Göran Löfroth

Environmental tobacco smoke: overview of chemical composition and genotoxic components

Tobacco smoke contains numerous compounds emitted as gases and condensed tar particles. The sidestream smoke emissions, which constitute the major part of environmental tobacco smoke (ETS), are generally larger than the mainstream smoke emissions. Many of the organic compounds, belonging to a variety of chemical classes, are known to be genotoxic and carcinogenic. These include the known constituents, alkenes, nitrosamines, aromatic and heterocyclic hydrocarbons and amines. Emission of sidestream smoke in indoor environments with relatively low ventilation rates can result in pollutant concentrations above those generally encountered in ambient air in urban areas. The chemical characteristics of ETS thus support the indications that exposure to ETS can be causally associated with the induction of several types of cancer.

Indoor sources of mutagenic aerosol particulate matter: smoking, cooking and incense burning

The emission of aerosol particles and their mutagenic activity as well as the emission of some gaseous pollutants has been studied experimentally in order to compare the emission from some indoor pyrolysis processes. Cigarette (tobacco and herbal) smoking, incense and mosquito-coil burning and frying of experimental lean minced pork emitted particulate matter. Their extracts were mutagenic in the Ames Salmonella test with TA98 and activation as well as, with a higher response, in a microsuspension test with the same strain and activation condition. The response of the particles from the smoking and burning processes varied from 3000 to 50,000 revertants per gram of smoked or burnt material in the conventional Salmonella test and from 50,000 to 350,000 revertants per gram in the microsuspension assay. The frying of lean minced pork gave an airborne emission of about 53 and 560 revertants per gram of fried pork, respectively, in the 2 assays. The frying of some common food items following cookbook recipes also emitted mutagenic aerosol particles but the emitted activity was less than that in the pork experiment. Carbon monoxide, isoprene and benzene were present in the emissions from the smoking and burning processes but were not detectable in the frying fumes. The results suggest that incense and mosquito-coil burning can cause indoor air pollution akin to that from cigarette smoking. Indoor air pollution from cooking requires further study.

Evaluation of genetic risks of alkylating agents. IV. Quantitative determination of alkylated amino acids in haemoglobin as a measure of the dose after treatment of mice with methyl methanesulfonate.

Abstract The present study explores the possibilities of using specific amino acids in haemoglobin for tissue dosimetry of alkylating agents. The well-known directly alkylating compound methyl methanesulfonate has been used as a model compound. In one experiment 3 H-labelled methyl methanesulfonate was given to mice intraperitoneally at three dose levels. The degree of alkylation of haemoglobin exhibited a linear dependence on the quantity of methyl methanesulfonate injected. The degree of alkylation of guanine- N -7 in DNA indicated a slight positive deviation from linearity at high doses. After a single injection the degree of alkylation of cysteine- S and histidine- N -3 in haemoglobin decreased linearly with time reaching the value zero after about 40 days (the life-time of the erythrocytes in the mouse). This demonstrates a stability of these alkylated products, which is fundamental to their use as integral dose monitors. In a second experiment mice were treated with methyl methanesulfonate once a week over a period of 8 weeks. The experiment demonstrated an accumulation of alkylated groups in haemoglobin in agreement with expectation. A method for the quantitative determination of S -methylcysteine in a protein hydrolysate by gas chromatography was developed.

Formation of 7-methylguanine by dichlorvos in bacteria and mice

Abstract The methylating capability of dichlorvos, as assayed by the formation of labelled 7-methylguanine from dichlorvos radioactively labelled in the methyl groups, has been studied in an Escherichia coli test system and in mice. Labelled 7-methylguanine is present in both DNA and RNA isolated from E. coli exposed to dichlorvos. Mice exposed to dichlorvos by inhalation as well as by i.p. injection excrete in the urine labelled 7-methylguanine which most likely originates from the non-enzymatic methylation of guanine moieties. The methylating capability of dichlorvos is less, by a factor of 10 to 100, than that of strongly genotoxic methylating compounds.

