Multiwalled carbon nanotubes (MWCNTs) have the potential for widespread applications in engineering and materials science. However, because of their needle-like shape and high durability, concerns have been raised that MWCNTs may induce asbestos-like pathogenicity. Although recent studies have demonstrated that MWCNTs induce various types of reactivities, the physicochemical features of MWCNTs that determine their cytotoxicity and carcinogenicity in mesothelial cells remain unclear. Here, we showed that the deleterious effects of nonfunctionalized MWCNTs on human mesothelial cells were associated with their diameterdependent piercing of the cell membrane. Thin MWCNTs (diameter ∼ 50 nm) with high crystallinity showed mesothelial cell membrane piercing and cytotoxicity in vitro and subsequent inflammogenicity and mesotheliomagenicity in vivo. In contrast, thick (diameter ∼ 150 nm) or tangled (diameter ∼ 2-20 nm) MWCNTs were less toxic, inflammogenic, and carcinogenic. Thin and thick MWCNTs similarly affected macrophages. Mesotheliomas induced by MWCNTs shared homozygous deletion of Cdkn2a/2b tumor suppressor genes, similar to mesotheliomas induced by asbestos. Thus, we propose that different degrees of direct mesothelial injury by thin and thick MWCNTs are responsible for the extent of inflammogenicity and carcinogenicity. This work suggests that control of the diameter of MWCNTs could reduce the potential hazard to human health. environmental health | inflammation | nanotoxicology

, a commonly used industrial plasticizer, causes liver tumorigenesis presumably via activation of peroxisome proliferatoractivated receptor alpha (PPARα). The mechanism of DEHP tumorigenesis has not been fully elucidated, and to clarify whether DEHP tumorigenesis is induced via PPARα, we compared DEHP-induced tumorigenesis in wild-type and Pparα-null mice. Mice of each genotype were divided into three groups, and treated for 22 months with diets containing 0, 0.01 or 0.05% DEHP. Surprisingly, the incidence of liver tumors was higher in Pparα-null mice exposed to 0.05% DEHP (25.8%) than in similarly exposed wild-type mice (10.0%). These results suggest the existence of pathways for DEHP-induced hepatic tumorigenesis that are independent of PPARα. The levels of 8-OHdG increased dose-dependently in mice of both genotypes, but the degree of increase was higher in Pparα-null than in wild-type mice. NFκB levels also significantly increased in a dose-dependent manner in Pparα-null mice. The protooncogene c-jun-mRNA was induced, and c-fos-mRNA tended to be induced only in Pparα-null mice fed a 0.05% DEHP-containing diet. These results suggest that increases in oxidative stress induced by DEHP exposure may lead to the induction o f i n f l a m m a t i o n a n d / o r t h e e x p r e s s i o n o f protooncogenes, resulting in a high incidence of tumorigenesis in Pparα-null mice. (J Occup Health 2007; 49: 172-182)

Background Particles and fibres affect human health as a function of their properties such as chemical composition, size and shape but also depending on complex interactions in an organism that occur at various levels between particle uptake and target organ responses. While particulate pollution is one of the leading contributors to the global burden of disease, particles are also increasingly used for medical purposes. Over the past decades we have gained considerable experience in how particle properties and particle-bio interactions are linked to human health. This insight is useful for improved risk management in the case of unwanted health effects but also for developing novel medical therapies. The concepts that help us better understand particles’ and fibres’ risks include the fate of particles in the body; exposure, dosimetry and dose-metrics and the 5 Bs: bioavailability, biopersistence, bioprocessing, biomodification and bioclearance of (nano)particles. This includes the role of the biomolecule corona, immunity and systemic responses, non-specific effects in the lungs and other body parts, particle effects and the developing body, and the link from the natural environment to human health. The importance of these different concepts for the human health risk depends not only on the properties of the particles and fibres, but is also strongly influenced by production, use and disposal scenarios. Conclusions Lessons learned from the past can prove helpful for the future of the field, notably for understanding novel particles and fibres and for defining appropriate risk management and governance approaches.

These findings suggest that 1,2-DCP and/or DCM may cause cholangiocarcinoma in humans.

Objectives-To investigate the prevalence and risk factors of epicondylitis among cooks in nursery schools in a cross sectional study because they are suspected to have strenuous workloads on the hands and arms. Methods-Prevalence of epicondylitis among 209 nursery school cooks and 366 control workers aged 40-59 were studied. Both groups consisted of women workers chosen from 1299 subjects who agreed to participate from 1329 social welfare employees in a city. All workers were interviewed with a questionnaire and had a clinical examination of the tenderness to palpation of epicondyles and epicondylar pain provoked by resisted extension and flexion of the wrist. Results-Nursery school cooks had a significantly higher prevalence of epicondylitis (11.5%) than the controls (2.5%). In a logistic regression model, job title of the cook was also found to have a strong association with epicondylitis (odds ratio (OR) 5.4, 95% confidence interval (95% CI) 2.4 to 11.9) after adjustment for age, body length, and body mass index. Weaker associations were also found between epicondylitis and suspected job stress or workload scores for mechanical workload and psychosocial stressors based on factor analysis. Conclusions-This study supported the hypothesis that nursery school cooks had a higher prevalence of epicondylitis than other workers with less strenuous hand and arm tasks. It was suggested that risk factors of epicondylitis would be multifactorial, including mechanical workload and psychosocial factors. (Occup Environ Med 1998;55:172-179) Keywords: epicondylitis; cooks; cross sectional There have been several studies reporting a higher prevalence of musculoskeletal problems in cooks than in other occupational workers.