A walk in the PARC: developing and implementing 21st century chemical risk assessment in Europe.

Current approaches for the assessment of environmental and human health risks due to exposure to chemical substances have served their purpose reasonably well. Nevertheless, the systems in place for different uses of chemicals are faced with various challenges, ranging from a growing number of chemicals to changes in the types of chemicals and materials produced. This has triggered global awareness of the need for a paradigm shift, which in turn has led to the publication of new concepts for chemical risk assessment and explorations of how to translate these concepts into pragmatic approaches. As a result, next-generation risk assessment (NGRA) is generally seen as the way forward. However, incorporating new scientific insights and innovative approaches into hazard and exposure assessments in such a way that regulatory needs are adequately met has appeared to be challenging. The European Partnership for the Assessment of Risks from Chemicals (PARC) has been designed to address various challenges associated with innovating chemical risk assessment. Its overall goal is to consolidate and strengthen the European research and innovation capacity for chemical risk assessment to protect human health and the environment. With around 200 participating organisations from all over Europe, including three European agencies, and a total budget of over 400 million euro, PARC is one of the largest projects of its kind. It has a duration of seven years and is coordinated by ANSES, the French Agency for Food, Environmental and Occupational Health & Safety.

Diabetes and work: The need of a close collaboration between diabetologist and occupational physician.

AIM: The Italian Society of Occupational Medicine (SIML), the Italian Diabetes Society (SID) and the Association of Diabetologists (AMD) joined a working group that produced a consensus paper aimed to assess the available evidence regarding the interplay between specific working conditions, including shift- and night-time work, working activities at high risk of accidents and work at heights, working tasks requiring high-energy expenditure, working activities at extreme temperatures and diabetes. DATA SYNTHESIS: Diabetes is a group of metabolic disorders caused by defects in insulin secretion and/or action affecting millions of people worldwide, many of whom are or wish to be active members of the workforce. Although diabetes, generally, does not prevent a person from properly performing his/her working tasks, disease complications can significantly compromise a person's ability to work. Therefore, it appears evident the need to understand the relationship between occupational risk factors and diabetes. The working group included in the document some practical recommendations useful to ensure diabetic workers the possibility to safely and effectively undertake their jobs and to adequately manage and treat their disease, also in the workplace. In this perspective concerted action of all the workplace preventive figures, occupational physicians and diabetologists should be strongly encouraged. CONCLUSIONS: Further studies are necessary to define workplace-based interventions, which should be minimally invasive towards the work organization, allowing diabetic workers to fully realize their work skills while improving their wellbeing at work.

Socioeconomic disparities in clinical trials on Alzheimer's disease: a systematic review.

BACKGROUND AND PURPOSE: There is now a wide consensus at recognizing social and economic circumstances as main determinants of an individual's health status. Nevertheless, characteristics relating to socioeconomic status (SES) are poorly described in research reports. The aim of the present review was to verify whether the SES of participants is adequately reported in interventional studies targeting Alzheimer's disease (AD), and to explore the impact of SES proxy measures on the efficacy of the considered medications. METHODS: A systematic review of available randomized controlled trials (RCTs) on the currently marketed drugs for AD (i.e. cholinesterase inhibitors and memantine) was conducted by performing a structured search on PubMed and the Cochrane databases. The following indicators of SES were considered in the retained studies: (i) educational level, (ii) lifetime job category, (iii) income and (iv) wealth. The study quality was assessed using the Cochrane Risk of Bias Tool for Randomized Controlled Trials. RESULTS: A total of 48 articles were finally selected. Overall, only eight RCTs reported data concerning the four considered SES indicators. Indeed, only information pertaining to the educational level of participants was provided. Only one RCT (n = 60) performed ad hoc, secondary analyses accounting for the SES of participating subjects. CONCLUSIONS: The research and clinical relevance of SES has mistakenly been overlooked by the vast majority of RCTs on AD. A greater effort should be made to collect and report data on those SES indicators that may significantly affect the clinical manifestations and trajectories of patients with cognitive disturbances.

Carmine Melino and the Occupational Medicine.

