Biomarkers of exposure to aromatic hydrocarbons and methyl tert-butyl ether in petrol station workers

This cross-sectional study was aimed at reconstructing the exposure to gasoline in 102 petrol station attendants by environmental and biological monitoring of benzene, toluene, ethylbenzene and xylene (BTEX) and biomonitoring of methyl tert-butyl ether (MTBE). Airborne BTEX were higher for manual refuelers than self-service assistants and were highly correlated with each other. Significant relationships were found between airborne BTX and the corresponding urinary solvents (U-BTX) and beween airborne B and urinary MTBE (U-MTBE). Smokers eliminated higher values of U-B, trans,trans-muconic (t,t-MA) and S-phenylmercapturic (S-PMA) acids but not U-MTBE. All these biomarkers were, however, significantly raised during the shift, independently from smoking. Linear regression confirmed that occupational exposure was a main predictor of U-MTBE, U-B and S-PMA values, both the latter confounded by smoking habits. The study supports the usefulness of biomonitoring even at low exposure levels.     

The genotoxic risk of underground coal miners from Turkey

A cytogenetic monitoring study was carried out on a group of workers from a bituminous coal mine in Zonguldak province of Turkey, to investigate the genotoxic risk of occupational exposure to coal mine dust. Cytogenetic analysis, namely sister chromatid exchanges (SCEs), chromosomal aberrations (CAs) and micronucleus (MN) tests were performed on a strictly selected group of 39 workers and compared to 34 controls matched for gender, age, and habit. Smoking and age were considered as modulating factors. Both SCE and CA frequencies in coal miners appeared significantly higher than in controls. Similarly, there was a significant increase in the frequency of total micronuclei in exposed group as compared to control group. The effect of smoking on the level of SCE and MN was significant in the control group. A positive correlation between the age and the level of SCE was also found in controls. The frequencies of both SCE and CA were significantly enhanced with the years of exposure. The results of this study demonstrated that occupational exposure to coal mine dust leads to a significant induction of cytogenetic damage in peripheral lymphocytes of workers engaged in underground coal mining.     

The genotoxic risk of underground coal miners from Turkey

A cytogenetic monitoring study was carried out on a group of workers from a bituminous coal mine in Zonguldak province of Turkey, to investigate the genotoxic risk of occupational exposure to coal mine dust. Cytogenetic analysis, namely sister chromatid exchanges (SCEs), chromosomal aberrations (CAs) and micronucleus (MN) tests were performed on a strictly selected group of 39 workers and compared to 34 controls matched for gender, age, and habit. Smoking and age were considered as modulating factors. Both SCE and CA frequencies in coal miners appeared significantly higher than in controls. Similarly, there was a significant increase in the frequency of total micronuclei in exposed group as compared to control group. The effect of smoking on the level of SCE and MN was significant in the control group. A positive correlation between the age and the level of SCE was also found in controls. The frequencies of both SCE and CA were significantly enhanced with the years of exposure. The results of this study demonstrated that occupational exposure to coal mine dust leads to a significant induction of cytogenetic damage in peripheral lymphocytes of workers engaged in underground coal mining.     

Molecular biomonitoring of a population of nurses handling antineoplastic drugs

Many antineoplastic drugs have been found to have carcinogenic, mutagenic and teratogenic activity and so hospital personnel handling these substances are potentially exposed to health risk. Understanding this risk derived from protracted occupational exposure has great relevance even if the workers normally adopt individual and environmental protective measures. To address this question we have studied the presence of DNA and chromosome damage in a population of nurses employed in Italian oncology units and in matched controls. We used the comet assay to evidence the presence of DNA strand breaks, due to both acute and chronic exposure, and the micronucleus (MN) test, which is a measure of clastogenic and aneugenic events. Furthermore, since the individual response to the exogenous insults may be genetically determined, we studied the possible influence of single nucleotide polymorphism in XRCC1 and XRCC3 DNA repair genes on induced genetic damage. We also considered the effects of confounding factors like smoking, age and gender. The results indicated that the exposed subjects had significantly high levels of genetic damage. Age and gender were associated with increased values in MN, both in control and in exposed groups; the smoking habit affects MN frequency in controls, but not in workers. Furthermore we found that exposed subjects bearing at least one XRCC1 variant allele (399Gln) show higher values of MN. The present data provide the evidence to show that occupational exposure to antineoplastic drugs, even if in safety controlled conditions, represents a serious health risk. Furthermore we have shown that the presence of XRCC1 genetic polymorphism could contribute to increase the genetic damage in susceptible individuals who are occupationally exposed to dangerous substances.     

