Stepping backward to improve assessment of PCB congener toxicities.

Hansen, Larry G.

doi:10.1289/ehp.98106s1171

Cited by 262 publications

(211 citation statements)

References 148 publications

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“…Polychlorinated biphenyls (PCBs) are widespread environmental contaminants with a broad spectrum of biological effects (Safe 1994;Hansen 1998); however, there is little information regarding effects of direct PCB exposure on strictly terrestrial animals. Terrestrial PCBs can have direct effects on rodent enzymes and endocrine systems, and the enzyme effects are predictive of other characteristics of the environmental mixture Hansen 1996a, 1996b).…”

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confidence: 99%

“…Terrestrial PCBs can have direct effects on rodent enzymes and endocrine systems, and the enzyme effects are predictive of other characteristics of the environmental mixture Hansen 1996a, 1996b). High 2,3,7,8-tetrachloro-pdioxin (TCDD) equivalents are readily estimated from induction of CYP 1A1, commonly measured as 7-ethoxy resorufin O-dealkylase (EROD) activity (Safe 1994;Hansen 1996a, 1996b;Hansen 1998). Noncoplanar PCBs cause phenobarbital-type induction of 7-pentoxy and 7-benzoxyresorufin O-dealkylase activities (PROD, reflecting CYP 2B1, and BROD, reflecting CYP 2B1 ϩ CYP 3A23) (Safe 1994;Li and Hansen 1996a;Hansen 1998).…”

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confidence: 99%

“…High 2,3,7,8-tetrachloro-pdioxin (TCDD) equivalents are readily estimated from induction of CYP 1A1, commonly measured as 7-ethoxy resorufin O-dealkylase (EROD) activity (Safe 1994;Hansen 1996a, 1996b;Hansen 1998). Noncoplanar PCBs cause phenobarbital-type induction of 7-pentoxy and 7-benzoxyresorufin O-dealkylase activities (PROD, reflecting CYP 2B1, and BROD, reflecting CYP 2B1 ϩ CYP 3A23) (Safe 1994;Li and Hansen 1996a;Hansen 1998). These enzyme changes are not considered toxic responses per se, but are markers for types of toxicants and may modulate the types of toxicities observed (Safe 1994;Li and Hansen 1996b;Hansen 1998).…”

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confidence: 99%

“…Other reported alterations include suppression of the humoral and cell-mediated immune responses in vivo and in vitro (DeKrey et al 1994;Harper et al 1995a;Ross et al 1995). Different PCBs have different potencies and efficacies and, within a mixture, may antagonize as well as contribute to other actions (Safe 1994;Harper et al 1995b;Li and Hansen 1996b;Hansen 1998). Thus, the changes in immune responses resulting from exposure to PCB mixtures may provide important information regarding the mixture of concern.…”

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confidence: 99%

“…Appropriate and accurate risk assessment of specific environmental PCB mixtures is critical because of the widespread contamination of the environment (Hansen 1998). Limited resources do not permit remediation of every contaminated site, and the method of remediation depends on the type of hazard present.…”

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confidence: 99%

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Immunological, Hematological, and Biochemical Responses in Immature White-Footed Mice Following Maternal Aroclor 1254 Exposure: A Possible Bioindicator

Greeley

Hansen

et al. 1999

Arch. Environ. Contam. Toxicol.

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A number of hematological, immunological, and biochemical parameters were measured in Peromyscus leucopus pups born from dams exposed to a single dose (300 mg/kg body weight) of Aroclor 1254. To increase the chances of uncovering even modest consequences of the exposure, in one protocol the pups were weaned at 3 weeks and examined at 6 weeks of age, while in a second protocol the pups were kept with their mother for 4 weeks, at which time they were examined. The older pups showed significant decreases in body weight, ratio of spleen weight to body weight, numbers of peripheral white blood cells and lymphocytes, and number and percentage of monocytes. They also showed significant increases in the stimulation index in response to the mitogen phytohemagglutinin (PHA), percentage of peripheral blood neutrophils and liver EROD induction. Pups sacrificed at 4 weeks of age showed even more significant differences. Their body and liver weights, percentage and number of peripheral blood lymphocytes, and serum antibody titers were significantly lower than those of their controls, while spleen to body weight ratios, percent of neutrophils in their peripheral blood, and liver EROD, PROD, and BROD levels were significantly higher than those of the controls. The primary implication of this work is that white-footed mouse pups could be used as biomonitors of contaminated sites. Females could be captured at the sites and bred in captivity with normal males. The vulnerable parameters identified in this study could then be measured in the resulting offspring and compared with a database collected from normal pups.