This short article, which describes the significant contribution Prof. Carmine Melino made to Occupational Medicine, underlines the Professor's great interest in this field and his outstanding ability in combining the lessons of the past with the most innovative aspects of this discipline.

Toxicological effects of titanium dioxide nanoparticles: a review of in vitro mammalian studies.

BACKGROUND AND OBJECTIVE: Recent rapid advances in nanotechnology raise concerns about development, production route, and diffusion in industrial and consumer products of titanium dioxide nanoparticles (TiO2-NPs). In fact, compared to recent increase in applications of this nanomaterial, the health effects of human exposure have not been systematically investigated. The aim of this review was to provide a comprehensive overview on the current knowledge regarding the effects of TiO2-NPs on mammalian cells. EVIDENCE AND INFORMATION SOURCES: This review is based on an analysis of the current literature on this topic. STATE OF THE ART: Fine TiO2 particles have been considered as safe and to pose little risk to humans, suggesting that exposure to this material is relatively harmless. However, available data in the literature showed that TiO2-NPs can cause several adverse effects on mammalian cells such as increase of reactive oxygen species (ROS) production and cytokines levels, reduction of cell viability and proliferation, induction of apoptosis and genotoxicity. PERSPECTIVES AND CONCLUSIONS: Additional research is needed to obtain up-to-date knowledge on health effects of TiO2-NPs and to avoid any potential risk correlated to their exposure. Consequently, future studies need to: (1) use an homogeneous and rigorous exposure classification to clarify how the physicochemical properties of TiO2-NPs correlate with their toxicological effects; (2) assess the potential adverse effects of low level exposures to TiO2-NPs, as most of the information currently available originates from studies in which exposure levels were excessively and unrealistically high; (3) identify the possible roles of TiO2-NPs in genotoxicity and carcinogenicity (4) carry out epidemiologic studies of exposed workers to provide an assessment of possible risks correlated to the occupational exposure to TiO2-NPs.

Shift or night shift work and dementia risk: a systematic review.

OBJECTIVE: Dementia is a neurodegenerative disorder characterized by a progressive decline in multiple cognitive domains. Individual and/or environmental risk factors, i.e., aging, are involved in its pathogenesis. It is possible that shift and night works, affecting circadian rhythms, may contribute to the occurrence/progression of the disease. Therefore, aim of this review was to provide an overview on the possible association between shift or night work and cognitive decline. MATERIALS AND METHODS: A systematic review of literature studies available in PubMed, Scopus, and ISI Web of Science databases, addressing the possible relationship between shift or night work and dementia was performed. RESULTS: Not-homogeneous findings emerged from the revised studies. Some results supported a positive association between shift work and increased risk of dementia, although with a not unique evidence concerning the role of night work schedules and the consequent circadian misalignment in disease pathogenesis. Cardiometabolic disorders, underlying lifestyles, and additional occupational risk factors, including, psychosocial stress, may act as mediators in the shift work-dementia relationship, that may be overall affected by the individual genetic susceptibility too. Length of employment in shift works was also suggested to be responsible for cognitive damaging effects. CONCLUSIONS: The limited number of available studies, the several and different work schedules analyzed, together with the possible co-exposure to other occupational risk factors prevent to draw conclusions on shift work-dementia relationship. Further research should confirm such association and the causal relation with early cognitive alterations in order to guide suitable occupational risk assessment, as well as to promote healthy lifestyle and occupational management strategies, with the ultimate goal of preventing cognitive decline of shift workers. This may overall support the active aging of the workforce while providing benefits for the public health system.

Inflammatory bowel diseases and work disability: a systematic review of predictive factors.

