Sister chromatid exchange frequency in workers exposed to high levels of ethylene oxide,in a hospital sterilization service

Summary Blood samples were taken from a group of 25 subjects professionally exposed to high levels of ethylene oxide (EO) during the past two years; the samples were compared to those from 22 control subjects, using sister chromatid exchange (SCE) methodology. The quantity of ethylene oxide inhaled during the two previous years was subsequently evaluated to fall between 500 and 5800 mg. When compared with the control group, the exposed group demonstrated a significant increase in the SCE rate. For certain individuals, the rate of increase rose 100% beyond the control mean. Smoking habits significantly influenced the data observed for the control group, but no significant differences in the SCE rate were found for the exposed group, regardless of smoking habits. Senior workers had the highest SCE mean levels. This observation indicated that the effect of exposure to EO was sufficient to produce a genetic reaction, was cumulative and in some cases persistent.     

DNA adducts in granulocytes of hospital workers exposed to ethylene oxide

BACKGROUND: Ethylene oxide (EtO), an important industrial chemical intermediate and sterilant, is classified as a human carcinogen. Occupational EtO exposure in many countries is regulated at 1 ppm (8-hr TWA), but levels of EtO-DNA adducts in humans with low occupational EtO exposures have not been reported. METHODS: We examined the formation of N7-(2'-hydroxyethyl)guanine (N7-HEG), a major DNA adduct of EtO, in 58 EtO-exposed sterilizer operators and six nonexposed workers from ten hospitals. N7-HEG was quantified in granulocyte DNA (0.1-11.5 microg) by a highly sensitive and specific gas chromatography-electron capture-mass spectrometry method. Cumulative exposure to EtO (ppm-hour) was estimated during the 4-month period before the collection of blood samples. RESULTS: There was considerable inter-individual variability in the levels of N7-HEG with a range of 1.6-241.3 adducts/10(7) nucleotides. The mean levels in the nonexposed, low (< or =32 ppm-hour), and high (>32 ppm-hour) EtO-exposure groups were 3.8, 16.3, and 20.3 adducts/10(7) nucleotides, respectively, after the adjustment for cigarette smoking and other potential confounders, but the differences were not statistically significant. CONCLUSIONS: This study has demonstrated for the first time, detectable levels of N7-HEG adducts in granulocytes of hospital workers with EtO exposures at levels less than the current U.S. standard of 1 ppm (8-hr TWA). A nonsignificant increase in adduct levels with increasing EtO exposure indicates that further studies of EtO-exposed workers are needed to clarify the relationship between EtO exposure and N7-HEG adduct formation.     

Sister chromatid exchanges and micronuclei in peripheral lymphocytes of shoe factory workers exposed to solvents

We examined sister chromatid exchanges (SCEs) and micronuclei (MN; cytokinesis-block method) in cultured peripheral lymphocytes from 52 female workers of two shoe factories and from 36 unexposed age- and sex-matched referents. The factory workers showed an elevated level of urinary hippuric acid, a biomarker of toluene exposure, and workplace air contained high concentrations of various organic solvents such as toluene, gasoline, acetone, and (in one of the plants only) ethylacetate and methylenediphenyl diisocyanate. The shoe factory workers showed a statistically significant higher frequency of micronucleated binucleate lymphocytes in comparison with the referents. This finding agreed with three preliminary MN determinations (each comprising 27-32 shoe workers and 16-20 controls) performed in one of the plants 2-5 years earlier. The shoe factory workers also had a lower average level of blood hemoglobin than the referents. In contrast, no difference was found between the groups in SCE analysis. Smokers showed significantly higher mean frequencies of SCEs per cell and high frequency cells (HFC) than nonsmokers. Aging was associated with increased MN rates and reduced cell proliferation. Polymorphism of the glutathione S-transferase M1 gene (GSTM1) did not affect the individual level of SCEs; but in smoking shoe workers an effect of the occupational exposure on the frequency of micronucleated cells could be seen only in GSTM1 null subjects. The low prevalence of the glutathione S-transferase T1 (GSTT1) null genotype precluded the evaluation of the influence of GSTT1 polymorphism. Our results show that the shoe factory workers have experienced genotoxic exposure, which is manifest as an increase in the frequency of MN, but not of SCEs, in peripheral lymphocytes. The exposures responsible for the MN induction could not be identified with certainty, but exposure to benzene in gasoline and methylenediphenyl diisocyanate may explain some of the findings.     

