Human biomonitoring and personal air monitoring. An integrated approach to assess exposure of stainless-steel welders to metal-oxide nanoparticles.

In welding, there is a potential risk due to metal-oxide nanoparticles (MONPs) exposure of workers. To investigate this possibility, the diameter and number particles concentration of MONPs were evaluated in different biological matrices and in personal air samples collected from 18 stainless-steel welders and 15 unexposed administrative employees engaged in two Italian mechanical engineering Companies. Exhaled breath condensate (EBC) and urine were sampled at pre-shift on 1st day and post-shift on 5th day of the workweek, while plasma and inhalable particulate matter (IPM) at post-shift on 5th day and analysed using the Single Particle Mass Spectrometry (SP-ICP-MS) technique to assess possible exposure to Cr2O3, Mn3O4 and NiO nanoparticles (NPs) in welders. The NPs in IPM at both Companies presented a multi-oxide composition consisting of Cr2O3 (median, 871,574 particles/m3; 70 nm), Mn3O4 (median, 713,481 particles/m3; 92 nm) and NiO (median, 369,324 particles/m3; 55 nm). The EBC of welders at both Companies showed Cr2O3 NPs median concentration significantly higher at post-shift (64,645 particles/mL; 55 nm) than at pre-shift (15,836 particles/mL; 58 nm). Significantly lower Cr2O3 NPs median concentration and size (7762 particles/mL; 44 nm) were observed in plasma compared to EBC of welders. At one Company, NiO NPs median concentration in EBC (22,000 particles/mL; 65 nm) and plasma (8248 particles/mL; 37 nm) were detected only at post-shift. No particles of Cr2O3, Mn3O4 and NiO were detected in urine of welders at both Companies. The combined analyses of biological matrices and air samples were a valid approach to investigate both internal and external exposure of welding workers to MONPs. Overall, results may inform suitable risk assessment and management procedures in welding operations.

The endocrine disrupting effects of nanoplastic exposure: A systematic review.

Good mechanical properties and low costs have led to a global expansion of plastic production and use. Unfortunately, much of this material can be released into the environment as a waste product and cleaved into micro- and nanoplastics (NPs) whose impact on the environment and human health is still largely unknown. Considering the growing worldwide awareness on exposure to chemicals that can act as endocrine disruptors, a systematic review was performed to assess the impact of NPs on the endocrine function of in vitro and in vivo models. Although a limited number of investigations is currently available, retrieved findings showed that NPs may induce changes in endocrine system functionality, with evident alterations in reproductive and thyroid hormones and gene expression patterns, also with a trans-generational impact. Nanoplastic size, concentration, and the co-exposure to other endocrine disrupting pollutants may have an influencing role on these effects. Overall, although it is still too early to draw conclusions regarding the human health risks derived from NPs, these preliminary results support the need for further studies employing a wider range of plastic polymer types, concentrations, and time points as well as species and life stages to address a great variety of endocrine outcomes and to achieve a broader and shared consensus on the role of NPs as endocrine disruptors.

Health Promotion Interventions in Occupational Settings: Fact-finding Survey among Italian Occupational Physicians.

BACKGROUND:  Occupational Physicians (OPs) are essential for health promotion (HP) at the workplace, although their HP knowledge and perception are still under-searched. METHODS: Between September and December 2022, the Italian Society of Occupational Medicine (SIML) - HP working group performed a cross-sectional survey on SIML-OPs aimed to address their approach, experience, strategies, and needs concerning HP plans. RESULTS: A total of 336 OPs completed the questionnaire. Regarding HP's OP perception, this was reported as a social investment (34.45%) and shared responsibility for all the company's preventive figures (30.18%). Over half of the enrolled OPs declared to have been involved as HP plans' organizers (57.30%) or collaborators (54.80%) in the previous 5 years. The greatest percentage of organizers were in the younger age groups (40-59 years; 50%). Additionally, following a more limited number of companies, prevalently of medium-high dimensions, and more than 500 workers were positively associated with greater OP participation in HP initiatives. Promoting healthy lifestyles was the main target of the HP plans (88.64%). Interdisciplinary collaboration, OP training on HP procedures and information on the targeted population have been reported as effective issues to support an active engagement of OPs in HP. CONCLUSIONS: A general interest of the Italian OPs with respect to HP was demonstrated, however, information on the potential benefits of HP in workplace aligned with OP perceptions and needs seem necessary to successfully implement HP interventions.

