The Single Exposure Carcinogen Database: assessing the circumstances under which a single exposure to a carcinogen can cause cancer.
A relational retrieval database has been developed compiling toxicological studies that assess whether a single dose of a chemical or physical agent, without exogenous promotional stimuli, could cause tumor development in animal models. This database allows for an evaluation of these studies over numerous parameters important to tumor outcome, which include type and quality of the studies as well as physical/chemical properties of the agents. An assessment of the database, which currently contains approximately 5500 studies involving about 800 chemicals from 2000 articles, reveals that a single dose of an agent can cause tumors to develop in males and females of numerous animal models in all principal age groups. In addition, the range of the 426 agents causing a positive response is chemically diverse, with representatives from over several dozen chemical classes. The dose caused a tumor endpoint was generally not acutely life threatening and was frequently a low proportion of the LD50 (i.e., less than 1/50 LD50). Positive responses also were reported via multiple routes of exposure, mainly oral, by injection, or dermal. These findings indicate that the phenomenon of single-exposure carcinogenesis is widespread and highly generalizable across chemical class, route, dose range, species, age, and gender. Single-exposure carcinogenesis, a concept long de-emphasized by regulatory agencies, requires a careful and formal consideration, especially as it may pertain to accidental spills, leaks, fires, explosions, and exposure excursions, but not necessarily limited to these.
Calabrese
E J
EJ
Environmental Health Sciences, School of Public Health, University of Massachusetts, Amherst 01003, USA. edwardc@schoolph.umass.edu
Blain
R B
RB
D000367:Age Factors; D015197:Carcinogenicity Tests / Q000379:methods*; D002273:Carcinogens / Q000008:administration & dosage* / Q000145:classification / Q000633:toxicity*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D006801:Humans; D009369:Neoplasms / Q000139:chemically induced* / Q000453:epidemiology; D018570:Risk Assessment; D012737:Sex Factors; D013997:Time Factors
D002273:Carcinogens