Maria Hedmer - Academia.edu (original) (raw)

Papers by Maria Hedmer

Annals of Occupational Hygiene, 2005

Workplaces, e.g. hospital pharmacies and hospital departments, where antineoplastic drugs are han... more Workplaces, e.g. hospital pharmacies and hospital departments, where antineoplastic drugs are handled might be contaminated with these drugs, and pharmacy personnel and health care workers may be exposed. In this study potential sources for exposure of antineoplastic drugs were investigated. Unbroken drug vials and tablet blister packages, both containing cyclophosphamide (CP) and their outer packaging were wipe sampled. Analysis was performed by liquid chromatography combined with tandem mass spectrometry (LC-MS/MS). The result showed that almost every part of the primary packaging was contaminated with CP and ifosfamide (IF). However, the amounts of CP and IF were low, and most likely not harmful for the personnel handling these packaging in association with drug preparation. The contamination must originate from the pharmaceutical manufacturer. Different surfaces in the preparation unit of a Swedish hospital pharmacy were also investigated at two different occasions by wipe sampling. In the preparation unit CP and IF were found as contaminants on the majority of the investigated surfaces. After the first measurement the hospital pharmacy improved its routines. Lower amounts of CP and IF were detected at the second measurement. A low degree of contamination with CP and IF was also detected on the floor outside the preparation unit and this indicated a small distribution of antineoplastic drugs to the surroundings.

Journal of Environmental Monitoring, 2012

The use of antineoplastic drugs in health care steadily increases. Health care workers can be occ... more The use of antineoplastic drugs in health care steadily increases. Health care workers can be occupationally exposed to antineoplastic drugs classified as carcinogenic or teratogenic. Monitoring of surface contamination is a common way to assess occupational exposure to antineoplastic drugs, since wipe sampling is used as a surrogate measure of dermal exposure. Since no occupational limits for antineoplastic drugs in work environments exist, &amp;amp;amp;#39;hygienic guidance values&amp;amp;amp;#39; (HGVs) should be used instead. HGVs are practicable, achievable levels, not health based, and can be calculated from exposure data from representative workplaces with good occupational hygiene practices. So far, guidance values for surface monitoring of antineoplastic drugs only exist for pharmacies where antineoplastic drugs are prepared. The objective was to propose HGVs for surface monitoring of cyclophosphamide (CP) and ifosfamide (IF) in Swedish hospitals where antineoplastic drugs are administered to patients. In total, 17 workplaces located at six hospitals in Sweden were surveyed by wipe sampling. Wipe samples were collected, worked up and then analyzed with liquid chromatography tandem mass spectrometry. Surface contamination of CP and IF was found on 80% and 73% of the sampled surfaces, thus indicating that there is potential for health care workers to be exposed to CP and IF via the skin. The median surface load of CP was 3.3 pg cm(-2) (range &amp;amp;amp;lt;0.05-10,800 pg cm(-2)). The corresponding value for IF was 4.2 pg cm(-2) (range &amp;amp;amp;lt;0.13-95,000 pg cm(-2)). The highest surface loads were found on the floors. The proposed HGVs were set at 90th percentile values, and can be applicable to hospital workplaces where patients are treated with CP or IF. Surface monitoring combined with HGVs is a useful tool for health care workers to regularly benchmark their own surface loads which could control and reduce the occupational exposure to CP and IF in hospital workplaces. Thus, the occupational safety of the health care workers will be increased.

