Assessing Chemical Mixtures and Human Health: Use of Bayesian Belief Net Analysis

Abstract

Background: Despite humans being exposed to complex chemical mixtures, much of the available research continues to focus on a single compound or metabolite or a select subgroup of compounds inconsistent with the nature of human exposure. Uncertainty regarding how best to model chemical mixtures coupled with few analytic approaches remains a formidable challenge and served as the impetus for the study. Objectives: To identify the polychlorinated biphenyl (PCB) congener(s) within a chemical mixture that was most associated with an endometriosis diagnosis using novel graphical modeling techniques. Methods: Bayesian Belief Network (BBN) models were developed and empirically assessed in a cohort comprising 84 women aged 18 - 40 years who underwent a laparoscopy or laparotomy between 1999 and 2000; 79 (94%) women had serum concentrations for 68 PCB congeners quantified. Adjusted odds ratios (AOR) for endometriosis were estimated for individual PCB congeners using BBN models. Results: PCB congeners #114 (AOR = 3.01; 95% CI = 2.25, 3.77) and #136 (AOR = 1.79; 95% CI = 1.03, 2.55) were associated with an endometriosis diagnosis. Combinations of mixtures inclusive of PCB #114 were all associated with higher odds of endometriosis, underscoring its potential relation with endometriosis. Conclusions: BBN models identified PCB congener 114 as the most influential congener for the odds of an endometriosis diagnosis in the context of a 68 congener chemical mixture. BBN models offer investigators the opportunity to assess which compounds within a mixture may drive a human health effect.