Occupational genotoxicity risk evaluation through the comet assay and the micronucleus test

The micronucleus (MN) test and the alkaline single cell gel or comet assay were applied to exfoliated cells of the buccal mucous in order to evaluate the genotoxic risk associated with occupational exposure of 10 storage battery renovation workers, and 10 car painters, with age matched controls, in Pelotas, RS, in southern Brazil. In the MN test, 2000 exfoliated buccal cells were analyzed for each individual, while 100 cells were examined in the comet assay. In the comet test, both comet tail length and a damage index were calculated. Highly significant effects of occupational exposure were found with both the MN test and the comet assay (P<0.001). The comet assay was found to be rapid, of simple visualization, and it is a sensitive technique for measuring and analyzing DNA damage in human cells.     

Personal exposure to different levels of benzene and its relationships to the urinary metabolites S-phenylmercapturic acid and trans,trans-muconic acid

This report is part of an extensive study to verify the validity, specificity, and sensitivity of biomarkers of benzene at low exposures and assess their relationships with personal exposure and genetic damage. The study population was selected from benzene-exposed workers in Tianjin, China, based on historical exposure data. The recruitment of 130 exposed workers from glue-making or shoe-making plants and 51 unexposed subjects from nearby food factories was based on personal exposure measurements conducted for 3-4 weeks prior to collection of biological samples. In this report we investigated correlation of urinary benzene metabolites, S-phenylmercapturic acid (S-PMA) and trans,trans-muconic acid (t,t-MA) with personal exposure levels on the day of urine collection and studied the effect of dose on the biotransformation of benzene to these key metabolites. Urinary S-PMA and t,t-MA were determined simultaneously by liquid chromatography-tandem mass spectrometry analyses. Both S-PMA and t,t-MA, but specifically the former, correlated well with personal benzene exposure over a broad range of exposure (0.06-122 ppm). There was good correlation in the subgroup that had been exposed to <1 ppm benzene with both metabolites (P-trend <0.0001 for S-PMA and 0.006 for t,t-MA). Furthermore, the levels of S-PMA were significantly higher in the subgroup exposed to <0.25 ppm than that in unexposed subjects (n=17; P=0.001). There is inter-individual variation in the rate of conversion of benzene into urinary metabolites. The percentage of biotransformation of benzene to urinary S-PMA ranged from 0.005 to 0.3% and that to urinary t,t-MA ranged from 0.6 to approximately 20%. The percentage of benzene biotransformed into S-PMA and t,t-MA decreased with increasing concentration of benzene, especially conversion of benzene into t,t-MA. It appears that women excreted more metabolites than men for the same levels of benzene exposures. Our data suggest that S-PMA is superior to t,t-MA as a biomarker for low levels of benzene exposure.     

