Association of birth outcomes with fetal exposure to parabens, triclosan and triclocarban in an immigrant population in Brooklyn, New York

Abstract

Background

Prior studies suggest associations between fetal exposure to antimicrobial and paraben compounds with adverse reproductive outcomes, mainly in animal models. We have previously reported elevated levels of these compounds for a cohort of mothers and neonates.

Objective

We examined the relationship between human exposure to parabens and antimicrobial compounds and birth outcomes including birth weight, body length and head size, and gestational age at birth.

Methods

Maternal third trimester urinary and umbilical cord blood plasma concentrations of methylparaben (MePB), ethylparaben (EtPB), propylparaben (PrPB), butylparaben (BuPB), benzylparaben (BePB), triclosan (2,4,4′-trichloro-2′-hydroxydiphenyl ether or TCS) and triclocarban (1-(4-chlorophenyl)-3-(3,4-dichlorophenyl) urea or TCC), were measured in 185 mothers and 34 paired singleton neonates in New York, 2007–2009.

Results

In regression models adjusting for confounders, adverse exposure-outcome associations observed included increased odds of PTB (BuPB), decreased gestational age at birth (BuPB and TCC) and birth weight (BuPB), decreased body length (PrPB) and protective effects on PTB (BePB) and LBW (3′-Cl-TCC) (p < 0.05). No associations were observed for MePB, EtPB, or TCS.

Conclusions

This study provides the first evidence of associations between antimicrobials and potential adverse birth outcomes in neonates. Findings are consistent with animal data suggesting endocrine-disrupting potential resulting in developmental and reproductive toxicity.

Introduction

Various classes of environmental phenols including parabens, triclosan (2,4,4′-trichloro-2′-hydroxydiphenyl ether; TCS), and the (non-phenolic) carbanilide triclocarban (1-(4-chlorophenyl)-3-(3,4-dichlorophenyl)urea; TCC), have the propensity to cause hormonal disturbances in both in utero and ex utero development. Exposure to these compounds occurs primarily through use of cosmetics and antimicrobial consumer products in adults and, in neonates, ingestion of breast milk containing chemical residues. Numerous studies have been conducted that examined the presence of parabens [1], TCC [2] and TCS [3] in human blood at significant levels following the use of personal care products containing these compounds. Estrogenic effects from exposure to phenols have been documented [4], including decreases in body length [5] and effects on birth weight [6] in humans, and disruptions in the reproductive endocrine system in relevant animal models, as well as early onset of puberty in sheep [7]. In vitro assays have allowed for the identification of antagonistic activity of androgen receptors for compounds such as TCC [8]. These data provide sufficient grounds to investigate occurrence of adverse reproductive effects on humans at typical levels of exposure.

Parabens are a class of chemicals used in cosmetics and foodstuffs as preservatives and known to affect the endocrine system. Similar to other phenols, parabens and butyl paraben (BuPB) in particular have been found to exhibit estrogenic properties [9] in both human and murine studies, directly binding to estrogen receptors, albeit at an efficacy 10,000 weaker than 17β-estradiol and to a lower biological effect than phenols [10], [12]. These compounds have been found to exhibit antiandrogenic properties in vitro with an androgen receptor-mediated transcriptional activity assay [20]. Parabens have also been found to promote murine adipocyte differentiation in in vitro assays, which may explain the increased birth weight associated with their presence in human maternal urine samples [11]. Paraben exposure has been linked to the disruption of uterine blastocyst implantation in mice [12], and decreases in sperm count as a result of maternal exposure to butylparaben in the diet of rats [13], lending evidence to the reproductive toxic potential of parabens.

The antibacterial agents TCS and TCC, commonly used in numerous products from personal care to industrial cleaning, have also been shown to exhibit endocrine-disrupting potential. For example, in a recent cohort study, Philippat et al. [6] found an inverse correlation between increases in TCS levels in maternal urine and decreases in neonate head circumference (correlation coefficient = 0.5–0.6). Various studies have revealed several other associations, such as TCS exposure being associated with a reduction of thyroxine (T4) in female Long-Evans and Wistar rats [14], [15], the sensitization of body tissue toward allergens in humans [16], and the inhibition of muscle function in mice [17]. Structural similarities between TCS and thyroid hormones may serve to explain this action [14]. In a study looking at exposure and birth outcomes, TCS was inversely associated with body length and birth weight, but this result was only seen in young males [18]. TCC is more often found as an antimicrobial in soaps and its associated metabolites have been discovered at quantifiable amounts in urine samples after exposure from soap use during even a single shower [19]. TCC is also a strong inhibitor of epoxide hydrolase [2], an enzyme involved in the process of cholesterol synthesis [20]. In rats, TCC has an effect of increasing the size of male sex accessory organs [21], likely through synergism with the androgen hormone receptor ligand [22]. Liver tumor formation has been associated with TCS exposure of mice following oral dosing [23]. In this paper, we explored the extent of human fetal exposure to the above endocrine-disrupting preservatives and antimicrobials with particularly focus on associations with a range of potential adverse birth outcomes identified previously mostly in animal models.