Synthesis of the Octa- and Nonachlorobiphenyl Isomers and Congeners and Their Quantitation Commercial Polychlorinated Biphenyls and Identification in Human Breast Milk

Mullin, Michael D.; Sawka, G.; Safe, L.; McCrindle, Shelia.; Safe, Stephen

doi:10.1093/jat/5.3.138

Cited by 35 publications

(31 citation statements)

References 8 publications

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“…The analysis of environmental extracts by low-resolution packed column GLC utilizes specific peaks present in the chromatograms ofthe commercial PCBs (or reconstituted mixtures ofdifferent products) to estimate the PCB levels (4). This method relies heavily on the limited pattern recognition of selected peaks; however, in many cases the GLC pattern of PCBs in many environmental extracts do not resemble the corresponding patterns observed for any ofthe commercial PCBs (5)(6)(7)(8)(9).…”

Section: Pcb Analysis and Environmental Impactmentioning

confidence: 99%

Toxicology, structure-function relationship, and human and environmental health impacts of polychlorinated biphenyls: progress and problems.

Safe

1993

Environ Health Perspect

365

128

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Polychlorinated biphenyls (PCBs) are industrial compounds that have been detected as contaminants in almost every component ofthe global ecosystem including the air, water, sediments, riu, and wildlife and human adipose tissue, milk, and serum. PCBs in commercial products and environmental extracts are complex mixtures of isomers and congeners that can now be analyzed on a congener-specific basis using high-resolution gas chromatographic analysis. PCBs are metabolized prarily via mixed-function adxdaes intoa broadspectrum of m-tIbolites. The resuts indicate that metabolk activation is not required for PCB toxicity, and the parent hydrocarbons are responsible for most of the biochemical and toxic responses elicited by these compounds. Some of these responses include developmental and reproductive toxicity, dermal toxicity, endocrine effects, hepatotoxicity, carcinogenesis, and the induction of diverse phase I and phase I drugmetabolizing enzymes. Many of the effects observed for the commercial PCBs are similar to those reported for 2,3,7,-tetrachlorodibenzo-p-dioxin (TCDD) and related compounds. Strctur-function relaionships for PCB congeners have identified two major stnctural classes ofPCBs that elicit "TCDD-lik"' responses, namely, the coplanar PCBs (e.g., 3,3',4A,'-tetraCB, 3,3' 4,4 ,5-pentaCB and 3,3',4,4,,5'-hexaCB) and their mono-ortho coplanar derivatives. These compounds competitively bind to the TCDD or aryl hydrocarbon (Ah) receptor and exhibit Ah receptor agonist activity. In addition, other structural dasses of PCBs elicit biochemical and toxic responses that are not mediated through the Ah receptor. The shor-term effects of PCBs on occupationally exposed humans appear to be reversible, and no consistent changes in overall mortality and cancer mortality have been reported. Recent studies have demonstrated that some developmental deficits in infants and children correlated with in utero exposure to PCBs; however, the etiologic agent(s) or structural clas of PCBs responsible for these effects have not been dlinated. In contrast, based on a toxic equivalency factor approach, the reproductive and developmental problems in certain wildlife populations appear to be related to the TCDD-like PCB congeners.

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Section: Pcb Analysis and Environmental Impactmentioning

confidence: 99%

Toxicology, structure-function relationship, and human and environmental health impacts of polychlorinated biphenyls: progress and problems.

Safe

1993

Environ Health Perspect

365

128

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“…The quantitation might also be made after a perchlorination of PCB residues to form decachlorobiphenyl. The analytical procedures for organohalogens are discussed in an EPA manual (EPA 1980), by Brevik (1978), by Mullin et al (1981) and by Mes (1981).…”

Section: E) Analytical Chemistrymentioning

confidence: 99%

Chemical contaminants in human milk

1983

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“…3) and determining the mixed-function oxidase enzyme-inducing activities in immature male Wistar and Long-Evans rats (50,56,57 (60). These data indicate that at least five of the mono-ortho analogs of the coplanar PCBs elicit toxic effects which resemble (qualitatively) 2,3,7,8-TCDD, and several of these compounds (2,3,3',4,4'-penta, 2,3',4,4',5-penta-, 2,3,3' ,4,4' ,5-hexachlorobiphenyl) have been identified in commercial PCBs and as residues in human tissues (32,61,62). Future research should establish the quantitative contributions of this group of compounds to the toxic and biologic effect of commercial PCBs and the PCB residues which persist in human tissues.…”

