Stability of mineral fibres in contact with human cell cultures. An in situ µXANES, µXRD and XRF iron mapping study.

Relevant mineral fibres of social and economic importance (chrysotile UICC, crocidolite UICC and a fibrous erionite from Jersey, Nevada, USA) were put in contact with cultured diploid human non-tumorigenic bronchial epithelial (Beas2B) and pleural transformed mesothelial (MeT5A) cells to test their cytotoxicity. Slides of each sample at different contact times up to 96 h were studied in situ using synchrotron XRF, µ-XRD and µ-XAS (I18 beamline, Diamond Light Source, UK) and TEM investigations. XRF maps of samples treated for 96 h evidenced that iron is still present within the chrysotile and crocidolite fibres and retained at the surface of the erionite fibres, indicating its null to minor mobilization in contact with cell media; this picture was confirmed by the results of XANES pre-edge analyses. µ-XRD and TEM data indicate greater morphological and crystallinity modifications occurring in chrysotile, whereas crocidolite and erionite show to be resistant in the biological environment. The contact of chrysotile with the cell cultures seems to lead to earlier amorphization, interpreted as the first dissolution step of these fibres. The formation of such silica-rich fibre skeleton may prompt the production of HO in synergy with surface iron species and could indicate that chrysotile may be much more reactive and cytotoxic in vitro in the (very) short term whereas the activity of crocidolite and erionite would be much more sluggish but persistent in the long term.

Combined circulating epigenetic markers to improve mesothelin performance in the diagnosis of malignant mesothelioma.

OBJECTIVES: Malignant mesothelioma (MM) is a highly aggressive tumor with poor prognosis. A major challenge is the development and application of early and highly reliable diagnostic marker(s). Serum biomarkers, such as 'soluble mesothelin-related proteins' (SMRPs), is the most studied and frequently used in MM. However, the low sensitivity of SMRPs for early MM limits its value; therefore, additional biomarkers are required. In this study, two epigenetically regulated markers in MM (microRNA-126, miR-126, and methylated thrombomodulin promoter, Met-TM) were combined with SMRPs and evaluated as a potential strategy to detect MM at an early stage. MATERIALS AND METHODS: A total of 188 subjects, including 45 MM patients, 99 asbestos-exposed subjects, and 44 healthy controls were prospectively enrolled, serum samples collected, and serum levels of SMRPs, miR-126 and Met-TM evaluated. Logistic regression analysis was performed to evaluate the diagnostic value of the three biomarkers. Using this approach, the performance of the '3-biomarker classifier' was tested by calculating the overall probability score of the MM and control samples, respectively, and the ROC curve was generated. RESULTS AND CONCLUSION: The combination of the three biomarkers was the best predictor to differentiate MM patients from asbestos-exposed subjects and healthy controls. The accuracy and cancer specificity was confirmed in a second validation cohort and lung cancer population. We propose that the combination of the two epigenetic biomarkers with SMRPs as a diagnosis for early MM overcomes the limitations of using SMRPs alone.

Circadian Modulation of 8-Oxoguanine DNA Damage Repair.

The DNA base excision repair pathway is the main system involved in the removal of oxidative damage to DNA such as 8-Oxoguanine (8-oxoG) primarily via the 8-Oxoguanine DNA glycosylase (OGG1). Our goal was to investigate whether the repair of 8-oxoG DNA damage follow a circadian rhythm. In a group of 15 healthy volunteers, we found a daily variation of Ogg1 expression and activity with higher levels in the morning compared to the evening hours. Consistent with this, we also found lower levels of 8-oxoG in morning hours compared to those in the evening hours. Lymphocytes exposed to oxidative damage to DNA at 8:00 AM display lower accumulation of 8-oxoG than lymphocytes exposed at 8:00 PM. Furthermore, altered levels of Ogg1 expression were also observed in a group of shift workers experiencing a deregulation of circadian clock genes compared to a control group. Moreover, BMAL1 knockdown fibroblasts with a deregulated molecular clock showed an abolishment of circadian variation of Ogg1 expression and an increase of OGG1 activity. Our results suggest that the circadian modulation of 8-oxoG DNA damage repair, according to a variation of Ogg1 expression, could render humans less susceptible to accumulate 8-oxoG DNA damage in the morning hours.

