Inhalative Exposure to Vanadium Pentoxide Causes DNA Damage in Workers: Results of a Multiple End Point Study

Background

Inhalative exposure to vanadium pentoxide (V₂O₅) causes lung cancer in rodents.

Objective

The aim of the study was to investigate the impact of V₂O₅ on DNA stability in workers from a V₂O₅ factory.

Methods

We determined DNA strand breaks in leukocytes of 52 workers and controls using the alkaline comet assay. We also investigated different parameters of chromosomal instability in lymphocytes of 23 workers and 24 controls using the cytokinesis-block micronucleus (MN) cytome method.

Results

Seven of eight biomarkers were increased in blood cells of the workers, and vanadium plasma concentrations in plasma were 7-fold higher than in the controls (0.31 μg/L). We observed no difference in DNA migration under standard conditions, but we found increased tail lengths due to formation of oxidized purines (7%) and pyrimidines (30%) with lesion-specific enzymes (formamidopyrimidine glycosylase and endonuclease III) in the workers. Bleomycin-induced DNA migration was higher in the exposed group (25%), whereas the repair of bleomycin-induced lesions was reduced. Workers had a 2.5-fold higher MN frequency, and nucleoplasmic bridges (NPBs) and nuclear buds (Nbuds) were increased 7-fold and 3-fold, respectively. Also, apoptosis and necrosis rates were higher, but only the latter parameter reached statistical significance.

Conclusions

V₂O₅ causes oxidation of DNA bases, affects DNA repair, and induces formation of MNs, NPBs, and Nbuds in blood cells, suggesting that the workers are at increased risk for cancer and other diseases that are related to DNA instability.     

Differential Aerosol Challenge Studies in Byssinosis

Cotton textile mill workers with conditions diagnosed as byssinosis or not byssinosis by a modified Medical Research Council (MRC) questionnaire were challenged with extracts of cotton dust fractionated by filter membrane dialysis, and volatilization. Byssinotic subjects responded with a significant decrease in FEV_1.0 and with clinical symptoms to the inhalation of whole raw cotton extract and nonvolatile, nondialyzable cotton extract compared to saline, volatile extract, and dialyzable extract. Subjects without byssinosis responded the same to saline as to all other extracts. Comparison of responses of byssinotic and nonbyssinotic subjects showed no statistically significant differences with any extract. It was concluded that the active agent in cotton dust is water soluble, filterable at 0.22μ, nonvolatile at 40C, and nondialyzable but may not be active only in that group of patients identified as byssinotic by questionnaire.     

职业性镍接触工人DNA链断裂的研究

[目的]观察不锈钢冶炼职业性镍接触对工人淋巴细胞DNA损伤的影响。[方法]对某不锈钢冶炼厂相关作业环境进行监测,根据作业工种的不同,选取该厂镍接触的炼钢工（60名）、钢渣处理工（65名）及轧钢工（40名）,共165名男性工人为接触组,同时选取该企业67名水处理工为对照组,通过问卷调查收集研究对象的一般情况、职业暴露、吸烟和饮酒情况等,应用彗星试验检测工人外周血淋巴细胞的DNA损伤。[结果]炼钢工的尾惯量为（23．33±7．10）％,钢渣处理工为（22．87±10．67）％;轧钢工为（21．67±9．32）％,3组均高于对照组（10．53±5．08）％（P〈0．01）;炼钢工的尾长为（1．20±0．21）μm,钢渣处理工为（1．18土0．22）μm,轧钢工为（1．14±0．24）μm,3组也均高于对照组（0．91±0．19）μm（P〈0．01）;炼钢工、钢渣处理工和的轧钢工Olive尾矩（olive tail moment,OTM）分别为0．495±0．055、0．455±0．045和0．429±0．069,均高于对照组（0．103±0．054）（P〈0．01）。各工龄组之间OTM差异均有统计学意义（P〈0．01）;吸烟与非吸烟组之间比较,OTM值差异也有统计学意义（P〈0．05）。经相关分析表明：OTM与尿镍浓度呈正相关（r=0．576,P〈0．01）。[结论]淋巴细胞DNA损伤可能是镍职业接触工人的早期损害之一。     

