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1.
Toxins (Basel) ; 16(3)2024 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-38535805

RESUMO

The mycotoxin deoxynivalenol (DON) was one of the priority substances in the European Joint Human Biomonitoring Initiative (HBM4EU) project. In this study, to better interpret the actual internal exposure of DON in the general population and safeguard public health, human biomonitoring guidance values of DON for the general population (HBM-GVGenPop) were derived. The HBM-GVGenPop of DON was based on either the total DON (DON and its glucuronides) or DON's main metabolite (DON-15-GlcA) levels in 24-h urine samples, resulting in a HBM-GVGenPop of 0.023 µg/mL for the total DON or a HBM-GVGenPop of 0.020 µg/mL for DON-15-GlcA. The use of 24-h urine samples is recommended based on the fact that DON and its metabolites have a short elimination half-life (T1/2), and 95% of the cumulative amount was excreted within 12 h after DON intake. The T1/2 for DON, DON-15-GlcA, and total DON were estimated to be 2.55 h, 2.95 h, and 2.95 h, respectively. Therefore, a 24-h urine sample reflects almost all of the DON exposure from the previous day, and this type of sample was considered for the derivation of a HBM-GVGenPop for DON.


Assuntos
Monitoramento Biológico , Micotoxinas , Tricotecenos , Humanos , Glucuronídeos
2.
Int J Hyg Environ Health ; 234: 113747, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33862487

RESUMO

Cadmium (Cd) is a toxic heavy metal widespread in the environment leading to human exposure in particular through diet (when smoking is excluded), as documented by recent human biomonitoring (HBM) surveys. Exposure to Cd at environmental low-exposure levels has been associated with adverse effects such as renal toxicity and more recently bone effects. The implication, even if limited, of Cd in the etiology of osteoporosis can be of high importance at the population level given the significant prevalence of osteoporosis and the ubiquitous and life-long exposure to Cd. Therefore, the osteoporosis cases attributable to Cd exposure was estimated in three European countries (Belgium, France and Spain), based on measured urinary Cd levels from HBM studies conducted in these countries. The targeted population was women over 55 years old, for which risk levels associated with environmental Cd exposure were available. Around 23% of the cases were attributed to Cd exposure. Moreover, in a prospective simulation approach of lifelong urinary Cd concentrations assuming different intakes scenarios, future osteoporosis attributable cases were calculated, based on urinary Cd levels measured in women aged under 55. Between 6 and 34% of the considered populations under 55 years were at risk for osteoporosis. Finally, the costs associated to the burden of osteoporosis-related fractures attributable to Cd for each country targeted in this paper were assessed, standing for a major contributing role of Cd exposure in the overall social costs related to osteoporosis. Absolute costs ranged between 0.12 (low estimate in Belgium) and 2.6 billion Euros (high estimate in France) in women currently over 55 years old and at risk for fractures. Our results support the importance of reducing exposure of the general population to Cd.


Assuntos
Cádmio , Osteoporose , Bélgica/epidemiologia , Exposição Ambiental/análise , Feminino , França/epidemiologia , Humanos , Pessoa de Meia-Idade , Osteoporose/epidemiologia , Estudos Prospectivos , Espanha/epidemiologia
3.
Int J Hyg Environ Health ; 234: 113722, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33711757