Circadian gene expression and extremely low-frequency magnetic fields: an in vitro study.

It is well known that circadian clocks are mainly regulated by light targeting signaling pathways in the hypothalamic suprachiasmatic nucleus. However, an entrainment mediated by non-photic sensory stimuli was also suggested for peripheral clocks. Exposure to extremely low frequency (ELF) electromagnetic fields might affect circadian rhythmicity. The goal of this research was to investigate effects of ELF magnetic fields (ELF-MF) on circadian clock genes in a human fibroblast cell line. We found that an ELF-MF (0.1 mT, 50 Hz) exposure was capable of entraining expression of clock genes BMAL1, PER2, PER3, CRY1, and CRY2. Moreover, ELF-MF treatment induced an alteration in circadian clock gene expression previously entrained by serum shock stimulation. These results support the hypothesis that ELF-MF may be able to drive circadian physiologic processes by modulating peripheral clock gene expression.

Wood dust exposure induces cell transformation through EGFR-mediated OGG1 inhibition.

A high risk of neoplastic transformation of nasal and paranasal sinuses mucosa is related to the occupational exposure to wood dust. However, the role of occupational exposures in the aetiology of the airway cancers remains largely unknown. Here, an in vitro model was performed to investigate the carcinogenic effect of wood dusts. Human bronchial epithelial cells were incubated with hard and soft wood dusts and the DNA damage and response to DNA damage evaluated. Wood dust exposure induced accumulation of oxidised DNA bases, which was associated with a delay in DNA repair activity. By exposing cells to wood dust at a prolonged time, wood dust-initiated cells were obtained. Initiated-cells were able to form colonies in soft agar, and to induce blood vessel formation. These cells showed extensive autophagy, reduced DNA repair, which was associated with reduced OGG1 expression and oxidised DNA base accumulation. These events were found related to the activation of EGFR/AKT/mTOR pathway, through phosphorylation and subsequent inactivation of tuberin. The persistence in the tissue of wood dusts, their repetitious binding with EGFR may continually trigger the activation switch, leading to chronic down-regulation of genes involved in DNA repair, leading to cell transformation and proliferation.

Raw and thermally treated cement asbestos exerts different cytotoxicity effects on A549 cells in vitro.

Raw cement asbestos (RCA) undergoes a complete solid state transformation when heated at high temperatures. The secondary raw material produced, high temperatures-cement asbestos (HT-CA) is composed of newly-formed crystals in place of the asbestos fibers present in RCA. Our previous study showed that HT-CA exerts lower cytotoxic cell damage compared to RCA. Nevertheless further investigations are needed to deepen our understanding of pathogenic pathways involving oxidative and nitrative damage. Our aim is to deepen the understanding of the biological effects on A549 cells of these materials regarding DNA damage related proteins (p53, its isoform p73 and TRAIL) and nitric oxide (NO) production during inducible nitric oxide synthase (iNOS)-mediated inflammation. Increments of p53/p73 expression, iNOS positive cells and NO concentrations were found with RCA, compared to HT-CA and controls mainly at 48 h. Interestingly, ferrous iron causing reactive oxygen species (ROS)-mediated DNA damage was found in RCA as a contaminant. HT-CA thermal treatment induces a global recrystallization with iron in a crystal form poorly released in media. HT-CA slightly interferes with genome expression and exerts lower inflammatory potential compared to RCA on biological systems. It could represent a safe approach for storing or recycling asbestos and an environmentally friendly alternative to asbestos waste.