职业接触灭蚁药物对人体淋巴细胞DNA的损伤作用

[目的]探讨职业性接触灭蚁药物氯丹、含砷化合物对作业人员外周血淋巴细胞DNA损伤水平的影响。 [方法]采用碱性单细胞凝胶电泳技术检测灭蚁药物作业工人外周血淋巴细胞的DNA损伤,研究灭蚁药物对职业接触人群的遗传毒性,观察指标包括DNA断裂分级(将DNA断裂损伤细胞按其损伤程度分级)及DNA彗星尾长(彗头末端到彗尾的长度)。并对工龄、吸烟、饮酒和体内毒物的浓度对外周血淋巴细胞DNA损伤水平各项指标的影响进行统计学分析。[结果]职业接触灭蚁药物工人外周血淋巴细胞DNA断裂程度及DNA彗星尾长两个指标,均明显高于对照组,差异有显著性(P<0．01),并与体内毒物水平、接触工龄有明显正相关关系,吸烟、饮酒能加重含氯丹、砷化合物对DNA的损伤水平。[结论] 职业性接触灭蚁药物可对职业工人外周血淋巴细胞DNA造成损伤,并存在遗传毒性。     

Neurobehavioural effects of occupational exposure to cadmium: a cross sectional epidemiological study

BACKGROUND—A patient with unexplained minor behavioural changes associated with an axonal sensorimotor polyneuropathy had a history of chronic occupational exposure to cadmium (Cd). Although animal studies have shown that Cd is a potent neurotoxicant, little is known about its toxicity for the human central nervous system. The aim of this study was to investigate the toxic potential of chronic occupational exposure to Cd on neurobehavioural functions.
METHODS—A cross sectional epidemiological study was conducted in a group of Cd workers and an age matched control group. Eighty nine adult men (42 exposed to Cd and 47 control workers) were given a blinded standardised examination that consisted of computer assisted neurobehavioural tests (neurobehavioural examination system), a validated questionnaire to assess neurotoxic complaints (neurotoxicity symptom checklist-60, NSC-60), and a standardised self administered questionnaire to detect complaints consistent with peripheral neuropathy and dysfunction of the autonomic nervous system. Historical and current data on biomonitoring of exposure to Cd, either the highest value of Cd in urine (CdU in µg Cd/g creatinine) of each Cd worker during work (CdU_max) or the current value (CdU_current) of each control, were available as well as data on microproteinuria.
RESULTS—Cd workers (CdU_max: mean (range), 12.6 (0.4-38.4)) performed worse than the controls (CdU_current: mean (range), 0.7 (0.1-2.0)) on visuomotor tasks, symbol digit substitution (p=0.008), and simple reaction time to direction (p=0.058) or location (p=0.042) of a stimulus. In multiple linear regression analysis, symbol digit substitution, simple direction reaction time test, and simple location reaction time test were significantly related to CdU_max, (β=0.35 ( p<0.001), β= 0.25 (p=0.012), and β=0.23 (p=0.021) respectively). More complaints consistent with peripheral neuropathy (p=0.004), complaints about equilibrium (p=0.015), and complaints about concentration ability (p=0.053) were found in the group exposed to Cd than in the control group, and these variables correlated positively with CdU_max (peripheral neuropathy: β=0.38, p<0.001; equilibrium: β=0.22, p=0.057; concentration ability: β=0.27, p=0.020).
CONCLUSION—Slowing of visuomotor functioning on neurobehavioural testing and increase in complaints consistent with peripheral neuropathy, complaints about equilibrium, and complaints about concentration ability were dose dependently associated with CdU. Age, exposure to other neurotoxicants, or status of renal function could not explain these findings. The present study also indicates that an excess of complaints may be detected in Cd workers before signs of microproteinuria induced by Cd occur.


Keywords: cadmium; neurotoxicity; occupational exposure     

The impact of environmental and biological factors on paraoxonase 1 and γ-glutamyltranspeptydase activities in the blood of smelters

Disorders of paraoxonase and γ-glutamyltranspeptydase activities can induce development of the atherosclerotic process. The aim of the study was to examine the effect of occupational exposure to heavy metals, tobacco smoke and alcohol consumption on the activities of paraoxonase and γ-glutamyltranspeptydase as well as glutathione concentration. We have observed reduced paraoxonase activity and higher γ-glutamyltranspeptydase activity in serum of smelters when compared to control groups. In the blood of smoking smelters was demonstrated a negative correlation between paraoxonase activity and BMI value as well as between paraoxonase activity and tobacco smoke and consumption of 40 % alcohol. Also, negative correlation was found for the activity of paraoxonase and glutathione concentration as well as γ-glutamyltranspeptydase activity. Higher γ-glutamyltranspeptydase activity and lower paraoxonase activity in the serum of smelters exposed to heavy metals and tobacco smoke can cause disorders in functioning of the body.     

