Renal disorders induced by organic solvents

Organic solvents are a class of chemical substances that are widely used in large volume in various manufacturing plants. Due to their high lipophilicity, organic solvents may produce physicochemical damage to renal glomeruli and tubuli. Many reports have been published abroad, though only a few in Japan, on organic solvent-induced nephropathy such as Goodpasture syndrome, a form of renal damage mediated by anti-basement membrane antibodies. This article reviews the epidemiological studies published in the literature and stresses that organic solvent exposure is one of the etiological factors involved in the development of chronic nephropathy. At present in Japan there are 60,000 patients with terminal renal failure undergoing hemodialysis, 50,000 young men placed under observation each year for abuse of organic solvents, and one million workers exposed to organic solvents in factories. Attention should be focused on the occurrence of renal damage due to organic solvents in Japan.     

Chronic glomerulonephritis and organic solvents

Summary Fifty patients with histologically confirmed chronic glomerulonephritis (34 males, 16 females, average age 42 years) and 50 control patients, age and sex-matched, with a variety of internal diseases, were selected. Both cases and controls completed an extensive questionnaire and additional information was sampled by means of a personal interview, especially concerning the exposure to organic solvents. In contrast to three other recently published case-control studies, no difference in exposure between cases and controls was found in our study. A relative risk of 1.1 with an upper 95% confidence limit of 2.7 was calculated. It is suggested that one particular solvent, contaminant, or additive present, which is less used in the Amsterdam region than in other areas, may explain the discrepancy with previous studies.This study was supported by the Dutch Ministry of Labour Affairs     

Non-Hodgkin's lymphomas and organic solvents

Organic solvents have been suggested as a possible risk factor for non-Hodgkin's lymphomas (NHL). We studied 109 NHL incident cases and 276 controls with other cancers (1990/1996) in the city of Salvador, Brazil. Occupational exposure to organic solvents was evaluated through standardized questionnaires and defined by industrial hygienists, taking into account individuals' lifetime history. An association between occupational exposure to organic solvents and NHL was observed, OR = 1.67 (95% CI, 0.97 to 2.87), especially among individuals less than 64 years, OR = 1.91 (95% CI, 0.99 to 3.67), and among those who used domestic insecticides, OR = 2.24 (95% CI, 1.01 to 3.97). Odds ratios were similar for nodal and diffuse NHL. These results suggest that organic solvents may contribute to the causation of NHL, especially among young individuals, and that synergism may play a role in the process of lymphomagenesis.     

Exposure to organic solvents and personality

OBJECTIVES—Although cognitive and neuropsychological changes have been found after high cumulative exposures to solvents, it is not clear whether such exposures are associated with personality characteristics. To study this two groups of British and Chinese dockyard painters who had been heavily exposed to paint solvents have been investigated.
METHODS—260 Male dockyard painters in the United Kingdom, 539 local community controls, 109 Chinese dockyard painters, and 255 dockyard controls completed the Eysenck personality questionnaire, neuroticism (N) and social conformity or dissimulation (L) scales. The non-parametric Kruskal-Wallis test was used to evaluate differences in scores of personality traits between painters and controls. Adjusted relative risks for painters having high N and L scores were calculated in a Breslow-Cox regression analysis, and exposure-response relations were examined in multivariate logistic regression analysis. Non-parametric Spearman's correlation was used to examine relations between previously determined neuropsychological symptoms and personality.
RESULTS—Both British and Chinese data showed that mean neuroticism scores of painters were significantly higher than controls, whereas scores of social conformity did not differ. Relative risk of being a painter increased significantly with increasing N scores, but L scores showed no such trend. In a case-control analysis, there were significant exposure-response relations for the N score. In the United Kingdom the odds ratios (ORs) (95% confidence interval (95% CI), were 2.03 (0.79 to 5.22) for 1-4 years of exposure, 2.38 (0.82 to 6.91) for 5-9 years, 7.05 (1.27 to 39.25) for 10-14 years, and 1.76 (0.63 to 4.89) for 15-41 years. In the Chinese painters, ORs were 4.66 (1.38 to 15.75) for 2-14 years, 10.03 (2.96 to 34.04) for 15-18 years, and 13.56 (3.78 to 48.59) for 19-43 years. Neuroticism was significantly positively related to neuropsychological symptoms in all subjects. Social conformity showed no association with neuropsychological symptoms in British painters and a negative relation among the Chinese painters.
CONCLUSION—Increasing symptoms suggesting neuroticism seemed to relate to the duration of painting whereas scores for social conformity and dissimulation did not. The relation between exposure time and response suggests that increased neuroticism may be caused by long term occupational exposure to organic solvents.


Keywords: organic solvents; painter; dockyards; personality; neuroticism; social conformity     

Inhibition of synaptosome membrane-bound integral enzymes by organic solvents

The possible mechanism of the depressive effect of organic solvents on the central nervous system (CNS) was studied with synaptosome membranes as a model. The changes in the activities of the membrane-bound integral enzymes acetylcholinesterase, total adenosinetriphosphatase, and magnesium-activated adenosinetriphosphatase were determined after treatment with different concentrations of organic solvents in vitro. Aromatic hydrocarbons and chlorinated aliphatic hydrocarbons inhibited all the enzyme activities concentration dependently. Alcohols had no significant effect at the same dose levels. The results of the present study suggest that the CNS depressive effect of organic solvents may be based on their interaction with membrane integral proteins.     

