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3078. No simple test for skin irritancy
516
Pathology. Cancer research
3078. No simple test for skin irritancy Nixon, G. A., Tyson, C. A. 8~ Wertz, W. C. (1975). Interspecies comparisons of skin irritancy. Tosic. up/A. P/wmm. 31, 481. Results of irritancy determinations on rabbit skin using modifications of the Draize test (Tosic. nppl. Pkarrmc. 1971, 19, 276) do not always correlate well with those of tests on human skin; nevertheless comparative tests have confirmed the rabbit as a suitable animal for preliminary irritancy testing, since in general it was more sensitive than other test animals (Cited iri F.C.?: 1973, 11, 346). Further reflections on the problems of inter-species comparison arise from the paper now under review. Fifteen household products and nine industrial chemicals were tested for irritancy on intact and abraded skin of rabbits. guinea-pigs and man by a 4-hr application. Isopropyl alcohol, sodium tripolyphosphate, lO?d sulphuric acid and table salt gave insignificant reactions in all test species. High- and low-carbonate detergents, phosphate detergent, enzyme detergent. liquid detergent, liquid cleaner.
soap, antiperspirant, lemon juice and sodium carbonate produced slight to moderate irritation in rabbits, guinea-pigs or both, but not in man. Pine oil cleaner, liquid shampoo and sodium lauryl sulphate were slightly irritant to human skin and moderately irritant to rabbits, guinea-pigs or both. Three materials produced more severe reactions in man than in the test animals: hypochlorite bleach, slightly irritant in rabbits and guinea-pigs. caused eschar and weeping on the intact skin of four of seven human subjects, fatty acids (Cs-Ci,,) caused slight reactions in guineapigs, moderate to severe erythema in rabbits and weeping and eschar formation on the intact skin of two of seven humans, and metasilicate/carbonate detergent produced severe erythema and vesication of intact human skin and severe necrosis in rabbits, but a negligible reaction in guinea-pigs. Much discrepancy between human and animal observations arose when abraded skin sites were tested, and it is recommended that such tests should be discontinued to avoid unnecessary confusion in interpretation. It is recommended, moreover, that neither the rabbit nor the guinea-pig should be relied upon exclusively in testing for’ potential human-skin irritants.
PATHOLOGY 3079. Cloudy swelling clarified? Ling, G. N. & Walton, C. L. (1976). What retains water in living cells? Science, N.Y. 191, 293. According to the classical theory, intracellular water is retained by means of an intact cell membrane, while the water content is regulated by a variety of complex biochemical ‘pumps’, which need ATP to function. A second hypothesis suggests, however, that an undamaged membrane is not essential to the retention of water within the cell. Support for this view has come from some recent studies on the frog sartorius muscle. Under carefully controlled conditions, centrifugatinn of the intact muscle for 4 min at a relative centrifugal force. varying between 400 and 1500g extracted a constant volume of tissue water equal to the volume of the extracellular fluid in the muscle. The volume of fluid removed in this way was found to be the same even when the cell membranes had been damaged by a series of carefully placed incisions in
CANCER 3080. Bladder amine
tumours
from
RESEARCH
nitrosomethyldadecyl-
Lijinsky, W. & Taylor, H. W. (1975). Induction urinary bladder tumors in rats by administration nitrosomethyldodecylamine. Cancer Res. 35, 958.
the muscle tissue, which consists of parallel, elongated cells each about 3 cm long. Furthermore, intact and cut muscle tissue swelled to the same degree when immersed in a hypotonic solution. These experiments, and others involving inhibition of tissue metabolism, suggest that the integrity of the cell membrane is not essential for the retention of cell water. It is thought that intracellular water is adsorbed on to cell proteins, with ATP functioning not as a ‘fuel’ but in a key physico-chemical role. This involves its attachment to critical sites on the protein molecule, which is thereby maintained in an extended conformation allowing the backbone peptide groups to polarize, orient themselves and retain deep layers of water. [This new concept is of some interest to the pathologist. Minor accumulation of intracellular water, called ‘cloudy swelling’, cannot be accounted for satisfactorily by the old hypothesis, since biochemically and ultrastructurally there is little evidence of breakdown of cell components. The new hypothesis suggests that cloudy swelling could be due to minor conformational changes in the protein molecule.]
of of
A study of 65 different nitrosamines revealed that asymmetric dialkylnitrosamines are generally oesophageal carcinogens (Cited in F.C.T. 1968, 6, 648).
