Identification of a possible biomarker for colophony exposure.

Colophony is known to cause occupational asthma and dermatitis. Biological monitoring may be useful in assessing exposure. This paper describes a method for the analysis of dehydroabietic acid in urine and its potential use as a marker of colophony exposure. The method involves hydrolysis, solvent extraction, derivatization and analysis by gas chromatography-mass spectrometry. Twenty-eight workers from a soldering factory in South Africa were monitored. Results showed that levels of dehydroabietic acid in urine may be correlated with a subjective assessment of exposure.     

Salivary acetylcholinesterase as a biomarker for organophosphate exposure

Background Workers exposed to organophosphate (OP) pesticidesare required to undergo periodic statutory medical surveillancein several countries. Aim To study the relationship between serum, erythrocyte andsaliva acetylcholinesterase (AChE) levels and to explore theuse of salivary AChE as potential biomarker for OP exposure. Methods A cross-sectional study was conducted on 19 healthyadult male lead-exposed workers who were undergoing six monthlystatutory medical examination. Passive drool saliva sampleswere collected from each worker. Each blood sample was testedfor serum and erythrocyte AChE, and each saliva sample was testedfor AChE. Results Among the 19 subjects, the mean (±standard deviation)of salivary, erythrocyte and serum AChE/cholinesterase were22.7 (±17.4), 17171 (±1467), 8861 (±1876)U/l, respectively. There was a moderate correlation betweensalivary and erythrocyte AChE (r = 0.42, P = 0.071), but notsalivary and serum AChE (r = –0.17, P = 0.48). The levelof AChE in saliva was 1820 times lower than AChE in erythrocytes. Conclusion It is probably not feasible to use saliva as a replacementfor blood for the measurement of AChE levels. This is becauseof the much lower levels of AChE in saliva relative to erythrocytes,the weak correlation between the two measurements and the previouslyreported high intra-individual variation of salivary AChE.     

Biological monitoring and exposure to mercury

Occupational health professionals' interest in controlling mercury (Hg) exposure, and the use of biological monitoring in this context, has been ongoing for a number of years. Evidence from urinary Hg results in a number of UK firms who have undertaken some form of biological monitoring or occupational health surveillance suggest that exposure has decreased over the last 10-15 years. This decrease precedes the establishment in the UK of an advisory biological monitoring guidance value (HGV) for urinary Hg and the production of updated medical guidance from the Health & Safety Executive on Hg exposure (MS12 1996). This latter document recommends a urinary sampling interval for urinary Hg of between 1 and 3 months, which is consistent with the reported toxicokinetics of Hg excretion, but we highlight that urinary Hg represents integrated exposure over many previous months. Mercury is a recognized nephrotoxin and MS12 1996 mentions the use of regular dipstick protein estimations. We review our experience of investigating proteinuria and enzymuria in a large-scale cross-sectional occupational study. The incidence of Hg-induced renal disease is probably very rare at current exposure levels. Therefore acceptance of a high false-positive rate of proteinuria not related to Hg exposure needs to be considered in any urinary protein testing regime of Hg workers. The establishment of an HGV for urinary Hg has raised questions about the uncertainty associated with a urinary Hg result, including factors such as diurnal variation, whether urine correction by creatinine or specific gravity is preferable and the possibility of non-occupational sources of Hg contributing significantly towards breaching the HGV. Correction of urinary Hg results by creatinine or specific gravity and the use of a fixed sampling time, such as the beginning or end of the day, substantially reduce the uncertainty in a urinary Hg measurement. But even with good laboratory precision, an individual with a true urinary Hg excretion of 20 nmol/mmol creatinine could supply urine samples of between 14 and 26 nmol/mmol creatinine. The influence of dietary sources in the UK contributing to urinary Hg values approaching or exceeding the HGV is unlikely. The use of tribal or ethnic cosmetics and remedies needs to be considered if a urinary Hg result looks inappropriately high, as some such preparations have been found to contain Hg and can be absorbed through the skin. The ability of excessive chewers or teeth grinders who have a large number of dental amalgam fillings to breach the urinary HGV in the absence of substantial occupational Hg exposure has been reported in a few Scandanavian studies. We report here a likely case of this phenomenon. Since the establishment of the HGV, our biological monitoring Hg data from a number of industry sectors using inorganic or metallic Hg have suggested that a minority of samples (13%) are still greater than the HGV.     

