Occupational exposure to mycotoxins: aspects to consider for the aggregate and cumulative risk assessment

Mycotoxins are an important group of naturally occurring substances known to contaminate a huge variety of agricultural products, feed and food commodities. The main concern is their widespread presence and toxic effects on humans and animals as they have been described as cytotoxic, nephrotoxic, hepatotoxic, teratogenic, immunosuppressive, mutagenic and/or carcinogenic. However, until now, risk assessments and regulations have usually been performed on individual mycotoxins despite humans and animals are being frequently exposed to a multitude of mycotoxins simultaneously. Moreover, even though some exposures through inhalation and dermal contact may potentially occur, only oral ingestion has been considered as the sole route of exposure in all the evaluations. However, more recent studies have also demonstrated airborne exposure to mycotoxins in different occupational settings with emphasis on agricultural professions. In these cases, skin contact with mold-infested substrates and inhalation of spore-borne toxins are the most important sources of exposure. Still, mycotoxins are not normally recongnize as na occupational hazard and exposure is different from the one ocurring by food intake. In this case, exposure is charaterized to be acute and simultaneous to other mycotoxins and also to fungi and dust. All these features increase the challenge implicated in the risk assessment process. Some topics will be presented and discussed in detailed such as: What occupational settings should be consider in this case; possible exposure routes; exposure characterization; how to assess exposure; co-exposure; aggregate exposure and cumulative risk assessment.

An exploratory study of the relationship between psychosocial hazard and ambulatory physiological response in higher education employees.

Purpose: as exposure to psychosocial hazard at work represents a substantial risk factor for employee health in many modern occupations, being able to accurately assess how employees cope with their working environment is crucial. As the workplace is generally accepted as being a dynamic environment consideration should be given to the interaction between employees and the acute environmental characteristics of their workplace. The aim of this study was to investigate the effects of both acute demand and chronic work-related psychosocial hazard upon employees through ambulatory assessment of heart rate variability and blood pressure. Design: a within-subjects repeated measures design was used to investigate the relationship between exposure to work-related psychosocial hazard and ambulatory heart rate variability and blood pressure in a cohort of higher education employees. Additionally the effect of acute variation in perceived work-related demand was investigated. Results: two dimensions of the Management Standards were found to demonstrate an association with heart rate variability; more hazardous levels of “demand” and “relationships” were associated with decreased SDNN. Significant changes in blood pressure and indices of heart rate variability were observed with increased acute demand.

Is there a health risk concerning the children´s consumption of cereal-based products? A cumulative mycotoxin risk assessment approach

Historically, the health risk of mycotoxins had been evaluated on the basis of single-chemical and single-exposure pathway scenarios. However, the co-contamination of foodstuffs with these compounds is being reported at an increasing rate and a multiple-exposure scenario for humans and vulnerable population groups as children is urgently needed. Cereals are among the first solid foods eaten by child and thus constitute an important food group of their diet. Few data are available relatively to early stages child´s exposure to mycotoxins through consumption of cereal-based foods. The present study aims to perform the cumulative risk assessment of mycotoxins present in a set of cereal-based foods including breakfast cereals (BC), processed cereal-based foods (PCBF) and biscuits (BT), consumed by children (1 to 3 years old, n=75) from Lisbon region, Portugal. Children food consumption and occurrence of 12 mycotoxins (aflatoxins, ochratoxin A, fumonisins and trichothecenes) in cereal-based foods were combined to estimate the mycotoxin daily intake, using deterministic and probabilistic approaches. Different strategies were used to treat the left censored data. For aflatoxins, as carcinogenic compounds, the margin of exposure (MoE) was calculated as a ratio of BMDL (benchmark dose lower confidence limit) and aflatoxin daily exposure. For the remaining mycotoxins, the output of exposure was compared to the dose reference values (TDI) in order to calculate the hazard quotients (HQ, ratio between exposure and a reference dose). The concentration addition (CA) concept was used for the cumulative risk assessment of multiple mycotoxins. The combined margin of exposure (MoET) and the hazard index (HI) were calculated for aflatoxins and the remaining mycotoxins, respectively. Main results revealed a significant health concern related to aflatoxins and especially aflatoxin M1 exposure according to the MoET and MoE values (below 10000), respectively. HQ and HI values for the remaining mycotoxins were below 1, revealing a low concern from a public health point of view. These are the first results on cumulative risk assessment of multiple mycotoxins present in cereal-based foods consumed by children. Considering the present results, more research studies are needed to provide the governmental regulatory bodies with data to develop an approach that contemplate the human exposure and, particularly, children, to multiple mycotoxins in food. The last issue is particularly important considering the potential synergistic effects that could occur between mycotoxins and its potential impact on human and, mainly, children health.

