Occupational chronic exposure to organic solvents

Summary A group of printing workers (n = 34) exposed to toluene was examined according to the concentrations of hippuric acid, phenol, o-cresol, and (m+p)-cresol in urine. The average concentration in the air of the workroom was 23 ppm. It is shown that, besides hippuric acid, small amounts of o-cresol. which is not a normal constituent of urine, were formed from toluene. The occurrence of o-cresol could be proved by mass spectrometry. On account of the small amounts of benzene present in industrially used toluene—in this case 0.025%—the average concentration of phenol in urine of the exposed group was significantly higher statistically than in urine from the controls .     

Occupational chronic exposure to organic solvents

Summary Four female assistants using a mixture of xylenes and ethylbenzeneas solvent in a histology laboratory were examined according to the concentrations of solvents in blood and the excretion of phenolic compounds in urine during 24 h. The average concentrations of (m+p)-xylene and ethylbenzene in air were between 56 and 68 ppm and 34 and 41 ppm respectively. It is shown that about 1.1–1.4% of the retained ethylbenzene is metabolized to 2-ethyl-phenol. 2,4-Dimethylphenol as a metabolite of m-xylene could not be detected. It is supposed that a competitive reaction mechanism between xylenes and ethylbenzene takes place preventing m-xylene from oxidation at the aromatic nucleus. Possible carcinogenic properties of epoxides formed as intermediates must be considered.-The estimation of threshold values for the concentration of solvents in blood was attempted.     

Occupational chronic exposure to organic solvents

Summary Two groups of workers occupationally exposed to glycol ethers in a varnish production plant or the ceramic industry were examined. For 19 persons the external and internal exposure was assessed on the Monday and Tuesday after an exposure-free weekend. In the varnish production area the concentrations of 2-ethoxy-ethanol (EE) 2-ethoxyethyl acetate (EEAc), and 2-butoxyethanol (BE) in air averaged 2.9, 0.5, and 0.5 ppm, respectively, on the Monday, and 2.1, 0.1, and 0.6 ppm, respectively, on the Tuesday. At the same workplaces the mean urinary 2-ethoxyacetic acid (EAA) and 2-butoxyacetic acid (BAA) concentrations were 53.2 and 0.2 mg/l on Monday preshift and 53.8 and 16.4 mg/l on Tuesday postshift. The results show that glycol ethers are very well absorbed through the skin. Therefore biological monitoring is indispensable. To study the kinetics of the toxic metabolite, 17 persons were examined for their excretion of EAA in urine during an exposure-free weekend. The median values of the calculated half-times were 57.4 and 63.4 h, respectively, which are longer than the values presented in literature until now. According to our calculations the limit value should not exceed 50 mg EAA per liter of urine, which is the current German biological tolerance value (BAT value) for EAA in urine. The maximum concentration value at the work place (MAK value) for EE and EEAc in air should be revised. Finally, the subjects from the varnish production plant as well as a group of reference persons were studied for cytogenetic effects of glycol ethers (sister chromatid exchange, micronucleus test). Such effects could not be detected.     

Occupational chronic exposure to organic solvents

Summary Seventeen persons (2 women and 15 men), who were exposed to glycolethers in a varnish production plant, were examined according to their external and internal solvent exposure. The workers in the production plant (n =12) were exposed to average concentrations of ethoxyethanol, ethoxyethyl acetate, butoxyethanol, 1-methoxypropanol-2, 2-methoxypropyl-1-acetate and xylene of 2.8; 2.7; 1.1; 7.0; 2.8 and 1.7 ppm. In the air of the store (n = 3) and in the laboratory (n = 2) only minor concentrations of xylene respectively xylene and ethoxyethyl acetate could be measured. Internal exposure was estimated by measuring butoxyethanol (BE) in blood as well as ethoxyacetic acid (EAA) and butoxyacetic acid (BAA) in urine samples. Urine samples were taken pre- and post-shift. As expected, the highest values were found in the varnish production. The average post shift concentrations of BE, EAA and BAA were 121.3 g/l; 167.8 and 10.5 mg/l. The relatively high concentrations of EAA and BAA in pre-shift samples can be explained by the long half-lives of these metabolites. According to our findings most of the glycolethers were taken up through the skin. Comparing our results with those reported in the literature we think that a future tolerable limit value for the concentration of ethoxyacetic acid in urine should be in the order of 100 to 200 mg/l.     