HBM4EU chromates study - Usefulness of measurement of blood chromium levels in the assessment of occupational Cr(VI) exposure.

Occupational exposures to hexavalent Chromium (Cr(VI)) can occur in welding, hot working stainless steel processing, chrome plating, spray painting and coating activities. Recently, within the human biomonitoring for Europe initiative (HBM4EU), a study was performed to assess the suitability of different biomarkers to assess the exposure to Cr(VI) in various job tasks. Blood-based biomarkers may prove useful when more specific information on systemic and intracellular bioavailability is necessary. To this aim, concentrations of Cr in red blood cells (RBC-Cr) and in plasma (P-Cr) were analyzed in 345 Cr(VI) exposed workers and 175 controls to understand how these biomarkers may be affected by variable levels of exposure and job procedures. Compared to controls, significantly higher RBC-Cr levels were observed in bath plating and paint application workers, but not in welders, while all the 3 groups had significantly greater P-Cr concentrations. RBC-Cr and P-Cr in chrome platers showed a high correlation with Cr(VI) in inhalable dust, outside respiratory protective equipment (RPE), while such correlation could not be determined in welders. In platers, the use of RPE had a significant impact on the relationship between blood biomarkers and Cr(VI) in inhalable and respirable dust. Low correlations between P-Cr and RBC-Cr may reflect a difference in kinetics. This study showed that Cr-blood-based biomarkers can provide information on how workplace exposure translates into systemic availability of Cr(III) (extracellular, P-Cr) and Cr(VI) (intracellular, RBC-Cr). Further studies are needed to fully appreciate their use in an occupational health and safety context.

HBM4EU chromates study - Overall results and recommendations for the biomonitoring of occupational exposure to hexavalent chromium.

Exposure to hexavalent chromium [Cr(VI)] may occur in several occupational activities, e.g., welding, Cr(VI) electroplating and other surface treatment processes. The aim of this study was to provide EU relevant data on occupational Cr(VI) exposure to support the regulatory risk assessment and decision-making. In addition, the capability and validity of different biomarkers for the assessment of Cr(VI) exposure were evaluated. The study involved nine European countries and involved 399 workers in different industry sectors with exposures to Cr(VI) such as welding, bath plating, applying or removing paint and other tasks. We also studied 203 controls to establish a background in workers with no direct exposure to Cr(VI). We applied a cross-sectional study design and used chromium in urine as the primary biomonitoring method for Cr(VI) exposure. Additionally, we studied the use of red blood cells (RBC) and exhaled breath condensate (EBC) for biomonitoring of exposure to Cr(VI). Personal measurements were used to study exposure to inhalable and respirable Cr(VI) by personal air sampling. Dermal exposure was studied by taking hand wipe samples. The highest internal exposures were observed in the use of Cr(VI) in electrolytic bath plating. In stainless steel welding the internal Cr exposure was clearly lower when compared to plating activities. We observed a high correlation between chromium urinary levels and air Cr(VI) or dermal total Cr exposure. Urinary chromium showed its value as a first approach for the assessment of total, internal exposure. Correlations between urinary chromium and Cr(VI) in EBC and Cr in RBC were low, probably due to differences in kinetics and indicating that these biomonitoring approaches may not be interchangeable but rather complementary. This study showed that occupational biomonitoring studies can be conducted successfully by multi-national collaboration and provide relevant information to support policy actions aiming to reduce occupational exposure to chemicals.

Towards a toxic-free environment: perspectives for chemical risk assessment approaches.