Sister chromatid exchange and oxidative DNA damage in paving workers exposed to PAHs

Paving workers are exposed during road paving to several polycyclic aromatic hydrocarbons (PAHs) contained in asphalt fumes. In this study early genotoxic and oxidative effects of exposure to bitumen fumes were evaluated in 19 paving workers and 22 controls. Environmental and biological monitoring of exposure was carried out, measuring, on personal air samples from exposed workers collected during three working days, the concentration of 14 PAHs and urinary OH-pyrene at the end of each of the three working days. Genotoxic effect was evaluated analysing sister chromatid exchange (SCE) frequency and direct-oxidative DNA damage by formamido-pyrimidine-glycosylase (Fpg)-modified comet assay on lymphocytes. Tail moment values from Fpg-enzyme treated cells (TMenz) and from untreated cells (TM) were used as parameters of direct and oxidative DNA damage, respectively. For each subject, the TMenz/TM ratio >2.0 was used to indicate the presence of oxidative damage. DNA damage was also evaluated analysing comet percentage. Personal air samples showed low level of total PAHs (2.843 microg m(-3)) with prevalence of 2-3 ring PAHs (2.693 microg m(-3)). Urinary OH-pyrene after work-shift of the three working days was significantly higher than that found at the beginning of the working week. SCE analysis did not show any difference between two groups while an oxidative DNA damage was found in 37% of exposed with respect to the absence in controls. Comet percentage was significantly higher (P = 0.000 ANOVA) in the exposed than in controls. The results demonstrate the high sensitivity of comet assay to assess early oxidative effects induced by exposure to bitumen fumes at low doses and confirm the suitability of urinary OH-pyrene as a biomarker of PAH exposure. In conclusion the study suggests the use of Fpg-modified comet test as a biomarker of early genotoxic effects and that of urinary OH-pyrene as a biomarker of PAH exposure to furnish indications in terms of characterization, prevention and management of risk in occupational exposure to mixtures of potentially carcinogenic substances.     

Concentration of ethylene oxide in the alveolar air of occupationally exposed workers

Ethylene oxide was tested in environmental air and in the alveolar air of 10 workers employed in a hospital sterilizer unit at hourly intervals during the work shift. Alveolar ethylene oxide concentrations (Ca) were correlated with environmental concentration (Ci) in all the workers studied (r = 0.89-0.99). The ratio between alveolar and environmental concentration (Ca/Ci) given by the slope of the regression line obtained for all the data collected was 0.24. This means that the alveolar retention of ethylene oxide, expressed as 1 - (Ca/Ci), corresponded, on average, to about 75% of the environmental concentration.     

环氧乙烷气体的灭菌效果监测及评价

本文通过对环氧乙烷气体灭菌过程进行全程监测,发现灭菌效果与消毒物品的摆放和消毒物品的材质有密切关系     

Ambient and biochemical effect monitoring of workers exposed to ethylene oxide

Objectives: Ethylene oxide is an alkylating agent known to be a directly acting mutagen and carcinogen. This study describes the relationship between workplace ambient air concentrations of ethylene oxide and the concentration of N-2-hydroxyethylvaline in the globin of exposed workers. Methods: During the sterilization of medical equipment, 12 workers were occupationally exposed to ethylene oxide. Personal and stationary ambient air measurements were carried out to monitor the external exposure. The determination of the protein adducts was based on the N-alkyl-Edman method, introducing a new commercially available dipeptide standard for calibration purposes. Results: Ethylene oxide concentrations ranging from 0.2 to 8.5 ppm were found in the workplace air. The adduct concentrations ranged from 5,219 to 32,738 pmol N-2-hydroxyethylvaline/g globin in the case of regularly exposed workers (n = 9) and from 518 to 3,321 pmol N-2-hydroxyethylvaline/g globin for three persons with occasional contact with ethylene oxide. Conclusions: The Deutsche Forschungsgemeinschaft established in 1993 a relationship between the ethylene oxide concentration in ambient air and the amount of N-2-hydroxyethylvaline in human globin. By extrapolation, constant exposure to 1 ppm ethylene oxide should yield approximately 4,000 pmol N-2-hydroxyethylvaline/g globin. The ambient air concentrations of ethylene oxide and the amount of N-2-hydroxyethylvaline determined within the present study confirm this extrapolation in practice. In addition, the determination of adducts based on the use of commercially available dipeptide standards for calibration purposes turned out to be an advantageous alternative to the commonly used protein standards. Received: 18 February 1997 / Accepted: 9 June 1997     

