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Objective: In this study we reviewed the half-life data in the literature for the 29 dioxin, furan, and polychlorinated biphenyl congeners named in the World Health Organization toxic equivalency factor scheme, with the aim of providing a reference value for the half-life of each congener in the human body and a method of half-life estimation that accounts for an individual's personal characteristics. Data Sources and extraction: We compared data from > 30 studies containing congener-specific elimination rates. Half-life data were extracted and compiled into a summary table. We then created a subset of these data based on defined exclusionary criteria. Data synthesis: We defined values for each congener that approximate the half-life in an infant and in an adult. A linear interpolation of these values was used to examine the relationship between half-life and age, percent body fat, and absolute body fat. We developed predictive equations based on these relationships and adjustments for individual characteristics. Conclusions: The half-life of dioxins in the body can be predicted using a linear relationship with age adjusted for body fat, smoking, and breast-feeding. Data suggest an alternative method based on a linear relationship between half-life and total body fat, but this approach requires further testing and validation with individual measurements.

Background: Polychlorinated biphenyls (PCBs) manufactured in Anniston, Alabama, from 1929 to 1971 caused significant environmental contamination. The Anniston population remains one of the most highly exposed in the world. Objectives: Reports of increased diabetes in PCB-exposed populations led us to examine possible associations in Anniston residents. Methods: Volunteers (n = 774) from a cross-sectional study of randomly selected households and adults who completed the Anniston Community Health Survey also underwent measurements of height, weight, fasting glucose, lipid, and PCB congener levels and verification of medications. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to assess the relationships between PCBs and diabetes, adjusting for diabetes risk factors. Participants with prediabetes were excluded from the logistic regression analyses. Results: Participants were 47% African American, 70% female, with a mean age of 54.8 years. The prevalence of diabetes was 27% in the study population, corresponding to an estimated prevalence of 16% for Anniston overall; the PCB body burden of 35 major congeners ranged from 0.11 to 170.42 ppb, wet weight. The adjusted OR comparing the prevalence of diabetes in the fifth versus first quintile of serum PCB was 2.78 (95% CI: 1.00, 7.73), with similar associations estimated for second through fourth quintiles. In participants < 55 years of age, the adjusted OR for diabetes for die highest versus lowest quintile was 4.78 (95% CI: 1.11, 20.6), whereas in those < 55 years of age, we observed no significant associations with PCBs. Elevated diabetes prevalence was observed with a 1 SD increase in log PCB levels in women (OR = 1.52; 95% CI: 1.01, 2.28); a decreased prevalence was observed in men (OR = 0.68; 95% CI: 0.33,1.41). Conclusions: We observed significant associations between elevated PCB levels and diabetes mostly due to associations in women and in individuals < 55 years of age.

Seventy eight out of the 209 possible polychlorinated biphenyl (PCB) congeners are chiral, 19 of which exist under ambient conditions as stable rotational isomers that are non-superimposable mirror images of each other. These congeners (C-PCBs) represent up to 6 % by weight of technical PCB mixtures and undergo considerable atropisomeric enrichment in wildlife, laboratory animals, and humans. The objective of this review is to summarize our current knowledge of the processes involved in the absorption, metabolism, and excretion of C-PCBs and their metabolites in laboratory animals and humans. C-PCBs are absorbed and excreted by passive diffusion, a process that, like other physicochemical processes, is inherently not atropselective. In mammals, metabolism by cytochrome P450 (P450) enzymes represents a major route of elimination for many C-PCBs. In vitro studies demonstrate that C-PCBs with a 2,3,6-trichlorosubstitution pattern in one phenyl ring are readily oxidized to hydroxylated PCB metabolites (HO-PCBs) by P450 enzymes, such as rat CYP2B1, human CYP2B6, and dog CYP2B11. The oxidation of C-PCBs is atropselective, thus resulting in a species- and congener-dependent atropisomeric enrichment of C-PCBs and their metabolites. This atropisomeric enrichment of C-PCBs and their metabolites likely plays a poorly understood role in the atropselective toxicity of C-PCBs and, therefore, warrants further investigation.

