birth, increased number of stillborns, and reduced survival and growth of 

 young in both the F^ and F2 generations. Reproduction was not affected in 

 rats at daily dosages of 0.001 ug/kg body weight, which are equivalent to 12 

 to 30 ppt or ng/kg of 2,3,7,8-TCDD in the diet. Abortion and weight loss were 

 reported in rhesus monkeys ( Macaca mulatta ) at dietary levels as low as 50 ppt 

 2,3,7,8-TCDD (about 0.0017 ug/kg body weight daily) after 7 to 29 months. 

 However, comparatively high dosages (200 ppt in diets equivalent to 0.0095 

 ug/kg body weight daily) could be tolerated by monkeys for short periods (3X 

 weekly for 3 weeks) with no adverse effects on reproduction. Higher dose 

 levels for extended periods (i.e., 500 ppt in diets equivalent to about 0.011 

 ug/kg body weight daily for 9 months) caused death (63%) or, among survivors, 

 abortion, chloracne, nail loss, scaly and dry skin, and progressive weakness. 

 Most treated monkeys remained fairly alert to external stimuli until just 

 prior to death. On removal from the 500 ppt 2,3,7,8-TCDD diet and transfer to 

 an uncontaminated diet, a severely affected monkey became pregnant and gave 

 birth to a well -developed infant after an uneventful gestation. This suggests 

 that some 2,3,7,8-TCDD damage effects are not permanent. 



Androgenic deficiency in male rats given a single oral dose of 15 ug 

 2,3,7,8-TCDD/kg BW was evident as early as 2 days posttreatment, with 

 persistence up to 12 days. ' These deficiencies may account for male 

 reproductive pathology and dysfunction in rats treated with overtly toxic 

 doses of TCDD. Findings included depression in plasma testosterone 

 concentrations, as well as decreased weight of seminal vesicles (by 68%), 

 ventral prostate gland (by 48%), testes, and epididymis (Moore et al. 1985). 



Accumulation of 2,3,7,8-TCDD is reported in the liver of rats during 

 lifetime exposure to diets containing 0.022 ug 2,3,7,8-TCDD/kg (Newton and 

 Snyder 1978), or when administered orally at 0.01 ug/kg body weight once a 

 week for 45 weeks (Cantoni et al . 1981). Liver residues of rats fed 

 2,3,7,8-TCDD were 0.54 ug/kg, or about 25X dietary levels; livers of rats 

 dosed orally contained 1.05 ug/kg, or about 2.3X the total dose received on a 

 unit weight basis. 



Unlike toxicity, elimination rates of accumulated 2,3,7,8-TCDO were 

 within a relatively narrow range. The estimated retention times of 

 2,3,7,8-TCDD in small laboratory mammals (rats, mice, guinea pigs, and 

 hamsters) extended from 10.8 to 30.2 days for 50% elimination and seemed to be 

 little influenced by species, concentration administered, duration of dose, or 

 route of administration (Blair 1973; Olson et al. 1980b; NRCC 1981; Koshakji 

 et al. 1984). 



Histopathological effects have been reported in rabbits and horses 

 poisoned by 2,3,7,8-TCDO. Rabbits surviving exposure to an industrial 

 accident in Seveso, Italy, in which 2,3,7,8-TCDD was released, had edema, 

 hemorrhagic tracheitis, pleural hemorrhage, and dystrophic lesions of hepatic 

 tissue (Fanelli et al. 1980b). Horses from Missouri that died after waste 

 oil contaminated with 2,3,7,8-TCDD was applied as a dust control agent in 

 riding arenas had liver lesions, skin hyperkeratosis, gastric ulcers, and lung 

 and kidney lesions (Kimbrough 1984). Since 2,3,7,8-TCDD is an extremely 



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