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Immunological, Hematological, and Biochemical Responses in Immature White-Footed Mice Following Maternal Aroclor 1254 Exposure: A Possible Bioindicator

Greeley

Hansen

et al. 1999

Arch. Environ. Contam. Toxicol.

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Correlations among polychlorinated biphenyls, dioxins, and furans in humans

1999

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Background Correlations among human levels of polychlorinated biphenyls, polychlorinated dibenzo‐p‐dioxins, and polychlorinated dibenzofurans potentially complicate interpretation of studies of their individual health effects. Outcomes attributed to one may, in fact, be due to another. Methods We present correlations among dioxins, furans, and PCBs in blood collected in 1991–1992 from 44 American Vietnam veterans from Michigan. Results Correlations among specific dioxins and furans ranged from 0.26 to 0.80, with the higher‐chlorinated congeners being more highly correlated. Correlations among PCBs ranged from 0.06 to 0.94, with those occurring at highest concentrations being more highly correlated. Correlations of PCBs with dioxins and furans ranged from ‐0.09 to 0.59. Correlations of individual chemicals with total dioxin toxic equivalents ranged from 0.31 to 0.76. Discussion/Conclusions If confirmed in other populations, such correlations may allow the use of simpler assays but may also raise issues of confounding and calibration. Am. J. Ind. Med. 35:15–20, 1999. Published 1999 Wiley‐Liss, Inc.

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Dioxin‐Like Compounds, Screening Assays

Bunce

Petrulis

2000

Encyclopedia of Analytical Chemistry

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A dioxin‐like compound (DLC) is a halogenated aromatic compound that has toxicological properties similar to those of the reference toxicant 2,3,7,8‐tetrachlorodibenzo‐p‐dioxin (TCDD). The DLCs include other halogenated dibenzo‐p‐dioxins and dibenzofurans (especially those that are chlorinated in the 2‐,3‐,7‐, and 8‐positions), and coplanar polychlorinated biphenyls (PCBs). They associate with the aryl hydrocarbon receptor (AhR) protein, and share some biological end‐points with TCDD, notably the induction of Phase 1 monooxygenase enzymes. Because DLCs normally occur as complex mixtures in environmental and biological samples, it is common to refer to the TCDD equivalent concentration [toxic equivalence (TEQ)], which is obtained by summing for each congener its actual amount or concentration by an empirical toxic equivalency factor (TEF). Conventional analysis of DLCs by gas chromatography/mass spectrometry (GC/MS) is cumbersome and expensive, and much attention has been given to developing bioassays that will yield a measure of the TEQ in a single determination. Many such bioassays are mechanism‐based, meaning that the assay end‐point is one of the steps along the pathway of the mechanism of action. This article begins with an overview of bioassay methods in general, pointing out similarities and differences between chemical assays and bioassays, before describing particular assays that have been developed for DLCs. Among mechanism‐based assays, AhR binding assays are well established, and are useful because they include the dioxin‐like activity of both productive and unproductive compounds. In assays based on subsequent stages of the mechanism of action, unproductive substances can antagonize the responses of productive compounds, a phenomenon that is explicable in terms of target molecule antagonism, in which the AhR protein is the target molecule. Immunoassays for DLCs have recently received much attention; although their spectrum of cross‐reactivity does not always correlate well with TEFs, there has been important recent progress in terms of the sensitivity and detection limit (DL) of these assays. Finally, early life stage bioassays are becoming increasingly important as research has revealed the toxicological effects of DLCs during development.

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Stepping backward to improve assessment of PCB congener toxicities.

Cited by 262 publications

References 148 publications

Immunological, Hematological, and Biochemical Responses in Immature White-Footed Mice Following Maternal Aroclor 1254 Exposure: A Possible Bioindicator

Immunological, Hematological, and Biochemical Responses in Immature White-Footed Mice Following Maternal Aroclor 1254 Exposure: A Possible Bioindicator

Correlations among polychlorinated biphenyls, dioxins, and furans in humans

Dioxin‐Like Compounds, Screening Assays

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