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3267. Vinyl chloride and the gene
192
The chemical environment
there was no lipid accumulation in the vacuoles. Liver changes in rats fed chlorinated gluten suggested proliferation of the smooth endoplasmic reticulum, which like the increase in dry matter in the fourth experiment was considered indicative of enzyme induction. Studies with 36CI showed that in flour chlorinated
at 0.2 and 1~ the lipid fraction contained 45 and 27~ of the chlorine respectively, the remainder being found in the flour residue. The 0"2~o level did not affect the amino acid content of the flour, but at 1~o the levels of methionine and tyrosine were appreciably reduced.
THE CHEMICAL ENVIRONMENT
3267. Vinyl chloride and the gene Szentesi, I., Horny~ik, I~., Ungv~iry, G., Czeizel, A., Bognfir, Z. & Timar, M. (1976). High rate of chromosomal aberration in PVC workers. Mutation Res. 37, 313. Acro-osteolysis. Raynaud's syndrome and angiosarcoma of the liver are well-known consequences of industrial exposure to high levels of vinyl chloride (Cited in F.C.T. 1976, 14, 347 & 498). Although the in vivo mutagenic properties of the monomer are less well established, a number of recent investigations have demonstrated chromosomal aberrations in workers exposed to vinyl chloride (e.g. Ducatman et al. Mutation Res. 1975, 31, 163). Further evidence of the mutagenic activity of vinyl chloride in man is provided by the present study. Chromosomal analyses of the peripheral blood were performed on a group of 45 workers in the PVC industry who were exposed to vinyl chloride, a control group of 44 individuals engaged in other plants but not directly exposed to chemicals, and a second control group of 49 subjects with no occupational exposure to chemicals. The rate of numerical chromosome aberrations did not differ significantly between PVC workers and controls but the frequency of chromatid-type and unstable chromosome-type aberrations was significantly higher (P < 0.001) in the exposed than in either of the two control groups. Five of the 12 men who had been exposed to vinyl chloride for at least 12 yr showed abnormal incidences of both chromatid- and unstable chromosome-type aberrations. In addition, there was one such case among those with 6-7 yr plant experience and another with 10-11 yr experience. However, no cases were found among the 21 PVC workers with 1-5 yr plant experience.
3268. Nasty vinyl chloride associates? Rannug, U. & Ramel, C. (1977). Mutagenicity of waste products from vinyl chloride industries. J. Toxicol. envir. Hhh 2, 1019. While the industrial practices associated with the polymerization of vinyl chloride have been the subject of thorough examination, the manufacture of the monomer itself has been given much less attention.
The synthesis of vinyl chloride from acetylene or ethylene results in the formation of a by-product, ethylene dichloride tar (EDG-tar), a complex mixture of ethylene dichloride and other chlorinated aliphatic hydrocarbons. This tar has been shown to be toxic to fish and bacteria. The present study reports on its mutagenic activity in vitro. Extracts of EDC-tar in ethanol, dimethyl sulphoxide (DMSO) or 10~ Tween 80 (in 0'9~ saline solution) were incubated, at levels of 100, 300, 600 or 900pg per plate, with strain TA1535 of Salmonella typhimurium. Methylmethane sulphonate and 2-aminoanthracene were used as positive controls. EDC-tar was both toxic and mutagenic in all three solvents. At the highest concentration in ethanol and DMSO solutions the survival of the bacteria was reduced by 40~ and the incidence of mutation was about five times the control value. The Tween emulsion killed 30% of the bacteria and produced a tenfold increase in mutation rate. Similarly, the extracts were all mutagenic and toxic when incubated with the bacteria in the presence of a microsomal fraction obtained from rat liver. However, under these conditions the Tween emulsion was more toxic than the other two EDC-tar solutions, killing 80~ of the bacteria at the highest concentration of extract compared with a 50~ reduction in survival for both the ethanol and DMSO preparations. The microsomes increased the mutagenicity of all three systems by a factor of two or three and this mutagenic activity was still demonstrable at the lowest dose of 100#g per plate, a dose at which there was little reduction in survival of the bacteria. Again the Tween emulsion was unusual in that the observed mutagenicity varied only slightly from the lowest to the highest dose of the tar, indicating that a plateau was reached just above the lowest dose. The authors attribute this to possible inhibition of the mutagen-metabolizing system by the Tween 80. When NADPH was omitted, both the potential of the microsomal preparation to enhance the mutagenicity and the toxic activity of the extract were significantly reduced, suggesting that the mixedfunction oxidases were involved in the activation step. Both ethylene dichloride and vinyl chloride have been shown to be mutagenic in the Ames system. However the authors were satisfied that at the very low concentrations at which the compounds were present in the tar, neither could have contributed significantly to the observed mutagenicity and other direct and indirect mutagens must have been present.