Section: Mono-ortho Coplanar Pcbsmentioning

confidence: 99%

“…Both of these compounds are among the most active di-ortho coplanar PCB inducers of rat hepatic microsomal AHH and cytochromes P450c. Based on the relatively low activities of this group of compounds, future toxicologic research should focus on the effects of 2,2',3,4,4',5'-hexachlorobiphenyl since this isomer is a major component of commercial PCBs and preferentially bioconcentrates in human blood, adipose tissue and breast milk (32)(33)(34)61,62 (38,40,42,(68)(69)(70). Administration of the coplanar PCBs or 2,3,7,8-TCDD to C57BL/6J mice results in the induction of hepatic microsomal AHH, immunotoxicity and weight loss whereas the nonresponsive mice are much less susceptible to the effects of these compounds (e.g., Fig.…”

Section: Di-ortho Coplanar Pcbsmentioning

confidence: 99%

PCBs: structure–function relationships and mechanism of action

Safe¹,

Bandiera²,

Sawyer³

et al. 1985

Environ Health Perspect

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Numerous reports have illustrated the versatility of polychlorinated biphenyls (PCBs) and related halogenated aromatics as inducers of drug-metabolizing enzymes and the activity of individual compounds are remarkably dependent on structure. The most active PCB congeners,3,4,4',3,3',4,3,3',4,4',3',4,4',5,, are substituted at both para and at two or more meta positions. The four coplanar PCBs resembled 3-methylcholanthrene (3-MC) and 2,3,7,3,7, in their mode of induction of the hepatic drug-metabolizing enzymes. These compounds induced rat hepatic microsomal benzo(a)pyrene hydroxylase (aryl hydrocarbon hydroxylase, AHH) and cytochromes P-450a, P-450c and P-450d. 3,4,4',5-Tetrachlorobiphenyl, the least active coplanar PCB, also induced dimethylaminoantipyrine N-demethylase and cytochromes P-450b + e and resembled Aroclor 1254 as an inducer of the mixed-function oxidase system. Like Aroclor 1254, all the mono-ortho-and at least eight di-ortho-chloro analogs of the coplanar PCBs exhibited a "mixed-type" induction pattern and induced microsomal AHH, dimethylaminoantipyrine NM-demethylase and cytochromes P-450a-P-450e. Quantative structure-activity relationships (QSARs) there was an excellent correlation between AHH induction potencies and receptor binding avidities of these compounds and the order of activity was coplanar PCBs (3,3',4,3,3',4,4',3',4,4',5,5'-hexachlorobiphenyls) > 3,4,4',5-tetrachlorobiphenyl -mono-ortho coplanar PCBs > di-ortho coplanar PCBs. It was also apparent that the relative toxicities of this group of PCBs paralleled their biological potencies.The coplanar and mono-ortho coplanar PCBs also exhibit differential effects in the inbred C57BL/6J and DBA/2J mice. These compounds induce AHH and cause thymic atrophy in the former "responsive" mice whereas at comparable or higher doses none of these effects are observed in the nonresponsive DBD/ 2J mice. Since the responsiveness of these two mice strains is due to the presence of the Ah receptor protein in the C57BL/6J mice and its relatively low concentration in the DBA/2J mice, the results for the PCB cogeners support the proposed receptor-mediated mechanism of action.Although the precise structural requirements for ligand binding to the receptor have not been delineated, the halogenated aromatic hydrocarbons which exhibit the highest binding affinities for the receptor protein are approximate isostereomers of 2,3,7,8-TCDD. 2,3,4,4',5-Pentachlorobiphenyl elicits effects which are qualitatively similar to that of TCDD and the presence of the lateral 4'-substituent is required for this activity. Thus the 4'-substituted 2,3,4,5-tetrachlorobiphenyls have been used as probes for determining the substituent characteristics which favor binding to the receptor protein. Multiple regression analysis of the competitive binding EC50 values for 13 substituents gave the following equation: log (1/EC5O) = 1.53a + 1.47T + 1.09 HB + 4.08 where a is electronegativity, a is hydrophobicity, HB is hydrogen bonding and r is the correlation coefficient (r = 0.978). The ut...

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Synthesis of the Octa- and Nonachlorobiphenyl Isomers and Congeners and Their Quantitation Commercial Polychlorinated Biphenyls and Identification in Human Breast Milk

Cited by 35 publications

References 8 publications

Toxicology, structure-function relationship, and human and environmental health impacts of polychlorinated biphenyls: progress and problems.

Toxicology, structure-function relationship, and human and environmental health impacts of polychlorinated biphenyls: progress and problems.

Chemical contaminants in human milk

PCBs: structure–function relationships and mechanism of action

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