Regulatory frameworks to control chemical exposure in general living and occupational environments have changed exposure scenarios towards a widely spread contamination at relatively low doses in developed countries. In such evolving context, some critical aspects should be considered to update risk assessment and management strategies. Risk assessment in low-dose chemical exposure scenarios should take advantage of: toxicological investigations on emerging substances of interest, like those recognised as endocrine disruptors or increasingly employed nanoscale materials; human biological monitoring studies aimed to identify innovative biomarkers for known chemical exposure; "omic" technologies useful to identify hazards of chemicals and their modes of action. For updated risk assessment models, suitable toxicological studies, analyses of dose-responses at low-concentrations, environmental and biological monitoring of exposure, together with exposome studies, and the proper definition of susceptible populations may all provide helpful contributions. These may guide defining preventive measures to control the exposure and develop safe and sustainable chemicals by design. Occupational medicine can offer know-how and instruments to understand and manage such evolution towards a toxic-free environment to protect the safety and health of the workforce and, in turn, that of the general population.

Duration of SARS-CoV-2 shedding and infectivity in the working age population: a systematic review and meta-analysis.

BACKGROUND: During the COVID-19 pandemic, working age individuals have been implicated in sustaining the resurgence of SARS-CoV-2 infections, and multiple outbreaks have been observed in several occupational settings. In this regard, Occupational Physicians play a crucial role in the management of infected workers, particularly in the safe return-to-work of subjects after clinical resolution. To this end, knowledge of the duration of the infective phase in the working age population is essential, taking into account previous evidence suggesting that PCR positivity does not coincide with virus viability. METHODS: A systematic review and meta-analysis, searching major scientific databases, including PubMed/MEDLINE, Scopus and Web of Science, were performed in order to synthesize the available evidence regarding the mean and maximal duration of infectivity compared to the mean and maximal duration of viral RNA shedding. A subgroup analysis of the studies was performed according to the immunocompetent or immunocompromised immune status of the majority of the enrolled individuals. RESULTS: Twenty studies were included in the final qualitative and quantitative analysis (866 individuals). Overall, a mean duration of RT-PCR positivity after symptom onset was found equal to 27.9 days (95%CI 23.3-32.5), while the mean duration of replicant competent virus isolation was 7.3 days (95%CI 5.7-8.8). The mean duration of SARS-CoV-2 shedding resulted equal to 26.5 days (95%CI 21.4-31.6) and 36.3 days (95%CI 21.9-50.6), and the mean duration of SARS-CoV-2 infectivity was 6.3 days (95%CI 4.9-7.8) and 29.5 days (95%CI 12.5-46.5), respectively considering immunocompetent and immunocompromised individuals. The maximum duration of infectivity among immunocompetent subjects was reported after 18 days from symptom onset, while in immunocompromised individuals it lasted up to 112 days. CONCLUSIONS: These findings suggest that the test-based strategy before return-to-work might not be warranted after 21 days among immunocompetent working age individuals, and could keep many workers out of occupation, reducing their livelihood and productivity.

Spirometric reference values in the occupational medicine practice.

INTRODUCTION: Spirometry is the main pulmonary function test routinely employed in the occupational medicine practice. Its interpretation depends on the choice of the theoretical reference values. Therefore, our objective was to retrospectively evaluate the differences in the spirometric interpretation according to the reference values used. METHODS: A total of 2462 spirometries performed during health surveillance programs were analyzed. Forced vital capacity (FVC), forced expiratory volume in one second (FEV1), and FEV1/FVC ratio were compared according to three different reference values: the European Coal and Steel Community (ECSC) 1971, the European Respiratory Society (ERS) 1993, and the Global Lung Initiative (GLI) 2012. RESULTS: The GLI 2012 provided significantly higher predicted mean FVC and FEV1 values compared to the ERS 1993 and significantly lower compared to the ECSC 1971. The GLI 2012 were able to detect all the obstructive deficits and mixed patterns diagnosed with ECSC 1971 and ERS 1993, in addition to others not diagnosed by these two latter reference values. The number of restrictive patterns identified through the GLI 2012 was significantly reduced and increased compared to those diagnosed using the ECSC 1971 and the ERS 1993, respectively. DISCUSSION: In comparison to the GLI 2012, the ERS 1993 values significantly underestimated obstructive and restrictive alterations. Conversely, the ECSC 1971 significantly underestimated obstructive changes, while overestimated restrictive patterns, compared to GLI. Although the GLI reference values may provide a correct spirometric interpretation, their validation in an Italian worker population is necessary to confirm their possible use in routine occupational health programs.