Occupational chronic exposure to organic solvents

Summary A study was carried out among 20 workers employed in a printing, office at three different work places (methanol concentration: 85, 101, and 134 ppm) to determine whether the concentration of formic acid in blood or urine and the methanol content of alveolar air permit the estimation of methanol exposure.For this purpose blood, urine, and end expiratory air were collected at the beginning and the end of the shift. For comparison formic acid concentrations were determined in the morning and in the afternoon in blood and urine of 36 and 15 control persons, respectively.The concentration of formic acid in blood increased significantly from 3.2 ± 2.4 mg/l before to 7.9 ± 3.2 mg/l after the shift in the exposed workers (mean increase 4.7 ± 3.8 mg/l). The corresponding concentrations in urine were 13.1 ± 3.9 mg/l and 20.2 ± 7 mg/l, respectively, with a mean increase of 7.1 ± 5.3 mg/l. This difference is also significant. On the contrary, in the control groups there was a small but significant decrease of formic acid concentration in blood from 5.6 ±4.5 mg/l in the morning to 4.9 ± 4.2 mg/l in the afternoon. In urine, the formic acid concentrations in the morning (11.9 ± 6.4 mg/l) and in the afternoon (11.7 ±5.6 mg/l) were not significantly different. The increase of formic acid concentration in blood during the shift is the most useful parameter for monitoring methanol exposed persons. In contrast determinations of methanol concentrations in the ambient air or in the exhaled air are only crude estimates.(Direktor: Prof. Dr. G. Lehnert)     

Occupational chronic exposure to organic solvents

Summary Twenty persons occupationally exposed to methanol were examined according to their methanol levels in blood and urine and their formic acid excretion. An 8-h exposure to a methanol concentration of 93 ml/m³ (geometric mean) in the air at the working area caused average methanol levels in blood and urine of (8.9 ± 14.7) mg/l and (21.8 ± 20.0) mg/l, respectively, and a mean formic acid excretion of (29.9 ± 28.6) mg/l. These average concentrations for the exposed group showed statistically significant increases compared to those of a control group. For the methanol workers we succeeded in] correlating their methanol levels in blood and urine. When considering the possible application of these parameters for biological monitoring, difficulties were encountered, especially for the individual case from the overlapping range in the concentrations of exposed and unexposed persons for each of the applied parameters. This range is minimum for the methanol concentration in urine. About 80% of the urinary levels from the methanol workers lies above the upper limit within the control group range. Based on our results a rough estimate shows the corresponding methanol content in urine to be about 40 mg/l for an 8-h exposure at 200 ml/m³ (German MAK value).     

Occupational chronic exposure to organic solvents XII. O-cresol excretion after toluene exposure

Summary Thirty-five printing workers were investigated according to their external and internal exposure to toluene. The concentration of toluene in the air of the working place was determined using stationary air sampling and gas chromatography. To determine the levels of toluene in blood as well as the concentrations of o-cresol, hippuric acid, and phenol in urine, biological specimens were collected at the end of exposure. The parameters were determined by gas chromatography and gas chromatography/mass spectrometry. According to our results, o-cresol concentrations higher than 5.3 mg per litre of post-shift urine might indicate an external exposure higher than the present MAK-value of 200 ppm.     

Occupational exposure to organic solvents and pregnancy. Review of current epidemiologic knowledge

The findings and methodological issues of recent epidemiological studies (1989-1999) on adverse developmental effects of maternal occupational exposure to organic solvents are reviewed. Several studies suggest the possibility of a moderate increase in the risk of spontaneous abortion and congenital malformations, especially facial clefts, associated with maternal exposure to solvents. A common methodological weakness of these studies is the inaccuracy of data on exposures. Positive findings encourage further epidemiological studies of high-quality design and use of protective measures to minimize exposure to these agents from the preconceptional period to the end of pregnancy.     

