Isobutylparaben

Isobutylparaben is the ester of isobutyl alcohol and p-hydroxybenzoic acid. Much more research needs to be conducted in order to determine its human risk and its safety as a cosmetic ingredient.

Scientific Research


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Table of contents:

1. Sources

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.[1]

The Cosmetic Ingredient Review Expert Panel concluded in their safety assessment in 2008 that isobutylparaben is safe for use in cosmetics,[1] 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.[2][3]

2. Safety

2.1 Genotoxicity

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%,[4] results that have been replicated elsewhere.[5] Another study reported that isobutylparaben was positive in a chromosomal aberration assay but negative in an Ames test and in a rec assay.[6]

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.[7] It has also been shown to alter anxiety and passive avoidance test performance in adult male rats,[8] as well as impair social recognition in adult female rats.[9]

2.3 Potential endocrine disruptor

Simplified models of interaction indicate that isobutylparaben can theoretically displace estradiol at estrogen receptors.[10] This is supported by receptor binding assays that show that isobutylparaben binds to both estrogen receptor α and β.[11][12]

Isobutylparaben exhibited estrogenic effects in rodent uterotrophic assays.[13][11] 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.[14] A similar study on prepubertal female rats found that the same dose of isobutylparaben also decreased the concentrations of serum estradiol and thyroxine.[11]

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.[13][11]

Interestingly, isobutylparaben appears to be eliminated in the presence of the enzyme laccase and the redox mediator 1-hydroxybenzotriazole (HBT), thereby abolishing its estrogenicity.[15]

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.[16]

Isobutylparaben has been detected in human breast cancer tissues at concentrations up to 803 ng/g.[17] It has also been demonstrated to stimulate proliferation of human breast cancer cells in 2 separate studies, albeit much more weakly than estradiol.[12][18]

Scientific References


  1. Cosmetic Ingredient Review Expert Panel. Final amended report on the safety assessment of Methylparaben, Ethylparaben, Propylparaben, Isopropylparaben, Butylparaben, Isobutylparaben, and Benzylparaben as used in cosmetic products. Int J Toxicol. (2008)
  2. Scientific Committee on Consumer Safety. Opinion on parabens, 2013. SCCS. (2013)
  3. Scientific Committee on Consumer Products. Opinion on parabens, 2008. SCCP. (2008)
  4. Ishidate M Jr, Odashima S. Chromosome tests with 134 compounds on Chinese hamster cells in vitro--a screening for chemical carcinogens. Mutat Res. (1977)
  5. Ishidate M Jr, et. al. Primary mutagenicity screening of food additives currently used in Japan. Food Chem Toxicol. (1984)
  6. Odashima S. Cooperative programme on long-term assays for carcinogenicity in Japan. IARC Sci Publ. (1980)
  7. Kawaguchi M, et. al. Maternal isobutyl-paraben exposure decreases the plasma corticosterone level in dams and sensitivity to estrogen in female offspring rats. J Vet Med Sci. (2009)
  8. Kawaguchi M, et. al. Maternal isobutyl-paraben exposure alters anxiety and passive avoidance test performance in adult male rats. Neurosci Res. (2009)
  9. Kawaguchi M, et. al. Maternal exposure to isobutyl-paraben impairs social recognition in adult female rats. Exp Anim. (2010)
  10. Guadarrama P, et. al. Construction of simplified models to simulate estrogenic disruptions by esters of 4-hydroxy benzoic acid (parabens). Biophys Chem. (2008)
  11. Vo TT, et. al. Potential estrogenic effect(s) of parabens at the prepubertal stage of a postnatal female rat model. Reprod Toxicol. (2010)
  12. Okubo T, et. al. ER-dependent estrogenic activity of parabens assessed by proliferation of human breast cancer MCF-7 cells and expression of ERalpha and PR. Food Chem Toxicol. (2001)
  13. Koda T, et. al. Uterotrophic effects of benzophenone derivatives and a p-hydroxybenzoate used in ultraviolet screens. Environ Res. (2005)
  14. Vo TT, Jeung EB. An evaluation of estrogenic activity of parabens using uterine calbindin-d9k gene in an immature rat model. Toxicol Sci. (2009)
  15. Mizuno H, et. al. Removal of estrogenic activity of iso-butylparaben and n-butylparaben by laccase in the presence of 1-hydroxybenzotriazole. Biodegradation. (2009)
  16. Kjaerstad MB, et. al. Mixture effects of endocrine disrupting compounds in vitro. Int J Androl. (2010)
  17. Barr L, et. al. Measurement of paraben concentrations in human breast tissue at serial locations across the breast from axilla to sternum. J Appl Toxicol. (2012)
  18. Darbre PD, et. al. Oestrogenic activity of isobutylparaben in vitro and in vivo. J Appl Toxicol. (2002)