N-Methylsuccinimide in plasma and urine as a biomarker of exposure to N-methyl-2-pyrrolidone

Objective: N-Methyl-2-pyrrolidone (NMP) is a selective and powerful organic solvent. The aim of this study was to investigate whether the NMP metabolite N-methylsuccinimide (MSI) in plasma and urine can be used as a biomarker of exposure to NMP. Methods: Six healthy subjects were exposed to 10, 25, and 50 mg NMP/m³ in an exposure chamber for 8 h. The air levels were monitored by XAD-7 solid sorbent sampling, and analysed by gas chromatography (GC). Plasma and urine were sampled for two days following the exposure, and the levels of MSI were analysed by GC with mass spectrometric detection. Results: The concentration of MSI in plasma and urine rose during the exposure, and reached a peak at about 4 h after the end of the exposure. The concentration then decayed according to a one-compartment model with a half-time of approximately 8 h. About 1% of the inhaled NMP was excreted in urine as MSI. There were very close correlations between the NMP air levels and, on the one hand, the MSI concentrations in plasma collected at the end of exposure (r=0.98), or the urinary MSI concentration collected during the last 2 h of exposure (r=0.96), on the other. Conclusions: MSI in plasma or urine is applicable as a biomarker of exposure to NMP. The concentration in plasma and urine mainly reflects the exposure over one day. Received: 5 May 2000 / Accepted: 1 November 2000     

Urinary methylhippuric acid isomer levels after occupational exposure to a xylene mixture

Summary The quantitative relationship between exposure to xylene vapor and urinary excretion of methylhippuric acid (MHA) isomers were studied in the second half of a working week. The participants in the study were 121 male workers engaged in dip-coating of metal parts who were predominantly exposed to three xylene isomers. The intensity of exposure measured by diffusive sampling during an 8-h shift was such that the geometric mean vapor concentration was 3.8 ppm for xylenes (0.8 ppm for o-xylene, 2.1 ppm for m-xylene, and 0.9 ppm for p-xylene), 0.8 ppm for toluene, and 0.9 ppm for ethylbenzene. Urine samples were collected at the end of the shift and analyzed for metabolities by HPLC. The statistical analysis showed that there is a linear relationship between the intensity of exposure to xylenes and the concentration of MHA in urine, that the regression line passes very close to the origin, and that the increment in observed (i.e., noncorrected) MHA concentrations as a function of increasing xylene concentration was 17.8 mg × 1^–1 ppm^–1. Further examination on the basis on individual xylene isomers showed that the slopes of the regression lines for o- and m-isomers were similar (i.e., 17.1 and 16.6 mg l^–1 ppm^–1, respectively), whereas that for p-xylene was larger (21.3 mg l^–1 ppm^–1).     

Dermal exposure assessment in occupational medicine

The importance of dermal exposure has increased during the last few years, mainly because of the reduction of respiratory exposure to toxicants. Pesticides, aromatic amines and polycyclic aromatic hydrocarbons are considered to be the chemicals at highest dermal risk. In the occupational exposure limit lists of the American Conference of Governmental Industrial Hygienists (ACGIH) and of many countries, compounds that can be absorbed through the skin are identified by a skin notation. However, a generally accepted criterion for assigning skin notation does not exist. The recent attempts to develop health-based dermal occupational exposure limits (DOELs) have not been accepted, thus in practice their use has remained limited. To predict the systemic risk associated with dermal exposure and to enable agencies to set safety standards, penetration data are needed. Moreover, there is a need for a practical risk assessment model, particularly for small and medium-sized enterprises.     

