Exposure to airborne particulate matter in working from office and working from home employees.

The main aim of this study is to quantitatively evaluate the differences, in terms of exposure to PM (particulate matter), between WFO (working-from-office) and WFH (working-from-home) conditions. Two measurement surveys were performed: a long-term and a short-term campaign, focused on the monitoring of personal exposure to size-fractionated PM in these different working conditions. Results of the long-term campaign show that the WFH subject is exposed to higher (up to 4 times) PM concentration, compared to the WFO subject. Specific activities performed by the subjects impacted their exposure concentrations, even if the most relevant contribution to total exposure was made by desk work. Results of the short-term campaign indicate that the subjects can be divided into two groups: subjects most exposed during the WFH mode (HE_H - Higher_Exposure_Home) and subjects most exposed during the WFO mode (HE_O - Higher_Exposure_Office). HE_H group is exposed to levels of pollutants up to 4 times higher in the domestic than in the office environment, during the moment of desk work. The HE_O group is exposed to higher (double) concentration levels during desk work during the WFO day. Considering the possible growing trend towards remote work it is important to evaluate these "new domestic offices" comprehensively.

An In-Field Assessment of the P.ALP Device in Four Different Real Working Conditions: A Performance Evaluation in Particulate Matter Monitoring.

This study aimed to assess the performance, in terms of precision and accuracy, of a prototype (called "P.ALP"-Ph.D. Air Quality Low-cost Project) developed for monitoring PM2.5 concentration levels. Four prototypes were co-located with reference instrumentation in four different microenvironments simulating real-world and working conditions, namely (i) office, (ii) home, (iii) outdoor, and (iv) occupational environments. The devices were evaluated for a total of 20 monitoring days (approximately 168 h) under a wide range of PM2.5 concentrations. The performances of the prototypes (based on the light-scattering working principle) were tested through different statistical methods. After the data acquisition and data cleaning processes, a linear regression analysis was performed to assess the precision (by comparing all possible pairs of devices) and the accuracy (by comparing the prototypes against the reference instrumentation) of the P.ALP. Moreover, the United States Environmental Protection Agency (US EPA) criteria were applied to assess the possible usage of this instrumentation, and to evaluate the eventual error trends of the P.ALP in the data storage process, Bland-Altman plots were also adopted. The outcomes of this study underlined that the P.ALP performed differently depending on the microenvironment in which it was tested and, consequently, on the PM2.5 concentrations. The device can monitor PM2.5 variations with acceptable results, but the performance cannot be considered satisfactory at extremely low and remarkably high PM2.5 concentrations. Thanks to modular components and open-source software, the tested device has the potential to be customized and adapted to better fit specific study design needs, but it must be implemented with ad hoc calibration factors depending on the application before being used in field.

Evolution and Applications of Recent Sensing Technology for Occupational Risk Assessment: A Rapid Review of the Literature.

Over the last decade, technological advancements have been made available and applied in a wide range of applications in several work fields, ranging from personal to industrial enforcements. One of the emerging issues concerns occupational safety and health in the Fourth Industrial Revolution and, in more detail, it deals with how industrial hygienists could improve the risk-assessment process. A possible way to achieve these aims is the adoption of new exposure-monitoring tools. In this study, a systematic review of the up-to-date scientific literature has been performed to identify and discuss the most-used sensors that could be useful for occupational risk assessment, with the intent of highlighting their pros and cons. A total of 40 papers have been included in this manuscript. The results show that sensors able to investigate airborne pollutants (i.e., gaseous pollutants and particulate matter), environmental conditions, physical agents, and workers' postures could be usefully adopted in the risk-assessment process, since they could report significant data without significantly interfering with the job activities of the investigated subjects. To date, there are only few "next-generation" monitors and sensors (NGMSs) that could be effectively used on the workplace to preserve human health. Due to this fact, the development and the validation of new NGMSs will be crucial in the upcoming years, to adopt these technologies in occupational-risk assessment.

Occupational Exposure to Halogenated Anaesthetic Gases in Hospitals: A Systematic Review of Methods and Techniques to Assess Air Concentration Levels.

