Metabolism and biochemical effects of 3,3′,4,4′-tetrachlorobiphenyl in pregnant and fetal rats

Morse, D.C.; Wehler, E. Klasson; Paš, Maja; Bie, A.T.H.J. De; Bladeren, P.J. van; Brouwer, Abraham

doi:10.1016/0009-2797(94)03347-1

Cited by 46 publications

(11 citation statements)

References 25 publications

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“…These relative potency factors correspond very well with factors of 3–10 reported for other hydroxyl metabolites of PCBs in several studies [29], [71], [72]. Because TTR plays a significant role in transport of thyroid hormones through the placental and blood-brain barriers, high affinity of hydroxyl-PCBs to TTR and thyroid hormone displacement potentially results in an efficient transport and accumulation of hydroxyl-PCBs into the fetal compartment and brain at the cost of thyroid hormones [68], [73], [74]. Chemical analysis revealed dose-dependently increasing concentrations of 3′-OH-PCB 180 in livers of the rats of the present study (Al-Anati et al , in preparation).…”

Section: Discussionsupporting

confidence: 84%

Toxicological Profile of Ultrapure 2,2′,3,4,4′,5,5′-Heptachlorbiphenyl (PCB 180) in Adult Rats

et al. 2014

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PCB 180 is a persistent non-dioxin-like polychlorinated biphenyl (NDL-PCB) abundantly present in food and the environment. Risk characterization of NDL-PCBs is confounded by the presence of highly potent dioxin-like impurities. We used ultrapure PCB 180 to characterize its toxicity profile in a 28-day repeat dose toxicity study in young adult rats extended to cover endocrine and behavioral effects. Using a loading dose/maintenance dose regimen, groups of 5 males and 5 females were given total doses of 0, 3, 10, 30, 100, 300, 1000 or 1700 mg PCB 180/kg body weight by gavage. Dose-responses were analyzed using benchmark dose modeling based on dose and adipose tissue PCB concentrations. Body weight gain was retarded at 1700 mg/kg during loading dosing, but recovered thereafter. The most sensitive endpoint of toxicity that was used for risk characterization was altered open field behavior in females; i.e. increased activity and distance moved in the inner zone of an open field suggesting altered emotional responses to unfamiliar environment and impaired behavioral inhibition. Other dose-dependent changes included decreased serum thyroid hormones with associated histopathological changes, altered tissue retinoid levels, decreased hematocrit and hemoglobin, decreased follicle stimulating hormone and luteinizing hormone levels in males and increased expression of DNA damage markers in liver of females. Dose-dependent hypertrophy of zona fasciculata cells was observed in adrenals suggesting activation of cortex. There were gender differences in sensitivity and toxicity profiles were partly different in males and females. PCB 180 adipose tissue concentrations were clearly above the general human population levels, but close to the levels in highly exposed populations. The results demonstrate a distinct toxicological profile of PCB 180 with lack of dioxin-like properties required for assignment of WHO toxic equivalency factor. However, PCB 180 shares several toxicological targets with dioxin-like compounds emphasizing the potential for interactions.

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Section: Discussionsupporting

confidence: 84%

Toxicological Profile of Ultrapure 2,2′,3,4,4′,5,5′-Heptachlorbiphenyl (PCB 180) in Adult Rats

et al. 2014

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“…37,38 Also of major concern are the developmental effects in pregnant and fetal mammals. 36,39 Hydroxylated PCB metabolites have also been detected in human milk. 40,41 The prevalence of PCBs and their biologically more potent metabolites in mother's breast milk is a great human threat because of the potential risk imposed on the young infants.…”

Section: Pcb Metabolitesmentioning

confidence: 98%

Enantioselective semipreparative HPLC separation of PCB metabolites and their absolute structure elucidation using electronic and vibrational circular dichroism

Pham-Tuan¹,

Larsson²,

Hoffmann³

et al. 2005

Chirality

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Polychlorinated biphenyls (PCBs) remain one of the most important groups of environmental contaminants. The fate (transformation) as well as the toxicological implications of the different metabolism steps are subject to considerable debate. The aim of this study is to start a comprehensive investigation of atropisomeric PCB metabolites, i.e., hydroxy, methoxy, methylthionyl, and methylsulfonyl PCBs in different biota. For this purpose, enantioselective semipreparative liquid chromatography is used to obtain pure enantiomers of PCB metabolites. Electronic circular dichroism (UV-CD) and vibrational circular dichroism (VCD) in combination with computational techniques were applied to determine their absolute structures. Approximately 18-25 mg of each enantiomer of the following metabolites were obtained using semipreparative HPLC on beta-cyclodextrin-based columns: 4-MeO-CB149, 4-MeS-CB149, 4-MeSO2-CB149, 3-MeS-CB149, and 3-MeSO2-CB149. The enantiomeric purity of the separated enantiomers was in the range of 95.0-99.9%. Rotational angles and absolute configurations were also determined. This study establishes a sound method for future preparation and absolute structure determination of compounds belonging to the same class.

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“…Moreover, TTR has been suggested to facilitate the transport of bound ligands across the blood-brain barrier and the placenta and thus, binding to TTR may also play a role in the distribution of OH-PCBs to the placenta and the brain (Brouwer et al, 1998, Lans et al, 1993, Mortimer et al, 2012). In fact, exposure of pregnant mice to PCBs resulted in elevated serum and brain levels of OH-PCBs in the developing fetus (Meerts et al, 2002, Meerts et al, 2004, Morse et al, 1995, Morse et al, 1996). After birth, the OH-PCBs in brain were no longer detected, suggesting an increased susceptibility exists in this highly sensitive moment of brain development (Jacobson et al, 1990, Boucher et al, 2009, Darras, 2008).…”

Section: Pcb Metabolite Associated Toxicitiesmentioning

confidence: 99%

Metabolism and metabolites of polychlorinated biphenyls

Grimm

Kania-Korwel

et al. 2015

Critical Reviews in Toxicology

351

414

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The metabolism of polychlorinated biphenyls (PCBs) is complex and has an impact on toxicity and thereby assessment of PCB risks. A large number of reactive and stable metabolites are formed in the processes of biotransformation in biota in general and in humans in particular. The aim of this document is to provide an overview of PCB metabolism and to identify metabolites of concern and their occurrence. Emphasis is given to mammalian metabolism of PCBs and their hydroxyl, methylsulfonyl, and sulfated metabolites, especially those that persist in human blood. Potential intracellular targets and health risks are also discussed.

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Metabolism and biochemical effects of 3,3′,4,4′-tetrachlorobiphenyl in pregnant and fetal rats

Cited by 46 publications

References 25 publications

Toxicological Profile of Ultrapure 2,2′,3,4,4′,5,5′-Heptachlorbiphenyl (PCB 180) in Adult Rats

Toxicological Profile of Ultrapure 2,2′,3,4,4′,5,5′-Heptachlorbiphenyl (PCB 180) in Adult Rats

Enantioselective semipreparative HPLC separation of PCB metabolites and their absolute structure elucidation using electronic and vibrational circular dichroism

Metabolism and metabolites of polychlorinated biphenyls

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