Comparisons of Estimated Human Body Burdens of Dioxinlike Chemicals and TCDD Body Burdens in Experimentally Exposed Animals

DeVito, Michael J.; Birnbaum, Linda S.; Farland, William H.; Gasiewicz, Thomas A.

doi:10.2307/3432395

Cited by 55 publications

(69 citation statements)

References 40 publications

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“…Retrospective analysis of 1189 chemical plant workers exposed to dioxin and furans reported a highly significant 2.5-fold (95% confidence interval-1.3-4.7) increase in relative-risk of death from heart disease due to dioxin exposure (FleschJanys et al, 1995;Pelclova et al, 2002). The body burden at which these effects were seen ranges from 110 to 4000 ng/kg of TCDD in blood fat, well below the body burden of TCDD shown to induce cancer in rodents (100-140000 ng/kg) (DeVito et al, 1995). These observations were later supported in hyperlipidemic mice subchronicly treated with TCDD (150 ng/kg, 3 times weekly), resulting in increased blood pressure and atherogenic lipids; the two most important clinical risk factors for atherosclerotic plaque formation.…”

Section: Effects Of Tcdd Exposure On Development Ahr In Developmentmentioning

confidence: 90%

“…As a result, clear-cut dose-response assessments of TCDD are made difficult by the complexity of biologic responses to TCDD, the variety of tissues affected by TCDD and gaps in our understanding of the mechanisms relating exposure to toxicity. As a result, body burden rather than daily intake (administration) has been suggested as the best dose metric for interspecies comparisons and extrapolation, although the vast majority of studies describing TCDD toxicity express dose in terms of acute, subchronic and chronic exposures (DeVito et al, 1995).…”

Section: Introductionmentioning

confidence: 99%

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Induction of Oxidative Stress Responses by Dioxin and other Ligands of the Aryl Hydrocarbon Receptor

et al. 2005

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ᮀTCDD and other polyhalogenated aromatic hydrocarbon ligands of the aryl hydrocarbon receptor (AHR) have been classically considered as non-genotoxic compounds because they fail to be directly mutagenic in either bacteria or most in vitro assay systems. They do so in spite of having repeatedly been linked to oxidative stress and to mutagenic and carcinogenic outcomes. Oxidative stress, on the other hand, has been used as a marker for the toxicity of dioxin and its congeners. We have focused this review on the connection between oxidative stress induction and the toxic effects of fetal and adult dioxin exposure, with emphasis on the large species difference in sensitivity to this agent. We examine the roles that the dioxin-inducible cytochromes P450s play in the cellular and toxicological consequences of dioxin exposure with emphasis on oxidative stress involvement. Many components of the health consequences resulting from dioxin exposure may be attributable to epigenetic mechanisms arising from prolonged reactive oxygen generation.

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Section: Effects Of Tcdd Exposure On Development Ahr In Developmentmentioning

confidence: 90%

Section: Introductionmentioning

confidence: 99%

Induction of Oxidative Stress Responses by Dioxin and other Ligands of the Aryl Hydrocarbon Receptor

et al. 2005

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“…Therefore, humans, wildlife, and laboratory animals are exposed daily to a complex mixture of these chemicals via trace amounts present in food and the environment [1,2]. Due to their hydrophobic nature and resistance to metabolism, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and related PHAH congeners accumulate in tissues of exposed populations [1][2][3][4][5]. Therefore, repeated exposures to small amounts of PHAH may evoke adverse health effects due to chronic accumulation in target tissues [6].…”

Section: Introductionmentioning

confidence: 99%

Accumulation of M1dG DNA adducts after chronic exposure to PCBs, but not from acute exposure to polychlorinated aromatic hydrocarbons