MicroRNA-126 suppresses mesothelioma malignancy by targeting IRS1 and interfering with the mitochondrial function.

AIMS: MiR126 was found to be frequently lost in many types of cancer, including malignant mesothelioma (MM), which represents one of the most challenging neoplastic diseases. In this study, we investigated the potential tumor suppressor function of MiR126 in MM cells. The effect of MiR126 was examined in response to oxidative stress, aberrant mitochondrial function induced by inhibition of complex I, mitochondrial DNA (mtDNA) depletion, and hypoxia. RESULTS: MiR126 was up-regulated by oxidative stress in nonmalignant mesothelial (Met5A) and MM (H28) cell lines. In Met5A cells, rotenone inhibited MiR126 expression, but mtDNA depletion and hypoxia up-regulated MiR126. However, these various stimuli suppressed the levels of MiR126 in H28 cells. MiR126 affected mitochondrial energy metabolism, reduced mitochondrial respiration, and promoted glycolysis in H28 cells. This metabolic shift, associated with insulin receptor substrate-1 (IRS1)-modulated ATP-citrate lyase deregulation, resulted in higher ATP and citrate production. These changes were linked to the down-regulation of IRS1 by ectopic MiR126, reducing Akt signaling and inhibiting cytosolic sequestration of Forkhead box O1 (FoxO1), which promoted the expression of genes involved in gluconeogenesis and oxidative stress defense. These metabolic changes induced hypoxia-inducible factor-1α (HIF1α) stabilization. Consequently, MiR126 suppressed the malignancy of MM cells in vitro, a notion corroborated by the failure of H28(MiR126) cells to form tumors in nude mice. INNOVATION AND CONCLUSION: MiR126 affects mitochondrial energy metabolism, resulting in MM tumor suppression. Since MM is a fatal neoplastic disease with a few therapeutic options, this finding is of potential translational importance.

Rotating-shift nurses after a day off: peripheral clock gene expression, urinary melatonin, and serum 17-ß-estradiol levels.

OBJECTIVE: Impairment of clock gene expression and changes in melatonin and 17-ß-estradiol levels may constitute biological alterations underlying the increased risk of breast cancer among shift workers. The aim of this study was to compare levels of selected core clock gene expression, 6-sulfatoxymelatonin (aMT6s), and 17-ß-estradiol between rotational shift work (SW) and daytime (DT) workers after a day off. METHODS: The cross-sectional study comprised 60 nurses with ≥2 years of SW and 56 permanent DT nurses. Transcript levels of circadian genes BMAL1, CLOCK, NPAS2, CRY1, CRY2, PER1, PER2, PER3, and REVERBα were determined by quantitative real-time polymerase chain reaction (PCR) in lymphocytes. All participants were tested in the early follicular phase of the menstrual cycle. Samples were collected at the beginning of the morning-shift after a regular night's sleep on a day off. Chronotype and sociodemographic characteristics were also evaluated. RESULTS: We found a significantly higher expression of BMAL1, CLOCK, NPAS2, PER1, PER2, and REVERBα and a lower expression of PER3, CRY1 and CRY2 among SW compared to DT nurses. SW participants did not demonstrate a significant difference in aMT6s levels, but they did show significantly higher 17-ß-estradiol levels compared to DT nurses. Multiple linear regression analysis confirmed the role of SW on expression of BMAL1 (ß 0.21, P=0.040), CLOCK (ß 0.35, P=0.008), NPAS2 (ß 0.30, P=0.012), PER1 (ß 0.33, P=0.008), PER2 (ß 0.19, P=0.047), PER3 (ß -0.27, P=0.012), CRY1 (ß -0.33, P=0.002), CRY2 (ß -0.31, P=0.005), REVERBα (ß 0.19, P=0.045), and on 17-ß-estradiol levels (ß 0.32, P=0.003). The analysis also confirmed the role of chronotype as an independent factor for PER1 (ß 0.48, P=0.001) and PER2 (ß -0.22, P=0.022) expression, and 17-ß-estradiol levels (ß 0.26, P=0.011). CONCLUSIONS: Rotating SW nurses show alterations in peripheral clock gene expression and 17-ß-estradiol levels at the beginning of the morning shift after a day off.