Epidemiologic studies of postnatal PCB exposure and behavior have not reported consistent evidence of adverse associations, possibly because of challenges in exposure estimation. We previously developed a pharmacokinetic model to improve estimation of children's PCB exposure. We aimed to assess whether estimated serum PCB levels in infancy are associated with attention deficit/hyperactivity disorder (ADHD)-related behaviors at 8 years of age among children whose cord serum PCB levels were previously shown to be associated with ADHD-related behaviors. We used a pharmacokinetic model to estimate monthly serum polychlorinated biphenyl (PCB)-153 levels in 441 infants (ages 1-12 months) based on parameters such as breastfeeding and cord serum PCB-153 levels. Behavior was evaluated at age 8 using the Conners' Rating Scale for Teachers (CRS-T). Associations between PCB-153 levels and ADHD-related CRS-T indices were assessed using multivariable quantile regression at the 50th and 75th percentiles of CRS-T scores, where higher percentiles reflect more adverse behaviors. Cord serum PCB-153 levels (median, 38 ng/g lipids) were associated with ADHD-related behaviors, although statistical significance was observed with quantile regression models only at the 75th percentile. Associations with postnatal exposure estimates were attenuated. For example, hyperactive-impulsive behavior scores at age 8 years were 0.9 points (95% CI: 0.2, 2.5), 0.5 points (95% CI: 0.3, 2.3), and 0.3 points (95% CI: -0.2, 1.5) higher in association with interquartile range increases in serum PCB-153 at birth, 2 months, and 12 months of age, respectively. Associations between estimated postnatal PCB-153 exposures and ADHD-related behaviors at 8 years of age were weaker than associations with PCB-153 concentrations measured in cord serum at birth. Verner MA, Hart JE, Sagiv SK, Bellinger DC, Altshul LM, Korrick SA. 2015. Measured prenatal and estimated postnatal levels of polychlorinated biphenyls (PCBs) and ADHD-related behaviors in 8-year-old children. Environ Health Perspect 123:888-894; http://dx.doi.org/10.1289/ehp.1408084.

Nineteen polychlorinated biphenyls (chiral or C-PCBs) exist as two stable rotational isomers (atropisomers) that are non-superimposable mirror images of each other. C-PCBs are released into the environment as racemic (i.e., equal) mixtures of both atropisomers and undergo atropisomeric enrichment due to biological, but not abiotic, processes. In particular, toxicokinetic studies provide important initial insights into atropselective processes involved in the disposition (i.e., absorption, distribution, biotransformation, and excretion) of C-PCBs. The toxicokinetic of C-PCBs is highly congener and species dependent. In particular, at lower trophic levels, abiotic processes play a predominant role in C-PCB toxicokinetics. Biotransformation plays an important role in the elimination of C-PCBs in mammals. The elimination of C-PCB follows the approximate order mammals > birds > amphibians > fish, mostly due to a corresponding decrease in metabolic capacity. A few studies have shown differences in the toxicokinetics of C-PCB atropisomers; however, more work is needed to understand the toxicokinetics of C-PCBs and the underlying biological processes. Such studies will not only contribute to our understanding of the fate of C-PCBs in aquatic and terrestrial food webs but also facilitate our understanding of human exposures to C-PCBs.

Migration of neural crest cells (NCC) is a fundamental developmental process, and test methods to identify interfering toxicants have been developed. By examining cell function endpoints, as in the ‘migration-inhibition of NCC (cMINC)’ assay, a large number of toxicity mechanisms and protein targets can be covered. However, the key events that lead to the adverse effects of a given chemical or group of related compounds are hard to elucidate. To address this issue, we explored here, whether the establishment of two overlapping structure–activity relationships (SAR)—linking chemical structure on the one hand to a phenotypic test outcome, and on the other hand to a mechanistic endpoint—was useful as strategy to identify relevant toxicity mechanisms. For this purpose, we chose polychlorinated biphenyls (PCB) as a large group of related, but still toxicologically and physicochemically diverse structures. We obtained concentration-dependent data for 26 PCBs in the cMINC assay. Moreover, the test chemicals were evaluated by a new high-content imaging method for their effect on cellular re-distribution of connexin43 and for their capacity to inhibit gap junctions. Non-planar PCBs inhibited NCC migration. The potency (1–10 µM) correlated with the number of ortho-chlorine substituents; non-ortho-chloro (planar) PCBs were non-toxic. The toxicity to NCC partially correlated with gap junction inhibition, while it fully correlated (p < 0.0004) with connexin43 cellular re-distribution. Thus, our double-SAR strategy revealed a mechanistic step tightly linked to NCC toxicity of PCBs. Connexin43 patterns in NCC may be explored as a new endpoint relevant to developmental toxicity screening.

