The Use of Toxic Equivalency Factor Distributions in Probabilistic Risk Assessments for Dioxins, Furans, and PCBs

Toxic equivalency factors (TEFs) for 2,3,7,8-substituted polychlorinated dibenzo-p-dioxins (PCDD) and dibenzofurans (PCDFs) and coplanar polychlorinated biphenyl (PCB) congeners have been developed by the World Health Organization (WHO). Each TEF was derived from a range of relative potency (REP) es...

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Published inJournal of Toxicology and Environmental Health, Part A Vol. 66; no. 6; pp. 533 - 550
Main Authors Finley, Brent, Connor, Kevin, Scott, Paul
Format Journal Article
LanguageEnglish
Published London Informa UK Ltd 28.03.2003
Taylor and Francis
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Abstract Toxic equivalency factors (TEFs) for 2,3,7,8-substituted polychlorinated dibenzo-p-dioxins (PCDD) and dibenzofurans (PCDFs) and coplanar polychlorinated biphenyl (PCB) congeners have been developed by the World Health Organization (WHO). Each TEF was derived from a range of relative potency (REP) estimates obtained from in vivo and in vitro studies wherein the potency of the congener was evaluated relative to 2,3,7,8-TCDD (or some other appropriate benchmark). For most congeners, the range of REP values spans several orders of magnitude, and the degree of conservatism varies widely among the congeners. Although some TEFs are greater than the maximum REP value, others are less than the minimum. This suggests that the point estimate TEFs introduce a significant amount of variability and uncertainty into the PCB and PCDD/F risk assessment process. The use of REP data distributions, rather than point estimate TEFs, would permit a more informed evaluation of the variability and uncertainty in the attendant risk estimates. Further, a standardized method of choosing a TEF from an REP distribution would ensure a uniform degree of conservatism in the TEF values. In this analysis, distributions of REP values were derived for the coplanar PCBs and 2,3,7,8-substituted PCDD/Fs. There are 936 REP values in the WHO database; the number of values per congener ranges from 1 (1,2,3,7,8,9-HxCDF) to 117 (PCB126). Twenty REP values qualified by WHO as "<" were replaced with one-half the stated value; 65 values qualified as ">" were not used. Fit tests indicate that most distributions are lognormal. Mean, standard deviation, and 50th and 95th percentile values for each REP distribution are presented. In general, the WHO TEFs for the PCDD/Fs are at the upper bound (75th percentile or greater) of the underlying REP distributions, while the PCB TEFs tend to be more representative of the central tendency of the underlying REP distribution. A simplistic weighting scheme that emphasizes long-term in vivo studies suggests that the REP distributions may not be overly sensitive to weighting techniques--that is, the statistical descriptors of the weighted distributions were similar to those of the unweighted distributions. A case study using fish tissue PCB and PCDD/F data suggests that in some settings the use of WHO TEFs may understate upper bound PCB risks relative to PCDD/F risks. A preliminary sensitivity analysis suggests that measurement endpoint, tissue-type and species (or strain) may be significant contributors to the variability and heterogeneity in the underlying REP data for some congeners. Although there are fundamental shortcomings inherent in any TEF scheme, evidence suggests that some form of REP distributions should be used in lieu of or in addition to point estimate TEFs in settings where PCBs and PCDD/Fs are commingled.