OBJECTIVE: Inflammatory bowel diseases (IBD), including Crohn's disease (CD) and Ulcerative Colitis (UC), are chronic, relapsing intestinal disorders that may severely compromise patients' labour force participation. In this context, the present review aims to provide an overview on possible IBD pathological, socio-demographic, and treatment-related factors predictive for work disability with the purpose to provide guidance for a successful clinical and occupational management. MATERIALS AND METHODS: A systematic review of PubMed, Scopus, and ISI Web of Science databases was performed to retrieve all the studies addressing IBD-related predictors for work disability. RESULTS: Several factors have been suggested to predict work disability in the 15 revised investigations, although with not homogeneous results. Having CD was reported as a significantly better predictor for permanent work disability compared to UC, maybe in relation to the generally more serious disease course. Activity and severity of IBD, also indicated by the need for surgical treatment and comorbidities, was related to a significantly greater risk for work disability, although the exact role of other variables, i.e., specific symptoms, disease pattern and inflammatory parameters are still unclear. Among demographic factors, a significant predictive role has been suggested for female gender. CONCLUSIONS: Further research seems necessary to confirm the role of IBD related factors on work disability, and on other parameters of work impairment, i.e., absenteeism, presenteeism, activity and productivity loss. Additionally, work disability should be evaluated in relation to specific occupational risk factors. Overall, this may require a multidisciplinary approach aimed to achieve an adequate IBD clinical evaluation and management, an improvement of patients' psychosocial and professional well-being, while appropriately assessing and managing risks in the workplace.

Effects of palladium nanoparticles on the cytokine release from peripheral blood mononuclear cells of non-atopic women.

The object of this study is to determine the cytokine release from PBMCs exposed to Pd model nanoparticles emitted from catalytic converters. PBMCs of 8 healthy non-atopic women were incubated in the presence of Pd nanoparticles (5-10 nm) or salt (potassium hexa-chloropalladate) 10-5 and 10-6 M. Release of cytokines in supernatant of PBMCs was then determined. In cultures without LPS, IL-10 and IL-17 release from PBMCs was inhibited by Pd salt, while Pd nanoparticles inhibited TNF-alpha and IL-17 release. In LPS-stimulated cultures, release of IFN-gamma, TNF-alpha, IL-10 and IL-17 was inhibited by Pd salt, whereas IFN-gamma release was enhanced and TNF-alpha and IL-17 release was inhibited by Pd nanoparticles. In conclusion, Pd salt inhibits cytokine release, whereas Pd nanoparticles exert modulatory effects enhancing the release of IFN-gamma, a Th1 cytokine typical of delayed allergic reactions. This result is interesting considering the increase of allergic contact dermatitis to Pd in people exposed to Pd nanoparticles in urban environments.

Incidence of metabolic syndrome among night-shift healthcare workers.

OBJECTIVE: Night-shift work is associated with ischaemic cardiovascular disorders. It is not currently known whether it may be causally linked to metabolic syndrome (MS), a risk condition for ischaemic cardiovascular disorders. The syndrome presents with visceral obesity associated with mild alterations in glucidic and lipidic homeostasis, and in blood pressure. The aim of this study was to assess whether a causal relationship exists between night-shift work and the development of MS. METHODS: Male and female nurses performing night shifts, free from any component of MS at baseline, were evaluated annually for the development of the disorder during a 4-year follow-up. Male and female nurses performing daytime work only, visited during the same time period, represented the control group. RESULTS: The cumulative incidence of MS was 9.0% (36/402) among night-shift workers, and 1.8% (6/336) among daytime workers (relative risk (RR) 5.0, 95% CI -2.1 to 14.6). The annual rate of incidence of MS was 2.9% in night-shift workers and 0.5% in daytime workers. Kaplan-Meier survival curves of the two groups were significantly different (log-rank test; p<0.001). Multiple Cox regression analysis (forward selection method based on likelihood ratio) showed that among selected variables (age, gender, smoking, alcohol intake, familiar history, physical activity, and work schedule) the only predictors of occurrence of MS were sedentariness (hazard ratio (HR) 2.92; 95% CI 1.64 to 5.18; p = 0.017), and night-shift work (HR 5.10; 95% CI 2.15 to 12.11; p<0.001). CONCLUSIONS: The risk of developing MS is strongly associated with night-shift work in nurses. Medical counselling should be promptly instituted in night-shift workers with the syndrome, and in case of persistence or progression, a change in work schedule should be considered.

[Health effects of engineered nanomaterials]. / Effetti sulla salute dei nanomateriali ingegnerizzati.

