Carcinogenicity studies carcinogenic potential assessment

No information on the carcinogenic potential of polyalphaolefin hydraulic fluids was located. Studies designed to assess carcinogenicity in animals exposed via inhalation, oral, and dermal routes or a well-controlled cohort retrospective or prospective study would be useful for determining the carcinogenic potential of polyalphaolefin hydraulic fluids. 

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. 

Limited epidemiological information exists for carcinogenicity in humans following inhalation exposure to kerosene (vapor) (Chan et al. 1979) and other fuel oils such as diesel fuel (vapor) (Partanen et al. 1991). These studies either test kerosene exposure by use of kerosene stoves, and so are limited for the same reasons as the respiratory studies described above, or measure fuel oil exposures according to occupation. In the latter case, confounding from exposure to other chemicals, such as gasoline, exists. Both studies are limited since the duration and level of fuel oil exposure were not identified. Other available data are also reported to be inadequate to assess the carcinogenic potential of fuel oils (lARC 1989 Lam and Du 1988). 

If oncogenicity studies have been conducted by the oral route and another clinical route is to be used in man, the need to repeat such studies should be assessed critically. Oncogenic potential is related to the concentration of the carcinogen at its site of action. Thus, if the oral route results in adequate exposure of the lung, there should be no need to perform additional inhalation oncogenicity studies. Inhalation studies of 1-3 months duration should be performed to assess possible local effects on respiratory tissue and also to gain pharmacokinetic data. 

There is currently no information on the carcinogenic potential of 2-hexanone. Chronic-duration studies conducted via any route of exposure should assess this potential effect, since persons living in the vicinity of hazardous waste sites or in occupational settings may be chronically exposed to low levels of 2-hexanone via the oral, inhalation, and dermal routes. 

Chronic Toxicity The effect of a chemical (or test substance) in a mammalian species (usually rodent) following prolonged and repeated exposure for the major part of the lifetime of the species used for the test. Chronic exposure studies over two years are often used to assess the carcinogenic potential of chemicals. 

In summary, in studies of chemical toxicity, pathways and rates of metabolism as well as effects resulting from toxicokinetic factors and receptor affinities are critical in the choice of the animal species and experimental design. Therefore it is important that the animal species chosen as a model for humans in safety evaluations metabolize the test chemical by the same routes as humans and, furthermore, that quantitative differences are considered in the interpretation of animal toxicity data. Risk assessment methods involving the extrapolation of toxic or carcinogenic potential of a chemical from one species to another must consider the metabolic and toxicokinetic characteristics of both species. 

Action level for dioxin and dioxin-like compounds in soil. Action levels are concentrations of chemicals at which consideration of action to interdict exposure occurs 1 ppb TCDD in residential soil was identified by Kimbrough et al. (1984) as a "level of concern" and recommended as "a reasonable level to begin consideration of action to limit exposure." The conclusions of Kimbrough et al. (1984) were derived in part from an evaluation of the carcinogenic potential of TCDD, based on a 2-year oral chronic toxicity and oncogenicity study in rats (Kociba et al. 1978). With the advancement of knowledge about dioxin-like chemicals and their assumed common mechanism of toxicity, the TEQs were introduced into the risk assessment process. Since then, 1 ppb of total dioxins (expressed as TEQs) in soil has been used as an action level by ATSDR. 

Aldurazyme polymorphic variation of human a-L-iduronidase lysosomal hydrolase hydrolysis of terminal a-L-iduronic acid residues of dermatan sulfate and heparin sulfate No genotoxicity studies clinical trials Studies to assess mutagenic and carcinogenic potential have not been conducted No warnings or precautions regarding carcinogenic risk... 

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