Institute for Occupational Medicine

Edinburgh, United Kingdom

Institute for Occupational Medicine

Edinburgh, United Kingdom
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Johnston H.J.,Napier University | Hutchison G.,Napier University | Christensen F.M.,European Commission - Joint Research Center Ispra | Peters S.,Institute for Occupational Medicine | And 2 more authors.
Critical Reviews in Toxicology | Year: 2010

This review is concerned with evaluating the toxicity associated with human exposure to silver and gold nanoparticles (NPs), due to the relative abundance of toxicity data available for these particles, when compared to other metal particulates. This has allowed knowledge on the current understanding of the field to be gained, and has demonstrated where gaps in knowledge are. It is anticipated that evaluating the hazards associated with silver and gold particles will ultimately enable risk assessments to be completed, by combining this information with knowledge on the level of human exposure. The quantity of available hazard information for metals is greatest for silver particulates, due to its widespread inclusion within a number of diverse products (including clothes and wound dressings), which primarily arises from its antibacterial behaviour. Gold has been used on numerous occasions to assess the biodistribution and cellular uptake of NPs following exposure. Inflammatory, oxidative, genotoxic, and cytotoxic consequences are associated with silver particulate exposure, and are inherently linked. The primary site of gold and silver particulate accumulation has been consistently demonstrated to be the liver, and it is therefore relevant that a number of in vitro investigations have focused on this potential target organ. However, in general there is a lack of in vivo and in vitro toxicity information that allows correlations between the findings to be made. Instead a focus on the tissue distribution of particles following exposure is evident within the available literature, which can be useful in directing appropriate in vitro experimentation by revealing potential target sites of toxicity. The experimental design has the potential to impact on the toxicological observations, and in particular the use of excessively high particle concentrations has been observed. As witnessed for other particle types, gold and silver particle sizes are influential in dictating the observed toxicity, with smaller particles exhibiting a greater response than their larger counterparts, and this is likely to be driven by differences in particle surface area, when administered at an equal-mass dose. A major obstacle, at present, is deciphering whether the responses related to silver nanoparticulate exposure derive from their small size, or particle dissolution contributes to the observed toxicity. Alternatively, a combination of both may be responsible, as the release of ions would be expected to be greater for smaller particles. © 2010 Informa UK Ltd.

Johnston H.J.,Napier University | Hutchison G.R.,Napier University | Christensen F.M.,European Commission - Joint Research Center Ispra | Peters S.,Institute for Occupational Medicine | And 3 more authors.
Nanotoxicology | Year: 2010

This critical review of the available human health safety data, relating to carbon nanotubes (CNTs), was conducted in order to assess the risks associated with CNT exposure. Determining the toxicity related to CNT exploitation is of great relevance and importance due to the increased potential for human exposure to CNTs within occupational, environmental and consumer settings. When this information is combined with knowledge on the likely exposure levels of humans to CNTs, it will enable risk assessments to be conducted to assess the risks posed to human health. CNTs are a diverse group of materials and vary with regards to their wall number (single and multi-walled CNTs are evident), length, composition, and surface chemistry. The attributes of CNTs that were identified as being most likely to drive the observed toxicity have been considered, and include CNT length, metal content, tendency to aggregate/agglomerate and surface chemistry. Of particular importance, is the contribution of the fibre paradigm to CNT toxicity, whereby the length of CNTs appears to be critical to their toxic potential. Mechanistic processes that are critical to CNT toxicity will also be discussed, with the findings insinuating that CNTs can exert an oxidative response that stimulates inflammatory, genotoxic and cytotoxic consequences. Consequently, it may transpire that a common mechanism is responsible for driving CNT toxicity, despite the fact that CNTs are a diverse population of materials. The similarity of the structure of CNTs to that of asbestos has prompted concern surrounding the exposure of humans, and so the applicability of the fibre paradigm to CNTs will be evaluated. It is also necessary to determine the systemic availability of CNTs following exposure, to determine where potential targets of toxicity are, and to thereby direct in vitro investigations within the most appropriate target cells. CNTs are therefore a group of materials whose useful exploitable properties prompts their increased production and utilization within diverse applications, so that ensuring their safety is of vital importance. © 2010 Informa UK Ltd.

