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Isopropylparaben is the ester of isopropyl alcohol and p-hydroxybenzoic acid. It is used in personal care products, but to a much smaller extent than other parabens. According to the US FDA's records, industry reported a mere 48 personal care products containing isopropylparaben in 2006. These included a bath preparation, makeup preparations, fragrance preparations, hair preparations, a shaving preparation, skin care preparations and suntan preparations. A survey conducted by the Cosmetic, Toiletry and Fragrance Association (CTFA) in 2004 found that the use concentrations of isopropylparaben in such products ranged from 0.00001% to 0.3%.
Although the Cosmetic Ingredient Review Expert Panel concluded in 2008 that isopropylparaben is a safe cosmetic ingredient, Europe's Scientific Committee of Consumer Safety considers the human risk of isopropylparaben unevaluable due to the lack of data, and has stated that more information is needed to determine the maximum concentration allowable in cosmetic products.
Isopropylparaben was negative in Ames tests using 6 strains of S. typhimurium, at a concentration of 1 mg/plate in DMSO with and without metabolic activation. A chromosomal aberration assay using a Chinese hamster fibroblast cell line treated with 0.125 mg/ml isopropylparaben in ethanol led to 2% polyploid cells and a 1% incidence of structural chromosomal aberrations, which was below the control incidence of 3% and hence negative.
2.2 Potential endocrine disruptor
The estrogenic activity of the parabens is known to increase with increasing length of the alkyl chain and with branching in the alkyl chain, indicating that isopropylparaben has higher estrogenicity than methylparaben, ethylparaben and propylparaben.
Indeed, receptor binding assays indicate that isopropylparaben has binding affinities to human estrogen receptors α and β that are stronger those of methylparaben and ethylparaben and stronger or equal to that of propylparaben, but weaker than those of butylparaben and isobutylparaben and much weaker than that of estradiol.
High doses of isopropylparaben (1000 mg/kg body weight/day) also resulted in a significant delay in vaginal opening, shortened the estrous cycle length and caused myometrial hypertrophy in prepubertal female rats, in addition to significant decreases in serum estradiol and thyroxine concentrations. Taken together, these findings suggest that long-term exposure to isopropylparaben can produce a suppressive effect on hormonal responsiveness and disrupt the morphology of reproductive target tissues.
Isopropylparaben also has some androgen receptor antagonist activity and can partially inhibit the binding of testosterone to androgen receptors.
2.3 Link to breast cancer
Isopropylparaben has been shown to stimulate the proliferation of a human breast cancer cell line. The stimulation is estrogen receptor-dependent, as it was abolished by the addition of an antiestrogen. However, the concentration of isopropylparaben had to be 100,000 times higher than the concentration of estradiol tested in order to increase the proliferation to approximately the same level, indicating that is it much weaker stimulant than estradiol.
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