Rabbit studies

Alkylamines and diamines are generally classified as corrosive to the skin based on results from laboratory animal (rabbit) studies performed in accordance with the Department of Transportation (DOT) test method (84) rabbits are considered to be especially sensitive to alkylamines which even at low concentrations can induce skin redness and swelling. Oleylamine has been shown to induce mild to moderate skin irritation in laboratory rats when appHed at a concentration of 0.3% in mineral oil (Chemical Manufacturer s Association, 1985). Fatty amines which contain alkyl chains of 10—14 carbons are considered more irritating than related products which contain alkyl chains of 14—18 carbon atoms. Ethoxylation generally decreases the irritation potential of alkylamines. 

Human sensitization studies were negative at 10% solution (47). Undiluted benzyl alcohol produces moderate dermal irritation in guinea pigs and mild dermal irritation in rabbits (48,49). Severe eye irritation was noted in a rabbit study (50). Acute oral rat LD q values were reported between 1.23 and 3.10 g/kg (50—52). A dermal rabbit LD q value of 2.0 g/kg has been reported (49). Rats died after 2 h when exposed to a 200-ppm vapor concentration (53). Benzyl alcohol is readily oxidized in animals and humans to benzoic acid [65-85-0] which is then conjugated with glycine [56-40-6], and rapidly eliminated in the urine as hippuric acid [495-69-2] (54). 

Ganapathy, V. and F. H. Leibach. Role of pH gradient and membrane potential in dipeptide transport in intestinal and renal brush-border membrane vesicles from the rabbit. Studies with L-camosine and glycyl-L-proline. J. Biol. Chem. 1983, 258, 14189-14192. 

In the rat and mouse studies by Higgins et al. (1972) and the rat and rabbit studies by Ballantyne (1983), LC50 values differed by less than a factor of two... 

DCE gel formulations displayed minimal irritation in two separate in vivo rabbit studies. 

The mammalian result was considered indicative of a teratogenic potential when either the rodent or rabbit studies were positive. Therefore, a negative FETAX result was considered non-predictive if either the rat or rabbit were positive. To some extent, this biased the determined predictivity with respect to human hazard against FETAX, as for aspirin (see above). 

Dermal toxicity is evaluated by applying the chemical to the skin for 6h a day for 21 days in rat studies, or 28 days in rabbit studies. Feeding studies are used to evaluate the toxicological effects of the chemical when a known dose is administered orally. 

Before any practical work is carried out, all possible sources of information on skin irritation should be tapped, including manufacturers data on raw materials. However, this is often no more than basic Draize data from a regulatory rabbit study and is unlikely to be of great utility for safety assessment. In addition, the safety assessor must be aware that the skin irritation potential of a formulation is not... 

Toxicity Dimethylamine induces adverse effects such as irritation to skin and lungs. Repeated exposure to the chemical has caused corneal injury in experimental guinea pigs and rabbits. Studies of Hollinger and Rowe,34 Coon et al.,35 and others36 revealed inflammatory changes in the lungs, ulcerative rhinitis, nasal turbinates, and corneal ulceration in laboratory rabbits and nonhuman primates. 

B14. Barter, P. J., and Lally, J. I., Metabolism of esterified cholesterol in the plasma very low density lipoproteins of the rabbit Studies in vivo and in vitro. Atherosclerosis 31, 355-364 (1978). 

Hynynen, K., Clement, G.T., McDannold, N., Vykhodtseva, N., King, R., White, P.J., Vitek, S., and Jolesz, F A. (2004) 500-element ultrasound phased array system for noninvasive focal surgery of the brain A preliminary rabbit study with ex vivo human skulls. Magn. Reson. Med. 52,100-107. 

The Army s interim RfD of 1 x 10 " mg/kg per day for lewisite was based on two oral studies a two-generation reproductive study and a 90-day toxicity study in rats. In both studies, necrosis and hyperplasia of the forestomach were observed. After considering those studies and other potential studies, the subcommittee concludes that a 1987 teratogenicity study conducted in rabbits is more appropriate than the rat studies for deriving the RfD, because there is evidence that the rabbit might be more susceptible to lewisite than the rat. On the basis of the rabbit study, in which maternal mortality and gastric lesions were observed, the snbcommittee believes that the RfD for lewisite should be lowered from 1 x 10 mg/kg per day to 1 x 10 mg/kg per day. 

The approach used by ORNL to calculate the RfD for lewisite is consistent with the guidelines of the EPA. The subcommittee does not agree, however, with ORNL s proposed RfD of 1 x lO mg/kg per day, which is based on studies in the rat, and recommends deriving the RfD on the basis of a rabbit study. The RfD for lewisite recommended by the subcommittee is 1 x 10" mg/kg per day, which is an order of magnitude more conservative than the Army s interim RfD. 

One of the first cases of possible molecular mimicry was that of rheumatic fever, in which the symptoms were caused by antigens that mimic cardiac myosin.56-59 A simple rabbit study demonstrated how the administration of the key antigen induced strong inflammatory and myocardial changes as a result of host immune response to self antigens.59... 

In a rabbit study, hydroquinone at 150 mg kg day produced minimal developmental alterations in the presence of maternal toxicity. The no-observed-effect level for developmental toxicity was 75mgkg day In rat studies, maternal toxic effects from exposure to hydroquinone included changes in the ovaries, fallopian tubes, and menstrual cycle. Postimplantation mortality was also observed in rat studies. Observed paternal toxic effects from exposure to hydroquinone included changes in the testes, epididymis, sperm duct, prostate, seminal vesicle, Cowper s gland, accessory glands, and male fertility index. Further, exposure to hydroquinone produced skeletal malformations in chickens and ocular and skeletal malformations in rabbits. Hydroquinone can induce renal tubule adenomas, bladder carcinomas, hepatocellular neoplasms, and mononuclear cell leukemia in experimental animals. 

Clouzeau, J. and Read, M.H., Evaluation of Ocular Irritation in the Rabbit, Study performed at the Centre International de Toxicologie, Evereux, France, Technical report, July, 1990. 

Cyclodextrins and their derivatives, which can form inclusion complexes with some drugs, have shown promising results in rabbit studies. Both drug solubility and/or ocular bioavailability are increased, and sometimes tolerability is improved. However, the properties of cyclodextrins in ophthalmic drug delivery are poorly understood, and their benefits are still to be proven in the clinic (Jarvinen et al. 1995). 

Both short- and long-term studies of the effectiveness of permanently implanted probes have been undertaken in the rabbit eye, and in one study probes remained in place for up to six months (48,49,54-58). An early rabbit study of microdialysis probes determined the optimum surgical technique to insert the probes and examined... 

Fetal toxicity has been identified as a sensitive toxic endpoint in rat and rabbit studies involving Octa-BDE. Exposure in the womb resulted in bone malformations and decreased fetal weight in rat and rabbit offspring beginning at doses of 2 mg/kg with fetal death occurring at higher doses" (p.22)... 

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