Some Alkyl Hydroxy Benzoate Preservatives (Parabens) Are Estrogenic

doi:10.1006/taap.1998.8544

Toxicology and Applied Pharmacology

Volume 153, Issue 1, November 1998, Pages 12-19

https://doi.org/10.1006/taap.1998.8544 Get rights and content

Abstract

The inadvertent estrogenicity of certain synthetic chemicals, and their subsequent effects on the endocrine system of humans and wildlife, is of concern. In this paper we report findings fromin vitroandin vivo(uterotrophic) studies which confirm that a range of alkyl hydroxy benzoate preservatives (parabens) are weakly estrogenic. In a receptor-binding assay, butylparaben was able to compete with³H-estradiol for binding to the rat estrogen receptor with an affinity approximately 5 orders of magnitude lower than that of diethylstilboestrol, and between 1 and 2 orders of magnitude less than nonylphenol. In anin vitroyeast-based estrogen assay, the four most widely used parabens (namely methyl-, ethyl-, propyl-, and butylparaben) were all found to be weakly estrogenic with the most potent (butylparaben) being 10,000-fold less potent than 17β-estradiol. The estrogenic activity of parabens was inhibited by 4-hydroxy tamoxifenin vitro,illustrating the requirement of these chemicals to interact with the estrogen receptor in order to activate the yeast. When administered orally to immature rats, the parabens were inactive. However, subcutaneous administration of butylparaben produced a positive uterotrophic responsein vivo,although it was approximately 100,000 times less potent than 17β-estradiol. Given their use in a wide range of commercially available topical preparations, it is suggested that the safety in use of these chemicals should be reassessed, with particular attention being paid to estimation of the actual levels of systemic exposure of humans exposed to these chemicals. The acquisition of such data is a prerequisite to the derivation of reliable estimates of the possible human risk of exposure to parabens.

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Butylparaben (BuP) is a common antibacterial preservative utilized extensively in food, medical supplies, cosmetics, and personal care products. The current study reports the use of Zebrafish (Danio rerio) embryos to investigate potential developmental toxicity caused by exposure to BuP. The development of Neural crest cells (NCCs) is highly active during gastrulation in Zebrafish embryos. Thus, we utilized 0.5 mg/L, 0.75 mg/L, and 1 mg/L BuP solutions, respectively, in accordance with the international safety standard dosage. We observed severe craniofacial cartilage deformities, periocular edema, cardiac dysplasia, and delayed otolith development in the Zebrafish larvae 5 days after exposure. The oxidative stress response was significantly enhanced. In addition, the biochemical analysis revealed that the activities of catalase (CAT) and superoxide dismutase (SOD) were significantly reduced relative to the control group, whereas the concentration of malondialdehyde (MDA) was significantly elevated. Furthermore, ALP activity, a marker of osteoblast activity, was also reduced. Moreover, the RT-qPCR results indicated that the expression of chondrocyte marker genes sox9a, sox9b, and col2a1a was down-regulated. In addition, the morphology of maxillofacial chondrocytes was altered in Zebrafish larvae, and the proliferation of cranial NCCs was inhibited. Accordingly, our findings indicate that strong oxidative stress induced by BuP inhibits the proliferation of NCCs in larval Zebrafish, leading to craniofacial deformities.
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Regular ArticleSome Alkyl Hydroxy Benzoate Preservatives (Parabens) Are Estrogenic

Abstract

Regul. Toxicol. Pharmacol.

J. Pharm. Sci.

J. Pharm. Sci.

Regul. Toxicol. Pharmacol.

J. Biol. Chem.

Decline in semen quality among fertile men in Paris during the past 20 years

N. Engl. J. Med.

Declining semen quality and increasing incidence of testicular cancer: Is there a common cause

Environ. Health Perspect.

Evidence for decreasing quality of semen during past 50 years

Br. Med. J.

Percutaneous absorption of parabens from cosmetic formulations

Int. J. Cosmetic Sci.

Inhibition ofClostridium botulinumbyp-hydroxybenzoic acidn-alkyl esters

Antimicrob. Agents Chemother.

Final report on the safety assessment of methylparaben, ethylparaben, propylparaben, and butylparaben

J. Am. Coll. Toxicol.

Immunolocalisation of oestrogen receptor-α within the testis and excurrent ducts of the rat and marmoset monkey from perinatal life to adulthood

J. Endocrinol.

Transformations related to the angular and the square root

Ann. Math. Stats.

Estrogen receptor (α & β) expression in the excurrent ducts of the adult male rat reproductive tract

J. Androl.

A role for oestrogens in the male reproductive system

Nature

The study on the biological fate of paraben at the dose of practical usage in rat. I. The metabolism and excretion of ethyl p-hydroxybenzoate (ethyl paraben) and p-hydroxybenzoic acid

J. Pharm. Dyn.

The study on the biological fate of paraben at the dose of practical usage in rat. II. The pharmacokinetic study on the blood concentration after the administration of ethyl paraben or p-hydroxybenzoic acid

J. Pharm. Dyn.

Regular Article
Some Alkyl Hydroxy Benzoate Preservatives (Parabens) Are Estrogenic