positions (2,3,7, 8 positions) and at least one of the adjacent ring positions 

 being nonhalogenated (Kociba and Schwetz 1982a, b). Comparative toxicity data 

 for selected PCDD isomers to the guinea pig ( Cavia sp.) and the mouse ( Mus 

 sp.) confirmed this generalization and demonstrated significant interspecies 

 differences in sensitivity (Table 5). Other PCDD isomers tested (2,8-di CDD, 

 octa-CDD) were relatively nontoxic to mice and guinea pigs (NRCC 1981). 



Acute toxicity studies with 2>,3,7,8-TCDD have shown marked 

 differences--up to 8,400X--between the single oral LD-50 dose for the guinea 

 pig and the hamster ( Cricetus sp.) (Table 6). The acute oral LD-50 value of 

 0.6 ug/kg body weight for guinea pigs, suggests that 2,3,7,8-TCDD may be the 

 most toxic compound ever tested on small laboratory animals. The unusual 

 resistance of hamsters may be associated with its enhanced rate of metabolism 

 and excretion of 2,3,7,8-TCDD relative to other PCDD isomers examined (Olson 

 et al. 1980b; NRCC 1981). Poisoning in mammals by 2,3,7,8-TCDD is typically 

 characterized by loss of body weight and delayed lethality; large interspecies 

 differences exist in lethal dosages and toxic effects (Vos 1978; Neal et al . 

 1979; Kociba and Schwetz 1982a, b; Josephson 1983; Matsumura 1983; Kimbrough 

 1984; Seefeld et al . 1984). For example, 2,3,7,8-TCDD produces prominent 

 chloracne-type skin lesions in man and monkeys, edema formation in birds, and 

 severe liver damage in rats, mice, and rabbits. 



Intraspecies differences in sensitivity to 2,3,7,8-TCDD--up to 14 

 fold--were recently reported among 3 strains of mice; no reasons were given to 

 account for these differences. Oral LD-50 (30 day) values varied from 182 ug 

 2,3,7,8-TCDD per kg body weight in strain C57, the most sensitive strain 

 tested, and 296 for strain BD6, to 2,570 for strain DBA (Chapman and Schiller 

 1985). All 3 strains of mice evidenced a 25 to 34% weight loss prior to 

 death; however, there was no measurable decline in food consumption. 



Atrophy of the thymus is a consistent finding in mammals poisoned by 

 2,3,7,8-TCDD, and suppression of thymus-dependent cellular immunity, 

 particularly in young animals, may contribute to their death. Although the 

 mechanisms of 2,3,7,8-TCDD toxicity are unclear, current research areas 

 include the role of thyroid hormones (Rozman et al. 1984), interference with 

 plasma membrane functions (Matsumura 1983), alterations in ligand receptors 

 (Vickers et al . 1985), the causes of hypophagia (reduced desire for food) and 

 subsequent attempts to alter or reverse the pattern of weight loss (Courtney 

 et al. 1978; Seefeld et al . 1984; Seefeld and Peterson 1984), and excretion 

 kinetics of biotransformed metabolites (Koshakji et al . 1984). 



Developing mammalian fetuses are especially sensitive to 2,3,7,8-TCDD, 

 and maternal exposure results in increased frequencies of stillbirths. Among 

 live births, exposure to it produces teratogenic effects such as cystic 

 kidney, cleft palate, and spinal column deformities (Ramel 1978). Effects of 

 2,3,7,8-TCDD on reproduction are reported for rats (McNulty 1977; Murray et 

 al . 1979; Kociba and Schwetz 1982a, b) and monkeys (Ramel 1978; Barsotti et al . 

 1979; NRCC 1981; Kociba and Schwetz 1982a, b). In a 3-generation study with 

 rats, daily dose levels of 0.01 ug of 2,3,7,8-TCDD/kg body weight (equivalent 

 to 120 to 290 ppt or ng/kg in the diet), produce decreased litter size at 



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