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Alternative plasticizers such as diisononyl-1,2-cyclohexanedicarboxylate (DINCH), di(2-ethylhexyl) terephthalate (DEHTP), and di(2-ethylhexyl) adipate (DEHA) are progressively replacing phthalates in many consumer and professional products because of adverse effects on reproduction associated with some phthalates. Human exposures to these phthalate substitutes can occur through ingestion, skin absorption and inhalation. Skin uptake can lead to greater concentration at the target organs compared to ingestion because the skin exposure route bypasses the first-pass effect. Skin absorption studies are almost absent for these alternative plasticizers. We therefore wanted first, to characterize skin absorption of a mixture containing DINCH, DEHA and DEHTP in vitro using a flow-through diffusion cell system with ex vivo human skin, quantifying their respective monoester metabolites (mono-isononyl-cyclohexane-1,2-dicarboxylate (MINCH), mono-2-ethylhexyl adipate (MEHA), mono-2-ethylhexyl terephthalate (MEHTP), respectively); second, to validate these results by exposing five human volunteers to this mixture on their forearm and quantifying the corresponding urinary metabolites (including the monoesters and their oxidation products). Our study showed that two of these alternative plasticizers, DEHTP and DINCH, did not permeate skin showing as quantifiable metabolite levels in vitro and only traces of DEHA were quantified as its monoester metabolite, MEHA. Permeation coefficient (Kp) 0.06 and 55.8*10-7cm/h for neat and emulsified DEHA, respectively, while the permeation rate (J) remained low for both (0.005 and 0.001µg/cm2/h, respectively). Participants exposed to a mixture of these three plasticizers did not have noteworthy urinary concentrations of their respective metabolites after 24hours post-application. However, the alternative plasticizer mixture was completely absorbed after six hours post-application on the forearms of the human volunteers, and the urinary elimination curves showed a slight increase after 24hours post-application. Further studies on skin absorption of these substances should follow the urinary elimination kinetics of these metabolites more than 24hours post-application. We also recommend quantifying the parent compounds in the in vitro diffusion experiments.
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Exposure assessments to metalworking fluids (MWF) is difficult considering the complex nature of MWF. This study describes a comprehensive exposure assessment to straight and water-based MWFs among workers from 20 workshops. Metal and organic carbon (OC) content in new and used MWF were determined. Full-shift air samples of inhalable particulate and gaseous fraction were collected and analysed gravimetrically and for metals, OC, and aldehydes. Exposure determinants were ascertained through observations and interviews with workers. Determinants associated with personal inhalable particulate and gaseous fractions were systematically identified using mixed models. Similar inhalable particle exposure was observed for straight and water-based MWFs (64-386 µg/m3). The gaseous fraction was the most important contributor to the total mass fraction for both straight (322-2362 µg/m3) and water-based MWFs (101-699 µg/m3). The aerosolized particles exhibited low metal content irrespective of the MWF type; however, notable concentrations were observed in the sumps potentially reaching hazardous concentrations. Job activity clusters were important determinants for both exposure to particulate and gaseous fractions from straight MWF. Current machine enclosures remain an efficient determinant to reduce particulate MWF but were inefficient for the gaseous fraction. Properly managed water-based MWF meaning no recycling and no contamination from hydraulic fluids minimizes gaseous exposure. Workshop temperature also influenced the mass fractions. These findings suggest that exposures may be improved with control measures that reduce the gaseous fraction and proper management of MWF.
