Abstract

The major toxicological problem today is to establish a useful method to cope with a low level and prolonged pollution. The toxicological method under such circumstances should include ecotoxicology and biotoxicology as well as classical toxicology, and is named as eco-biotoxicology. This method includes not only investigations on kinetics and levels of chemicals in the environment, human reaction and adaptation to chemicals or biophysiological and pathophysiological clarification of the effects, but also the establishment of countermeasures to prevent health hazards from chemicals, including biological monitoring and development of exposure parameters. The followings were the results recently obtained in our laboratory in support of the object of eco-biotoxicology. 1. Two low-molecular-weight chromium binding substances were purified from the liver of dogs. Chromium bound to them showed a lower toxicity and higher rates of urinary excretion than inorganic chromium compounds. A low-molecular-weight nickel binding substance was also purified from the liver of rats. Nickel bound to it showed a lower cytotoxity, but a higher malignant transformation induction of cultured cells than inorganic nickel compounds. These results indicate that chemical form of metals and binding protein in the body are important factors in their toxicity. 2. Triphenyl and tributyltins showed to inhibit insulin release from pancreas, collagen-induced aggregation of platelets, O2-production and chemotaxis of leukocytes, histamine release from mast cells, etc. A common mechanism seemed to be an inhibition of the stimulus-response coupling in the cell membrane. 3. Carcinogenic heterocyclic amines were measured in food and biological materials by a newly developed method. Their levels in plasma of uremic patients were higher than normal subjects and decreased by the treatment with hemodialysis. 4. Safety evaluation of bis (tri-n-butyltin) oxide (TBTO) in fishes was carried out according to a toxicological approach. Acceptable daily intake of TBTO in food was estimated to be 1.6 μg/kg/d.

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