Animal studies rabbits

Lu-EDTMP was evaluated as a bone pain palliation agent and found in animal studies (rabbits) to be comparable to 153Sm-EDTMP.187... 

Administration is by direct injection of 0.05 ml product into the eye (intravitreal injection), initially once every 2 weeks and subsequently once every 4 weeks. Animal studies (rabbits) indicated that the product is cleared from the eye over the course of 7-10 days, with direct nuclease-mediated metabolism representing the primary route of elimination. The most commonly observed side effect is ocular inflammation, which typically occurs in one in every four patients. 

Ocular Effects. JP-5 vapor were irritating to the eyes of two individuals and were associated with hyperemic conjunctiva in one case (Porter 1990). Eye irritation was also reported in workers who were chronically exposed to unspecified jet fuels, which may or may not include JP-5 (Knave et al. 1978). Deodorized kerosene vapor were shown to induce eye irritation in some individuals (Carpenter et al. 1976). Dermal exposure to diesel fuel and/or inhalation of its vapor was associated with subconjunctival hemorrhages in an individual who used it as a shampoo (Barrientos et al. 1977). In the only available animal studies, rabbits exposed dermally to diesel fuel (API 1979b), marine diesel fuel, or JP-5 (Cowan and Jenkins 1981 Schultz et al. 1981) showed no signs of ocular irritation. These data suggest that fuel oils, in general, may induce eye irritation in some individuals, although only one or two individuals... 

Evidence of chromosomal aberrations was equivocal in an animal study. Rabbits exposed to high natural background levels of radon-222 (12 WLM) for over 28 months displayed an increased frequency of chromosomal aberrations (Leonard et al. 1981). However, when a similar study was conducted under controlled conditions (10.66 WLM), chromosomal aberrations were not found. According to the authors, the increased chromosomal aberrations in somatic cells of rabbits exposed to natural radiation were mainly due to the gamma radiation from sources other than radon. 

Animal studies indicate that trichloroethylene can sensitize the heart to epinephrine-induced arrhythmias. Other chemicals can affect these epinephrine-induced cardiac arrhythmias in animals exposed to trichloroethylene. Phenobarbital treatment, which increases the metabolism of trichloroethylene, has been shown to reduce the trichloroethylene-epinephrine-induced arrhythmias in rabbits (White and Carlson 1979), whereas high concentrations of ethanol, which inhibits trichloroethylene metabolism, have been found to potentiate trichloroethylene-epinephrine-induced arrhythmias in rabbits (White and Carlson 1981). These results indicate that trichloroethylene itself and not a metabolite is responsible for the epinephrine-induced arrhythmias. In addition, caffeine has also been found to increase the incidence of epinephrine-induced arrhythmias in rabbits exposed to trichloroethylene (White and Carlson 1982). 

Respiratory effects have been observed in one dermal toxicity study. Of six rabbits exposed to an unspecified amount of Cellulube 220 for an intermediate duration, one died on day 36 of weakness and dyspnea of 48-hour duration (Carpenter et al. 1959). Respiratory effects were not observed in rabbits dermally exposed to 1,000 mg/kg of cyclotriphosphazene for an intermediate duration (Kinkead et al. 1989c, 1990). No acute- or chronic-duration animal studies examining respiratory tract effects were located. 

Information is available on the renal toxicity of ingested lead in several species, including rats, dogs, monkeys, and rabbits. The results indicate that histopathological changes in the kidneys of lead-treated animals are similar to those in humans (see Section 2.2.1.2). Reduced glomerular filtration rates and aminoaciduria were reported in some of the animal studies. Key animal studies on lead-induced renal toxicity will be discussed 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. 

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. 

No studies were located regarding reproductive effects in animals after dermal exposure to mirex. The only animal study that referred to reproductive effects following dermal exposure to chlordecone was conducted in rabbits by Allied Chemical. This study was not available for review. A published review of the study (Epstein 1978) indicated that chlordecone applied to shaved skin at dose levels of 5 or 10 mg/kg for 8 hours/day, 5 days/week, for 3 weeks induced testicular atrophy in two of six rabbits at 5 mg/kg and in one of six rabbits at 10 mg/kg. No other toxic effects were noted. This study is limited by the lack of dose response and lack of a NOAEL for the effect observed. 

No studies were located in humans regarding the inhalation absorption of 1,2-dibromoethane. The available animal toxicity data (see Section 2.2.1) indicate that absorption of 1,2-dibromoethane occurs in rats, mice, rabbits, guinea pigs, and monkeys exposed via inhalation for acute, intermediate, and chronic durations (Rowe et al. 1952 Stott and McKenna 1984). Based on the findings in animal studies, 1,2-dibromoethane is expected to be absorbed in humans exposed via the inhalation route. 

The fume (concentrations unspecified) is reported to cause irritation of the eyes, nose, throat, lungs, and skin. No reports are available from animal studies on the toxic effects of fume inhalation. Administered into rabbit eyes, the liquid caused mild to severe irritation. 

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