potent porphyrogenic agent, it is probable that these animals also exhibited 



porphyria, a condition characterized by fragility of the skin, 



photosensitivity, and accumulation of porphyrins in the liver (Cantoni et al . 

 1981). 



Teratogenic and fetotoxic effects of 2,3,7,8-TCDD are well -documented in 

 several species of animals (Harless et al. 1982; Kociba and Schwetz 1982a, b; 

 Kimbrough 1984; Weber et al . 1985). Cleft palate in young mice was associated 

 with daily dosages of 1.0 ug 2,3,7,8-TCDD per kg body weight in pregnant 

 females (no-effect level at 0.1 ug/kg), and intestinal hemorrhage was found in 

 sensitive strains of rats given daily dosages of 0.125 ug/kg body weight 

 (no-effect level at 0.03 ug/kg) (Kociba and Schwetz 1982a, b). The 

 2,3,7,8-TCDD isomer has been studied for carcinogenic potential in rats and 

 mice. There is a good correlation between carcinogenicity in both species and 

 long-term ingestion of higher dose levels that induce toxicity. In rats, 

 carcinomas in liver, pharynx, skin, lung, and thyroid were documented at daily 

 dosages of 0.01 to 0.1 ug of 2,3,7,8-TCDD/kg body weight; comparable values 

 for mice were 0.03 to 0.07 ug/kg body weight (Kociba and Schwetz 1982a, b). No 

 response occurred at continuous daily dose levels of 0.001 to 0.0014 ug/kg 

 body weight in rats and 0.001 to 0.03 in mice. Carcinogenic or cocarcinogenic 

 effects were also induced by 1,2,3,6,7,8-hexa CDD and 1,2,3,7,8,9-hexa CDD, 

 but only at higher dose levels (Rappe 1984). It appears that 2,3,7,8-TCDO has 

 a greater effect on growth, survival, and reproduction of animals than on 

 tumor formation. 



Interaction effects of PCDDs with other polychlorinated compounds or 

 mixtures are not extensively documented. For example, certain polychlorinated 

 hexachlorobiphenyls (PCBs) have a low toxic potency to induce cleft palate 

 deformities in mice (Birnbaum et al . 1985). However, mixtures of 2,3,7,8-TCDn 

 and 2,3,4,5,3' ,4' hexachlorobiphenyl resulted in a 10-fold increase in 

 incidence of cleft palate in mice. Thus, the toxicity of compounds such as 

 2,3,7,8-TCDD may be enhanced by compounds of relatively low acute toxicity 

 such as selected PCBs. Birnbaum et al . (1985) concluded that the widespread 

 environmental occurrence of such combinations suggests a need for further 

 evaluation of the mechanism of this interaction. 



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