Utility of injection site tumorigenicity in assessing the carcinogenic risk of chemicals to man

Abstract

The nature of tumorigenic responses at the injection site is reviewed and responses produced by subcutaneous injection of chemicals are compared with responses produced by other routes of administration. The tumorigenic effects of chemicals reported in the first 26 volumes of the IARC Monographs on the Evaluation of Carcinogenic Risk of Chemicals to Man were examined, segregating the chemicals which produced only local tumors at the site of subcutaneous injection from those chemicals which produced distant tumors. Those chemicals which produced distant tumors were almost always tumorigenic by at least one other route of administration. However, nearly half of the chemicals which produced only local tumors by subcutaneous injection were not tumorigenic by any other tested routes of administration. It is recommended that when distant tumors are produced after injection, the results should be considered as significant as those obtained by routes of administration more relevant to man. However, if tumors are produced only at the site of injection and humans are exposed to the substance tested only by inhalation, ingestion, or absorption through the skin, the substance should be tested by other routes of administration before assessing the carcinogenic risk it may present to man.