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Poluentes Ocupacionais do Ar , Exposição por Inalação , Metalurgia , Exposição Ocupacional , Material Particulado , Exposição Ocupacional/análise , Humanos , Exposição por Inalação/análise , Material Particulado/análise , Poluentes Ocupacionais do Ar/análise , Metais/análise , Adulto , Água/química , Masculino , Gases/análise , Monitoramento Ambiental/métodos , Pessoa de Meia-Idade , FemininoRESUMO
Population studies reveal widespread exposure to phthalates. Understanding their absorption, distribution, metabolism, and excretion is vital to reduce exposure. However, data on skin absorption remain limited. We thus aim to characterize the skin permeation of three phthalates in a mixture, neat or in emulsion; di(2-ethylhexyl) phthalate (d4-DEHP), dibutyl phthalate (d4-DBP), and diethyl phthalate (d4-DEP), by comparing in vitro human skin (800⯵m) permeation (24â¯hours) results using flow-through diffusion cells with urine results obtained from volunteers exposed to the same mixture applied to a forearm (40â¯cm2). Metabolites were analyzed in receptor fluids and urine. Phthalates crossed the skin barrier and metabolized into monoesters before elimination. Increased permeation was observed for phthalates in emulsion compared to neat substances, with polyethylene glycol (PEG) in the receptor fluid enhancing emulsion permeation, but not affecting neat substances. In vitro results mirrored in vivo findings: DEP showed rapid permeation (J: â¼2â¯ug/cm2/h) and urinary excretion peaking at six hours post-application, whereas DBP exhibited slower kinetics (J: â¼0.1â¯ug/cm2/h), with a urinary peak at 15-17â¯hours post-application. DEHP had minimal permeation (J: â¼0.0002â¯ug/cm2/h) with no observable urinary peak. These findings underscore the importance of comprehending phthalate skin absorption for effective exposure mitigation strategies.
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Dibutilftalato , Ácidos Ftálicos , Absorção Cutânea , Pele , Humanos , Ácidos Ftálicos/farmacocinética , Ácidos Ftálicos/urina , Ácidos Ftálicos/metabolismo , Adulto , Masculino , Dibutilftalato/farmacocinética , Dibutilftalato/urina , Dibutilftalato/metabolismo , Pele/metabolismo , Feminino , Dietilexilftalato/farmacocinética , Dietilexilftalato/metabolismo , Dietilexilftalato/urina , Adulto Jovem , Pessoa de Meia-Idade , Administração Cutânea , EmulsõesRESUMO
More than eight million premature deaths annually can be attributed to air pollution, with 99% of the world's population residing in areas below recommended air quality standards. Hence, the present study aimed to examine the association between primary DNA damage and air pollution data among 123 participants enrolled between 2011 and 2015 in Zagreb, Croatia. While most measured air pollutants adhered to regulatory limits, benzo[a]pyrene concentrations bound to PM10 exceeded them. Factorial analysis narrowed down air pollution data to four exposure factors (particulate matter, two metal factors, and other pollutants). Despite the absence of significant positive associations between modeled air pollution exposure factors and comet assay descriptors (tail length, tail intensity, tail moment, and highly damaged nuclei), the critical health implications of air pollution warrant further investigations, particularly with biomarkers of exposure and different biomarkers of effect in populations facing air pollution exposure.
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OBJECTIVE: In this pilot study on subway workers, we explored the relationships between particle exposure and oxidative stress biomarkers in exhaled breath condensate (EBC) and urine to identify the most relevant biomarkers for a large-scale study in this field. METHODS: We constructed a comprehensive occupational exposure assessment among subway workers in three distinct jobs over 10 working days, measuring daily concentrations of particulate matter (PM), their metal content and oxidative potential (OP). Individual pre- and post-shift EBC and urine samples were collected daily. Three oxidative stress biomarkers were measured in these matrices: malondialdehyde (MDA), 8-hydroxy-2'deoxyguanosine (8-OHdG) and 8-isoprostane. The association between each effect biomarker and exposure variables was estimated by multivariable multilevel mixed-effect models with and without lag times. RESULTS: The OP was positively associated with Fe and Mn, but not associated with any effect biomarkers. Concentration changes of effect biomarkers in EBC and urine were associated with transition metals in PM (Cu and Zn) and furthermore with specific metals in EBC (Ba, Co, Cr and Mn) and in urine (Ba, Cu, Co, Mo, Ni, Ti and Zn). The direction of these associations was both metal- and time-dependent. Associations between Cu or Zn and MDAEBC generally reached statistical significance after a delayed time of 12 or 24 h after exposure. Changes in metal concentrations in EBC and urine were associated with MDA and 8-OHdG concentrations the same day. CONCLUSION: Associations between MDA in both EBC and urine gave opposite response for subway particles containing Zn versus Cu. This diverting Zn and Cu pattern was also observed for 8-OHdG and urinary concentrations of these two metals. Overall, MDA and 8-OHdG responses were sensitive for same-day metal exposures in both matrices. We recommend MDA and 8-OHdG in large field studies to account for oxidative stress originating from metals in inhaled particulate matter.
