Laboratory animal

Colourless prisms m.p. 49-50 C, b.p. 184 C. Prepared by the action of ammonia on ethyl chloroformate. Used as a long-acting anaesthetic for laboratory animals. 

The toxicity of these fluoroaluminates is mainly as inorganic fluorides. The ACGIH adopted (1992—1993) values for fluorides as F is TLV 2.5 mg/m. The oral toxicity in laboratory animal tests is reported to be LD q rat 2.15 mg/kg (41). Because of the fine nature of the products they can also be sources of chronic toxicity effects as dusts. 

Saccharin. Sacchatin [81-07-2] C H NO S, which is approximately 300 times as sweet as sucrose ia coaceatratioas up to the equivaleat of a 10% sucrose solutioa, has beea used commercially as a nonnutritive sweeteaer siace before 1900, predomiaanfly ia carboaated soft drioks, tabletop sweeteaers, and dietetic foods marketed primarily to diabetics. In 1977, the FDA proposed a ban on sacchatin because of its association with bladder cancer ia laboratory animals. At the time, it was the only commercially available nonnutritive sweetener, and pubflc outcry led to a delay of the ban, which was officially withdrawn ia 1991. Instead, the FDA required that warning labels be placed on all foods that contained the iagredient. Although sacchatin is heat stable, the pubflc debate over its safety, as well as the fact that approximately one-third of the population perceives it to have a bitter aftertaste, has limited its use. 

Daylight fluorescent pigments (qv) are considered to be nontoxic. Since they are combinations of polymers and dyestuffs, the combined effect of the ingredients must be taken into account when considering the net toxic effect of these materials. Table 5 gives results of laboratory animal toxicity tests of standard modified melamine—formaldehyde-type pigments, the Day-Glo A Series, and the products recommended for plastic mol ding, Day-Glo Z-series. 

Table 5. Results of Laboratory Animal Toxicity Tests...

A comprehensive study of the tolerance of laboratory animals to vapors of 2-nitropropane was reported in 1952 (100). In a study pubHshed in 1979, rabbits and rats survived exposure to nitromethane for six months at 750 and 100 ppm, respectively, with no unexpected findings (101). Similarly, no compound-related effects were found for rabbits exposed to 2-nitropropane at 200 ppm or for rabbits or rats exposed at 27 ppm. Liver damage was extensive in male rats exposed at 207 ppm for six months, and hepatocellular carcinomas were observed. Subsequendy, the International Agency for Research on Cancer (lARC) found that there is "sufficient evidence" to conclude that 2-nitropropane causes cancer in rats but that epidemiologic data are inadequate to reinforce the conclusion in humans (102). The National Toxicology Program also concluded that it "may reasonably be anticipated to be a carcinogen" (103). 

W. J. Hayes, Jr., and E. R. Laws, Jr., eds.. Handbook of Pesticide Toxicology, Academic Press, Inc., San Diego, Calif., 1990. Three volume set provides detailed toxicological profiles of more than 250 insecticides, herbicides, and fungicides each compound described by identity, properties, and uses toxicity to humans, laboratory animals, domestic animals, and wildlife includes comprehensive coverage of diagnosis, treatment, prevention of injury, effects on domestic animals, wildlife, and humans - ISjOOO references. 

The therapeutically active dmg can be extracted from plant or animal tissue, or be a product of fermentation (qv), as in the case of antibiotics. Frequentiy, it is synthesized and designed to correlate stmcture with therapeutic activity. Pharmacologic activity is first tested on laboratory animals. When the results ate encouraging, physical and chemical properties are determined in the so-called preformulation stage, and analytical procedures are developed for quahty control (see Qualityassurance/qualitycontrol). 

Subchronic effects of overexposure have been studied in feeding tests of PPS powder at dietary levels of up to 5%. No detrimental effects in laboratory animals were observed (157). 

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. 

Based on tests with laboratory animals, aniline may cause cancer. The National Cancer Institute (NCI) and the Chemical Industry Institute of Toxicology (CUT) conducted lifetime rodent feeding studies, and both studies found tumors of the spleen at high dosage (100 —300 mg/kg pet day of aniline chloride). CUT found no tumors at the 10—30 mg/kg per day feeding rates. The latter value is equivalent to a human 8-h inhalation level of 17—50 ppm aniline vapor. In a short term (10-d) inhalation toxicity test by Du Pont, a no-effect level of 17 ppm aniline vapor was found for rats. At high levels (47—87 ppm), there were blood-related effects which were largely reversible within a 13-d recovery period (70). 

The microdialysis sampling process which allows the monitoring of small molecules in circulation within an animal, is an example. An artificial capillary is placed in the tissue region of interest, and a sample is coUected via dialysis. In the case of a laboratory animal such as a rat, a probe is placed in the jugular vein under anesthesia. Elow rates ate of the order of 1 p.L/min. 

Toxicity. No mortahty in laboratory animals was induced in percutaneous doses up to 3.8 g/kg body weight (19,20). Subcutaneous adininistration of sulfolane gives LD q values for rats, mice, and rabbits of 1.606, 1.360, and 1.900—3.500 g/kg body weight, respectively (21). LD q values... 

Sulfolane causes minimal and transient eye and skin irritation (19,20). Inhalation of sulfolane vapors in a saturated atmosphere is not considered biologically significant. However, when aerosol dispersions have been used to elevate atmospheric concentration, blood changes and convulsions have been observed in laboratory animals (22,31). Convulsions caused by sulfolane injected intraperitoneaHy have also been studied (32). 

Legislation to stay the ban has been passed in the U.S. Congress periodically. In December, 1991, the FDA withdrew its proposed ban. AH saccharin-containing packaged products are required to carry a warning label indicating that saccharin has been determined to cause cancer in laboratory animals. 

Thermal neutron activation analysis has been used for archeological samples, such as amber, coins, ceramics, and glass biological samples and forensic samples (see Forensic chemistry) as weU as human tissues, including bile, blood, bone, teeth, and urine laboratory animals geological samples, such as meteorites and ores and a variety of industrial products (166). 

Acute toxicity in laboratory animals and target species, including eye and skin irritation and toxicity. 

Chronic toxicity in laboratory animals by two-year or lifetime feedings in two species of laboratory animals, multiple-generation teratogenicity, and, not always required, one-year feeding of dogs. 

In veterinary medicine, the Hst of inhalation anesthetics generally includes only two agents, halothane [151 -67-7] and methoxyflurane [76-38-0]. Although ether (ethyl ether) is used extensively in experimental work with laboratory animals, the risks associated with its use and the advantages of halothane and methoxyflurane have removed ether from general use by the practitioner. 

Antimony is not known to cause cancer, birth defects, or affect reproduction in humans. However, antimony has been shown to cause lung cancer in laboratory animals that inhaled antimony-containing dusts and prolonged exposure to antimony can cause irritation of the eyes, skin, lungs, and stomach, in the form of vomiting and diarrhea. Heart problems can also result from overexposure to antimony (33). 

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