Objective During the induction of gaseous anaesthesia, waste anaesthetic gases (WAGs) can be released into workplace air. Occupational exposure to high levels of halogenated WAGs may lead to adverse health effects; hence, it is important to measure WAGs concentration levels to perform risk assessment and for health protection purposes. Methods A systematic review of the scientific literature was conducted on two different scientific databases (Scopus and PubMed). A total of 101 studies, focused on sevoflurane, desflurane and isoflurane exposures in hospitals, were included in this review. Key information was extracted to provide (1) a description of the study designs (e.g., monitoring methods, investigated occupational settings, anaesthetic gases in use); (2) an evaluation of time trends in the measured concentrations of considered WAGs; (3) a critical evaluation of the sampling strategies, monitoring methods and instruments used. Results Environmental monitoring was prevalent (68%) and mainly used for occupational exposure assessment during adult anaesthesia (84% of cases). Real-time techniques such as photoacoustic spectroscopy and infrared spectrophotometry were used in 58% of the studies, while off-line approaches such as active or passive sampling followed by GC-MS analysis were used less frequently (39%). Conclusions The combination of different instrumental techniques allowing the collection of data with different time resolutions was quite scarce (3%) despite the fact that this would give the opportunity to obtain reliable data for testing the compliance with 8 h occupational exposure limit values and at the same time to evaluate short-term exposures.

Estimation of the Inhaled Dose of Pollutants in Different Micro-Environments: A Systematic Review of the Literature.

Recently, the need to assess personal exposure in different micro-environments has been highlighted. Further, estimating the inhaled dose of pollutants is considerably one of the most interesting parameters to be explored to complete the fundamental information obtained through exposure assessment, especially if associated with a dose-response approach. To analyze the main results obtained from the studies related to the estimation of the inhaled dose of pollutants in different micro-environments (environments in which an individual spends a part of his day), and to identify the influence of different parameters on it, a systematic review of the literature was performed. The principal outcomes from the considered studies outlined that (i) exposure concentration and residence time are among the most important parameters to be evaluated in the estimation of the inhaled dose, especially in transport environments. Further, (ii) the pulmonary ventilation rate can be of particular interest during active commuting because of its increase, which increases the inhalation of pollutants. From a methodological point of view, the advent of increasingly miniaturized, portable and low-cost technologies could favor these kinds of studies, both for the measurement of atmospheric pollutants and the real-time evaluation of physiological parameters used for estimation of the inhaled dose. The main results of this review also show some knowledge gaps. In particular, numerous studies have been conducted for the evaluation (in terms of personal exposure and estimation of the inhaled dose) of different PM fractions: other airborne pollutants, although harmful to human health, are less represented in studies of this type: for this reason, future studies should be conducted, also considering other air pollutants, not neglecting the assessment of exposure to PM. Moreover, many studies have been conducted indoors, where the population spends most of their daily time. However, it has been highlighted how particular environments, even if characterized by a shorter residence time, can contribute significantly to the dose of inhaled pollutants. These environments are, therefore, of particular importance and should be better evaluated in future studies, as well as occupational environments, where the work results in a high pulmonary ventilation rate. The attention of future studies should also be focused on these categories of subjects and occupational studies.

Features and Practicability of the Next-Generation Sensors and Monitors for Exposure Assessment to Airborne Pollutants: A Systematic Review.

In the last years, the issue of exposure assessment of airborne pollutants has been on the rise, both in the environmental and occupational fields. Increasingly severe national and international air quality standards, indoor air guidance values, and exposure limit values have been developed to protect the health of the general population and workers; this issue required a significant and continuous improvement in monitoring technologies to allow the execution of proper exposure assessment studies. One of the most interesting aspects in this field is the development of the "next-generation" of airborne pollutants monitors and sensors (NGMS). The principal aim of this review is to analyze and characterize the state of the art and of NGMS and their practical applications in exposure assessment studies. A systematic review of the literature was performed analyzing outcomes from three different databases (Scopus, PubMed, Isi Web of Knowledge); a total of 67 scientific papers were analyzed. The reviewing process was conducting systematically with the aim to extrapolate information about the specifications, technologies, and applicability of NGMSs in both environmental and occupational exposure assessment. The principal results of this review show that the use of NGMSs is becoming increasingly common in the scientific community for both environmental and occupational exposure assessment. The available studies outlined that NGMSs cannot be used as reference instrumentation in air monitoring for regulatory purposes, but at the same time, they can be easily adapted to more specific applications, improving exposure assessment studies in terms of spatiotemporal resolution, wearability, and adaptability to different types of projects and applications. Nevertheless, improvements needed to further enhance NGMSs performances and allow their wider use in the field of exposure assessment are also discussed.

