Systemic uptake of diethyl phthalate, dibutyl phthalate, and butyl paraben following whole-body topical application and reproductive and thyroid hormone levels in humans.
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.
Janjua
Nadeem Rezaq
NR
Department of Dermatology, Bispebjerg Hospital, Denmark. nrjanjua@hotmail.com
Mortensen
Gerda Krogh
GK
Andersson
Anna-Maria
AM
Kongshoj
Brian
B
Skakkebaek
Niels E
NE
Wulf
Hans Christian
HC
D000287:Administration, Topical; D000328:Adult; D003993:Dibutyl Phthalate / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology; D012739:Gonadal Steroid Hormones / Q000097:blood*; D006801:Humans; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects; D008297:Male; D010226:Parabens / Q000008:administration & dosage* / Q000032:analysis / Q000493:pharmacokinetics* / Q000494:pharmacology; D010795:Phthalic Acids / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics* / Q000494:pharmacology; D010913:Pituitary-Adrenal System / Q000187:drug effects; D013963:Thyroid Hormones / Q000097:blood*