A critical review of methods for decontaminating filtering facepiece respirators.

Various decontamination methods that may be used to extend respirator inventories have been examined for over a decade. In light of the ongoing coronavirus disease 2019 pandemic, many health-care settings are now implementing these techniques amid respirator shortages. We sought to perform a critical review of the available literature regarding decontamination methods to determine which strategies are effective at inactivating the target organism, preserve performance (filter efficiency and fit) of the respirator, leave no residual toxicity from the treatment, and are fast-acting, inexpensive, and readily available. We also identified areas for future research. We found that ultraviolet germicidal irradiation (UVGI) is the most widely studied method, and treatments are effective at inactivating SARS-CoV-2 without diminishing filtration efficiency or fit. These treatments were found to leave no residual toxicity for the wearer, have a relatively short cycle time of less than 1 h, and existing systems can likely be retrofitted to accommodate this method. Further, UVGI (among other treatment methods) has been recommended by the Centers for Disease Control and Prevention (CDC), Occupational Safety and Health Administration (OSHA), and respirator manufacturers. Methods involving microwave-generated steam also show potential in that they are likely effective against SARS-CoV-2, preserve performance, have no residual toxicity, require a short duration treatment cycle (often less than 10 min), and microwave ovens are inexpensive and readily available. Steam methods are currently recommended by the CDC, OSHA, and manufacturers. These respirator decontamination methods are likely also useful against other viruses or pathogens.

Personalised Medicine: implication and perspectives in the field of occupational health.

"Personalised medicine" relies on identifying and integrating individual variability in genomic, biological, and physiological parameters, as well as in environmental and lifestyle factors, to define "individually" targeted disease prevention and treatment. Although innovative "omic" technologies supported the application of personalised medicine in clinical, oncological, and pharmacological settings, its role in occupational health practice and research is still in a developing phase. Occupational personalised approaches have been currently applied in experimental settings and in conditions of unpredictable risks, e.g.. war missions and space flights, where it is essential to avoid disease manifestations and therapy failure. However, a debate is necessary as to whether personalized medicine may be even more important to support a redefinition of the risk assessment processes taking into consideration the complex interaction between occupational and individual factors. Indeed, "omic" techniques can be helpful to understand the hazardous properties of the xenobiotics, dose-response relationships through a deeper elucidation of the exposure-disease pathways and internal doses of exposure. Overall, this may guide the adoption/implementation of primary preventive measures protective for the vast majority of the population, including most susceptible subgroups. However, the application of personalised medicine into occupational health requires overcoming some practical, ethical, legal, economical, and socio-political issues, particularly concerning the protection of privacy, and the risk of discrimination that the workers may experience. In this scenario, the concerted action of academic, industry, governmental, and stakeholder representatives should be encouraged to improve research aimed to guide effective and sustainable implementation of personalised medicine in occupational health fields.

Setting up a collaborative European human biological monitoring study on occupational exposure to hexavalent chromium.

The EU human biomonitoring initiative, HBM4EU, aims to co-ordinate and advance human biomonitoring (HBM) across Europe. Within its remit, the project is gathering new, policy relevant, EU-wide data on occupational exposure to relevant priority chemicals and developing new approaches for occupational biomonitoring. In this manuscript, the hexavalent chromium [Cr(VI)] study design is presented as the first example of this HBM4EU approach. This study involves eight European countries and plans to recruit 400 workers performing Cr(VI) surface treatment e.g. electroplating or stainless steel welding activities. The aim is to collect new data on current occupational exposure to Cr(VI) in Europe and to test new methods for Cr biomonitoring, specifically the analysis of Cr(VI) in exhaled breath condensate (EBC) and Cr in red blood cells (RBC) in addition to traditional urinary total Cr analyses. Furthermore, exposure data will be complemented with early biological effects data, including genetic and epigenetic effects. Personal air samples and wipe samples are collected in parallel to help informing the biomonitoring results. We present standard operational procedures (SOPs) to support the harmonized methodologies for the collection of occupational hygiene and HBM samples in different countries.

