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88. Long-term safety of irradiated foods
124
MISCELLANEOUS DIRECT ADDITIVES
possessed a predominantly narcotic or hepatotoxic effect. Death within 24 hr was generally associated with a strong narcotic effect and delayed deaths, with a strong hepatotoxic effect in the compounds studied. The prolongation of sleeping time method gave satisfactorily parallel dose-response curves for all the substances tested. This method is therefore suitable for giving absolute values for hepatotoxicity, where this has also been shown to occur in sulphobromophthalein and histological studies, and is also economical in the use of mice. Based on the LDs0 values in this test, the relative hepatoxic potencies were CC14, 100; CBr4, 200; CH3I, 70; CHI3, 10; and CHBrs, 8. Kutob, S. D. & Plaa, G. L. (1962). A procedure for estimating the hepatotoxic potential of certain industrial solvents. Toxicol. appl. PharmacoL 4, 354. 86. TOXICITY OF CHLORINATED ALIPHATIC HYDROCARBON SOLVENTS A useful review is available which describes the hazards occasioned by exposure to common solvents of this type and of the maximum acceptable concentrations in the atmosphere adopted for industrial use. The compounds discussed include methylene chloride, trichloroethane, trichloroethylene, tetrachloroethylene, ethylenedichloride, chloroform and carbon tetrachloride. Exposure hazards are generally well-recognized, but that due to chloroform is not well documented; the information concerning its use as an anaesthetic is not of great value in this respect. Some chronic studies have been carried out on chloroform at the Dow Chemical Co.'s Biochemical Research Laboratory and are shortly to be published. This solvent should be classed with carbon tetrachloride for industrial toxicity purposes. Irish, D. D. (1962). Common chlorinated aliphatic hydrocarbon solvents. Arch. environ. Hlth. 4, 320. 87. THE HEPATOTOXIC EFFECTS OF TRI- AND TETRACHLOROETHYLENE It is believed by many that tetrachloroethylene (I) is less toxic than trichloroethylene (II) (Plaa et al., J. Pharmacol, 1958, 123, 224), but this is disputed by others (von Oettingen, 'The halogenated aliphatic, olefinic, cyclic, aromatic, and aliphatic-aromatic hydrocarbons including the halogenated insecticides, their toxicity and potential dangers', U.S. publ. Hlth. Set. 1955, No. 414). Plaa et al. gave these compounds in a single subcutaneous dose. The present paper describes experiments in which mice were exposed for 4 hr to various concentrations of I and II. After 3 days the animals were sacrificed and the livers examined for fatty infiltration, lI produced only slight infiltration at 6,400 ppm, whereas I caused infiltration at 400 ppm; no necrosis was observed however. For comparison, chloroform gave rise to infiltration at 200 ppm and necrosis at 800 ppm. The authors suggest that the discrepancy between their results and those of Plaa et aLIoc, cit.
is probably due to the different routes by which I and II were administered. Kylin, B., Reichard, H., Siimegi, I. & Yllner, S. (1962). Hepatotoxic effect of tri- and tetrachloroethylene on mice. Nature, Lond. 193, 395. Miscellaneous Direct Additives 88. LONG-TERM SAFETY OF IRRADIATED FOODS Nine foods (bacon, beef, haddock, fresh ham, powdered milk, beets, green beans, "military" cereal and peaches) were subject to 5.58 Mrad, and incorporated into a composite diet which was fed to 4 successive generations of rats. The biological effects produced were compared with those in rats given non-irradiated but otherwise identical batches of these foods. A non-irradiated vitamin supplement was given to make good any loss of vitamin E that took place during irradiation. A significant decrease in the growth in the irradiated food group of rats was not seen save in 1 group of females, where the effect may have been due to marginal inadequacy of the diet. Overall reproductive performances did not differ in the 2 groups, although variations whose effects cancelled out over the 4 generations were noted in the irradiated food group. Differences were not detected between the 2 groups as regards life-span, mortality, or during histological examination of 203 animals taken from all 4 generations. The incidence of neoplasms was nearly identical in the 2 groups but a higher, although statistically insignificant, number of multiple neoplasms was seen in the irradiated food group. Six liver and blood enzyme levels were assayed as indices of possible harmful effects but no indications of toxicity were found. Read, M. S., Kraybill, H. F., Worth, W., Thompson, S. W. & Issac, G. J. (1961). Successive generation rat feeding studies with a composite diet of gamma-irradiated foods. Toxicol. appl. Pharmacol. 3, 153. 89. SAFETY TESTING OF X-IRRADIATED FOODSTUFFS The authors had earlier shown that feeding irradiated pork to rats led to a depression in the activity of certain enzymes, apparently as a result of vitamin E deficiency in the rats, brought about by the destruction of the vitamin during irradiation. In the present study, irradiated pork, bread, shrimps and green beans were incorporated into separate diets at 35, 80 and 85 and 35~o respectively, and vitamin E supplements were given in all cases to replace that destroyed during irradiation. Foods irradiated at the following levels were fed to rats: bread, 25 and 50 Krad and the other foods at 2.79 and 5.58 Mrad. No difference in growth rates were seen after 12 weeks when compared with rats on diets containing foods which had not been irradiated. The levels of 6 different enzymes in the blood were also studied on the assumption that biochemical