RESUMO

Ubiquitous use of plasticizers has led to a widespread internal exposure of the European population. Until today, metabolites are detected in almost every urine sample analysed. This raised the urgent need for a toxicological interpretation of the internal exposure levels. The European Human Biomonitoring Initiative (HBM4EU) contributes substantially to the knowledge on the actual exposure of European citizens to chemicals prioritised within HBM4EU, on their potential impact on health and on the interpretation of these data to improve policy making. On that account, human biomonitoring guidance values (HBM-GVs) are derived for the general population and the occupationally exposed population agreed at HBM4EU consortium level. These values can be used to assess phthalate exposure levels measured in HBM studies in a health risk assessment context. HBM-GVs were derived for five phthalates (DEHP, DnBP, DiBP, BBzP and DPHP) and for the non-phthalate substitute Hexamoll® DINCH. For the adult general population, the HBM-GVs for the specific metabolite(s) of the respective parent compounds in urine are the following: 0.5 mg/L for the sum of 5-oxo-MEHP and 5-OH-MEHP; 0.19 mg/L for MnBP, 0.23 mg/L for MiBP; 3 mg/L for MBzP; 0.5 mg/L for the sum of oxo-MPHP and OH-MPHP and 4.5 mg/L for the sum of OH-MINCH and cx-MINCH. The present paper further specifies HBM-GVs for children and for workers.


Assuntos
Poluentes Ambientais , Ácidos Ftálicos , Adulto , Monitoramento Biológico , Criança , Exposição Ambiental/análise , Monitoramento Ambiental , Humanos , Plastificantes
4.
Environ Int ; 147: 106337, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33385924

RESUMO

AIMS: The methodology agreed within the framework of the HBM4EU project is used in this work to derive HBM-GVs for the general population (HBM-GVGenPop) and for workers (HBM-GVWorker) exposed to cadmium (Cd) and its compounds. METHODS: For Cd, a significant number of epidemiological studies with dose-response relationships are available, in particular for kidney effects. These effects are described in terms of a relation between urinary Cd (U-Cd) or blood Cd (B-Cd) levels and low molecular weight proteinuria (LMWP) markers like beta-2-microglobulin (ß2M) and retinol-binding protein (RBP). In order to derive HBM-GVs for the general population and workers, an assessment of data from evaluations conducted by national or international organisations was undertaken. In this work, it appeared relevant to select renal effects as the critical effect for the both groups, however, differences between general population (including sensitive people) and workers (considered as an homogenous population of adults who should not be exposed to Cd if they suffer from renal diseases) required the selection of different key studies (i.e. conducted in general population for HBM-GVGenPop and at workplace for HBM-GVWorker). RESULTS AND CONCLUSIONS: For U-Cd, a HBM-GVGenPop of 1 µg/g creatinine (creat) is recommended for adults older than 50 years, based on a robust meta-analysis performed by EFSA (EFSA, 2009a). To take into account the accumulation of Cd in the human body throughout life, threshold or 'alert' values according to age were estimated for U-Cd. At workplace, a HBM-GVWorker of 2 µg/g creat is derived from the study of Chaumont et al., (2011) for U-Cd, and in addition to this recommendation a HBM-GVworker for B-Cd of 5 µg/L is also proposed. The HBM-GVWorker for U-Cd is similar to the biological limit value (BLV) set by the new amendment of the European Carcinogens and Mutagens Directive in June 2019 (2 µg/g creat for U-Cd).


Assuntos
Cádmio , Nefropatias , Adulto , Monitoramento Biológico , Biomarcadores , Cádmio/toxicidade , Humanos , Rim
5.
Environ Int ; 154: 106563, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-33894553

