels after delivering the test substance under the animals tongue (sublingual). Free BPA was much higher when dosing sublingually, compared to gavage. BPA is thought to be taken up through the mouth’s mucosa and transferred directly into the blood stream, thus surpassing liver detoxification. On the contrary, gavaged BPA is taken up via the gastro-intestinal tract and most BPA is immediately conjugated to BPA-glucuronide in the liver.
In this study, dogs were used to test sublingual absorption, because their mouth mucosa is similar to that of humans. Rats on the other hand have a different, less permeable mucosa.
While gavage is commonly used for oral dosing of test animals, it surpasses the sublingual uptake. The French study adds a further puzzle piece to the scientific debate on BPA and appropriate risk assessment for this estrogenic compound. But what is more, the study also questions the common practice of gavage dosing for oral toxicity studies: this route of exposure may not adequately reflect human exposure to food components. Gavage dosing has recently also been implicated in gene expression changes in the brains of control-treated animals (Cao et al. 2013), but further research is needed to understand the full implications of these findings.
Cao, J., et al. (2013). “Prenatal Bisphenol A Exposure Alters Sex-Specific Estrogen Receptor Expression in the Neonatal Rat Hypothalamus and Amygdala.” Toxicological Sciences (published online March 1, 2013).
Gayrard, V., et al. (2013). “High Bioavailability of Bisphenol A from Sublingual Exposure.”Environmental Health Perspectives (published online June 12, 2013).