Sister chromatid exchanges in peripheral lymphocytes of workers exposed to benzene,trichloroethylene, or tetrachloroethylene,with reference to smoking habits

Summary The frequencies of sister chromatid exchanges (SCE) were studied in peripheral lymphocytes from four groups of solvent workers, i.e. 36 nonsmoking women exposed to benzene at about 50 ppm on the average, 38 men and women (male smokers and nonsmokers, and female nonsmokers) exposed to trichloroethylene (TRI) at 7 ppm, 27 men and women (both smokers and nonsmokers) with tetrachloroethylene (TETRA) exposure, and 19 workers (both smokers and nonsmokers in men, and nonsmokers in women) exposed to a mixture of TRI (at 8 ppm) and TETRA (at 17 ppm) (TRI + TETRA). The results were compared with the findings in control subjects matched by age, sex, smoking habits and place of residence. No significant increase in SCE frequencies was observed in association with exposure to benzene, TRI, TETRA or TRI + TETRA. The SCE frequency was, however, significantly higher in the TRI-, TETRA-or TRI + TETRA-exposed smoking men than in the concurrent nonsmoking controls of the same sex. Possible synergism between solvent exposure and smoking is discussed.     

Adverse health effects of ethylene oxide and occupational exposure limits

The proposed revision of the US standard for occupational exposure to ethylene oxide has recently been topical and controversial. Most of the recent experimental and epidemiological evidence of health effects, which provoked lowering the permissible exposure limit, appears to be unreliable and insufficient for risk assessment.     

组合型医疗器械的环氧乙烷残留量测试采样方法的讨论

阐述了对环氧乙烷残留量测试中，如何对组合型医疗器械产品进行取样的问题。     

Evaluation of workers exposed to dust containing hard metals and aluminum oxide

Background Fourteen workers exposed to hard metals and aluminum oxide were evaluated. Methods Six heavily exposed workers underwent bronchoscopy and bronchoalveolar lavage, and five workers underwent transbronchial biopsy. Results Microchemical analysis of transbronchial biopsies showed a high lung burden of exogenous particles, especially metals related to their hard metals exposure. Lung tissue and cellular changes, which were associated with exposure to hard metal and aluminum oxide, corresponded well with the microanalytic test results. Conclusions Three workers had at biopsy diffuse interstitial inflammatory changes: two of them were asymptomatic with normal chest X-ray films, and one had clinically evident disease with severe giant cell inflammation. Two other workers showed focal inflammation. The worker showing clinical disease and one asymptomatic worker with interstitial inflammatory changes had elevated bronchoalveolar lavage fluid-eosinophilia counts. These two were father (with clinical disease) and son (asymptomatic). Am. J. Ind. Med. 34:177–182, 1998. © 1998 Wiley-Liss, Inc.     

An epidemiological study of cancer risk among workers exposed to ethylene oxide using hemoglobin adducts to validate environmental exposure assessments

Summary Cancer morbidity was investigated in a cohort of 2,170 ethylene oxide (EO)-exposed workers from 2 plants producing disposable medical equipment. The subjects had been employed for at least 1 year during the periods 1970–1985 and 1964–1985, respectively. The exposure to EO was assessed for each of six job categories in the plants with respect to each calendar year, on which basis values for individual cumulative exposure to EO (ppm-years) were calculated. The levels of hydroxyethyl adducts to N-terminal valine (HOEtVal) in hemoglobin fitted well with the values estimated for airborne exposure to EO. No increased cancer incidence was found [standardized morbidity ratio (SMR), 0.78; 95% CI, 0.49–1.21)]. No leukemia was observed, but one case No leukemia was observed, but one case of non-Hodgkin's lymphoma, one case of myeloma, and one case of polycythemia vera were diagnosed as compared with two expected hematopoietic and lymphatic tumors (SMR, 1.54; 95% Cl, 0.32–4.5). No stomach cancer was detected as compared with the 0.5 case expected. There were no significant exposure-response associations between estimates of exposure to EO and cancer morbidity.     