Occupational chronic exposure to organic solvents XI. Alkylbenzene exposure of varnish workers: effects on hematopoetic system

Summary Thirty-five spraymen, who were varnishing vehicles with alkyd-, phenol- and polyestervarnishes, which were dissolved in solvent mixtures mainly containing o-, m-, p-xylene and ethylbenzene, have been investigated. The concentrations of these solvents in air were 2.1, 7.9, 2.8 and 4.0 ppm on average. The levels of alkylbenzenes in blood and those of their metabolites in urine have been determined. At two of the six working places the spraymen were additionally exposed to n-butanol, respectively 1,1,1-trichloroethane, and several C₉-aromatic hydrocarbons. Some of the lacquers contained lead pigments. Alterations of blood cell counts have been observed under the described conditions of exposure. On average the number of lymphocytes was higher than that of segmented granulocytes. Erythrocytes and hemoglobin level of the spraymen were lower than those of the controls.     

Occupational chronic exposure to organic solvents XVI. Ambient and biological monitoring of workers exposed to toluene

Object Ambient air and biological monitoring of an occupational toluene exposure was carried out on a group of 33 workers. Method The biological monitoring of the workers was based on determination of the concentration of toluene in blood and on quantification of the urinary metabolites o-cresol and hippuric acid. All blood and urine samples were collected post-shift. Results The average toluene concentration in the workplace air was 65?ppm, ranging from 13 to 151?ppm. An average concentration of toluene in blood of 911?μg/l was found, corresponding to an average urinary concentration of 2.9?mg/l (2.3?mg/g creatinine) o-cresol and 2.4?g/l (1.9?g/g creatinine) hippuric acid. Both urinary metabolites can be correlated with the concentration of toluene in ambient air and blood, respectively. Conclusions The results of our study indicate that the determination of the urinary o-cresol excretion represents a diagnostically specific and sensitive parameter for the estimation of an individual toluene uptake. In contrast, monitoring of the concentration of hippuric acid in urine cannot be recommended for assessment of individual exposure. To set up a biological tolerance value (BAT) for o-cresol, a urinary concentration of 3?mg/l o-cresol should be in accordance with the current MAK value of 50?ppm toluene.     

Occupational chronic exposure to organic solvents XVII. Ambient and biological monitoring of workers exposed to xylenes

Ambient-air and biological monitoring of occupational xylene exposure were carried out on 2 groups of workers (13 and 10 men, respectively) exposed to a mixture of xylenes during the production of paints or during spraying. Methods: Personal ambient-air monitoring was performed for one complete work shift. Blood and urine samples were collected directly at the end of the shift. Biological monitoring was based on the determination of the concentration of xylenes in blood and on the quantification of the sum of the three methylhippuric acids in urine. Results: Average xylene ambient-air concentrations were 29 ppm (production) and 8 ppm (spraying), ranging from 5 to 58 ppm and from 3 to 21 ppm, respectively. The concentrations of xylenes in blood ranged from 63 to 715 μg/l and from 49 to 308 μg/l, with average values being 380 and 130 μg/l, respectively. Accordingly, the workers engaged in paint production also excreted more methylhippuric acids in their urine (average 1221 mg/l, range 194–2333 mg/l) than did the sprayers (average 485 mg/l, range 65–1633 mg/l). Discussion: Our results as well as a literature review indicate that occupational xylene exposure on average barely exceeds the threshold limit value of 100 ppm as proposed by both American and German institutions. Biological monitoring based on the determination of xylenes in blood and of methylhippuric acids in urine provides sufficient sensitivity and specificity for occupational health surveillance. The results also confirm the current limit values (BAT values) proposed by the Deutsche Forschungsgemeinschaft for xylenes in blood (1500 μg/l) and methylhippuric acids in urine (2000 mg/l). Received: 27 May 1998 / Accepted: 3 September 1998     

Sleep disturbances and exposure to organic solvents.

An inquiry about sleep habits and sleep disturbances revealed a significantly higher prevalence of insomnia in a solvent-exposed group than in a comparable group that had no occupational exposure to organic solvents. In the solvent-exposed group was also registered an increased consumption of hypnotics, and a significant increase occurred in the number of individuals who had consulted physicians because of sleep disorders. The results indicate that solvent exposure could induce sleep disturbance.     