Percutaneous absorption of organic solvents

Organic solvents pass the cutaneous barriers and may quickly be absorbed in substantial amounts, such that several solvents have "skin" denotations in lists of occupational exposure limit values. Solvents may be absorbed from liquids, upon direct skin contact, and in some cases also from contact with vapors. Environmental factors such as temperature, humidity, vehicle, and ventilation influence absorption. Absorption rates vary considerably; several amphiphilic solvents are absorbed at high rates. Since solvents are volatile, unoccluded repeated exposures result in less absorption than does continuous contact, and adequate ventilation may reduce absorption considerably. Risk assessments of skin absorption of organic solvents have benefited from calculation of quantitative structure-activity relationships based on log P(o/w), which enables skin absorption to be calculated with reasonable accuracy.     

深圳市宝安区有机溶剂职业中毒的经济负担研究

目的评价有机溶剂职业中毒企业的经济负担。方法对深圳市宝安区2001年1月1日～2002年12月30日所有发生有机溶剂职业中毒的企业进行现场调查。结果实际调查现患企业24间,现患病例96人,另外有4间企业(7个病例)搬迁和倒闭除外。引起中毒的有机溶剂为正己烷、三氯乙烯、二氯乙烷和混合有机溶剂。宝安地区企业有机溶剂职业中毒2年总经济负担为8059095.2元,确诊患者的治疗时间总计124人年,平均经济负担为64992.7元/人年。经济负担中直接经济负担4756313.2元,占59.0%;误工时间28517d,间接经济负担为922782.0元,占11.5%;无形损失2380000元,占29.5%。2年内24间企业共投入职业卫生整改资金899966元。整改投入与总经济负担呈直线相关关系(相关系数r=0.80,P=0.00),职业中毒的损失与整改投入的比值为8.95∶1。结论有机溶剂职业中毒经济负担沉重。做好有机溶剂职业中毒防治工作,对确保广大劳动者的身心健康,促进地区经济的发展,有着重要的意义。     

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.

 

     

Permeation of eleven protective garment materials by four organic solvents

The resistance of 11 different protective garment materials to permeation by epichlorohydrin, perchloroethylene, trichloroethylene, and 1,2-dibromoethane were determined. Water was the collection medium in the epichlorohydrin tests with samples taken periodically and analyzed by gas chromatography. Because of the relatively low solubilities of the other three challenge liquids in water, air was used as the collection medium. The concentrations of the permeant vapors in an airstream which passed across the downstream sides of the membranes were determined automatically every 2 min with a flame ionization detector. Butyl rubber offers good protection against epichlorohydrin, with breakthrough occurring after 8 hrs. With the halogenated hydrocarbons, Viton and Vitrile provide protection for at least 12 and 24 hrs, respectively, while PVA showed no breakthrough in 24 hrs with trichloroethylene and dibromoethane. With perchloroethylene, nitrile breakthrough occurred in 5 hrs. The weight and volume changes which occurred when the materials were soaked in each of the challenge liquids were also determined. The log of these changes correlated moderately well with the log of the breakthrough time normalized by the square of the material thickness.     

毛细管柱气相色谱法测定恩替卡韦中8种残留溶剂

目的:建立毛细管柱气相色谱法测定恩替卡韦中残留的有机溶剂。方法:采用HP-624毛细管色谱柱、顶空进样、氢火焰离子化检测器,进样口温度为250℃,检测器温度为300℃,柱温为80℃保持7 min,再以20℃/min升至220℃。结果:甲醇、乙醇、二氯甲烷、叔丁基甲基醚、正己烷、乙酸乙酯、四氢呋喃与甲苯相邻峰间的分离度及检测灵敏度均符合要求。结论:该法简便、快速、灵敏、结果准确可靠,可用于恩替卡韦中残留有机溶剂的测定。     

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 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 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.     

The cytotoxicity of some organic solvents

The cytotoxicity of 33 organic solvents was determined using Ehrlich-Landschütz diploid (ELD) ascites tumour cells during short-time in vitro incubations. Among the organic solvents studied, tetralin, crotonic aldehyde, formaldehyde, and acrolein were highly toxic to ELD cells. Benzyl chloride, carbon tetrachloride, methyl ethyl ketone, and 1,1,1,2-tetrachloroethane were found to be moderately toxic. Tumour cells treated with crotonic aldehyde were reinoculated into mice. The growth capacity of the inoculated population was shown to be dependent on the frequency of surviving cells after treatment with the organic solvents indicating that true cell mortality was studied.     

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.     

Vapor-liquid equilibria for multicomponent organic solvents

Most organic solvents used in the workplace are mixed solvents consisting of several components. It is therefore very important to know the equilibrated vapor concentrations in order to control the work environment. In this study, the vapor-liquid equilibrium for multicomponent organic solvents is estimated by introducing the activity coefficients, which are calculated with the UNIFAC (Universal Quasichemical Functional Group Activity Coefficient) model. For two-component solvents, that is, the toluene-methanol and o-xylene-methanol systems, the calculated values of the vapor fraction and the equilibrated vapor concentrations are in good agreement with the reference ones. For three- or four-component solvents that are used as thinners, the calculated values are also generally in good agreement with the reference ones.     

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).     

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).