Occupational styrene exposure induces stress-responsive genes involved in cytoprotective and cytotoxic activities.

OBJECTIVE: The aim of this study was to evaluate the expression of a panel of genes involved in toxicology in response to styrene exposure at levels below the occupational standard setting. METHODS: Workers in a fiber glass boat industry were evaluated for a panel of stress- and toxicity-related genes and associated with biochemical parameters related to hepatic injury. Urinary styrene metabolites (MA+PGA) of subjects and environmental sampling data collected for air at workplace were used to estimate styrene exposure. RESULTS: Expression array analysis revealed massive upregulation of genes encoding stress-responsive proteins (HSPA1L, EGR1, IL-6, IL-1ß, TNSF10 and TNFα) in the styrene-exposed group; the levels of cytokines released were further confirmed in serum. The exposed workers were then stratified by styrene exposure levels. EGR1 gene upregulation paralleled the expression and transcriptional protein levels of IL-6, TNSF10 and TNFα in styrene exposed workers, even at low level. The activation of the EGR1 pathway observed at low-styrene exposure was associated with a slight increase of hepatic markers found in highly exposed subjects, even though they were within normal range. The ALT and AST levels were not affected by alcohol consumption, and positively correlated with urinary styrene metabolites as evaluated by multiple regression analysis. CONCLUSION: The pro-inflammatory cytokines IL-6 and TNFα are the primary mediators of processes involved in the hepatic injury response and regeneration. Here, we show that styrene induced stress responsive genes involved in cytoprotection and cytotoxicity at low-exposure, that proceed to a mild subclinical hepatic toxicity at high-styrene exposure.

Styrene altered clock gene expression in serum-shocked cultured human fibroblasts.

The circadian clock can regulate the metabolic process of xenobiotics, but little is known as to circadian rhythms can be perturbed by xenobiotics. Styrene is a organic chemical widely used in occupational settings. The effects of styrene on the circadian genes of HuDE cells were evaluated after serum-shocking synchronization. A subtoxic dose of 100 µM of styrene altered the expression of clock genes BMAL1, PER2, PER3, CRY1, CRY2, and REV-ERB-α.

Clinical significance of circulating miR-126 quantification in malignant mesothelioma patients.

OBJECTIVES: Aim of this study was to evaluate the accuracy and precision of the detection of individual miRNA as clinical biomarkers in the serum. DESIGN AND METHODS: miRNA-126 was quantified in serum using endogenous and exogenous controls for normalization and the accuracy and precision of the method evaluated. The diagnostic value of serum miRNA-126 was evaluated in malignant mesothelioma (MM) and non-small-cell lung cancer (NSCLC) patients using both relative and absolute qRT-PCR methods. RESULTS: The use of endogenous invariant and exogenous synthetic controls as well sample dilution markedly improves the accuracy and precision of the assay. The inter- and intra-assay analyses revealed that relative qRT-PCR is a more reliable method. Circulating miR-126 detected in the serum by relative qRT-PCRs was found low-expressed in both malignancies, significantly differentiated MM patients from healthy controls and NSCLC from MM, but do not discriminate NSCLC patients from control subjects. Kaplan-Meier analysis revealed that low level of circulating miR-126 in MM patients was strongly associated with worse prognosis. CONCLUSIONS: We propose that this approach can be adopted for accurate analysis of other suitable circulating miRNA markers of different types of cancer.

Effect of ascorbic acid-rich diet on in vivo-induced oxidative stress.