Changes in Poly(ADP-Ribosyl)ation Patterns in Workers Exposed to BTX

Occupational exposure to (benzene, toluene and xylene, BTX is common in the Chinese workplace. Chronic occupational exposure to benzene is associated with an increased risk of hematological malignancies such as acute myeloid leukemia (AML), but the underlying mechanisms are still unclear. This study investigates changes in poly(ADP-ribosyl)ation and DNA methylation in subjects occupationally exposed to a BTX. Blood DNA samples and exposure data were obtained from subjects with different levels of exposure, including 132 decorators, 129 painters, and 130 unexposed referents in a container-manufacturing factory in Shenzhen, China. Occupational exposure assessment included personal monitoring of airborne benzene, toluene and xylene. Hematological parameters were measured and the cytokinesis-block micronucleus (CBMN) assay was used to detect DNA damage in peripheral lymphocytes. Quantitative real-time PCR was used to detect the mRNA expression of poly(ADP-ribose) polymerase 1 (PARP1) and poly(ADP-ribose) glycohydrolase (PARG), DNA methyltransferases (DNMTs) including DNMT1, DNMT3a and DNMT3b, methyl-CpG-binding domain protein 2(MBD2). PARP1 assay was used to measure PARP activity. Airborne levels of benzene, toluene and xylene in the two exposed groups were significantly higher than those of controls (P<0.001). The two exposed groups (decorators, painters) showed decreased PARP1, DNMTs and MBD2 expression relative to controls (P<0.05), and PARP activity was also decreased (P<0.05). Decreased PARP1, DNMT1, DNMT3a, DNMT3b and MBD2 mRNA expression was correlated with increased airborne BTX (Pearson''s r: −0.587, −0.314, −0.636, −0.567 and −0.592 respectively, P<0.001). No significant differences in hematological parameters and CBMN were found among the three groups. Together, these results suggest that decreased DNMTs, MBD2 and PARP1 might be involved in the global hypomethylation associated with BTX exposure, and the imbalance of PARP/PARG might participate in the down-regulation of DNMTs. This is the first human study to link altered poly(ADP-ribosyl)ation patterns, which reproduce the aberrant epigenetic patterns found in benzene-treated cells, to chronic occupational exposure to BTX.     

Cytogenetic analysis of buccal cells from shoe-workers and pathology and anatomy laboratory workers exposed to n-hexane, toluene, methyl ethyl ketone and formaldehyde.

People employed in the shoe manufacture and repair industry are at an increased risk for cancer, the strongest evidence being for nasal cancer and leukaemia. A possible causal role for formaldehyde is likely for cancer of the buccal cavity and nasopharynx. Exfoliated buccal cells are good source of tissue for monitoring human exposure to inhaled and ingested occupational and environmental genotoxicants. To assess the cytogenetic damage related to occupational exposure to airborne chemicals during shoe-making and the processes in pathology and anatomy laboratories, the micronuclei (MN) count per 3000 cells was measured in buccal smears from shoe-workers (group I, n = 22) exposed to mainly n-hexane, toluene and methyl ethyl ketone (MEK) and from anatomy and pathology staff (group II, n = 28) exposed to formaldehyde (FA). Eighteen male university staff were used as controls. The mean time-weighted average (TWA) concentrations of n-hexane, toluene and MEK in 10 small shoe workshops were 58.07 p.p.m., 26.62 p.p.m. and 11.39 p.p.m., respectively. The measured air concentrations of FA in the breathing zone of the anatomy and pathology laboratory workers were between 2 and 4 p.p.m. Levels of 2,5-hexadione (2,5-HD) and hippuric acid (HA), metabolic markers of n-hexane and toluene exposure, respectively, were significantly higher in the urine of workers in group I than in control subjects (p < 0.001 and p < 0.01, respectively). The mean (+/- SD) MN (0/00) [corrected] frequencies in buccal mucosa cells from workers in group I, group II and controls were 0.62 +/- 0.45%, 0.71 +/- 0.56% and 0.33 +/- 0.30%, respectively (p < 0.05 and p < 0.05 compared with controls for group I and group II, respectively). The effects of smoking, age and duration of exposure on the frequency of micronucleated buccal cells from workers in all three groups studied were also evaluated. Overall, the results suggest that occupational exposure to organic solvents, mainly n-hexane, toluene, MEK and FA, may cause cytogenetic damage in buccal cells and that use of exfoliated buccal cells seems to be appropriate to measure exposure to organic solvents.     

