Quantitative cancer risk assessments for 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)

Obfuscating transparency?

“…MTD dose/response data can be made to fit virtually any of these functions, but so fitted functions result in low-dose extrapolations contrasting by several orders of magnitude. (10) Theoretically the choice of a model could be validated by reliable mechanistic evidence of the underlying biological processes, but the utter complexity of possible mechanisms make such evidence generally speculative. In practice, the choice appears to depend on whether low-dose extrapolations suit the ideological, conjectural or precautionary disposition of a risk assessor or of an Agency policy.…”

Obfuscating transparency?

“…MTD dose/response data can be made to fit virtually any of these functions, but so fitted functions result in low-dose extrapolations contrasting by several orders of magnitude. (10) Theoretically the choice of a model could be validated by reliable mechanistic evidence of the underlying biological processes, but the utter complexity of possible mechanisms make such evidence generally speculative. In practice, the choice appears to depend on whether low-dose extrapolations suit the ideological, conjectural or precautionary disposition of a risk assessor or of an Agency policy.…”

A Response to Comments

“…Others (e.g., see Refs. [3][4][5] question the reliability of point estimates of risk generically, including models such as the TD,,.…”

Statistically Enhanced Spectral Counting Approach to TCDD Cardiac Toxicity in the Adult Zebrafish Heart

“…The chemical stability and hydrophobicity of TCDD has contributed to its widespread distribution in the environment and accumulation within the food chain, which poses health hazards to multiple animal species including man. TCDD causes a wide spectrum of toxic effects in experimental animals and human beings including fetotoxicity 4, 5 , hepatotoxicity 6, 7 , immunotoxicity 8, 9 , teratogenicity 10, 11 and carcinogenicity 12–15 . TCDD is known to cause disruption of cardiovascular development in vertebrates 16–19 .…”

“…The chemical stability and hydrophobicity of TCDD has contributed to its widespread distribution in the environment and accumulation within the food chain, which poses health hazards to multiple animal species including man. TCDD causes a wide spectrum of toxic effects in experimental animals and human beings including fetotoxicity, , hepatotoxicity, , immunotoxicity, , teratogenicity , and carcinogenicity. − TCDD is known to cause disruption of cardiovascular development in vertebrates. − The zebrafish ( Danio rerio ) has been used as an important vertebrate model to study the cardiovascular toxicity of TCDD, and a spectrum of developmental defects have been reported such as smaller ventricle size, reduced cardiac myocyte numbers, altered heart morphology, pericardial edema, hemorrhage and circulatory failure. ,, The observed heart defects are associated with altered gene expression by TCDD as revealed by microarray analysis . These studies revealed a very rapid induction of putative aryl hydrocarboan receptor (AHR) target genes within 1–4 h of TCDD exposure, followed by a striking down-regulation of a large set of genes involved in cell cycle progression .…”

Obfuscating transparency?

“…MTD dose/response data can be made to fit virtually any of these functions, but so fitted functions result in low-dose extrapolations contrasting by several orders of magnitude. (10) Theoretically the choice of a model could be validated by reliable mechanistic evidence of the underlying biological processes, but the utter complexity of possible mechanisms make such evidence generally speculative. In practice, the choice appears to depend on whether low-dose extrapolations suit the ideological, conjectural or precautionary disposition of a risk assessor or of an Agency policy.…”

A Response to Comments

“…Others (e.g., see Refs. [3][4][5] question the reliability of point estimates of risk generically, including models such as the TD,,.…”

Statistically Enhanced Spectral Counting Approach to TCDD Cardiac Toxicity in the Adult Zebrafish Heart

“…The chemical stability and hydrophobicity of TCDD has contributed to its widespread distribution in the environment and accumulation within the food chain, which poses health hazards to multiple animal species including man. TCDD causes a wide spectrum of toxic effects in experimental animals and human beings including fetotoxicity 4, 5 , hepatotoxicity 6, 7 , immunotoxicity 8, 9 , teratogenicity 10, 11 and carcinogenicity 12–15 . TCDD is known to cause disruption of cardiovascular development in vertebrates 16–19 .…”

“…The chemical stability and hydrophobicity of TCDD has contributed to its widespread distribution in the environment and accumulation within the food chain, which poses health hazards to multiple animal species including man. TCDD causes a wide spectrum of toxic effects in experimental animals and human beings including fetotoxicity, , hepatotoxicity, , immunotoxicity, , teratogenicity , and carcinogenicity. − TCDD is known to cause disruption of cardiovascular development in vertebrates. − The zebrafish ( Danio rerio ) has been used as an important vertebrate model to study the cardiovascular toxicity of TCDD, and a spectrum of developmental defects have been reported such as smaller ventricle size, reduced cardiac myocyte numbers, altered heart morphology, pericardial edema, hemorrhage and circulatory failure. ,, The observed heart defects are associated with altered gene expression by TCDD as revealed by microarray analysis . These studies revealed a very rapid induction of putative aryl hydrocarboan receptor (AHR) target genes within 1–4 h of TCDD exposure, followed by a striking down-regulation of a large set of genes involved in cell cycle progression .…”

Obfuscating transparency?

“…MTD dose/response data can be made to fit virtually any of these functions, but so fitted functions result in low-dose extrapolations contrasting by several orders of magnitude. (10) Theoretically the choice of a model could be validated by reliable mechanistic evidence of the underlying biological processes, but the utter complexity of possible mechanisms make such evidence generally speculative. In practice, the choice appears to depend on whether low-dose extrapolations suit the ideological, conjectural or precautionary disposition of a risk assessor or of an Agency policy.…”

A Response to Comments

“…Others (e.g., see Refs. [3][4][5] question the reliability of point estimates of risk generically, including models such as the TD,,.…”

Statistically Enhanced Spectral Counting Approach to TCDD Cardiac Toxicity in the Adult Zebrafish Heart

“…The chemical stability and hydrophobicity of TCDD has contributed to its widespread distribution in the environment and accumulation within the food chain, which poses health hazards to multiple animal species including man. TCDD causes a wide spectrum of toxic effects in experimental animals and human beings including fetotoxicity 4, 5 , hepatotoxicity 6, 7 , immunotoxicity 8, 9 , teratogenicity 10, 11 and carcinogenicity 12–15 . TCDD is known to cause disruption of cardiovascular development in vertebrates 16–19 .…”

“…The chemical stability and hydrophobicity of TCDD has contributed to its widespread distribution in the environment and accumulation within the food chain, which poses health hazards to multiple animal species including man. TCDD causes a wide spectrum of toxic effects in experimental animals and human beings including fetotoxicity, , hepatotoxicity, , immunotoxicity, , teratogenicity , and carcinogenicity. − TCDD is known to cause disruption of cardiovascular development in vertebrates. − The zebrafish ( Danio rerio ) has been used as an important vertebrate model to study the cardiovascular toxicity of TCDD, and a spectrum of developmental defects have been reported such as smaller ventricle size, reduced cardiac myocyte numbers, altered heart morphology, pericardial edema, hemorrhage and circulatory failure. ,, The observed heart defects are associated with altered gene expression by TCDD as revealed by microarray analysis . These studies revealed a very rapid induction of putative aryl hydrocarboan receptor (AHR) target genes within 1–4 h of TCDD exposure, followed by a striking down-regulation of a large set of genes involved in cell cycle progression .…”