Significance of the dog as 'second animal species' in toxicity testing for establishing the lowest 'no-toxic-effect level'

Significance of the dog as 'second animal species' in toxicity testing for establishing the lowest 'no-toxic-effect level'

Appelman, L.M.
Feron, V.J.
Centraal Instituut voor Voedingsonderzoek TNO

1986

The toxicity data of 66 compounds adequately tested in the rat (as 'prime animal species') and in the dog (as 'second animal species') were studied to find out for how many of these compounds the study in dogs led to a lower 'no-toxic-effect level' (NTEL) than that found in the rat. From a quantitative point of view such information would contribute to a better insight into the desirability of toxicity studies in dogs, because acceptable daily intakes and permissible exposure levels in man are generally based on the lowest NTEL. For 44% of the compounds the NTEL in the dog was lower than that in the rat. When rat NTEL was divided by the arbitrary factor of 10, the adjusted NTEL was lower than the dog NTEL for 86% of the compounds tested in sub-chronic studies, and for 80% of the compounds tested in chronic studies. Whether it is justifiable to substitute such an adjusted NTEL for a study in dogs should be judged from compound to compound. It mainly depends on the size of the margin between the NTEL in the rat (as 'prime animal species') and the (expected) actual exposure level in humans, and also on the acceptability of loosing additional qualitative toxicological information. When this margin is large enough (e.g. 1000 or more), a study in dogs might be superfluous, despite the loss of qualitative data. Such an approach could lead to a reduction of the number of animals in toxicity testing and also to a reduction of the costs. Chemicals/CAS: Food Additives; Pesticides

Animal experiment
Comparative toxicology
Dog
Economic aspect
Intoxication
No toxic effect level
Nonhuman
Rat
Toxicity testing
Animal
Dogs
Drug Toxicity
Food Additives
Maximum Allowable Concentration
Pesticides
Rats
Species Specificity
Support, Non-U.S. Gov't

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230083

0260-437X

Journal of Applied Toxicology, 6 (4), 271-279

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