Carbon Nanotubes: Probabilistic Approach for Occupational Risk Assessment.

In this study, the occupational risk assessment of carbon nanotubes (CNTs) was performed by means of a probabilistic approach. Chronic and subchronic inhalation exposure studies were retrieved during the hazard identification phase of the study. These studies were then used to obtain a guidance value (BMCh, expressed as a lognormal distribution with geometric mean ± geometric standard deviation = 10.0 ± 4.2 µg/m3) for occupational inhalation exposure to CNTs. An exposure scenario was selected from the scientific literature: three different work events (WEs) related to the production of conductive films were considered: (WE1) manufacturing of single walled carbon nanotubes films during normal operation using local exhaust ventilation (LEV); (WE2) manufacturing of SWCNT film without LEV; and (WE3) cleaning of one of the reactors. For each WE, a probability distribution function was applied, considering exposure expressed as mass concentration, as derived from three different measurement techniques. The ratio of the exposure and the BMCh distributions (i.e., the risk characterization ratio-RCR) was used to calculate the probability of occurrence of a relevant occupational risk. All the considered WEs indicated the presence of a risk (i.e., RCR distributions ≥ 1); however, only WE2 resulted in a statistically significant level of risk.

Retrospective Exposure Assessment Methods Used in Occupational Human Health Risk Assessment: A Systematic Review.

As part of the assessment and management of chemical risk and occupational hygiene, retrospective exposure assessment (REA) to chemical agents can be defined as the estimate of exposure associated with a person's work history. The fundamental problem underlying the reconstruction of the exposure is that of transforming this type of information in quantitative terms to obtain an accurate estimate. REA can follow various approaches, some of which are technically complicated and both time and resource consuming. The aim of this systematic review is to present the techniques mainly used for occupational REA. In order to carry out this evaluation, a systematic review of the scientific literature was conducted. Forty-four studies were identified (published from 2010 to date) and analyzed. In exposure reconstruction studies, quantitative approaches should be preferable, especially when estimates will be used in the context of health impact assessment or epidemiology, although it is important to stress how, ideally, the experimental data available for the considered scenario should be used whenever possible as the main starting information base for further processing. To date, there is no single approach capable of providing an accurate estimate of exposure for each reasonably foreseeable condition and situation and the best approach generally depends on the level of information available for the specific case. The use of a combination of different reconstruction techniques can, therefore, represent a powerful tool for weighting and integrating data obtained through qualitative and quantitative approaches, in order to obtain the best possible estimate.

Estimation of the Inhaled Dose of Airborne Pollutants during Commuting: Case Study and Application for the General Population.

During rush hours, commuters are exposed to high concentrations and peaks of traffic-related air pollutants. The aims of this study were therefore to extend the inhaled dose estimation outcomes from a previous work investigating the inhaled dose of a typical commuter in the city of Milan, Italy, and to extend these results to a wider population. The estimation of the dose of pollutants inhaled by commuters and deposited within the respiratory tract could be useful to help commuters in choosing the modes of transport with the lowest exposure and to increase their awareness regarding this topic. In addition, these results could provide useful information to policy makers, for the creation/improvement of a mobility that takes these results into account. The principal result outcomes from the first part of the project (case study on a typical commuter in the city of Milan) show that during the winter period, the maximum deposited mass values were estimated in the "Other" environments and in "Underground". During the summer period, the maximum values were estimated in the "Other" and "Walking (high-traffic conditions)" environments. For both summer and winter, the lowest values were estimated in the "Car" and "Walking (low-traffic conditions)" environments. Regarding the second part of the study (the extension of the results to the general population of commuters in the city of Milan), the main results show that the period of permanence in a given micro-environment (ME) has an important influence on the inhaled dose, as well as the pulmonary ventilation rate. In addition to these results, it is of primary importance to report how the inhaled dose of pollutants can be strongly influenced by the time spent in a particular environment, as well as the subject's pulmonary ventilation rate and pollutant exposure levels. For these reasons, the evaluation of these parameters (pulmonary ventilation rate and permanence time, in addition to the exposure concentration levels) for estimating the inhaled dose is of particular relevance.

