Biological Monitoring Of Occupational Exposure Research Articles

101 PAH Exposure During Construction of Railroad Swithes with Creosote Impregnated Ties

Abstract Coal tar creosote, or creosote, is a by-product of the carbonization of coal to produce coke and has been used as a wood preservative since the late 19th century. Creosote is a mixture of many different compounds such as polycyclic aromatic hydrocarbons (PAH)s, phenols and cresols. Even though several PAHs are carcinogenic to humans, creosote is still used in impregnation of railway ties and electricity and telephone poles. Occupational exposure can occure from inhalation of creosote vapour or through skin contact. Dermal uptake is considered to be the most important route of exposure to PAHs. Even though the ratio between different PAHs may vary, measurements of 1-hydroxy-pyrene (1-HP) in urine is the common method for biological monitoring of occupational exposure to PAH. This study was conducted indoors in a facility where railroad switches are assembled with concrete or creosote impregnated wood ties. The aim of the study was to assess the workers´exposure to PAHs by (i) measuring PAH 16 in the breathing zone from whole shift samples, (ii) examining the dermal exposure of pyrene using a tape stripping technique, (iii) assessing the workers´ internal exposure by measuring 1-OHP in urine samples. The study show that during construction of railroad switches made from creosote impregnated ties workers get urinary levels of 1-OPH above the Biological Guidance Value during the work week. Dermal uptake seems to be the main route of exposure and preventive measures should be focused upon reducing the dermal exposure. Speaker Biography Pål Graff works as a Professor at the Norwegian National Institute of Occupational Health and Norwegian University of Life Sciences. His main research interests are exposure assessment and epidemiology.

Quantification of bromide ion in biological samples using headspace gas chromatography-mass spectrometry.

ObjectivesIn this study, we aimed to establish a method for quantifying bromide ions (Br−) in blood and urine using gas chromatograph‐mass spectrometer (GC‐MS) equipped with a headspace sampler, for biological monitoring of workers exposed to methyl bromide.MethodsSamples were mixed with dimethyl sulfate, and Br− ions were detected using GC‐MS with a headspace sampler. The validity of the proposed method was evaluated based on most of the US FDA guidance. The values obtained were compared with reference values by analysis using SeronormTM Trace Elements Whole Blood L‐1 RUO.ResultsThe calibration curve showed good linearity in the Br− concentration range of 0.1−20.0 mg/L, and the coefficient of determination R2 value was >.999. Intraday and interday accuracy values were 99.3%−103.1% and 97.4%−101.8%, respectively. The measured and reference values of Seronorm were concordant. Herein, eight urine and serum samples of workers were analyzed; the samples' Br− concentrations were known. The correlation coefficients of urine and serum samples were 0.97 and 0.96, respectively, and results were consistent.ConclusionsThis study established a simple and rapid method for the determination of Br− concentration in biological samples using GC‐MS with a headspace sampler. Moreover, it can be used for biological monitoring of occupational exposure to methyl bromide and for the determination of Br− concentration in a wide range of biological samples.

A highly sensitive UHPLC-MS/MS method for urine biological monitoring of occupational exposure to anthracycline antineoplastic drugs and routine application

Anthracycline antineoplastic drugs (doxorubicin, epirubicin, daunorubicin) are “hazardous drugs for handling” by healthcare professionals. To monitor their occupational exposure, a highly sensitive ESI-UHPLC-MS/MS method for the assay of anthracyclines in urine was developed. The urine extraction consisted of SPE extraction method. A good linearity (r > 0.996), precision (CV < 14.4%), and accuracy (bias < 13.6%) were achieved for the three drugs. The lower limit of quantification (LOQ) was 10 ng/L. This LOQ value is equal to the LOQ of published methods except for epirubicin, for which the LOQ value is better by a factor of 10 (best published LOQ value: 100 ng/L). Applying this method in routine, more than 77 healthcare professionals occupationally exposed to anthracyclines were monitored and 77 urines were analyzed. Two healthcare professionals (2.6%) were found to be contaminated to doxorubicin and/or epirubicin. The measured concentrations ranged from 17.7 to 218 ng/L. Such an efficient analytical tool, combining both high specificity and sensitivity is essential for reliable highlight of contamination during biological monitoring of healthcare professionals widely exposed to these drugs. This anthracycline antineoplastic drugs exposure monitoring allows healthcare professionals for assessing effectiveness individual and collective protective measures and for ensuring traceability of occupational exposure to these drugs.

