Table of contents:
1.1 In personal care products
Benzylparaben is the ester of benzyl alcohol and p-hydroxybenzoic acid. It is much less commonly used in cosmetics than methylparaben, propylparaben, ethylparaben and butylparaben. Data submitted by industry to the US FDA in 2006 showed only 3 uses of benzylparaben, all in underarm deodorants, down from the 45 uses reported in 1984. Further, in 1984 most uses of benzylparaben were less than or equal to 0.1% (excepting one underarm deodorant in the 0.1-1% range), whereas an industry survey conducted later in 2003 was not able to find any reported uses or use concentrations of benzylparaben.
More recently, tests on 170 personal care products bought in 2012 from the US revealed the presence of benzylparaben in 7% of rinse-off products, 11% of leave-on products and 15% of baby care products, at concentrations up to 8.18 μg/g (0.0008%). An investigation that same year of 52 personal care products bought from Tianjin, China, did not find benzylparaben in any of the samples analyzed, confirming its infrequency of use relative to the other parabens.
The Cosmetic Ingredient Review Expert Panel considered benzylparaben to be a safe cosmetic ingredient in its amended safety assessment on parabens published in 2008. However, the European Commission's Scientific Committee on Consumer Safety reiterated in 2013 its view that the human risk of benzylparaben could not be evaluated due to the limited amount of information available.
1.2 In food
Benzylparaben has been found in foodstuffs from the United States, though it was less frequently detected and present at lower concentrations compared to methylparaben, ethylparaben and propylparaben.
1.3 In the environment
Benzylparaben has been detected in aquatic environments. Its highest measured concentration is 4.4 ng/L in the Glatt River in Switzerland, which is significantly lower than the highest concentrations observed for the other parabens. Benzylparaben is both photodegradable and biodegradable, limiting its persistence in water sources.
An analysis of 253 paper products found benzylparaben in 25% of the products, at concentrations up to 281 ng/g. The highest concentrations were detected in sanitary wipes and currency bills.
Since benzylparaben is less commonly found in cosmetics, in food and in the environment, it stands to reason that exposure to benzylparaben should be lower than that of the other parabens. Indeed, benzylparaben was detected in the urine samples of only 39 out of 100 anonymous adults from the United States, compared to methylparaben (99%), propylparaben (96%), ethylparaben (58%) and butylparaben (69%). These results were similar to those found in 60 Danish men, where benzylparaben was measurable in the urine from only 7% of the men, unlike methylparaben (98%), ethylparaben (80%), propylparaben (98%) and butylparaben (83%). Likewise, a study in China on 109 Chinese young adults detected benzylparaben in only 19% of the urine samples, compared to methylparaben, propylparaben and ethylparaben which were detected in all samples, and butylparaben which was detected in 61% of the samples.
The urinary and serum concentrations of benzylparaben are also consistently among the lowest of the parabens analyzed. The highest urinary concentrations measured were 0.13 μg/L in Chinese young adults, 0.5 μg/L in a study in the US, 0.8 μg/L in a study in Greece and 2.06 μg/L in a study of Danish men.
Measured serum concentrations of benzylparaben are even lower, with the highest observed concentration at just 0.29 μg/L. Other studies which analyzed plasma samples for parabens were not able to detect benzylparaben at all.
3. Topical bioavailability
It has been reported that the permeability coefficient varies as a function of chain length for the parabens using full-thickness human skin, such that those with shorter alkyl chains have higher permeability coefficients. This suggests that benzylparaben penetrates the skin more poorly compared to methylparaben, ethylparaben, propylparaben and butylparaben.
Benzylparaben is at least partly metabolized after penetrating the skin; one study demonstrated that when benzylparaben was applied to dermatomed human breast skin, 4% was still on the skin surface 24 hours later, 36% remained unmetabolized in the skin, 17% had penetrated through the skin as the native paraben, and 2% had been metabolized to p-hydroxybenzoic acid before crossing the skin.
4.1 Skin irritation and sensitization
Parabens are among the least sensitizing commercial preservatives, with most studies showing sensitization rates up to 3%. This is true of patch test data from North America, Europe and the Asia-Pacific. These patch tests usually utilize a mix of paraben esters however, and some did not include benzylparaben. We were only able to find 2 reports of contact allergy/dermatitis to benzylparaben alone.
4.2 Potential endocrine disruptor
Benzylparaben has demonstrated estrogenic activity in a mouse uterine weight bioassay. When applied topically at 33 mg/mouse once daily for 3 days, estrogenic activity was reported, but not when applied daily at a 100 mg level. Moreover, like the other parabens the estrogenic potency was low compared to estradiol and there was no dose response. After comparing these results with those methylparaben from an earlier study, the authors concluded that the estrogenic activity of parabens increases with the addition of an aryl group.
Benzylparaben was also estrogenic in an in vitro yeast bioassay, with an estrogenic activity that was 4000 times lower than estradiol. In a competitive binding assay, its relative binding affinity for the estrogen receptor was ~30,000 times weaker than that of estradiol.
4.3 Link to breast cancer
Benzylparaben displayed several effects when tested on a human breast cancer cell line. It displaced estradiol from cytosolic estrogen receptors (ER) of human breast cancer cells in a dose-dependent manner, increased the expression of a estrogen responsive reporter gene in these cells, and was also able to increase the cells' proliferation. The growth effects were ER-mediated, as they were inhibited by a pure antiestrogen. In addition, benzylparaben was capable of increasing the growth of a second estrogen-dependent human breast cancer cell line but not an estrogen-insensitive cell line, providing further evidence of ER-mediation.
A recent study observed that benzylparaben possessed inverse antagonist activity on human estrogen-related receptor γ (ERRγ), a known diagnostic biomarker and treatment target of breast cancer. Its 50% relative effective concentration was 134 μg/L.
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