Hygienic guidance values for wipe sampling of antineoplastic drugs in Swedish hospitals.

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, 'hygienic guidance values' (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 <0.05-10 800 pg cm(-2)). The corresponding value for IF was 4.2 pg cm(-2) (range <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

148. Carbon Nanotubes

Carbon nanotubes (CNTs) can be seen as graphene sheets rolled to form cylinders. CNTs may be categorised as single- (SWCNT) or multi-walled (MWCNT). Due to the small size, the number of particles as well as the surface area per mass unit is extremely high. CNTs are highly diverse, differing with respect to e.g., diameter, length, chiral angles, chemical functionalisation, purity, stiffness and bulk density. Today, CNTs are utilised primarily for the reinforcement of composite polymers, but there is considerable potential for other applications. The rapidly growing production and use of CNTs increases the risk for occupational exposure. Since CNTs in bulk form are of very low density and much dust is produced during their handling, exposure by inhalation appears to represent the greatest potential risk in the work place. However, most work place measurements involved sampling periods that are too short, varying sampling techniques and non-specific analytical methods. CNTs may be absorbed via inhalation and ingestion. Systemic uptake via the skin has not been demonstrated. Human toxicity data on CNTs are lacking and interpretation of animal studies is often problematic since the physical properties and chemical composition are diverse, impurities may be present and data are sometimes omitted. Because of the physical similarities between asbestos and CNTs, it can be suspected that the latter may also cause lung fibrosis, mesothelioma and lung cancer following inhalation. Intraperitoneal and intrascrotal administration of CNTs causes mesothelioma in animals, but no inhalation carcinogenicity studies have been conducted. Thus, it is too early conclude whether CNTs cause mesothelioma and lung cancer in humans. Both SWCNTs and MWCNTs cause inflammation and fibrosis in the lungs of relevant animal types and for MWCNTs these effects are also seen in the pleura. For instance, minimal histiocytosis and mild granulomatous inflammation in the lungs and lung-draining lymph nodes have been observed in rats exposed for 13 weeks to 0.1 mg/m3 MWCNTs (lowest observed adverse effect level, LOAEL), with more pronounced inflammation in both mice and rats at higher doses. Thus, inflammatory responses in the lungs may be considered as the critical effect. However, the LOAEL of CNTs should be interpreted cautiously, since their toxicity is likely to vary widely, depending on the structure and physicochemical properties, as well as the contribution from non-carbon components. It is also uncertain which dose metric (e.g., mass, number or surface area per air volume unit) is most appropriate. Some studies indicate that longer straight CNTs evoke more pronounced biological effects than shorter or tangled fibres

Aerosol formation and emissions from realistic compartment fires

Firefighters are occupationally exposed to a large number of toxic compounds (IARC 2010). The occupational exposure of firefighters has been classified as potentially carcinogenic (class 2B, IARC; (Straif K. et al. 2007)). Poorly quantified emission factors and low understanding of when various aerosol emissions are likely to form during a fire event (initiation, combustion, extinguishing) inhibit efforts to reduce exposure by interventions to the firefighting strategy. The study was designed to evaluate firefighters’ exposure to air pollutants and to allow identification of how aerosol emissions respond to burning conditions and interventions of the firefighting. The study was conducted at the MSB firefighter training facility in Revinge outside Lund, Sweden. Eight small (5x3x2 m) sheds were built to imitate small compartment environments: apartment, bedroom, workshop, etc. These sheds were ignited under realistic fire scenarios (e.g., accident, arson) and later used for training new fire investigators (forensic police). Firefighter students and teachers monitored and extinguished the fires in similar procedures to real fire events. A supervisor monitored the combustion conditions, allowing or restricting fresh-air flow into the fire by opening or closing of the main door.Fire emissions were extracted from the fire through a 10 m (Ø 6 mm) stainless steel pipe, diluted ~1:50 with HEPA and active charcoal filtered air. The diluted emissions were monitored with a battery of aerosol monitoring instruments. Instrumentation included an aerosol mass spectrometer (Aerodyne SP-AMS, Billerica USA), an aethalometer (AE33, Magee Sci. USA), a differential mobility spectrometer (DMS500, Cambustion, UK), CO2 monitor (LI-COR, USA), and a NO/NO2 monitor (2BTech, USA). Complementary background measurements were positioned downwind or sidewind of the fires. With this equipment we collected data with the aim to resolve relationships between combustion conditions and pollution formation during different phases of a fire response. The results showed that total particle mass (PM1) emissions correlated with CO2 emissions and thus fire intensity. The emissions were speciated according to equivalent black carbon (eBC), organic aerosol (OA) and polycyclic aromatic hydrocarbon (PAH) derived from AMS data. When speciated, different particle emissions were found to depend on activities of the firefighting and the supervisor responsible for allowing or restricting fresh air into the combustion environment. Most evidently, we found that restricting the access to O2 by closing the door resulted in a sharp increase of OA and even more pronounced, PAH. PAH increased by several orders of magnitude, suggesting that PAH exposure-risks may increase drastically when fires become under-ventilated. Extinguishing the fire with water quickly decreased all particle emissions. The results described are illustrated in Figure 1.Further analysis involves additional off-line analyses, derivation of emission factors, time-resolved speciated emission analysis and evaluation of relationships between emissions, burning conditions and firefighting strategies

Exposure and Emission Measurements During Production, Purification, and Functionalization of Arc-Discharge-Produced Multi-walled Carbon Nanotubes.

Background: 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

MWCNTs of different physicochemical properties cause similar inflammatory responses, but differences in transcriptional and histological markers of fibrosis in mouse lungs

Multi-walled carbon nanotubes (MWCNTs) are extensively produced and used in composite materials and electronic applications, thus increasing risk of worker and consumer exposure. MWCNTs are an inhomogeneous group of nanomaterials that come in various lengths, shapes and with different metal contaminations, which makes hazard evaluation difficult. However, several studies suggest that length plays an important role in the toxicity induced by MWCNTs. How the length influences toxicity at the molecular level is yet to be characterized. Female C57BL/6 mice were exposed by single intratracheal instillation to 18, 54 or 162 µg/mouse of a short MWCNT (NRCWE-026, 847±102 nm in length) or long MWCNT (NM-401, 4048±366 nm in length). The two MWCNTs were extensively characterized. Lung tissues were harvested 24 h, 3 d and 28 d after exposure. We employed DNA microarrays, bronchoalveolar lavage fluid analysis, comet assay and dichlorodihydrofluorescein assay in order to profile the pulmonary responses. Bioinformatics tools were then applied to compare and contrast the expression profiles and to build a length dependent property-response matrix for gene-by-gene comparison. The toxicogenomic analysis of the global mRNA changes after exposure to the short, entangled NRCWE-026 or the longer, stiffer NM-401 showed high degree of similarities. The toxicity of both MWCNTs was driven by strong inflammatory and acute phase responses, which peaked at day 3 and was observed both in bronchoalveolar lavage cell influx and in gene expression profiles. The inflammatory response was sustained at post-exposure day 28. Also, at the sub-chronic level, we identified a sub-set of 14 fibrosis related genes that were uniquely differentially regulated after exposure to NM-401. Acellular ROS production occurred almost exclusively with NRCWE-026, however the longer NM-401 induced in vivo DNA strand breaks and differential regulation of genes involved in free radical scavenging more readily than NRCWE-026. Our results indicate that the global mRNA response after exposure to MWCNTs is length independent at the acute time points, but that fibrosis may be length dependent sub-chronic end point.JRC.H.6-Digital Earth and Reference Dat