Validation of an HPLC/MS/MS method with isotopic dilution for quantitative determination of trans,trans-muconic acid in urine samples of workers exposed to low benzene concentrations

Urinary trans,trans-muconic acid (t,t-MA), a biomarker of benzene exposure, is usually determined by HPLC methods with detection by either UV or, more recently, electrospray tandem mass spectrometry. However, not all these methods have been fully validated for quantitative analysis. This paper presents an HPLC/MS/MS method for reliable quantitative determination of t,t-MA that uses a commercial deuterium-labeled isotope as internal standard; the matrix effect has been evaluated and LOD is 0.22 microg/L. We used this method to test 200 urine samples, 175 of them collected at end-of-shift from workers in an oil refinery.     

DNA damage in lymphocytes of benzene exposed workers correlates with trans,trans-muconic acids and breath benzene levels

Benzene causes many kinds of blood disorders in workers employed in many different environments. These diseases include myelodisplastic syndrome and acute and chronic myelocytic leukemia. In the present study, five occupational work places, including six industrial process types, namely, printing, shoe-making, methylene di-aniline (MDA), nitrobenzene, carbomer, and benzene production were selected, and the levels of breath benzene, and trans,trans-muconic acids (t,t-MA) and phenol in urine were evaluated, as well as hematological changes and lymphocyte DNA damage. The concentration of benzene in breath was less than 3 ppm in the workplaces, and benzene exposure was found to be higher in work places where benzene is used, than in those where benzene is produced. At low levels of benzene exposure, urinary t,t-MA correlated strongly with benzene in air. Highest Olive tail moments were found in workers producing carbomer. Levels of breathzone benzene were found to be strongly correlated with Olive tail moment values in the lymphocytes of workers, but not with hematological data in the six workplaces types. In conclusion, the highest benzene exposures found occurred in workers at a company, which utilized benzene in the production of carbomer. In terms of low levels of exposure to benzene, urinary t,t-MA and DNA damage exhibited a strong correlation with breath benzene, but not with hematological data. We conclude that breath benzene, t,t-MA and lymphocytic DNA damage are satisfactory biomonitoring markers with respect to benzene exposure in the workplace.     

No increase in micronuclei frequency in cultured blood lymphocytes from a group of filling station attendants

Service station attendants are workers that are definitely exposed to petroleum derivatives. Taking into account that this exposure has been considered to possess genotoxic risk, here we present data on the biomonitoring of a group of 50 service station workers and 43 controls. Micronuclei (MN) from peripheral blood lymphocytes has been considered as the genetic endpoint to be studied and, in addition, data on the concentration of aromatic hydrocarbons at the workplace, urinary metabolites and differential white blood cell count have also been analysed. The results obtained indicate no significant differences between petrol station attendants and controls, when the effects of petrol exposure were investigated by differential white blood cell count and analysis of MN frequencies in phytohaemagglutinin-stimulated lymphocytes. Regarding the urinary metabolites, a significant increase in the phenol level was found in the exposed workers.     

Biological monitoring among benzene-exposed workers in Bangalore city, India.

Environmental and biological monitoring was carried out in the winter season of 2004 for 30 gasoline station workers (study subjects) and 30 office workers (controls) of Bangalore city, India. Personal air sampling was carried out in the breathing zone of workers using an Anasorb CSC sorbent tube (SKC 226-01) fitted to the low-flow personal samplers (PCXR4 and pocket pump Model No. 210-1002) at a flow rate of 200 ml min(-1) during the shift work of 8 h. The benzene content adsorbed in the sorbent tube (SKC 226-01) was desorbed with 1 ml of benzene-free carbon disulfide on a developing vibrator and later analysed by Trace GC fitted with MXT-624 column and flame ionization detector. The mean time weighted average benzene concentration found among study and controls was 1.10+/-1.08 and 0.070+/-0.035 mg m(-3), respectively. Biological monitoring for benzene exposure was performed by measuring trans,trans muconic acid (t,t-MA) in the end shift urine samples using HPLC-UV technique. End-shift urine samples (1 ml) were adjusted to pH 7-9 with phosphate buffer pH 7.4 passed through the preconditioned Q-SAX anion-exchange cartridge and the (t,t-MA) is extracted with 10% acetic acid and later analysed by HPLC-UV detection The mean t,t-MA found among study and controls were 563.16+/-281.81 and 266.88+/-110.65 microg g(-1) creatinine. About 50% of the study subjects (15) have higher t,t-MA values than the biological exposure index of the American Conference of Government Industrial Hygienist (ACGIH). Correlation is significant at 5% level (p<0.05) between personal air benzene concentration and urinary t,t-MA in the study group. Based on these findings, the t,t-MA can be used as a biomarker for benzene exposure.     