RESUMO

The "European Human Biomonitoring Initiative" (HBM4EU) derives human biomonitoring guidance values (HBM-GVs) for the general population (HBM-GVGenPop) and/or for occupationally exposed adults (HBM-GVWorker) for several priority substances and substance groups as identified by policy makers, scientists and stakeholders at EU and national level, including bisphenol A (BPA). Human exposure to BPA is widespread and of particular concern because of its known endocrine-disrupting properties. Unlike the conjugated forms of BPA circulating in the body, free BPA is known to interact with the nuclear estrogen receptors. Because free BPA is considered to be more toxicologically active than the conjugated forms (e.g. BPA-glucuronide (BPA-G) and BPA-sulfate (BPA-S)), its measurement in blood provides the superior surrogate of the biologically effective dose. However, considering the difficulty of implementing blood sampling in large HBM cohorts, as well as the current analytical capacities complying with the quality assurance (QA)/quality control (QC) schemes, total BPA in urine (i.e. the sum of free and conjugated forms of BPA measured after an hydrolysis of phase II metabolites) was retained as the relevant exposure biomarker for BPA. HBM-GVGenPop for total BPA in urine of 230 µg/L and 135 µg/L for adults and children, respectively, were developed on the basis of toxicological data. To derive these values, the concentrations of urinary total BPA consistent with a steady-state exposure to the temporary Tolerable Daily Intake (t-TDI) of 4 µg/kg bw/day set in 2015 by the European Food Safety Authority (EFSA) were estimated. The BPA human physiologically-based pharmacokinetic (PBPK) model developed by Karrer et al. (2018) was used, assuming an oral exposure to BPA at the t-TDI level averaged over 24 h. Dermal uptake of BPA is suspected to contribute substantially to the total BPA body burden, which in comparison with the oral route, is generating a higher ratio of free BPA to total BPA in blood. Therefore, an alternative approach for calculating the HBM-GVGenPop according to the estimated relative contributions of both the oral and dermal routes to the global BPA exposure is also discussed. Regarding BPA exposure at the workplace, the steady-state concentration of urinary total BPA was estimated after a dermal uptake of BPA that would generate the same concentration of free BPA in plasma (considered as the bioactive form) as would a 24 h-averaged intake to the European Chemicals Agency (ECHA)'s oral DNEL of 8 µg BPA/kg bw/day set for workers. The predicted concentration of urinary total BPA at steady-state is equivalent to, or exceeds the 95th percentile of total BPA in urine measured in different European HBM studies conducted in the general population. Thus, no HBM-GVWorker was proposed, as the high background level of BPA coming from environmental exposure - mostly through food intake - is making the discrimination with the occupational exposure to BPA difficult.


Assuntos
Monitoramento Biológico , Monitoramento Ambiental , Adulto , Compostos Benzidrílicos/análise , Biomarcadores , Criança , Exposição Ambiental/análise , Humanos , Fenóis
6.
Int J Hyg Environ Health ; 236: 113778, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34089975

RESUMO

The European Human Biomonitoring Initiative (HBM4EU1) has established a European Union-wide human biomonitoring (HBM) programme to generate knowledge on human internal exposure to chemical pollutants and their potential health impacts in Europe, in order to support policy makers' efforts to ensure chemical safety and improve health in Europe. A prioritisation strategy was necessary to determine and meet the most important needs of both policy makers and risk assessors, as well as common national needs of participating countries and a broad range of stakeholders. This strategy consisted of three mains steps: 1) mapping of knowledge gaps identified by policy makers, 2) prioritisation of substances using a scoring system, and 3) generation of a list of priority substances reflective of the scoring, as well as of public policy priorities and available resources. For the first step, relevant ministries and agencies at EU and national levels, as well as members of the Stakeholder Forum each nominated up to 5 substances/substance groups of concern for policy-makers. These nominations were collated into a preliminary list of 48 substances/substance groups, which was subsequently shortened to a list of 23 after considering the total number of nominations each substance/substance group received and the nature of the nominating entities. For the second step, a panel of 11 experts in epidemiology, toxicology, exposure sciences, and occupational and environmental health scored each of the substances/substance groups using prioritisation criteria including hazardous properties, exposure characteristics, and societal concern. The scores were used to rank the 23 substances/substance groups. In addition, substances were categorised according to the level of current knowledge about their hazards, extent of human exposure (through the availability of HBM data), regulatory status and availability of analytical methods for biomarker measurement. Finally, in addition to the ranking and categorisation of the substances, the resources available for the project and the alignment with the policy priorities at European level were considered to produce a final priority list of 9 substances/substance groups for research activities and surveys within the framework of the HBM4EU project.