Toluene in blood as a marker of choice for low-level exposure to toluene

The validity of two new biological exposure markers of toluene in blood (TOL-B) and toluene in urine (TOL-U) was examined in comparison with that of the traditional marker of hippuric acid in urine (HA-U) in 294 male workers exposed to toluene in workroom air (TOL-A), mostly at low levels. The exposure was such that the geometric mean for toluene was 2.3 ppm with a maximum of 132 ppm; the workers were also exposed to other solvents such as hexane, ethyl acetate, styrene, and methanol, but at lower levels. The chance of cutaneous absorption was remote. Higher correlation with TOL-A and better sensitivity in separating the exposed workers from the nonexposed subjects were taken as selection criteria. When workers exposed to TOL-A at lower concentrations (< 50 ppm, < 10 ppm, < 2 ppm, etc.) were selected and correlation with TOL-A was examined, TOL-B showed the largest correlation coefficient which was significant even at TOL-A of < 1 ppm, whereas correlation of HA-U was no longer significant when TOL-A was < 10 ppm. TOL-U was between the two extremes. The sensitivities of TOL-B and TOL-U were comparable; HA-U showed the lowest sensitivity. Thus, it was concluded that TOL-B is the indicator of choice for detecting toluene exposure at low levels.     

Biological monitoring of occupational exposure to isopropyl alcohol vapor by urinalysis for acetone

Summary The relationship of the intensity of occupational vapor exposure to isopropyl alcohol (IPA) with urinary excretion of acetone and unmetabolized IPA was studied in 99 printers of both sexes, who were exposed to up to 66 ppm IPA (as time-weighted average), together with toluene, xylenes, methyl ethyl ketone and/or ethyl acetate. Acetone and IPA concentrations in urine were studied also in 34 non-exposed subjects. Acetone was detectable in the urine of most of the non-exposed, and the urinary acetone concentration increased in proportion to the IPA exposure intensity (r = 0.84 for observed, non-corrected values), whereas the correction for creatinine concentration or specific gravity of urine did not give a larger correlation coefficient. IPA itself was not found in the urine of the non-exposed, and was detectable in urine of only those who were exposed to IPA above a certain level, e.g. 5 ppm. The present study results suggest that urinary acetone is a valuable index for biological monitoring of occupational exposure to IPA as low as 70 ppm.A part of this work was presented at 62nd Annual Meeting of Japan Association of Industrial Health, held in Hirosaki, Japan, on 27th–30th, April, 1989     

红细胞中铬含量作为铬盐接触者生物标志物的研究

目的通过对职业接触可溶性铬盐劳动者红细胞中铬浓度的研究,了解红细胞中铬浓度与个体环境可溶性铬盐接触之间的相关性及其在职业人群中分布的特点、影响因素,探讨其作为职业接触可溶性铬盐接触性生物标志物的可行性。方法采用横断面现场研究,对山东省济南市某铬盐生产企业进行了流行病学调查。接触组选择重铬酸钾制造业铬盐作业劳动者114名(男74名、女40名);年龄范围25~52岁,平均年龄(35.83±6.14)岁;工龄1~37年,平均工龄(14.20±6.77)年;接触铬盐年限范围0.5~28年,平均接触铬盐年限(9.80±5.97)年。对照组为无毒物接触史的健康人员30名(男22名,女8名),年龄范围25~47岁,平均年龄(36.13±6.17)岁。接触组与对照组两组人群在年龄、性别和吸烟状况等方面相匹配。通过问卷调查了解研究对象的一般情况、职业接触情况、吸烟饮酒情况、既往疾病史、个人防护情况等。作业环境铬盐浓度的测定:采用双滤膜个体采样器8 h工作日连续采样,滤膜铬盐含量采用火焰原子吸收分光光度法测定;红细胞中铬浓度测定采用石墨炉原子吸收分光光度法;血浆还原能力测定采用二苯碳酰二肼分光光度法;总维生素C、还原型维生素C含量的测定采用2,4二-硝基苯肼法。用SPSS10.0统计软件进行单因素统计分析和多元回归分析。结果职业接触可溶性铬盐劳动者红细胞中铬浓度为(15.79±31.01)μg/L,高于对照组的(3.21±2.20)μg/L,差异有统计学意义。当空气中个体铬盐暴露浓度小于106.00μg/m3时,职业接触可溶性铬盐劳动者红细胞中铬浓度随个体铬盐接触水平的增加而增加,并呈明显的剂量-反应关系。相关分析结果表明:红细胞中铬浓度与空气中个体铬盐暴露水平之间呈显著的正相关。多元回归证实:在α=0.10水平,血浆中维生素C、血浆六价铬的还原能力可以作为可溶性铬盐接触氧化应激水平的指标,并可影响红细胞内铬的摄取。结论红细胞中铬含量可以作为可溶性铬盐职业接触者的有效接触性生物标志物,尤其适于个体低剂量铬盐接触的评价。     