Toxic trace metals in size-segregated fine particulate matter: Mass concentration, respiratory deposition, and risk assessment.

To characterise the mass concentration, size-distribution, and respiratory deposition of selected trace metals (Cr, Mn, Fe, Ni, Cu, Zn, Ba, and Pb) in size-segregated PM2.5, a long-term monitoring campaign was undertaken at an urban background site in Como (Northern Italy). 96-h aerosol samples were collected weekly, from May 2015 to March 2016, using a 13-stage low pressure impactor and analysed via laser ablation-inductively coupled plasma-mass spectrometry. Significantly higher levels of trace metals were generally found during the heating season (two to more than four times) compared to the non-heating period at all size ranges, especially for concentrations in PM0.1-1. Distinct distribution profiles characterised the different elements, even though the corresponding heating and non-heating shapes always exhibited similar features, with negligible seasonal shifts in the average mass median aerodynamic diameters. Fe, Ba, and Cu had >70% of their mass in PM1-2.5, whereas Pb, Zn, and Ni showed higher contributions in the accumulation mode (>60%). Finally, broad size-distributions were found for Cr and Mn. The multiple-path particle dosimetry model estimated the overall deposition fractions in human airways varying between 27% (Pb) and 48% (Ba). The greatest deposition variability was always registered in the head region of the respiratory system, with the highest contributions for those metals predominantly accumulated in the PM2.5 coarse modes. In contrast, the deposition in the deepest respiratory tract maintained nearly constant proportions over time, becoming notably important for Pb, Ni, and Zn (∼13%) with respect to their total deposition. The comparison with national limits established for Pb and Ni suggested the absence of significant risks for the local population, as expected, with average concentrations two orders of magnitude lower than the corresponding annual limit and objective value. Similar findings were reported for all the other metals, for which the estimated hazard quotients were always well <1.

Commuters' Personal Exposure Assessment and Evaluation of Inhaled Dose to Different Atmospheric Pollutants.

Several studies evaluating exposure to pollutants in microenvironments (MEs) are available in the scientific literature, but studies that evaluate the inhaled doses of pollutants are few in number. Therefore, this study aimed to evaluate the exposure of commuters to different pollutants (i.e., nitrogen dioxide [NO2] and fractionated particulate matter [PM], including ultrafine particles [UFPs]) using miniaturized and portable real-time monitoring instruments in selected MEs; the inhaled doses of these pollutants were estimated for each of these MEs. Measurements were performed along a typical commute, considering different traffic and nontraffic MEs. Experimental data were collected over four working weeks in two different seasons (winter and summer). Different portable and miniaturized instruments were used to evaluate PM and NO2 exposure. Furthermore, physiological parameters were evaluated using a heart rate monitor. The principal results show that higher exposure levels were measured in Underground (for all PM fractions and NO2) and in Car (UFP), while lower levels were measured in Car (PM and NO2) and in Train (UFP). In contrast, higher values of the inhaled cumulative dose were estimated in environments defined as Other, followed by Walking (ht), while lower values were observed in Walking (lt) and in Car.

Indoor gaseous air pollutants determinants in office buildings-The OFFICAIR project.

The aim of this study was to identify determinants of aldehyde and volatile organic compound (VOC) indoor air concentrations in a sample of more than 140 office rooms, in the framework of the European OFFICAIR research project. A large field campaign was performed, which included (a) the air sampling of aldehydes and VOCs in 37 newly built or recently retrofitted office buildings across 8 European countries in summer and winter and (b) the collection of information on building and offices' characteristics using checklists. Linear mixed models for repeated measurements were applied to identify the main factors affecting the measured concentrations of selected indoor air pollutants (IAPs). Several associations between aldehydes and VOCs concentrations and buildings' structural characteristic or occupants' activity patterns were identified. The aldehyde and VOC determinants in office buildings include building and furnishing materials, indoor climate characteristics (room temperature and relative humidity), the use of consumer products (eg, cleaning and personal care products, office equipment), as well as the presence of outdoor sources in the proximity of the buildings (ie, vehicular traffic). Results also showed that determinants of indoor air concentrations varied considerably among different type of pollutants.

How to Obtain a Reliable Estimate of Occupational Exposure? Review and Discussion of Models' Reliability.

