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

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.

Hepatocellular carcinoma and the risk of occupational exposure

“…Dye production and use; clinical laboratories [220,247] Group 1 [76] 1 Not all of them are to be referred to group Non-infective risk As 7440-38-2 Timber manufacturing; pesticide use; As extraction industry; lead processing; pharmaceutical industry; glass industry; leather preservatives; antifouling paints; agrochemical production; microelectronics and optical industries; non-ferrous metal smelters; coal-fired power plants [254][255][256][257][258] Group 1 [263] Cd 7440-43-9 Cd mining; manufacturing of Cd-containing ores and products; Ni-Cd battery manufacturing, Cd alloy production [275,277,278] Group 1 [263] As: Arsenic; Cd: Cadmium; IARC: International Agency for Research on Cancer; CAS No. : Chemical abstract service number.…”

“…Burning municipal waste leads to inhalation of Cd. Workers in the metal and plastic product industry and workers involved in the construction of solar panels are exposed to Cd [277,278] . In 2011, Cd production was estimated to be 600 metric tons in United States.…”

An Ecological Study of the Association between Air Pollution and Hepatocellular Carcinoma Incidence in Texas

“…The liver is the most common site of tumor origin in experimental animals exposed to carcinogenic chemicals [18]. Moreover, some epidemiological studies on cancer incidence and mortality have shown that individuals in occupations that involve exposure to chemicals are at a higher risk of developing primary liver cancer [19].…”

Carcinogenesis: Basic Principles

“…Sites of tumor formation in humans show some similarities to those produced in rodent carcinogenicity bioassays (Huff et al, 1991). The lung, hematopoetic system, mammary gland, urinary bladder, and uterus are among the ten most frequent sites of tumor development in both the United States population and in rodent bioassays.…”

“…Over 400 long-term chemical carcinogenesis studies using rats and mice have recently been reviewed (Huff et al, 1991), and some similarities in incidence and site of tumor development were found. For example, in both species of rodents, liver is the most common tumor site, and, although mice are more likely to experience liver tumors, there is an 80% interspecies concordance for hepatocarcinogenicity.…”