Biological monitoring values for occupational exposure: a United Kingdom perspective

Policy developments in the United Kingdom have been aimed at facilitating the appropriate use of biological monitoring. Recent initiatives have established clear criteria for the interpretation of biological monitoring results, and new guidance that deals with the ethical and practical issues involved in operating an effective biological monitoring programme has been promulgated. The United Kingdom now has a system of non-statutory biological monitoring guidance values. There are two types, the health guidance value and the benchmark guidance value. Over a number of years, biological monitoring programmes have shown that they help in reducing exposure by regular monitoring and demonstrating adequate control. Received: 2 March 1999 / Accepted: 25 March 1999     

Urinary sevoflurane and hexafluoro-isopropanol as biomarkers of low-level occupational exposure to sevoflurane

Objectives: Sevoflurane is an inhalation halogenated anaesthetic widely used in day and paediatric surgery. We were interested in evaluating biological markers of exposure to sevoflurane, which should improve the health surveillance of occupationally exposed personnel. Methods: A group of 36 subjects (13 male, 23 female) occupationally exposed to volatile anaesthetics in paediatric operating rooms was studied in a 2-week survey. Post-shift urine samples and specimens from passive samplers (for personal monitoring) were collected after 1.75–6 h morning exposure and analysed by headspace gas chromatography–mass spectrometry (GC–MS). Multiple determinations were assumed as independent values (in total, n=78: 24 from men, 54 from women; 25 from smokers, 53 from non-smokers). Results: Median sevoflurane external values were 0.13 parts per million (ppm) (range 0.03–18.82) (n=78), urinary sevoflurane 0.6 g/l_urine (ND–18.5)(n=76) and total urinary hexafluoro-isopropanol (HFIP) 0.49 mg/l_urine (ND–6833.4) (n=75). A lower limit of detection (LOD) was achieved for urinary sevoflurane (0.03 g/l_urine), allowing quantitation of all but one of the samples; >25% of urine samples were unquantifiable by HFIP and were assigned a value equal to half the LOD of 0.10 mg/l_urine. Urinary sevoflurane correlated well with breathing-zone data (r²=0.697 at log–log linear regression), whereas total urinary HFIP (r²=0.562 at log–log linear regression) seemed to be better described by a three-parameter logistic function and appeared to be influenced by smoking habits. Biological indices corresponding to National Institute for Occupational Safety and Health (NIOSH) exposure limits, calculated as means of linear regression slope and y intercept, were 3.9 g/l_urine and 1.4 g/l_urine for sevoflurane (corresponding to 2 ppm and 0.5 ppm, respectively), and 2.66 mg/l_urine and 0.82 mg/l_urine for HFIP. Conclusions: On the basis of our data, urinary unmodified, sevoflurane seems to be a more sensitive and reliable biomarker of short-term exposure to sevoflurane with respect to total urinary metabolite HFIP, which appears to be influenced by physiological and/or genetic individual traits, and seems to provide an estimate of integrated exposure.     

Occupational molybdenum exposure and a gouty electrician

BACKGROUND: Molybdenum is an essential trace element and a component of xanthine oxidase, which catalyses the formation of urate. The toxicity of molybdenum in humans is considered to be low, but hyperuricaemia and gout-like symptoms have been observed sporadically. METHODS: A case of hyperuricaemia and gouty arthritis in a young man with occupational exposure to molybdenum is described. Improvement during an exposure-free period was followed by a relapse after a reconstruction designed to quantify his molybdenum exposure. CONCLUSION: This case seems to represent the first observation of gout associated with occupational molybdenum exposure, but the association might also be entirely circumstantial.     