Nanotechnology--the manipulation of matter on a near-atomic scale to produce new structures, materials and devices--offers the promise of unprecedented scientific advancement for sectors, such as medicine, consumer products, energy, and materials. Nanotechnology has the power not only to improve existing technologies, but to dramatically enhance the effectiveness of new applications. While nanomaterials present seemingly limitless possibilities, they bring with them new challenges to understanding, predicting, and managing potential safety and health risk to workers. On the basis of available knowledge on ultrafine particles (non-engineered nanoparticles) and on preliminary data on engineered nanoparticles, it may be postulated a potential health risk by these materials. A precautionary approach in occupational setting is therefore needed.

Enhanced morphological transformation of human lung epithelial cells by continuous exposure to cellulose nanocrystals.

Cellulose nanocrystals (CNC), also known as nanowhiskers, have recently gained much attention due to their biodegradable nature, advantageous chemical and mechanical properties, economic value and renewability thus making them attractive for a wide range of applications. However, before these materials can be considered for potential uses, investigation of their toxicity is prudent. Although CNC exposures are associated with pulmonary inflammation and damage as well as oxidative stress responses and genotoxicity in vivo, studies evaluating cell transformation or tumorigenic potential of CNC's were not previously conducted. In this study, we aimed to assess the neoplastic-like transformation potential of two forms of CNC derived from wood (powder and gel) in human pulmonary epithelial cells (BEAS-2B) in comparison to fibrous tremolite (TF), known to induce lung cancer. Short-term exposure to CNC or TF induced intracellular ROS increase and DNA damage while long-term exposure resulted in neoplastic-like transformation demonstrated by increased cell proliferation, anchorage-independent growth, migration and invasion. The increased proliferative responses were also in-agreement with observed levels of pro-inflammatory cytokines. Based on the hierarchical clustering analysis (HCA) of the inflammatory cytokine responses, CNC powder was segregated from the control and CNC-gel samples. This suggests that CNC may have the ability to influence neoplastic-like transformation events in pulmonary epithelial cells and that such effects are dependent on the type/form of CNC. Further studies focusing on determining and understanding molecular mechanisms underlying potential CNC cell transformation events and their likelihood to induce tumorigenic effects in vivo are highly warranted.

Distribution and elimination of palladium in male wistar rats following 14-day oral exposure in drinking water.

The Pd tissue distribution and elimination in rats following oral exposure in drinking water of dipotassium hexachloropalladate at doses of 100 or 250 ng/ml for 14 d were determined. The sector field inductively coupled plasma mass spectrometry used for Pd quantification showed the adequate sensitivity (10 ng/l) and accuracy (96-105%), and all the more in consideration of the very low levels of Pd accumulated. Tissues were taken and analyzed after 14 d. The tissue containing the highest Pd concentration was the kidney (4 ng/g dry weight in controls and 75 ng/g dry weight at the maximum dose), with left and right kidneys showing a comparable accumulation. The Pd kidney levels rose, but not significantly, with the administered dose. None of the other organs (liver, lung, spleen, adrenal glands, and bones) appeared to accumulate Pd, even at the highest dose. At the 250-ng/ml dose, small amounts of Pd were found in serum (0.27 ng/ml vs. 0.19 ng/ml in controls), while they were higher in urine (1.2 ng/ml vs. 0.16 ng/ml in controls) and in feces (3,231 ng/g dry weight vs. 69 ng/g dry weight in controls). Feces were the main excretion route for Pd, with a significant linear correlation with exposed dose, which is likely due to low intestinal absorption of Pd.

Chemical hazard for dental hygienists: a systematic review.