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Ferrovias , Humanos , Estudos Prospectivos , Projetos Piloto , Material Particulado/análise , Metais , Biomarcadores/urina , Estresse Oxidativo , Testes RespiratóriosRESUMO
BACKGROUND: Electronic nicotine-delivery systems - also called e-cigarettes - are used by some tobacco smokers to assist with quitting. Evidence regarding the efficacy and safety of these systems is needed. METHODS: In this open-label, controlled trial, we randomly assigned adults who were smoking at least five tobacco cigarettes per day and who wanted to set a quit date to an intervention group, which received free e-cigarettes and e-liquids, standard-of-care smoking-cessation counseling, and optional (not free) nicotine-replacement therapy, or to a control group, which received standard counseling and a voucher, which they could use for any purpose, including nicotine-replacement therapy. The primary outcome was biochemically validated, continuous abstinence from smoking at 6 months. Secondary outcomes included participant-reported abstinence from tobacco and from any nicotine (including smoking, e-cigarettes, and nicotine-replacement therapy) at 6 months, respiratory symptoms, and serious adverse events. RESULTS: A total of 1246 participants underwent randomization; 622 participants were assigned to the intervention group, and 624 to the control group. The percentage of participants with validated continuous abstinence from tobacco smoking was 28.9% in the intervention group and 16.3% in the control group (relative risk, 1.77; 95% confidence interval, 1.43 to 2.20). The percentage of participants who abstained from smoking in the 7 days before the 6-month visit was 59.6% in the intervention group and 38.5% in the control group, but the percentage who abstained from any nicotine use was 20.1% in the intervention group and 33.7% in the control group. Serious adverse events occurred in 25 participants (4.0%) in the intervention group and in 31 (5.0%) in the control group; adverse events occurred in 272 participants (43.7%) and 229 participants (36.7%), respectively. CONCLUSIONS: The addition of e-cigarettes to standard smoking-cessation counseling resulted in greater abstinence from tobacco use among smokers than smoking-cessation counseling alone. (Funded by the Swiss National Science Foundation and others; ESTxENDS ClinicalTrials.gov number, NCT03589989.).
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Sistemas Eletrônicos de Liberação de Nicotina , Abandono do Hábito de Fumar , Adulto , Humanos , Nicotina/administração & dosagem , Nicotina/efeitos adversos , Abandono do Hábito de Fumar/métodos , Dispositivos para o Abandono do Uso de Tabaco/efeitos adversosRESUMO
BACKGROUND: Chemicals are not required to be tested systematically for their neurotoxic potency, although they may contribute to the development of several neurological diseases. The absence of systematic testing may be partially explained by the current Organisation for Economic Co-operation and Development (OECD) Test Guidelines, which rely on animal experiments that are expensive, laborious, and ethically debatable. Therefore, it is important to understand the risks to exposed workers and the general population exposed to domestic products. In this study, we propose a strategy to test the neurotoxicity of solvents using the commonly used glycol ethers as a case study. OBJECTIVE: This study aims to provide a strategy that can be used by regulatory agencies and industries to rank solvents according to their neurotoxicity and demonstrate the use of toxicokinetic modeling to predict air concentrations of solvents that are below the no observed adverse effect concentrations (NOAECs) for human neurotoxicity determined in in vitro assays. METHODS: The proposed strategy focuses on a complex 3D in vitro brain model (BrainSpheres) derived from human-induced pluripotent stem cells (hiPSCs). This model is accompanied by in vivo, in vitro, and in silico models for the blood-brain barrier (BBB) and in vitro models for liver metabolism. The data are integrated into a toxicokinetic model. Internal concentrations predicted using this toxicokinetic model are compared with the results from in vivo human-controlled exposure experiments for model validation. The toxicokinetic model is then used in reverse dosimetry to predict air concentrations, leading to brain concentrations lower than the NOAECs determined in the hiPSC-derived 3D brain model. These predictions will contribute to the protection of exposed workers and the general population with domestic exposures. RESULTS: The Swiss Centre for Applied Human Toxicology funded the project, commencing in January 2021. The Human Ethics Committee approval was obtained on November 16, 2022. Zebrafish experiments and in vitro methods started in February 2021, whereas recruitment of human volunteers started in 2022 after the COVID-19 pandemic-related restrictions were lifted. We anticipate that we will be able to provide a neurotoxicity testing strategy by 2026 and predicted air concentrations for 6 commonly used propylene glycol ethers based on toxicokinetic models incorporating liver metabolism, BBB leakage parameters, and brain toxicity. CONCLUSIONS: This study will be of great interest to regulatory agencies and chemical industries needing and seeking novel solutions to develop human chemical risk assessments. It will contribute to protecting human health from the deleterious effects of environmental chemicals. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/50300.