MISCELLANEOUS DIRECT ADDITIVES
possessed a predominantly narcotic or hepatotoxic effect. Death within 24 hr was generally associated with a strong narcotic effect and delayed deaths, with a strong hepatotoxic effect in the compounds studied. The prolongation of sleeping time method gave satisfactorily parallel dose-response curves for all the substances tested. This method is therefore suitable for giving absolute values for hepatotoxicity, where this has also been shown to occur in sulphobromophthalein and histological studies, and is also economical in the use of mice. Based on the LDs0 values in this test, the relative hepatoxic potencies were CC14, 100; CBr4, 200; CH3I, 70; CHI3, 10; and CHBrs, 8. Kutob, S. D. & Plaa, G. L. (1962). A procedure for estimating the hepatotoxic potential of certain industrial solvents. Toxicol. appl. PharmacoL 4, 354. 86. TOXICITY OF CHLORINATED ALIPHATIC HYDROCARBON SOLVENTS A useful review is available which describes the hazards occasioned by exposure to common solvents of this type and of the maximum acceptable concentrations in the atmosphere adopted for industrial use. The compounds discussed include methylene chloride, trichloroethane, trichloroethylene, tetrachloroethylene, ethylenedichloride, chloroform and carbon tetrachloride. Exposure hazards are generally well-recognized, but that due to chloroform is not well documented; the information concerning its use as an anaesthetic is not of great value in this respect. Some chronic studies have been carried out on chloroform at the Dow Chemical Co.'s Biochemical Research Laboratory and are shortly to be published. This solvent should be classed with carbon tetrachloride for industrial toxicity purposes. Irish, D. D. (1962). Common chlorinated aliphatic hydrocarbon solvents. Arch. environ. Hlth. 4, 320. 87. THE HEPATOTOXIC EFFECTS OF TRI- AND TETRACHLOROETHYLENE It is believed by many that tetrachloroethylene (I) is less toxic than trichloroethylene (II) (Plaa et al., J. Pharmacol, 1958, 123, 224), but this is disputed by others (von Oettingen, 'The halogenated aliphatic, olefinic, cyclic, aromatic, and aliphatic-aromatic hydrocarbons including the halogenated insecticides, their toxicity and potential dangers', U.S. publ. Hlth. Set. 1955, No. 414). Plaa et al. gave these compounds in a single subcutaneous dose. The present paper describes experiments in which mice were exposed for 4 hr to various concentrations of I and II. After 3 days the animals were sacrificed and the livers examined for fatty infiltration, lI produced only slight infiltration at 6,400 ppm, whereas I caused infiltration at 400 ppm; no necrosis was observed however. For comparison, chloroform gave rise to infiltration at 200 ppm and necrosis at 800 ppm. The authors suggest that the discrepancy between their results and those of Plaa et aLIoc, cit.
is probably due to the different routes by which I and II were administered. Kylin, B., Reichard, H., Siimegi, I. & Yllner, S. (1962). Hepatotoxic effect of tri- and tetrachloroethylene on mice. Nature, Lond. 193, 395. Miscellaneous Direct Additives 88. LONG-TERM SAFETY OF IRRADIATED FOODS Nine foods (bacon, beef, haddock, fresh ham, powdered milk, beets, green beans, "military" cereal and peaches) were subject to 5.58 Mrad, and incorporated into a composite diet which was fed to 4 successive generations of rats. The biological effects produced were compared with those in rats given non-irradiated but otherwise identical batches of these foods. A non-irradiated vitamin supplement was given to make good any loss of vitamin E that took place during irradiation. A significant decrease in the growth in the irradiated food group of rats was not seen save in 1 group of females, where the effect may have been due to marginal inadequacy of the diet. Overall reproductive performances did not differ in the 2 groups, although variations whose effects cancelled out over the 4 generations were noted in the irradiated food group. Differences were not detected between the 2 groups as regards life-span, mortality, or during histological examination of 203 animals taken from all 4 generations. The incidence of neoplasms was nearly identical in the 2 groups but a higher, although statistically insignificant, number of multiple neoplasms was seen in the irradiated food group. Six liver and blood enzyme levels were assayed as indices of possible harmful effects but no indications of toxicity were found. Read, M. S., Kraybill, H. F., Worth, W., Thompson, S. W. & Issac, G. J. (1961). Successive generation rat feeding studies with a composite diet of gamma-irradiated foods. Toxicol. appl. Pharmacol. 3, 153. 89. SAFETY TESTING OF X-IRRADIATED FOODSTUFFS The authors had earlier shown that feeding irradiated pork to rats led to a depression in the activity of certain enzymes, apparently as a result of vitamin E deficiency in the rats, brought about by the destruction of the vitamin during irradiation. In the present study, irradiated pork, bread, shrimps and green beans were incorporated into separate diets at 35, 80 and 85 and 35~o respectively, and vitamin E supplements were given in all cases to replace that destroyed during irradiation. Foods irradiated at the following levels were fed to rats: bread, 25 and 50 Krad and the other foods at 2.79 and 5.58 Mrad. No difference in growth rates were seen after 12 weeks when compared with rats on diets containing foods which had not been irradiated. The levels of 6 different enzymes in the blood were also studied on the assumption that biochemical