Mouse effects

Corchero J, Granvil CP, Akiyama TE, Hayhurst GP, Pimprale S, et al. 2001. The CYP2D6 humanized mouse effect of the human CYP2D6 transgene and HNF4alpha on the disposition of debrisoquine in the mouse. Mol Pharmacol 60 1260-1267. 

Several studies in rats, mice, and rabbits demonstrate that cycloheximide is embry-otoxic, fetotoxic, and teratogenic. Intraperi-toneal administration of doses as low as 250 pg/kg on day 10 of gestation produced central nervous system, craniofacial, and cardiovascular system abnormalities in rats. Musculoskeletal abnormalities were produced in mice after intraperitoneal administration of doses as low as 30mg/kg on day 9 of gestation. Subcutaneous administration of 5 mg/1 cycloheximide on day 11 caused postimplantation mortality in the mouse. Effects on fertility were observed in pregnant rabbits administered as little as 5 pg/kg on day 1 of gestation. 

Gordon CJ, Fogelson L, Stead AG. 1989. Temperature regulation following nickel intoxication in the mouse Effect of ambient temperature. Comp Biochem Physiol 92 73-76. 

Okine, L.K., Goochee. J.M. Gram, T.E. (1985) Studies on the distribution and covalent binding of 1,1-dichloroethylene in the mouse. Effect of various pretreatments on covalent binding in vivo. Biochem. Pharmacol., 34, 4051-4057... 

Volkl H, Greger R, Lang F. 1987. Potassium conductance in straight proximal tubule cells of the mouse. Effect of barium, verapamil and quinidine. Biochim Biophys Acta 900 275-281. 

L.L. Sarlieve, R. Bouchon, C. Koehl and N.M. Neskovic, Cerebroside and sulfatide biosynthesis in the brain of Snell Dwarf mouse effects of thyroxine and growth hormone in the early postnatal period, J. NeurochCTi. 40 1058 (1983). 

Oral LD q levels have been deterrnined in the mouse at 470 mg/kg (21) and the guinea pig at 7750 mg/kg (22). Several other studies (23—25) have shown that large quantities of both synthetic and natural glycerol can be adniinistered orally to experimental animals and humans without the appearance of adverse effects. Intravenous adniinistration of solutions containing 5% glycerol to animals and humans has been found to cause no toxic or otherwise undesirable effects (26). 

The LC q (lowest possible lethal concentration) has been reported to be 23 ppm for a 30 min exposure time (mouse), 53 ppm for an exposure time of 100 min (rat, rabbit, and guinea pig), and 200 ppm for an exposure time of 10 min (monkey). No toxic effects were reported upon exposure to 1 ppm for 7 h/d over 55 days. The oral LD q (rat) of ketene is 1300 mg/kg, the low level of toxicity probably being due to the almost immediate formation of acetic acid and other acetates in the digestive tract. 

The effect of pyrogaHol on algae has also been studied (27). Acute toxicity data include oral LD q (rat) = 789 mg/kg, intraperitoneal LD3Q (mouse) = 400 mg/kg, and oral LD q (rabbit) = 1600 mg/kg (28). 

Teratogenic effects have been noted with 2- and 4-aminophenol in the hamster, but 3-aminophenol was without effect in the hamster and rat (129,130). 4-Aminophenol is known to inhibit DNA synthesis and alter DNA stmcture in human lymphoblasts (131,132) and is mutagenic in mouse micronuclei tests (133). The aminophenols have been shown to be genotoxic, as evidenced by the induction of sister chromatid exchanges (134,135), but they also exert a protective effect against DNA interaction with other noxious chemicals (136). After assessment of available data a recent report stated that the aminophenols were safe as cosmetic ingredients in their present uses and concentrations (137). 

Chinese Herbal Medicines. Many traditional Chinese medicines have been screened for radioprotective activity in experimental animals. In one study of more than a thousand Chinese herbs, a number of agents increased the survival rate of dogs exposed to a lethal dose of y-rays by 30—40%, and some symptoms of radiation injury were ameHorated. These effects are potentially related to stimulation of the hemopoietic and immune systems (130). Extracts of five Chinese dmg plants, as weU as aspirin, effectively protected mice exposed to 7.5—8.0 Gy (750—800 rad) of y-radiation, and increased survival rates by 8—50% (131). Several Chinese traditional medicines, adininistered ip before or after irradiation, protected against Hpid peroxidation in a variety of mouse tissues, including BM, Hver, and spleen, as weU as in mouse Hver microsomal suspensions irradiated in vitro (132). 

Diethjidithiocarbamate [20624-25-3] (DDC) is both an inhibitor of SOD and a thiol, and exerts both radiosensitizing and radioprotective properties in mice, depending on factors such as the time of its adniinistration relative to irradiation. For neutrons, DDC shows only protective effects (141). DDC (1 mg/g ip) given 30 min before 15 Gy (1500 rad) also protects mouse jejunal crypt ceUs and reduces the frequency of micronuclei in splenic lymphocytes (134). 

Health and Safety Factors. Carbonyl sulfide is dangerously poisonous, more so because it is practically odorless when pure. It is lethal to rats at 2900 ppm. Studies show an LD q (rat, ip) of 22.5 mg/kg. The mechanism of toxic action appears to iavolve breakdowa to hydrogea sulfide (36). It acts principally on the central nervous system with death resulting mainly from respiratory paralysis. Little is known regarding the health effects of subacute or chronic exposure to carbonyl sulfide a 400-p.g/m max level has been suggested until more data are available (37). Carbon oxysulfide has a reported inhalation toxicity in mice LD q (mouse) = 2900 ppm (37). 

Reproductive Toxicity. No data are available that impHcate either hexavalent or trivalent chromium compounds as reproductive toxins, unless exposure is by way of injection. The observed teratogenic effects of sodium dichromate(VI), chromic acid, and chromium (HI) chloride, adininistered by injection, as measured by dose-response relationships are close to the amount that would be lethal to the embryo, a common trait of many compounds (111). Reported teratogenic studies on hamsters (117,118), the mouse (119—121), and rabbits (122) have shown increased incidence of cleft palate, no effect, and testicular degeneration, respectively. Although the exposures for these experiments were provided by injections, in the final study (122) oral, inhalation, and dermal routes were also tried, and no testicular degeneration was found by these paths. 

Landgrebe J, Welzl G, Metz T et al (2002) Molecular characterisation of antidepressant effects in the mouse brain using gene expression profiling. J Psychiatr Res 36 119-129... 

Anticytokine antibodies Infliximab Chimeric (mouse/human) monoclonal antibody against TNEa. Effective in the treatment of severe forms of rheumatoid arthritis where it can halt disease progression, or inflammatory bowel disease (EBD). 

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