The chemical environment
there was no lipid accumulation in the vacuoles. Liver changes in rats fed chlorinated gluten suggested proliferation of the smooth endoplasmic reticulum, which like the increase in dry matter in the fourth experiment was considered indicative of enzyme induction. Studies with 36CI showed that in flour chlorinated
at 0.2 and 1~ the lipid fraction contained 45 and 27~ of the chlorine respectively, the remainder being found in the flour residue. The 0"2~o level did not affect the amino acid content of the flour, but at 1~o the levels of methionine and tyrosine were appreciably reduced.
THE CHEMICAL ENVIRONMENT
3267. Vinyl chloride and the gene Szentesi, I., Horny~ik, I~., Ungv~iry, G., Czeizel, A., Bognfir, Z. & Timar, M. (1976). High rate of chromosomal aberration in PVC workers. Mutation Res. 37, 313. Acro-osteolysis. Raynaud's syndrome and angiosarcoma of the liver are well-known consequences of industrial exposure to high levels of vinyl chloride (Cited in F.C.T. 1976, 14, 347 & 498). Although the in vivo mutagenic properties of the monomer are less well established, a number of recent investigations have demonstrated chromosomal aberrations in workers exposed to vinyl chloride (e.g. Ducatman et al. Mutation Res. 1975, 31, 163). Further evidence of the mutagenic activity of vinyl chloride in man is provided by the present study. Chromosomal analyses of the peripheral blood were performed on a group of 45 workers in the PVC industry who were exposed to vinyl chloride, a control group of 44 individuals engaged in other plants but not directly exposed to chemicals, and a second control group of 49 subjects with no occupational exposure to chemicals. The rate of numerical chromosome aberrations did not differ significantly between PVC workers and controls but the frequency of chromatid-type and unstable chromosome-type aberrations was significantly higher (P < 0.001) in the exposed than in either of the two control groups. Five of the 12 men who had been exposed to vinyl chloride for at least 12 yr showed abnormal incidences of both chromatid- and unstable chromosome-type aberrations. In addition, there was one such case among those with 6-7 yr plant experience and another with 10-11 yr experience. However, no cases were found among the 21 PVC workers with 1-5 yr plant experience.
3268. Nasty vinyl chloride associates? Rannug, U. & Ramel, C. (1977). Mutagenicity of waste products from vinyl chloride industries. J. Toxicol. envir. Hhh 2, 1019. While the industrial practices associated with the polymerization of vinyl chloride have been the subject of thorough examination, the manufacture of the monomer itself has been given much less attention.
The synthesis of vinyl chloride from acetylene or ethylene results in the formation of a by-product, ethylene dichloride tar (EDG-tar), a complex mixture of ethylene dichloride and other chlorinated aliphatic hydrocarbons. This tar has been shown to be toxic to fish and bacteria. The present study reports on its mutagenic activity in vitro. Extracts of EDC-tar in ethanol, dimethyl sulphoxide (DMSO) or 10~ Tween 80 (in 0'9~ saline solution) were incubated, at levels of 100, 300, 600 or 900pg per plate, with strain TA1535 of Salmonella typhimurium. Methylmethane sulphonate and 2-aminoanthracene were used as positive controls. EDC-tar was both toxic and mutagenic in all three solvents. At the highest concentration in ethanol and DMSO solutions the survival of the bacteria was reduced by 40~ and the incidence of mutation was about five times the control value. The Tween emulsion killed 30% of the bacteria and produced a tenfold increase in mutation rate. Similarly, the extracts were all mutagenic and toxic when incubated with the bacteria in the presence of a microsomal fraction obtained from rat liver. However, under these conditions the Tween emulsion was more toxic than the other two EDC-tar solutions, killing 80~ of the bacteria at the highest concentration of extract compared with a 50~ reduction in survival for both the ethanol and DMSO preparations. The microsomes increased the mutagenicity of all three systems by a factor of two or three and this mutagenic activity was still demonstrable at the lowest dose of 100#g per plate, a dose at which there was little reduction in survival of the bacteria. Again the Tween emulsion was unusual in that the observed mutagenicity varied only slightly from the lowest to the highest dose of the tar, indicating that a plateau was reached just above the lowest dose. The authors attribute this to possible inhibition of the mutagen-metabolizing system by the Tween 80. When NADPH was omitted, both the potential of the microsomal preparation to enhance the mutagenicity and the toxic activity of the extract were significantly reduced, suggesting that the mixedfunction oxidases were involved in the activation step. Both ethylene dichloride and vinyl chloride have been shown to be mutagenic in the Ames system. However the authors were satisfied that at the very low concentrations at which the compounds were present in the tar, neither could have contributed significantly to the observed mutagenicity and other direct and indirect mutagens must have been present.