尿邻甲酚作为接触甲苯生物监测指标的探讨

目的探讨尿邻甲酚作为接触甲苯生物监测指标的可能性。方法建立柱前衍生高效液相色谱法测定人体尿中邻甲酚,且使用该方法测定非职业及职业接触甲苯人群尿中邻甲酚水平,并进行接触评定。结果甲苯接触者尿邻甲酚水平为(2.61±1.94)mg/L,明显高于对照组[(0.32±0.23)mg/L],差异有显著性(P<0.001),且接触甲苯工人班后尿邻甲酚水平比班前明显升高,最高可达29倍。接触甲苯者尿邻甲酚水平与个体接触甲苯浓度明显相关(r=0.6295,P<0.01)。结论尿邻甲酚可以作为接触甲苯的生物监测指标。     

Window renovation and exposure to lead--an observational study

BACKGROUND: Renovation of windows in old houses has recently established itself as an industry. A recognizable occupational lead exposure exists, which has not been studied previously. AIM: To compare lead exposure amongst window renovators with other groups of lead-exposed workers. METHODS: Using blood lead results measured at the Health and Safety Laboratory (HSL), Sheffield, comparisons were made between three cohorts: window renovation workers, all male workers monitored by HSL during the period 1999-2001 and 63 male subjects involved in chemical paint-stripping of wood. RESULTS: Both the window renovation and the wood-stripping cohorts show significantly higher blood lead distributions than the 'all workers' cohort (P < 0.001). A similar pattern was also found for comparison of the prevalence of subjects above the UK suspension level of 60 microg/dl (2.89 microM) (window renovation, P < 0.001; wood-stripping, P < 0.0001). Blood lead results at or above the suspension level in wood-strippers were significantly higher compared to window renovators (P = 0.034). CONCLUSION: Window renovation is shown to present a potential for significant lead exposure, and suspension from work under The Control of Lead at Work Regulations 2002. Two groups of risk factors predominate: the well-documented potential for release of lead from old paint, and the peripatetic nature of the work.     

Compliance with follow-up after occupational exposure to hepatitis C

BACKGROUND: Accidental percutaneous exposure to blood containing hepatitis C virus (HCV) is reported by health care workers more frequently than exposure to human immunodeficiency and hepatitis B virus. The transmission rate following such an exposure is approximately 1.9%. Little is known about the attendance rate of such staff for follow-up testing following exposure to HCV. AIM: To determine whether our follow-up programme for staff exposed to hepatitis C would allow the early detection and treatment of infected staff members. METHOD: We reviewed all staff exposures to hepatitis C reported to the occupational health department of a London teaching hospital over a 8-year period. RESULTS: Of 105 exposures, 21% of staff attended for early (6 or 12 weeks) and late (26 weeks) post-exposure follow-up. Thirty-seven per cent attended early follow-up only and 1% attended late having not attended early follow-up. Forty per cent did not attend any follow-up appointments with us. CONCLUSION: With the availability of effective treatment for early HCV infection, it is vital that occupational health departments encourage staff to attend at least for early follow-up. Access to HCV-RNA testing at this early stage should allow detection and early treatment of the small proportion who seroconvert.     

苯接触标志物尿中苯巯基尿酸的分析与评价

尿中苯巯基尿酸(SPMA)与苯接触存在良好相关性,是低浓度苯接触特异和敏感的生物标志物。SPMA可用高效液相色谱法(HPLC)、液质联谱(LC/MS)、气质联谱(GC/MS)和酶联免疫吸附试验(ELISA)等方法检测。本文详细介绍了国外检测尿SPMA的方法,评价了尿SPMA作为职业苯接触生物标志物的有效性和应用。     

Respiratory health effects of long-term exposure to different chromium species in stainless steel production

