The relative susceptibility of animals and humans to the carcinogenic hazard posed by exposure to 2,3,7,8-TCDD: an analysis using standard and internal measures of dose.
An analysis of the carcinogenic dose-response for 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in humans and animals was performed based on measured tissue and serum concentrations and using alternatives to administered dose as the dosimetric. The TCDD-related carcinogenic response in rats (female rat liver tumors from Kociba et al., using revised pathology from Goodman and Sauer, was compared to that in humans (lung cancer rates in Fingerhut et al.,). Three dosimetries were used: serum lipid TCDD area-under-the-curve (AUC), peak serum lipid concentration (Cpeak) and average serum lipid concentration (Cavg). Rat serum concentration-time profiles were estimated based on measured adipose lipid TCDD concentrations at the end of the Kociba et al. bioassay, assuming first-order elimination and a half-life of 25 days. Human concentration-time profiles were estimated based on measured serum lipid TCDD concentrations and known dates of first and last exposure, with an assumed 7.5 year half-life and first-order elimination. Comparison of rat and human responses indicated that, using all three of these dosimetries, humans are much less sensitive than rats to the carcinogenic effects of TCDD. Regardless of the dosimetric chosen, the cancer mortality in humans in the NIOSH cohort, if due to TCDD, is relatively insensitive to dose as defined in Fingerhut et al., [3]. Our analysis indicates that human exposure to background levels of TCDD (about 5 ppt serum lipid concentration) is not likely to produce an incremental cancer risk.
Hays
S M
SM
ChemRisk, A Division of McLaren/Hart, Cleveland, OH 44122, USA.
Aylward
L L
LL
Karch
N J
NJ
Paustenbach
D J
DJ
D000273:Adipose Tissue / Q000737:chemistry; D000818:Animals; D001681:Biological Assay; D015197:Carcinogenicity Tests; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008099:Liver / Q000737:chemistry; D000072317:Polychlorinated Dibenzodioxins / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012015:Reference Standards; D018570:Risk Assessment
D000072317:Polychlorinated Dibenzodioxins