Animal studies carcinogenicity

In the first step of the evaluation, the available data are evaluated to determine the likelihood that the agent is a human carcinogen. The evidence is characterized separately for human studies and animal studies as sufficient. 

Animal studies have shown that tumors can result from both inhalation (Fukuda et al. 1983 Henschler et al. 1980 Maltoni et al. 1986) and oral exposure (Aima et al. 1994 Henschler et al. 1984 NCI 1976 NTP 1990) to trichloroethylene. Unfortunately, some of these studies (NCI 1976) are limited in that they use carcinogenic epoxide stabilizers with the trichloroethylene, which may contribute to the carcinogenicity. The studies also show different responses depending on the sex, species, and strains of animals used and do not point to a particular target organ for increased tumor incidence. Other studies are flawed because of excess... 

Carcinogenicity Evidence of adverse effects Suggestive animal studies No basis for concern... 

Chronic animal studies of organophosphates are few in number, but those that do exist provide a useful base from which to draw toxicological insight. In rats and mice exposed orally to tricresyl phosphate for 2 years, endocrine effects were found in a dose-response pattern and hepatic effects were found. Ovarian interstitial hyperplasia was also observed but was not dose related. No chronic-duration MRLs could be derived because of the limited number of studies. Tricresyl phosphate, a component of certain hydraulic fluids, produced no evidence of carcinogenic activity in assays with rats and mice (NTP 1994). However, another component, tributyl phosphate, was associated with an increased incidence of bladder tumors in rats and mice (FMC 1994a, 1994b). 

The International Agency for Research on Cancer (IARC 1987) concluded that the evidence for carcinogenicity of lead and inorganic lead compounds was inadequate in humans and sufficient in animals. IARC (1987) classified lead and inorganic lead compounds in IARC Group 2B, possible human carcinogen. The Department of Health and Human Services (DHHS) has determined that lead acetate and phosphate may reasonably be anticipated to be carcinogens based on sufficient evidence from animal studies, but inadequate evidence from human studies (NTP 1994). 

Data adequacy The key study was well designed, conducted, and documented used 20 human subjects and utilized a range of concentrations and exposure durations. Occupational exposures support the 8-h AEGL value. The mechanism of headache induction (vasodilation) is well understood and occurs following therapeutic administration of nitrate esters to humans. Animal studies utilized several mammalian species and addressed metabolism, neurotoxicity, developmental and reproductive toxicity, and potential carcinogenicity. ... 

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... 

The data base for HCFC-141b is extensive and contains studies with human subjects as well as several mammalian species. The study with human subjects was well conducted and addressed clinical symptoms, respiratory effects, cardiotoxicity, hematology and clinical chemistry effects, and pharmacokinetics. The study with humans established a no-effect level (AEGL-1) that may be conservative, because a lowest-observed-effect level was not attained. The AEGL-1 of 1,000 ppm is supported by the animal data, which show an absence of effects at concentrations that are higher by a factor of 10. Animal studies addressed both acute and chronic exposure durations as well as neurotoxicity, genotoxicity, carcinogenicity, and cardiac sensitiza... 

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