Sub-chronic palladium nanoparticle effects on the endocrine reproductive system of female Wistar rats: Preliminary data.

The technologically interesting properties of palladium nanoparticles (Pd-NPs) allowed their widespread industrial application, although concerns emerged on increasing general and occupational levels of exposure. In this context, to assess the toxicological behavior of Pd-NPs, and particularly their endocrine disruptive potential, has become a public health priority. Therefore, we evaluated Pd-NP impact on the female endocrine reproductive system of Wistar rats sub-chronically treated for 90 days with increasing doses of this xenobiotic (0.12, 1.2, and 12 µg/kg, administered at days 1, 30, and 60 for cumulative doses of 0.36, 3.6, and 36 µg/kg) via the intravenous route. In this regard, we investigated potential alterations in different sex hormone, for example, estradiol, follicle-stimulating hormone (FSH), luteinizing hormone, progesterone, and testosterone, serum concentrations. All treated groups showed significantly greater levels of FSH compared to controls, suggesting a possible impact of Pd-NPs on the regulatory system that controls the normal physiology of female reproductive function. Although relevant, since obtained under sub-chronic, low-dose conditions of exposure resembling those encountered in real-world scenarios, the present results are preliminary and require confirmation as well as identification of the possible underlining molecular mechanisms. From a public and occupational health perspective, implications for the reproductive health of exposed subjects and the next generations of women exposed during their childbearing age or pregnancy should be elucidated. This information is essential to elaborate adequate preventive strategies for assessing and controlling possible Pd-NPs adverse effects on the endocrine system.

[Nanoparticle exposure in research laboratories.] / Esposizione a nanoparticelle nei laboratori di ricerca.

SUMMARY: Aims. A growing number of workers are employed in research laboratories where nanomaterials (NMs) are synthesized, characterized, processed and investigated for their physico-chemical and toxicological properties. To adequately evaluate occupational risks in such contexts, a suitable exposure assessment is necessary. Methods. A critical review of the scientific and grey literature on NM exposure in laboratories has been performed. Results. The evaluation of the exposure, in general, includes a preliminary analysis of the working processes and of the features of NMs employed. Environmental and personal monitoring can be used for a quantitative assessment of the exposure, although the current uncertainties relating to the metrological parameters to be measured and the occupational exposure limits to be compared with collected data make the interpretation of the results and the definition of shared sampling strategies a challenging issue. Conclusions. To date, qualitative information on NM exposure can be used in "control banding" instruments useful for the precautionary assessment and management of risks in research laboratories involved with NMs. Future NM environmental and personal exposure assessments should be pursued to define appropriate monitoring strategies and guide the adoption of appropriate preventive measures to protect the health of workers.

The reference values in the interpretation of toxicological data.

The worldwide gradual expansion of industrialization has led to a dramatic increase in the production and use of chemical substances. This has resulted in a greater dispersion of these elements in the environment and in an increased exposure of the general population and workers. In this scenario, a thorough knowledge of exposure levels is needed in order to assess chemical risks in environmental and occupational settings. Biological monitoring is among the most useful tools for assessing exposure. However, in order to provide really effective guidance in the application/implementation of risk management measures, biomonitoring results need to be compared with appropriate references. Reference values (RVs) are an excellent resource since useful information for a correct interpretation of toxicological data can be obtained by comparing them with biomonitoring results. In the field of public health, this may enable us to identify potential sources of exposure, define the principal and most frequently exploited routes of exposure, and outline chemical absorption. Similarly, in occupational medicine, RVs can be used to give meaning to biomonitoring findings, especially when a biological limit value is not available for the chemical in question. Furthermore, these values are a valid tool for assessing exposure to chemical carcinogens. Therefore, by integrating reference values in an appropriate and complete system of guide values that also includes action levels and biological limit values, we could obtain both an adequate assessment of exposure and a better understanding of toxicological data.

Nanomaterial exposure and sterile inflammatory reactions.