Polychlorinated biphenyls (PCBs) have been classified as human carcinogens. Mutagenicity of lower chlorinated biphenyls as well as activation of transcription factors by some other congeners may contribute to the carcinogenicity of PCBs. Recently, we reported that human CYP2E1 activates mono- and dichlorobiphenyls to mutagens. However, mutagenicity of other PCBs and the involvement of other CYPs remained unknown. In this study, Chinese hamster V79-derived cell lines genetically engineered for expression of individual human CYP enzymes and a human hepatocyte (L-02) line endogenously expressing various CYPs were used to determine the activities of several tri- and tetrachlorobiphenyls to induce micronuclei and gene mutations. 2,3,4′-Trichlorobiphenyl, 2,3,3′-trichlorobiphenyl, 2,4,4′,5-tetrachlorobiphenyl and 2,2′,5,5′-tetrachlorobiphenyl efficiently induced micronuclei and/or gene mutations in V79-derived cells at low micromolar concentrations, depending on human CYP2E1, while they were inactive in parental V79-Mz cells and weakly positive or inactive in V79-derived cells expressing human CYP1A1, 1A2, 1B1 or 3A4. The induction of gene mutations in human CYP2E1-expressing V79 cells by 2,3,4′-trichlorobiphenyl and 2,4,4′,5-tetrachlorobiphenyl was more potent than that of N -nitrosodimethylamine, a strong carcinogen activated by CYP2E1. As representative PCB compounds, 2,3,3′-trichlorobiphenyl and 2,3,4′-trichlorobiphenyl induced micronuclei in L-02 cells, and this effect was blocked by specific CYP2E1 inhibition, wherein the effects of benzo[ a ]pyrene and aflatoxin B 1 (activated by some CYPs other than CYP2E1) were unaffected. This study demonstrates that some non-planar tri- and tetrachlorobiphenyls are potent mutagens in mammalian cells—more potent than previously tested mono- and dichlorobiphenyls—and that among several human CYP enzymes, CYP2E1 is most efficient in activating these environmental contaminants.

Copper sulfates (CuSO4) are widely used as the primary component of fungicides in the grape industry. The agricultural-grade CuSO4 that we collected from Chinese nationwide markets were found to be contaminated by polychlorinated dibenzo-p-dioxins and dibenzofurans and high levels of polychlorinated biphenyls (Σ19PCBs: 0.32~9.51 ng/g). In the following research, we studied the impact of CuSO4 application on PCB levels in grape products through a field experiment, and conducted a national survey to speculate the role that CuSO4 played on the occurrence of PCB in grapes. In the field experiment, an obvious increase of PCBs in grape leaves (from 174 to 250 pg/g fw) was observed after Bordeaux mixture (the main component of which is CuSO4) application. As to the main PCB congener in CuSO4, the most toxic CB 126 (toxic equivalency factor = 0.1) also increased in grape peels (from 1.66 to 2.93 pg/g fw) after pesticide spray. Both the correlation study and the principal component analysis indicated that environmental factors were dominant PCB contributors to grapes, and grapes from e-waste dismantling area containing the highest PCBs also proved the notion. It is worth noting that this report describes the first research examining PCBs in CuSO4 and its influence on agricultural products to date.

Polychlorinated biphenyls (PCBs), which cause environmental pollution, are found in animal-based fatty foods. Due to their long half-life and lipophilic properties, they can accumulate in the fat tissues of cattle. The study was conducted to compare the PCB levels (PCB28, 52, 101, 118, 138, 153, and 180) in the different fat tissues (muscle, liver, kidney, spinal cord, lung, back fat, perihepatic fat, and perirenal fat) of cattle by age and gender. This information is also useful to evaluate the exposure risks for different bovine edible tissues. Therefore, 15 female and 15 male cattle under 24 months of age and 15 female and 15 male cattle over 24 months of age were used, and 480 samples were analyzed for target PCBs using gas chromatography-mass spectrometry. Of all the samples, two (50.2 µg/kg in perihepatic fat and 51.1 µg/kg in kidney) were found above the maximum residue limit; these samples were taken from the animals in the elderly female group (over 24 months). There were more PCBs in cattle older than 2 years. Muscle, kidney, and perihepatic fat presented higher PCB concentrations than other tissues, and perirenal fat presented lower PCB concentrations than other tissues. PCB101, PCB153, and PCB138 were found to have the highest contribution to the PCB concentration. Thus, it is concluded that perihepatic fat, muscle, or kidney should be sampled, particularly in routine residue monitoring, and specifically analyzed for PCB101, PCB153, and PCB138.

Determining the biotransformation potential of commercial chemicals is critical for estimating their persistence in the aquatic environment. In vitro systems are becoming increasingly important as screening methods for assessing the potential for chemical metabolism. Depletion rate constants (kd) for several organic chemicals with high octanol–water partition coefficient (Kow) values (9-methylanthracene, benzo(a)pyrene, chrysene, and PCB-153) in rainbow trout hepatocytes were determined to estimate biotransformation rate constants (kMET) that were used in fish bioconcentration factor (BCF) models. Benzo[a]pyrene was rapidly biotransformed when incubated singly; however, its depletion rate constant (kd) declined 79% in a mixture of all four chemicals. Chrysene also exhibited significant biotransformation and its depletion rate constant declined by 50% in the mixture incubation. These data indicate that biotransformation rates determined using single chemicals may overestimate metabolism in environments containing chemical mixtures. Incubations with varying cell concentrations were used to determine whether cell concentration affected kd estimates. No statistically significant change in depletion rate constants were seen, possibly due to an increase in nonspecific binding of hydrophobic chemicals as cell density increased, decreasing overall biotransformation. A new model was used to estimate BCFs from kMET values calculated from empirically derived kd values. The inclusion of kMET in models resulted in significantly lower BCF values (compared kMET = 0). Modelled BCF values were consistent with empirically derived BCF values from the literature.