An article published on April 5, 2017 in the peer-reviewed journal Toxicology and Applied Pharmacology highlighted the influence of parabens on the metabolism and detoxification of a natural estrogen hormone 17β-estradiol (E2, CAS 50-28-2) and a xenoestrogen bisphenol A (BPA, CAS 80-05-7). Parabens are antimicrobial preservatives used in various consumer products. BPA is used among others in polycarbonate plastics and epoxy can coatings.

Tyler Pollock and colleagues from the Department of Psychology, Neuroscience & Behavior, McMaster University, Hamilton, Canada, performed simultaneous exposures of adult mice to parabens and isotopically labeled BPA (14C-BPA).  The two parabens tested individually, butyl paraben (CAS 94-26-8) and propyl paraben (CAS 94-13-3), were injected subcutaneously to simulate skin exposure, while 14C-BPA was delivered orally with a portion of peanut butter. Internal concentrations of 14C-BPA were measured one hour after exposure. In a separate experiment, concentration of Ewas measured in urine collected up to 12 hours post-injection with one of the parabens.

Butyl paraben exposure resulted in significantly elevated concentrations of 14C-BPA in the blood of both sexes, as well as in the lungs, uterus, and ovaries of females, and testes and epididymis in males. This chemical also caused a significant increase in E2 levels in urine 6-10 hours post-injection in females, and 8 hours post injection in males. Upon propyl paraben exposure, an increase in 14C-BPA levels was significant only in the uterus, and E2 levels in urine were not affected.

The study’s findings are consistent with the fact that parabens can inhibit several enzymes that are involved in the metabolism of (xeno)estrogens, including cytochrome P450s (CYP), sulfotransferases (SULT), and UDP-glucuronosyltransferases (UGT). Enzyme inhibition impairs detoxification and excretion of (xeno)estrogens, resulting in a build-up of internal concentrations. Previously, similar elevation of internal levels of 14C-BPA and E2 has been observed with another widely used antimicrobial chemical, triclosan (CAS 3380-34-5), which is also known to inhibit SULT and UGT enzymes.

The authors concluded that their work demonstrates “the importance of considering concurrent exposure to multiple chemicals when determining regulatory exposure limits.”

Read more

ChemWatch (April 20, 2017). “Parabens may affect BPA metabolism, say Canadian researchers.

References

Pollock, T., et al. (2017). “Butyl paraben and propyl paraben modulate bisphenol A and estradiol concentrations in female and male mice.Toxicology and Applied Pharmacology (published April 5, 2017).

Pollock, T., et al. (2016). “Triclosan elevates estradiol levels in serum and tissues of cycling and peri-implantation female mice.Reproductive Toxicology, 65: 394-401.

Pollock, T., et al. (2014). “Triclosan exacerbates the presence of 14C-bisphenol A in tissues of female and male mice.Toxicology and Applied Pharmacology, 278: 116-123.

Ozaki, H., et al. (2016). “Cytochrome P450-inhibitory activity of parabens and phthalates used in consumer products.” Journal of Toxicological Sciences, 41: 551-560.

Prusakiewicz, J., et al. (2007). “Parabens inhibit human skin estrogen sulfotransferase activity: Possible link to paraben estrogenic effects.Toxicology, 232: 248-256.

Abbas, S., et al. (2010). “Metabolism of parabens (4-hydroxybenzoic acid esters) by hepatic esterases and UDP-glucuronosyltransferases in man.Drug Metabolism and Pharmacokinetics, 25: 568-577.

James, M., et al. (2010). “Triclosan is a potent inhibitor of estradiol and estrone sulfonation in sheep placenta.Environment International, 36: 942-949.

Wang, L., et al. (2004). “Triclosan as a substrate and inhibitor of 3’-phosphoadenosine 5’-phosphosulfate-sulfotransferase and UDP-glucuronosyl transferase in human liver fractions.Pharmacology, 32: 1162-1169.

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