Animal studies hamsters, inhalation

Intermediate-Duration Exposure.No studies are available on the adverse health effects from intermediate-duration exposure in humans by any route. Studies in animals indicate that exposure to endrin via inhalation can be lethal and causes effects on the nervous and respiratory systems, the liver, the brain, adrenals, and kidneys (Treon et al. 1955). Since systemic effects were observed at levels which caused death, data are not sufficient to derive an intermediate-duration inhalation MRL. Animal studies also demonstrate that oral intermediate-duration exposure can lead to death in several species (rat, mouse, hamster, rabbit, monkeys, cat) (Treon et al. 1955). Endrin was lethal in rabbits following dermal exposure (Treon et al. 1955). No other treatment-related disorders are known. Additional studies for oral and dermal routes using a range of exposure levels would be useful in identifying potential target tissues. 

In animal studies the 4-hour inhalation LCso was 17,000 ppm for hamsters and 13,300ppm for rats." Exposure to 5000ppm for 10 minutes produced a 50% decrease in respiration rate in mice in anesthetized rats significant increases in blood pressure were observed at 1700 ppm and concentrations above 6000 ppm significantly increased heart rate. ... 

In animal studies, significant increases in adenocarcinomas and squamous cell carcinomas of the lung have occurred in rats after inhalation or intratracheal instillation in rats, but not in hamsters. Increasing in vitro and in vivo evidence suggests that the rat lung tumor response to crystalline silica exposure is a result of marked and persistent inflammation and epithelial proliferation. However, other pathways such as a role for crystalline silica surfacegenerated oxidants or a direct genotoxic effect cannot be ruled out. 

Acetaldehyde and cancer Laboratory animal studies indicate that exposure through inhalation to vapors of acetaldehyde causes nasal tumors in rats and laryngeal tumors in hamsters. However, no adequate data are available regarding acetaldehyde as a human carcinogen. The U.S. EPA has classified acetaldehyde as group 2B that is, it is a possible human carcinogen. - - ... 

One report noted renal tubular nephritis in a worker killed after an explosion inside a plant manufacturing CS agent (Cookson and Nottingham, 1969). Hepatocellular injury has been linked to serious CS inhalation (Krapf and Thahnann, 1981). To date, animal studies have not documented any relationship between RCA exposure and teratogenicity (Himsworth et ah, 1971 Upshall, 1973 Folb and Talmud, 1989). CS did not demonstrate mutagenic potential with the Ames assay (Rietveld et ah, 1983). Similarly, CR did not have carcinogenic effects in mice or hamsters (Blain, 2003) CS lacks mutagenicity in several test systems (Daniken et al, 1981 Wild eta/., 1983). 

In intermediate-duration animal studies, golden Syrian hamsters exposed to camotite uranium ore dust (AMAD=1.5-2.1 pm) at a concentration of 19 mg U/m by inhalation for 16 months failed to shown signs of cancer development upon examination of selected tissues including lungs, trachea, liver, kidneys, spleen, heart, and any abnormal tissue. As compared to unexposed controls, the hamsters had significantly more necrotic liver foci and inflammatory lung responses (Cross et al. 1981b). 

Phenanthrene may cause skin allergy, and is considered phototoxic. It has induced sister chromatid exchanges in Chinese hamster cells. The available data are inadequate to permit an evaluation of the carcinogenicity of phenanthrene to experimental animals however, a number of other PAHs have caused tumors in laboratory animals via oral, inhalation, and dermal exposures. A single oral dose of phenanthrene did not induce mammary tumors in rats, and a single subcutaneous injection did not result in treatment-related increases in tumor incidence in mice. Neonate mice administered intraperitoneal or subcutaneous injections of phenanthrene also did not develop tumors. No skin tumors were reported in two skin painting assays with mice. Phenanthrene was also tested in several mouse skin initiation-promotion assays. It was active as an initiator in one study, inactive as an initiator in four others, and inactive as a promoter in one study. 

Inorganic mercury exposure caused a significant increase in the incidence of resorptions in hamsters (Gale 1974). No other human or animal studies were available on developmental effects following inorganic mercury exposure. Therefore, additional studies for inhalation, oral, and dermal exposures are... 