Evaluation and validation studies of quantitative exposure models for occupational exposure assessment are still scarce and generally only consider a limited number of exposure scenarios. The aim of this review was to report the current state of knowledge of models' reliability in terms of precision, accuracy, and robustness. A systematic review was performed through searches of major scientific databases (Web of Science, Scopus, and PubMed), concerning reliability of Tier1 ("ECETOC TRA"-European Centre for Ecotoxicology and Toxicology of Chemicals Targeted Risk Assessment, MEASE, and EMKG-Expo-Tool) and Tier2 models (STOFFENMANAGER® and "ART"-Advanced Registration, Evaluation, Authorization and Restriction of Chemicals (REACH) Tool). Forty-five studies were identified, and we report the complete information concerning model performance in different exposure scenarios, as well as between-user reliability. Different studies describe the ECETOC TRA model as insufficient conservative to be a Tier1 model, in different exposure scenarios. Contrariwise, MEASE and EMKG-Expo-Tool seem to be conservative enough, even if these models have not been deeply evaluated. STOFFENMANAGER® resulted the most balanced and robust model. Finally, ART was generally found to be the most accurate and precise model, with a medium level of conservatism. Overall, the results showed that no complete evaluation of the models has been conducted, suggesting the need for correct and harmonized validation of these tools.

In-vehicle airborne fine and ultra-fine particulate matter exposure: The impact of leading vehicle emissions.

Airborne particulate matter (PM) concentrations inside vehicle cabins are often extremely high compared to background levels. The present study was motivated by the fact that in the last few decades, the implementation of new emission standards has led to the reduction of vehicle particle emissions. This study addresses for the first time the relationship between leading vehicle (LV) emissions and in-cabin PM exposure levels in the immediately following vehicle (henceforth called the study vehicle - SV), with particular emphasis on the role of the LV's emission reduction technologies (e.g., diesel particulate filter-DPF) as an effective risk management measure. The study was performed using an instrumented study vehicle (always to be considered as the following vehicle) on a 26-km fixed route where 10 repeated tests were conducted during 60-minute trips. On-line monitoring of the fine 0.3-1 µm and 1-2.5 µm (PM0.3-1 and PM1-2.5) and ultra-fine particle (UFP) concentrations was performed inside the SV's car cabin with fixed ventilation settings (i.e., windows closed, air conditioning off, and recirculation fan off). Simultaneously, the license plate numbers of the LVs along the route were recorded to retrieve information pertaining to their fuel type and Euro emission standard category. The results clearly showed that the in-cabin PM levels were significantly affected by the LV's Euro emission standard. Regarding petrol-fuelled LVs, the median in-cabin particle exposure levels were statistically lower (e.g., -34% for PM0.3-1) when following vehicles with stricter emission standards (in particular, Euro 6) than when following a low-emission standard vehicle (i.e., Euro 0-2). Concerning diesel-fuelled LVs, a strong and significant decrease in the in-cabin median exposure levels (up to -62%, -44%, and -48% for UFPs, PM0.3-1, and PM1-2.5, respectively) was observed for recent-emission standards LVs (i.e., Euro 5-6) with respect to older-emission standard LVs (i.e., Euro 0-4). A specific analysis revealed that the in-cabin median exposure concentrations of PM were highly and significantly reduced by DPF-equipped LVs. For UFPs, this resulted in a 47% reduction compared to diesel-fuelled (non-DPF) LVs. For PM0.3-1, an approximate 80% reduction was observed compared to both petrol-fuelled and diesel-fuelled (non-DPF) LVs. For PM1-2.5, an approximate 38% reduction was observed compared to petrol-fuelled LVs and a 46% reduction compared to non-DPF LVs.

Probabilistic approach for the risk assessment of nanomaterials: A case study for graphene nanoplatelets.

