Premium
Part IV. The concept of threshold in carcinogenesis
Author(s) -
Mantel Nathan
Publication year - 1963
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1002/cpt196341104
Subject(s) - carcinogen , threshold dose , mechanism (biology) , hazard , carcinogenesis , computer science , cancer , toxicology , risk analysis (engineering) , biology , medicine , genetics , epistemology , ecology , philosophy
Whether or nat there is a threshold level of a carcinogen depends on the nature of the cancer‐inducing mechanisms. It may be that under some mechanisms thresholds do exist. In general, with the mechanisms proposed, the carcinogenic hazard never disappears with diminishing dose but rather becomes indefinitely small. A more practical approach is then not to attempt to determine the threshold level of a carcinagen, but rather to determine some arbitrarily safe (1/100,000,000) level. Such levels can be established from knawledge of the carcinagenic mechanism or, when the mechanism is not known, through the use of conservative procedures. The concept of a carcinogenic threshold becomes further obscured when one considers alterations which may occur in the environment. Safe or threshold levels of a carcinogen may become unsafe if a promoting agent is introduced into the environment. From these considerations various recommendations are made as to the conduct of a carCinogen testing program. These recommendations include testing over a wide dose range, testing in conjunction with knawn promoters or initiators, use of both skin‐painting tests and tests which permit the agent to be metabolized by the host.