Induction of Altered Hepatic Foci by a Mixture of Dioxin-like Compounds with and without 2,2′,4,4′,5,5′-Hexachlorobiphenyl in Female Sprague–Dawley Rats

Plas, S.A. van der; Haag‐Grönlund, Marie; Scheu, Gunilla; Wärngård, Lars; Berg, Martin van den; Wester, Piet W.; Koeman, J.H.; Brouwer, Abraham

doi:10.1006/taap.1999.8629

Cited by 12 publications

(8 citation statements)

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“…Two subchronic animal experiments were performed, both approved by the animal welfare committee before starting the experiments. The treatment protocol used for these experiments was based on the altered hepatic foci (AHF) tumor promotion protocol introduced by Pitot et al (1978) and described in detail by van der Plas et al (1999van der Plas et al ( , 2000. In short, an initiation step, consisting of a diethylnitrosamine injection (i.p.…”

Section: Methodsmentioning

confidence: 99%

“…However, in most studies the focus was on individual PHAH congeners or combinations of two or three congeners (Bager et al, 1995;van Birgelen et al, 1994a,b;Haag-Gro ¨nlund et al, 1998;Sargent et al, 1991). Our major aim of this study was to evaluate the applicability of the TEF concept for the tumor promotion potential of complex environmentally relevant PHAH mixtures (van der Plas et al, 1999Plas et al, , 2000. In addition, the effects of subchronic exposure to these PHAH mixtures was determined on endocrine parameters, in particular on the vitamin A and thyroid hormone system.…”

mentioning

confidence: 99%

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Effects of Subchronic Exposure to Complex Mixtures of Dioxin-like and Non-Dioxin-like Polyhalogenated Aromatic Compounds on Thyroid Hormone and Vitamin A Levels in Female Sprague-Dawley Rats

Plas¹

2001

Toxicological Sciences

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The aim of this study was to determine the effects of subchronic exposure to complex mixtures of polyhalogenated aromatic hydrocarbons (PHAHs) on the thyroid hormone and retinoid status in female Sprague-Dawley rats and to investigate the predictability of these effects by the toxic equivalency factor (TEF) concept. In the first experiment, the focus was on a complex dioxin-like PHAH mixture, which covered > 90% of the total toxic equivalents (TEQ) present in Baltic herring. In the second experiment, the contribution of non-dioxin-like polychlorinated biphenyls (PCBs) was investigated by testing the commercial PCB mixture Aroclor 1260, its 0-1 ortho and 2-4 ortho fractions and the reconstituted 0-4 ortho fraction. Hepatic retinoid levels were severely decreased ( approximately 70%) after treatment with the dioxin-like PHAH mixture, similar to the effect of a TEQ equivalent dose of 1 microg 2,3,7,8-TCDD/kg bw/week. However, the TEF concept failed to predict the effect on plasma retinol; a decrease (21%) was observed after treatment with the PHAH mixture, whereas an increase (21%) was found after treatment with TCDD. A more severe decrease of total thyroid hormone in plasma was observed after exposure to the PHAH mixture compared to treatment with TCDD ( approximately 60% vs. 38%). The discrepancy found between the predicted and observed effects for plasma retinol and thyroid hormone is possibly due to an additional effect of hydroxylated PCBs, formed from metabolizable PCBs present in the PHAH mixture. Aroclor 1260 and its fractions did not significantly alter the retinoid and thyroid hormone status at the dose levels tested, indicating that in case of exposure to complex PCB mixtures at environmental levels, no effects, or at best, only marginal effects can be expected on the retinoid and thyroid hormone status.

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Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 99%

Effects of Subchronic Exposure to Complex Mixtures of Dioxin-like and Non-Dioxin-like Polyhalogenated Aromatic Compounds on Thyroid Hormone and Vitamin A Levels in Female Sprague-Dawley Rats

Plas¹

2001

Toxicological Sciences

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“…In yet another study using altered hepatic foci as an intermediate marker for a tumor endpoint following N-nitrosodiethylamine exposure, there was less than an additive effect for different combinations of congeners 126 and 153, although the authors showed increasing levels of these congeners in the adipose and liver tissues (111). There also are data to show that the mixture of organochlorine compounds with high TEF particularly overestimates the promoting effects (100,104,110). Further, the TEF approach assumes that dose-response curves are parallel.…”

