Marja Sorsa

Mutagenicity in urine of workers in rubber industry

Epidemiological studies have shown that those who work in rubber industry have an increased risk of cancer. In the working environment they are exposed, probably, to several hundred different chemicals some of them being known or suspected carcinogens and mutagens. The bacterial fluctuation test was used to detect the mutagenicity in the urines of exposed workers. A group of unexposed office clerks served as controls. Both groups consisted of smokers and non-smokers, and that was taken into consideration in the results. Rubber workers, either smokers or non-smokers, exhibited significantly higher mutagenic activity in their urine than the occupationally unexposed controls when the base-pair substitution strain E. coli WP2 uvrA was used as indicator organism. Use of the frameshift strain S. typhimurium TA98 revealed increased mutagenicity in the urine of occupationally exposed smokers, nonsmokers and unexposed smokers. The extent of mutagenicity in the urine of workers who smoked suggested a synergistic effect of smoking and occupational exposure. The bacterial fluctuation test with urine samples as sources of mutagenicity is able to detect chemical exposure if the excreted compounds are still in active form or can be activated. The method can be used to identify hazardous working conditions long before the manifestation of possible pathological changes in exposed individuals.

Biological and environmental monitoring of occupational exposure to cyclophosphamide in industry and hospitals

The aims of the study were to clarify potential exposure situations to anticancer agents during industrial processing, drug manufacture and hospital administration, using cyclophosphamide (CP) as the model compound. CP is considered an animal and human carcinogen, and it is shown to be an indirect mutagen in various test systems using several genetic endpoints. Environmental monitoring was performed by collecting ambient air samples during the different processing and handling stages. Both stationary and personal sampling was used. CP was analyzed by liquid chromatography (HPLC) and mass spectrometry (MS). The process materials and intermediates were also analyzed for genotoxic activity using the Ames test and SCE induction in CHO cells as endpoints. Biological monitoring studies were performed on 147 persons representing 5 groups of workers, control subjects and patients. In the experimental part of the project, the intermediates in the CP manufacturing process, CP I (nor-nitrogen mustard) and CP II (phosphoroxydichloride mustard) were found directly active in the 2 genotoxicity tests. These findings led to improvements in work hygiene when handling CP I and CP II in the process. The CP measurements showed that the highest potential-exposure sites occurred during specific operations of the process, e.g., during emptying of the drying drum and during tablet mass preparation (the range of CP concentrations in air was 0.16-0.49 mg/m3). The correlation between indirect genotoxicity and chemical analyses of the ambient air samples was good, revealing the activity to be due to cyclophosphamide. However, the air samples were found mutagenic without metabolic activation also in the beginning of the process; this is obviously due to CP II particles in the ambient air, since no CP was detected chemically. The personal protection of workers in the plant collaborating in the study is efficient and the production unit is equipped with the best available techniques to protect both the personnel and the quality of the drug. Both the urine mutagenicity analyses using strain TA1535 of Salmonella typhimurium as indicator and the cytogenetic analyses of peripheral blood lymphocytes using sister-chromatid exchanges or structural chromosomal aberrations as endpoints were negative. However, a statistically nonsignificant trend in increased number of micronuclei was observed in binucleated lymphocytes of the worker groups as compared with controls. The studies on the hospital use of CP were performed in 3 oncological units and 1 pharmacy unit.(ABSTRACT TRUNCATED AT 400 WORDS)

Polynuclear aromatic compounds and genotoxicity in particulate and vapor phases of ambient air: effect of traffic, season, and meteorological conditions