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BACKGROUND: Semivolatile organic compounds (SVOCs) comprise several different chemical families used mainly as additives in many everyday products. SVOCs can be released into the air as aerosols and deposit on particulate matter during use by dispersion, evaporation, or abrasion. Phthalates are SVOCs of growing concern due to their endocrine-disrupting effects. Human data on the absorption, distribution, metabolism, and excretion (ADME) of these compounds upon inhalation are almost nonexistent. OBJECTIVE: The goal of this study is to develop a method for repeated inhalation exposures to SVOCs to characterize their ADME in humans. METHODS: We will use diethylhexyl phthalate (DEHP), a major indoor air pollutant, as a model SVOC in this novel protocol. The Swiss official Commission on Ethics in Human Research, Canton de Vaud, approved the study on October 14, 2020 (project-ID 2020-01095). Participants (n=10) will be repeatedly exposed (2 short daily exposures over 4 days) to isotope-labeled DEHP (DEHP-d4) to distinguish administered exposures from background exposures. DEHP-d4 aerosols will be generated with a small, portable, aerosol-generating device. Participants will inhale DEHP-d4-containing aerosols themselves with this device at home. Air concentrations of the airborne phthalates will be less than or equal to their occupational exposure limit (OEL). DEHP-d4 and its metabolites will be quantified in urine and blood before, during, and after exposure. RESULTS: Our developed device can generate DEHP-d4 aerosols with diameters of 2.5 µm or smaller and a mean DEHP-d4 mass of 1.4 (SD 0.2) µg per puff (n=6). As of May 2023, we have enrolled 5 participants. CONCLUSIONS: The portable device can be used to generate phthalate aerosols for repeated exposure in human studies. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/51020.
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Like many other consumer and occupational products, pesticide formulations may contain active ingredients or co-formulants which have the potential to cause skin sensitisation. Currently, there is little evidence they do, but that could just reflect lack of clinical investigation. Consequently, it is necessary to carry out a safety evaluation process, quantifying risks so that they can be properly managed. A workshop on this topic in 2022 discussed how best to undertake quantitative risk assessment (QRA) for pesticide products, including learning from the experience of industries, notably cosmetics, that already undertake such a process routinely. It also addressed ways to remedy the matter of clinical investigation, even if only to demonstrate the absence of a problem. Workshop participants concluded that QRA for skin sensitisers in pesticide formulations was possible, but required careful justification of any safety factors applied, as well as improvements to the estimation of skin exposure. The need for regulations to stay abreast of the science was also noted. Ultimately, the success of any risk assessment/management for skin sensitisers must be judged by the clinical picture. Accordingly, the workshop participants encouraged the development of more active skin health monitoring amongst groups most exposed to the products.
