Toxic equivalents mixtures

Ah-receptor-mediated toxicity is particularly associated with the highly toxic compound 2,3,7,8-tetrachloro-dibenzo-p-dioxin (TCDD), commonly referred to as dioxin. TCDD, and the concept of toxicity equivalency factors (TEFs) based on TCDDs, will be dealt with in Chapter 7. The main point to make at this juncture is that the toxicity of each individual coplanar congener in a mixture can be expressed in terms of a toxic equivalent calculated relative to the toxicity of dioxin. Summation of the toxic equivalents of the individual coplanar PCBs gives a measure of the toxicity of the whole mixture, as expressed through the Ah receptor mechanism. 

Safe, S. (1998) Hazard and Risk Assessment of Chemical Mixtures Using the Toxic Equivalency Factor Approach. Environmental Health Perspectives, 106(Suppl. 4), 1051-1058. 

Newsted, J.L., J.P. Giesy, G.T. Ankley, D.E. Tillitt, R.A. Crawford, J.W. Gooch, P.D. Jones, and M.S. Denison. 1995. Development of toxic equivalency factors for PCB congeners and the assessment of TCDD and PCB mixtures in rainbow trout. Environ. Toxicol. Chem. 14 861-871. 

Commercial PCB mixtures frequently contain impurities that may contribute to the 2,3,7,8-TCDD toxic equivalency factor. These impurities may include other PCBs, dioxins, dibenzofurans, naphthalenes, diphenyl ethers and toluenes, phenoxy and biphenyl anisoles, xanthenes, xanthones, anthracenes, and fluorenes (Jones etal. 1993). PCB concentrations in avian tissues sometimes correlate positively with DDE concentrations (Mora et al. 1993). Eggs of peregrine falcons (Falco peregrinus) from California, for example, contained measurable quantities of various organochlorine compounds, including dioxins, dibenzofurans, mirex, hexachlorobenzene, and / ,//-DDE at 7.1 to 26.0 mg/kg FW PCB 126 accounted for 83% of the 2,3,7,8-TCDD equivalents, but its interaction with other detectable organochlorine compounds is largely unknown (Jarman et al. 1993). 

The dioxin toxic equivalency factor (TEF) approach is currently used worldwide for assessing and managing the risks posed by exposure to mixtures of certain dioxin-like compounds (DLCs). World Health Organization-TEF (WHO-TEE) values have been established for humans and mammals, birds, and (For new, refined values, see Ref. 12g.) It should be mentioned that 16 PCBs, the coplanar isomers with nonortho, monoortho, and diortho substitution by chlorine (overall, there are 209 isomers for this class of compounds) show dioxin-like toxic behavior. I-TE values are smaller, in the range of 0.0001-0.1. The most toxic isomers is 3,3, 4,4, 5-pentachlorodiphenyl with I-TE of 0.1. Polybrominated dibenzodioxins and furans with the 2,3,7,8 pattern also show dioxin-like toxicity, but their I-TE values are lower compared to PCDD/F. 

Hamm JI, Chen CY, Birnbaum LS A mixture of dioxin, furans, and non-ortho PCBs based upon consensus toxic equivalency factors produces dioxin-like reproductive effects. Toxicol Sci 2003 74 182. [PMID 12730615]... 

NORTH ATLANTIC TREATY ORGANISATION, COMMITTEE ON THE CHALLENGES of MODERN SOCIETY. International Toxicity Equivalency Factor (I-TEF) method of risk assessment for complex mixtures of dioxins and related compounds. Pilot study on international information exchange on dioxins and related compounds . CCMS Report Number 176, Environmental Protection Agency, Washington D.C., 1988. 

Although this public health statement will focus on CDDs, it is important to note that CDDs are found in the environment together with other structurally related chlorinated chemicals, such as chlorinated dibenzofurans (CDFs) and polychlorinated biphenyls (PCBs). Therefore, people are generally exposed to mixtures of CDDs and other classes of toxicologically and structurally similar compounds. 2,3,7,8-TCDD is one of the most toxic and extensively studied of the CDDs and serves as a prototype for the toxicologically relevant or dioxin-like CDDs. Based on results from animal studies, scientists have learned that they can express the toxicity of dioxin-like CDDs as a fraction of the toxicity attributed to 2,3,7,8-TCDD. For example, the toxicity of dioxin-like CDDs can be half or one tenth or any fraction of that of 2,3,7,8-TCDD. Scientists call that fraction a Toxic Equivalent Factor (TEF). More information on TEFs can be found in Section 2.5. 

Toxic Equivalency Factors (TEFs) and Toxic Equivalents (TEQs). Humans are exposed to complex mixtures of CDDs and other halogenated aromatic hydrocarbons such as CDFs and PCBs which... 

Stahl BU, Kettrup A, Rozman K. 1992. Comparative toxicity of four chlorinated dibenzo-p-dioxins (CDDs) and their mixture. Part I Acute toxicity and toxic equivalency factors (TEFs). Arch Toxicol 66(7) 471-7. 

TEQ Toxicity equivalent (TEQ) is defined as the product of the concentration, C , of an individual dioxin-like compound in a complex environmental mixture and the corresponding TCDD toxicity equivalency factor (TEF ) for that compound. The total TEQs is the sum of the TEQs for each of the congeners in a given mixture n Total TEQs = (C TEF ). i=l... 

FIGURE 4.2 Mortality of fathead minnows in relation to acetylcholinesterase activity.3 a As measured in the brain tissue following (A) a 14-day exposure to a ternary mixture of azinphos-methyl, diazinon, and chlorpyrifos in a concentration-response study and (B) a 7-day exposure to a ternary mixture of azinphos-methyl, diazinon, and chlorpyrifos applied as equipotent (toxic equivalent [TE]) mixtures. Note Dashed lines correspond to 50% reduction in AChE activity the dashed-dotted line corresponds to 50% mortality. Source Redrawn from Sibley et al. (2000). 

A tiered system for mixture extrapolation is proposed. The lowest tier is based on extrapolation using toxicological point-estimate information such as EC50 values. This translates into the use of toxic units, toxic equivalencies, and similar techniques. The use of the entire concentration-response relationships of the separate compounds is recommended for Tier-2, in conjunction with the use of either concentration or response addition as a modeling approach. In Tier-3, a mixed-model approach can be considered, to more specifically address considerations on toxic modes of action. In the latter case, the approach may be extended to allow incorporation of the responses of different ecological receptors (Tier-4). Research needs have been clearly identified in community-level mixture assessments. 

Safe S. 1998. Hazard and risk assessment of chemical mixtures using the toxic equivalency factor approach. Environ Hlth Perspect 106 1051-1062. 

NATO/CCMS (1988). In International Toxicity Equivalency Factors (I-TEF) Method of Risk Assessment for Complex Mixtures of Dioxin and Related Compounds, NATO, Brussels, Report no.176. 

Since dioxins and furans have varying levels of toxicity, emissions of mixtures of these compounds are typically expressed in TEQs (Toxic EQuivalents). TEQs relate the toxicity of all dioxin and furan compounds to the known toxicity of 2,3,7,8-TCDD using a weighting scheme adopted by the EPA and most European countries.1,2 Therefore, a quantity of combined PCDDs and PCDFs... 

As already introduced in Chapter 1, a widely used application of CA is the toxic equivalence factor (TEF) concept for the assessment of mixtures of polychlorinated dioxins and furans (PCDDs/Fs) (Van den Berg et al. 2006). Under the additional assumption of parallel dose-response curves, doses of specific PCDD/F isomers are all expressed in terms of the dose of a reference chemical, 2,3,7,8-... 

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