Systemic Uptake of Diethyl Phthalate, Dibutyl Phthalate, and Butyl Paraben Following Whole-Body Topical Application and Reproductive and Thyroid Hormone Levels in Humans

Abstract

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.

Current exposure of 200 pregnant Danish women to phthalates, parabens and phenols

“…Several, in vitro, animal and a few human studies have shown that a major part of orally administered paraben is excreted in urine as the unspecific metabolite, p-hydroxybenzoic acid, while only a minor part is excreted as free paraben and its glucuronic and sulphuric acid conjugates (Soni et al 2005, Ye et al 2006, CIR Expert Panel 2008. Following skin application, a minor part of the parabens was excreted in urine as the parent paraben in free (unconjugated) and conjugated form (glucuronidated and sulphated) (Janjua et al 2007). Hence, as our estimated daily excretion of parabens is based on the fraction that was excreted as the conjugated and unconjugated parent compound, it most likely only represents a minor fraction of the true exposure and as such is a very conservative estimate.…”

Occurrence of parabens in foodstuffs from China and its implications for human dietary exposure

“…Parabens can be absorbed via skin and via the gastrointestinal tract (Akomeah et al, 2004;Janjua et al, 2007;Lobemeier et al, 1996) and are excreted in urine (Andersen, 2008;Soni et al, 2005). A few biomonitoring studies have reported the occurrence of parabens in human urine, plasma, serum, and milk (Calafat et al, 2010;Casas et al, 2011;Darbre and Harvey, 2008;Frederiksen et al, 2011;Janjua et al, 2007;Schlumpf et al, 2010;Ye et al, 2006aYe et al, , 2006bYe et al, , 2008.…”

Relationship between everyday use cosmetics and female breast cancer

“…13,20 Several European studies have confirmed the presence of parabens in urine, blood, human milk samples, and semen in the European population. It is also possible that systemically absorbed low -dose chemicals might accumulate and result in diffusion to the breast region 13,17,19,20 However, the above clinical studies did not establish a clear correlation between parabens and breast cancer development.…”

“…[13][14][15] Elder 16 identified parabens in 99% of the cosmetics tested. Janjua et al 17 demonstrated that parabens can be rapidly absorbed through the skin into the human body even from a single dose of a body care product and long -term exposure results in the accumulation of these chemicals.…”