Occupational exposure to solvents and male infertility

OBJECTIVES—To determine whether, in a case-referent study of infertility patients, cases with low motile sperm count were more likely than referents to have had exposure to organic solvents.
METHODS—Occupations of men attending fertility clinics in Canada were assigned codes reflecting probable exposure to organic solvents, at four grades of intensity, using a job exposure matrix previously developed. A case referent design was used, with cases being defined as men with <12×10⁶/ml motile sperm. Information from 656 men in manual work attending a single clinic in Montreal in 1972-91 was used for the main study. A separate analysis was conducted with information for 574 men in manual work attending 10 further clinics across Canada in 1984-7.
RESULTS—In the Montreal series a significant association was found between intensity of exposure to solvents and clinical findings of <12×10⁶/ml motile sperm. Odds ratios (ORs), after allowing for confounding, were 2.07 (95% confidence interval (95% CI) 1.24 to 3.44) for moderate exposure to solvents and 3.83 (95% CI 1.37 to 10.65) for high exposure. In the second series of 568 men, the effect was confirmed at high exposure to solvents (OR 2.90, 95% CI 1.01 to 8.34) but not at moderate exposure (OR 1.01, 95% CI 0.53 to 1.92).
CONCLUSIONS—Exposure to organic solvents is common both at work and in recreational pursuits. The results of this study suggest that efforts should be made to identify the compounds hazardous to male fertility, and if the risk is confirmed, to regulate their use.


Keywords: infertility; solvents; male manual workers     

Chronic occupational exposure to organic solvents

Summary Twenty-two persons (20 men and 2 women) were examined for their external and internal exposure to the glycol ether 1-methoxypropan-2-ol (PGME) during the production, leak testing and mounting of brake-hoses. For the measurement of external exposure, personal air monitoring was the method of choice. Average concentrations of PGME of 82.2 mg/m³ (22.3 ppm), 68.6 mg/m³ (18.6 ppm) and 11.3 mg/m³ (3.1 ppm) were found in the air of the brakehose production, leak test and mounting areas, respectively. For the estimation of internal exposure to PGME, this glycol ether was measured in both urine and blood. The biological samples were taken post-shift. The highest internal exposure levels were found in the brakehose production section and in the leak test area. The average post-shift concentrations for PGME in workers in the brakehose production section were 4.6 mg/l in urine and 13.5 mg/l in blood; the corresponding figures for workers in the leak test area were 4.2 mg/l in urine and 11.0 mg/l in blood. In blood and urine samples of workers engaged in the mounting area, PGME levels were below the detection limits. The elimination kinetics of PGME were also studied in three highly exposed persons, and mean excretion half-lives of PGME of approximately 4.4 h were found. On the basis of our results we made a rough calculation of a future biological tolerance value: we would except that concentrations of 38-109 mg per litre of blood and 10–31 mg per litre of urine would correspond to the German MAK value for PGME (375 mg/m³).     

Occupational exposure to solvents and hairy cell leukaemia

OBJECTIVES: The role of occupational exposures in hairy cell leukaemia was investigated through a multicentre, hospital based, case-control study. This paper analyses the role of exposure to solvents other than benzene in hairy cell leukaemia. METHODS: The study included 226 male cases and 425 matched controls, exposure to solvents was evaluated by expert case by case review of the detailed data on occupational exposures generated by specific interviews. Also, exposure to solvents was evaluated with an independently constructed job exposure matrix (JEM). RESULTS: No association was found between hairy cell leukaemia and previous employment in a job exposed to solvents (odds ratio (OR) 0.9 95% confidence interval (95% CI) 0.6 to 1.3). ORs for the main occupational tasks exposed to solvents were around 1 and did not increase with the frequency or the duration of the tasks. No specific type of paint or glue was found to be significantly associated with hairy cell leukaemia. No association was found with exposure to solvents, taken as a whole, with either expert assessments or the JEM. No association was found with aromatic, chlorinated, or oxygenated subgroups of solvents. The ORs did not increase with the average intensity of exposure assessed by the experts, with the frequency of use, or with the duration of exposure. Finally, no association was found with non-occupational exposure to solvents. CONCLUSIONS: The study did not show any association between exposure to solvents and hairy cell leukaemia.     