Environmental and Molecular Mutagenesis, 2015

Evidence suggests that exposure to welding fumes is a risk factor for lung cancer. We examined re... more Evidence suggests that exposure to welding fumes is a risk factor for lung cancer. We examined relationships between low-to-moderate occupational exposure to particles from welding fumes and cancer-related biomarkers for oxidative stress, changes in telomere length, and alterations in DNA methylation. We enrolled 101 welders and 127 controls (all currently nonsmoking men) from southern Sweden. We performed personal sampling of respirable dust and measured 8-oxodG concentrations in urine using a simplified liquid chromatography tandem mass spectrometry method. Telomere length in peripheral blood was measured by quantitative polymerase chain reaction. Methylation status of 10 tumor suppressor genes was determined by methylation-sensitive high-resolution melting analysis. All analyses were adjusted for age, body mass index, previous smoking, passive smoking, current residence, and wood burning stove/boiler at home. Welders were exposed to respirable dust at 1.2 mg/m(3) (standard deviation, 3.3 mg/m(3) ; range, 0.1-19.3), whereas control exposures did not exceed 0.1 mg/m(3) (P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.001). Welders and controls did not differ in 8-oxodG levels (β = 1.2, P = 0.17) or relative telomere length (β = -0.053, P = 0.083) in adjusted models. Welders showed higher probability of adenomatous polyposis coli (APC) methylation in the unadjusted model (odds ratio = 14, P = 0.014), but this was not significant in the fully adjusted model (P = 0.052). Every working year as a welder was associated with 0.0066 units shorter telomeres (95% confidence interval -0.013 to -0.00053, P = 0.033). Although there were no clear associations between concentrations of respirable dust and the biomarkers, there were modest signs of associations between oxidative stress, telomere alterations, DNA methylation, and occupational exposure to low-to-moderate levels of particles. Environ. Mol. Mutagen., 2015. © 2015 Wiley Periodicals, Inc.

Annals of Occupational Hygiene, 2014

The production and use of carbon nanotubes (CNTs) is rapidly growing. With increased production, ... more The production and use of carbon nanotubes (CNTs) is rapidly growing. With increased production, there is potential that the number of occupational exposed workers will rapidly increase. Toxicological studies on rats have shown effects in the lungs, e.g. inflammation, granuloma formation, and fibrosis after repeated inhalation exposure to some forms of multi-walled CNTs (MWCNTs). Still, when it comes to health effects, it is unknown which dose metric is most relevant. Limited exposure data for CNTs exist today and no legally enforced occupational exposure limits are yet established. The aim of this work was to quantify the occupational exposures and emissions during arc discharge production, purification, and functionalization of MWCNTs. The CNT material handled typically had a mean length <5 μm. Since most of the collected airborne CNTs did not fulfil the World Health Organization fibre dimensions (79% of the counted CNT-containing particles) and since no microscopy-based method for counting of CNTs exists, we decided to count all particle that contained CNTs. To investigate correlations between the used exposure metrics, Pearson correlation coefficient was used.

Journal of Environmental Monitoring, 2004

Methods to monitor contamination of workplaces with antineoplastic drugs have been developed and ... more Methods to monitor contamination of workplaces with antineoplastic drugs have been developed and validated. Cyclophosphamide (CP) was used as a model compound as it is one of the most commonly used antineoplastic drugs. A wipe sampling method to detect contamination with CP at surfaces was developed. A personal air sampling method to sample gas and vapour on solid sorbent tubes and particles with filters was also developed. Wipe and filter samples were extracted and sorbent samples were eluted, all with ethyl acetate. The samples were analysed with liquid chromatography tandem mass spectrometry. 2 H 6 -labelled cyclophosphamide was used as an internal standard. The between-day precision was 2-5% for wipe samples, 4-6% for sorbent samples and 3-8% for filter samples. The limit of detection was 0.02 ng CP per sample for the wipe and filter methods and 0.03 ng CP per sample for the solid sorbent method. Wipe sampling on surfaces made of different materials resulted in mean recoveries between 78-106%. The desorption recovery was between 97-102% for the wipe samples, 97% for the sorbent samples and 101% for the filter samples. Samples were stable for up to 2 months at 5 1C and À20 1C and for about 2 d at room temperature. The developed methods were applied to the measurement of contamination with CP in a hospital pharmacy. Trace amounts of CP, 1.3 and 1.4 ng, were detected on surfaces in the pharmacy. P A P E R

