Systemic uptake of diethyl phthalate, dibutyl phthalate, and butyl paraben following whole-body topical application and reproductive and thyroid hormone levels in humans. 2007

Nadeem Rezaq Janjua, and Gerda Krogh Mortensen, and Anna-Maria Andersson, and Brian Kongshoj, and Niels E Skakkebaek, and Hans Christian Wulf
Department of Dermatology, Bispebjerg Hospital, Denmark. nrjanjua@hotmail.com

In vitro and animal studies have reported endocrine-disrupting activity of chemicals used commonly as additives in cosmetics and skin care products. We investigated whether diethyl phthalate (DEP), dibutyl phthalate (DBP), and butyl paraben (BP) were systemically absorbed and influenced endogenous reproductive and thyroid hormone levels in humans after topical application. In a two-week single-blinded study, 26 healthy young male volunteers were assigned to daily whole-body topical application of 2 mg/cm2 basic cream formulation each without (week one) and with (week two) the three 2% (w/w) compounds. The concentrations of BP and the main phthalate metabolites monoethyl (MEP) and monobutyl phthalate (MBP) were measured in serum together with the following reproductive hormones: follicle stimulating hormone (FSH), lutenising hormone (LH), testosterone, estradiol, and inhibin B and thyroid hormones (thyroid stimulating hormone (TSH), free thyroxine (FT4), total triiodothyroxine (T3), and total thyroxine (T4)). MEP, MBP, and BP peaked in serum a few hours after application, reaching mean +/- SEM levels of 1001 +/- 81 microg/L, 51 +/- 6 microg/ L, and 135 +/- 11 microg/L, respectively. Only MEP was detectable in serum before treatment. Minor differences in inhibin B, LH, estradiol, T4, FT4, and TSH were observed between the two weeks, but these were not related to exposure. We demonstrated for the first time that DEP, DBP, and BP could be systemically absorbed in man after topical application. The systemic absorption of these compounds did not seem to have any short-term influence on the levels of reproductive and thyroid hormones in the examined young men.

UI MeSH Term Description Entries
D007030 Hypothalamo-Hypophyseal System A collection of NEURONS, tracts of NERVE FIBERS, endocrine tissue, and blood vessels in the HYPOTHALAMUS and the PITUITARY GLAND. This hypothalamo-hypophyseal portal circulation provides the mechanism for hypothalamic neuroendocrine (HYPOTHALAMIC HORMONES) regulation of pituitary function and the release of various PITUITARY HORMONES into the systemic circulation to maintain HOMEOSTASIS. Hypothalamic Hypophyseal System,Hypothalamo-Pituitary-Adrenal Axis,Hypophyseal Portal System,Hypothalamic-Pituitary Unit,Hypothalamic Hypophyseal Systems,Hypothalamic Pituitary Unit,Hypothalamo Hypophyseal System,Hypothalamo Pituitary Adrenal Axis,Portal System, Hypophyseal
D008297 Male Males
D010226 Parabens Methyl, propyl, butyl, and ethyl esters of p-hydroxybenzoic acid. They have been approved by the FDA as antimicrobial agents for foods and pharmaceuticals. (From Hawley's Condensed Chemical Dictionary, 11th ed, p872) 4-Hydroxybenzoic Acids,Paraben,para-Hydroxybenzoic Acids,4 Hydroxybenzoic Acids,para Hydroxybenzoic Acids
D010795 Phthalic Acids A group of compounds that has the general structure of a dicarboxylic acid-substituted benzene ring. The ortho-isomer is used in dye manufacture. (Dorland, 28th ed) Acids, Phthalic
D010913 Pituitary-Adrenal System The interactions between the anterior pituitary and adrenal glands, in which corticotropin (ACTH) stimulates the adrenal cortex and adrenal cortical hormones suppress the production of corticotropin by the anterior pituitary. Pituitary Adrenal System,Pituitary-Adrenal Systems,System, Pituitary-Adrenal,Systems, Pituitary-Adrenal
D003993 Dibutyl Phthalate A plasticizer used in most plastics and found in water, air, soil, plants and animals. It may have some adverse effects with long-term exposure. Butyl Phthalate,Di-n-Butyl Phthalate,Di n Butyl Phthalate,Phthalate, Butyl,Phthalate, Di-n-Butyl,Phthalate, Dibutyl
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000287 Administration, Topical The application of drug preparations to the surfaces of the body, especially the skin (ADMINISTRATION, CUTANEOUS) or mucous membranes. This method of treatment is used to avoid systemic side effects when high doses are required at a localized area or as an alternative systemic administration route, to avoid hepatic processing for example. Drug Administration, Topical,Administration, Topical Drug,Topical Administration,Topical Drug Administration,Administrations, Topical,Administrations, Topical Drug,Drug Administrations, Topical,Topical Administrations,Topical Drug Administrations
D000328 Adult A person having attained full growth or maturity. Adults are of 19 through 44 years of age. For a person between 19 and 24 years of age, YOUNG ADULT is available. Adults
D012739 Gonadal Steroid Hormones Steroid hormones produced by the GONADS. They stimulate reproductive organs, germ cell maturation, and the secondary sex characteristics in the males and the females. The major sex steroid hormones include ESTRADIOL; PROGESTERONE; and TESTOSTERONE. Gonadal Steroid Hormone,Sex Hormone,Sex Steroid Hormone,Sex Steroid Hormones,Sex Hormones,Hormone, Gonadal Steroid,Hormone, Sex,Hormone, Sex Steroid,Hormones, Gonadal Steroid,Hormones, Sex Steroid,Steroid Hormone, Gonadal,Steroid Hormone, Sex,Steroid Hormones, Gonadal,Steroid Hormones, Sex

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