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Reply to Comments: On the Relationship of Toxicity and Carcinogenicity
Author(s) -
Zeise Lauren,
Crouch Edmund A. C.,
Wilson Richard
Publication year - 1985
Publication title -
risk analysis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.972
H-Index - 130
eISSN - 1539-6924
pISSN - 0272-4332
DOI - 10.1111/j.1539-6924.1985.tb00181.x
Subject(s) - energy (signal processing) , center (category theory) , citation , library science , sociology , computer science , chemistry , physics , quantum mechanics , crystallography
The article by Lauren Zeise, Richard Wilson, and Edmund Crouch on the “Use of Acute Toxicity to Estimate Carcinogenic ksk,” in Volume 4, Number 3 of Risk Analysis, reported a good correlation between acute toxicity (i.e., LDSO) and carcinogenic potency for chemicals tested (under “high, not lethal but usually toxic doses”) in mice and rats by the National Cancer Institute. The authors note that, without long-term bioassay data, an estimate of carcinogenic potency could be based on acute toxicity and the observed correlation. This result raises scientific issues quite distinct from the potential regulatory application described by the authors. It is my understanding that mechanisms underlying an acute toxic effect and a long-term carcinogenic effect are generally thought to be unrelated for most chemicals. In simple terms, carcinogens at low doses ciassified as genotoxic are thought to change genetic materials through a probabilistic process (e. g., the one hit and multistage models of carcinogenic potency refer to the number of stages of genetic transformation associated with carcinogenesis). Epigenetic carcinogens are not thought to act directly on DNA, but are thought to be associated with genetic changes. Acute toxics are thought to operate differently (e. g., by producing disequilibrium