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Cosméticos , Dermatite Alérgica de Contato , Praguicidas , Humanos , Dermatite Alérgica de Contato/etiologia , Praguicidas/toxicidade , Pele , Medição de Risco , Cosméticos/toxicidadeRESUMO
The current evidence on nanomaterial toxicity is mostly derived from experimental studies making it challenging to translate it into human health risks. We established an international cohort (N = 141 workers) within the EU-LIFE project "NanoExplore" to address possible health effects from occupational exposures to nanomaterials. We used a handheld direct-reading optical particle counter to measure airborne nanoparticle number concentrations (PNC) and lung-deposited surface areas (LDSAs). Airborne particles were characterized by TEM and SEM-EDAX. We assessed oxidative/nitrosative stress with a panel of biomarkers in exhaled breath condensate (EBC) (8-isoprostane, malondialdehyde, nitrotyrosine), inflammation (high-sensitivity C reactive protein (hs-CRP), IL-1ß, TNF-α, IL-10) and KL-6 (considered as biomarker of interstitial lung fibrosis) and urine (total antioxidant power (TAP), 8-isoprostane, and malondialdehyde). Exhaled breath sampled in gas-sampling bags were assessed for oxidative potential. These biomarkers were quantified pre-shift at the beginning of the workweek and post-shift the 4th day. Relationships between airborne nanoparticle concentration and biomarkers were assessed by multiple linear regression with log-transformed exposure and biomarker concentrations adjusted for potential confounders. We found a positive dose-response relationship for three inflammation biomarkers (IL-10, IL-1ß and TNF-α) in EBC with both PNC and LDSA. A negative dose-response relationship was observed between PNC and TAP. This study suggests that occupational exposures to nanoparticles can affect the oxidative balance and the innate immunity in occupationally exposed workers. However, owing to the intrinsic variability of biomarkers, the observed changes along with their health significance should be assessed in a long-term perspective study.
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Nanoestruturas , Exposição Ocupacional , Humanos , Interleucina-10 , Fator de Necrose Tumoral alfa , Biomarcadores , Exposição Ocupacional/efeitos adversos , Antioxidantes , InflamaçãoRESUMO
Few epidemiological studies use exposure determinants specifically tailored to assess pesticide or plant protection product (PPP) exposures when assessing presumed association between occupational exposure and health outcomes among agricultural workers. This lack of exposure specificity could lead to results that fail to detect an association. It could be related to the lack of consensus on exposure assessment methods and the choice of exposure determinants. We conducted a meta-analysis following the PRISMA checklist to identify PPP exposure determinants used in occupational studies and identified exposure determinants that best characterized agricultural exposures to PPPs. Out of 1436 studies identified, 71 were included. The exposure determinants identified were active ingredients, chemical classes, types of PPP, crops, tasks, frequencies, duration, lifetime exposure days, and intensity-weighted exposure days. Only six over 17 associations between exposure determinants and health outcomes were found with moderate quality of evidence. Overall, epidemiological studies had difficulty defining relevant determinants to characterize PPP exposures for agricultural workers. We recommend that a standardized list of determinants for PPP exposures in occupational exposure studies should include information on formulations, intensity, duration, and frequency of PPP exposure. Harmonized data collection on exposure and health outcomes are required as well as standard units for each exposure determinant.
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The environmental impact on health is an inevitable by-product of human activity. Environmental health sciences is a multidisciplinary field addressing complex issues on how people are exposed to hazardous chemicals that can potentially affect adversely the health of present and future generations. Exposure sciences and environmental epidemiology are becoming increasingly data-driven and their efficiency and effectiveness can significantly improve by implementing the FAIR (findable, accessible, interoperable, reusable) principles for scientific data management and stewardship. This will enable data integration, interoperability and (re)use while also facilitating the use of new and powerful analytical tools such as artificial intelligence and machine learning in the benefit of public health policy, and research, development and innovation (RDI). Early research planning is critical to ensuring data is FAIR at the outset. This entails a well-informed and planned strategy concerning the identification of appropriate data and metadata to be gathered, along with established procedures for their collection, documentation, and management. Furthermore, suitable approaches must be implemented to evaluate and ensure the quality of the data. Therefore, the 'Europe Regional Chapter of the International Society of Exposure Science' (ISES Europe) human biomonitoring working group (ISES Europe HBM WG) proposes the development of a FAIR Environment and health registry (FAIREHR) (hereafter FAIREHR). FAIR Environment and health registry offers preregistration of studies on exposure sciences and environmental epidemiology using HBM (as a starting point) across all areas of environmental and occupational health globally. The registry is proposed to receive a dedicated web-based interface, to be electronically searchable and to be available to all relevant data providers, users and stakeholders. Planned Human biomonitoring studies would ideally be registered before formal recruitment of study participants. The resulting FAIREHR would contain public records of metadata such as study design, data management, an audit trail of major changes to planned methods, details of when the study will be completed, and links to resulting publications and data repositories when provided by the authors. The FAIREHR would function as an integrated platform designed to cater to the needs of scientists, companies, publishers, and policymakers by providing user-friendly features. The implementation of FAIREHR is expected to yield significant benefits in terms of enabling more effective utilization of human biomonitoring (HBM) data.