Characterization of TCDD-receptor ligands present in extracts of urban particulate matter

Extracts of filter-collected urban airborne particulate matter contain compounds which can competitively inhibit 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) binding to the rat liver TCDD-receptor protein. The concentration of conventional polycyclic aromatic hydrocarbons (PAHs) or chlorinated dioxins and dibenzofurans cannot account for more than 1%–30% of the observed competition for TCDD-binding to the receptor protein. Chemical fractionation of an extract of a well-characterized particulate air sample collected in Washington, DC showed the highest activity residing in the hexane/benzene fraction, although significant levels of activity were found also in other fractions. Analysis of extracts of gasoline exhaust particulate matter and fractions thereof gave similar results. A series of pure PAHs and nitro-and chloroderivatives of PAHs was tested for competition with TCDD for receptor binding. Among the most potent compounds with EC50-values similar to tetrachlorodibenzofuran were 1- and 3-nitrobenzo(a)-pyrene. Other highly active compounds included dibenzo(a,h)anthracene, benzo(j)fluoranthene, benzo(k)fluoranthene, picene, indeno(1,2,3-cd)pyrene, 3-nitroperylene, and 3,9-and 3,10-dinitroperylene. the EC50-value for aryl hydrocarbon hydroxylase induction in hepatoma cells and the EC50-value for TCDD-receptor binding were similar for dibenzo(a,h)anthracene and for a PAH-containing fraction of an extract of gasoline exhaust particulates. The presence of active TCDD-receptor ligands in extracts of urban particulate matter and their ability to be taken up by cells and cause biological alterations represent a potential health risk. The identity of these compounds are largely unknown although certain PAHs and possibly some nitroderivatives of PAHs are likely to play a role.

Salmonella/microsome mutagenicity assays of exhaust from diesel and gasoline powered motor vehicles

Abstract Motor vehicle exhaust from prechamber injection diesel and gasoline powered passenger cars, sampled during US FTP 1973 test cycles and comprising both particulate matter and compounds condensable at ambient temperature, has been assayed for mutagenicity in the Salmonella/microsome test. Mutagenic components were to a large extent active in the absence of the mammalian microsomal preparation. The mutagenicity of both particulate matter and condensate from diesel exhaust and condensate from gasoline exhaust was decreased in the presence of the microsomal preparation whereas the mutagenicity of particulate matter from gasoline exhaust was enhanced by microsomal activation. A comparison between the investigated diesel and gasoline exhaust samples shows that the mutagenic effect in the Salmonella test of the diesel exhaust is more than ten times higher than that of the gasoline exhaust. Fractionation with respect to polarity indicates that the mutagenic components mainly are distributed in neutral aliphatic, aromatic, and oxygenated fractions. Tests for mutagenic monofunctional nitroarenes by an anaerobic assay indicate that such compounds at most are marginally present in the exhaust samples as compared with their presence in airborne particulate matter collected in an urban environment.

Comparison of the Mutagenic Activity in Carbon Particulate Matter and in Diesel and Gasoline Engine Exhaust

Airborne carbon particulate matter is a variable and complex mixture of components, including a variety of organic compounds. Its origin in urbanized and industrialized areas is primarily through various combustion processes. Motor vehicles are often viewed as a major source.

Salmonella/microsome mutagenicity of monochloro derivatives of some di-, tri- and tetracyclic aromatic hydrocarbons.

A series of 8 monochloroarenes have been tested for mutagenicity in the Salmonella/microsome assay. None of the compounds was detectably active in the absence of mammalian activation whereas, depending on structure, some of the compounds were mutagenic in its presence having responses higher than those reported for the parent compounds.

Passive Smoking and Urban Air Pollution: Salmonella /Microsome Mutagenicity Assay of Simultaneously Collected Indoor and Outdoor Particulate Matter

The mutagenic and carcinogenic potential of ambient airborne particulate matter originating from mobile and stationary combustion sources has attracted a renewed interest since it was discovered that extracts of such particles contained substances, detectable by the Salmonella mutagenicity assay, that were not conventional polycyclic aromatic hydrocarbons (PAH) (Pitts et al., 1977; Talcott and Wei, 1977). It is now indicated that the responsible compounds, which can be present in both combustion emissions and ambient air, might be nitrated or oxygenated PAH derivatives (Alfheim et al., 1982), but the relative and absolute health implications of these components and PAH are not known.

Public exposure to environmental tobacco smoke.

Airborne particulate matter has been collected by personal samplers in public indoor areas and travel situations with environmental tobacco smoke pollution. Following extraction, the samples were assayed for mutagenicity in the presence of S9 with a sensitive microsuspension test using Salmonella TA98. The mutagenic responses of indoor air from public areas were much higher than those of ambient outdoor air. Depending on the circumstances, the mutagenic response varied in trains and airplanes but the results show that physical separation of non-smoking sections from smoking sections is necessary in order to achieve genuine non-smoking areas. Chemical fractionation and mutagenicity assay of the basic fraction show that Salmonella mutagenicity of airborne particulate matter might be used as a tobacco smoke-specific indicator, as the basic fraction of environmental tobacco smoke contains a large part of the mutagenic activity whereas this is not the case for outdoor ambient airborne particulate matter.