Using hyperbaric oxygen (HBO) therapy as an in vivo oxidation model, we investigated the effect of a diet enriched in ascorbic acid (AA) on HBO-induced oxidative stress. Volunteers (n 46) were allocated to the AA-rich diet group or the control group. Blood samples were collected at the basal time, after the 1-week diet before and immediately after the HBO treatment, and 1 week after the HBO treatment. AA level, total antioxidant status (TAS), hydroperoxides (HP), lymphocyte DNA oxidation and DNA repair capacity were assessed. The expression of genes involved in oxidative stress was evaluated in lymphocytes and the protein activity of the modulated genes was determined in the plasma. The AA level and the antioxidant status of plasma were increased by AA-rich food consumption. HBO exposure did not affect the AA levels or TAS, but induced HP formation in the control group. The lymphocytes isolated from dietary-supplemented subjects were resistant to ex vivo DNA oxidation, showing an increased DNA repair capacity compared with controls. A difference in gene expression pattern was observed between the groups. AA-rich foods provide dual protection against oxidative stress, enhancing plasma antioxidant levels and stimulating genes involved in cell detoxification.

Angiogenic effect induced by mineral fibres.

Due to the toxic effect of asbestos, other materials with similar chemical-physical characteristics have been introduced to substitute it. We evaluate the angiogenic effect of certain asbestos substitute fibres such as glass fibres (GFs), ceramic fibres (CFs) and wollastonite fibres (WFs) and then compare angiogenic responses to those induced by crocidolite asbestos fibres (AFs). An in vitro model using human endothelial cells in small islands within a culture matrix of fibroblasts (Angio-Kit) was used to evaluate vessel formation. The release of IL-6, sIL-R6, IL-8, VEGF-A and their soluble receptors, sVEGFR-1, sVEGFR-2, was determined in the conditioning medium of Angio-Kit system after fibre treatment. ROS formation and cell viability were evaluated in cultured endothelial cells (HUVEC). To evaluate the involvement of intracellular mechanisms, EGFR signalling, ROS formation and nuclear factor-κB (NFκB) pathway were then inhibited by incubating HUVEC cells with AG1478, NAC and PDTC respectively, and the cytokine and growth factor release was analyzed in the culture medium after 7 days of fibre incubation. Among the mineral fibres tested, WFs markedly induced blood vessel formation which was associated with release of IL-6 and IL-8, VEGF-A and their soluble receptors. ROS production was observed in HUVEC after WFs treatment which was associated with cell cytotoxicity. The EGFR-induced ERK phosphorylation and ROS-mediated NFκB activation were involved in the cytokine and angiogenic factor release. However, only the EGFR activation was able to induce angiogenesis. The WFs are potential angiogenic agents that can induce regenerative cytokine and angiogenic factor production resulting in the formation of new blood vessels.

Asbestos exposure affects poly(ADP-ribose) polymerase-1 activity: role in asbestos-induced carcinogenesis.

Asbestos is known to induce malignant mesothelioma (MM) and other asbestos-related diseases. It is directly genotoxic by inducing DNA strand breaks and cytotoxic by promoting apoptosis in lung target cells. Poly(ADP-ribose) polymerase-1 (PARP1) is a nuclear zinc-finger protein with a function as a DNA damage sensor. To determine whether PARP1 is involved in asbestos-induced carcinogenesis, PARP1 expression and activity as well as DNA damage and repair were evaluated in circulating cells of asbestos-exposed subjects, MM patients and age-matched controls. PARP1 expression and activity were also evaluated in pleural biopsies of MM patients and compared with normal tissue. Accumulation of the pre-mutagenic 8-hydroxy-2'-deoxyguanosine and elevated PARP1 expression were found both in asbestos-exposed subjects and MM patients. Although PARP1 was highly expressed, its activity was relatively low. Low DNA repair efficiency was observed in lymphocytes from MM patients. High expression of PARP1 associated with low PARP activity was also found in MM biopsies. To mimic PARP1 dysfunction, PARP1 expression and activity were induced in immortalised mesothelial cells by their exposure to asbestos in the presence of a PARP1 inhibitor, which resulted in transformation of the cells. We propose that exposure to asbestos inhibits the PARP1 activity possibly resulting in higher DNA instability, thus causing malignant transformation.

