- Email: [email protected]
1608. Naphthalene metabolism—a slight advance
546
THE CHEMICALENVIRONMENT
potent alkylating agent in man. The negative result of previous investigations was probably due to a short duration of exposure. The long latent period emphasizes the importance of careful and prolonged follow-up of cases exposed to suspected carcinogenic agents and underlines the conclusions of Case & Hosker (Br. J. prey. soc. Med. 1954, 8, 39) from their studies on 2-naphthylamine. There is also an important lesson here for the experimentalist. A limited intensive exposure of the mammalian organs to a carcinogenic agent suffices to induce a significant increase over the natural incidence of tumours if the test animals are capable of surviving for the duration of their natural life span. Is continued treatment till the 'bitter end' really necessary in carcinogenicity testing ?]
1608. Naphthalene metabolism--a slight advance Holtzman, J., Gillette, J. R. & Milne, G. W. A. (1967). The metabolic products of naphthalene in mammalian systems. J. A m chem. Soc. 89, 6341. Naphthalene (I) is metabolized to various major products, including a-naphthol (II), 1,2-dihydro-l,2-dihydroxynaphthalene (III) and S-(1,2-dihydro-2-hydroxy-l-naphthyl)glutathione (IV) (Cited in F.C.T. 1965, 3, 661 ; Young, Biochem. J. 1947, 41,417; Booth et al. ibid. 1960, 77, 182). The conversion of I to II and Ili is catalysed by liver microsomal enzymes requiring both reduced nicotinamide-adenine dinucleotide phosphate and molecular oxygen. But the exact metabolic pathway is still unknown. Holtzman et al. (cited above) have now found that conversion of I to II and III by liver homogenates is catalysed by a mono-oxygenase (only one atom of molecular oxygen is incorporated, the second oxygen being apparently derived from water), that the initial attack on I takes place at the a position and that the trans form of III is produced. It also appears likely that II and III (neither of which serves as a precursor of the other) are formed from I via a common precursor, which, if the postulated structure is correct, could also readily be converted into IV. 1609. Toluene through the skin Dutkiewicz, T. & Tyras, H. (1968). The quantitative estimation of toluene skin absorption in man. Arch. Gewerbepath. Gewerbehyg. 24, 253. We recently reported cases of acute poisoning in man following exposure to high atmospheric concentrations of toluene (Cited in F.C.T. 1968, 6, 291). Some quantitative data have now been presented on the extent to which this solvent, widely used as a paint thinner and in many industrial processes, may be absorbed through the human skin. The rate of absorption of undiluted toluene and of toluene in aqueous solution was measured through the skin of the hand and forearm of human volunteers. As the same authors found in a similar study on ethylbenzene (ibid. 1968, 6, 105), the absorption rate for toluene was high, being 14--23 mg/cm2/hr for the undiluted liquid. This compared with 22-33 mg for ethylbenzene, 0.4 mg for benzene and 9-15 mg for styrene. From aqueous solutions the absorption rate was 0.16--0.60 mg/cm2/hr for concentrations ranging from 180 to 600 mg/1. These results indicate that percutaneous absorption of toluene occurs more readily than has generally been assumed and may be of considerable significance in the overall picture of industrial exposure to this solvent.
THE CHEMICALENVIRONMENT
potent alkylating agent in man. The negative result of previous investigations was probably due to a short duration of exposure. The long latent period emphasizes the importance of careful and prolonged follow-up of cases exposed to suspected carcinogenic agents and underlines the conclusions of Case & Hosker (Br. J. prey. soc. Med. 1954, 8, 39) from their studies on 2-naphthylamine. There is also an important lesson here for the experimentalist. A limited intensive exposure of the mammalian organs to a carcinogenic agent suffices to induce a significant increase over the natural incidence of tumours if the test animals are capable of surviving for the duration of their natural life span. Is continued treatment till the 'bitter end' really necessary in carcinogenicity testing ?]
1608. Naphthalene metabolism--a slight advance Holtzman, J., Gillette, J. R. & Milne, G. W. A. (1967). The metabolic products of naphthalene in mammalian systems. J. A m chem. Soc. 89, 6341. Naphthalene (I) is metabolized to various major products, including a-naphthol (II), 1,2-dihydro-l,2-dihydroxynaphthalene (III) and S-(1,2-dihydro-2-hydroxy-l-naphthyl)glutathione (IV) (Cited in F.C.T. 1965, 3, 661 ; Young, Biochem. J. 1947, 41,417; Booth et al. ibid. 1960, 77, 182). The conversion of I to II and Ili is catalysed by liver microsomal enzymes requiring both reduced nicotinamide-adenine dinucleotide phosphate and molecular oxygen. But the exact metabolic pathway is still unknown. Holtzman et al. (cited above) have now found that conversion of I to II and III by liver homogenates is catalysed by a mono-oxygenase (only one atom of molecular oxygen is incorporated, the second oxygen being apparently derived from water), that the initial attack on I takes place at the a position and that the trans form of III is produced. It also appears likely that II and III (neither of which serves as a precursor of the other) are formed from I via a common precursor, which, if the postulated structure is correct, could also readily be converted into IV. 1609. Toluene through the skin Dutkiewicz, T. & Tyras, H. (1968). The quantitative estimation of toluene skin absorption in man. Arch. Gewerbepath. Gewerbehyg. 24, 253. We recently reported cases of acute poisoning in man following exposure to high atmospheric concentrations of toluene (Cited in F.C.T. 1968, 6, 291). Some quantitative data have now been presented on the extent to which this solvent, widely used as a paint thinner and in many industrial processes, may be absorbed through the human skin. The rate of absorption of undiluted toluene and of toluene in aqueous solution was measured through the skin of the hand and forearm of human volunteers. As the same authors found in a similar study on ethylbenzene (ibid. 1968, 6, 105), the absorption rate for toluene was high, being 14--23 mg/cm2/hr for the undiluted liquid. This compared with 22-33 mg for ethylbenzene, 0.4 mg for benzene and 9-15 mg for styrene. From aqueous solutions the absorption rate was 0.16--0.60 mg/cm2/hr for concentrations ranging from 180 to 600 mg/1. These results indicate that percutaneous absorption of toluene occurs more readily than has generally been assumed and may be of considerable significance in the overall picture of industrial exposure to this solvent.