An experimental probabilistic approach for health risk assessment was applied for graphene nanoplatelets (GNPs). The hazard assessment indicated a low level of toxicity for the GNPs. The benchmark dose method, based on sub-chronic and chronic inhalation exposure studies, was used to quantify a guidance value (BMCh) for occupational inhalation exposure to GNPs, expressed as a lognormal distribution with a geometric mean ±â€¯geometric standard deviation of 0.212 ±â€¯7.79 mg/m3 and 9.37 × 104 ±â€¯7.6 particle/cm3. Exposure scenarios (ES) were defined based on the scientific literature for large-scale production (ES1) and manufacturing (ES2) of GNPs; a third ES, concerning in-lab handling of GNPs (ES3) was based on results of experiments performed for this study. A probability distribution function was then assumed for each ES. The risk magnitude was calculated using a risk characterization ratio (RCR), defined as the ratio of the exposure distributions and the BMCh distribution. All three ES resulted in RCR distributions ≥1 (i.e. risk present); however, none of the ES had a statistically significant level of risk at a 95% confidence interval. A sensitivity analysis indicated that ∼75% of the variation in the RCR distributions was due to uncertainties in the BMCh calculation.

Exposure to airborne particles associated with the handling of graphene nanoplatelets.

BACKGROUND: It is recognized that engineering control measures are needed to reduce occupational exposure to engineered nanomaterials (NMs): of these, fume hoods are among the most widespread collective protection equipment used while handling NMs in occupational settings.  It is known that in some circumstances, handling NMs in fume hoods can result in a significant release of NMs. OBJECTIVE: To assess the effectiveness of fume hoods in reducing exposure while handling graphene nanoplatelets and to define the conditions that result in a lower dispersion of particles and thus less operator exposure. METHODS: An experimental protocol was established to monitor the variations of airborne particle concentrations while handling graphene in fume hoods (transferring and pouring). The measurement locations were at the laboratory, inside the hood and at operator's breathing zone. Handling tasks were performed under different operating conditions: the variable factors included hood face velocity and sash height. RESULTS: Results of this study indicate that the handling of graphene nanoplatelets may pose a potential risk of contamination of the work environment and hence exposure of the involved operators, if adequate control measures are not taken. In fact, when inadequate or not sufficiently cautionary operational conditions were utilized, non-negligible increases in airborne graphene particle concentrations during the nanomaterial manipulation phases were observed. CONCLUSIONS: Some operating conditions (e.g., face velocity, sash height) can be adjusted to avoid relevant personal exposure conditions and contamination of the work environment by NMs, thus ensuring safer conditions.

Precision and Accuracy of a Direct-Reading Miniaturized Monitor in PM2.5 Exposure Assessment.

The aim of this study was to evaluate the precision, accuracy, practicality, and potential uses of a PM2.5 miniaturized monitor (MM) in exposure assessment. These monitors (AirBeam, HabitatMap) were compared with the widely used direct-reading particulate matter monitors and a gravimetric reference method for PM2.5. Instruments were tested during 20 monitoring sessions that were subdivided in two different seasons to evaluate the performance of sensors across various environmental and meteorological conditions. Measurements were performed at an urban background site in Como, Italy. To evaluate the performance of the instruments, different analyses were conducted on 8-h averaged PM2.5 concentrations for comparison between direct-reading monitors and the gravimetric method, and minute-averaged data for comparison between the direct-reading instruments. A linear regression analysis was performed to evaluate whether the two measurement methods, when compared, could be considered comparable and/or mutually predictive. Further, Bland-Altman plots were used to determine whether the methods were characterized by specific biases. Finally, the correlations between the error associated with the direct-reading instruments and the meteorological parameters acquired at the sampling point were investigated. Principal results show a moderate degree of agreement between MMs and the reference method and a bias that increased with an increase in PM2.5 concentrations.

Miniaturized Monitors for Assessment of Exposure to Air Pollutants: A Review.

Air quality has a huge impact on different aspects of life quality, and for this reason, air quality monitoring is required by national and international regulations. Technical and procedural limitations of traditional fixed-site stations for monitoring or sampling of air pollutants are also well-known. Recently, a different type of miniaturized monitors has been developed. These monitors, due to their characteristics (e.g., low cost, small size, high portability) are becoming increasingly important for individual exposure assessment, especially since this kind of instrument can provide measurements at high spatial and temporal resolution, which is a notable advantage when approaching assessment of exposure to environmental contaminants. The aim of this study is indeed to provide information regarding current knowledge regarding the use of miniaturized air pollutant sensors. A systematic review was performed to identify original articles: a literature search was carried out using an appropriate query for the search of papers across three different databases, and the papers were selected using inclusion/exclusion criteria. The reviewed articles showed that miniaturized sensors are particularly versatile and could be applied in studies with different experimental designs, helping to provide a significant enhancement to exposure assessment, even though studies regarding their performance are still sparse.