Combined exposure to multiple mycotoxins in food: are we ready for risk assessment and risk management?

It is nowadays recognized that the risk of human co-exposure to multiple mycotoxins is real. In the last years, a number of studies have approached the issue of co-exposure and the best way to develop a more precise and realistic assessment. Likewise, the growing concern about the combined effects of mycotoxins and their potential impact on human health has been reflected by the increasing number of toxicological studies on the combined toxicity of these compounds. Nevertheless, risk assessment of these toxins, still follows the conventional paradigm of single exposure and single effects, incorporating only the possibility of additivity but not taking into account the complex dynamics associated to interactions between different mycotoxins or between mycotoxins and other food contaminants. Considering that risk assessment is intimately related to the establishment of regulatory guidelines, once the risk assessment is completed, an effort to reduce or manage the risk should be followed to protect public health. Risk assessment of combined human exposure to multiple mycotoxins thus poses several challenges to scientists, risk assessors and risk managers and opens new avenues for research. This presentation aims to give an overview of the different challenges posed by the likelihood of human co-exposure to mycotoxins and the possibility of interactive effects occurring after absorption, towards knowledge generation to support a more accurate human risk assessment and risk management. For this purpose, a physiologically-based framework that includes knowledge on the bioaccessibility, toxicokinetics and toxicodynamics of multiple toxins is proposed. Regarding exposure assessment, the need of harmonized food consumption data, availability of multianalyte methods for mycotoxin quantification, management of left-censored data and use of probabilistic models will be highlight, in order to develop a more precise and realistic exposure assessment. On the other hand, the application of predictive mathematical models to estimate mycotoxins’ combined effects from in vitro toxicity studies will be also discussed. Results from a recent Portuguese project aimed at exploring the toxic effects of mixtures of mycotoxins in infant foods and their potential health impact will be presented as a case study, illustrating the different aspects of risk assessment highlighted in this presentation. Further studies on hazard and exposure assessment of multiple mycotoxins, using harmonized approaches and methodologies, will be crucial towards an improvement in data quality and contributing to holistic risk assessment and risk management strategies for multiple mycotoxins in foodstuffs.

Application of mathematical models to mycotoxins children risk assessment: a case study of Portuguese children exposure to co-occurring mycotoxins in processed cereal-based foods

People, animals and the environment can be exposed to multiple chemicals at once from a variety of sources, but current risk assessment is usually carried out based on one chemical substance at a time. In human health risk assessment, ingestion of food is considered a major route of exposure to many contaminants, namely mycotoxins, a wide group of fungal secondary metabolites that are known to potentially cause toxicity and carcinogenic outcomes. Mycotoxins are commonly found in a variety of foods including those intended for consumption by infants and young children and have been found in processed cereal-based foods available in the Portuguese market. The use of mathematical models, including probabilistic approaches using Monte Carlo simulations, constitutes a prominent issue in human health risk assessment in general and in mycotoxins exposure assessment in particular. The present study aims to characterize, for the first time, the risk associated with the exposure of Portuguese children to single and multiple mycotoxins present in processed cereal-based foods (CBF). Portuguese children (0-3 years old) food consumption data (n=103) were collected using a 3 days food diary. Contamination data concerned the quantification of 12 mycotoxins (aflatoxins, ochratoxin A, fumonisins and trichothecenes) were evaluated in 20 CBF samples marketed in 2014 and 2015 in Lisbon; samples were analyzed by HPLC-FLD, LC-MS/MS and GC-MS. Daily exposure of children to mycotoxins was performed using deterministic and probabilistic approaches. Different strategies were used to treat the left censored data. For aflatoxins, as carcinogenic compounds, the margin of exposure (MoE) was calculated as a ratio of BMDL (benchmark dose lower confidence limit) to the aflatoxin exposure. The magnitude of the MoE gives an indication of the risk level. For the remaining mycotoxins, the output of exposure was compared to the dose reference values (TDI) in order to calculate the hazard quotients (ratio between exposure and a reference dose, HQ). For the cumulative risk assessment of multiple mycotoxins, the concentration addition (CA) concept was used. The combined margin of exposure (MoET) and the hazard index (HI) were calculated for aflatoxins and the remaining mycotoxins, respectively. 71% of CBF analyzed samples were contaminated with mycotoxins (with values below the legal limits) and approximately 56% of the studied children consumed CBF at least once in these 3 days. Preliminary results showed that children exposure to single mycotoxins present in CBF were below the TDI. Aflatoxins MoE and MoET revealed a reduced potential risk by exposure through consumption of CBF (with values around 10000 or more). HQ and HI values for the remaining mycotoxins were below 1. Children are a particularly vulnerable population group to food contaminants and the present results point out an urgent need to establish legal limits and control strategies regarding the presence of multiple mycotoxins in children foods in order to protect their health. The development of packaging materials with antifungal properties is a possible solution to control the growth of moulds and consequently to reduce mycotoxin production, contributing to guarantee the quality and safety of foods intended for children consumption.