International Archives of Occupational and Environmental Health, 2008

Objectives Exposure to antineoplastic drugs should be avoided due to the risk of getting adverse ... more Objectives Exposure to antineoplastic drugs should be avoided due to the risk of getting adverse health eVects. Antineoplastic drugs such as cyclophosphamide (CP) and ifosfamide (IF) are commonly used in medical attendance. In this study the variability of surface contamination of CP and IF was investigated by repeated wipe sampling over time in four workplaces in a university hospital. The surface contamination levels were also evaluated and health care workers were biologically monitored. Methods A hospital pharmacy, two oncology wards and one oncology outpatient department were selected. Between 10 and 13 diVerent surface areas such as work areas, Xoors and handles were selected in each workplace and wiped between 7 and 8 times during 9 months. Pre-and post-shift urine samples were collected from the workers in the investigated workplaces. Analysis was performed by liquid chromatography combined with tandem mass spectrometry. Results Measurable amounts of CP and IF were detected on the majority of the sampled surfaces. The highest concentrations were found on the Xoors in the patient lavatories and utility rooms (up to 95 ng cm ¡2 ). In general, the surface contamination of CP and IF on Xoors did not vary much over time. Work areas and handles had larger variability. Neither CP nor IF were detected in any of the collected urine samples.

International Archives of Occupational and Environmental Health, 2007

Objectives Cyclophosphamide (CP) is an alkylating agent classiWed as a human carcinogen. Health c... more Objectives Cyclophosphamide (CP) is an alkylating agent classiWed as a human carcinogen. Health care workers handling this drug may be exposed during, e.g., preparation or administration. Cyclophosphamide is readily absorbed by inhalation and by dermal uptake. A biomarker, CP in urine, has frequently been used to assess the occupational exposure to CP, but has not been fully validated. The aim of this study was to investigate if the proportion of the CP dose that is excreted in urine (renal clearance) is constant over diVerent plasma drug concentrations and other pharmacokinetic parameters, e.g., urine Xow. Methods Pharmacokinetics of CP were studied in 16 breast cancer patients that were treated with postoperative adjuvant chemotherapy including CP. Plasma and urine from the patients were collected at diVerent occasions up to 12 days after the dose. Urine was collected during 4-h periods and blood was sampled at the end of each period. Analysis of CP was performed by liquid chromatography tandem mass spectrometry. The limit of detection for CP in urine and plasma was 0.01 and 0.02 ng/ml, respectively. The precisions of the developed methods were determined to ·8%. Results The administered doses of CP in absolute amounts ranged between 800 and 2,240 mg. Mean renal clearance of CP was 8.6 (conWdence interval 6.5-10.7) ml/min and was not signiWcantly dependent of the plasma drug concentration. However, a signiWcant correlation between renal clearance and urine Xow was observed. There was a large inter-individual variation in the plasma and urine concentrations even when the same doses were given. Conclusions Cyclophosphamide in urine can be continued to be used as a biomarker to monitor occupational exposure to CP, however the inter-individual variability of excretion of CP in urine, and its dependency on urine Xow must be taken into consideration in future applications.