Accuracy Evaluation of Three Modelling Tools for Occupational Exposure Assessment.

OBJECTIVES: The objective of this study is to evaluate the accuracy and robustness of three exposure-modelling tools [STOFFENMANAGER® v.6, European Centre for Ecotoxicology and Toxicology of Chemical Target Risk Assessment v.3.1 (ECETOC TRA v.3.1), and Advanced REACH Tool (ART v.1.5)], by comparing available measured data for exposure to organic solvents and pesticides in occupational exposure scenarios (ESs). METHODS: Model accuracy was evaluated by comparing the predicted and the measured values, expressed as an underestimation or overestimation factor (PRED/EXP), and by regression analysis. Robustness was quantitatively described by the so-called variable 'Uncertainty Factor' (UF), which was attributed to each model's input: a higher UF score indicates greater model uncertainty and poorer robustness. RESULTS: ART was the most accurate model, with median PRED/EXP factors of 1.3 and 0.15 for organic solvent and pesticide ESs, respectively, and a significant correlation (P < 0.05) among estimated and measured data. As expected, Tier 1 model ECETOC TRA demonstrated the worst performance in terms of accuracy, with median PRED/EXP factors of 2.0 for organic solvent ESs and 3545 for pesticide ESs. Simultaneously, STOFFENMANAGER® showed a median UF equal to 2.0, resulting in the most robust model. DISCUSSION: ECETOC TRA was not considered acceptable in terms of accuracy, confirming that this model is not appropriate for the evaluation of the selected ESs for pesticides. Conversely, STOFFENMANAGER® was the best choice, and ART tended to underestimate the exposure to pesticides. For organic solvent ESs, there were no cases of strong underestimation, and all models presented overall acceptable results; for the selected ESs, ART showed the best accuracy. Stoffenmanager was the most robust model overall, indicating that even with a mistake in ES interpretation, predicted values would remain acceptable. CONCLUSION: ART may lead to more accurate results when well-documented ESs are available. In other situations, Stoffenmanager appears to be a safer alternative because of its greater robustness, particularly when entry data uncertainty is difficult to assess. ECETOC TRA cannot be directly compared to higher tiered models because of its simplistic nature: the use of this tool should be limited only to exceptional cases in which a strong conservative and worst-case evaluation is necessary.

Genotype-specific mutations in the polymerase gene of hepatitis B virus potentially associated with resistance to oral antiviral therapy.

The evolution of hepatitis B virus (HBV) and the role of different variants during antiviral therapy may be influenced by HBV genotype. We have therefore analysed substitutions potentially related to nucleos(t)ide analogues (NAs) resistance at 42 positions within RT-region in a cohort of patients with chronic hepatitis B in relation to HBV-genotype. RT mutations analysis was performed by direct sequencing in 200 NAs-naïve patients and in 64 LAM or LAM+ADV experienced patients with NAs resistance, infected mainly by HBV-genotypes D and A. 27 polymorphic-sites were identified among the 42 positions analysed and 64 novel mutations were detected in 23 positions. Genotype-D displayed the highest mutation frequency (6.4%) among all HBV-genotypes analysed. Single or multiple mutations were detected in 80% of naïve patients. Overall, the most frequent single mutations were at residues rt54, rt53 and rt91 which may associate with significantly lower HBV-DNA levels (p=0.001). Comparison with sequencing data of patients failing LMV or LAM+ADV therapy revealed an higher frequency of novel genotype-specific mutations if compared with naïve patients: 3 mutations under LAM monotherapy in HBV-D (rtS85F; rtL91I; rtC256G) and 3 mutations under ADV therapy in HBV-A (rtI53V; rtW153R; rtF221Y). In HBV-D treated patients the dominant resistance mutation was rtL80V (31.4%) and rtM204I (60%) in LAM+ADV group while LAM-treated patients showed a preference of rtM204V (51.9%). Interestingly, none of HBV-A patients had mutation rtM204I under ADV add-on treatment but all of them had the "V" AA substitution. These results suggested that in patients with CHB, HBV-genotype might be relevant in the evolution and development of drug resistance showing also different mutation patterns in the YMDD motif between HBV genotype D and A.