Abstract
BackgroundPolychlorinated biphenyls (PCBs) remain ubiquitous environmental contaminants. Developmental exposures are suspected to impact reproduction. Analysis of mixtures of PCBs may be problematic as components have a complex correlation structure, and along with limited sample sizes, standard regression strategies are problematic. We compared the results of a novel, empirical method to those based on categorization of PCB compounds by (1) hypothesized biological activity previously proposed and widely applied, and (2) degree of ortho- substitution (mono, di, tri), in a study of the relation of maternal serum PCBs and daughter’s time to pregnancy.MethodsWe measured PCBs in maternal serum samples collected in the early postpartum in 289 daughters in the Child Health and Development Studies birth cohort. We queried time to pregnancy in these daughters 28–31 years later. We applied a novel weighted quantile sum approach to find the bad-actor compounds in the PCB mixture found in maternal serum. The approach includes empirical estimation of the weights through a bootstrap step which accounts for the variation in the estimated weights.ResultsBootstrap analyses indicated the dominant functionality groups associated with longer TTP were the dioxin-like, anti-estrogenic group (average weight, 22%) and PCBs not previously classified by biological activity (54%). In contrast, the unclassified PCBs were not important in the association with shorter TTP, where the anti-estrogenic groups and the PB-inducers group played a more important role (60% and 23%, respectively). The highly chlorinated PCBs (average weight, 89%) were mostly associated with longer TTP; in contrast, the degree of chlorination was less discriminating for shorter TTP. Finally, PCB 56 was associated with the strongest relationship with TTP with a weight of 47%.ConclusionsOur empirical approach found some associations previously identified by two classification schemes, but also identified other bad actors. This empirical method can generate hypotheses about mixture effects and mechanisms and overcomes some of the limitations of standard regression techniques.
Highlights
Polychlorinated biphenyls (PCBs) remain ubiquitous environmental contaminants
Using a weighted quartile score approach within a parametric proportional hazards model, empirical estimates of weights per PCB congener were estimated in a weighted quartile score that was positively associated with the hazard of pregnancy and a score that was negatively associated with the hazard of pregnancy
Using a bootstrap analysis to accommodate the variation in the estimated weights, the dominant functionality groups associated with longer time to pregnancy (TTP) were the dioxin-like, anti-estrogenic group and the ‘uncategorized’ group (PCBs not characterized by Wolff et al.; 54%)
Summary
Polychlorinated biphenyls (PCBs) remain ubiquitous environmental contaminants. Developmental exposures are suspected to impact reproduction. We compared the results of a novel, empirical method to those based on categorization of PCB compounds by (1) hypothesized biological activity previously proposed and widely applied, and (2) degree of ortho- substitution (mono, di, tri), in a study of the relation of maternal serum PCBs and daughter’s time to pregnancy Despite their ban in the 1970s, polychlorinated biphenyls (PCBs) remain ubiquitous environmental contaminants due to their chemical stability and lipophilic properties [1]. Cohn et al [4] tested the hypothesis that in utero exposure to PCBs alters TTP in humans using data from the Child Health Development Studies (CHDS) Their data included measures of maternal exposures in blood samples collected near delivery (days 1–3 after daughter’s birth during 1960–63) in relation to her daughter’s TTP decades later. Their analysis was based on a previous categorization of PCB congeners by Wolff et al [9] based on functionality and inclusion in CHDS maternal serum samples: Group 1: potentially estrogenic and persistent: PCB 101, 187, 201; Group 2: potentially anti-estrogenic, immunotoxic, dioxin-like o Group 2A: non-ortho or mono-ortho in structure: PCB 66, 74, 105, 118, 156, 167 o Group 2B: di-ortho and limited dioxin-like activity: PCB 138, 170
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