Predicting the risk of tumor occurrence under the effect of small doses of carcinogens

Abstract

Basic methodological approaches were formulated for determining the permissible levels of carcinogens in man's environment on the basis of current experimental oncological data dealing with the interaction of the organism and carcinogenic compounds. The tumor is proposed as a specific index of the harmfulness criterion of carcinogenic action. Under these conditions, both the frequency and the development time of tumors must be considered. Results are given of an experimental study of the carcinogenic activity of various doses of benz[a]pyrene (0.005, 0.02, 0.1, 0.5, and 2.5 mg) on rats by using a tenfold intratracheal administration. On the basis of mathematical models of the obtained dose-time-effect relationship, the risk of cancer occurrence due to small carcinogen doses is predicted. Small doses were not tested in the experiment. On the basis of the data obtained in the experiment, a maximally permissible concentration of benz a pyrene in the ambient air can be determined. A benz[a]pyrene dose of 0.02 mg is recommended as the basis of the calculation. The effect of this dose is shown at time periods longer than the limits of human life.

PIP: Quantitative criteria of the action of chemical carcinogenic compounds serve as the basis for establishing the degree of danger they pose and of safety levels. The presence of the tumor is proposed as a specific index of the harmfulness of carcinogenic action. There are no indices for determining the initial stages of the neoplastic process before the tumor appears. Both the frequency and the time required for development are important. A study was made of the carcinogenic activity of benz(a)pyrene on rats. The drug was given by intratracneal administration in doses of .005, .02, .01, .05, and 2.5 mg repeated 10 times over a 10-month period. A total dose of .1 mg was minimally effective. However, .02 mg benz(a)pyrene was selected as the minimum effective single dose amount for estimated time periods longer than the life span of the animals and of the comparative span of human life. Tumors were produced in the lungs and other organs of the rats. Histological types varied. The dose given had an effect on the histological type of lung cancer. Large doses tended to produce epidermoid cancer while lower doses produced mostly adenocarcinoma. Some types found have not been recorded as spontaneously occurring in rats. The number of tumor-bearing animals diminished as the dose was reduced and the time for appearance of tumors increased. The number of spontaneous tumors in control animals increased with time. Animal strains with a high cancer susceptibility are needed in testing the small doses of a carcinogen since spontaneous tumors are an indication of sensitivity to carcinogenic substances. However, random-bred animals have a closer approximation to the human population and may be better for some experiments. For the optimal experiment, administration of a carcinogen should be over the entire life span of the individual. Another procedure is by using different doses in a short-term experiment to obtain a dose-time effect. On the basis of data obtained, the maximum permissible concentration of benz(a)pyrene in the ambient air can be determined.