"Sterile inflammation" is a type of pathogen-free inflammation which may be induced by various physical, chemical, or metabolic insults, including environmental particles e.g. silica dioxide crystals and asbestos. The possible role of nanomaterials as danger signals able to trigger sterile inflammatory responses is not yet fully understood. Therefore, the aim of this review was to investigate conditions of sterile inflammation induced by nanomaterial exposure with a specific focus on possible modes of action. Metal-, metal-oxide- and carbon-based nanomaterials may trigger a sterile inflammatory cascade by means of different damage-associated molecular patterns, including chromatin associated protein high-mobility group box-1 secretion, ATP, ADP and adenosine purinergic signaling, interleukin-1α alarmin, and NLPR-3 inflammasome activation. However, such preliminary results do not enable us to draw definite conclusions regarding the sterile inflammatory potential of nanomaterials and possible underlying molecular mechanisms. Therefore, further research is required to understand the complex "interplay" between the multitude of nanomaterial intrinsic or acquired physico-chemical properties and the extremely changeable immunological competence of organisms. The identification of possible nanomaterial modes of action in sterile inflammation could provide early indicators of the biological reactivity of nano-sized chemicals and could direct "safe by design" efforts for improving occupational safety and that of the general population. Moreover, the possible pathological consequences of nanomaterial-induced sterile inflammatory reactions need to be clarified in order to define suitable preventive measures to protect the health of chronically exposed subjects.

Palladium Nanoparticles: Toxicological Effects and Potential Implications for Occupational Risk Assessment.

The increasing technological applications of palladium nanoparticles (Pd-NPs) and their consequent enhancing release into the community and occupational environments, have raised public health concerns regarding possible adverse effects for exposed subjects, and particularly for workers chronically and highly exposed to these materials, whose toxico-kinetic and dynamic behavior remains to be fully understood. Therefore, this review aimed to critically analyze literature data to achieve a more comprehensive knowledge on the toxicological profile of Pd-NPs. Results from available studies demonstrated the potential for these chemicals to affect the ecosystem function, to exert cytotoxic and pro-inflammatory effects in vitro as well as to induce early alterations in different target organs in in vivo models. However, our revision pointed out the need for future studies aimed to clarify the role of the NP physico-chemical properties in determining their toxicological behavior, as well as the importance to carry out investigations focused on environmental and biological monitoring to verify and validate experimental biomarkers of exposure and early effect in real exposure contexts. Overall, this may be helpful to support the definition of suitable strategies for the assessment, communication and management of Pd-NP occupational risks to protect the health and safety of workers.

Nanoparticle Exposure and Hormetic Dose-Responses: An Update.

The concept of hormesis, as an adaptive response of biological systems to moderate environmental challenges, has raised considerable nano-toxicological interests in view of the rapid pace of production and application of even more innovative nanomaterials and the expected increasing likelihood of environmental and human exposure to low-dose concentrations. Therefore, the aim of this review is to provide an update of the current knowledge concerning the biphasic dose-responses induced by nanoparticle exposure. The evidence presented confirmed and extended our previous findings, showing that hormesis is a generalized adaptive response which may be further generalized to nanoscale xenobiotic challenges. Nanoparticle physico-chemical properties emerged as possible features affecting biphasic relationships, although the molecular mechanisms underlining such influences remain to be fully understood, especially in experimental settings resembling long-term and low-dose realistic environmental exposure scenarios. Further investigation is necessary to achieve helpful information for a suitable assessment of nanomaterial risks at the low-dose range for both the ecosystem function and the human health.

The occupational health and safety dimension of Industry 4.0.

BACKGROUND: In recent years, an increase in the worldwide demand for consumer goods and the need for a sustainable type of manufacturing have led to the so-called "fourth industrial revolution" or Industry 4.0. This 4.0 technological revolution, designed to make industrial production more efficient, more flexible and of higher quality, is characterized by greater automation and computerization. This trend will inevitably affect the way work is organized and carried out, and may affect the health and safety of workers. OBJECTIVES: To provide a comprehensive overview of the opportunities and problematical aspects of Industry 4.0 in relation to the health and safety of workers. METHODS: We conducted a critical review of the literature currently available on this topic. RESULTS: Automated machines and robots can either replace workers or sustain them by making their tasks more flexible, safer, and socially more inclusive. On the other hand, workers will be engaged in tasks requiring decision-making, responsibility and management, as well as man-machine interaction that will expose them both to health and safety risks intrinsically related to automated tools and to greater psychosocial stress. DISCUSSION: Occupational health professionals, responsible for safeguarding health in the workplace, should make an adequate assessment of the risks attributable to 4.0 tools and should promote and protect the health and safety of workers through careful risk management based on continuous occupational training and information.

