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2608. Serum enzyme studies in toxicity testing
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METHODS FOR ASSESSING TOXICITY
that lower concentrations of wool alcohols provide a conclusive test for lanolin allergy, although other work (ibid 1969, 7, 703) suggests that this may be so. The author of this work concludes that lanolin allergy, although fairly infrequent, is more common than allergy to preservatives such as parabens, and has an incidence similar to that of formaldehyde allergy. However, while lanolin may provoke allergic reactions relatively infrequently, their diagnosis is particularly important on account of the wide range of products in which lanolin is used.
METHODS FOR ASSESSING TOXICITY
2608. Serum enzyme studies in toxicity testing Korsrud, G. O., Grice, H. C. & McLaughlan, J. M. (1972). Sensitivity of several serum enzymes in detecting carbon tetrachloride-induced liver damage in rats. Toxic. appl. Pharmac. 22, 474. Members of the group cited above have already reported a study in which they related the development of detectable changes in serum enzyme levels and isozyme patterns to the appearance of morphological damage in the liver and kidney, following treatment of rats with carbon tetrachloride (CC14), mercuric chloride, diethanolamine and thioacetamide (Grice et al. Fd Cosmet. ToxicoL 1971, 9, 847). They found that light- and electron-microscopy were more sensitive indicators of toxic effect than the commonly used serum enzyme activities, obvious morphological damage being induced by dose levels considerably lower than those required to produce detectable changes in serum glutamic-oxalacetic transaminase and lactic dehydrogenase. The study has now been extended to a search for enzymes that would respond quantitatively to varying doses of CC14 and would indicate minimal liver damage. Attention was concentrated on enzymes normally found mainly in the liver and occurring only at low levels in the serum and erythrocytes. The studies were carried out in male rats (80--100 days old) fed a standard commercial diet (in the first experiment) or the same commercial diet or a semi-purified diet (in the second experiment). They were killed 18 hr after receiving a single oral dose of CC14 within the range 0.001-2.50 ml/kg. In the first study, activities of serum sorbitol dehydrogenase (SDH), fructose-l-phosphate aldolase, isocitrate dehydrogenase and glutamic-oxalacetic and glutamic-pyruvic transaminases were found to be increased in rats given 0.025 ml CCl4/kg, but higher doses were required to increase the activities of alcohol dehydrogenase, 6-phosphogluconate dehydrogenase, malic dehydrogenase and lactic dehydrogenase. The activities of several of the enzymes were dose-dependent over a wide dose range. Liver weight and fat content and serum urea also increased with a dose of 0.025 ml/kg or more, while serum arginine showed a dose-related decrease. In the second experiment, the enzyme activities were less sensitive to CC14, most enzyme activities showing an increase only with a dose of 0.1 ml/kg. SDH was increased by 0.025 ml CCl,/kg, but only in rats on the semipurified diet. However, liver fat was increased in animals given 0.025 ml/kg and liver weight was increased in those given 0.05 ml/kg, while morphological damage was detectable in the liver following a dose of 0.0125 ml/kg, the lowest dose given to rats studied histologically. Increasing liver damage was paralleled by increases in some serum-enzyme activities, but overt liver-cell necrosis was not a prerequisite of detectable changes in enzyme activity.
METHODS FOR ASSESSING TOXICITY
that lower concentrations of wool alcohols provide a conclusive test for lanolin allergy, although other work (ibid 1969, 7, 703) suggests that this may be so. The author of this work concludes that lanolin allergy, although fairly infrequent, is more common than allergy to preservatives such as parabens, and has an incidence similar to that of formaldehyde allergy. However, while lanolin may provoke allergic reactions relatively infrequently, their diagnosis is particularly important on account of the wide range of products in which lanolin is used.
METHODS FOR ASSESSING TOXICITY
2608. Serum enzyme studies in toxicity testing Korsrud, G. O., Grice, H. C. & McLaughlan, J. M. (1972). Sensitivity of several serum enzymes in detecting carbon tetrachloride-induced liver damage in rats. Toxic. appl. Pharmac. 22, 474. Members of the group cited above have already reported a study in which they related the development of detectable changes in serum enzyme levels and isozyme patterns to the appearance of morphological damage in the liver and kidney, following treatment of rats with carbon tetrachloride (CC14), mercuric chloride, diethanolamine and thioacetamide (Grice et al. Fd Cosmet. ToxicoL 1971, 9, 847). They found that light- and electron-microscopy were more sensitive indicators of toxic effect than the commonly used serum enzyme activities, obvious morphological damage being induced by dose levels considerably lower than those required to produce detectable changes in serum glutamic-oxalacetic transaminase and lactic dehydrogenase. The study has now been extended to a search for enzymes that would respond quantitatively to varying doses of CC14 and would indicate minimal liver damage. Attention was concentrated on enzymes normally found mainly in the liver and occurring only at low levels in the serum and erythrocytes. The studies were carried out in male rats (80--100 days old) fed a standard commercial diet (in the first experiment) or the same commercial diet or a semi-purified diet (in the second experiment). They were killed 18 hr after receiving a single oral dose of CC14 within the range 0.001-2.50 ml/kg. In the first study, activities of serum sorbitol dehydrogenase (SDH), fructose-l-phosphate aldolase, isocitrate dehydrogenase and glutamic-oxalacetic and glutamic-pyruvic transaminases were found to be increased in rats given 0.025 ml CCl4/kg, but higher doses were required to increase the activities of alcohol dehydrogenase, 6-phosphogluconate dehydrogenase, malic dehydrogenase and lactic dehydrogenase. The activities of several of the enzymes were dose-dependent over a wide dose range. Liver weight and fat content and serum urea also increased with a dose of 0.025 ml/kg or more, while serum arginine showed a dose-related decrease. In the second experiment, the enzyme activities were less sensitive to CC14, most enzyme activities showing an increase only with a dose of 0.1 ml/kg. SDH was increased by 0.025 ml CCl,/kg, but only in rats on the semipurified diet. However, liver fat was increased in animals given 0.025 ml/kg and liver weight was increased in those given 0.05 ml/kg, while morphological damage was detectable in the liver following a dose of 0.0125 ml/kg, the lowest dose given to rats studied histologically. Increasing liver damage was paralleled by increases in some serum-enzyme activities, but overt liver-cell necrosis was not a prerequisite of detectable changes in enzyme activity.