Simultaneous determination for metabolites of benzene compounds in urine by high performance liquid chromatography

Objective: To describe for the determination of contents of metabolites of benzene compounds in urine sample by high performance liquid chromatography. Methods: After acidification with hydrochloric acid, metabolites in urine were first extracted by acetonitrile and isopropanol (V∶V, 9∶1) with excessive sodium chloride, then gradient separated on a C18 column and then determined by DAD detector. Results: There were good linear relationship between peak areas and injection quality in range of 2.00-100 mg/L (r>0.999). The detection limit and quantitative limit of this method were 4.15-70.7 μg/L and 13.8-235 μg/L respectively. The precision for the analysis of urine was1.78%-8.23% (n =6). The average recovery of metabolites was 85.4%-105.5% at thee spiked levels in the range of 2.00-100 mg/L. Conclusion: The accuracy and reproducibility obtained make this method useful for the biological monitoring of occupational exposure to toluene, xylene, styrene and ethylbenzene.

Biological Monitoring of Occupational Exposure to Metals in Electric Steel Foundry Workers and Its Contribution to 8-Oxo-7,8-Dihydro-2'-Deoxyguanosine Levels.

In this study, the urinary concentrations of selected metals in workers from an electric steel foundry in Tunisia were assessed and compared with existing biological limit values and general population reference values. Moreover, the association between oxidative DNA damage, measured as urinary 8-oxo-7,8-dihydro-2’deoxyguanosine (8-oxodG) and co-exposure to metals and polycyclic aromatic hydrocarbons (PAHs) was evaluated. Urinary levels of 12 metals were determined by inductively coupled plasma-mass spectrometry (ICP-MS) in end-shift spot samples from 89 workers. The urinary levels of phenanthrene (U-PHE), as marker of exposure to PAHs, and 8-oxodG were also available. Median levels ranged from 0.4 µg/L (cobalt, Co, and thallium, Tl) to 895 µg/L (zinc, Zn). Only 1% of samples was above the biological limit values for Co, and up to 13.5% of samples were above limit values for Cd. From 3.4% (Co) to 72% (lead, Pb) of samples were above the reference values for the general population. Multiple linear regression models, showed that manganese (Mn), Zn, arsenic (As), barium (Ba), Tl, and Pb were significant predictors of 8-oxodG (0.012 ≤ p ≤ 0.048); U-PHE was also a significant predictor (0.003 ≤ p ≤ 0.059). The variance explained by models was low (0.11 ≤ R2 ≤ 0.17, p < 0.005), showing that metals and PAHs were minor contributors to 8-oxodG. Overall, the comparison with biological limit values showed that the study subjects were occupationally exposed to metals, with levels exceeding biological limit values only for Cd.

Simple and reliable method to simultaneously determine urinary 1- and 2-naphthol using in situ derivatization and gas chromatography-mass spectrometry for biological monitoring of naphthalene exposure in occupational health practice.

ObjectivesThe aim of this study was to develop and validate a simple and reliable gas chromatography‐mass spectrometry (GC‐MS) method to simultaneously determine urinary 1‐naphthol (1‐NAP) and 2‐naphthol (2‐NAP) for biological monitoring of occupational exposure to naphthalene.MethodsNAPs were derivatized in situ with acetic anhydride after enzymatic hydrolysis, extracted with n‐hexane, and analyzed using GC‐MS. Validation of the proposed method was conducted in accordance with US Food and Drug Administration guidance. A final validation was performed by analyzing a ClinChek®‐Control for phenolic compounds.ResultsThe linearity of calibration curves was indicated by a high correlation coefficient (>0.999) in the concentration range 1‐100 μg/L for each NAP. The limits of detection and quantification for each NAP were 0.30 and 1.00 μg/L, respectively. The recovery was 90.8%‐98.1%. The intraday and interday accuracies, expressed as the deviation from the nominal value, were 92.2%‐99.9% and 93.4%‐99.9%, respectively. The intraday and interday precision, expressed as the relative standard deviation, was 0.3%‐3.9% and 0.4%‐4.1%, respectively. The ClinChek® values obtained using our method were sufficiently accurate.ConclusionsThe proposed method is simple, reliable, and appropriate for routine analyses, and is useful for biological monitoring of naphthalene exposure in occupational health practice.