This study included a variety of N-methyl-h’ .alkylnitrosamines of chain length up to C, (n-heptyl-). For symmetrical dialkylnitrosamines, the primary site of action is typically the liver, although dibutylnitrosamine is also a potent bladder carcinogen (ibid 196.5, 3, 498). The latter effect is attributed to the hydroxylated metabolite, butyl-(4-hydroxybutyI)nitrosamine which, when administered to mice in the drinkingwater, produced lethal bladder tumours without the appearance of other toxic effects-in males much ear-
Pathology. Cancer research
3078. No simple test for skin irritancy Nixon, G. A., Tyson, C. A. 8~ Wertz, W. C. (1975). Interspecies comparisons of skin irritancy. Tosic. up/A. P/wmm. 31, 481. Results of irritancy determinations on rabbit skin using modifications of the Draize test (Tosic. nppl. Pkarrmc. 1971, 19, 276) do not always correlate well with those of tests on human skin; nevertheless comparative tests have confirmed the rabbit as a suitable animal for preliminary irritancy testing, since in general it was more sensitive than other test animals (Cited iri F.C.?: 1973, 11, 346). Further reflections on the problems of inter-species comparison arise from the paper now under review. Fifteen household products and nine industrial chemicals were tested for irritancy on intact and abraded skin of rabbits. guinea-pigs and man by a 4-hr application. Isopropyl alcohol, sodium tripolyphosphate, lO?d sulphuric acid and table salt gave insignificant reactions in all test species. High- and low-carbonate detergents, phosphate detergent, enzyme detergent. liquid detergent, liquid cleaner.
soap, antiperspirant, lemon juice and sodium carbonate produced slight to moderate irritation in rabbits, guinea-pigs or both, but not in man. Pine oil cleaner, liquid shampoo and sodium lauryl sulphate were slightly irritant to human skin and moderately irritant to rabbits, guinea-pigs or both. Three materials produced more severe reactions in man than in the test animals: hypochlorite bleach, slightly irritant in rabbits and guinea-pigs. caused eschar and weeping on the intact skin of four of seven human subjects, fatty acids (Cs-Ci,,) caused slight reactions in guineapigs, moderate to severe erythema in rabbits and weeping and eschar formation on the intact skin of two of seven humans, and metasilicate/carbonate detergent produced severe erythema and vesication of intact human skin and severe necrosis in rabbits, but a negligible reaction in guinea-pigs. Much discrepancy between human and animal observations arose when abraded skin sites were tested, and it is recommended that such tests should be discontinued to avoid unnecessary confusion in interpretation. It is recommended, moreover, that neither the rabbit nor the guinea-pig should be relied upon exclusively in testing for’ potential human-skin irritants.
PATHOLOGY 3079. Cloudy swelling clarified? Ling, G. N. & Walton, C. L. (1976). What retains water in living cells? Science, N.Y. 191, 293. According to the classical theory, intracellular water is retained by means of an intact cell membrane, while the water content is regulated by a variety of complex biochemical ‘pumps’, which need ATP to function. A second hypothesis suggests, however, that an undamaged membrane is not essential to the retention of water within the cell. Support for this view has come from some recent studies on the frog sartorius muscle. Under carefully controlled conditions, centrifugatinn of the intact muscle for 4 min at a relative centrifugal force. varying between 400 and 1500g extracted a constant volume of tissue water equal to the volume of the extracellular fluid in the muscle. The volume of fluid removed in this way was found to be the same even when the cell membranes had been damaged by a series of carefully placed incisions in
CANCER 3080. Bladder amine
tumours
from
RESEARCH
nitrosomethyldadecyl-
Lijinsky, W. & Taylor, H. W. (1975). Induction urinary bladder tumors in rats by administration nitrosomethyldodecylamine. Cancer Res. 35, 958.
the muscle tissue, which consists of parallel, elongated cells each about 3 cm long. Furthermore, intact and cut muscle tissue swelled to the same degree when immersed in a hypotonic solution. These experiments, and others involving inhibition of tissue metabolism, suggest that the integrity of the cell membrane is not essential for the retention of cell water. It is thought that intracellular water is adsorbed on to cell proteins, with ATP functioning not as a ‘fuel’ but in a key physico-chemical role. This involves its attachment to critical sites on the protein molecule, which is thereby maintained in an extended conformation allowing the backbone peptide groups to polarize, orient themselves and retain deep layers of water. [This new concept is of some interest to the pathologist. Minor accumulation of intracellular water, called ‘cloudy swelling’, cannot be accounted for satisfactorily by the old hypothesis, since biochemically and ultrastructurally there is little evidence of breakdown of cell components. The new hypothesis suggests that cloudy swelling could be due to minor conformational changes in the protein molecule.]
of of
A study of 65 different nitrosamines revealed that asymmetric dialkylnitrosamines are generally oesophageal carcinogens (Cited in F.C.T. 1968, 6, 648).
This study included a variety of N-methyl-h’ .alkylnitrosamines of chain length up to C, (n-heptyl-). For symmetrical dialkylnitrosamines, the primary site of action is typically the liver, although dibutylnitrosamine is also a potent bladder carcinogen (ibid 196.5, 3, 498). The latter effect is attributed to the hydroxylated metabolite, butyl-(4-hydroxybutyI)nitrosamine which, when administered to mice in the drinkingwater, produced lethal bladder tumours without the appearance of other toxic effects-in males much ear-