Association of MiR-126 with soluble mesothelin-related peptides, a marker for malignant mesothelioma.

BACKGROUND: Improved detection methods for diagnosis of malignant pleural mesothelioma (MPM) are essential for early and reliable detection as well as treatment. Since recent data point to abnormal levels of microRNAs (miRNAs) in tumors, we hypothesized that a profile of deregulated miRNAs may be a marker of MPM and that the levels of specific miRNAs may be used for monitoring its progress. METHODS AND RESULTS: miRNAs isolated from fresh-frozen biopsies of MPM patients were tested for the expression of 88 types of miRNA involved in cancerogenesis. Most of the tested miRNAs were downregulated in the malignant tissues compared with the normal tissues. Of eight significantly downregulated, three miRNAs were assayed in cancerous tissue and adjacent non-cancerous tissue sample pairs collected from 27 formalin-fixed, paraffin-embedded MPM tissues by quantitative RT-PCR. Among the miRNAs tested, only miR-126 significantly remained downregulated in the malignant tissues. Furthermore, the performance of the selected miR-126 as biomarker was evaluated in serum samples of asbestos-exposed subjects and MPM patients and compared with controls. MiR-126 was not affected by asbestos exposure, whereas it was found strongly associated with VEGF serum levels. Levels of miR-126 in serum, and its levels in patients' serum in association with a specific marker of MPM, SMRPs, correlate with subjects at high risk to develop MPM. CONCLUSIONS AND SIGNIFICANCE: We propose miR-126, in association with SMRPs, as a marker for early detection of MPM. The identification of tumor biomarkers used alone or, in particular, in combination could greatly facilitate the surveillance procedure for cohorts of subjects exposed to asbestos.

Risk of bacterial cross infection associated with inspiration through flow-based spirometers.

BACKGROUND: Bacterial contamination of spirometers has been documented in water-sealed devices, mouthpieces, and connection tubes. Little information is available about bacterial contamination of flow-based apparatuses such as turbine-type spirometers and pneumotachographs. Inspiration through contaminated equipment is a potential source of cross infection. To investigate bacteria mobilization (ie, bacteria detachment and aerosolization from the instrument) during routine spirometric testing, 2 types of flow-based spirometers were used. Bacteria mobilization during artificial inspiration through in-line filters or cardboard mouthpieces was evaluated. METHODS: Nine hundred workers undergoing periodic spirometric testing were enrolled at the occupational physician office in 30 sessions of 30 subjects each. The participants were asked to perform a forced vital capacity test in a turbine-type spirometer and in an unheated pneumotachograph fitted with disposable in-line filters or cardboard mouthpieces. To evaluate bacterial mobilization, an artificial inspiration was performed and bacterial growth determined. The bacterial growth analysis was assessed after the first and the thirtieth spirometric tests of each session without disinfecting the instruments between tests. In addition, instrument bacterial contamination was evaluated. RESULTS: No significant bacterial mobilization and instrument contamination were found in spirometric tests executed with in-line filters. Conversely, a significant bacterial mobilization and instrument contamination were observed in tests performed with cardboard mouthpieces. Differences between the 2 spirometers were not significant. CONCLUSION: In-line filters may effectively reduce the risk of bacterial cross infection. Inspiration through flow-based spirometers fitted with disposable cardboard mouthpieces is completely safe when combined with spirometer disinfection/sterilization between subjects.

In vitro effect of aspartame in angiogenesis induction.