Biological monitoring of occupational exposure to dichloromethane by means of urinalysis for un-metabolized dichloromethane.

The objective of the study is to establish exposure-excretion relationship between dichlorometane (DCM) in air (DCM-A) and in urine (DCM-U) in workplace to confirm a previous report. Male workers in a screen-printing plant participated in the study. Time-weighted average DCM-A was measured by diffusive sampling followed by gas-chromatography (GC), and DCM in end-of-shift urine samples was by head-space GC. The data were subjected to regression and other statistical analyses. In practice, 30 sets of DCM-A and DCM-U values were available. The geometric mean DCM-A was 8.4 ppm and that of DCM-U (as observed) was 41.1 µg/l. The correlation coefficients (0.70–0.85) were statistically significant across the correction for urine density. Thus, the analysis for un-metabolized DCM in end-of-shift urine samples is applicable for biological monitoring of occupational exposure to DCM, in support of and in agreement with the previous report. In conclusion, biological monitoring of occupational DCM exposure is possible by use of analysis for un-metabolized DCM in end-of-shift urine.

Direct methyl esterification with 2,2-dimethoxypropane for the simultaneous determination of urinary metabolites of toluene, xylene, styrene, and ethylbenzene by gas chromatography-mass spectrometry.

ObjectivesThe purpose of this study was to develop a simple and accurate gas chromatography‐mass spectrometry (GC‐MS) method for simultaneous determination of four urinary metabolites from four organic solvents, that is, hippuric acid (HA) from toluene, methylhippuric acid (MHA) from xylene, and mandelic acid (MA) and phenylglyoxylic acid (PGA) from styrene or ethylbenzene for biological monitoring.MethodsThe four metabolites were directly methyl‐esterified with 2,2‐dimethoxypropane and analyzed using GC‐MS. The proposed method was validated according to the US Food and Drug Administration guidance. The accuracy of the proposed method was confirmed by analyzing a ClinChek®—Control for occupational medicine (RECIPE Chemicals +Instruments GmbH).ResultsCalibration curves showed linearity in the concentration range of 10‐1000 mg/L for each metabolite, with correlation coefficients >0.999. For each metabolite, the limits of detection and quantification were 3 mg/L and 10 mg/L, respectively. The recovery was 93%‐117%, intraday accuracy, expressed as the deviation from the nominal value, was 92.7%‐103.0%, and intraday precision, expressed as the relative standard deviation (RSD), was 1.3%‐4.7%. Interday accuracy and precision were 93.4%‐104.0% and 1.2%‐9.5%, respectively. The analytical values of ClinChek obtained using the proposed method were sufficiently accurate.ConclusionsThe proposed method is a simple and accurate which is suitable for routine analyses that could be used for biological monitoring of occupational exposure to four organic solvents.

Environmental and biological monitoring of occupational exposure to polynuclear aromatic hydrocarbons during highway pavement construction in Italy

ObjectivesWe performed a cross-sectional study with the main aim of evaluating occupational exposure to polycyclic aromatic hydrocarbons (PAHs) in workers involved in the pavement construction of a new highway in Northern Italy, where modified bitumen was used as binder for Hot Mix Asphalt. MethodsWe applied a combined approach of air and biological monitoring. Both the aerosol and vapour phases of bitumen were collected applying the NIOSH 5506 method. The 16 PAHs listed as high priority by EPA were determined by HPLC-UV. End-of-shift urine samples were collected from 144 workers to determine 1-hydroxypyrene (1-OHP) and 2-naphthol (2-NAP) concentrations after enzyme digestion and HPLC-UV analysis. Socio-demographic and lifestyle information was collected by a questionnaire. ResultsPaving workers were actually exposed to PAHs, including carcinogenic compounds, that were measurable only in the aerosol phase. Higher exposure as well as dose levels were measured for the paver group. Biological monitoring confirmed that 1-OHP was less affected by smoking habits as compared to 2-NAP and showed a higher association with occupational exposure. ConclusionCarcinogenic PAH compounds were detectable only in the aerosol phase and this must be taken into account in the adoption of preventive measures. Biomonitoring supported the superiority of 1-OHP as compared to 2-NAP in assessing the internal dose in such workers.

