Oestrogenic activity of isobutylparaben in vitro and in vivo
Article first published online: 18 JUL 2002
Copyright © 2002 John Wiley & Sons, Ltd.
Journal of Applied Toxicology
Volume 22, Issue 4, pages 219–226, July/August 2002
How to Cite
Darbre, P. D., Byford, J. R., Shaw, L. E., Horton, R. A., Pope, G. S. and Sauer, M. J. (2002), Oestrogenic activity of isobutylparaben in vitro and in vivo. J. Appl. Toxicol., 22: 219–226. doi: 10.1002/jat.860
- Issue published online: 18 JUL 2002
- Article first published online: 18 JUL 2002
- Manuscript Accepted: 2 MAY 2002
- Manuscript Revised: 24 APR 2002
- Manuscript Received: 8 FEB 2002
- Seedcorn Programme of the Veterinary Laboratories Agency.
- University of Reading Research Endowment Trust Fund.
- breast cancer cells;
- environmental oestrogen;
- mouse uterus
The alkyl esters of p-hydroxybenzoic acid (parabens) are used widely as preservatives in foods, pharmaceuticals and cosmetics to which the human population is exposed. Recent studies have reported that methylparaben, ethylparaben, n-propylparaben and n-butylparaben all possess oestrogenic activity in several in vitro assays and in animal models in vivo. This study reports on the oestrogenic activity of isobutylparaben in a panel of assays in vitro and in vivo. Isobutylparaben was able to displace [3H]oestradiol from cytosolic oestrogen receptor α of MCF7 human breast cancer cells by 81% at 100 000-fold molar excess. Using a clonal line of MCF7 cells containing a stably transfected oestrogen-responsive ERE-CAT reporter gene, CAT gene expression could be increased by isobutylparaben such that the magnitude of the response was the same at 10−5 M isobutylparaben as with 10−8 M 17β-oestradiol. Isobutylparaben could also increase expression of the endogenous oestrogen-responsive pS2 gene in MCF7 cells and maximal expression at 10−5 M isobutylparaben could be inhibited with the anti-oestrogen ICI 182 780. The proliferation of two oestrogen-dependent human breast cancer cell lines MCF7 and ZR-75-1 could be increased with isobutylparaben such that at concentrations of 10−5 M the proliferation response was of the same magnitude as with 10−8 M 17β-oestradiol. Evidence for oestrogen receptor mediation of proliferation effects was provided by the inability of isobutylparaben to influence the growth of oestrogen-unresponsive MDA-MB-231 human breast cancer cells and by the ability of the anti-oestrogen ICI 182 780 to inhibit the isobutylparaben effects on MCF7 cell growth. The proliferation response to 10−10 M 17β-oestradiol was not antagonized with isobutylparaben at any concentration from 10−9 M to 10−4 M in either MCF7 or ZR-75-1 cells. Finally, subcutaneous administration of isobutylparaben was able to increase the uterine weight in the immature mouse after three daily doses of 1.2 or 12.0 mg per mouse. Previous work using linear-alkyl-chain parabens has shown that oestrogenic activity increases with alkyl chain length from methylparaben to n-butylparaben. The results here show that branching of the alkyl chain to isobutylparaben increases oestrogenic activity beyond that of the equivalent length linear alkyl chain in n-butylparaben. Copyright © 2002 John Wiley & Sons, Ltd.