Recent Research Activities from the EOM Working Groups

Evaluation of exposure biomarkers in offshore workers exposed to low benzene and toluene concentrations

Nancy B. Hopf, Jorunn Kirkeleit, Magne Bråtveit, Paul Succop, bGlenn Talaska, Bente E. Moen

International Archives of Occupational and Environmental Health, April 2012, Volume 85, Issue 3, pp 261-271

Purpose: Characterize ethylbenzene and xylene air concentrations, and explore the biological exposure markers (urinary t,t-muconic acid (t,t-MA) and unmetabolized toluene) among petroleum workers offshore. Offshore workers have increased health risks due to simultaneous exposures to several hydrocarbons present in crude oil. We discuss the pooled benzene exposure results from our previous and current studies and possible co-exposure interactions.

Methods: BTEX air concentrations were measured during three consecutive 12-h work shifts among 10 tank workers, 15 process operators, and 18 controls. Biological samples were collected pre-shift on the first day of study and post-shift on the third day of the study.

Results: The geometric mean exposure over the three work shifts were 0.02 ppm benzene, 0.05 ppm toluene, 0.03 ppm ethylbenzene, and 0.06 ppm xylene. Benzene in air was significantly correlated with unmetabolized benzene in blood (r = 0.69, p < 0.001) and urine (r = 0.64, p < 0.001), but not with urinary t,t-MA (r = 0.27, p = 0.20). Toluene in air was highly correlated with the internal dose of toluene in both blood (r = 0.70, p < 0.001) and urine (r = 0.73, p < 0.001). Co-exposures were present; however, an interaction of metabolism was not likely at these low benzene and toluene exposures.

Conclusion: Urinary benzene, but not t,t-MA, was a reliable biomarker for benzene at low exposure levels. Urinary toluene was a useful biomarker for toluene exposure. Xylene and ethylbenzene air levels were low. Dermal exposure assessment needs to be performed in future studies among these workers.

Expression of adhesion molecules, monocyte interactions and oxidative stress in human endothelial cells exposed to wood smoke and diesel exhaust particulate matter

Lykke Forchhammer, Steffen Loft, Martin Roursgaard, Yi Cao, Ingunn Skogstad Riddervold, Torben Sigsgaard, Peter Møller

Toxicology Letters, Volume 209, Issue 2, 7 March 2012, Pages 121–128

Toxicological effects of wood smoke particles are less investigated than traffic-related combustion particles. We investigated the effect of wood smoke particles, generated by smouldering combustion conditions, on human umbilical endothelial cells (HUVECs) co-cultured with or without monocytic THP-1 cells. Standard reference material (SRM) 2975 diesel exhaust particles were used as benchmark particles. Wood smoke particles at 50 ?g/ml or 100 ?g/ml caused adhesion of THP-1 monocytes onto HUVECs in co-cultures, whereas SRM2975 had no such effect. Both types of particles from 1 ?g/ml increased VCAM-1 expression on HUVECs in mono-cultures. However, only the exposure to wood smoke particles was associated with increased expression of TNF and IL8 mRNA in THP-1 cells. We found no effect on the intracellular production of reactive oxygen species by the fluorescent probe DCFH-DA, whereas especially the wood smoke particles caused increased level of DNA strand breaks and oxidised guanines at concentrations with low cytotoxicity. In conclusion, our results indicate that the adherence of monocytes on endothelial cells in wood smoke particle exposed cultures depend on activation of both cell types.

Controlled human wood smoke exposure: oxidative stress, inflammation and microvascular function

Lykke Forchhammer, Peter Møller, Ingunn Skogstad Riddervold, Jakob Bønløkke, Andreas Massling, Torben Sigsgaard and Steffen Loft

Particle and Fibre Toxicology, 2012, 9:7

Background: Exposure to wood smoke is associated with respiratory symptoms, whereas knowledge on systemic effects is limited. We investigated effects on systemic inflammation, oxidative stress and microvascular function (MVF) after controlled wood smoke exposure.

Methods: In a randomised, double-blinded, cross-over study 20 non-smoking atopic subjects were exposed at rest to 14, 220, or 354 ?g/m3 of particles from a well-burning modern wood stove for 3 h in a climate controlled chamber with 2 week intervals. We investigated the level of oxidatively damaged DNA, inflammatory markers and adhesion molecules before and 0, 6 and 20 h after exposure. Six h after exposure we measured MVF non-invasively by digital peripheral artery tonometry following arm ischemia.

Results: The MVF score was unaltered after inhalation of clean air (1.58 ± 0.07; mean ± SEM), low (1.51 ± 0.07) or high (1.61 ± 0.09) concentrations of wood smoke particles in atopic subjects, whereas unexposed non-atopic subjects had higher score (1.91 ± 0.09). The level of oxidatively damaged DNA, mRNA of ITGAL, CCL2, TNF, IL6, IL8, HMOX1, and OGG1 and surface marker molecules ICAM1, ITGAL and L-selectin in peripheral blood mononuclear cells were not affected by inhalation of wood smoke particles.

Conclusions: Exposure to wood smoke had no effect on markers of oxidative stress, DNA damage, cell adhesion, cytokines or MVF in atopic subjects.

Notification of occupational disease and the risk of work disability: a two-year follow-up study

Kolstad HA, Christensen MV, Jensen LD, Schlünssen V, Thulstrup AM, Bonde JP

Scandinavian Journal of Work, Environment & Health [2012], doi:10.5271/sjweh.3336

OBJECTIVES: The aim of this study was to analyze if notification of an occupational disease increases the risk of work disability.

METHODS: We included 2304 patients examined at the Department of Occupational Medicine, Aarhus University Hospital, 1998-2005 and followed them for two years. A total of 564 patients were notified of an occupational disease when they were examined at baseline and 1740 patients were not. We obtained weekly information on sick payment, unemployment payment, disability pension, rehabilitation benefit, and other social benefits during the two years of follow-up from a national register. Using Cox regression models, we analyzed notification and adjusted hazard ratios (HR (adj)) of work disability (defined as >12 weeks of social benefits during the first or second year of follow-up).

RESULTS: Prior to notification, notified patients had higher levels of clinical, occupational, and social characteristics that predict poorer vocational prognosis. Analyses that adjusted for these differences showed an increased risk of work disability following notification for patients who were working when notified at baseline (HR (adj)1.46, 95% CI 1.17-1.82). No effect was seen for patients who were not working.

CONCLUSIONS: Notification of an occupational disease may, as an unintended side effect, increase the risk of work disability. A cautious interpretation is warranted because data analyses may not fully have accounted for the poorer vocational prognosis already present at baseline.