Peripubertal serum levels of dioxins, furans and PCBs in a cohort of Russian boys: can empirical grouping methods yield meaningful exposure variables?

Abstract

Background: Dioxins, furans and polychlorinated biphenyls (PCBs) are endocrine disruptors with half-lives of months to years in humans. Peripubertal exposure to these chemicals may disrupt pubertal timing. Biomarker exposure metrics like the sum of non-dioxin-like PCBs in serum (∑NDL-PCBs) involve chemicals with different hypothetical effects. Empirical exposure metrics represent an alternative that requires no knowledge of biological mechanisms.

Methods: From 2003 to 2005, 516 Russian boys aged 8-9 residing near a plant that historically produced organochlorine pesticides were enrolled in the Russian Children's Study. At enrollment, blood was collected for measurement of organochlorine chemicals by the Centers for Disease Control and Prevention (CDC). Variable cluster analysis was used to empirically group serum levels of 45 dioxins, furans and PCBs into eight cluster scores. These scores were compared to the sum of dioxin-like toxic equivalents (∑TEQs) and ∑NDL-PCBs using Spearman correlation coefficients.

Results: Clustering appeared to reflect number and position of chlorine atoms. Clusters 4, 7 and 1 contained, respectively, tri/tetra-, tetra/penta-, and hexa/hepta-chlorinated PCBs with chlorines at the 4,4' positions. Clusters 2, 8 and 5 contained, respectively, tetra-to hexa-, hexa/hepta-, and hepta/octa-chlorinated PCBs with chlorines at the 2,2' positions. ∑NDL-PCBs were highly correlated with 4,4'-chlorinated clusters 1 and 7 (Spearman's ρ = 0.8) and less so with all other clusters (Spearman's ρ = 0.4-0.5).

Conclusions: In this cohort of Russian boys, baseline serum dioxins, furans and PCBs seemed to cluster by chlorination pattern, possibly reflecting shared persistence, metabolism or source of exposure. The widely used measure ∑NDL-PCB seemed most representative of 4,4'-chlorinated PCBs.

Keywords: Cluster analysis; Dioxins; Endocrine disruptors; Polychlorinated biphenyls; Principal component analysis; Puberty.

Figure 1.

Variable clustering^a and principal component analysis loadings^b of congeners in serum of 498 boys from Russian Children’s Study at enrollment, 2003–2005^{c a} The selected cluster solution, consisting of 8 clusters, explained 67% of the variance in the data. The X axis indicates the proportion of total variance that is attributable to a particular clustering solution (e.g., a two-cluster solution, a three-cluster solution, etc). ^bPrincipal components 1–7 together explained 71% of the variance in the data. ^cAbbreviations: PCDDs: Polychlorinated dibenzodioxins; PCDFs: polychlorinated dibenzofurans; PCBs: polychlorinated biphenyls; NDL-PCBs: non-dioxin-like PCBs; TEQs: toxic equivalents, based on 2005 toxic equivalent factors (TEFs); Tri-, Tetra-, Penta-, Hexa-, Hepta- and Octa- refer to number of chlorine atoms of a particular congener.

Figure 2.

Spearman correlations^a between cluster scores, principal component scores, and summary measures of congeners in serum of 498 boys from Russian Children’s Study at enrollment, 2003–2005^{b a}Area I contains correlations among the cluster scores; Area II contains correlations among the principal component scores; and cluster scores; and Area V contains correlations between PC/cluster scores and ∑PCBs/∑TEQs. ^b Abbreviations: PCDDs: Polychlorinated dibenzodioxins; PCDFs: polychlorinated dibenzofurans; PCBs: polychlorinated biphenyls; NDL-PCBs: non-dioxin-like PCBs; TEQs: toxic equivalents, based on 2005 toxic equivalent factors (TEFs); Tri-, Tetra-, Penta-, Hexa-, Hepta- and Octa- refer to number of chlorine atoms of a particular congener.

Figure 3.

Selected Spearman correlations among clusters of congeners in serum of 498 boys from Russian Children’s Study at enrollment, 2003–2005 Numbers denote Spearman correlation coefficients. Where Spearman correlations between clusters were <0.5, the correlation coefficients and connecting lines were omitted. Abbreviations: PCDDs: Polychlorinated dibenzodioxins; PCDFs: polychlorinated dibenzofurans; PCBs: polychlorinated biphenyls; NDL-PCBs: non-dioxin-like PCBs; Tri-, Tetra-, Penta-, Hexa-, Hepta- and Octa- refer to number of chlorine atoms of a particular congener.