OBJECTIVE: Dental hygienists (DHs) are professionals responsible for oral health. They deal with professional oral hygiene, counselling, and screening patients for oral health, as well as preventing and treating oral diseases. However, DH responsibilities and duties may vary worldwide, characterising changeable occupational exposure scenarios and making it difficult to achieve a suitable evaluation of workplace risks, particularly regarding chemical exposure. Therefore, the aim of the present work was to provide a comprehensive overview on the current knowledge on DH chemical risks. MATERIALS AND METHODS: According to the PRISMA guidelines, a systematic review of PubMed, Scopus, and Isi Web of Knowledge databases was performed to retrieve all articles assessing DH occupational chemical exposures. RESULTS: Fragmented data are currently available on DH chemical risk, due to the limited number of studies on the topic and few DHs enrolled, as well as their frequent assimilation to other oral healthcare professionals. The majority of the retrieved investigations focused on possible hypersensitivity reactions caused by natural rubber latex exposure, but not on potential risks derived from other currently employed substances or innovative wide-spreading compounds. CONCLUSIONS: Future research should be focused on assessing DH chemical risks according to a more comprehensive and toxicologically standardised approach to achieve an appropriate awareness among the DH workforce concerning the possibility for hazardous exposure and adverse health effects. Overall, this may lead to the adoption/implementation of adequate preventive measures to protect the health and safety of these oral healthcare professionals.

Effects of sub-chronic exposure to palladium (as potassium hexachloro-palladate) on cytokines in male Wistar rats.

Palladium (Pd) is a heavy metal belonging to the platinum group elements. It has been shown that Pd and its compounds can cause sensitization, asthma and dermatologic disorders. In this study, Wistar rats were exposed for 3 months to 0, 1, 10, 100, and 250 ng/ml of Pd (as potassium hexachloro-palladate) in drinking water. At the end of exposure, possible changes in two type-1 cytokines [interleukin (IL)-2, interferon (INF)-gamma] and one type-2 cytokine (IL-4) in the serum were measured. After the sub-chronic exposure, analysis of variance of IL-2 and INF-gamma response shows that the difference between mean values in the groups of animals exposed reaches statistical significance for IL-2 (P = 0.001), showing a J-shaped dose-response relationship. At the higher dose of 250 ng/ml Pd, it was observed a significant increase in IL-2 production when compared with the controls. Furthermore at 1 and 10 ng/ml of Pd we observed an increase of INF-gamma production that was significant at 100 ng/ml of Pd, while at the higher dose of 250 ng/ml of Pd the response was indistinguishable from the control. At the doses investigated, Pd has been shown not to determine a modification of IL-4 response (P = 0.10). These preliminary findings indicate the need to carry out further investigations regarding the effect of other Pd compounds and the measurement of other types of cytokines both in the animal model used in our study and other models.

Biological monitoring of workers exposed to engineered nanomaterials.

As the number of nanomaterial workers increase there is need to consider whether biomonitoring of exposure should be used as a routine risk management tool. Currently, no biomonitoring of nanomaterials is mandated by authoritative or regulatory agencies. However, there is a growing knowledge base to support such biomonitoring, but further research is needed as are investigations of priorities for biomonitoring. That research should be focused on validation of biomarkers of exposure and effect. Some biomarkers of effect are generally nonspecific. These biomarkers need further interpretation before they should be used. Overall biomonitoring of nanomaterial workers may be important to supplement risk assessment and risk management efforts.

Palladium nanoparticle effects on endocrine reproductive system of female rats.

The widespread industrial application of nanomaterials (NMs) has dramatically increased the likelihood of environmental and occupational exposure of humans to such xenobiotics. This issue, together with the increasing public health interest in understanding the effects of chemicals on endocrine system, encouraged to investigate the disruptive potential of NMs on the endocrine function. Therefore, the aim of this study was to evaluate the effects of palladium nanoparticles (Pd-NPs) on the female reproductive system of Wistar rats, intravenously exposed to different doses (0.12, 1.2, and 12 µg/kg), through the assessment of possible quantitative changes in the serum concentrations of several sex hormones. Our results demonstrated that the highest exposure doses significantly reduced the estradiol and testosterone concentrations, while increased the luteinizing hormone levels in treated animals compared to controls. Such alterations are indicative for an abnormal reproductive axis function. However, further investigations are needed to clarify the role of the different NP physicochemical properties in determining such effects, and possible underlining molecular mechanisms, as well as their relevance for the development of diseases in the female reproductive system. Overall, this may be helpful to define accurate risk assessment and management strategies to protect the health of the general and occupational populations exposed to Pd-NPs.

