ToxSci Advance Access originally published online on June 23, 2005
Toxicological Sciences 2005 87(1):3-10; doi:10.1093/toxsci/kfi236
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
REVIEW |
Issues in Risk Assessment for Developmental Effects of 2,3,7,8-Tetrachlorodibenzo-p-Dioxin and Related Compounds
* Exponent, Inc., Alexandria, Virginia 22314; The Weinberg Group, Washington, DC 20036-2400; and Integrative Policy & Science, Inc., Washington, New Jersey 07882
Received March 2, 2005; accepted June 15, 2005
Recent risk assessments for 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and related compounds have focused on adverse effects observed in rodent offspring exposed while in utero during critical gestational periods as among the most sensitive adverse effects attributable to TCDD exposure. In addition, these risk assessments have converged on the use of body concentration (or "body burden") of TCDD as a dose metric superior to administered dose for cross-species comparisons and risk assessments, due to the interspecies differences in elimination kinetics and substantial persistence of these compounds. The detailed, although incomplete, data that are available on maternal–fetal distribution of TCDD and related compounds illustrate differences in distribution among these compounds that impact assessments on a body-burden basis. These data also demonstrate differences in distribution after subchronic or chronic administration compared to acute administration. Some data are now also available addressing inconsistencies that may arise from the use of TCDD toxic equivalency factors (TEFs), which were derived on an administered-dose basis, in evaluating responses to mixtures of dioxins on a body-burden basis in the context of chronic exposure situations. Finally, the use of body burden as a dose metric does not account for or eliminate the substantial differences in sensitivity to dioxin observed across species or between different strains of the same species and, thus, does not eliminate the need to consider the relative sensitivity of humans compared to laboratory animal models in risk assessments. Additional research areas that may increase the foundation for interspecies extrapolations are discussed.
Key Words: TCDD; 2,3,7,8-tetrachlorodibenzo-p-dioxin; TEF; TEQ; risk assessment.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  D. R. Bell, S. Clode, M. Q. Fan, A. Fernandes, P. M. D. Foster, T. Jiang, G. Loizou, A. MacNicoll, B. G. Miller, M. Rose, et al. Relationships between Tissue Levels of 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD), mRNAs, and Toxicity in the Developing Male Wistar(Han) Rat Toxicol. Sci., October 1, 2007; 99(2): 591 - 604. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P Guzelian, L Quattrochi, N Karch, L Aylward, and R Kaley Does dioxin exert toxic effects in humans at or near current background body levels?: an evidence-based conclusion Human and Experimental Toxicology, February 1, 2006; 25(2): 99 - 105. [Abstract] [PDF]
|
|