Aspartame (APM) is the most widely used artificial sweetener and is added to a wide variety of foods, beverages, drugs, and hygiene products. In vitro and in vivo tests have reported contradictory data about APM genotoxicity. We evaluated the angiogenic effect of APM in an in vitro model using blood vessel development assay (Angio-Kit), cultured endothelial cells and fibroblasts. The release of IL-6, VEGF-A, and their soluble receptors sIL-R6 and sVEGFR-2 were determined over time in the conditioned medium of the Angio-Kit system, endothelial cells and cell lines with fibroblast properties after APM treatment. Reactive oxygen species (ROS) formation, cell viability, and stimulation of the extracellular signal-regulated kinases (erk1/2) and protein p38 were also evaluated. Exposure to APM induced blood vessel formation. ROS production was observed in endothelial cells after APM treatment, which was associated with a slight cell cytotoxicity. Neither intracellular ROS formation nor cell death was observed in fibroblasts. APM increases the levels of inflammatory mediator IL-6, VEGF and their soluble receptors released from endothelial cells into the medium. APM treatment induces VEGF-pathway activation by erk1/2 and p38 phosphorylation. APM at low doses is an angiogenic agent that induces regenerative cytokine production leading to the activation of MAPKs and resulting in the formation of new blood vessels.

[LaboRisCh: an algorithm for assessment of health risks due to chemicals in research laboratories and similar workplaces]. / LaboRisCh: un algoritmo per la valutazione dei rischi per la salute da agenti chimici nei laboratori di ricerca e negli ambienti di lavoro affini.

BACKGROUND: Chemical risk assessment in research laboratories is complicated by factors such as the large number of agents to be considered, each present in small quantities, and the very short and erratic periods of exposure, all of which make reliable environmental and biological monitoring particularly difficult and at times impossible. In such environments, a preliminary evaluation procedure based on algorithms would be useful to establish the hazard potential of a given situation and to guide the appropriate intervention. OBJECTIVES: The LaboRisCh model was expressly designed to assess the health risk due to chemicals in research laboratories and similar workplaces. METHODS: The model is based on the calculation of the value of a synthetic single risk index for each substance and compound found in a laboratory and, subsequently, of a further synthetic single risk index for the whole laboratory or, where required, a section thereof. This makes LaboRisCh a compromise between need for information, ease of use, and resources required for the assessment. The risk index includes several items, chiefly the physical and chemical properties, intrinsic hazard potential, amount, dilution, and time of exposure to each agent; waste management; possible interactions; presence and efficiency of collective and individual protection devices, and staff training in good laboratory practices. The value of the synthetic single index corresponds to one of three areas: no risk (green), possible risk (yellow), and certain risk (red). CONCLUSIONS: Preliminary data confirm the model. LaboRisCh appears to be a reliable method for chemical risk assessment in research laboratories and similar workplaces.

[The LaboRisCh algorithm, a tool for the assessing chemical risk for health: scientific uncertainty management]. / L'algoritmo LaboRisCh, uno strumento per la valutazione del rischio per la salute da agenti chimici: gestione dell'incertezza scientifica.

The LaboRisCh algorithm is a practical tool for the first-level assessment of the health risk from chemicals in research laboratories and similar workplaces. Through the assessment of the risk index related to each agent (Ra), the algorithm leads to the calculation of the value of a baseline risk index (Rb), and finally to a corrected risk index (Rc). The value of Rc sets the relevant condition in one of three health risk zones. The algorithm also includes carcinogens and mutagens, whose presence mandates the addition of the c/m subscript (Rc(c/m)). The addition is automatic for agents allocated the EU risk phrases R40, R45, R46, R49 and R68; whereas it is at the discretion of the evaluator for non EU-classified agents that belong to EU categories 1 or 2 and/or to IARC categories 1, 2A or 2B. Further research has led to integration of the algorithm. For instance, similarly to the provision for carcinogens and mutagens, the r subscript (Rc(r)) is now required for agents that are considered toxic to reproduction allocated or attributable to risk phrases R60, R61, R62 and R63.