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Isobutylparaben is the ester of isobutyl alcohol and p-hydroxybenzoic acid. Like the other parabens, it is used in cosmetics as an antimicrobial preservative. In 2006, industry reported to the US FDA that isobutylparaben was used in 642 products across a wide range of categories, including baby products, bath preparations, makeup preparations, fragrance preparations, hair preparations, nail care products, personal cleanliness products, shaving preparations, skin care preparations and suntan preparations. Use concentrations ranged from 0.000007% to 0.5% in 2004.
The Cosmetic Ingredient Review Expert Panel concluded in their safety assessment in 2008 that isobutylparaben is safe for use in cosmetics, but the opinion of the Scientific Committee on Consumer Safety in Europe is that there is insufficient data to evaluate the human risk of isobutylparaben or to formulate a final statement on the maximum concentration of isobutylparaben that is allowed in cosmetic products.
Isobutylparaben was negative at a concentration of 1 mg/plate in Ames tests using 6 different S. typhimurium strains, as well as in an a chromosomal aberration assay using a Chinese hamster fibroblast cell line at a concentration of 0.03%, results that have been replicated elsewhere. Another study reported that isobutylparaben was positive in a chromosomal aberration assay but negative in an Ames test and in a rec assay.
2.2 Developmental toxicity
Maternal exposure to isobutylparaben in rats decreased the plasma corticosterone concentration and increased the uterus weight in dams and increased uterine sensitivity to estrogen in adult female offspring in one study. It has also been shown to alter anxiety and passive avoidance test performance in adult male rats, as well as impair social recognition in adult female rats.
2.3 Potential endocrine disruptor
Simplified models of interaction indicate that isobutylparaben can theoretically displace estradiol at estrogen receptors. This is supported by receptor binding assays that show that isobutylparaben binds to both estrogen receptor α and β.
Isobutylparaben exhibited estrogenic effects in rodent uterotrophic assays. High doses of isobutylparaben (1000 mg/kg body weight/day) also induced the expression of calbindin-D9k, a potent biomarker used in the screening estrogen-like environmental chemicals, and the expression of estrogen receptor α, but decreased the expression of a progesterone receptor in immature female rats. A similar study on prepubertal female rats found that the same dose of isobutylparaben also decreased the concentrations of serum estradiol and thyroxine.
It is important to note that the relative potency of isobutylparaben is much weaker compared to estradiol and is only 1/4,000,000 that of ethinyl estradiol (a synthetic derivative of estradiol) however.
Interestingly, isobutylparaben appears to be eliminated in the presence of the enzyme laccase and the redox mediator 1-hydroxybenzotriazole (HBT), thereby abolishing its estrogenicity.
Apart from its estrogenic activity, isobutylparaben also appears to possess antiandrogenic activity, for it antagonized androgen receptors at concentrations above 25 µm in one study.
2.4 Link to breast cancer
Isobutylparaben has been detected in human breast cancer tissues at concentrations up to 803 ng/g. It has also been demonstrated to stimulate proliferation of human breast cancer cells in 2 separate studies, albeit much more weakly than estradiol.
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