Subchronic exposure to palladium nanoparticles affects serum levels of cytokines in female Wistar rats.

Recently, palladium nanoparticles (PdNPs) have been increasingly used in many industrial sectors, and this has led to a significant release of nano-sized palladium particles into the environment. However, despite the increase in occupational and general population exposure, information on the potential adverse effects of these PdNPs is still limited and their impact on the immune system constitutes a major health concern. Therefore, the aim of this study was to investigate the potential adverse effects induced by subchronic intravenous administration of PdNPs on the immune system of female Wistar rats by evaluating alterations in Interleukin (IL)-1α, IL-2, IL-4, IL-6, IL-10, IL-12, granulocyte-macrophage colony-stimulating factor (GM-CSF), Interferon (INF)-γ, and Tumor Necrosis Factor (TNF)-α serum levels. Exposed and control animals were randomly divided into five groups (0, 0.012, 0.12, 1.2, and 12 µg PdNPs per kg body weight) which were treated with repeated intravenous injections of vehicle or PdNPs (on day 1, 30, and 60). Subchronic exposure to PdNPs induced a decreasing trend in serum levels in most of the cytokines investigated, with the highest concentration (12 µg/kg) determining significant inhibitory effects. Overall, these results showed that PdNPs are able to alter cytokine serum levels in subchronically treated Wistar rats, suggesting a possible impact of these xenobiotics on the immune system after long-term exposures.

[Modifications of hepatic transaminases in workers exposed to low doses of isopropanol]. / Modificazioni delle transaminasi epatiche in lavoratori esposti a basse dosi di isopropanolo.

Isopropanol (IPA) is a volatile solvent that is used in many industrial process. The major symptoms of acute isopropanol toxicity include dizziness, incoordination, headache, hypothermia, eye ataxia, irritation of upper respiratory tract and shortness of breath. Vomiting, hematemesis, diarrhoea and hypotension may occur following accidental ingestion of IPA. No data regarding subchronic or chronic toxicity of IPA were identified. The aim of this study was to measure the serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and of gamma-glutamyltransferase (gamma-GT) of the last five years in 40 printer workers after the removal of IPA from the industry. The serum levels of ALT, AST and gamma-GT were higher in the exposed workers than in non exposed. In conclusion, the results of this study show that the removal of IPA from the industry had a positive health effect improving the hepatic function of the workers.

[Application and effects of smoking ban in bars and restaurants of Rome]. / Applicazione ed effetti del divieto di fumare (Legge n. 3 del 16/01/2003) nei bar e ristoranti di Roma.

Both active and passive tobacco smoke is carcinogenic. In the last years the most important countries of European Community developed and passed smoke-free public places and smoke-free workplace legislations. The aim of this study was to investigate the real application of smoking ban in bars and restaurants of Rome and to value social, economic and health effects caused by the application of the law. The study was carried out in 200 public places (100 restaurants and 100 bars) with an inspection of the sites and the administration of a questionnaire to the managers of the public places. Results demonstrate that smoking ban in public places is widely respected and that the application of the law had a very positive impact on the quality of life and health of workers and general population.

[Prevalence and risk factors of urinary incontinence in female workers of hotels]. / Prevalenza e fattori di rischio dell'incontinenza urinaria nelle lavoratrici del settore alberghiero.

The International Continence Society defines urinary incontinence (UI) as "a condition in which involuntary loss of urine is a social or hygienic problem and is objectively demonstrable". There are three different jorms of UI. stress urinary incontinence, urge urinary incontinence and mixed incontinence. The aim of this study was to investigate the prevalence of UI in a group of female workers in the hotel sector. The International Consultation on Incontinence Questionnaire Urinary Incontinence short form (ICIQ-UI Short Form) was administered to all female workers and data were collected about age, body mass index, number of vaginal and Caesarean delivery. Results showed a prevalence of UI widely bigger in the plans waitress than in video display terminal workers and suggest the hypothesis that manual handling of loads representing a possible occupational risk for UI.