Developmental toxicity of 2,3,7,8-TCDD in the rat and hamster

Comparative developmental toxicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin in the hamster, rat and guinea pig

“…Although mature animals display a wide interspecies variability to the acute toxic effects of TCDD, demonstrated by the 5000-fold difference in the acute LD 50 among species, evidence suggests that the developing embryo and fetus are uniquely sensitive to TCDD (McNulty, 1984;Olson et al, 1990;Peterson et al, 1993). There has been frequent use of the rat Gray et al, 1997;Huuskonen et al, 1994;Ikeda et al, 2005;Mably et al, 1992a,b,c) and mouse (Birnbaum et al, 1991;Ko et al, 2002;Neubert et al, 1973;Thackaberry et al, 2005;Weber and Birnbaum, 1985;Willey et al, 1998) as model systems to study the developmental toxicity of TCDD.…”

“…There has been frequent use of the rat Gray et al, 1997;Huuskonen et al, 1994;Ikeda et al, 2005;Mably et al, 1992a,b,c) and mouse (Birnbaum et al, 1991;Ko et al, 2002;Neubert et al, 1973;Thackaberry et al, 2005;Weber and Birnbaum, 1985;Willey et al, 1998) as model systems to study the developmental toxicity of TCDD. However, only a few studies have utilized the hamster Olson and McGarrigle, 1992;Olson et al, 1990;Wolf et al, 1999) or guinea pig (Olson and McGarrigle, 1992). Our use of the guinea pig, rat and hamster (mature animal LD 50 values of 0.6-2, 22-60 and 1157-5051 g/kg, respectively) in this current study has allowed us to evaluate species that display a relatively low, medium and high sensitivity to TCDD.…”

“…There is upwards of a 5000-fold difference in the acute lethal potency between the guinea pig, rhesus monkey, rat, mouse and hamster with reported LD 50 values of 0.6-2, 1-70, 22-60, 114-536 and1157-5051 g/kg, respectively (McNulty, 1984;Olson et al, 1990). However, when compared to mature animals, the developing embryo and fetus are uniquely vulnerable to TCDD and related compounds.…”

Persistent hematologic and immunologic disturbances in 8-year-old Dutch children associated with perinatal dioxin exposure.

“…Shiverick and Muther (1983) showed that fetuses of pregnant rats treated with a daily oral dosage of 1 µg/kg TCDD had a 66% incidence of visceral lesions, characterized by intestinal hemorrhage. Olson et al (1990) found gastrointestinal bleeding to be the most sensitive indicator of in utero exposure to TCDD, in the fetuses of maternal rats exposed to 1.5 µg/kg. The incidence of bleeding was 7.7 ± 5.5%.…”

Developmental Effects of Dioxins

“…Thymic and splenic atrophy were observed in the fetus in several species, and subcutaneous edema was noted at higher doses in mouse fetuses. Hemorrhage, both in the gastrointestinal tract and in the kidney, were observed in rats and hamsters (32 Structural defects following dioxin exposure have been reported in the mouse at doses that do not cause either maternal or fetal toxicity. The best described malformation is cleft palate.…”