High-volume samples of ambient air were collected by glass-fiber filter (particulate) and XAD-2 resin (vapor) from three locations in Finland: two cities and a rural area. Samples were analyzed for polynuclear aromatic hydrocarbons (PAH) and selected other polynuclear compounds. Genotoxocity of the samples was assayed in the Ames Salmonella/microsome test and sister chromatid exchange assay before and after fractionation into four fractions of increasing polarity. The ratio of PAH in the vapor and particulate phases of the samples varied considerably with the season, and the scavenging effect of snow and rain was as well clearly demonstrated. The rural samples showed minimal or no genotoxic activity, whereas at the urban sites not only the particulate-phase but also the vapor-phase samples were mutagenic. The genotoxicity was mainly associated with the most polar fractions of both phases. Studies with the nitroreductase-deficient Salmonella strain TA98NR indicated, that in the urban air samples collected in winter, a considerable part of the mutagenicity detected in the Ames test was due to NO/sub 22/-substituted compounds. Traffic is suggested to be the major determinant for the genotoxic activity in the ambient air.

Occupational styrene exposure and chromosomal aberrations

Abstract Results from a study on the clastogenicity of styrene in vivo are reported. The chromosomes in cultured blood lymphocytes from ten men occupationally exposed to styrene and 5 controls were examined. Styrene-exposed men showed an increase in the rate of chromosomal aberrations. The incidence of aberrant cells ranged from 11 to 26% in the lymphocytes of the exposed subjects and was 3% or less in those of the control group.

Assessment of exposure to butadiene in the process industry

Occupational exposure levels to 1,3-butadiene (BD) are variable but generally below 1 ppm in the European process industry. A preliminary analysis showed that hemoglobin adduct levels of butadiene monoxide (BMO) were increased among the worker groups with higher potential exposure to BD (process work, bomb voiding, repair duties) than among less exposed workers in maintenance and laboratory or control persons. In the same workers no exposure related effects were seen in the cytogenetic parameters studied, i.e. chromosomal aberrations, sister chromatid exchanges or micronuclei in peripheral blood lymphocytes. However, the glutathione-S-transferase polymorphism in the T1 gene might play a role in determining interindividual sensitivity to BD-induced chromosomal aberrations. Chromosomal aberrations (gaps excluded) were significantly (P < 0.05) increased among the workers lacking the GSTT1 gene as compared to the BD workers with the gene, while the other polymorphic GSTM1 gene showed no association with the cytogenetic parameters. More work needs to be done to study the adducts by other active BD metabolites than BMO and the role of the genetic polymorphisms controlling the variability of individual responses.

Passive smoking at work: biochemical and biological measures of exposure to environmental tobacco smoke

SummarySeveral biochemical and biological measures of tobacco smoke intake were used to evaluate exposure of restaurant personnel to environmental tobacco smoke as compared with active smokers and non-exposed non-smokers. All of the measured parameters — carboxyhaemoglobin (COHb), thiocyanate (SCN) and cotinine in plasma, cotinine and mutagenicity in urine, total white blood cell count (WBC), and sister chromatid exchange (SCE) frequency in cultured lymphocytes — were significantly elevated in the smoker group (n = 22) compared to the non-exposed group (n = 20). Work-related passive exposure (n = 27) was seen most clearly in the cotinine values, both from plasma (mean P-cot in passive smokers 10 ng/ml vs 5.2 ng/ml in non-exposed) and from urine (mean U-cot in passive smokers 56 ng/ml vs 8.3 ng/ml in non-exposed), but significant increases were also seen in the thiocyanate levels (mean P-SNC in passive smokers 58 μmol/1 vs 46 μmol/1 in non-exposed) and, as a preliminary finding, in total leucocyte count (in passive smokers 8.0 × 109/1 vs 6.8 x 109/1 in non-exposed). The results demonstrate that environmental tobacco smoke may be an occupational health hazard.

