Guinea pigs, 2,3,7,8-TCDD

TCDF is not very toxic to the mouse (acute oral LDjq < 6000 pg/kg) but is highly toxic to the guinea pig (acute oral LD50 5-10 pg/kg). Symptoms of toxicity in the gninea pig were similar to those fonnd with 2,3,7,8-TCDD. Thus, the selectivity pattern was similar to that for 2,3,7,8-TCDD, but toxicity was considerably less (see Environmental Health Criteria 88). 

TCDD is much more toxic than the other chlorodibenzodioxins studied the LD.50 ranged from 0.6 ixg/kg in male guinea pigs to 115 ftg/kg in rabbits. Dogs appear to be less sensitive than rabbits. Others have reported 100% mortality in rabbits treated with 10 / g/kg (10) and chick embryos treated with 0.05 yg/egg (4). 

We were surprised to find that no method existed that was sensitive enough to detect TCDD in animal tissues even after administration in some species of lethal doses. An example is the guinea pig, the most susceptible species of the few that have been tested, and therefore a good choice for establishing desirable limits of detection. The lethal single oral dose (LD50) in males of this species is 0.6 /xg/kg body weight... 

This means that if all of the TCDD were retained, the level of TCDD would be less than 1 part per billion (ppb) in the whole animal. The lowest reported limit of detection for TCDD in whole tissue is 50 ppb (6). Thus, a guinea pig could be killed with TCDD, and it would be impossible to establish this fact with the analytical procedures in current use. 

Accumulation of 2,3,7,8-TCDD is reported in the liver of rats during lifetime exposure to diets containing 0.022 pg 2,3,7,8-TCDD/kg (Newton and Snyder 1978), or when administered orally at 0.01 pg/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 pg/kg, or about 25 times dietary levels livers of rats dosed orally contained 1.05 pg/kg, or about 2.3 times the total dose received on a unit weight basis. Unlike toxicity, elimination rates of accumulated 2,3,7,8-TCDD 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... 

Dioxins are extremely toxic compounds. LD50 for the most toxic dioxin (2,3,7,8-TCDD) at intragastric injection was 0,6-2,0 mcg/kg for guinea pigs, 3000-5000 mcg/kg for various species of hamsters, about 70 mcg/kg for monkeys and 25-45 mcg/kg for rats. 

This substance (TCDD) is very toxic. In addition to the dermatitis it produces, it is a potent teratogen (induces birth abnormalities). The lethal dose is less than 10 6 g for guinea pigs. Its presence in 2,4,5-T can be eliminated, but the conditions by which it is formed are pertinent to our present discussion. 

Decreased body weight gain was observed in guinea pigs after a single dose of 6 g/kg 2,3,7,8-TCDD in oil vehicle but not after 12 g/kg in soil (Umbreit et al. 1985). A decreased weight gain was recorded in... 

Relative spleen weight was increased at 0.047 g 2,3,7,8-TCDD/kg/day. Decreased cell-mediated immunity was found in mice and guinea pigs exposed by gavage to 0.71 g/kg/day for 4 weeks and 0.03 g/kg/day for 8 weeks, respectively (Vos et al. 1973). Guinea pigs seem to be especially sensitive to 2,3,7,8-TCDD toxicity an intermediate-duration exposure to 0.001 g/kg/day reduced the lymphocyte counts, and exposure to 0.03 g/kg/day caused decreased humoral immunity and thymic atrophy (Vos et al. 1973). A recent study examined the effect of low-level dietary exposure to... 

TCDD given to the most sensitive species, guinea pigs, in the diet (DeCaprio et al. 1986). The NOAEL value of 0.0007 g/kg/day was used to derive an intermediate-duration oral MRL for... 

TCDD-treated dogs is about 100 times less toxic to rats and guinea pigs than pure 2,3,7,8-TCDD (Poiger et al. 1982). The lack of toxicity of the 2,3,7,8-TCDD metabolites suggests that autoinduction of its own metabolism in animals is a detoxification mechanism. 

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