Multi-walled carbon nanotube physicochemical properties predict pulmonary inflammation and genotoxicity

<p>Lung deposition of multi-walled carbon nanotubes (MWCNT) induces pulmonary toxicity. Commercial MWCNT vary greatly in physicochemical properties and consequently in biological effects. To identify determinants of MWCNT-induced toxicity, we analyzed the effects of pulmonary exposure to 10 commercial MWCNT (supplied in three groups of different dimensions, with one pristine and two/three surface modified in each group). We characterized morphology, chemical composition, surface area and functionalization levels. MWCNT were deposited in lungs of female C57BL/6J mice by intratracheal instillation of 0, 6, 18 or 54 μg/mouse. Pulmonary inflammation (neutrophil influx in bronchoalveolar lavage (BAL)) and genotoxicity were determined on day 1, 28 or 92. Histopathology of the lungs was performed on day 28 and 92. All MWCNT induced similar histological changes. Lymphocytic aggregates were detected for all MWCNT on day 28 and 92. Using adjusted, multiple regression analyses, inflammation and genotoxicity were related to dose, time and physicochemical properties. The specific surface area (BET) was identified as a positive predictor of pulmonary inflammation on all post-exposure days. In addition, length significantly predicted pulmonary inflammation, whereas surface oxidation (–OH and –COOH) was predictor of lowered inflammation on day 28. BET surface area, and therefore diameter, significantly predicted genotoxicity in BAL fluid cells and lung tissue such that lower BET surface area or correspondingly larger diameter was associated with increased genotoxicity. This study provides information on possible toxicity-driving physicochemical properties of MWCNT. The results may contribute to safe-by-design manufacturing of MWCNT, thereby minimizing adverse effects.</p

Differences in inflammation and acute phase response but similar genotoxicity in mice following pulmonary exposure to graphene oxide and reduced graphene oxide

We investigated toxicity of 2-3 layered >1 μm sized graphene oxide (GO) and reduced graphene oxide (rGO) in mice following single intratracheal exposure with respect to pulmonary inflammation, acute phase response (biomarker for risk of cardiovascular disease) and genotoxicity. In addition, we assessed exposure levels of particulate matter emitted during production of graphene in a clean room and in a normal industrial environment using chemical vapour deposition. Toxicity was evaluated at day 1, 3, 28 and 90 days (18, 54 and 162 μg/mouse), except for GO exposed mice at day 28 and 90 where only the lowest dose was evaluated. GO induced a strong acute inflammatory response together with a pulmonary (Serum-Amyloid A, Saa3) and hepatic (Saa1) acute phase response. rGO induced less acute, but a constant and prolonged inflammation up to day 90. Lung histopathology showed particle agglomerates at day 90 without signs of fibrosis. In addition, DNA damage in BAL cells was observed across time points and doses for both GO and rGO. In conclusion, pulmonary exposure to GO and rGO induced inflammation, acute phase response and genotoxicity but no fibrosis

Influence of lifestyle factors on long-term sickness absence among female healthcare workers:a prospective cohort study

BACKGROUND: While previous research has indicated that unhealthy lifestyle is associated with sickness absence, this association may be confounded by occupational class. To avoid this potential confounding, we examined the association between lifestyle factors (smoking, leisure-time physical activity and body mass index) and the occurrence of long-term sickness absence (LTSA; more than three consecutive weeks of registered sickness absence) within a cohort of female health care workers. METHODS: A total of 7401 employees filled out a questionnaire about their health behaviour and work environment. Subsequently, they were followed for 12 months in a national register on social transfer payments (DREAM register). Cox’s regression analyses, applied to grouped survival data, were used to estimate the prospective association between these lifestyle factors and LTSA. RESULTS: We found significant associations between all three lifestyle factors and risk of LTSA. The strongest lifestyle factor was current smoking, which increased the risk of LTSA by 35% (95% CI: 1.17-1.54) compared to non- smokers. For body mass index, the risk of LTSA increased with the distance away from 18.5 kg/m(2) in either direction (below 18.5 kg/m(2): HR: 1.32 per kg/m(2); 95% CI. 1.06-1.66; above 18.5 kg/m(2): HR: 1.04 per kg/m(2); 95% CI: 1.03-1.05). In other words, the more underweight or overweight the women were, the higher the risk of LTSA. A dose–response relationship was found between LTSA and leisure-time physical activity (trend test p-value = 0.01), so that increasing physical activity results in decreasing risk of LTSA. CONCLUSION: In female healthcare workers, an unhealthy lifestyle (too high/ too low body mass index, smoking, and low physical activity) is associated with higher risk of LTSA

A multilevel study on the association of observer-assessed working conditions with depressive symptoms among female eldercare workers from 56 work units in 10 care homes in Denmark

OBJECTIVES: Eldercare workers in Denmark have a higher prevalence of poor psychological health than other occupational groups. We examined the association between working conditions assessed by trained observers and depressive symptoms assessed by self-report in a study of female Danish eldercare workers. METHODS: Working conditions were observed based on action regulation theory and defined as (1) regulation requirements, a workplace resource providing opportunity for decision-making and skill development and (2) barriers for task completion. We examined the associations of individual and work unit averaged working conditions with depressive symptoms in a sample of 95 individually observed eldercare workers. Further, we examined the association of work unit averaged working conditions with depressive symptoms in a sample of 205 care workers, including both observed and non-observed individuals. We used regression models that allowed for correlations within work units and care homes and adjusted these models for demographics, job characteristics and stressful life events. RESULTS: Higher levels of regulation requirements were associated with lower depressive symptoms at the individual level (p=0.04), but not at the workplace level. Barriers were not associated with depressive symptoms at the individual level. At the workplace level, a higher number of qualitatively different barriers (p=0.04) and a higher number of barriers for equipment use (p=0.03) were associated with lower levels of depressive symptoms in the age and cohabitation adjusted model, however statistical significance was lost in the fully adjusted model. CONCLUSIONS: Low level of regulation requirements was associated with a high level of depressive symptoms. The study highlights the importance of examining both individual and workplace levels of working conditions