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Nanotechnology applications are fast-growing in many industrial fields. Consequently, health effects of engineered nanomaterials (ENMs) should be investigated. Within the EU-Life project NanoExplore, we developed a harmonized protocol of an international multicenter prospective cohort study of workers in ENM-producing companies. This article describes the development of the protocol, sample size calculation, data collection and management procedures and discusses its relevance with respect to research needs. Within this protocol, workers' ENM exposure will be assessed over four consecutive working days during the initial recruitment campaign and the subsequent follow-up campaigns. Biomonitoring using noninvasive sampling of exhaled breath condensate (EBC), exhaled air, and urine will be collected before and after 4-day exposure monitoring. Both exposure and effect biomarkers, will be quantified along with pulmonary function tests and diagnosed diseases reported using a standardized epidemiological questionnaire available in four languages. Until now, this protocol was implemented at seven companies in Switzerland, Spain and Italy. The protocol is well standardized, though sufficiently flexible to include company-specific conditions and occupational hygiene measures. The recruitment, to date, of 140 participants and collection of all data and samples, enabled us launching the first international cohort of nanotechnology workers. All companies dealing with ENMs could join the NanoExplore Consortium, apply this harmonized protocol and enter in the cohort, concieved as an open cohort. Its protocol meets all requirements of a hypotheses-driven prospective study, which will assess and reassess effects of ENM exposure on workers' health by updating the follow-up of the cohort. New hypothesis could be also considered.
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Nanoestruturas , Exposição Ocupacional , Humanos , Estudos Prospectivos , Exposição Ocupacional/análise , Nanotecnologia , Nanoestruturas/toxicidade , Monitoramento Biológico , Estudos Multicêntricos como AssuntoRESUMO
Glycol ethers are solvents used in a plethora of occupational and household products exposing the users to potential toxic effects. Several glycol ethers derived from ethylene glycol induce hematological toxicity, such as anemia in workers. The exposure effects on blood cells of glycol ethers derived from propylene glycol are unknown in humans. The aim of our study was to evaluate blood parameters indicative of red blood cell (RBC) hemolysis and oxidative stress in participants exposed to propylene glycol (propylene glycol monobutyl ether (PGBE) and propylene glycol monomethyl ether (PGME)), two extensively used propylene glycol derivatives worldwide. Seventeen participants were exposed 2 h in a control inhalation exposure chamber to low PGME (35 ppm) and PGBE (15 ppm) air concentrations. Blood was regularly collected before, during (15, 30, 60, and 120 min), and 60 min after exposure for RBC and oxidative stress analyses. Urine was also collected for clinical effects related to hemolysis. Under the study conditions, our results showed that the blood parameters such as RBCs, hemoglobin concentration, and white blood cells tended to increase in response to PGME and PGBE exposures. These results raise questions about the possible effects in people regularly exposed to higher concentrations, such as workers.