The aim of this study was to determine whether occupational exposure to chromite, trivalent chromium (Cr(3+)) or hexavalent chromium (Cr(6+)) causes respiratory diseases, an excess of respiratory symptoms, a decrease in pulmonary function or signs of pneumoconiosis among workers in stainless steel production. Altogether, 203 exposed workers and 81 referents with an average employment of 23 years were investigated for indicators of respiratory health on two occasions, in 1993 and in 1998. Data collection with a self-administered questionnaire, flow volume spirometry, measurement of diffusing capacity, chest radiography and laboratory tests were carried out by a mobile research unit. Exposure to different chromium species and other metals was monitored regularly and studied separately. No adverse respiratory health effects were observed in the group exposed to Cr(6+), either in comparison with the control group in the first cross-sectional study or during the additional 5 year follow-up. Among the Cr (3+) exposed people, the production of phlegm, shortness of breath and breathlessness on exertion were significantly more frequent than in the control group, but the frequency of the symptoms did not increase during the follow-up; no differences were observed in the lung function tests and the radiographic findings did not progress. In the chromite group, the prevalence of breathlessness on exertion was higher than in the control group. However, in the follow-up, the occurrence of symptoms did not differ from 1993 to 1998. In the first study, most parameters of lung function were lower among the smokers in the chromite group than among the smoking controls, but in 1998 the difference was less marked. An average exposure time of 23 years in modern ferrochromium and stainless steel production and low exposure to dusts and fumes containing Cr(6+), Cr(3+), nickel and molybdenum do not lead to respiratory changes detectable by lung function tests or radiography. The workers exposed to Cr(3+) had more respiratory symptoms than those in the control group. The workers in the chromite mine had lower lung function test results than the control group due to earlier exposure to higher dust concentrations.     

Occupational exposure to HIV and the use of post-exposure prophylaxis

The use of antiretroviral therapy as post-exposure prophylaxis against human immunodeficiency virus (HIV) is now routine following high-risk exposure to the HIV virus. This article summarizes the management of health care workers and others exposed to HIV in an occupational setting, and the evidence behind it.     

Occupational toxicology and the control of exposure to pharmaceutical agents at work

BACKGROUND: The pharmaceutical industry employs >350 000 people worldwide in operations including research and development (R&D), manufacturing, sales and marketing. Workers employed in R&D and manufacturing sectors are potentially exposed to drug substances in the workplace that are designed to modify physiology and also to chemical precursors that are potentially hazardous to health. Pharmaceutical workers are at risk from adverse health effects, including occupational asthma, pharmacological effects, adverse reproductive outcomes and dermatitis. AIM: This study aimed to describe the approaches taken by pharmaceutical companies for identifying and communicating potential adverse health effects that may result from workplace exposures and in setting 'in-house' exposure control limits and to highlight the challenges in controlling workplace exposures to increasingly potent compounds. METHOD: The literature was reviewed by searching the Medline and HSELine databases. RESULTS: The findings are presented in five sections, covering: test methods and approaches to occupational toxicology; hazard communication; approaches to setting health-based occupational exposure limits for pharmaceutically active agents; recent approaches to risk control; and occupational hygiene and exposure controls. CONCLUSION: Significant efforts have been directed at predicting and evaluating potential occupational health hazards in the pharmaceutical industry. The pharmaceutical industry has provided leadership in controlling exposure to hazardous substances. Much of this work has been driven by a real need to control occupational exposures to substances that can have profound adverse health effects in exposed employees and that are becoming increasingly more potent.     

Severe headache associated with occupational exposure to Stoddard solvent

We report a case of recurrent headaches in a woman with a workplace exposure to airborne (misted) lubricating fluid containing Stoddard solvent. For 2 months, the employee was seen by her family physician, a neurologist and an ophthalmologist. All attempted to diagnose the cause of and treat her headaches. Despite extensive testing, no etiology was discovered. Her headaches continued despite the use of medications. The employee, suspecting an occupational connection, changed the lubricating fluid at her workstation to a non-Stoddard solvent. Within 2 days she reported the complete resolution of her headaches with no further recurrences. A thorough occupational history and literature review supported exposure to Stoddard solvent as the probable source of her headaches.