Cytogenetic analysis of buccal cells from shoeworkers and pathology and anatomy laboratory workers exposed to n-hexane,toluene, methyl ethyl ketone and formaldehyde

People employed in the shoe manufacture and repair industry are at an increased risk for cancer, the strongest evidence being for nasal cancer and leukaemia. A possible causal role for formaldehyde is likely for cancer of the buccal cavity and nasopharynx. Exfoliated buccal cells are good source of tissue for monitoring human exposure to inhaled and ingested occupational and environmental genotoxicants. To assess the cytogenetic damage related to occupational exposure to airborne chemicals during shoe-making and the processes in pathology and anatomy laboratories, the micronuclei (MN) count per 3000 cells was measured in buccal smears from shoe-workers (group I, n = 22) exposed to mainly n-hexane, toluene and methyl ethyl ketone (MEK) and from anatomy and pathology staff (group II, n = 28) exposed to formaldehyde (FA). Eighteen male university staff were used as controls. The mean time-weighted average (TWA) concentrations of n-hexane, toluene and MEK in 10 small shoe workshops were 58.07 p.p.m., 26.62 p.p.m. and 11.39 p.p.m., respectively. The measured air concentrations of FA in the breathing zone of the anatomy and pathology laboratory workers were between 2 and 4 p.p.m. Levels of 2,5-hexadione (2,5-HD) and hippuric acid (HA), metabolic markers of n-hexane and toluene exposure, respectively, were significantly higher in the urine of workers in group I than in control subjects (p < 0.001 and p < 0.01, respectively). The mean (±SD) MN frequencies in buccal mucosa cells from workers in group I, group II and controls were 0.62±0.45%, 0.71±0.56% and 0.33±0.30%, respectively (p < 0.05 and p < 0.05 compared with controls for group I and group II, respectively). The effects of smoking, age and duration of exposure on the frequency of micronucleated buccal cells from workers in all three groups studied were also evaluated. Overall, the results suggest that occupational exposure to organic solvents, mainly n-hexane, toluene, MEK and FA, may cause cytogenetic damage in buccal cells and that use of exfoliated buccal cells seems to be appropriate to measure exposure to organic solvents.     

Cytogenetic damage in workers from a coal-fired power plant

The aim of this study was to investigate the genotoxic risk to workers occupationally exposed to coal combustion products in Afsin-Elbistan A power plant, located in south-eastern Turkey. We analysed chromosomal aberrations (CAs), polyploidy, sister-chromatid exchanges (SCEs), and micronuclei (MN) in 48 male workers without a history of smoking, tobacco chewing, or alcohol consumption. The results were compared with a control group of 30 healthy male individuals without exposure to any known genotoxic agents. The mean frequencies of CA, polyploidy, SCEs (P<0.01), and MN (P<0.05) were significantly higher in workers than in the control group, by the Mann-Whitney U-test. Spearman's rho correlation analysis revealed a significant increase in the frequency of CA and MN with increasing years of exposure (P<0.05). However, there was no significant effect of age on the cytogenetic markers analysed in both groups (P>0.05). The data obtained from this study clearly showed chromosomal hazard in the peripheral lymphocytes of workers exposed to coal combustion products in Afsin-Elbistan A power plant for several years. This cytogenetic damage might be attributed to the cumulative effects of several substances due to chemical complexity of the coal ash and gaseous emissions rather than a specific substance.     