Occupational exposure to organic solvents during paint stripping and painting operations in the aeronautical industry

Summary The exposure of workers to methylene chloride and phenol in an aeronautical workshop was measured during stripping of paint from a Boeing B 747. Methylene chloride exposure was measured during two work days by personal air sampling, while area sampling was used for phenol. During paint stripping operations, methylene chloride air concentrations ranged from 299.2 mg/m³ (83.1 ppm) to 1888.9 mg/m³ (524.7 ppm). The exposures to methylene chloride calculated for an 8-h work day ranged from 86 mg/m³ (23.9 ppm) to 1239.5 mg/m³ (344.3 ppm). In another aeronautical workshop, exposure to organic solvents, especially ethylene glycol monoethyl-ether acetate (EGEEA), was controlled during the painting of an Airbus A 320. The external exposure to solvents and EGEEA was measured by means of individual air sampling. The estimation of internal exposure to EGEEA was made by measuring its urinary metabolite, ethoxyacetic acid (EAA). Both measurements were made during the course of 3 days. The biological samples were taken pre-and post-shift. During painting operations, methyl ethyl ketone, ethyl acetate, n-butyl alcohol, methyl isobutyl ketone, toluene, n-butyl acetate, ethylbenzene, xylenes and EGEEA were detected in working atmospheres. For these solvents, air concentrations ranged from 0.1 ppm to 69.1 ppm. EGEEA concentrations ranged from 29.2 mg/m³ (5.4 ppm) to 150.1 mg/m³ (27.8 ppm). For biological samples, the average concentrations of EAA were 108.4 mg/g creatinine in pre-shift and 139.4 mg/g creatinine in post-shift samples. Despite the fact that workers wore protective respiratory equipment during paint spraying operations, EEA urinary concentrations are high and suggest that percutaneous uptake is the main route of exposure for EGEEA. The introduction of new paint stripping processes in the aeronautical industry could help to reduce future exposure to methylene chloride.     

Occupational exposure to solvents and the risk of lymphomas

BACKGROUND: A number of studies have shown possible associations between occupational exposures, particularly solvents, and lymphomas. The present investigation aimed to evaluate the association between exposure to solvents and lymphomas (Hodgkin and non-Hodgkin) in a large population-based, multicenter, case-control study in Italy. METHODS: All newly diagnosed cases of malignant lymphoma in men and women age 20 to 74 years in 1991-1993 were identified in 8 areas in Italy. The control group was formed by a random sample of the general population in the areas under study stratified by sex and 5-year age groups. We interviewed 1428 non-Hodgkin lymphoma cases, 304 Hodgkin disease cases, and 1530 controls. Experts examined the questionnaire data and assessed a level of probability and intensity of exposure to a range of chemicals. RESULTS: Those in the medium/high level of exposure had an increased risk of non-Hodgkin lymphoma with exposure to toluene (odds ratio = 1.8; 95% confidence interval = 1.1-2.8), xylene 1.7 (1.0-2.6), and benzene 1.6 (1.0-2.4). Subjects exposed to all 3 aromatic hydrocarbons (benzene, toluene, and xylene; medium/high intensity compared with none) had an odds ratio of 2.1 (1.1-4.3). We observed an increased risk for Hodgkin disease for those exposed to technical solvents (2.7; 1.2-6.5) and aliphatic solvents (2.7; 1.2-5.7). CONCLUSION: This study suggests that aromatic and chlorinated hydrocarbons are a risk factor for non-Hodgkin lymphomas, and provides preliminary evidence for an association between solvents and Hodgkin disease.     

Dementia and occupational exposure to organic solvents

OBJECTIVES: To investigate whether occupational exposure to organic solvents increases the risk of dementia. METHODS: Cases of dementia were identified from the computed tomography records of eight neuroradiology centres in England and Wales, and were compared with two sets of controls investigated at the same centres. The first set of controls were patients with brain cancer and the second set were patients with other disorders that were not chronically disabling. Lifetime occupational histories were obtained through a postal questionnaire completed by the subjects or their next of kin. Associations between dementia and occupation were examined by logistic regression. RESULTS: Usable questionnaires were returned for 204 (61%) of the cases, 225 (51%) of the controls with brain cancer, and 441 (61%) of the other controls. The findings with each of the two sets of controls were similar. In comparison with all controls combined, cases had less often worked ever as a painter or printer (odds ratio (OR) 0.6, 95% confidence interval (95% CI) 0.3 to 1.2), and were less likely to have worked for > 1 year as a printer, painter, or launderer or dry cleaner (OR 0.6, 95% CI 0.3 to 1.4). CONCLUSIONS: These findings provide no support for the hypothesis that occupational exposure to solvents is a cause of dementia. An excess risk in subsets of workers with extremes of exposure cannot be discounted, but the data indicate that any influence of exposure to solvents on the overall incidence of severe dementia in the general population of England and Wales is small.