Polycyclic aromatic hydrocarbons at fire stations: firefighters’ exposure monitoring and biomonitoring, and assessment of the contribution to total internal dose

This work characterizes levels of eighteen polycyclic aromatic hydrocarbons (PAHs) in the breathing air zone of firefighters during their regular work shift at eight Portuguese fire stations, and the firefighters' total internal dose by six urinary monohydroxyl metabolites (OH-PAHs). Total PAHs (ΣPAHs) concentrations varied widely (46.4-428ng/m(3)), mainly due to site specificity (urban/rural) and characteristics (age and layout) of buildings. Airborne PAHs with 2-3 rings were the most abundant (63.9-95.7% ΣPAHs). Similarly, urinary 1-hydroxynaphthalene and 1-hydroxyacenaphthene were the predominant metabolites (66-96% ΣOH-PAHs). Naphthalene contributed the most to carcinogenic ΣPAHs (39.4-78.1%) in majority of firehouses; benzo[a]pyrene, the marker of carcinogenic PAHs, accounted with 1.5-10%. Statistically positive significant correlations (r≥0.733, p≤0.025) were observed between ΣPAHs and urinary ΣOH-PAHs for firefighters of four fire stations suggesting that, at these sites, indoor air was their major exposure source of PAHs. Firefighter's personal exposure to PAHs at Portuguese fire stations were well below the existent occupational exposure limits. Also, the quantified concentrations of post-shift urinary 1-hydroxypyrene in all firefighters were clearly lower than the benchmark level (0.5μmol/mol) recommended by the American Conference of Governmental Industrial Hygienists.

French good practice guidelines for management of the risk of low back pain among workers exposed to manual material handling: Hierarchical strategy of risk assessment of work situations

International audience

Assessment of Seismic Damage of Buildings and Related Environmental Impacts

Sustainable development has only recently started examining the existing infrastructure, and a key aspect of this is hazard mitigation. To examine buildings under a sustainable perspective requires an understanding of a building's life-cycle environmental costs, including the consideration of associated environmental impacts induced by earthquake damage. Damage repair costs lead to additional material and energy consumption, leading to harmful environmental impacts. Merging results obtained from a seismic evaluation and life-cycle analysis for buildings will give a novel outlook on sustainable design decisions. To evaluate the environmental impacts caused by buildings, long-term impacts accrued throughout a building's lifetime and impacts associated with damage repair need to be quantified. A method and literature review for completing this examination has been developed and is discussed. Using software Athena and HAZUS-MH, this study evaluated the performance of steel and concrete buildings considering their life-cycle assessments and earthquake resistance. It was determined that code design-level greatly effects a building repair and damage estimations. This study presented two case study buildings and found specific results that were obtained using several premade assumptions. Future research recommendations were provided to make this methodology more useful in real-world applications. Examining cost and environmental impacts that a building has through, a cradle-to-grave analysis and seismic damage assessment will help reduce material consumption and construction activities from taking place before and after an earthquake event happens.

