Immunotoxicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin in a complex environmental mixture from the Love Canal

Silkworth, Jay B.; Cutler, D. S.; Sack, G.

doi:10.1016/0272-0590(89)90047-x

Cited by 31 publications

(2 citation statements)

References 13 publications

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“…The calculated and experimentally derived TEQs for this mixture have been analyzed using different TEF values and there was a good correspondence between the two sets of values for several different responses in the guinea pig. This research group has extensively investigated soil extracts and organic phase leachate from Love Canal, which was a complex mixture of PCDDs/PCDFs (low levels) plus numerous other compounds including chlorinated benzenes, toluenes, and hydrocarbons [48][49][50]. They utilized multiple AhR-mediated responses in Ah-responsive and less responsive mice and their results indicated that the toxicity of the mixtures was both additive or non-additive (synergism or antagonism) depending on the specific response and species.…”

Section: Use and Validation Of Tefs For Hahsmentioning

confidence: 99%

Limitations of the toxic equivalency factor approach for risk assessment of TCDD and related compounds

Safe

1997

Teratog. Carcinog. Mutagen.

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Halogenated aromatic hydrocarbons (HAHs), such as polychlorinated biphenyls (PCBs), dibenzo‐ρ‐dioxins (PCDDs), and dibenzofurans (PCDFs), are industrial compounds or by‐products that have been widely identified as environmental contaminants. Hazard and risk assessment of complex HAH mixtures have utilized a toxic equivalency factor (TEF) approach, where the toxic equivalents (TEQs) of any mixture are equal to the sum of the concentration of individual (i) congeners times their potencies (TEFi) relative to 2,3,7,8‐tetrachlorodibenzo‐ρ‐dioxin (TCDD, TEF = 1.0). TEQ = Σ [PCDDi] · TEFi + Σ [PCDFi] · TEFi + Σ [PCBi] · TEFi The TEQ (or TCDD equivalents) can be readily calculated from analytical data and provides an estimate of the toxicity of any mixture containing HAHs. Several in vivo and in vitro studies with some PCDD/PCDF and PCB mixtures have demonstrated correlations between experimentally determined and calculated TEQs. However, results of several studies have also shown that for specific responses, the TEQ for some HAH mixtures are non‐additive. For example, PCB mixtures and individual PCB congeners such as 2,2′,4,4′,5,5′‐hexachlorobiphenyl inhibit toxic and biochemical responses induced by TCDD and related compounds. Another problem associated with hazard and risk assessment of background exposure to HAHs is the relative contribution of trace levels of HAHs (exodioxins) compared to relatively high exposure to naturally occurring aryl hydrocarbon receptor (AhR) agonists, which act through the same mechanistic pathway. Teratogenesis Carcinog. Mutagen. 17:285–304, 1997/98. © 1998 Wiley‐Liss, Inc.

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Section: Use and Validation Of Tefs For Hahsmentioning

confidence: 99%

Limitations of the toxic equivalency factor approach for risk assessment of TCDD and related compounds

Safe

1997

Teratog. Carcinog. Mutagen.

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“…For example, exposure to PCBs at 18 months of age is associated with blunted vaccine efficacy at 5 and 7 years of age in children (Heilmann et al, 2010). In peripheral tissues of adult rodents, exposure to industrial mixtures of different PCBs, called Aroclors (A) 1242, 1248, and 1254, suppressed adaptive immune responses (Exon et al, 1985;Davis and Safe, 1989;Silkworth et al, 1989;Hamers et al, 2011), while other specific PCB congeners increase innate immune responses (Choi et al, 2012). PCBs may also affect inflammatory molecules in the neural tissues, but this phenomenon has not been well-studied (Voie and Fonnum, 2000;Mariussen et al, 2002;Sipka et al, 2008).…”

Section: Introductionmentioning

confidence: 99%

Sex differences in effects of gestational polychlorinated biphenyl exposure on hypothalamic neuroimmune and neuromodulator systems in neonatal rats

Bell

Dryden

Will

et al. 2018

Toxicology and Applied Pharmacology

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Polychlorinated biphenyls (PCBs) are ubiquitous in the environment and exposure to them is associated with immune, endocrine and neural dysfunction. Effects of PCBs on inflammation and immunity are best described in spleen and blood, with fewer studies on neural tissues. This is an important gap in knowledge, as molecules typically associated with neuroinflammation also serve neuromodulatory roles and interact with hormones in normal brain development. The current study used Sprague-Dawley rats to assess whether gestational PCB exposure altered hypothalamic gene expression and serum cytokine concentration in neonatal animals given an immune challenge. Dams were fed wafers containing a mixture of PCBs at an environmentally relevant dose and composition (20 μg/kg, 1:1:1 Aroclor 1242:1248:1254) or oil vehicle control throughout their pregnancy. One day old male and female offspring were treated with an inflammatory challenge (lipopolysaccharide, LPS, 50 μg/kg, sc) or saline vehicle control approximately 3.5 h prior to tissue collection. Across both basal and activated inflammatory states, PCB exposure caused greater expression of a subset of inflammatory genes in the hypothalamus and lower expression of genes involved in dopamine, serotonin, and opioid systems compared to oil controls. PCB exposure also altered reactions to inflammatory challenge: it reversed the normal decrease in Esr2 hypothalamic expression and induced an abnormal increase in IL-1b and IL-6 serum concentration in response to LPS. Many of these effects were sex specific. Given the potential long-term consequences of neuroimmune disruption, our findings demonstrate the need for further research.

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Dioxins and Dioxin‐Like Chemicals

Gallo

Lippmann

2008

Environmental Toxicants

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Immunotoxicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin in a complex environmental mixture from the Love Canal

Cited by 31 publications

References 13 publications

Limitations of the toxic equivalency factor approach for risk assessment of TCDD and related compounds

Limitations of the toxic equivalency factor approach for risk assessment of TCDD and related compounds

Sex differences in effects of gestational polychlorinated biphenyl exposure on hypothalamic neuroimmune and neuromodulator systems in neonatal rats

Dioxins and Dioxin‐Like Chemicals

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