In Vitro Toxicity Profiling of Ultrapure Non–Dioxin-like Polychlorinated Biphenyl Congeners and Their Relative Toxic Contribution to PCB Mixtures in Humans
Timo HamersJorke H. KamstraPeter CenijnKateřina PěnčíkováLenka PálkováPavlína ŠimečkováJan VondráčekPatrik L. AnderssonMia StenbergMiroslav Machala
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Abstract:
The toxic equivalency concept used for the risk assessment of polychlorinated biphenyls (PCBs) is based on the aryl hydrocarbon receptor (AhR)–mediated toxicity of coplanar dioxin-like (DL) PCBs. Most PCBs in the environment, however, are non-dioxin-like (NDL) PCBs that cannot adopt a coplanar structure required for AhR activation. For NDL-PCBs, no generally accepted risk concept is available because their toxicity is insufficiently characterized. Here, we systematically determined in vitro toxicity profiles for 24 PCBs regarding 10 different mechanisms of action. Prior to testing, NDL-PCB standards were purified to remove traces of DL compounds. All NDL-PCBs antagonized androgen receptor activation and inhibited gap junctional intercellular communication (GJIC). Lower chlorinated NDL-PCBs were weak estrogen receptor (ER) agonists, whereas higher chlorinated NDL-PCBs were weak ER antagonists. Several NDL-PCBs inhibited estradiol-sulfotransferase activity and bound to transthyretin (TTR) but with much weaker potencies than reported for hydroxylated PCB metabolites. AhR-mediated expression of uridine-glucuronyl transferase isozyme UGT1A6 was induced by DL-PCBs only. Hierarchical cluster analysis of the toxicity profiles yielded three separate clusters of NDL-PCBs and a fourth cluster of reference DL-PCBs. Due to small differences in relative potency among congeners, the highly abundant indicator PCBs 28, 52, 101, 118, 138, 153, and 180 also contributed most to the antiandrogenic, (anti)estrogenic, antithyroidal, tumor-promoting, and neurotoxic potencies calculated for PCB mixtures reported in human samples, whereas the most potent AhR-activating DL-PCB-126 contributed at maximum 0.2% to any of these calculated potencies. PCB-168 is recommended as an additional indicator congener, given its relatively high abundance and antiandrogenic, TTR-binding, and GJIC-inhibiting potencies.Keywords:
Polychlorinated biphenyl
Congener
Polychlorinated biphenyl
Biphenyl
Polychlorinated dibenzofurans
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A case study is presented of two sites considered to be potential polychlorinated biphenyl (PCB) sources to a waterway that were sampled with site source and waterway sediment samples analyzed for PCB congeners using Method 1668A. Site 1 historical activities included storage and burning of spent PCB-containing transformer fluids. Site 2 contained paved areas that historically used PCB-containing concrete joint material. Several approaches to congener profile comparisons were used to compare the potential source samples presented in this work with sediment samples collected from three cores in the waterway. In addition to qualitative (visual) comparisons, other methods included principal component analysis, the coefficient of determination R2 metric, the cosine theta metric, and homologue double ratio analysis. Collectively, these methods were able to quantitatively determine the degree of similarity between the potential sources and the samples from the three waterway cores and identify the predominant source of contamination.
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Biphenyl
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Polychlorinated biphenyl
Biphenyl
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Abstract The feasibility of using specific PCB congeners was studied in two parts: a questionnaire to obtain information on the methodology used in various countries for quantification of PCBs and an international check sample program to evaluate the accuracy of the specific PCB congener approach. Information from the questionnaires indicated the use of a wide variety of PCB quantification procedures and considerable interest in using specific PCB congeners. In the check sample program, participants were requested to analyze two mixtures of Aroclor 1242 and 1254 in different proportions, and a human milk extract. The results indicated that when individual congeners were present at less than approximately 5 pg/μl per injection, the coefficients of variation for reproducibility were unsatisfactory for many congeners, some of which could not be detected by the participants. Interlaboratory coefficients of variation were generally acceptable (<20%) for many congeners at concentrations >5 pg/μl with the exception of congener No. 28, which is known to co-elute with PCB congener No. 31 and thus affect its estimation.
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Polychlorinated biphenyl
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The polychlorinated biphenyl (PCB) residues in the aquatic sediments from six PCB spill sites showed changes in PCB isomer and homolog (congener) distribution that indicated the occurrence of reductive dechlorination. The PCB dechlorinations exhibited several distinct congener selection patterns that indicated mediation by several different localized populations of anaerobic microorganisms. The higher (more heavily chlorinated) PCB congeners that were preferentially attacked by the observed dechlorination processes included all those that are either pharmacologically active or persistent in higher animals. All the lower (less heavily chlorinated) PCB congeners formed by the dechlorinations were species that are known to be oxidatively biodegradable by the bacteria of aerobic environments.
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Abstract Abstract—The dechlorination potential of polychlorinated biphenyl (PCB)‐contaminated sediments from the St. Lawrence River was investigated in laboratory incubations over a 39‐month period. During the first 4 months, dechlorination reduced the average total chlorines in the General Motors 001 sediments from 3.2 to 2.5 per biphenyl, an additional 22% beyond the in situ level, for an overall 36% reduction from the original Aroclor 1248 contaminant. With continued incubation, however, an additional dechlorination of a single peak 2,4′,5+2,4,4′‐chlorobiphenyl ensued after a lag that reduced the average chlorines from 2.5 to 2.4. After this, there was no further transformation until the end of incubation. The extent of dechlorination and congener pattern of Aroclor 1248‐spiked sediments were similar to those of the native sediments after a comparable period of time despite differences in sediment sources and starting congener composition. The results indicate that most dechlorination occurs during a relatively short period of the initial rapid phase and any further transformation, if it occurs, would be extremely slow, and its contribution to the total dechlorination may not be significant.
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