Models and methods for damage and quantitative risk assessment of Natech scenarios

Natural events are a widely recognized hazard for industrial sites where relevant quantities of hazardous substances are handled, due to the possible generation of cascading events resulting in severe technological accidents (Natech scenarios). Natural events may damage storage and process equipment containing hazardous substances, that may be released leading to major accident scenarios called Natech events. The need to assess the risk associated with Natech scenarios is growing and methodologies were developed to allow the quantification of Natech risk, considering both point sources and linear sources as pipelines. A key element of these procedures is the use of vulnerability models providing an estimation of the damage probability of equipment or pipeline segment as a result of the impact of the natural event. Therefore, the first aim of the PhD project was to outline the state of the art of vulnerability models for equipment and pipelines subject to natural events such as floods, earthquakes, and wind. Moreover, the present PhD project also aimed at the development of new vulnerability models in order to fill some gaps in literature. In particular, a vulnerability model for vertical equipment subject to wind and to flood were developed. Finally, in order to improve the calculation of Natech risk for linear sources an original methodology was developed for Natech quantitative risk assessment methodology for pipelines subject to earthquakes. Overall, the results obtained are a step forward in the quantitative risk assessment of Natech accidents. The tools developed open the way to the inclusion of new equipment in the analysis of Natech events, and the methodology for the assessment of linear risk sources as pipelines provides an important tool for a more accurate and comprehensive assessment of Natech risk.

Data-driven multivariate flood hazard modeling

The present Dissertation shows how recent statistical analysis tools and open datasets can be exploited to improve modelling accuracy in two distinct yet interconnected domains of flood hazard (FH) assessment. In the first Part, unsupervised artificial neural networks are employed as regional models for sub-daily rainfall extremes. The models aim to learn a robust relation to estimate locally the parameters of Gumbel distributions of extreme rainfall depths for any sub-daily duration (1-24h). The predictions depend on twenty morphoclimatic descriptors. A large study area in north-central Italy is adopted, where 2238 annual maximum series are available. Validation is performed over an independent set of 100 gauges. Our results show that multivariate ANNs may remarkably improve the estimation of percentiles relative to the benchmark approach from the literature, where Gumbel parameters depend on mean annual precipitation. Finally, we show that the very nature of the proposed ANN models makes them suitable for interpolating predicted sub-daily rainfall quantiles across space and time-aggregation intervals. In the second Part, decision trees are used to combine a selected blend of input geomorphic descriptors for predicting FH. Relative to existing DEM-based approaches, this method is innovative, as it relies on the combination of three characteristics: (1) simple multivariate models, (2) a set of exclusively DEM-based descriptors as input, and (3) an existing FH map as reference information. First, the methods are applied to northern Italy, represented with the MERIT DEM (∼90m resolution), and second, to the whole of Italy, represented with the EU-DEM (25m resolution). The results show that multivariate approaches may (a) significantly enhance flood-prone areas delineation relative to a selected univariate one, (b) provide accurate predictions of expected inundation depths, (c) produce encouraging results in extrapolation, (d) complete the information of imperfect reference maps, and (e) conveniently convert binary maps into continuous representation of FH.

Assessment Of The Fixation Of Mandibular Symphysis Fractures Using Conical Cannulated Screws: Mechanical And Photoelastic Tests.

The aim of this study was to use mechanical and photoelastic tests to compare the performance of cannulated screws with other fixation methods in mandibular symphysis fractures. Ten polyurethane mandibles were allocated to each group and fixed as follows: group PRP, 2 perpendicular miniplates; group PLL, 1 miniplate and 1 plate, parallel; and group CS, 2 cannulated screws. Vertical linear loading tests were performed. The differences between mean values were analyzed with the Tukey test. The photoelastic test was carried out using a polariscope. The results revealed differences between the CS and PRP groups at 1, 3, 5, and 10 millimeters of displacement. The photoelastic test confirmed higher stress concentration in all groups close to the mandibular base, whereas the CS group showed it throughout the region assessed. Conical cannulated screws performed well in mechanical and photoelastic tests.

Cardiac Magnetic Resonance Assessment Of Interstitial Myocardial Fibrosis And Cardiomyocyte Hypertrophy In Hypertensive Mice Treated With Spironolactone.