Biological monitoring of occupational exposure to dust among aluminium foundry workers

Aim - The purpose of the study was to evaluate the biological monitoring of occupational exposure to aluminium (AL) dust in foundry workers in south of Tehran. Material and Methods - This cross-sectional study was carried out on 63 workers in A and B foundries and 50 unexposed individuals as the control group. AL dust were sampled using Higgins-Dewell cyclone (HD) and cellulose ester membrane filter (MEC) with a flow of 2.2 l/min in the breathing zone of workers for 4 hours. Urinary samples were taken at the end of work shifts per week and were analyzed using graphite furnace atomic absorption. Data were analyzed using SPSS v.21 and statistical methods including t-test, one-way ANOVA and linear regression. Results - Airborne concentration of AL aerosols differed statistically significant in occupational groups (P 0.05). However, there was a significant difference between urinary concentrations of the exposed group and the control group (P 0.05). Conclusion - Determination of AL concentration in urine is not enough to serve as a biomarker. Estimation of AL nanoparticles in the air and biomarkers that determine the actual absorption rate seems to be an adequate method for occupational exposure monitoring of AL.

Trisaminohexyl isocyanurate, a urinary biomarker of HDI isocyanurate exposure

Biological monitoring of occupational exposure to 1,6-hexamethylene diisocyanate (HDI)-containing spray-paints is limited to analysis of metabolites of HDI monomer although polymeric HDI isocyanurate constitutes the predominant inhalation and skin exposure for workers in the automotive paint industry. A novel method using nanoflow ultra-performance liquid chromatography coupled to nano-electrospray ionization tandem mass spectrometry (nano-UPLC-ESI-MS/MS) was developed to quantify trisaminohexyl isocyanurate (TAHI), a hydrolysis product of HDI isocyanurate, in the urine of spray-painters. Analytical and internal standards were synthesized in-house and weighted linear regression calibration curves were generated using spiked control urine from non-exposed persons (0.06–7.98 μg/L; N = 13; w = x−2; r = 0.998). Urine samples collected from 15 exposed workers (N = 111) were subjected to acid hydrolysis and extracted with dichloromethane, then derivatized with acetic anhydride. The derivatized product, trisacetamidohexyl isocyanurate (TAAHI), was analyzed using nano-UPLC-ESI-MS/MS. The protocol was sensitive and specific for analysis of TAHI in the urine of exposed workers with a method detection limit at 0.03 μg/L. TAHI was detected in 33 of 111 urine samples and in 11 of 15 workers. This biomarker for HDI isocyanurate is critical to determine the relative potency and dose-relationships between the monomer and oligomer exposure on the development of diisocyanate induced health effects in future studies.

Biological monitoring of cobalt in hard metal factory workers.

The main aim of this study was to investigate the cobalt (Co) concentrations in urine along 4months and their relationship with Co concentrations in blood and haemoglobin (adducts) in 34 workers from a hard metal manufacturing plant where metallic Co and Co oxide were used. Furthermore, the excretion kinetics of Co was investigated and the half-lives of Co in blood, plasma and urine were calculated along 18days of non-exposure in the same workers. Co was analysed, in all biological samples, by ICP/MS. Wide fluctuations in the urinary Co concentration were observed throughout the work shift and during the work week. A highly significant linear correlation was found between Co concentration (geometrical mean) in urine samples provided each Thursday (end shift) during 16 subsequent weeks and levels of Co-haemoglobin adducts or blood Co concentrations at the end of the same period. The Co elimination kinetics in globin calculated along 18days without Co exposure was slow, being related to the physiological metabolism of haemoglobin, while in blood, plasma and urine Co half-lives were 12.3, 9.1 and 5.3days, respectively. Co concentrations in haemoglobin or blood are highly related to the geometrical mean concentration of urinary Co when samples are collected weekly for several subsequent weeks. The biological monitoring of occupational exposure to Co in hard metal facilities provides reliable results by using the Co concentrations in haemoglobin or in whole blood. The urinary findings, though, do not show the same reliability because of their wide daily and weekly fluctuations.

