Carcinogens subchronic

In additional EPA studies, subchronic inhalation was evaluated ia the rat for 4 and 13 weeks, respectively, and no adverse effects other than nasal irritation were noted. In the above-mentioned NTP chronic toxicity study ia mice, no chronic toxic effects other than those resulting from bronchial irritation were noted. There was no treatment-related increase ia tumors ia male mice, but female mice had a slight increase in bronchial tumors. Neither species had an increase in cancer. Naphthalene showed no biological activity in other chemical carcinogen tests, indicating Htde cancer risk (44). No incidents of chronic effects have been reported as a result of industrial exposure to naphthalene (28,41). 

To assess die overall potential for non carcinogenic effects posed by several exposure pathways, the total haziird index for each exposure duration (i.e., chronic, subchronic, and shorter-term) should be calculated separately. This equation is described below ... 

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 database for HFC-134a is extensive it contains studies with both human subjects and animal models. Potentially sensitive populations, including patients with COPD and adult and pediatric asthmatic patients, were tested with direct inhalation of HFC-134a from metered-dose inhalers. The response of these groups was no different than that of healthy adults. The animal studies covered acute, subchronic, and chronic exposure durations and addressed systemic toxicity as well as neurotoxicity, reproductive and developmental effects, cardiac sensitization, genotoxicity, and carcinogenicity. The metabolism of HFC-134a is well understood, and the relationship of exposure con... 

Dose selection is one of the most important activities in the design of a toxicology study. It is especially critical in carcinogenicity studies because of their long duration. Whereas faulty dose selection in an acute or subchronic toxicity study can easily be corrected by repeating the study, this situation is much less desirable in... 

The information used for dose selection usually comes from subchronic toxicity studies, but other information about the pharmacological effects of a drug and its metabolism and pharmacokinetics may also be considered. The maximum recommended human dose (MRHD) of the drug may be an additional criterion, if this is known when the carcinogenicity studies are being designed. 

EPA. 1992b. Heast Table 1 Subchronic and chronic toxicity (other than carcinogenicity). Health Effects Assessment Summary Tables. U.S. Environmental Protection Agency. NTIS Order No. PB92-921199. 

The term repeated dose toxicity comprises the adverse general (i.e., excluding reproductive, genotoxic, or carcinogenic effects) toxicological effects occurring as a result of repeated daily dosing with, or exposure to, a substance for a part of the expected life span (subacute or subchronic exposure) or for the major part of the fife span, in case of chronic exposure (EC 2003). 

UFm accounts for the quality and relevance of the database, i.e., accounts for the uncertainties in the establishment of a NOAEL for the critical effect. The UFm includes elements such as (1) the quality of the database, e.g., data on specific toxic endpoints are lacking or inadequate, default value of 1-10 (2) route-to-route extrapolation, e.g., no studies using the appropriate exposure route are available, no default value (3) LOAEL-to-NOAEL extrapolation, e.g., a NOAEL cannot be established for the critical effect, default value of 10 (4) subchronic-to-chronic extrapolation, e.g., no chronic studies on which to establish the NOAEL are available, default value of 10 and (5) nature and severity of toxicity, e.g., the critical effect is toxicity to reproduction, carcinogenicity or sensitization, default value of up to 10. A default value for UFm has not been recommended however, a value from 1 to 100 is generally used. The value is evaluated case-by-case based on expert judgment. 

Toxicology. Amitrole has low acute toxicity in experimental animal studies subchronic exposures were associated with changes in the thyroid and chronic exposures were carcinogenic. 

Freundenthal RI, Thake DC, Baron RL Project Summary-Carcinogenic Potential of Rotenone Subchronic Oral and Peritoneal Administration to Rats and Chronic Dietary Administration to Syrian Golden Hamsters, Health Effect Research Laboratory Report EPA-66/Si-81-037. Research Triangle Park, NC, US Environmental Protection Agency, 1981... 

Under the sponsorship of the National Cancer Institute and the National Toxicology Program, two chronic tests of CN and CS administered by inhalation are under way. > Preliminary data obtained in the subchronic studies preparatory to the definitive inhalation carcinogenicity tests are presented in the sections of this chapter dealing with CS and CN. One probable adverse effect, to judge from... 

The National Toxicology Program performed a subchronic study of CN to generate data on the maximally tolerated dose (MTD) of this agent preparatory to launching a full-scale chronic-toxicity and carcinogenicity bioassay.38 The test was conducted in Fischer 344... 

Rozman K, Roth WL, Greim H, et al. 1993. Relative potency of chlorinated dibenzo-p-dioxins (CDDs) in acute, subchronic and chronic (carcinogenicity) toxicity studies Implications for risk assessment of chemical mixtures. Toxicology 77(l-2) 39-50. 

The adverse health effects most readily associated with mycotoxin consumption are either acute or subchronic. Chronic effects, such as carcinogenicity, have been more difficult to directly relate to mycotoxin consumption. This is in spite of the fact that various data indicate that at least 45 mycotoxins are known to be either mutagenic or carcinogenic (1). The following mycotoxins may pose an adverse human health risk in respect to carcinogenicity aflatoxin, cyclochlorotine, griseofulvin, luteoskyrin, ochratoxin, patulin, penicillic acid, sterigmatocystin, T-2 toxin, and zearalenone. 

Lee, Y., Buchanan, B.G., and Rosenkranz, H.S., Carcinogenicity predictions for a group of 30 chemicals undergoing rodent cancer biossays based on rules derived from subchronic organic toxicities, Environ. Health Perspect., 104 (Suppl. 5), 1059-1064, 1996. 

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