职业接触环氧丙烷工人Hb加合物及其遗传毒性分析

目的 研究长期接触低浓度环氧丙烷工人的遗传效应。方法 采用气相色谱法对环氧丙烷作业现场进行监测的同时,采集工人血样,采用高灵敏的N-alkyl Edman气质谱法对血红蛋白加合物(HP-缬氨酸)含量进行了测定,同时对姐妹染色单体互换(SCE)进行检测。结果 环氧丙烷作业工人时间加权平均浓度(TWA)为2．6mg/m^3和6．9mg／m^3。环氧丙烷接触组工人的HP-缬氨酸水平明显高于对照组,差异有极显著性(P=0．0018)。接触组中的每个细胞SCE数明显高于对照组,差异有显著性(P=0．011)。血红蛋白加合物与姐妹染色单体互换的相关系数r为0．762．并且差异有极显著性(P=0．0014)。结论 低浓度环氧丙烷对职业人群具有细胞遗传学毒性。     

Proportionate mortality study of workers in the garment industry exposed to formaldehyde

In order to evaluate the human carcinogenicity of formaldehyde, we conducted a proportionate mortality study of garment workers engaged in the production of shirts from formaldehyde-treated cloth. This study included three plants, and was based upon 256 deaths identified from a death-benefit insurance fund. No deaths due to nasal cancer were observed, and the mortality from respiratory cancer (11 cases, PMR = 95) was slightly less than expected. Statistically significant (p less than .05) elevations in proportionate mortality were observed for malignant neoplasms of the "buccal cavity" (three cases, PMR = 750), for "biliary passages and liver" (four cases, PMR = 313) and for "other lymphatic and hematopoietic sites" (four cases, PMR = 400). A proportionate cancer mortality (PCMR) analysis also was conducted, and cancer of the "buccal cavity" (three cases, PCMR = 682), and other "lymphatic and hematopoietic sites" (four cases, PCMR = 342) were still significantly elevated. The observed excesses in cancer mortality were primarily experienced by white females, who made up the major portion of the workforce, and workers with more than 10 years of latency and duration of exposure, a criterion for inclusion for most workers in the study group. The neoplasms observed were not equally distributed among the three facilities included in the study. Because of the small number of deaths involved and the lack of consistency with other studies, we believe that these findings should be viewed cautiously, pending the outcome of more definitive studies.     

Primary DNA damage in peripheral mononuclear blood cells of workers exposed to bitumen-based products

The genotoxic effect of occupational exposure to bitumen-based products was determined by the extent of DNA strand breaks and alkali-labile sites of the DNA of peripheral mononuclear blood cells from seven roofers, 18 road paving workers, and nine bitumen painters. In order to evaluate short-term genotoxic effect the workers were investigated on Fridays and on Mondays after a weekend free of occupational exposure. The roofers (all cigarette smokers) showed a significantly (P < 0.002) 43% higher mean level of alkaline DNA strand breaks on Friday than did the ten smoking controls included in this study. Also, comparison of the individual levels of alkaline strand breaks on Mondays and on Fridays revealed a significant increase (P < 0.05, Wilcoxon test) during the work week. In the road paving workers and the bitumen painters no statistically significant difference in the mean levels of alkaline strand breaks could be found compared to controls either for the measurement on Mondays or for that on Fridays. However, interesting tendencies were observed. As in the group of roofers, the mean level of alkaline DNA strand breaks as well as the majority of the individual levels of alkaline strand breaks of road paving workers was higher on Fridays than on Mondays. In contrast, bitumen painters exhibited a relatively high level of alkaline DNA strand breaks on Mondays and a decreased mean level of strand breaks on Fridays. DNA adducts could be detected at a low level (up to 2.9 adducts per 10⁹ bases) in 10 of 14 road paving workers and bitumen painters using the ³²p-postlabelling assay. The number of DNA adducts correlated with the years spent in the present job. Road paving workers and bitumen painters showed only suggestive evidence for a possible genotoxic effect due to their occupational exposure. Because we cannot exclude the formation of DNA cross-links in these workers, a more detailed investigation of the hazard is urgently needed. For roofers, substantial genotoxic damage in peripheral mononuclear blood cells was observed in this study.This study contains parts of an M.D. thesis by G. Boettler     