Highly sensitive LC-MS/MS methods for urinary biological monitoring of occupational exposure to cyclophosphamide, ifosfamide, and methotrexate antineoplastic drugs and routine application.

Highly sensitive ESI-LC-MS/MS methods were developed for urinary biological monitoring of occupational exposure to cyclophosphamide (CP), ifosfamide (IF), and methotrexate (MTX), which are hazardous antineoplastic drugs frequently handled by healthcare professionals. Extraction methods consisted of liquid/liquid extraction for simultaneous urinary CP and IF assays, and of solid phase extraction for the urinary MTX assay. A good linearity (r2>0.997), precision (CV<14.6%), and accuracy (bias<9.9%) were achieved for all compounds. The limit of detection (LOD) was 10pg/ml and the lower limit of quantification (LOQ) was 20pg/ml for all three drugs. Applying these methods in routine, more than 116 healthcare professionals occupationally exposed to antineoplastic drugs were monitored and 635 urines were analysed. Eleven healthcare professionals (9.5%) were found to be contaminated to at least one of the three antineoplastic drugs. Among analysed urines, 22 samples were found positives. The measured concentrations ranged from 20.1 to 1850pg/ml and, for six samples, concentrations were at CP trace level, between the LOD and LOQ values (10-20pg/ml). Such efficient analytical tools combining high specificity with high sensitivity are essential for reliable detection and routine biological monitoring of healthcare professionals occupationally exposed to these widely used antineoplastic drugs. These methods allow to monitor the healthcare professionals exposure to antineoplastic drugs in the aim to assess the effectiveness of collective and individual protective measures.

Biological Monitoring of Occupational Exposure to Polycyclic Aromatic Hydrocarbons at an Electric Steel Foundry in Tunisia.

Occupational exposures during iron and steel founding have been classified as carcinogenic to humans, and the exposure to polycyclic aromatic hydrocarbons (PAHs) in this industrial setting may contribute to cancer risk. The occupational exposure to PAHs was assessed in 93 male workers at an electric steel foundry in Tunisia by biomonitoring, with the aims of characterizing the excretion profile and investigating the influence of job title and personal characteristics on the biomarkers. Sixteen 2-6 ring unmetabolized PAHs (U-PAHs) and eight hydroxylated PAH metabolites (OHPAHs) were analyzed by gas chromatography-triple quadrupole tandem mass spectrometry and liquid chromatography triple quadrupole tandem mass spectrometry, respectively. Among U-PAHs, urinary naphthalene (U-NAP) was the most abundant compound (median level: 643ng l(-1)), followed by phenanthrene (U-PHE, 18.5ng l(-1)). Urinary benzo[a]pyrene (U-BaP) level was <0.30ng l(-1) Among OHPAHs, 2-hydroxynaphthalene (2-OHNAP) was the most abundant metabolite (2.27 µg l(-1)). Median 1-hydroxypyrene (1-OHPYR) was 0.52 µg l(-1) Significant correlations among urinary biomarkers were observed, with Pearson's r ranging from 0.177 to 0.626. 1-OHPYR was correlated to benzo[a]pyrene, but not to five- and six-rings PAHs. A multiple linear regression model showed that job title was a significant determinant for almost all U-PAHs. In particular, employees in the steel smelter workshop had higher levels of high-boiling U-PAHs and lower levels of low-boiling U-PAHs than those of workers with other job titles. Among OHPAHs, this model was significant only for naphthols and 1-hydroxyphenanthrene (1-OHPHE). Smoking status was a significant predictor for almost all biomarkers. Among all analytes, U-PHE and 1-OHPHE were the less affected by tobacco smoke, and they were significantly correlated with both low- and high-molecular-weight compounds, and their levels were related to job titles, so they could be proposed as suitable biomarkers of PAH exposure at steel foundries. Based on 1-OHPYR levels, our findings show that occupational exposure of these workers was similar to that reported in recent studies of electric steel foundry workers. The multianalytic approach is useful in revealing different exposure levels among job titles.

