Immunosuppressive and Monooxygenase Induction Activities of Highly Chlorinated Diphenyl Ether Congeners in C57BL/6 and DBA/2 Mice

Harper, N.; Howie, L.; Connor, Kevin; Arellano, L.; Craig, Alison S.; Dickerson, R.; Safe, Stephen

doi:10.1093/toxsci/20.4.496

Cited by 3 publications

(9 citation statements)

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“…In addition, an interesting result was found (28) in certain highly chlorinated CDEs that contain multiple ortho substitutions, especially in both rings. The potencies were shown to be similar to those found (27) for the non-ortho-and monoortho-substituted compounds previously studied.…”

Section: Possible Relationships To Toxic Endpointsmentioning

confidence: 96%

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Polychlorinated biphenyls as hormonally active structural analogues.

McKinney

Waller

1994

Environ Health Perspect

295

173

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Among the environmental chemicals that may be able to disrupt the endocrine systems of animals and humans, the polychlorinated biphenyls (PCBs) are a chemical class of considerable concern. One possible mechanism by which PCBs may interfere with endocrine function is their ability to mimic natural hormones. These actions reflect a close relationship between the physicochemical properties encoded in the PCB molecular structure and the responses they evoke in biological systems. These physicochemical properties determine the molecular reactivities of PCBs and are responsible for their recognition at biological acceptors and receptors, as well as for triggering molecular mechanisms that lead to tissue response. "Coplanarity" of PCB phenyl rings and "laterality" of chlorine atoms are important structural features determining specific binding behavior with proteins and certain toxic responses in biological systems. We compare qualitative structure-activity relationships for PCBs with the limited information on the related non-coplanar chlorinated diphenyl ethers, providing further insights into the nature of the molecular recognition processes and support for the structural relationship of PCBs to thyroid hormones. Steroidlike activity requires conformational restriction and possibly hydroxylation. We offer some simple molecular recognition models to account for the importance of these different structural features in the structure-activity relationships that permit one to express PCB reactivities in terms of dioxin, thyroxine, and estradiol equivalents. The available data support the involvement of PCBs as mimics of thyroid and other steroidal hormones. The potential for reproductive and developmental toxicity associated with human exposure to PCBs is of particular concern.(ABSTRACT TRUNCATED AT 250 WORDS)Imagesp290-aFigure 2.Figure 3.Figure 4.Figure 5.Figure 6.

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Section: Possible Relationships To Toxic Endpointsmentioning

confidence: 96%

“…Recent work (27,28) has shown interesting differences in the structure-activity relationships for CDEs as compared to PCBs. The evidence suggests that both classes of compounds can produce dioxinlike toxic effects mediated by binding to the dioxin receptor.…”

Section: Possible Relationships To Toxic Endpointsmentioning

confidence: 99%

Polychlorinated biphenyls as hormonally active structural analogues.

McKinney

Waller

1994

Environ Health Perspect

295

173

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“…A number of penta-and hexachlorinated or more highly chlorinated PCDE congeners have been found to induce hepatic microsomal ethoxyresorufin-O-deethylase (EROD) activity in C57BL/6 mice and to a lesser extent in DBA/2 mice [24,29]. These findings indicate that an interaction of the PCDEs with the aryl hydrocarbon receptor (AhR) is responsible for the observed biological activity.…”

Section: Introductionmentioning

confidence: 99%

Ethoxyresorufin‐O‐deethylase induction potency of polychlorinated diphenyl ethers in H4IIE rat hepatoma cells

Koistinen

Sanderson

Giesy

et al. 1996

Enviro Toxic and Chemistry

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Abstract-Polychlorinated diphenyl ethers (PCDEs) are structurally similar to polychlorinated biphenyls (PCBs), and some PCDE congeners have been reported to cause toxic responses similar to those caused by some of the non-ortho-substituted PCBs, which are mediated by the aryl hydrocarbon receptor (AhR). Twenty-nine PCDEs were tested for their potency as AhR agonists relative to 2,3,7,3,7, by measuring their ability to induce the cytochrome P-450 1A1-associated enzyme activity, ethoxyresorufin-O-deethylase (EROD), in the H4IIE rat hepatoma cell bioassay. All PCDE congeners tested were found to be inactive as EROD inducers except for PCDE 156, which was a weak EROD inducer with a 2,3,7,8-TCDD equivalency factor of about 1.2 ϫ 10 Ϫ5 . During this study we determined that small amounts of polychlorinated dibenzofurans (PCDFs) that occurred as impurities in the PCDE preparations were the cause of the apparent EROD induction initially measured in our experiments. Once the PCDF impurities were removed by purification on florisil, little or no activity could be attributed to the PCDEs.

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“…Chu et al [82] reported that PCDE 184 is immunosuppressive in rats. Immunotoxicity of PCDEs has also been reported in mice [88,89]. Immunotoxicity of PCDEs correlated with enzyme induction activities in the study of Howie et al [88], who measured the dose-response suppression of the splenic plaque-forming cell response to sheep red blood cells in Ah-responsive C57BL/6 mice.…”

Section: Immunotoxicity and Developmental Toxicitymentioning

confidence: 93%

“…Immunotoxicity of PCDE has been studied in rat and mice [82,88,89]. Chu et al [82] reported that PCDE 184 is immunosuppressive in rats.…”

Section: Immunotoxicity and Developmental Toxicitymentioning

confidence: 99%

Polychlorinated Diphenyl Ethers (PCDE)

Koistinen

Volume 3 Anthropogenic Compounds Part K

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Polychlorinated diphenyl ethers (PCDE) are common impurities in chlorophenol formulations, which were earlier used as fungicides, slimicides, and as wood preservatives. PCDEs are structurally and by physical properties similar to polychlorinated biphenyls (PCB). They have low water solubility and are lipophilic. PCDEs are quite resistant to degradation and are persistent in the environment. In the aquatic environment, PCDEs bioaccumulate. These compounds are found in sediment, mussel, fish, bird, and seal. PCDEs show biomagnification potential, since levels of PCDEs increase in species at higher trophic levels. PCDEs are also detected in human tissue. Despite the persistence and bioaccumulation, the significance of PCDEs as environmental contaminants is uncertain. The acute toxicity and Ah-receptor-mediated (aryl hydrocarbon) activity of PCDEs is low compared to those of polychlorinated dibenzo-p-dioxins (PCDD) and dibenzofurans (PCDF). Due to structural similarity to thyroid hormone, PCDEs could bind to thyroid hormone receptor and alter thyroid function. Furthermore, PCDEs might be metabolized to toxic metabolites. In the environment, it is possible that photolysis converts PCDEs to toxic PCDDs and PCDFs.

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Immunosuppressive and Monooxygenase Induction Activities of Highly Chlorinated Diphenyl Ether Congeners in C57BL/6 and DBA/2 Mice

Cited by 3 publications

References 0 publications

Polychlorinated biphenyls as hormonally active structural analogues.

Polychlorinated biphenyls as hormonally active structural analogues.

Ethoxyresorufin‐O‐deethylase induction potency of polychlorinated diphenyl ethers in H4IIE rat hepatoma cells

Polychlorinated Diphenyl Ethers (PCDE)

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