Nanotechnology in agriculture: Opportunities, toxicological implications, and occupational risks.

Nanotechnology has the potential to make a beneficial impact on several agricultural, forestry, and environmental challenges, such as urbanization, energy constraints, and sustainable use of resources. However, new environmental and human health hazards may emerge from nano-enhanced applications. This raises concerns for agricultural workers who may become primarily exposed to such xenobiotics during their job tasks. The aim of this review is to discuss promising solutions that nanotechnology may provide in agricultural activities, with a specific focus on critical aspects, challenging issues, and research needs for occupational risk assessment and management in this emerging field. Eco-toxicological aspects were not the focus of the review. Nano-fertilizers, (nano-sized nutrients, nano-coated fertilizers, or engineered metal-oxide or carbon-based nanomaterials per se), and nano-pesticides, (nano-formulations of traditional active ingredients or inorganic nanomaterials), may provide a targeted/controlled release of agrochemicals, aimed to obtain their fullest biological efficacy without over-dosage. Nano-sensors and nano-remediation methods may detect and remove environmental contaminants. However, limited knowledge concerning nanomaterial biosafety, adverse effects, fate, and acquired biological reactivity once dispersed into the environment, requires further scientific efforts to assess possible nano-agricultural risks. In this perspective, toxicological research should be aimed to define nanomaterial hazards and levels of exposure along the life-cycle of nano-enabled products, and to assess those physico-chemical features affecting nanomaterial toxicity, possible interactions with agro-system co-formulants, and stressors. Overall, this review highlights the importance to define adequate risk management strategies for workers, occupational safety practices and policies, as well as to develop a responsible regulatory consensus on nanotechnology in agriculture.

The unrecognized occupational relevance of the interaction between engineered nanomaterials and the gastro-intestinal tract: a consensus paper from a multidisciplinary working group.

BACKGROUND: There is a fundamental gap of knowledge on the health effects caused by the interaction of engineered nanomaterials (ENM) with the gastro-intestinal tract (GIT). This is partly due to the incomplete knowledge of the complex physical and chemical transformations that ENM undergo in the GIT, and partly to the widespread belief that GIT health effects of ENM are much less relevant than pulmonary effects. However, recent experimental findings, considering the role of new players in gut physiology (e.g. the microbiota), shed light on several outcomes of the interaction ENM/GIT. Along with this new information, there is growing direct and indirect evidence that not only ingested ENM, but also inhaled ENM may impact on the GIT. This fact, which may have relevant implications in occupational setting, has never been taken into consideration. This review paper summarizes the opinions and findings of a multidisciplinary team of experts, focusing on two main aspects of the issue: 1) ENM interactions within the GIT and their possible consequences, and 2) relevance of gastro-intestinal effects of inhaled ENMs. Under point 1, we analyzed how luminal gut-constituents, including mucus, may influence the adherence of ENM to cell surfaces in a size-dependent manner, and how intestinal permeability may be affected by different physico-chemical characteristics of ENM. Cytotoxic, oxidative, genotoxic and inflammatory effects on different GIT cells, as well as effects on microbiota, are also discussed. Concerning point 2, recent studies highlight the relevance of gastro-intestinal handling of inhaled ENM, showing significant excretion with feces of inhaled ENM and supporting the hypothesis that GIT should be considered an important target of extrapulmonary effects of inhaled ENM. CONCLUSIONS: In spite of recent insights on the relevance of the GIT as a target for toxic effects of nanoparticles, there is still a major gap in knowledge regarding the impact of the direct versus indirect oral exposure. This fact probably applies also to larger particles and dictates careful consideration in workers, who carry the highest risk of exposure to particulate matter.