Degradation of benzene, toluene, and xylene isomers by a bacterial consortium obtained from rhizosphere soil of Cyperus sp. grown in a petroleum-contaminated area

Increasing contamination of soil and groundwater with benzene, toluene, and xylene (BTX) due to activities of the chemical and oil refinery industry has caused serious environmental damage. Efficient methods are required to isolate and degrade them. Microorganisms associated with rhizosphere soil are considered efficient agents to remediate hydrocarbon contamination. In this study, we obtained a stabilized bacterial consortium from the rhizosphere soil of Cyperus sp. grown in a petroleum-contaminated field in Southern Mexico. This consortium was able to completely degrade BTX in 14 days. Bacteria isolated from the consortium were identified by 16S rRNA gene sequence analysis as Ralstonia insidiosa, Cellulomonas hominis, Burkholderia kururiensis, and Serratia marcescens. The BTX-degradation capacity of the bacterial consortium was confirmed by the detection of genes pheA, todC1, and xylM, which encoded phenol hydroxylase, toluene 1,2-dioxygenase, and xylene monooxygenase, respectively. Our results demonstrate feasibility of BTX biodegradation by indigenous bacteria that might be used for soil remediation in Southern Mexico.     

Genotoxic effects of occupational exposure to lead and cadmium

This study was designed to assess genotoxic damage in somatic cells of workers in a Polish battery plant after high-level occupational exposure to lead (Pb) and cadmium (Cd), by use of the following techniques: the micronucleus (MN) assay, combined with in situ fluorescence hybridization (FISH) with pan-centromeric probes, analysis of sister chromatid exchanges (SCEs), and the comet assay. Blood samples from 44 workers exposed to lead, 22 exposed to cadmium, and 52 unexposed persons were used for SCE and MN analysis with 5'-bromodeoxyuridine (BrdU) or cytokinesis block, respectively. In parallel, the comet assay was performed with blood samples from the same persons for detection of DNA damage, including single-strand breaks (SSB) and alkali-labile sites (ALS). In workers exposed mostly to lead, blood Pb concentrations ranged from 282 to 655 microg/l, while the range in the controls was from 17 to 180 microg/l. Cd concentration in lead-exposed workers fell in the same range as for the controls. In workers exposed mainly to cadmium, blood Cd levels varied from 5.4 to 30.8 microg/l, with respective values for controls within the range of 0.2-5.7 microg/l. Pb concentrations were similar as for the controls. The incidence of MN in peripheral lymphocytes from workers exposed to Pb and Cd was over twice as high as in the controls (P<0.01). Using a combination of conventional scoring of MN and FISH with pan-centromeric probes, we assessed that this increase may have been due to clastogenic as well as aneugenic effects. In Cd- and Pb-exposed workers, the frequency of SCEs as well as the incidence of leukocytes with DNA fragmentation in lymphocytes were slightly, but significantly increased ( P<0.05) as compared with controls. After a 3h incubation of the cells to allow for DNA repair, a clear decrease was found in the level of DNA damage in the controls as well as in the exposed workers. No significant influence of smoking on genotoxic damage could be detected in metal-exposed cohorts. Our findings indicate that lead and cadmium induce clastogenic as well as aneugenic effects in peripheral lymphocytes, indicating a potential health risk for working populations with significant exposures to these heavy metals.     

Validation of an HPLC-MS/MS method for the simultaneous determination of phenylmercapturic acid, benzylmercapturic acid and o-methylbenzyl mercapturic acid in urine as biomarkers of exposure to benzene, toluene and xylenes

A liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed and fully validated, according to U.S. Food and Drug Administration guidance, for the simultaneous determination of phenylmercapturic acid, benzylmercapturic acid and o-methylbenzyl mercapturic acid in human urine as biomarkers of exposure to benzene, toluene and xylenes (BTX). After solid phase extraction and LC separation, samples were analyzed by a triple-quadrupole mass spectrometer operated in negative ion mode, using isotope-labeled analogs as internal standards (ISs). The method meets all the validation criteria required. The limits of detection of the three analytes, ranging from 0.30 to 0.40microgl(-1), and the high throughput make the method suitable for the routine biological monitoring of co-exposure to BTX both in the occupational and environmental settings. The validated method was applied to assess exposure to BTX in a group of 354 urban traffic wardens.     

