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1633. Benzene metabolism in vitro
668
THE CHEMICAL ENVIRONMENT
effects. Perhaps the most significant finding was that the toxicities of supposedly identical plasticizers obtained from different sources may differ widely. Commercial samples containing isomers and homologues can exhibit toxicities not inherent in freshly synthesized samples of the pure esters. And the picture can change again during the processes involved in incorporating the plasticizer in plastics, or during storage. For users of plastics in the medical field, the warnings are clear.
THE CHEMICAL E N V I R O N M E N T 1633. Benzene metabolism in vitro Snyder, R., Uzuki, F., Gonasun, L., Bromfeld, Esther & Wells, A. (1967). The metabolism of benzene in vitro. Toxic. appl. Pharmac. 11, 346. Phenol and its conjugates, phenyl sulphate and phenyl glucuronide, are known to be the main metabolites of benzene in vivo and in vitro (Cited in F.C.T. 1966, 4, 461). Recent work using rabbit- and rat-liver preparations has been concerned with the effect on subsequent benzene metabolism of pretreating the animal with benzene or phenobarbital. Stimulation of benzene metabolism occurred after pretreatment with either compound. A two- to threefold increase in phenol formation was seen in preparations from rabbits which had received 1-25 ml benzene/kg by subcutaneous injection on one or two consecutive days prior to sacrifice. At least two doses (80 mg/kg) over several days were required to obtain maximum stimulation with phenobarbital, following which both oxidation of the benzene ring and subsequent conjugation were increased. Both compounds caused an increase in the rate of amino-acid uptake into microsomal protein, which indicated that more benzene-metabolizing enzymes may have been induced by the pretreatment. It could be argued that the pretreatment resulted in depletion of the specific amino acid used in uptake studies but no such effects have as yet been demonstrated in animals treated with benzene. The increases in amino-acid uptake were observed within 12 hr of a single dose of benzene but were not appreciably greater when four doses were given over a 2-day period. Increases in the amount of benzene added to the liver preparations resulted only in an increased production of phenol, suggesting that saturation of the conjugating enzyme may have occurred. Alternatively, this observation may be explained by a lack of substrates and co-factors for conjugate formation. 1634. A no-effect level for benzopyrene? Neal, J. & Rigdon, R. H. (1967). Gastric tumors in mice fed benzo(a)pyrene: A quantitative study. Tex. Rep. Biol. Med. 25, 553. These authors have investigated the incidence of gastric tumours in mice fed benzo[a]pyrene (BP) at various levels and for varying lengths of time. Mice fed BP for 1 I0 days at levels of 1, I0 or 30 ppm in the diet developed no tumours, but gastric tumours occurred in 1/23 mice fed 20 ppm, 1/40 fed 40 ppm and 4/40 fed 45 ppm. A level of 50 ppm BP for 107197 days produced tumours in 70 Yo of the mice, whereas 250 ppm for 70-165 days caused a 90 Yo'tumour incidence. In another experiment mice were fed a diet containing BP for a few days, followed by untreated laboratory chow for a longer period, the total time of feeding being in each case
THE CHEMICAL ENVIRONMENT
effects. Perhaps the most significant finding was that the toxicities of supposedly identical plasticizers obtained from different sources may differ widely. Commercial samples containing isomers and homologues can exhibit toxicities not inherent in freshly synthesized samples of the pure esters. And the picture can change again during the processes involved in incorporating the plasticizer in plastics, or during storage. For users of plastics in the medical field, the warnings are clear.
THE CHEMICAL E N V I R O N M E N T 1633. Benzene metabolism in vitro Snyder, R., Uzuki, F., Gonasun, L., Bromfeld, Esther & Wells, A. (1967). The metabolism of benzene in vitro. Toxic. appl. Pharmac. 11, 346. Phenol and its conjugates, phenyl sulphate and phenyl glucuronide, are known to be the main metabolites of benzene in vivo and in vitro (Cited in F.C.T. 1966, 4, 461). Recent work using rabbit- and rat-liver preparations has been concerned with the effect on subsequent benzene metabolism of pretreating the animal with benzene or phenobarbital. Stimulation of benzene metabolism occurred after pretreatment with either compound. A two- to threefold increase in phenol formation was seen in preparations from rabbits which had received 1-25 ml benzene/kg by subcutaneous injection on one or two consecutive days prior to sacrifice. At least two doses (80 mg/kg) over several days were required to obtain maximum stimulation with phenobarbital, following which both oxidation of the benzene ring and subsequent conjugation were increased. Both compounds caused an increase in the rate of amino-acid uptake into microsomal protein, which indicated that more benzene-metabolizing enzymes may have been induced by the pretreatment. It could be argued that the pretreatment resulted in depletion of the specific amino acid used in uptake studies but no such effects have as yet been demonstrated in animals treated with benzene. The increases in amino-acid uptake were observed within 12 hr of a single dose of benzene but were not appreciably greater when four doses were given over a 2-day period. Increases in the amount of benzene added to the liver preparations resulted only in an increased production of phenol, suggesting that saturation of the conjugating enzyme may have occurred. Alternatively, this observation may be explained by a lack of substrates and co-factors for conjugate formation. 1634. A no-effect level for benzopyrene? Neal, J. & Rigdon, R. H. (1967). Gastric tumors in mice fed benzo(a)pyrene: A quantitative study. Tex. Rep. Biol. Med. 25, 553. These authors have investigated the incidence of gastric tumours in mice fed benzo[a]pyrene (BP) at various levels and for varying lengths of time. Mice fed BP for 1 I0 days at levels of 1, I0 or 30 ppm in the diet developed no tumours, but gastric tumours occurred in 1/23 mice fed 20 ppm, 1/40 fed 40 ppm and 4/40 fed 45 ppm. A level of 50 ppm BP for 107197 days produced tumours in 70 Yo of the mice, whereas 250 ppm for 70-165 days caused a 90 Yo'tumour incidence. In another experiment mice were fed a diet containing BP for a few days, followed by untreated laboratory chow for a longer period, the total time of feeding being in each case