Chemicals associated with site-specific neoplasia in 1394 long-term carcinogenesis experiments in laboratory rodents

Huff, J; Cirvello, J; Haseman, J; Bucher, J

HERO ID

41624

Reference Type

Journal Article

Subtype

Review

Year

1991

Language

English

PMID

1773796

HERO ID 41624
Material Type Review
In Press No
Year 1991
Title Chemicals associated with site-specific neoplasia in 1394 long-term carcinogenesis experiments in laboratory rodents
Authors Huff, J; Cirvello, J; Haseman, J; Bucher, J
Journal Environmental Health Perspectives
Volume 93
Page Numbers 247-270
Abstract The carcinogenicity data base used for this paper originated in the late 1960s by the National Cancer Institute and since 1978 has been continued and made more comprehensive by the National Toxicology Program. The extensive files contain among other sets of information detailed pathology data on more than 400 long-term (most often 24 month) chemical carcinogenesis studies, comprised of nearly 1600 individual experiments having at least 10 million tissue sections that have been evaluated for toxicity and carcinogenicity. Using the current data set of 379 studies made up of 1394 experiments, we have compiled listings of chemicals having like carcinogenic target sites for each of the 34 organs or systems for which histopathology diagnoses have been recorded routinely. The most common tumor site is the liver (15% of all experiments), followed in rank order by: lung, hematopoietic system and kidneys, mammary glands, forestomach, thyroid glands, Zymbal glands, urinary bladder, skin and uterus/cervix, and circulatory system and adrenal glands. These compilations are most useful for maintaining a historic perspective when evaluating the carcinogenicity of contemporary experiments. Equally important, the chemical-tumor-organ connection permits an evaluation of how well chemically induced cancers in a particular organ in one sex or species will predict or correlate with the other sex or species. Using liver cancers as an example, the overall interspecies concordance is 80%. Likewise target site predictions can be made for chemicals selected for study that may be similar to those already evaluated; thereby experimental protocols could be adjusted to allow, for example, more extensive pathology on preselected target organs (i.e., serial sections of the kidney). Further from these observations, one could decide to use two strains of mice to evaluate a short-chain chlorinated aliphatic compound or to study a human carcinogen in a sex-species known to develop chemically induced tumors in the same site observed in humans. Structural classes of chemicals having a propensity for certain organs can be easily identified from these data. Sex-species responders to particular induced cancers become clearly evident, such as in the ovary of female mice or in the kidney of male rats.
Doi 10.2307/3431195
Pmid 1773796
Wosid WOS:A1991GC05200036
Url http://www.jstor.org/stable/3431195?origin=crossref
Is Certified Translation No
Dupe Override No
Comments ECRIB.Environ. Health Perspect. 93: 247-270.
Is Public Yes
Language Text English
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