The Preservatives Ethyl‐, Propyl‐ and Butylparaben are Oestrogenic in an in vivo Fish Assay

Abstract

Abstract:The widely used phenolic preservatives ethylparaben, propylparaben, butylparaben and their common metabolite p-hydroxybenzoic acid were tested for their ability to evoke an oestrogenic response in vivo. Yolk protein induction in sexually immature rainbow trout was used as an oestrogen-specific endpoint after repeated injections of the compounds. All tested parabens were oestrogenic in doses between 100 and 300 mg/kg, while the metabolite showed no activity. Ethylparaben was found to be approximately sixty times weaker than propyl-and butylparaben which had oestrogenic potencies comparable to those previously found for bisphenol A.Chemicals known to mimic the steroid hormone oestrogen are structurally diverse, although some of the most potent i.e. alkylphenols (Routledge & Sumpter 1997) and bisphenol A (Gaido et al. 1997) share a para-substituted phenol as a common molecular feature. Another class of para-substituted phenols is the food and cosmetic preservatives alkyl hydroxybenzoates (alkylparabens). In a survey of 215 cosmetic products, methyl-, ethyl-, n-propyl-and n-butylparaben were detected in 98, 32, 38 and 16% respectively of the products (Rastogi et al. 1995). Parabens are often used in combinations rather than singly to ensure the most optimal preservation of the cosmetic products (Dal Pozzo & Pastori 1996). Furthermore, parabens are widely used as preservatives in several food and beverage products (Elder 1984). In an in vitro test system methyl-, ethyl-, n-propyl-and nbutylparaben were all found to be weakly oestrogenic (Routledge et al. 1998). In the same study methyl-and nbutylparaben were tested in a rat uterotrophic assay, but only n-butylparaben showed oestrogenic activity (Routledge et al. 1998). Using a similar test system a common metabolite of parabens, p-hydroxy-benzoic acid, has previously been reported to have oestrogenic effects (Lemini et al. 1997).A diverse range of screening systems by which oestrogenicity can be demonstrated is currently used, including in vivo induction of the yolk precursor protein vitellogenin in oviparous animals (Sumpter & Jobling 1995;Palmer & Palmer 1995;Palmer et al. 1998). The present paper describes the in vivo hazard identification of the oestrogenicity of p-hydroxybenzoate and ethyl-, n-propyl-and n-butylparaben using vitellogenin induction in rainbow trout as a test system. Author for correspondence: Poul Bjerregaard, Institute of Biology, USD, Odense University, Campusvej 55, DK-5230 Odense M, Denmark (fax π45 6593 0457, e-mail poul/biology.sdu.dk). Materials and MethodsExposure of animals. Juvenile rainbow trout (80-120 g) were kept under a photoperiod of 12 hr light:12 hr dark in 80 l steel tanks supplied with running freshwater. After an acclimation period of one week the fish were given an intraperitoneal injection of the compounds to be tested. Prior to injections and blood samplings, the fish were anaesthetizised with 0.02 % phenoxyethanol. All injection volumes were adjusted to 1 ml/kg fish. Groups of six or ten fish each were injected a...

Side Chains of Parabens Modulate Antiandrogenic Activity: In Vitro and Molecular Docking Studies

“…The ubiquitous presence of parabens in the environment has raised public concern about whether they potentially cause adverse reproductive effects and their safety has been widely discussed. − Exposure to parabens was reported to cause estrogenic disrupting effects. − Ethyl- and butyl parabens caused a significant increase in progesterone formation in the adrenal H295R steroidogenesis assay and interfered with the transport of cholesterol to the mitochondria . There has been a growing concern in recent years about the health risk of parabens to the androgen hormone system. − Parabens induced an adverse effect on the male reproductive system through reduced testosterone concentrations and sperm production in rats, potentially by influencing the biosynthesis, transport, and metabolism of steroid hormone .…”