AbstractList Toxic equivalency factors (TEFs) for 2,3,7,8-substituted polychlorinated dibenzo-p-dioxins (PCDD) and dibenzofurans (PCDFs) and coplanar polychlorinated biphenyl (PCB) congeners have been developed by the World Health Organization (WHO). Each TEF was derived from a range of relative potency (REP) estimates obtained from in vivo and in vitro studies wherein the potency of the congener was evaluated relative to 2,3,7,8-TCDD (or some other appropriate benchmark). For most congeners, the range of REP values spans several orders of magnitude, and the degree of conservatism varies widely among the congeners. Although some TEFs are greater than the maximum REP value, others are less than the minimum. This suggests that the point estimate TEFs introduce a significant amount of variability and uncertainty into the PCB and PCDD/F risk assessment process. The use of REP data distributions, rather than point estimate TEFs, would permit a more informed evaluation of the variability and uncertainty in the attendant risk estimates. Further, a standardized method of choosing a TEF from an REP distribution would ensure a uniform degree of conservatism in the TEF values. In this analysis, distributions of REP values were derived for the coplanar PCBs and 2,3,7,8-substituted PCDD/Fs. There are 936 REP values in the WHO database; the number of values per congener ranges from 1 (1,2,3,7,8,9-HxCDF) to 117 (PCB126). Twenty REP values qualified by WHO as "<" were replaced with one-half the stated value; 65 values qualified as ">" were not used. Fit tests indicate that most distributions are lognormal. Mean, standard deviation, and 50th and 95th percentile values for each REP distribution are presented. In general, the WHO TEFs for the PCDD/Fs are at the upper bound (75th percentile or greater) of the underlying REP distributions, while the PCB TEFs tend to be more representative of the central tendency of the underlying REP distribution. A simplistic weighting scheme that emphasizes long-term in vivo studies suggests that the REP distributions may not be overly sensitive to weighting techniques--that is, the statistical descriptors of the weighted distributions were similar to those of the unweighted distributions. A case study using fish tissue PCB and PCDD/F data suggests that in some settings the use of WHO TEFs may understate upper bound PCB risks relative to PCDD/F risks. A preliminary sensitivity analysis suggests that measurement endpoint, tissue-type and species (or strain) may be significant contributors to the variability and heterogeneity in the underlying REP data for some congeners. Although there are fundamental shortcomings inherent in any TEF scheme, evidence suggests that some form of REP distributions should be used in lieu of or in addition to point estimate TEFs in settings where PCBs and PCDD/Fs are commingled.
In recently refining toxic equivalency factor (TEF) values for PCDDs, PCDFs, and PCBs, WHO evaluated all relevant in vitro and in vivo studies and selected relative estimate of potency (REP) data that met specific criteria. In this study, the utility of developing REP distributions to represent PCDD/F and PCB TEFs is examined by comparing the degree of conservatism among the WHO TEFs, identifying REP distributions that best fit the existing data, and presenting a case study comparison of the risk estimates obtained using the WHO point TEFs versus the REP distributions derived here. Results show that there is significantly more variability associated with the PCB TEFs than with the PCDD/F TEFs, and the WHO PCB TEFs also appear to be generally less conservative than the PCDD/F TEFs. Results from the case study reveal that, when the WHO TEFs are replaced by REP distributions, the upper-bound PCB risk increases approximately tenfold, while the upper-bound PCDD/F risk remains unchanged.
Author Finley, Brent
Scott, Paul
Connor, Kevin
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Keywords Toxicity
Chlorine Organic compounds
Risk assessment
Toxic equivalency factor
Aromatic compound
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Polychlorobiphenyl
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Snippet Toxic equivalency factors (TEFs) for 2,3,7,8-substituted polychlorinated dibenzo-p-dioxins (PCDD) and dibenzofurans (PCDFs) and coplanar polychlorinated...
In recently refining toxic equivalency factor (TEF) values for PCDDs, PCDFs, and PCBs, WHO evaluated all relevant in vitro and in vivo studies and selected...
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SubjectTerms Animals
Biological and medical sciences
Chemical and industrial products toxicology. Toxic occupational diseases
Dioxins - toxicity
Endpoint Determination
Environmental Pollutants - toxicity
Humans
Medical sciences
Models, Statistical
Polychlorinated Biphenyls - toxicity
Polychlorinated Dibenzodioxins - analogs & derivatives
Polychlorinated Dibenzodioxins - toxicity
Risk Assessment
Sensitivity and Specificity
Soil Pollutants - toxicity
Structure-Activity Relationship
Toxicology
Various organic compounds
Title The Use of Toxic Equivalency Factor Distributions in Probabilistic Risk Assessments for Dioxins, Furans, and PCBs
URI https://www.tandfonline.com/doi/abs/10.1080/15287390306353
https://www.ncbi.nlm.nih.gov/pubmed/12712595
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Volume 66
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