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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

In vitro evaluation of the potential toxic effects of palladium nanoparticles on fibroblasts and lung epithelial cells.

Palladium nanoparticles have been increasingly used in catalytic processes, wastewater treatment, electronics, and biomedicine. However, recent evidence proved that these nanoparticles are able to induce adverse effects both in in vitro and in vivo models. Nevertheless, molecular mechanisms underlying the toxic effects are still poorly understood. Therefore, this study aimed to investigate the potential toxicological mechanisms of palladium nanoparticles assessing their effects on normal diploid rat fibroblast and lung carcinoma human epithelial cell lines. Several endpoints such as cell growth, cell cycle progression, DNA damage, induction of apoptosis, reactive oxygen species production and expression of cell cycle regulatory proteins were evaluated. Results showed that palladium nanoparticles inhibited cell growth in a dose- and time-dependent manner in both cell lines, although with a more evident action on fibroblasts. Interestingly, inhibition of cell growth was not associated with the induction of apoptosis. Cell cycle progression was arrested in the G0/G1 phase and DNA damage was evident in both cell lines even if only a slight increase in the intracellular reactive oxygen species levels was detected. These findings provide valuable insight into understanding the molecular mechanisms responsible of palladium nanoparticles toxicity whose identification is essential to define an adequate risk assessment process.

Occupational risk factors in inflammatory bowel disease.

OBJECTIVE: Crohn's disease and ulcerative colitis are the two main forms of inflammatory bowel disease (IBD). Although the aetiology of IBD is not completely understood, an interaction between genetic and environmental factors has been proposed. In this context, however, environmental epidemiology lacks a comprehensive evaluation of the possible role of occupational exposures in IBD development and progression. Therefore, aim of our review was to evaluate how certain occupational risk factors may affect IBD pathogenesis, clinical history and severity of disease manifestations. MATERIALS AND METHODS: A critical revision of available literature concerning exposure to groups of potential workplace hazardous agents and IBD, as it appears in Medline and Web of knowledge, was performed. RESULTS: The role of workplace exposures to chemical and biological agents, ionizing or non-ionizing radiations, shift-works, indoor, and sedentary works as well as job strain on IBD has been critically revised. However, the limited number of studies addressing these issues prevented us from extrapolating definite conclusions. CONCLUSIONS: Our review pointed out some critical aspects concerning the relationship between occupational factors and IBD, in terms of causative pathways, hazardous exposure, susceptibility and consequences of IBD functional limitations on career choice and fitness for work that need future investigations. Overall, this seems a challenging public health issue, considering the strong IBD impact on patients' quality of life, work productivity and costs to society. Moreover, this review may encourage concerted actions of health care specialists, occupational physicians, employers and IBD workers to plan preventive and protective measures for "healthier patterns of work" for IBD and to develop innovative perspectives for an integrated management of "IBD at work".

Metabolic effects of TiO2 nanoparticles, a common component of sunscreens and cosmetics, on human keratinocytes.

The long-term health risks of nanoparticles remain poorly understood, which is a serious concern given their prevalence in the environment from increased industrial and domestic use. The extent to which such compounds contribute to cellular toxicity is unclear, and although it is known that induction of oxidative stress pathways is associated with this process, the proteins and the metabolic pathways involved with nanoparticle-mediated oxidative stress and toxicity are largely unknown. To investigate this problem further, the effect of TiO2 on the HaCaT human keratinocyte cell line was examined. The data show that although TiO2 does not affect cell cycle phase distribution, nor cell death, these nanoparticles have a considerable and rapid effect on mitochondrial function. Metabolic analysis was performed to identify 268 metabolites of the specific pathways involved and 85 biochemical metabolites were found to be significantly altered, many of which are known to be associated with the cellular stress response. Importantly, the uptake of nanoparticles into the cultured cells was restricted to phagosomes, TiO2 nanoparticles did not enter into the nucleus or any other cytoplasmic organelle. No other morphological changes were detected after 24-h exposure consistent with a specific role of mitochondria in this response.

Hormesis: its impact on medicine and health.

This article offers a broad assessment of the hormetic dose response and its relevance to biomedical researchers, physicians, the pharmaceutical industry, and public health scientists. This article contains a series of 61 questions followed by relatively brief but referenced responses that provides support for the conclusion that hormesis is a reproducible phenomenon, commonly observed, with a frequency far greater than other dose-response models such as the threshold and linear nonthreshold dose-response models. The article provides a detailed background information on the historical foundations of hormesis, its quantitative features, mechanistic foundations, as well as how hormesis is currently being used within medicine and identifying how this concept could be further applied in the development of new therapeutic advances and in improved public health practices.

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.

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.

[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.

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.

Cardiac autonomic regulation after lung exposure to carbon nanotubes.

The ultrafine (UF) component of airborne pollution may impair cardiovascular autonomic control, a high-risk condition for cardiovascular adverse events. Since engineered nanoparticles, such as single-walled carbon nanotubes (SWCNTs) share physicochemical properties with UF, they might have similar adverse effects. Aim of the study was to evaluate arterial baroreflex function (BRF) at baseline, 24 h after the first instillation, immediately before the second one, and 2 weeks later, in adult Wystar-Kyoto conscious rats undergoing two intratracheal instillations of SWCNT (eight rats) or phosphate buffer saline (PBS) (five rats) at 2-week interval. During each session, 30-min continuous recording of arterial pressure and pulse interval was performed by a telemetered catheter implanted in the abdominal aorta of the rats. BRF was studied by the sequence technique. SWCNTs dispersed in PBS (1 mg/ml) were administered immediately after sonication (1 microg/g body weight). A significant decrease in the number of baroreflex sequences (from 498 +/- 27.1 at baseline to 287 +/- 40.2 at the recording performed after 4 weeks; P < 0.05) was observed in SWCNT-instilled rats, whereas no significant change was detected in controls. These data suggest that SWCNTs may alter the BRF, thus affecting the autonomic cardiovascular control regulation.