Suchergebnisse

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.

Flame retardants are chemical substances used in furniture, plastics, building materials, several household products and consumer goods to reduce their flammability. Their widespread use has resulted in measurable concentrations of the compounds or their residues in the environment, biota and human biological samples. The previously used brominated flame retardants were found to be persistent and to have bioaccumulative and neurotoxic potential, which raised public awareness. The use of the emerging organophosphorus compounds have increased after phasing out some brominated flame retardants. The chemical properties and health impacts of the organophosphorus flame retardants have not been studied to the same extent. The effects on public health and the environment due to the exposure from their widespread occurrence are therefore unclear. The aim of this study is to analyse exposure levels of the organophosphorus flame retardants TBP, TPP, TDCIPP and TBOEP in urine samples from a Swedish population of young men. The samples were collected through the enrolment for military service. Urine samples from year 2000, 2004, 2009 and 2013 were analysed for selected biomarkers of exposure with LC-MS/MS. The statistical analysis focused on temporal trends of the measured exposure levels. The metabolites DBP, DPP and BDCIPP were found in concentrations above LOD (0.03 – 0.1 ng/ml) in the majority of the samples, and DPP in all samples. BBOEP were only found above LOD in some samples and in very low concentrations. There was a statistically significant decreasing trend for the concentrations of DBP over time

AbstractHumans are continuously exposed to chemicals with suspected or proven endocrine disrupting chemicals (EDCs). Risk management of EDCs presents a major unmet challenge because the available data for adverse health effects are generated by examining one compound at a time, whereas real‐life exposures are to mixtures of chemicals. In this work, we integrate epidemiological and experimental evidence toward a whole mixture strategy for risk assessment. To illustrate, we conduct the following four steps in a case study: (1) identification of single EDCs ("bad actors")—measured in prenatal blood/urine in the SELMA study—that are associated with a shorter anogenital distance (AGD) in baby boys; (2) definition and construction of a "typical" mixture consisting of the "bad actors" identified in Step 1; (3) experimentally testing this mixture in an in vivo animal model to estimate a dose–response relationship and determine a point of departure (i.e., reference dose [RfD]) associated with an adverse health outcome; and (4) use a statistical measure of "sufficient similarity" to compare the experimental RfD (from Step 3) to the exposure measured in the human population and generate a "similar mixture risk indicator" (SMRI). The objective of this exercise is to generate a proof of concept for the systematic integration of epidemiological and experimental evidence with mixture risk assessment strategies. Using a whole mixture approach, we could find a higher rate of pregnant women under risk (13%) when comparing with the data from more traditional models of additivity (3%), or a compound‐by‐compound strategy (1.6%).

Background: Epidemiological studies have shown that many welders experience respiratory symptoms. During the welding process a large number of airborne nanosized particles are generated, which might be inhaled and deposited in the respiratory tract. Knowledge of the underlying mechanisms behind observed symptoms is still partly lacking, although inflammation is suggested to play a central role. The aim of this study was to investigate the effects of welding fume particle exposure on the proteome expression level in welders suffering from respiratory symptoms, and changes in protein mediators in nasal lavage samples were analyzed. Such mediators will be helpful to clarify the pathomechanisms behind welding fume particle-induced effects. Methods: In an exposure chamber, 11 welders with work-related symptoms in the lower airways during the last month were exposed to mild-steel welding fume particles (1 mg/m(3)) and to filtered air, respectively, in a double-blind manner. Nasal lavage samples were collected before, immediately after, and the day after exposure. The proteins in the nasal lavage were analyzed with two different mass spectrometry approaches, label-free discovery shotgun LC-MS/MS and a targeted selected reaction monitoring LC-MS/MS analyzing 130 proteins and four in vivo peptide degradation products. Results: The analysis revealed 30 significantly changed proteins that were associated with two main pathways; activation of acute phase response signaling and activation of LXR/RXR, which is a nuclear receptor family involved in lipid signaling. Connective tissue proteins and proteins controlling the degradation of such tissues, including two different matrix metalloprotease proteins, MMP8 and MMP9, were among the significantly changed enzymes and were identified as important key players in the pathways. Conclusion: Exposure to mild-steel welding fume particles causes measurable changes on the proteome level in nasal lavage matrix in exposed welders, although no clinical symptoms were manifested. The results suggested that the exposure causes an immediate effect on the proteome level involving acute phase proteins and mediators regulating lipid signaling Proteases involved in maintaining the balance between the formation and degradation of extracellular matrix proteins are important key proteins in the induced effects. ; Funding Agencies|Swedish Research Council for Health, Working Life and Welfare [FAS2006-0803]; Swedish Governmental Funding for Clinical Research; Skane County Councils research and development foundation (ALF); FORTE