Polycyclic organic material (POM) in urban air. Fractionation, chemical analysis and genotoxicity of particulate and vapour phases in an industrial town in Finland

Abstract Polycyclic organic material (POM) was collected by high-volume sampling on filter and on XAD-2 resin from the air of a small industrial town in Finland. Concurrent chemical analysis and the assays for genotoxic activity were performed on the particulate and the vapour phases of ambient air POM and their chemical fractions. Furthermore, correlations between seasonal meteorological parameters and POM concentrations were studied to reveal characteristic POM profiles for various emission sources. The range of total POM concentrations varied from 115 to 380 ng m −3 in late spring and from 17 to 83 ng m −3 in early winter. No direct correlation of ambient POM was seen with the temperature, but rather with the wind direction from various emission sources. Especially the low molecular weight compounds were associated with wind direction from industrial sources. Genotoxic activity, as detected by the Ames Salmonella /microsome test and the SCE assay in CHO cells, was found not only in the paniculate phase samples but also in the vapour phase. The polar fractions of some of the samples showed genotoxic activity, and also direct mutagenicity was observed with both the assay systems; these facts support the significance of compounds other than conventional polycyclic aromatic hydrocarbons (PAH) in the samples.

Occupational handling of cytostatic drugs

The bacterial fluctuation test and measurement of the frequency of sister chromatid exchanges were used for evaluation of the exposure of different groups of hospital personnel to cytostatic drugs.Increased mutagenic activity in the urine was detected only in personnel working with inadequate safety precautions, e.g., lack of a ventilated safety cabin for preparation of parenteral solutions. Although such a safety cabin was used within the hospital pharmacy, increased mutagenic activity was detected in the urine of prescriptionists preparing parenteral cytostatic drugs. After a change of glove material and improvement of ventilation in the safety cabin, no work-related increase in urinary mutagenic activity was seen. None of the different groups tested, showed any increase in the frequency of sister chromatid exchanges.It is therefore concluded that handling of cytostatic drugs according to the issued safety recommendations including working in a well ventilated safety cabin, will not result in any enhancement of mutagenic activity in the urine related to work.

1,3-Butadiene and its epoxides induce sister-chromatid exchanges in human lymphocytes in vitro

Sister-chromatid exchanges (SCEs) were induced in human lymphocytes by 1,3-butadiene and its epoxides 3,4-epoxy-1-butene and 1,2:3,4-diepoxybutane. After a pulse treatment of 2 h, 1,3-butadiene produced a weak but reproducible increase in SCEs both with and without S9 mix. The response was similar in cultures of whole blood and of isolated lymphocytes. The 2 epoxide metabolites of butadiene, studied in whole-blood lymphocyte cultures without exogenous metabolic activation, were highly active SCE inducers. The lowest effective concentrations of butadiene, monoepoxybutene, and diepoxybutane were 2000 microM, 25 microM and 0.5 microM, respectively. A slight but dose-dependent increase in SCEs was also observed without an exogenous metabolic system after a 48-h treatment with 1,3-butadiene. Already the lowest concentration tested (500 microM) was effective. Again, the response was similar in cultures of whole blood and isolated lymphocytes, suggesting that the lymphocytes are capable of metabolically activating 1,3-butadiene.

Human cytogenetic biomonitoring of occupational exposure to 1,3-butadiene

The association of occupational exposure to 1,3-butadiene and chromosomal damage in peripheral blood lymphocytes was studied in 40 workers from two production facilities. Control persons, 30 in all, were chosen from other departments of the same plants, and they were roughly matched for age and smoking habits. The exposure levels to ambient butadiene were measured both by personal sampling using diffuse monitors and by stationary sampling at production and handling sites. Chromosome aberrations (CA), micronuclei (MN) and sister-chromatid exchanges (SCE) in peripheral lymphocytes were analyzed as markers of exposure. Smoking had a slight effect on the frequency of MN, and the mean frequency of SCEs was also higher in smokers than in non-smokers. No effect of smoking, however, was seen in relation to chromosomal aberrations. No exposure related effects were seen in any of the three cytogenetic endpoints in either of the butadiene production plants, representing typical low (below 3 ppm) exposure levels of the butadiene manufacturing industry.