Vlaanderen J.,University Utrecht | Fransman W.,TNO | Miller B.,Institute for Occupational Medicine | Burstyn I.,University of Alberta | And 4 more authors.
Occupational and Environmental Medicine | Year: 2010

Introduction: In occupational epidemiology, differences in the temporal coverage of the exposure history by available exposure measurement data may affect the uncertainty of exposure estimates. In the reporting of results of studies, greater attention should be paid to the extent to which exposure assessments require extrapolation outside the timeframe for which exposure measurements are available. We propose a simple graphical method that can be used to visualise the temporal coverage of exposure history with exposure measurements and the extent of temporal extrapolation needed. Methods: We construct a graph that displays the accumulated work history years for which exposure had to be assessed in each calendar year. Years for which exposure measurements were available are shaded. The proportion of work history years covered by exposure measurements and the proportion of work history years accrued before the first measurements are summarised. When available, the actual number of measurements available in each calendar year is shown. Results: We demonstrate the application of the graphical tool in three nested case-control studies that reported on leukaemia in relation to low-level benzene exposures in the petroleum industry. Considerable differences in temporal coverage between the studies were illustrated, which may have resulted in differences in the reliability of the retrospective exposure estimates derived for these studies. Conclusion: We introduce a graphical tool for visualising the temporal coverage by available exposure measurement data in epidemiological studies and encourage others to use similar graphs to derive and share better qualitative insights into the uncertainty in exposure assessment.

Budnik L.T.,University of Hamburg | Kloth S.,University of Hamburg | Baur X.,University of Hamburg | Baur X.,Institute for Occupational Medicine | And 3 more authors.
PLoS ONE | Year: 2013

There is a need for a panel of suitable biomarkers for detection of environmental chemical exposure leading to the initiation or progression of degenerative diseases or potentially, to cancer. As the peripheral blood may contain increased levels of circulating cell-free DNA in diseased individuals, we aimed to evaluate this DNA as effect biomarker recognizing vulnerability after exposure to environmental chemicals. We recruited 164 individuals presumably exposed to halo-alkane-based pesticides. Exposure evaluation was based on human biomonitoring analysis; as biomarker of exposure parent halo-methanes, -ethanes and their metabolites, as well as the hemoglobin-adducts methyl valine and hydroxyl ethyl valine in blood were used, complemented by expert evaluation of exposure and clinical intoxication symptoms as well as a questionnaire. Assessment showed exposures to halo alkanes in the concentration range being higher than non-cancer reference doses (RfD) but (mostly) lower than the occupational exposure limits. We quantified circulating DNA in serum from 86 individuals with confirmed exposure to off-gassing halo-alkane pesticides (in storage facilities or in home environment) and 30 non-exposed controls, and found that exposure was significantly associated with elevated serum levels of circulating mitochondrial DNA (in size of 79 bp, mtDNA-79, p = 0.0001). The decreased integrity of mtDNA (mtDNA-230/mtDNA-79) in exposed individuals implicates apoptotic processes (p = 0.015). The relative amounts of mtDNA-79 in serum were positively associated with the lag-time after intoxication to these chemicals (r = 0.99, p<0.0001). Several months of post-exposure the specificity of this biomarker increased from 30% to 97% in patients with intoxication symptoms. Our findings indicate that mitochondrial DNA has a potential to serve as a biomarker recognizing vulnerable risk groups after exposure to toxic/carcinogenic chemicals. © 2013 Budnik et al.

