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

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). 

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. 

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-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. 

Poiger H, Weber H, Schlatter CH. 1982. Special aspects of metabolism and kinetics ofTCDD in dogs and rats Assessment of toxicity of TCDD-metabolites(s) in guinea pigs. In Hutzinger O, Frei RW, Merian E, et al., eds. Chlorinated dioxins and related compounds Impact on the environment. New York, NY Pergamon Press, 317-325. 

Weber H, Poiger H, Schlatter C. 1982. Acute oral toxicity of TCDD-metabolites in male guinea pigs. Toxicol Lett 14 117-122. 

TCDD is 0.6 yg/kg of body weight for male guinea pigs. Table I shows the acute toxicity of TCDD and the considerable species-dependence of TCDD (9). Reasons for these large differences may be different biochemical elimination or degradation pathways for different animals. 

The comparative data on the acute lethality of the chlorinated dibenzo-p-dioxins and furans in laboratory animals are included in Table I. Evaluation of these data indicates that TCDD is the most toxic of this series. For the guinea pig, the single dose oral LD50 value is reported to be 0.6-2.0 yg/kg B.W., while in the hamster the single dose oral LD50 value is reported to be 1157-5051 yg/kg B.W. 

The biologic factors that account for this large difference (up to 5000 fold) in species susceptibility in acute toxicity have not yet been defined. The other laboratory animal species (mouse, rat, monkey, rabbit and dog) in which TCDD has been tested have single dose oral LD50 values that are found to be somewhere between the most sensitive species (guinea pig) and the least sensitive species (hamster). 

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