Nearly 50% of patients with heart failure (HF) have preserved LV ejection fraction, with interstitial fibrosis and cardiomyocyte hypertrophy as early manifestations of pressure overload. However, methods to assess both tissue characteristics dynamically and noninvasively with therapy are lacking. We measured the effects of mineralocorticoid receptor blockade on tissue phenotypes in LV pressure overload using cardiac magnetic resonance (CMR). Mice were randomized to l-nitro-ω-methyl ester (l-NAME, 3 mg/mL in water; n=22), or l-NAME with spironolactone (50 mg/kg/day in subcutaneous pellets; n=21). Myocardial extracellular volume (ECV; marker of diffuse interstitial fibrosis) and the intracellular lifetime of water (τic; marker of cardiomyocyte hypertrophy) were determined by CMR T1 imaging at baseline and after 7 weeks of therapy alongside histological assessments. Administration of l-NAME induced hypertensive heart disease in mice, with increases in mean arterial pressure, LV mass, ECV, and τic compared with placebo-treated controls, while LV ejection fraction was preserved (>50%). In comparison, animals receiving both spironolactone and l-NAME (l-NAME+S) showed less concentric remodeling, and a lower myocardial ECV and τic, indicating decreased interstitial fibrosis and cardiomyocyte hypertrophy (ECV: 0.43 ± 0.09 for l-NAME versus 0.25 ± 0.03 for l-NAME+S, P<0.001; τic: 0.42 ± 0.11 for l-NAME groups versus 0.12 ± 0.05 for l-NAME+S group). Mice treated with a combination of l-NAME and spironolactone were similar to placebo-treated controls at 7 weeks. Spironolactone attenuates interstitial fibrosis and cardiomyocyte hypertrophy in hypertensive heart disease. CMR can phenotype myocardial tissue remodeling in pressure-overload, furthering our understanding of HF progression.

The Inadequacy Of The Y-axis Of Growth (sngn) For The Vertical Pattern Assessment In Patients With Sagittal Discrepancies.

The aim of this cephalometric study was to evaluate the influence of the sagittal skeletal pattern on the 'Y-axis of growth' measurement in patients with different malocclusions. Lateral head films from 59 patients (mean age 16y 7m, ranging from 11 to 25 years) were selected after a subjective analysis of 1630 cases. Sample was grouped as follows: Group 1 - class I facial pattern; group 2 - class II facial pattern; and Group 3 - class III facial pattern. Two angular measurements, SNGoGn and SNGn, were taken in order to determine skeletal vertical facial pattern. A logistic regression with errors distributed according to a binomial distribution was used to test the influence of the sagittal relationship (Class I, II, III facial patterns) on vertical diagnostic measurement congruence (SNGoGn and SNGn). RESULTS show that the probability of congruence between the patterns SNGn and SNGoGn was relatively high (70%) for group 1, but for groups II (46%) and III (37%) this congruence was relatively low. The use of SNGn appears to be inappropriate to determine the vertical facial skeletal pattern of patients, due to Gn point shifting throughout sagittal discrepancies. Clinical Significance: Facial pattern determined by SNGn must be considered carefully, especially when severe sagittal discrepancies are present.

Assessment Of Robustness On Analysis Using Headspace Solid-phase Microextraction And Comprehensive Two-dimensional Gas Chromatography Through Experimental Designs.

Plackett-Burman experimental design was applied for the robustness assessment of GC×GC-qMS (Comprehensive Two-Dimensional Gas Chromatography with Fast Quadrupolar Mass Spectrometric Detection) in quantitative and qualitative analysis of volatiles compounds from chocolate samples isolated by headspace solid-phase microextraction (HS-SPME). The influence of small changes around the nominal level of six factors deemed as important on peak areas (carrier gas flow rate, modulation period, temperature of ionic source, MS photomultiplier power, injector temperature and interface temperature) and of four factors considered as potentially influential on spectral quality (minimum and maximum limits of the scanned mass ranges, ions source temperature and photomultiplier power). The analytes selected for the study were 2,3,5-trimethylpyrazine, 2-octanone, octanal, 2-pentyl-furan, 2,3,5,6-tetramethylpyrazine, and 2-nonanone e nonanal. The factors pointed out as important on the robustness of the system were photomultiplier power for quantitative analysis and lower limit of mass scanning range for qualitative analysis.