Association of Phthalates, Parabens and Phenols Found in Personal Care Products With Pubertal Timing in Girls and Boys

Kim G. Harley; Kimberly P. Berger; Katherine Kogut; Kimberly Parra; Robert H. Lustig; Louise C. Greenspan; Antonia M. Calafat; Xiaoyun Ye; Brenda Eskenazi

Disclosures

Hum Reprod. 2019;34(1):109-117. 

In This Article

Abstract and Introduction

Abstract

Study Question: Are in-utero or peripubertal exposures to phthalates, parabens and other phenols found in personal care products associated with timing of pubertal onset in boys and girls?

Summary Answer: We found some associations of altered pubertal timing in girls, but little evidence in boys.

What is Known Already: Certain chemicals in personal care and consumer products, including low molecular weight phthalates, parabens and phenols, or their precursors, are associated with altered pubertal timing in animal studies.

Study Design, Size, Duration: Data were from the Center for the Health Assessment of Mothers and Children of Salinas (CHAMACOS) longitudinal cohort study which followed 338 children in the Salinas Valley, California, from before birth to adolescence.

Participants/Materials, Setting, Methods: Pregnant women were enrolled in 1999–2000. Mothers were mostly Latina, living below the federal poverty threshold and without a high school diploma. We measured concentrations of three phthalate metabolites (monoethyl phthalate [MEP], mono-n-butyl phthalate and mono-isobutyl phthalate), methyl and propyl paraben and four other phenols (triclosan, benzophenone-3 and 2,4- and 2,5-dichlorophenol) in urine collected from mothers during pregnancy and from children at age 9. Pubertal timing was assessed among 179 girls and 159 boys every 9 months between ages 9 and 13 using clinical Tanner staging. Accelerated failure time models were used to obtain mean shifts of pubertal timing associated with concentrations of prenatal and peripubertal biomarkers.

Main Results and the Role of Chance: In girls, we observed earlier onset of pubic hair development with prenatal urinary MEP concentrations and earlier menarche with prenatal triclosan and 2,4-dichlorophenol concentrations. Regarding peripubertal biomarkers, we observed: earlier breast development, pubic hair development and menarche with methyl paraben; earlier menarche with propyl paraben; and later pubic hair development with 2,5-dichlorophenol. In boys, we observed no associations with prenatal urinary biomarker concentrations and only one association with peripubertal concentrations: earlier genital development with propyl paraben.

Limitations, Reasons for Caution: These chemicals are quickly metabolized and one to two urinary measurements per developmental point may not accurately reflect usual exposure. Associations of peripubertal measurements with parabens may reflect reverse causality: children going through puberty early may be more likely to use personal care products. The study population was limited to Latino children of low socioeconomic status living in a farmworker community and may not be widely generalizable.

Wider Implications of the Findings: This study contributes to a growing literature that suggests that exposure to certain endocrine disrupting chemicals may impact timing of puberty in children.

Study Funding/Competing Interest(s): This study was funded by the National Institute of Environmental Health Sciences and the US Environmental Protection Agency. The authors declare no conflicts of interest.

Introduction

Over recent decades, girls and possibly boys have experienced pubertal onset at progressively younger ages (Euling et al., 2008). Earlier age at puberty is associated with increased risk of mental health problems and risk-taking behaviors (Flannery et al., 1993; Graber et al., 2004) as well as increased risk of breast and ovarian cancer in girls (Kelsey et al., 1993; Riman et al., 1998) and testicular cancer in boys (Forman et al., 1994). Although many factors have been promulgated to explain this phenomenon, one possible explanation is exposure to endocrine disrupting compounds in the environment (Buck Louis et al., 2008).

Several chemicals that are commonly used in cosmetics, personal care products and other scented household items have been shown to exhibit endocrine disrupting properties (Witorsch and Thomas, 2010). These chemicals include certain low molecular weight phthalates, such as diethyl phthalate (DEP), which is found in scented products such as perfumes, deodorants, soaps and shampoo, and di-n-butyl phthalate (DnBP) and di-isobutyl phthalate (DiBP), which can be used in nail polish and cosmetics (Dodson et al., 2012). In animal studies, developmental exposure to DnBP and DiBP induces anti-androgenic effects including feminized traits, abnormal reproductive development and later puberty in male rats, although the effects are less strong in females (Mylchreest et al., 2000; Saillenfait et al., 2008).

Parabens, including methyl and propyl paraben, are commonly used as preservatives in cosmetics (Guo and Kannan, 2013) and demonstrate weak estrogenic properties (Boberg et al., 2010), which induce changes in pubertal timing in female rats (Vo et al., 2010). Environmental phenols used in personal care products include triclosan, an antibacterial agent that can be used in hand soap and some toothpaste (Dann and Hontela, 2011), and benzophenone-3, a sunscreen agent that is also added to cosmetics such as lipsticks, hairsprays, shampoos and skin lotions to increase the products' durability (Han et al., 2016). In animal studies, triclosan has been found to have estrogenic potency (Stoker et al., 2010) which can disrupt LH, FSH and testosterone secretion (Kumar et al., 2008), and can alter pubertal timing in female rats (Rodriguez and Sanchez, 2010; Stoker et al., 2010). Research on benzophenone-3 is more limited, but it has exhibited weak estrogenic properties in vitro and in animal studies (Schlumpf et al., 2001). Other environmental phenols include 2,4-dichlorophenol, a photo-degradation product of triclosan (Canosa et al., 2005), which is also an intermediate in the manufacturing of the herbicide 2,4-dichlorophenoxyacetic acid, and 2,5-dichlorophenol, a metabolite of 1,4-dichlorobenzene, which is used in moth balls and room and toilet deodorizers (Ye et al., 2014).

Exposure to these phthalates, parabens, and phenols is widespread. In the United States, >96% of women participating in the nationally representative National Health and Nutrition Examination Survey (NHANES) had detectable concentrations of DEP, DnBP or DiBP metabolites in their urine (Zota et al., 2014). Methyl and propyl parabens were found in >90% of individuals (Calafat et al., 2010), triclosan in 75% (Calafat et al., 2008b), benzophenone-3 in 97% (Calafat et al., 2008a), and 2,4-dichlorophenol and 2,5-dichlorophenol in >80% (Ye et al., 2014) of women.

To date, very few human studies have examined associations of these phthalates, parabens and phenols with timing of puberty. The prenatal and peripubertal periods are critical windows in reproductive development that may be particularly sensitive to endocrine disruption. Only one study, the ELEMENT Study in Mexico City, has examined prenatal exposures in relation to pubertal timing in girls (Watkins et al., 2017b) and boys (Watkins et al., 2017a). A small number of studies have examined peripubertal exposures to these compounds, mainly in girls, but the results have been inconsistent (Mouritsen et al., 2010, Buttke et al., 2012; Frederiksen et al., 2012; Wolff et al., 2014, 2015; Binder et al., 2018).

In the present study, we examined urinary biomarker concentrations of several phthalates, parabens and other chemicals used in personal care and consumer products in relation to age at pubertal onset, as assessed by clinical Tanner staging in girls and boys. We examined biomarkers from mothers during pregnancy and from their children at age 9 years.

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