Assuntos
Monitoramento Biológico , Poluentes Ambientais , Biomarcadores , Monitoramento Ambiental , Poluentes Ambientais/análise , União Europeia , Humanos
7.
Int J Hyg Environ Health ; 230: 113622, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-33045523

RESUMO

The European Joint Program "HBM4EU" is a joint effort of 30 countries and the European Environment Agency, co-funded under the European Commission's Horizon 2020 program, for advancing and implementing human biomonitoring (HBM) on a European scale and for providing scientific evidence for chemical policy making. One important outcome will be a Europe-wide improvement and harmonization of health risk assessment following the coordinated derivation or update of health-related guidance values referring to the internal body burden. These guidance values - named HBM guidance values or HBM-GVs - can directly be compared with HBM data. They are derived within HBM4EU for priority substances identified by the HBM4EU chemicals prioritization strategy based on existing needs to answer policy relevant questions as raised by national and EU policy makers. HBM-GVs refer to both the general population and occupationally exposed adults. Reports including the detailed reasoning for the values' proposals are subjected to a consultation process within all partner countries of the consortium to reach a broad scientific consensus on the derivation approach and on the derived values. The final HBM-GVs should be applied first within the HBM4EU project, but may also be useful for regulators and risk assessors outside this project. The subsequent adoption of derived HBM-GVs at EU-level needs to be discussed and decided within the responsible EU bodies. Nevertheless, the establishment of HBM-GVs as part of HBM4EU is already a step forward in strengthening HBM-based policy efforts for public and occupational health. The strategy for deriving HBM-GVs which is based on already existing approaches from the German HBM Commission, the French Agency for Food, Environmental and Occupational Health & Safety (ANSES) as well as from the US-based scientific consultant Summit Toxicology, the allocation of a level of confidence to the derived values, and the consultation process within the project are comprehensively described to enlighten the work accomplished under the HBM4EU initiative.


Assuntos
Monitoramento Biológico , Formulação de Políticas , Adulto , Carga Corporal (Radioterapia) , Saúde Ambiental , Humanos , Medição de Risco
8.
Int J Hyg Environ Health ; 222(5): 727-737, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31176761

RESUMO

Human biomonitoring (HBM) is an important tool to survey the internal exposure of humans which represents the real life chemical body burden to chemicals and/or their metabolites. It results from total exposure to chemical substances from different sources and via different routes. These substances may be regulated under different legislative frameworks on chemicals (e.g., environmental, occupational, food safety etc). In occupational health, HBM has long traditions to control the exposures at workplaces. By providing accurate data on internal exposure, HBM data can improve human health risk assessment (RA) for both the general population and workers. Although the past few years have shown good examples on the use of HBM in the RA of chemicals, there is still quite some work to be done to improve its use in a regulatory RA. Under the scope of the European Human Biomonitoring Initiative (project HBM4EU, 2017-2021), the current study reviews the state-of-the-art of HBM use in chemicals RA with a special focus in Europe, and attempts to identify hurdles and challenges faced by regulators. To gather information on the use of HBM, including the availability of guidance on how to use it in RA, the RA schemes applied by different European or international organizations were analysed. Examples of such use were identified for a few selected groups of chemicals of concern for human health. In addition, we present the results of a survey, aimed at collecting information from national regulatory risk assessors on their day-to-day RA practices, the use of HBM data, and the obstacles and challenges related to their use. The results evidenced and explained some of the current obstacles of using HBM data in RA. These included the lack of HBM guidance values or biomonitoring equivalents (BEs), limited toxicokinetic information to support the interpretation of HBM data and, in the occupational health and safety (OSH) field, the lack of legal enforcement. Therefore, to support the integration of HBM in regulatory RA, we recommend, on one hand, the elaboration of a EU level guidance on the use of HBM in RA and, on the other hand, the continuation of research efforts to integrate HBM with new RA approaches using in vitro/in silico data and Adverse Outcome Pathways (AOPs).


Assuntos
Monitoramento Biológico , Previsões , Medição de Risco/tendências , Exposição Ambiental/análise , Poluentes Ambientais/toxicidade , Europa (Continente)/epidemiologia , Humanos , Medição de Risco/métodos , Organização Mundial da Saúde
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