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Éteres , Hemólise , Humanos , Éteres/toxicidade , Voluntários Saudáveis , Propilenoglicóis/toxicidade , Propilenoglicol/toxicidadeRESUMO
N-Nitrosamines are potent carcinogens and considered non-threshold carcinogens in various regulatory domains. However, recent data indicate the existence of a threshold for genotoxicity, which can be adequately demonstrated. This aspect has a critical impact on selecting the methodology that is applied to derive occupational exposure limits (OELs). OELs are used to protect workers potentially exposed to various chemicals by supporting the selection of appropriate control measures and ultimately reducing the risk of occupational cancer. Occupational exposures to nitrosamines occur during manufacturing processes, mainly in the rubber and chemical industry. The present study derives OELs for inhaled N-nitrosamines, employing the benchmark dose (BMD) approach if data are adequate and read-across for nitrosamines without adequate data. Additionally, benchmark dose lower confidence limit (BMDL) is preferred and more suitable point-of-departure (PoD) to calculate human health guidance values, including OEL. The lowest OEL (0.2 µg/m3 ) was derived for nitrosodiethylamine (NDEA), and nitrosopiperidine (NPIP) (OEL = 0.2 µg/m3 ), followed by nitrosopyrrolidine (NPYR) (0.4 µg/m3 ), nitrosodimethylamine (NDMA), nitrosodimethylamine (NMEA), and nitrosodipropylamine (NDPA) (0.5 µg/m3 ), nitrosomorpholine (NMOR) (OEL = 1 µg/m3 ), and nitrosodibutylamine (NDBA) (OEL = 2.5 µg/m3 ). Limits based on "non-threshold" TD50 slope calculation were within a 10-fold range. These proposed OELs do not consider skin absorption of nitrosamines, which is also a possible route of entry into the body, nor oral or other environmental sources. Furthermore, we recommend setting a limit for total nitrosamines based on the occupational exposure scenario and potency of components.
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Nitrosaminas , Exposição Ocupacional , Humanos , Carcinógenos/toxicidade , Dimetilnitrosamina , Benchmarking , Nitrosaminas/toxicidade , Dietilnitrosamina , Exposição Ocupacional/efeitos adversosRESUMO
Human biomonitoring (HBM) data measured in specific contexts or populations provide information for comparing population exposures. There are numerous health-based biomonitoring guidance values, but to locate these values, interested parties need to seek them out individually from publications, governmental reports, websites and other sources. Until now, there has been no central, international repository for this information. Thus, a tool is needed to help researchers, public health professionals, risk assessors, and regulatory decision makers to quickly locate relevant values on numerous environmental chemicals. A free, on-line repository for international health-based guidance values to facilitate the interpretation of HBM data is now available. The repository is referred to as the "Human Biomonitoring Health-Based Guidance Value (HB2GV) Dashboard". The Dashboard represents the efforts of the International Human Biomonitoring Working Group (i-HBM), affiliated with the International Society of Exposure Science. The i-HBM's mission is to promote the use of population-level HBM data to inform public health decision-making by developing harmonized resources to facilitate the interpretation of HBM data in a health-based context. This paper describes the methods used to compile the human biomonitoring health-based guidance values, how the values can be accessed and used, and caveats with using the Dashboard for interpreting HBM data. To our knowledge, the HB2GV Dashboard is the first open-access, curated database of HBM guidance values developed for use in interpreting HBM data. This new resource can assist global HBM data users such as risk assessors, risk managers and biomonitoring programs with a readily available compilation of guidance values.
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Monitoramento Biológico , Monitoramento Ambiental , Humanos , Monitoramento Ambiental/métodos , Saúde Global , Saúde PúblicaRESUMO
Oxidative stress can contribute to the development of diseases, and may originate from exposures to toxicants commonly found in air pollution and cigarette smoke such as polycyclic aromatic hydrocarbons (PAHs) and volatile organic compounds (VOCs). Yet, associations between these exposures and oxidative stress biomarkers are poorly characterized. We report here novel associations between 14 exposure biomarkers of PAHs and VOCs, and two oxidative stress biomarkers; 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) and 8-isoprostaglandin F2α (8-isoprostane) in urine obtained from smokers participating in an ongoing clinical study (ESTxENDS, NCT03589989). We also assessed associations between six biomarkers of tobacco smoke exposure (metabolites of nicotine and tobacco-specific nitrosamines (TSNAs)) and both oxidative stress biomarkers. We then quantified the relative importance of each family of the 20 exposure biomarkers on oxidative stress. Participating smokers (153 men and 117 women, median age 44 years) had on average smoked 25 [2-62] years and smoked about 17 [5-40] cigarettes per day at the time of the study. Multiple linear regression results showed an association between 8-oxodG concentrations and the following metabolites in decreasing relative importance: PAHs (beta coefficient ß = 0.105, p-value <0.001, partial R2 = 0.15) > VOCs (ß = 0.028, p < 0.001, partial R2 = 0.09) > nicotine (ß = 0.226, p < 0.001, partial R2 = 0.08); and between 8-isoprostane concentrations and metabolites of PAHs (ß = 0.117, p < 0.001, partial R2 = 0.14) > VOCs (ß = 0.040, p < 0.001, partial R2 = 0.14) > TSNAs (ß = 0.202, p = 0.003, partial R2 = 0.09) > nicotine (ß = 0.266, p < 0.001, partial R2 = 0.08). Behavioral factors known to contribute to oxidative stress, including sleep quality, physical activity, and alcohol consumption, did not play a significant role. Exposures to PAHs and VOCs among smokers were significantly associated with oxidative stress.