BACKGROUND: In December 2013, it was discovered that drinking water supplied to one third of the households in Ronneby, southern Sweden, was highly contaminated by PFAS (sum level >10,000 ng/L) originated from firefighting foams used at a nearby military airport. OBJECTIVES: To report serum PFAS levels of Ronneby residents participating in a biomonitoring program, and to describe the variation by age, sex and calendar period for residential exposure. In addition, a reference group living in a neighboring municipality without PFAS contaminated drinking water was examined. METHODS: Blood samples and demographic data were collected for 3297 Ronneby residents and 226 individuals from the reference group. Yearly residence addresses were available for 3086 Ronneby residents from the national population registry. Serum concentrations of PFHxS, PFOS and PFOA were determined in all participants, with additional PFHpA, PFNA and PFDA in subsets of the participants. RESULTS: The population geometric means for serum PFHxS, PFOS and PFOA were 114, 135 and 6.8 ng/mL for all Ronneby residents, i.e.135, 35 and 4.5 times higher than for the reference group. Ronneby residents who resided in the area with contaminated water supply during 2005-2013 showed much higher PFAS levels in 2014 than those exposed only before 2005. Ronneby residents who never resided in the area with contaminated water supply also had higher serum PFAS levels than the reference group. All three PFAS were highly correlated (rs > 0.9 for each pair). Serum PFAS levels were lowest in teenage years and then increased with age. Adult females had lower PFAS levels on average than males under the age of 60 but higher above 60. DISCUSSION: The results reveal high serum PFAS levels dominated by PFHxS and PFOS in the Ronneby residents highly exposed to PFAS originated from firefighting foams. The PFAS exposure in Ronneby permits studies of associations to a range of health parameters, as well as studies of the toxicokinetics of PFAS exposure.

WOS: 000319871200001 ; PubMed ID: 23198723 ; Aims: Urinary 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) is a widely used biomarker of oxidative stress. However, variability between chromatographic and ELISA methods hampers interpretation of data, and this variability may increase should urine composition differ between individuals, leading to assay interference. Furthermore, optimal urine sampling conditions are not well defined. We performed inter-laboratory comparisons of 8-oxodG measurement between mass spectrometric-, electrochemical- and ELISA-based methods, using common within-technique calibrants to analyze 8-oxodG-spiked phosphate-buffered saline and urine samples. We also investigated human subject- and sample collection-related variables, as potential sources of variability. Results: Chromatographic assays showed high agreement across urines from different subjects, whereas ELISAs showed far more inter-laboratory variation and generally overestimated levels, compared to the chromatographic assays. Excretion rates in timed 'spot' samples showed strong correlations with 24 h excretion (the 'gold' standard) of urinary 8-oxodG (r(p) 0.67-0.90), although the associations were weaker for 8-oxodG adjusted for creatinine or specific gravity (SG). The within-individual excretion of 8-oxodG varied only moderately between days (CV 17% for 24 h excretion and 20% for first void, creatinine-corrected samples). Innovation: This is the first comprehensive study of both human and methodological factors influencing 8-oxodG measurement, providing key information for future studies with this important biomarker. Conclusion: ELISA variability is greater than chromatographic assay variability, and cannot determine absolute levels of 8-oxodG. Use of standardized calibrants greatly improves intra-technique agreement and, for the chromatographic assays, importantly allows integration of results for pooled analyses. If 24 h samples are not feasible, creatinine- or SG-adjusted first morning samples are recommended. ; ECNIS (Environmental Cancer Risk, Nutrition and Individual Susceptibility), a network of excellence operating within the European Union 6th Framework Program, Priority 5:"Food Quality and Safety" [FOOD-CT-2005-513943]; ECNIS2, a coordination and support action within the European Union FP7 Cooperation Theme 2 Food, Agriculture, Fisheries and Biotechnologies; CISBO; Ingeborg; Leo Dannin Foundation; National Science Council, TaiwanNational Science Council of Taiwan [NSC 97-2314-B-040-015-MY3, NSC 100-2628-B-040-001-MY4]; US NIHUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USA [P30ES009089]; Instituto Carlos III division of the Government for Clinical Research [PI-10/00802, RD06/0045/0006]; Generalitat ValencianaGeneralitat Valenciana [ACOM/2012/238]; Swedish Council for Working Life and Social ResearchSwedish Research CouncilSwedish Research Council for Health Working Life & Welfare (Forte); TUBITAK (Technical and Scientific Research Council of Turkey)Turkiye Bilimsel ve Teknolojik Arastirma Kurumu (TUBITAK) [108Y049]; Grant Agency of the Czech RepublicGrant Agency of the Czech Republic [P503/11/0084]; Sahlgrenska University Hospital, Gothenburg; UK Medical Research Council via a People Exchange Programme Research Leader Fellowship award [G1001808/98136] ; Some of the authors of this work were partners in, and this work was partly supported by, ECNIS (Environmental Cancer Risk, Nutrition and Individual Susceptibility), a network of excellence operating within the European Union 6th Framework Program, Priority 5:"Food Quality and Safety" (Contract No. FOOD-CT-2005-513943), and also ECNIS 2 , a coordination and support action within the European Union FP7 Cooperation Theme 2 Food, Agriculture, Fisheries and Biotechnologies.; P Moller and S Loft are supported by CISBO and the Ingeborg and Leo Dannin Foundation.; M-R Chao and C-W Hu acknowledge financial support from the National Science Council, Taiwan (Grants NSC 97-2314-B-040-015-MY3 and NSC 100-2628-B-040-001-MY4).; R Santella acknowledges the contribution of Qiao Wang, and support from US NIH P30ES009089.; G Saez and C Cerda acknowledge financial support from the Instituto Carlos III division of the Government for Clinical Research (Grants PI-10/00802 and RD06/0045/0006) and Grant ACOM/2012/238 from Generalitat Valenciana.; K Broberg, C Lindh, and M Hossain acknowledge financial support from the Swedish Council for Working Life and Social Research; H Orhan and N Senduran acknowledge financial support from TUBITAK (Technical and Scientific Research Council of Turkey), grant number 108Y049.; P Rossner, Jr. and RJ Sram acknowledge support from the Grant Agency of the Czech Republic (P503/11/0084).; L Barregard acknowledges financial support from the Sahlgrenska University Hospital, Gothenburg.; MS Cooke acknowledges support from the UK Medical Research Council via a People Exchange Programme Research Leader Fellowship award (G1001808/98136).