The possible role of direct ingestion on the overall absorption of cadmium or arsenic in workers exposed to CdO or As2O3 dust

Six volunteers (two office and four cadmium (Cd)-exposed workers, all nonsmokers) from an electric condenser factory participated in a study involving the measurement of cadmium in air and in dust, the evaluation of hand and mouth contamination by cadmium, and the determination of fecal cadmium. The mean levels of total airborne cadmium measured with static and personal samplers were for the exposed workers 9.5 and 16.7 μg/m³, respectively, and for the office workers 0.3 and 0.5 μg/m³, respectively. In the office workers, hand contamination by Cd hardly changes over the workday (less than 10 μg/hand), whereas in the exposed workers important hand contamination by Cd was observed (up to 1,200 μg/hand during the workday and up to 300 μg/hand before lunch or before leaving the factory). Mouth contamination by Cd is rather similar in both groups on Monday morning, but increases 20- to 50-fold on Friday afternoon in the Cd workers against a slight increase for the office workers. The concentration of Cd in the feces was not much different between Sunday and Friday in the office workers, whereas in the exposed workers it was higher on Friday than on Sunday. There is suggestive evidence from a comparative study of fecal cadmium in two Cd-exposed volunteers who carried out their jobs with and without gloves that direct cadmium intake from hand contamination may contribute to the overall Cd absorption. A limited study in a glassware factory (As₂O₃ exposure) involving the measurement of total airborne arsenic, the determination of urinary arsenic, and the evaluation of hand and mouth contamination by arsenic before and after the workshift suggests that the high urinary arsenic levels (300 μg/g creatinine) are likely to be more related to an increased oral intake from contaminated hands than to an increased absorption from the lungs.     

Asbestos-induced lung injury among danish jewelry workers

Asbestos has been used extensively in a variety of occupations. In the jewelry industry, inadequate hygiene practices may often go unrecognized with resultant exposure to hazardous amounts of asbestos. We report on four retired jewelers. Two of these had both pleural and parenchymal changes. One had isolated pleural plaques and the final patient showed only parenchymal infiltrates. Their work involved hand cutting asbestos plates used for protection during soldering. In the soldering process asbestos fibers were then blown into the workroom air as the plates broke down. In addition, at the end of each work day the workroom floor was swept, with subsequent airborne asbestos dust distribution. Any patient with pleural plaques or interstitial lung disease should be questioned about potential sources of asbestos exposure in the past, regardless of present employment status.     

Agricultural seed dust as a potential cause of organic dust toxic syndrome

Aims

Episodes of serious work related health problems resembling organic dust toxic syndrome (ODTS) in workers of a grass seed quality inspection laboratory prompted the authors to study personal endotoxin exposure levels in this facility and in the agricultural seed processing industry. In addition, microbial and inflammatory characteristics of agricultural seeds were studied.

Methods

The authors assessed inhalable dust and endotoxin levels in 101 samples from 57 workers in grass, cereal, and vegetable seed plants who were handling mainly grass seeds as bulk product, and horticulture seeds in smaller quantities. Additionally, real‐time dust exposure was measured using a DataRAM monitor in 12 grass seed workers to obtain more information on exposure patterns during specific tasks. Endotoxin concentrations in seed extracts were determined by LAL assay and seed samples were analysed by scanning electron microscopy. Release of inflammatory cytokines was measured in supernatants of whole blood samples stimulated with lipopolysaccharide (LPS) or agricultural seed extracts in a human whole blood assay (WBA).

Results

Endotoxin concentrations in personal samples were high (geometric mean 1800 EU/m³), particularly in the grass seed quality inspection lab where endotoxin levels up to 274 000 EU/m³ were measured. The recommended health based endotoxin exposure limit of 50 EU/m³ was amply exceeded in almost all personal samples. Job tasks dumping and mixing were associated with highest dust and endotoxin exposures, which was confirmed by real‐time measurements. Microbial infestation was found in almost all seed samples. WBA results showed that most seed extracts were capable of inducing a pronounced dose dependent cytokine release.

Conclusions

Workers handling grass, cereal, or vegetable seeds are at risk of exposure to high levels of endotoxin containing seed dust. Occupational exposure to inhalable agricultural seed dust can induce inflammatory responses, and is a potential cause of ODTS.     

Development of Occupational Standards

Criteria and recommended occupational safety and health standards have been developed by the National Institute for Occupational Safety and Health as a basic adversary review and comment process.

Several changes in the process designed to alleviate problem areas include the preparation of work practice standards and the addition of supplementary requirements to the existing promulgated standards.     