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Nitrosaminas , Hidrocarbonetos Policíclicos Aromáticos , Poluição por Fumaça de Tabaco , Compostos Orgânicos Voláteis , Adulto , Feminino , Humanos , Masculino , 8-Hidroxi-2'-Desoxiguanosina , Biomarcadores/urina , Nicotina/análise , Nitrosaminas/urina , Estresse Oxidativo , Hidrocarbonetos Policíclicos Aromáticos/análise , Fumantes , Poluição por Fumaça de Tabaco/análise , Compostos Orgânicos Voláteis/análiseRESUMO
Air pollution is recognized as one of the most serious public health issues worldwide and was declared to be a leading environmental cause of cancer deaths. At the same time, the cytokinesis-block micronucleus (CBMN) assay serves as a cancer predictive method that is extensively used in human biomonitoring for populations exposed to environmental contamination. The objective of this cross-sectional study is two-fold: to evaluate genomic instability in a sample (N = 130) of healthy, general population residents from Zagreb (Croatia), chronically exposed to different levels of air pollution, and to relate them to air pollution levels in the period from 2011 to 2015. Measured frequencies of CBMN assay parameters were in agreement with the baseline data for the general population of Croatia. Air pollution exposure was based on four factors obtained from a factor analysis of all exposure data obtained for the examined period. Based on the statistical results, we did not observe a significant positive association between any of the CBMN assay parameters tested and measured air pollution parameters for designated time windows, except for benzo(a)pyrene (B[a]P) that showed significant negative association. Our results show that measured air pollution parameters are largely below the regulatory limits, except for B[a]P, and as such, they do not affect CBMN assay parameters' frequency. Nevertheless, as air pollution is identified as a major health threat, it is necessary to conduct prospective studies investigating the effect of air pollution on genome integrity and human health.
Assuntos
Poluição do Ar , Citocinese , Poluição do Ar/efeitos adversos , Croácia , Estudos Transversais , Dano ao DNA , Humanos , Linfócitos , Testes para Micronúcleos/métodos , Estudos ProspectivosRESUMO
Hydrogen peroxide (H2O2) is a strong oxidizing agent often used in hair coloring and as a component in disinfecting and bleaching processes. Exposures to H2O2 generate reactive oxygen species (ROS) that can cause significant airway irritation and inflammation. Even though workers have reported symptoms associated with sensitivity and irritation from acute exposures below the H2O2 occupational exposure levels (OELs), a lack of sensitive analytical methods for measuring airborne concentrations currently prevents evaluating low or peak H2O2 exposures. To fill these gaps, we propose two different sensitive approaches: (i) luminol chemiluminescence (CL) to specifically measure H2O2; and (ii) photonic sensor method based on the ferrous-xylenol orange assay to evaluate total oxidative potential (OP), a measure of ROS in sampled air. We chose two exposure scenarios: hairdressers preparing and applying hair color to clients (both in simulated and field environments) and workers operating disinfecting cycles at a bottling company. Hair coloring took about 1 h for each client, and the application of the coloring product generated the highest H2O2 concentrations. OP values were highly correlated with H2O2 concentrations (CL measurement) and allowed peak measurements as low as 6 µg m-3 of H2O2 concentrations. The bottling company used a disinfectant containing H2O2, acetic acid and peracetic acid (PAA) in an enclosed process. The photonic sensor was immediately saturated. The CL results showed that the process operator had the highest exposures during a 15-min cycle. There is still a need to develop these direct reading methods for operating in the field, but we believe that in the future an OEL for OP could protect workers from developing airway irritation and inflammation by reducing exposures to oxidizing chemicals.