Carcinogenicity experimental studies

Experimental studies with human subjects and several mammalian species (monkey, dog, rat, mouse, and rabbit) were located. Animal studies addressed neurotoxicity, genotoxicity, carcinogenicity, and cardiac sensitization and were conducted over acute, subchronic, and chronic exposure durations. 

The carcinogenicity of polycyclic aromatic compound-rich tyre extender oils has lead to the proposal of a legislative ban on their use in Europe. The suitability of naphthenic oils as non-toxic plasticisers in tyre treads is discussed and results are presented of experimental studies of the use of these plasticisers in SBR, EPDM, sulphur-cured EPDM and peroxide-cured EPDM. Despite their low aromatic content, the naphthenic plasticisers are shown to give good results in SBR, probably as a result of the contribution to solvent characteristics of the naphthenic molecular structure. The use of naphthenic oils is expected to increase worldwide as they are said to be one of the best alternatives to aromatic extracts with regard to solvent properties, compatibility, performance and availability. 

Dunnick JK, Melnick RL. 1993. Assessment of the carcinogenic potential of chlorinated water experimental studies of chlorine, chloramine, and trihalomethanes. J Nad Cancer Inst 85(10) 817-822. 

According to OECD (2001b), the term carcinogen denotes a chemical substance or a mixture of chemical substances, which induce cancer or increase its incidence. Substances which have induced benign and malignant tumors in well-performed experimental studies on animals are considered also to be presumed or suspected human carcinogens unless there is strong evidence that the mechanism of tumor formation is not relevant for humans. ... 

Certain hexavalent chromium compounds have been demonstrated to be carcinogenic on the basis of epidemiological investigations on workers and experimental studies in animals. In general, these compounds tend to be of low solubility in water and thus are subdivided into two subgroups ... 

Maltoni C, Ciliherti A, Lefemine G, et ah Results of a long-term experimental study on the carcinogenicity of vinyl acetate monomer in mice. Ann NY Acad Set 837 209-38, 1997... 

Sunderman FW Jr. 1989a. Carcinogenicity of metal alloys in orthopedic prostheses Clinical and experimental studies. Fundam Appl Toxicol 13 205-216. 

Bhide. Experimental studies on mutagenic and carcinogenic effects of tobacco chewing. J Cancer Res Clin Oncol 1985 109(3) 203-207. 

In this section, the relevant epidemiological and experimental data are summarized. Only reports, other than in abstract form, that meet the criteria outlined on p. 11 are considered for evaluating carcinogenicity. Inadequate studies are generally not summarized such studies are usually identified by a square-bracketed comment in the preceding text. 

Inadequate evidence of carcinogenicity. The studies cannot be interpreted as showing either the presence or absence of a carcinogenic effect because of major qualitative or quantitative limitations, or no data on cancer in experimental animals are available. 

There is sufficient evidence of carcinogenicity from studies in experimental animals which indicates there is an increased incidence of malignant and/or a combination of malignant and benign tumors (1) in multiple species or at multiple tissue sites, or (2) by multiple routes of exposure, or (3) to an unusual degree with regard to incidence, site, or type of tumor, and age at onset ... 

In the effects assessment step the relationship between the level of exposure and the incidence, nature, and severity of an (adverse) effect following the exposure is determined. For most types of effects, it is assumed that there is a minimum dose or concentration below which adverse effects will not occur the no effect level or threshold. To determine the threshold, different doses are tested, for most chemical hazards usually in laboratory animals. In toxicology, the highest tested dose without adverse effects is called the no observed adverse effect level (NOAEL). Based on the NOAEL established in an experimental study, a human limit value can be calculated, taking into account uncertainties and differences in experimental design and circumstances. Uncertainties and differences are accounted for by uncertainty factors (e.g., for interspecies differences, intraspecies variability, and exposure duration). For some types of substances, it is assumed that every level of exposure can result in adverse effects, in which case no threshold would exist. This, for instance, is assumed to apply for genotoxic carcinogens. 

There is direct evidence that children are more susceptible than adults to at least some kinds of carcinogens, including certain chemicals and various forms of radiation. Data from controlled experimental studies in animals also support the concept that susceptibility to some chemical carcinogens and to various forms of ionizing radiation is greatest during the early stages of life, both before and after birth (Tomatis Mohr, 1973 Napalkov et al., 1989 Bimbaum Fenton, 2003). There is also evidence of increased or even unique... 

Maltoni C, Conti B, Cotti G, et al. 1985. Experimental studies on benzene carcinogenicity at the Bologna Institute of Oncology Current results and ongoing research. Am J Ind Med 7 415-446. 

Reasonably anticipated to be a human carcinogen. There is limited evidence of carcinogenicity from studies in humans, but sufficient evidence of carcinogenicity from studies in experimental animals. 

Three-dimensional dose-rate/time/response surfaces for chronic exposure to carcinogens and ionizing radiation clarify the interactive roles of competing risks (Raabe, 1987). The three dimensions are average dose rate, exposure time, and risk. The unproved conceptualization afforded by them contributes to the planning and evaluation of epidemiological analyses and experimental studies involving chronic exposure to radiation toxicants (Raabe, 1987). 

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