A method for routine analysis of urinary 4,4'-methylenebis (2-chloroaniline) by gas chromatography-electron capture detection.

The purpose of this study was to develop a simple and cost-effective method for the determination of urinary 4,4'-methylenebis (2-chloroaniline) (MBOCA) by gas chromatography-electron capture detection (GC-ECD) for biological monitoring of occupational exposure to MBOCA. MBOCA was prepared by liquid-liquid extraction after alkaline hydrolysis, derivatized with N-methyl-bis (trifluoroacetamide) and then analyzed using GC-ECD. The proposed method was validated in accordance with the US Food and Drug Administration guidance. The calibration curve showed linearity in the range 1-100 µg/l, with a correlation coefficient of >0.999. The limits of detection and quantification were 0.3 µg/l and 1 µg/l, respectively. The recovery was 94-99%. Intraday accuracy, expressed as the deviation from the nominal value, was 90.5-100.3%, and intraday precision, expressed as the relative standard deviation, was 0.3-2.4%. Interday accuracy and precision were 87.8-100.2% and 0.3-4.1%, respectively. The proposed method is a simple and cost-effective method suitable for routine analyses and could be useful for biological monitoring of occupational exposure to MBOCA.

Correlation between styrene concentration in saliva and blood samples for the biological monitoring of occupational exposure

Correlation between styrene concentration in saliva and blood samples for the biological monitoring of occupational exposure

Development of an Analytical Method for the Determination of Arsenic in Urine by Gas Chromatography‐mass Spectrometry for Biological Monitoring of Exposure to Inorganic Arsenic

The purpose of this study was to develop an analytical method for the simultaneous determination of inorganic arsenic [As(III) and As(V)] and monomethylarsonic acid (MMA) in urine by gas chromatography-mass spectrometry (GC-MS) for the biological monitoring of exposure to inorganic arsenic. Arsenic compounds (after reduction of arsenic to the trivalent state) were derivatized with 2,3-dimercapto-1-propanol and then analyzed using a GC-MS. The proposed method was validated according to the US Food and Drug Administration guidelines. The accuracy of the proposed method was confirmed by analyzing Standard Reference Material (SRM) 2669 (National Institute of Standards and Technology). Calibration curves showed linearity in the range 1-100 μg/l for each of the arsenic species, with correlation coefficients of >0.999. For each of the arsenic species, the limits of detection and quantification were 0.2 μg/l and 1 μg/l, respectively. The recoveries were 96-100%, 99-102% and 99-112% for As(III), As(V) and MMA, respectively. Intraday accuracy and precision were 82.7-99.8% and 0.9-7.4%, respectively. Interday accuracy and precision were 81.3-100.0% and 0.8-9.9%, respectively. The analytical values of SRM 2669 obtained by the proposed method were sufficiently accurate. The proposed method overcame the disadvantages of high-performance liquid chromatography with inductively coupled plasma mass spectrometry. It was a robust, selective and cost-effective method suitable for routine analyses and could be useful for the biological monitoring of occupational exposure to inorganic arsenic.

External Quality Assessment Scheme for Biological Monitoring of Occupational Exposure to Toxic Chemicals