Jeong

Walker

Burgin

et al. 2008

Free Radical Biology and Medicine

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Oxidative DNA damage is one of the key events thought to be involved in mutation and cancer. The present study examined the accumulation of M 1 dG, 3-(2′-deoxy-β-D-erythro-pentofuranosyl)-pyrimido[1,2-a]-purin-10(3H)-one, DNA adducts after single dose or one-year exposure to polyhalogenated aromatic hydrocarbons (PHAH) in order to evaluate the potential role of oxidative DNA damage in PHAH toxicity and carcinogenicity. The effect of PHAH exposure on the number of M 1 dG adducts was explored initially in female mice exposed to a single dose of either 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) or a PHAH mixture. This study demonstrated that a single exposure to PHAH had no significant effect on the number of M 1 dG adducts compared to the corn oil control group. The role of M 1 dG adducts in polychlorinated biphenyl (PCB) induced toxicity and carcinogenicity was further investigated in rats exposed for a year to PCB 153, PCB 126, or a mixture of the two. PCB 153, at doses up to 3000 μg/kg/d, had no significant effect on the number of M 1 dG adducts in liver and brain tissues from the exposed rats compared to controls. However, 1000 ng/kg/ d of PCB 126 resulted in M 1 dG adduct accumulation in the liver. More importantly, co-administration of equal proportions of PCB 153 and PCB 126 resulted in dose-dependent increases in M 1 dG adduct accumulation in the liver from 300-1000 ng/kg/d of PCB 126 with 300-1000 μg/kg/d of PCB 153. Interestingly, the co-administration of different amounts of PCB 153 with fixed amounts of PCB 126 demonstrated more M 1 dG adduct accumulation with higher doses of PCB 153. These results are consistent with the results from cancer bioassays that demonstrated a synergistic effect between PCB 126 and PCB 153 on toxicity and tumor development. In summary, the results from the present study support the hypothesis that oxidative DNA damage plays a key role in toxicity and carcinogenicity following long-term PCB exposure.

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“…The higher PCDD/Fs concentrations in sera from study subjects than in the general population in Taiwan is indicative of the adverse impact of the Waelz plant and the nearby industrial site. Based on serum concentrations of PCDD/Fs, estimated body burden was 4.26 (Area D) and 3.95 (Area U) ng WHO 1998 -TEQ/kg of body weight (bw) for subjects, assuming dioxins are equally distributed in body fat and an adult has 22% body fat (DeVito et al, 1995). Their estimated lifetime average daily doses (LADDs) were 1.20 and 1.09 pg WHO 1998 -TEQ /kg/d, respectively.…”

Section: Serum Pcdd/fs Concentrationsmentioning

confidence: 99%

Health Risk from Exposure to PCDD/Fs from a Waelz Plant in Central Taiwan

Tsai¹,

Mao

Hsien

et al. 2014

Aerosol Air Qual. Res.

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This study combined ambient air sampling and biomonitoring data to determine the PCDD/Fs exposure levels and health risk for residents near a Waelz plant. In total, 457 adults completed questionnaires and 48 subjects also gave blood samples. We The estimated lifetime average daily doses (LADDs) were 1.20 and 1.09 pg WHO1998-TEQ/kg/d, which are below the tolerable daily intake (TDI) range of 1-4 pg TEQ/kg bw (World Health Organization). However, the concentration was higher than concentrations for the general population in Taiwan. The USEPA multimedia model showed that the median of lifetime exposure to PCDD/Fs was 1.90 × 10 -2 pg/kg bw/day and 3.19 × 10 -2 pg/kg bw/day for Area U (upwind site) and Area D (downwind site), respectively. The carcinogenic risk was 2.96 × 10 -6 (95th percentile = 1.61 × 10 -5 ), and 4.97 × 10 -6 (95th percentile = 2.59 × 10 -5 ) for Area U and Area D, respectively. In summary, residents near the plant had a higher body burden of PCDD/Fs than the general population in Taiwan. The health risk from exposure, including cancer mortality caused by chronic exposure to PCDD/Fs, needs to be clarified further.

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Comparisons of Estimated Human Body Burdens of Dioxinlike Chemicals and TCDD Body Burdens in Experimentally Exposed Animals

Cited by 55 publications

References 40 publications

Induction of Oxidative Stress Responses by Dioxin and other Ligands of the Aryl Hydrocarbon Receptor

Induction of Oxidative Stress Responses by Dioxin and other Ligands of the Aryl Hydrocarbon Receptor

Accumulation of M1dG DNA adducts after chronic exposure to PCBs, but not from acute exposure to polychlorinated aromatic hydrocarbons

Health Risk from Exposure to PCDD/Fs from a Waelz Plant in Central Taiwan

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