Section: Toxic Equivalency Factorsmentioning

confidence: 91%

“…It is unknown whether the experimental studies used for the determination of TEFs can be extrapolated to humans and what is the appropriateness of these toxicologic noncancer end points for predicting human cancer risk (195,196). Whether the mechanistic relationship of PCBs to tumorigenesis in animals is due solely to aryl hydrocarbon hydroxylase pathways also remains speculative; non -aryl hydrocarbon hydroxylaseinducing congeners can behave as tumor promoters (104). The TEF approach assumes that there is no interspecies difference in toxicity, which is not true (105,106), and some data show that humans are less sensitive than rodents (107).…”

Section: Toxic Equivalency Factorsmentioning

confidence: 99%

“…The two were poorly related (calculated values overestimated the tumor-inducing effect), and the PCBs with the greatest tumorigenicity potential (Aroclor 1254 and 1260) had low toxic equivalencies. The net effect of the TEF research method is to overstate PCB toxicity (104). Nonetheless, some epidemiologists have attempted to identify a relationship for PCBs to human cancer risk, conducting a congener-specific analysis and determining risk estimates for congeners with high TEFs; the results for PCBs and lymphoma were null (113).…”

Section: Toxic Equivalency Factorsmentioning

confidence: 99%

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Understanding Population and Individual Risk Assessment: The Case of Polychlorinated Biphenyls

Shields

2006

Cancer Epidemiology, Biomarkers &Amp; Prevention

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Decisions about how to improve or protect the public health can be, and sometimes necessarily are, made on imprecise science. The regulation of potential human carcinogens in the environment entails a population-risk assessment process intended to reduce risks to less than one additional cancer in 100,000 or 1,000,000 persons. These risk assessment processes, however, may be miscommunicated or misinterpreted in the context of individual cancer risks by scientists, regulators, the lay media, and the public. This commentary will review methods for establishing a causal relationship between carcinogen exposures and cancer risk. It will use the case of polychlorinated biphenyls (PCB) as an example of how to place scientific data into the context of human exposure and cancer risk. PCBs are widespread environmental contaminants and most people have detectable levels of PCBs in their bodies. The primary source for exposure in the general population is through the diet. PCBs are carcinogens in experimental animal models, but how this information can be extrapolated to human risk remains uncertain. PCB experimental studies provide data that are used to regulate and control human exposure, although the epidemiologic evidence fails to establish PCBs as human carcinogens. Thus, what is used for populationrisk assessment may not be appropriate for individual-risk assessment or concluding that a causal relationship exists between PCB exposure and cancer risk. The hazards from a carcinogen designated by regulatory and review agencies as a ''probable'' human carcinogen is often misunderstood out of context about the magnitude of the risk and in what settings. How scientists communicate their results in scientific articles can strongly influence how others interpret their data. Misunderstandings from both the use of regulatory and review-agency opinions and the conclusions espoused by scientists occur in the media, among private physicians counseling their patients about cancer risk, and in the legal settings where plaintiffs seek compensation for exposure and alleged harm (or future harm). This can lead to false conclusions about what caused a cancer in a specific patient, undue anxiety about future cancer risk, inappropriate cancer screening, and attendant increased morbidity due to increased uses of the medical system and complication rates from medical procedures. The communication of research findings by scientists must be presented with caution, resisting the temptation to extrapolate, inappropriately, research data to the general population. (Cancer Epidemiol Biomarkers Prev 2006;15(5):830 -9)

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Contribution of Planar (0–1 Ortho) and Nonplanar (2–4 Ortho) Fractions of Aroclor 1260 to the Induction of Altered Hepatic Foci in Female Sprague–Dawley Rats

Plas

Sundberg

Berg

et al. 2000

Toxicology and Applied Pharmacology

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Induction of Altered Hepatic Foci by a Mixture of Dioxin-like Compounds with and without 2,2′,4,4′,5,5′-Hexachlorobiphenyl in Female Sprague–Dawley Rats

Cited by 12 publications

References 50 publications

Effects of Subchronic Exposure to Complex Mixtures of Dioxin-like and Non-Dioxin-like Polyhalogenated Aromatic Compounds on Thyroid Hormone and Vitamin A Levels in Female Sprague-Dawley Rats

Effects of Subchronic Exposure to Complex Mixtures of Dioxin-like and Non-Dioxin-like Polyhalogenated Aromatic Compounds on Thyroid Hormone and Vitamin A Levels in Female Sprague-Dawley Rats

Understanding Population and Individual Risk Assessment: The Case of Polychlorinated Biphenyls

Contribution of Planar (0–1 Ortho) and Nonplanar (2–4 Ortho) Fractions of Aroclor 1260 to the Induction of Altered Hepatic Foci in Female Sprague–Dawley Rats

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