International Archives of Occupational and Environmental Health, 2013

Welding fume consists of metal fumes, e.g., manganese (Mn) and gases, e.g., ozone. Particles in t... more Welding fume consists of metal fumes, e.g., manganese (Mn) and gases, e.g., ozone. Particles in the respirable dust (RD) size range dominate. Exposure to welding fume could cause short- and long-term respiratory effects. The prevalence of work-related symptoms among mild steel welders was studied, and the occupational exposure to welding fumes was quantified by repeated measurements of RD, respirable Mn, and ozone. Also the variance components were studied. A questionnaire concerning airway symptoms and occupational history was answered by 79% of a cohort of 484 welders. A group of welders (N = 108) were selected and surveyed by personal exposure measurements of RD and ozone three times during 1 year. The welders had a high frequency of work-related symptoms, e.g., stuffy nose (33%), ocular symptoms (28%), and dry cough (24%). The geometric mean exposure to RD and respirable Mn was 1.3 mg/m(3) (min-max 0.1-38.3 mg/m(3)) and 0.08 mg/m(3) (min-max &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.01-2.13 mg/m(3)), respectively. More than 50% of the Mn concentrations exceeded the Swedish occupational exposure limit (OEL). Mainly, low concentrations of ozone were measured, but 2% of the samples exceeded the OEL. Of the total variance for RD, 30 and 33% can be attributed to within-worker variability and between-company variability, respectively. Welders had a high prevalence of work-related symptom from the airways and eyes. The welders&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39; exposure to Mn was unacceptably high. To reduce the exposure further, control measures in the welding workshops are needed. Correct use of general mechanical ventilation and local exhaust ventilation can, for example, efficiently reduce the exposure.

Lead in blood is a major concept in biomonitoring of exposure but investigations of its alternati... more Lead in blood is a major concept in biomonitoring of exposure but investigations of its alternatives are scarce. The aim of the study was to describe different lead biomarkers' variances, day-to-day and between individuals, estimating their fraction of the total variance. Repeated sampling of whole blood, plasma and urine were conducted for 48 lead-exposed men and 20 individuals under normal environmental lead exposure, in total 603 measurements. For lead workers, the fraction of the total variance attributed to differences between individuals was 91% for whole-blood lead (geometric mean 227 mg/l; geometric standard deviation (GSD): 1.55 mg/l); plasma 78% (0.57 mg/l; GSD: 1.84 mg/l); density-adjusted urine 82%; and unadjusted urine 75% (23.7 mg/l; GSD: 2.48 mg/l). For the individuals under normal lead exposure, the corresponding fractions were 95% of the total variance for whole blood (20.7 mg/l; GSD: 8.6 mg/l), 15% for plasma (0.09 mg/l; GSD: 0.04 mg/l), 87% for creatinine-adjusted urine and 34% for unadjusted (10.8 mg/l; GSD: 6.7 mg/l). Lead concentration in whole blood is the biomarker with the best ability to discriminate between individuals with different mean concentration. Urinary and plasma lead also performed acceptably in lead workers, but at low exposures plasma lead was too imprecise. Urinary adjustments appear not to increase the between-individual fraction of the total variance among lead workers but among those with normal lead exposure.

Journal of Nanoparticle Research, 2013

Nanotechnology gives us materials with enhanced or completely new properties. At the same time in... more Nanotechnology gives us materials with enhanced or completely new properties. At the same time inhalation of manufactured nano-objects has been related to an array of adverse biological effects. We characterized particle emissions, which occurred during maintenance of common metal nanoparticle generators and contrasted the properties of the emitted particles with those originally produced by the generators. A new approach using online aerosol mass spectrometry, for time and size resolved measurements of the particle chemical composition, was applied in combination with more conventional techniques for particle sampling and analysis, including electron microscopy. Emissions during maintenance work, in terms of mass and surface area concentration in the size range of 0.02-10 µm, were dominated by large agglomerates (1-5 µm). With aerosol mass spectrometry we show that the particle composition depends on both generator type and maintenance task being performed and that the instrument can be used for highly time resolved selective studies of metal nanoparticle emissions. The emitted agglomerates have a relatively high probability to be deposited in the lower respiratory tract, since the mean particle diameter coincided with a peak in the lung deposition curve. Each of these agglomerates consisted of a very high number (10 3 -10 5 /agglomerate) of nanometer sized primary particles originating from the particle synthesis process. This made them possess large surface areas, one of the key properties in nanotoxicology. Similar agglomerates may be emitted in a wide range of processes when nanoparticles are manufactured or handled. The fate of such agglomerates, once deposited in the respiratory tract, is unknown and should therefore be considered in future particle toxicological studies. Our results highlight the importance of including micrometer sized particles in exposure and emission assessments.