Inhalable Dust Measurements as a First Approach to Assessing Occupational Exposure in the Pharmaceutical Industry

Occupational exposure to active ingredients in the pharmaceutical industry has been the subject of very few published studies. Nevertheless, operations involving active powdered drugs or dusty operations potentially lead to operator exposure. The aim of this study was to collect occupational exposure data in the pharmaceutical industry for production processes involving powdered active ingredients. While the possibility of assessing drug exposure from dust level is examined, this article focuses on inhalable dust exposure, without taking chemical risk into account. A total of 377 atmospheric (ambient and personal) samples were collected in nine drug production sites (pharmaceutical companies and contract manufacturing organizations) and the dust levels were assessed. For each sample, relevant contextual information was collected. A wide range of results was observed, both site- and operation-dependent. Exposure to inhalable dust levels varied from 0.01 mg/m³to 135 mg/m³. Though restricted to dust exposure, the study highlighted some potentially critical situations or operations, in particular manual tasks (loading, unloading, mechanical actions) performed in open systems. Simple preventive measures such as ventilation, containment, and minimization of manual handling should reduce dust emissions and workers’ exposure to inhalable dust.     

Neurobehavioral effects of acute and chronic mixed-solvent exposure in the screen printing industry

This 2-year prospective study examined the neurobehavioral effects of acute and chronic exposure to mixed solvents in workers in a screen printing business. A total of 30 subjects participated in the study in two field testings over a 12 month period. Each subject completed a detailed medical and occupational questionnaire, had a neurological examination, and underwent a battery of neuropsychological tests. Industrial hygiene investigation identified the following chemical exposures as present: toluene, methyl ethyl ketone, mineral spirits, β-ether, methylene chloride, and acetic acid. Different departments and jobs had varying degrees of exposure to these chemicals, the highest exposures being in the ink mix area and the screen washroom area. However, all exposure levels were below recommended threshold limit values. Persons categorized as having higher acute exposure demonstrated significantly impaired test performance on tasks involving manual dexterity, visual memory, and mood. Those with higher chronic exposure demonstrated significantly poorer performance on visual memory tasks and mood. Results suggest that the mixed solvents used in the screen printing industy have an effect on central nervous system functioning in the absence of obvious clinical disease.     

镉致作业工人肾功能损害可逆性研究初探

[目的 ]观察接受依地酸二钠 (EDTA)治疗慢性镉接触工人尿镉和肾功能改变 ,以探讨镉接触致肾损害的可逆性。 [方法 ]收集 1986年以来某冶炼厂接受EDTA治疗的 17名镉接触工人 (其中男 14名 ,女 3名 )每年治疗前后尿镉和尿 β2 微球蛋白 (β2 MG)的记录 ,分析其变化的情况。 [结果 ]尿 β2 MG一直异常 (≥ 0 8mg/g·Cr)或由正常转为异常的工人 ,尿镉平均水平基本高于 10 μg/g·Cr ,治疗期间尿 β2 MG一直正常或出现异常又转为正常的工人 ,尿镉平均水平在 10μg/g·Cr以下 ;整个治疗过程中 ,不论尿镉升高或降低 ,尿 β2 MG异常率均有所上升 ;随着镉接触终止时间的延长 ,尿 β2 MG没有下降 ;尿镉水平低于 10 μg/gCr ,肾损害可以恢复 ,反之 ,则不可逆。[结论 ]尿镉的水平是影响镉接触工人肾功能变化的主要因素 ,EDTA对镉接触工人肾功能损害没有明显疗效。     

Organic acids and bases: review of toxicological studies

Organic acids and bases are among the most frequently used chemicals in the manufacturing industries. However, the toxicology of only a number of them has been fully characterized, and for fewer still have occupational exposure limits been established. This paper reviews the acute and chronic toxicity data of the organic acids and bases, and considers the mechanism by which these chemicals produce their effects. A methodology for establishing preliminary occupational exposure limits based on the physicochemical properties of these chemicals is presented. Workplace exposure limits for 20 organic acids and bases which currently have no exposure guidelines are suggested. Advice regarding appropriate medical treatment of exposure to these materials is discussed.     

Occupational exposure to lead and blood pressure: a study in 105 workers

A group of workers, occupationally exposed to lead and cadmium compounds (n = 53), was compared to a group of workers not exposed to these metals (n = 52). The average values of systolic, diastolic, and mean blood pressure were found to be higher in the exposed group (p less than 0.05). In contrast with the correlation between CdU and blood pressure, the correlation between PbB and systolic and mean blood pressure remained statistically significant after controlling for age and pulse rate (r = 0.22, p less than 0.05). The prevalence of potential hypertension (defined as systolic blood pressure greater than or equal to 160 mm Hg and/or diastolic blood pressure greater than or equal to 95 mm Hg and/or under treatment for hypertension) was higher in the exposed group, but the observed relative risk was not statistically significant: relative risk = 1.91 (95% confidence limits, 0.90-4.05). Furthermore, a significant correlation between PbB and Hgb (r = -0.28, p = 0.004) was observed. Differences in kidney function, as assessed in this study, were not detected.