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      Ex-vivo Studies for the Passive Transdermal Permeation and Extent of Metabolism of Methyl and Butyl Paraben from a Cream

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          Summary

          Concerns regarding the safety of cumulative exposure to parabens have been raised as a consequence of their estrogenic and endocrine effects. These antibacterial agents are commonly used in food, pharmaceutical and cosmetic products. Preliminary data from animal models has indicated potential links between paraben exposure and various conditions ranging from skin disorders to autism. Oral consumption of parabens is not a cause for concern because they are readily metabolised by the liver and excreted rapidly by the kidney. The presence of parabens in adipose tissue is thought to be due to dermal absorption of parabens where they are incompletely metabolised. Various studies have been performed on paraben absorption; however transdermal permeation of parabens from an emulsion has not been studied to date. In this preliminary study dermal permeation and metabolism across human skin were evaluated for methyl paraben (MP) and butyl paraben (BP) from an emulsion, using Franz Diffusion cell system with analysis by q-ToF (quadrupole time of flight) mass spectrometry. MP was observed to have lower permeation and lower extent of metabolism than BP.

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          Safety assessment of esters of p-hydroxybenzoic acid (parabens).

          Parabens are widely used as preservatives in food, cosmetic and pharmaceutical products. Acute, subchronic, and chronic studies in rodents indicate that parabens are practically non-toxic. Parabens are rapidly absorbed, metabolized, and excreted. In individuals with normal skin, parabens are, for the most part, non-irritating and non-sensitizing. However, application of compounds containing parabens to damaged or broken skin has resulted in sensitization. Genotoxicity testing of parabens in a variety of in vitro and in vivo studies primarily gave negative results. The paraben structure is not indicative of carcinogenic potential, and experimental studies support these observations. Some animal studies have reported adverse reproductive effects of parabens. In an uterotrophic assay, methyl and butyl paraben administered orally to immature rats were inactive, while subcutaneous administration of butyl paraben produced a weak positive response. The ability of parabens to transactivate the estrogen receptor in vitro increases with alkyl group size. The detection of parabens in a small number of breast tumor tissue samples and adverse reproductive effects of parabens in animals has provoked controversy over the continued use of these substances. However, the possible estrogenic hazard of parabens on the basis of the available studies is equivocal, and fails to consider the metabolism and elimination rates of parabens, which are dose, route, and species dependent. In light of the recent controversy over the estrogenic potential of parabens, conduct of a reproductive toxicity study may be warranted.
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            Combined prenatal and postnatal butyl paraben exposure produces autism-like symptoms in offspring: comparison with valproic acid autistic model.

            The aim of this work is to evaluate the impact of butyl paraben (BP) in brain of the pups developed for mothers administered BP from early pregnancy till weaning and its effect on studying the behavior, brain neurotransmitters and brain derived neurotrophic factor BDNF via comparing the results with valproic acid (VA) autistic-rat model preparing by a single oral injection dose of VA (800 mg/kg b.wt) at the 12.5 days of gestation. Butyl paraben was orally and subcutaneously administered (200 mg/kg b.wt) to pregnant rats from gestation day 1 to lactation day 21. The offspring male rats were subjected at the last 3 days of lactation to Morris water maze and three chamber sociability test then decapitated and the brain was excised and dissected to the cortex, hippocampus, cerebellum, midbrain and pons for the determination of norepinephrine, dopamine and serotonin (NE, DA and 5-HT) and cortex amino acids and whole brain BDNF. The results showed similar social and learning and memory behavioral deficits in VA rat model and the butyl paraben offspring in comparison with the controls. Also, some similar alterations were observed in monoamine content, amino acids and BDNF factor in the autistic-like model and butyl paraben offspring in comparison with the controls. The alterations were recorded notably in hippocampus and pons NE, midbrain DA, hippocampus and midbrain 5-HT, and frontal cortex GABA and asparagine. These data suggest that prenatal exposure to butyl paraben induced neuro-developmental disorders similar to some of the neurodevelopmental disorders observed in the VA model of autism.
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              Interplay between pro-inflammatory cytokines and brain oxidative stress biomarkers: Evidence of parallels between butyl paraben intoxication and the valproic acid brain physiopathology in autism rat model

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                Author and article information

                Journal
                BJPharm
                British Journal of Pharmacy
                University of Huddersfield Press
                2058-8356
                04 December 2017
                : 2
                : 2 , Proceedings of the 8 th APS International PharmSci 2017
                : S5-S6
                Affiliations
                [a ]School of Pharmacy and Pharmaceutical Sciences, Faculty of Health Sciences and Wellbeing, University of Sunderland, Sunderland, UK
                [b ]ESPA Research, Sunderland, UK
                [c ]Medical Toxicology Centre, Newcastle University, Newcastle, UK.
                Author notes
                *Corresponding author. Tel.: +44 191 515 2503 Fax: +44 191 515 2505 E-mail: kalliopi.dodou@ 123456sunderland.ac.uk
                Article
                10.5920/bjpharm.2017.13
                69b39a78-e735-426d-9ff9-88f6655cd8a5
                © 2017, Aida Hatami, Kevin Carr, Paul Whiteley, Simon Wilkinson, Kalliopi Dodou

                This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY) 4.0 https://creativecommons.org/licenses/by/4.0/.

                History
                : 13 March 2017
                : 07 August 2017

                Medicine,Pharmacology & Pharmaceutical medicine,Health & Social care
                Paraben,4-hydroxybenzoic acid,q-ToF mass spectrometry,Skin metabolism

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