ObjectivesIn this study, we summarized the External Quality Assessment Scheme (EQAS) for the biological monitoring of occupational exposure to toxic chemicals which started in 1995 and continued until a 31st round robin in the spring of 2010. The program was performed twice per year until 2009, and this was changed to once a year since 2010. The objective of the program is to ensure the reliability of the data related to biological monitoring from analytical laboratories.MethodsOne hundred and eighteen laboratories participated in the 31st round robin. The program offers 5 items for inorganic analysis: lead in blood, cadmium in blood, manganese in blood, cadmium in urine, and mercury in urine. It also offers 10 items for organic analysis, including hippuric acid, methylhippuric acid, mandelic acid, phenylglyoxylic acid, N-methylformamide, N-methylacetamide, trichloroacetic acid, total trichloro-compounds, trans,trans-muconic acid, and 2,5-hexanedione in urine. Target values were determined by statistical analysis using consensus values. All the data, such as chromatograms and calibration curves, were reviewed by the committee.ResultsThe proficiency rate was below 70% prior to the first round robin and improved to over 90% for common items, such as PbB and HA, while those for other items still remained in the range of 60-90% and need to be improved up to 90%.ConclusionThe EQAS has taken a primary role in improving the reliability of analytical data. A total quality assurance scheme is suggested, including the validation of technical documentation for the whole analytical procedure.

Exposure to hazardous drugs in Healthcare: An issue that will not go away

The Journal of Oncology Pharmacy Practice (JOPP) was first published in June 1995 as the official journal of the International Society of Oncology Pharmacy Practitioners (ISOPP). In a supplement to that issue, as part of a review of the ISOPP IV symposium presentations, an article by Professor Graham Sewell was included titled ‘Pharmaceutical issues: preparation and handling’. This article raised concerns about various aspects of quality and safety associated with cytotoxic drug reconstitution. It discussed the use of cytotoxic safety cabinets versus isolators, the use of early ‘closed systems’ and even the possible future use of robotics. In the 15 years since that first publication, interest in the handling of hazardous drugs used to treat cancer patients has not waned. At the recent ISOPP XII symposium held in Prague in May 2010, ten presentations and seven submitted abstracts on the topic of safe handling were included. From the highly technical use of robotics and the use of specialized closed systems to the basic use of personal protective equipment (PPE) in under-resourced countries, this subject remains highly topical. One reason for the interest in this topic is the inability to quantify the occupational risk of handling anticancer drugs. It is well recognized that patients treated with therapeutic doses of these drugs may develop second cancers years later. However, the risk associated with long-term very low level exposure to these agents is not currently measurable. A basic tenet of employment is the provision of a safe workplace. It may be impossible to remove all risk but it is imperative that risk is minimized. Large pharmaceutical companies manufacturing anti-cancer drugs do so in totally enclosed environments with workers wearing full respirator suits reminiscent of movies of outbreaks of a deadly virus. But it is financially completely beyond individual hospitals, institutions and clinics to supply such protective equipment. The smaller the preparation facility, the less viable it is to introduce expensive protective measures. Many pharmaceutical companies have improved the presentation of their anti-cancer drug products in several ways. The drugs are generally presented, when stability allows, in liquid form – this means less manipulation is required to prepare a dose. The drugs are generally packaged in plastic containers – this means less chance of vial breakage. When compatibility problems arise and do not permit plastic packaging, and glass containers are required, these are generally protected in some way to avoid breakage and leakage e.g., an ‘overcoat’ of plastic is placed over the vial. These improvements in packaging are applauded. However, it is known that external chemical contamination of drug vials arriving from the manufacturer is a problem. Manufacturers must accept responsibility for ensuring that only clean product leaves their facilities. It is discouraging when every safeguard is taken to protect staff preparing anti-cancer drugs, to find that a major source of contamination is the outside of the drug vials themselves. Before we place all the responsibility onto the manufacturers, we must first ensure that we are doing everything possible ourselves to reduce the contamination of the environment and ourselves and we still have quite a long way to go. The paper by Shin-ichi Sugiura et al. ‘Risks to health professionals from hazardous drugs in Japan: a pilot study of environmental and biological monitoring of occupational exposure to cyclophosphamide’ in this issue of The Journal describes a pilot study performed in 2006 looking at cytotoxic drug environmental contamination in two similar hospital departments.

Advance on biological monitoring of occupational exposure to toluene

甲苯作为一种有机溶剂广泛用于生产油漆、涂料、墨水、粘胶剂和清洗剂等行业,也作为原料用于生产尼龙、塑料、聚氨酯等高分子化合物.长期接触甲苯可导致黏膜刺激症、中枢神经系统功能下降和内分泌紊乱等急性、慢性中毒症状。