One of the stances of the plastics industry that has persuaded some government agencies to not take action against bisphenol A (BPA) has been that the liver aggressively metabolizes BPA and escorts those metabolites out through the urine.
This was supported by a study that was done by researchers at the University of Arizona (Pritchett et al. 2002). In the study, hepatocytes – liver cells – were taken from rats, mice and humans, and were incubated with 10, 20, and 35 microM of BPA. The in vitro study illustrated that these hepatocytes efficiently converted the BPA into excretable metabolites within three hours. This gave the researchers a formula to extrapolate the period for which the human liver should be able to break down and excrete the BPA in metabolite form. BPA only minimally poisoned the body, in other words. The researchers disclosed that the study was partially funded by The Society of Plastics Industry, Inc.
Prior studies also seemed to point to similar conclusions. Two studies (Pottenger et al. 2000 and Upmeier et al. 2000) had shown that BPA must first pass through the intestines and/or liver before it reaches the bloodstream and estrogen receptors. Other studies (Yokota et al. 1999, Nakagawa and Tayama 2000, and Inoue et al. 2001) showed that rat hepatocytes metabolize BPA into BPA monoglucuronide. Furthermore, Pottenger also confirmed that the BPA glucuronide metabolite is eliminated through the urine.
Given all of this, these studies were still hypothetical in that they relied primarily upon incubated hepatocytes, and their application to living organisms were made using extrapolation.
A new study from researchers at the University of Missouri (Taylor et al. 2010) has exposed the weaknesses of those prior studies, and clarified that the liver actually does a rather poor job at metabolizing BPA.
The researchers cruelly fed moderate levels of BP to mice and rhesus monkeys for seven days, and monitored their blood serum levels of BPA. Blood serum levels means that the body is already exposed to the BPA, following any initial screening by the intestines and liver. Once in the blood, BPA can wreck its havoc, in other words.
They found that the blood serum levels of unmetabolized BPA were much higher than any of the previous research had predicted. In the mice, for example, they recovered from the blood serum nearly 90% of the BPA fed to the mice.
The researchers converted their results to humans, as mice and monkey liver metabolization can now be compared to human livers. This led to the conclusion that most of us may be exposed to roughly eight times the 50 micrograms per kilogram of bodyweight the EPA considers safe BPA internal exposure.
Following these results, they concluded that:
“BPA pharmacokinetics in women, female monkeys and mice is very similar. By comparison with ~2 ng/ml serum unconjugated BPA reported in multiple human studies, the average 24 h serum unconjugated BPA concentration of 0.5 ng/ml in both monkeys and mice following a 400-µg/kg oral dose suggests that total daily human exposure is via multiple routes and much higher than previously assumed.” (Taylor et al. 2010)
The ultimate conclusion here is that BPA, which is a monomer used in the production of many plastics, epoxy-based resins, and the coatings on many food cans, is not as readily broken down and excreted out of the body as the plastics industry would like to think.
BPA is most known for weakly mimicking estrogen in the body. This means that it will attach to estrogen receptors (Krishnan et al. 1993, Kuiper et al. 1997). As such, it disrupts the normal processes of estrogen, which include many cellular processes, most importantly, reproductive and growth processes.
This research also confirms CDC’s studies that showed that 95% of the 400 Americans tested had (unmetabolized) BPA in their urine.
A recent review by the Environmental Working Group shows that BPA is linked to increases in the following diseases:
–Polycystic Ovarian Disease
Pottenger LH, Domoradzki JY, Markham DA, Hansen SC, Cagan SZ, Waechter JM, Jr (2000) The relative bioavailability and metabolism of bisphenol A in rats is dependent upon the route of administration. Toxicol Sci 54:3-18.
Krishnan AV, Stathis P, Permuth SF, Tokes L, Feldman D (1993) Bisphenol-A: an estrogenic substance is released from polycarbonate flasks during autoclaving. Endocrinology 132:2279-2286.
Kuiper G, Carlson B, Grandien K, Enmark E, Haggblad J, Nilsson S, Gustafsson JA (1997) Comparison of the ligand binding specificity and transcript tissue distribution of estrogen receptors α and β. Endocrinology 132:2279-2286.
Upmeier A, Degen GH, Diel P, Michna H, Bolt HM (2000) Toxicokinetics of bisphenol A in female DA/Han rats after a single i. v. and oral administation. Arch Toxicol 74:431-436.
Nakagawa Y, Tayama S (2000) Metabolism and cytotoxicity of bisphenol A and other bisphenols in isolated rat hepatocytes. Arch Toxicol 74:99-105.
Yokota H, Iwano H, Endo M, Kobayashi T, Inoue H, Ikushiro S, Yuasa A (1999) Glucuronidation of the environmental oestrogen bisphenol A by an isoform of UDP-glucuronosyltransferase, UGT2B1, in the rat liver. Biochem J 340:405-409.
Inoue H, Yokota H, Makino T, Yuasa A, Kato S (2001) Bisphenol A glucuronide, a major metabolite in rat bile after liver perfusion. Drug Metab Dispos 29:1084-1087.
Pritchett JJ, Kuester RK, Sipes IG. Metabolism of bisphenol a in primary cultured hepatocytes from mice, rats, and humans. Drug Metab Dispos. 2002 Nov;30(11):1180-5.
Taylor JA, Vom Saal FS, Welshons WV, Drury B, Rottinghaus G, Hunt PA, Vandevoort CA. Similarity of Bisphenol A Pharmacokinetics in Rhesus Monkeys and Mice: Relevance for Human Exposure. Environ Health Perspect. 2010 Sep 20.
Environmental Working Group. Bisphenol A: Toxic Plastics Chemical in Canned Food: BPA and human diseases on the rise. http://www.ewg.org/node/20937