Examination of various biomarkers measuring genotoxic endpoints from Barcelona airport personnel

Three different biomarkers: sister-chromatid exchanges (SCE), micronuclei (MN), and the Comet assay, were used to evaluate different kinds of genetic damage in peripheral blood lymphocytes from 34 male workers at Barcelona airport, exposed to low levels of hydrocarbons and jet fuel derivatives. The control group consisted of 11 unexposed men. We also investigated the ras p21 protein levels in plasma, in order to evaluate whether the ras gene could serve as a suitable potential marker of carcinogenic pollution in occupationally exposed cohorts. SCE and MN analyses failed to detect any statistically significant increase in the airport workers when compared with the controls, and in fact, the frequency of binucleated cells with MN in the exposed group was significantly lower than that obtained in the control. However, slight but significant differences in the mean comet length and genetic damage index were observed between the exposed and control groups when using the Comet assay. There were no statistically significant differences between both groups in p21 plasma levels. Smoking was shown to affect significantly both SCE and high frequency cells (HFC) in the exposed group.     

The micronucleus assay in human exfoliated cells of the nose and mouth: application to occupational exposures to chromic acid and ethylene oxide

We have applied the micronucleus (MN) assay to exfoliated cells of buccal and nasal cavities to monitor the genotoxic risk in a group of workers exposed to chromic acid and in another group exposed to ethylene oxide (EtO). The first group comprised 16 subjects working in a 'hard' type chrome-plating factory showing increased chromium absorption and chromium-induced rhinopathy. The second group comprised 9 subjects working in a sterilization unit, exposed to EtO concentrations lower than 0.38 ppm as timed weighted average (TWA) for a working shift; 3 of them were involved in a acute exposure too. The frequency of MN in buccal mucosa was within the norm for exposure both to chromium and to EtO. The MN frequency in nasal mucosa was not altered in chromium platers, whereas a significant increase (p less than 0.01) in MN was found in 2 out of 3 subjects involved in the accidental EtO leakage and a non-significant increase in MN was found in the group chronically exposed to EtO.     

Influence of various mixtures of inhaled toluene and xylene on the biological monitoring of exposure to these solvents in rats.

The present study was undertaken to describe the influence of simultaneous exposure by inhalation to toluene and xylene on some aspects of their respective metabolic disposition. Adult male rats were exposed acutely (5 h) to 75, 150, and 225 ppm of toluene or xylene and to various mixtures of these solvents: toluene (75 ppm) and xylene (225 ppm), toluene (150 ppm) and xylene (150 ppm), toluene (225 ppm) and xylene (75 ppm). Compared with single exposure, simultaneous exposure resulted in lower amounts of excreted hippuric acid (20-30%) and methylhippuric acids (4-40%) in urine over a period of 24 h, even though significant differences were seen only with the toluene (150 ppm) and xylene (150 ppm) combination. In addition, increased concentrations of solvents in blood (toluene, 230%; xylene, 500%) and in brain (toluene, 230%; xylene, 320%) were found during the immediate post-exposure period. Simultaneous exposure also enhanced the pulmonary elimination of both solvents (toluene, 190-240%; xylene, 340-650%). Influence of repeated simultaneous exposure (9 days) was investigated for the toluene (150 ppm) and xylene (150 ppm) combination and the results compared with those of repeated exposure to each solvent administered singly. Under these conditions, repeated simultaneous exposure decreased the excretion of urinary metabolites, but only after the first exposure. On the other hand, simultaneous exposure resulted in significantly higher concentrations of toluene (210%) and xylene (240%) in blood throughout the entire 9-day exposure period. These results strongly suggest mutual metabolic interactions (inhibition) between toluene and xylene that affect the metabolic disposition of both solvents and ultimately the biological monitoring of data of exposure to a combination of solvents in rats.