Comparative developmental toxicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin in the hamster, rat and guinea pig.
2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is a persistent environmental contaminant capable of causing a wide variety of adverse health effects including teratogenesis and altered development. The objective of this study was to compare the developmental toxicity of TCDD in the hamster, rat and guinea pig, which in mature animals exhibit a relatively low, medium and high sensitivity to TCDD, respectively. A single oral dose of TCDD was administered to pregnant rats (0, 1.5, 3.0, 6.0 or 18.0microg/kg) on gestation day 10, pregnant hamsters (0, 1.5, 3.0, 6.0 or 18.0microg/kg) on gestation day 9 and pregnant guinea pigs (0, 0.15 or 1.5microg/kg) on gestation day 14 with fetal analysis on gestation day 20, 15 and 56, respectively. The developmental toxicity of TCDD in the three species included increased fetal mortality, alterations to fetal body weight, body length, organ weight and significant changes to the fetal white blood cell differential counts. Additionally, teratogenic responses were observed in the hamster and rat consisting of cleft palate, kidney congestion, hydronephrosis and intestinal hemorrhaging. Furthermore, the results from this study demonstrate that despite the up to 5000-fold interspecies variability to the acute lethal potency of TCDD observed in mature guinea pigs, rats and hamsters, the developing fetus is uniquely vulnerable to gestational TCDD exposure and displays approximately a 10-fold variability in fetal lethal potency in these species. Together, these results will assist efforts to reduce the uncertainty in the risk assessment for TCDD in sensitive populations, such as the developing embryo and fetus.
Kransler
Kevin M
KM
Department of Pharmacology and Toxicology, School of Medicine and Biomedical Sciences, University at Buffalo, The State University of New York, Buffalo, NY 14214, USA.
McGarrigle
Barbara P
BP
Olson
James R
JR
D000818:Animals; D006224:Cricetinae; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D004785:Environmental Pollutants / Q000633:toxicity*; D005260:Female; D047109:Fetal Development / Q000187:drug effects; D006168:Guinea Pigs; D007958:Leukocyte Count; D007962:Leukocytes / Q000166:cytology / Q000187:drug effects; D008431:Maternal-Fetal Exchange; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology; D000072317:Polychlorinated Dibenzodioxins / Q000633:toxicity*; D011247:Pregnancy; D051381:Rats; D013723:Teratogens / Q000633:toxicity*
D004785:Environmental Pollutants; D000072317:Polychlorinated Dibenzodioxins; D013723:Teratogens; D003577:Cytochrome P-450 Enzyme System