Reproductive Effects. Data regarding the reproductive effects of hydrazines are limited to a few animal studies. Reproductive effects (ovarian and testicular atrophy, endometrial inflammation, aspermatogenesis) were observed in hamsters exposed to 1-5 ppm hydrazine by the inhalation route (Vemot et al. 1985). Tire incidence of endometrial cysts was significantly elevated in female mice exposed to 0.05 ppm 1,1-dimethylhydrazine (Haun et al. 1984). Spenn abnormalities and decreased caudal epididymal sperm counts were noted in mice injected with 8 mg/kg/day hydrazine or 12.5-68.8 mg/kg/day 1,1-dimethylhydrazine (Wyrobek and London 1973). These effects were not observed in hamsters exposed to 0.25 ppm hydrazine by die inhalation route (Vemot et al. 1985) or in mice and hamsters exposed to 5.3-9.5 mg/kg/day hydrazine by the oral route (Biancifiori 1970). No studies were located regarding the reproductive effects of 1,2-dimethylhydrazine. In addition, no studies were located which investigated effects of hydrazines on reproductive function. Despite the inconsistency of the findings from animal studies, the serious nature of the reproductive effects observed in the positive studies makes them one of concern for humans exposed to hydrazine. 

Becking(41) summarized two inhalation studies of type A sodium zeolite which rapidly decomposes to sodium silicate and amorphous aluminates under physiological conditions. In the first study, hamsters were exposed to approximately 20 mg/m of type A zeolite 3 days per week, 5 hours per day for 52 weeks. In the second study, Cynomolgus monkeys were exposed to 1 and 6 mg/m of type A zeolite for 24 months, and 50 mg/w type A zeolite for 12 months. No evidence of fibrosis was observed in the animals in either study. 

Likewise, no treatment-related gross reproductive tract alterations after intermediate-duration exposure were observed in male or female rabbits or in male hamsters continuously exposed to aerosols of Fyrquel 220 at concentrations <100 mg/m3 (MacEwen and Vemot 1983). Two male rabbits exposed for 1-4 hours/day, 4-5 days/week, for 11-26 days to 2,000 mg/m3 aerosol of Cellulube 220 (Carpenter et al. 1959) showed no histological evidence for effects on reproductive tissues. No acute or chronic inhalation studies examining reproductive effects in animals were located. 

No studies were located regarding genotoxic effects in animals after inhalation or dermal exposure to organophosphate ester hydraulic fluids. However, the incidence of nuclear anomalies in bone marrow interphase cells was significantly increased in Chinese hamsters gavaged on 2 consecutive days with 2,500 and 5,000 mg/kg/day of Reofos 50 (Ciba-Geigy 1984a), but not in those dosed with 1,250 mg/kg/day. 

Acute lethality data for inhalation exposure to monomethylhydrazine are available for monkey, dog, rat, mouse, and hamster. Based upon the available data, hamsters appear to be the most resistant species, and the squirrel monkey and beagle dog are the most sensitive. The lethality of monomethylhydrazine appeared to follow a linear relationship for exposures up to 1 h. Most animal data focus on lethality as the toxicity endpoint with very limited exposure-response information available regarding nonlethal effects. The most significant effect reported in the acute exposure studies was the notable hemolytic response that was reversible upon cessation of exposure. However, the preponderance of the data suggest that there is little margin between exposures associated with nonlethal, reversible effects and those that result in death. 

Developmental Effects. No studies were located regarding developmental effects in humans after any route of exposure and in animals after inhalation and dermal exposure. However, studies in rats (Singh 1981) and hamsters (Frakes et al. 1986a) fed a cassava diet suggested that cyanide may have teratogenic and fetotoxic effects at maternally toxic doses, but Singh (1981) indicated that the results... 

The metabolism of several 3,3 -dichlorobenzidine-based pigments has been studied in animal experiments to determine if they are metabolized to 3,3 -dichlorobenzidine. In a study where rats were exposed by inhalation to Pigment Yellow 17 (230 mg/m air) for 4 hours, 3,3 -dichlorobenzidine was not detected in either urine or blood during the following 14 days (Hofmann and Schmidt 1993). No detectable residues of 3,3 -dichlorobenzidine were found in urine samples of hamsters administered a single dose of... 

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