Associations between urinary phenol and paraben concentrations and markers of oxidative stress and inflammation among pregnant women in Puerto Rico

Abstract

Phenols and parabens are used in a multitude of consumer products resulting in ubiquitous human exposure. Animal and in vitro studies suggest that exposure to these compounds may be related to a number of adverse health outcomes, as well as potential mediators such as oxidative stress and inflammation. We examined urinary phenol (bisphenol A (BPA), triclosan (TCS), benzophenone-3 (BP-3), 2,4-dichlorophenol (24-DCP), 2,5-dichlorophenol (25-DCP)) and paraben (butyl paraben (B-PB), methyl paraben (M-PB), propyl paraben (P-PB)) concentrations measured three times during pregnancy in relation to markers of oxidative stress and inflammation among participants in the Puerto Rico Testsite for Exploring Contamination Threats (PROTECT) project. Serum markers of inflammation (c-reactive protein (CRP), IL-1β, IL-6, IL-10, and tumor necrosis factor-α (TNF-α)) were measured twice during pregnancy (n=105 subjects, 187 measurements) and urinary markers of oxidative stress (8-hydroxydeoxyguanosine (OHdG) and isoprostane) were measured three times during pregnancy (n=54 subjects, 146 measurements). We used linear mixed models to assess relationships between natural log-transformed exposure and outcome biomarkers while accounting for within individual correlation across study visits. After adjustment for urinary specific gravity, study visit, maternal pre-pregnancy BMI, and maternal education, an interquartile range (IQR) increase in urinary BPA was associated with 21% higher OHdG (p=0.001) and 29% higher isoprostane (p=0.0002), indicating increased oxidative stress. The adjusted increase in isoprostane per IQR increase in marker of exposure was 17% for BP-3, 27% for B-PB, and 20% for P-PB (all p<0.05). An IQR increase in triclosan (TCS) was associated with 31% higher serum concentrations of IL-6 (p=0.007), a pro-inflammatory cytokine. In contrast, IQR increases in BP-3 and B-PB were significantly associated with 16% and 18% lower CRP, a measure of systemic inflammation. Our findings suggest that exposure to BPA, select parabens, and TCS during pregnancy may be related to oxidative stress and inflammation, potential mechanisms by which exposure to these compounds may influence birth outcomes and other adverse health effects, but additional research is needed.

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.…”

“…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…”

“…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.…”

“…The remaining five publications were assigned to Tier 1. Two of those (Watkins et al 2015;Aker et al 2016) were longitudinal cohort studies that included three samples obtained at different times and examined associations with health outcomes, taking all three TCS measures into consideration. Allmyr et al (2009) conducted an experimental study comparing health biomarker levels before and after intentional TCS administration and observed significantly higher plasma TCS levels following the 14-day study intervention (0.009-0.81 ng/g and 26-296 ng/g: ranges before and after exposure, respectively).…”

“…This group included 11 different publications (many already discussed in the previous sections). Four of these publications were clinical trials (Allmyr et al 2009;Cullinan et al 2015a, 2015b, Poole et al 2016, two were cohort studies (Watkins et al 2015;Ashley-Martin et al 2016) and the remaining five studies were cross sectional (all NHANES-based). Only two of the studies examined a similar endpoint.…”