谷胱甘肽转移酶M1基因缺失与苯白血病的相关性分析

目的 探讨苯接触工人谷胱甘肽转移酶M1（GSTμ）基因缺失与苯白血病发病的相关性。方法 采用1：1配比的病例－对照研究和多因素条件Logistic回归分析。结果 GSTμ基因缺失者患苯白血病的危险性为GSTμ基因携带者的3．6倍，提示GSTμ基因缺失是苯白血病发病的危险因素。单因素条件Logistic回归分析显示，作用显著的因素依次是GSTμ基因缺失、GSTμ亚型酶活力、接苯工龄、GST总酶活力、吸烟总量和车间空气中苯的平均浓度。经多因素条件Logistic回归分析后，按相对危险度（OR）大小排列，依次是GSTμ基因缺失、接苯工龄和GSTμ亚型酶活力。结论 GSTμ基因缺失在苯白血病的发生过程中起重要作用，可作为探讨苯白血病人群易感性和发现高危人群的效应标志物。     

Occupational hazards to health care workers: report of a conference

Health care workers are exposed to an array of physical, chemical, biological, and psychosocial hazards. At a national conference in Seattle May 11-13, 1983, hospital occupational medicine programs were characterized as lagging far behind those in industries with comparable illness and injury rates. Participants and speakers recommended that health care workers be trained to recognize occupational hazards; that epidemiologic, laboratory, and clinical studies be undertaken to discern trends and establish the mechanisms of effects from hazardous exposures; and that adequate employee health and safety programs be established in health care settings.     

Effects on the nervous system in different groups of workers exposed to aluminium

OBJECTIVE—To investigate possible neurotoxic effects in groups of aluminium pot room and foundry workers, aluminium welders, and a small group of workers exposed to aluminium in the production of flake powder.
METHODS—Exposure to aluminium was evaluated with aluminium concentrations in blood and urine as well as a questionnaire. The groups exposed to aluminium were compared with a group of mild steel welders. Neurotoxic effects were studied with mood and symptom questionnaires and several psychological and neurophysiological tests.
RESULTS—The pot room and foundry workers showed very low aluminium uptake as their aluminium concentrations in blood and urine were close to normal, and no effects on the nervous system were detected. The group of workers exposed to flake powder had high concentrations of aluminium in blood and urine, even higher than those of the aluminium welders. However, aluminium could not be shown to affect the functioning of the nervous system in flake powder producers. Although significant effects could not be shown in the present analysis of the data on welders, the performance of the welders exposed to high concentrations of aluminium was affected according to the analyses in the original paper from this group.
CONCLUSIONS—For the pot room and foundry workers no effects related to the exposure to aluminium could be found. For the group of flake powder producers exposed for a short term no effects on the nervous systems were evident despite high levels of exposure. Due to the high concentrations of aluminium in the biological samples of this group, measures to reduce the exposure to aluminium are recommended, as effects on the central nervous system might develop after protracted exposures. However, this assumption needs to be verified in further studies.


Keywords: aluminium; workers; nervous system     

Fiber size and number in workers exposed to processed chrysotile asbestos, chrysotile miners, and the general population

We analyzed chrysotile and chrysotile-associated amphibole (largely tremolite) asbestos fibers in 21 workers exposed to various types of processed (milled) chrysotile ore, 20 long-term chrysotile miners, and 20 members of the general population (controls). Significantly greater amounts of both chrysotile and tremolite were found in processed-ore workers and miners than in controls. On average, the mean fiber lengths and aspect ratios for the mining and processed-ore-exposed workers were similar and were significantly greater than the values seen in the controls; within the processed-ore group, there was a marked variation in these parameters, and some workers appeared to be exposed to fairly long, thin fibers. It was found empirically that the fiber size data, and to a lesser extent the concentration data, could be used to classify workers accurately into those with processed-ore exposure and controls. We conclude that fiber sizes in the lungs of processed-ore-exposed workers are similar to those of chrysotile miners and are considerably longer than those found in the general population; some processed-ore workers have longer fibers which might be responsible for higher disease incidences in certain working groups; tremolite accompanies chrysotile in a variable proportion of workers exposed to processed chrysotile products and might be important in the genesis of mesothelioma in such workers; and mineralogic analysis will usually detect exposure even when chrysotile has largely disappeared from lung tissue.