Final Amended Report on the Safety Assessment of Methylparaben, Ethylparaben, Propylparaben, Isopropylparaben, Butylparaben, Isobutylparaben, and Benzylparaben as used in Cosmetic Products

Abstract

Parabens is the name given to a group of p-hydroxybenzoic acid (PHBA) esters used in over 22,000 cosmetics as preservatives at concentrations up to 0.8% (mixtures of parabens) or up to 0.4% (single paraben). The group includes Methylparaben, Ethylparaben, Propylparaben, Isopropylparaben, Butylparaben, Isobutylparaben, and Benzylparaben. Industry estimates of the daily use of cosmetic products that may contain parabens were 17.76 g for adults and 378 mg for infants. Parabens in cosmetic formulations applied to skin penetrate the stratum corneum in inverse relation to the ester chain length. Carboxylesterases hydrolyze parabens in the skin. Parabens do not accumulate in the body. Serum concentrations of parabens, even after intravenous administration, quickly decline and remain low. Acute toxicity studies in animals indicate that parabens are not significantly toxic by various routes of administration. Subchronic and chronic oral studies indicate that parabens are practically nontoxic. Numerous genotoxicity studies, including Ames testing, dominant lethal assay, host-mediated assay, and cytogenic assays, indicate that the Parabens are generally nonmutagenic, although Ethylparaben and Methylparaben did increase chromosomal aberrations in a Chinese Hamster ovary cell assay. Ethylparaben, Propylparaben, and Butylparaben in the diet produced cell proliferation in the forestomach of rats, with the activity directly related to chain length of the alkyl chain, but Isobutylparaben and Butylparaben were noncarcinogenic in a mouse chronic feeding study. Methylparaben was noncarcinogenic when injected subcutaneously in mice or rats, or when administered intravaginally in rats, and was not cocarcinogenic when injected subcutaneously in mice. Propylparaben was noncarcinogenic in a study of transplacental carcinogenesis. Methylparaben was nonteratogenic in rabbits, rats, mice, and hamsters, and Ethylparaben was nonteratogenic in rats. Parabens, even at levels that produce maternal toxicity, do not produce fetal anomalies in animal studies. Parabens have been extensively studied to evaluate male reproductive toxicity. In one in vitro study, sperm were not viabile at concentrations as low as 6 mg/ml Methylparaben, 8 mg/ml Ethylparaben, 3 mg/ml Propylparaben, or 1 mg/ml Butylparaben, but an in vivo study of 0.1% or 1.0% Methylparaben or Ethylparaben in the diet of mice reported no spermatotoxic effects. Propylparaben did affect sperm counts at all levels from 0.01% to 1.0%. Epididymis and seminal vesicle weight decreases were reported in rats given a 1% oral Butylparaben dose; and decreased sperm number and motile activity in F(1) offspring of rats maternally exposed to 100 mg/kg day(- 1) were reported. Decreased sperm numbers and activity were reported in F(1) offspring of female rats given Butylparaben (in DMSO) by subcutaneous injection at 100 or 200 mg/kg day(- 1), but there were no abnormalities in the reproductive organs. Methylparaben was studied using rats at levels in the diet up to an estimated mean dose of 1141.1 mg/kg d...

Diet as a Source of Exposure to Environmental Contaminants for Pregnant Women and Children from Six European Countries

“…Fish and vegetable intake were identified as potential emerging dietary sources OXBE, TCS, and parabens. Some parabens are permitted to be applied on food in the European Union, whereas besides such uses, parabens, along with OXBE and TCS, are widely used in cosmetics, personal care products, and pharmaceuticals as antimicrobial preservatives (Andersen 2008; Dann and Hontela 2011; DiNardo and Downs 2018; EFSA 2004; Sakhi et al. 2018).…”

Within-Day, Between-Day, and Between-Week Variability of Urinary Concentrations of Phenol Biomarkers in Pregnant Women

“…2016 ; INERIS 2014 ; NTP 2008 ). Parabens are used as preservatives in cosmetics, food, beverages, and pharmaceuticals; benzophenone-3, an ultraviolet-filter, is used in plastics and cosmetics; triclosan is used for its antibacterial properties in personal care products, clothing, or kitchenware ( Cosmetic Ingredient Review Expert Panel 2008 ; Krause et al. 2012 ; NLM 2016 ); 2,4-dichlorophenol is used in the production of certain pesticides; and 2,5-dichlorophenol is a major metabolite of 1,4-dichlorobenzene, which is used in moth balls and room deodorizers ( Crinnion 2010 ; HSDB 2016 ).…”

Effects of methylparaben on in vitro maturation of porcine oocytes

“…According to Meng et al (2020), the number of oocytes with apoptosis increased after IBP exposure; however, in another study, the toxic potential of PBs in hepatocytes was evaluated, and they determined that cytotoxicity is proportional to the size of PBs (Nakagawa & Moldeus, 1998). Therefore, the longer the carbon chain of PBs, the more their effect is exacerbated (Andersen, 2008;Soni et al, 2005).…”