Hellwig R.T.,FH Augsburg | Brasche S.,University Hospital Jena | Gebhardt H.,Institute for Occupational Medicine | Grun G.,Fraunhofer Institute for Building Physics | And 2 more authors.
Indoor Air 2014 - 13th International Conference on Indoor Air Quality and Climate | Year: 2014

A widely applied test used to measure selective attention and concentration is the d2-attention test. There is however, a training effect when this test is repeatedly carried out. The aim of this paper is to provide a methodological approach to adjust for training effects in studies designed to detect intra-individual differences. In total, the d2-attention test was presented 9 times to a total number of 20 subjects. It was presented 5 times under the same conditions. Taking into account the test results under the same conditions only, a logarithmic training effect function was developed for each subject. The constant varies between 290 and 520, and the factor varies between 50 and 150. Some subjects were already successful from the first application of the d2-test, while others showed a steeper learning curve. Performance test designs should generally consider possible training effects. Individual training effect functions to adjust for training effects are strongly recommended.

Hellwig R.T.,FH Augsburg | Noske I.,Fraunhofer Institute for Building Physics | Brasche S.,University Hospital Jena | Gebhardt H.,Institute for Occupational Medicine | And 3 more authors.
10th International Conference on Healthy Buildings 2012 | Year: 2012

A study was carried out to investigate whether an elevated room temperature in a summer heat wave affects a subject's mental status, self-assessed performance or impairs a subject's mental performance. In a simulated office environment 20 subjects were exposed to different air temperature conditions: 23-26°C, repeated once, 29-32°C and 33-35°C during outside summer conditions. In the course of 4.25 h selective attention, verbal and numerical thinking did not change significantly neither with temperature nor time. Slight effects on performance were found for text correction. The willingness to exert effort and the feeling of being relaxed decreased significantly both with temperature and time. Drowsiness tended to increase with temperature and rose significantly with time. The feeling of being well-adjusted and selfassessed performance tended to decrease with increasing temperature. The mental and physical work load were perceived to be higher when the temperatures where higher. The results imply the subject's ability to adjust their mental performance in relation to heat strain. A longer exposure time may lead to different results.

Kloth S.,University of Hamburg | Baur X.,Institute for Occupational Medicine | Goen T.,Friedrich - Alexander - University, Erlangen - Nuremberg | Budnik L.T.,University of Hamburg
Environmental Health: A Global Access Science Source | Year: 2015

Background: International phytosanitary standards ISPM 15 require (since 2007) fumigation or heat treatment for shipping and storage. Those dealing with fumigated freight might be accidentally exposed. In this paper we report a series of three accidents of six storage room workers in a medium sized company regularly importing electronic production parts from abroad. Methods: Patients (n = 6, aged from 32-54 yrs.) and control group (n = 30, mean 40 yrs.) donated blood and urine samples. The fumigants: ethylene oxide, methyl bromide, chloropicrin, ethylene dichloride, other halo-alkanes and solvents were analyzed by headspace gas chromatography/mass spectrometry (GCMS). For the quantitation of long term exposure/s, macromolecular reaction products (hemoglobin adducts) were used (with GCMS) as molecular dosimeter; additionally 8-OHdG and circulating mtDNA (cmtDNA) were analyzed as nonspecific biological effect markers. Results: The hemoglobin adducts N-methyl valine (MEV) and N-(2-hydroxy ethyl) valine (HEV) were elevated after exposure to the alkylating chemicals methyl bromide and ethylene oxide. Under the consideration of known elimination kinetics and the individual smoking status (biomonitored with nicotine metabolite cotinine and tobacco specific hemoglobin adduct: N-(2 cyan ethyl) valines, CEV), the data allow theoretical extrapolation to the initial protein adduct concentrations at the time of the accident (the MEV/CEV levels were from 1,616 pmol/g globin to 1,880 pmol/g globin and HEV/CEV levels from 1,407 pmol/g globin to 5,049 pmol/g globin, and correlated with inhaled 0.4-1.5 ppm ethylene oxide. These integrated, extrapolated internal doses, calculated on the basis of biological exposure equivalents, confirmed the clinical diagnosis for three patients, showing severe intoxication symptoms. Both, cmtDNA and 8-OHdG, as non-specific biomarkers of toxic effects, were elevated in four patients. Conclusion: The cases reported here, stress the importance of a suitable risk assessment and control measures. We put emphasis on the necessity of human biomonitoring guidelines and the urgency for the relevant limit values. © 2014 Kloth et al.; licensee BioMed Central.

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