Environmental phenols and pubertal development in girls

Abstract

Environmental exposures to many phenols are documented worldwide and exposures can be quite high (>1 micromolar of urine metabolites). Phenols have a range of hormonal activity, but knowledge of effects on child reproductive development is limited, coming mostly from cross-sectional studies. We undertook a prospective study of pubertal development among 1239 girls recruited at three U.S. sites when they were 6–8 years old and were followed annually for 7 years to determine age at first breast or pubic hair development. Ten phenols were measured in urine collected at enrollment (benzophenone-3, enterolactone, bisphenol A, three parabens (methyl-, ethyl-, propyl-), 2,5-dichlorophenol, triclosan, genistein, daidzein). We used multivariable adjusted Cox proportional hazards ratios (HR (95% confidence intervals)) and Kaplan-Meier survival analyses to estimate relative risk of earlier or later age at puberty associated with phenol exposures. For enterolactone and benzophenone-3, girls experienced breast development 5–6 months later, adjusted HR 0.79 (0.64–0.98) and HR 0.80 (0.65–0.98) respectively for the 5th vs 1st quintiles of urinary biomarkers (μg/g-creatinine). Earlier breast development was seen for triclosan and 2,5- dichlorophenol: 4–9 months sooner for 5th vs 1st quintiles of urinary concentrations (HR 1.17 (0.96–1.43) and HR 1.37 (1.09–1.72), respectively). Association of breast development with enterolactone, but not the other three phenols, was mediated by body size. These phenols may be antiadipogens (benzophenone-3 and enterolactone) or thyroid agonists (triclosan and 2,5- dichlorophenol), and their ubiquity and relatively high levels in children would benefit from further investigation to confirm these findings and to establish whether there are certain windows of susceptibility during which exposure can affect pubertal development.

Systematic review of the literature on triclosan and health outcomes in humans

“…Tier 2 included 13 publications. Twelve of those publications (Wolff et al , 2010(Wolff et al , 2015Philippat et al 2012Philippat et al , 2014Watkins et al 2015;Aker et al 2016;Ashley-Martin et al 2016;Buckley et al 2016;Lassen et al 2016;Smarr et al 2017;Geer et al 2017) were based on seven different cohorts assembled in France, Puerto Rico, Denmark, Canada, and various parts of the US. One paper ) presented a case-control study that used incident cases identified among members of a French cohort.…”

“…Similarly, three Australian papers (Cullinan et al 2012(Cullinan et al , 2015a(Cullinan et al , 2015b were based on the same study, as were two publications from Puerto Rico (Watkins et al 2015;Aker et al 2016), and three papers by Wolff et al (2008Wolff et al ( , 2010Wolff et al ( , 2015.…”

“…Of the 43 studies, 24 were conducted in North America (Wolff et al , 2010(Wolff et al , 2015Clayton et al 2011;You et al 2011;Buttke et al 2012;Savage et al 2012Savage et al , 2014Koeppe et al 2013;Lankester et al 2013;Buser et al 2014;Spanier et al 2014;Adgent and Rogan 2015;Li et al 2015;Ihde et al 2015;Shiue 2015aShiue , 2015bVelez et al 2015;Ashley-Martin et al 2016;Buckley et al 2016;Poole et al 2016;Scinicariello and Buser 2016;Smarr et al 2017;Geer et al 2017), two studies in the Caribbean (Watkins et al 2015;Aker et al 2016), 10 studies in Europe (Allmyr et al 2009;Chevrier et al 2012;Philippat et al 2012Philippat et al , 2014Bertelsen et al 2013;Buhl et al 2014;Den Hond et al 2013, 2015Geens et al 2015;Lassen et al 2016), four in Asia (Chen et al 2013;Wang et al 2015;Xue et al 2015;Zhu et al 2016), and three in Australia (Cullinan et al 2012(Cullinan et al , 2015a…”

“…Two of those studies were based on the same Breast Cancer and Environment Research Program (BCERP) cohort (Wolff et al 2010(Wolff et al , 2015 and the third study (Buttke et al 2012) The participants in the BCERP cohort study were enrolled at the age of 6-8 years and were followed for up to seven years. TCS was measured at baseline in a single urine sample collected at enrollment.…”

“…Another cohort study (Wolff et al 2015) followed 1170 girls (ages 6-8 years) with annual examinations over a period of up to seven years. TCS was measured at baseline in a single urine sample collected at enrollment.…”