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A special issue of Toxics (ISSN 2305-6304). This special issue belongs to the section "Exposome Analysis and Risk Assessment".

Deadline for manuscript submissions: closed (31 January 2024) | Viewed by 23455

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Dr. Carina Ladeira

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Escola Superior de Tecnologia da Saúde de Lisboa—Instituto Politécnico de Lisboa, Departamento das Ciências do Diagnóstico, Terapêutica e Saúde Pública, Av. D. João II, Lote 4.69.01 | 1990-096 Lisboa, Portugal
Interests: human biomonitoring; genetic toxicology; chemical mixtures; risk assessment; occupational health; in vitro
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Special Issue Information

Dear Colleagues,

Human beings live in constant contact with chemical agents—mainly through environmental exposure—which are derived from the occupational setting. Environmental exposure is ubiquitous, originating from air, water, and soil. While some chemicals are short-lived in the environment and may elicit no harmful effects in humans, other chemicals bioaccumulate or persist for a long time in the environment or the human body due to frequent exposure. However, environmental exposure also includes diet, lifestyle, and hobbies, and exposure to other substances such as drugs, food additives, pesticides, and nanomaterials, among other daily products, which are significant areas of research. Occupational exposure concerns the potentially harmful exposure to hazardous chemicals in the workplace; however, more specifically, it involves permanent and substantial contact with the determined substances. Possible health effects can arise from these types of exposure, which can be measured and prevented by biomonitoring, and the outcome should be integrated to ensure better regulatory decision making. With that objective and on behalf of this study, translation research should be conducted by using in vitro studies with exposures from real context scenarios adding to the body of knowledge and providing a better understanding of human biomonitoring outcomes, mainly in the chemical mixtures effects assessment.

The expectation is that the results taken from these studies can add data and integrated information to encourage national and international bodies to make decisions such as setting allowable concentrations for a wide range of substances from environmental and occupational exposures, with particular attention paid to newly identified chemical mixtures and agents, which should be swiftly regulated.

Original research articles and review articles on these topics are encouraged to be submitted and we look forward to receiving your contributions.

Prof. Dr. Carina Ladeira
Guest Editor

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Keywords

environmental exposure
occupational exposure
chemical agents
endocrine disruptors
exposome
chemical mixtures
regulatory toxicology
preventive healthcare
biomarkers
epigenetic toxicology
adverse outcome pathway (AOP)
new approach methodology (NAM)
chemical monitoring and emerging pollutants

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Published Papers (10 papers)

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Editorial

Jump to: Research, Review, Other

4 pages, 185 KiB

Open AccessEditorial

Environmental and Occupational Exposure to Chemical Agents and Health Challenges I—What Message Can Bring to Regulatory Science?

by Carina Ladeira

Toxics 2024, 12(11), 778; https://doi.org/10.3390/toxics12110778 - 25 Oct 2024

Viewed by 583

Abstract

Human beings live in constant contact with chemical agents—mainly through environmental exposure—and also derived from the occupational settings [...] Full article

(This article belongs to the Special Issue Environmental and Occupational Exposure to Chemical Agents and Health Challenges)

Research

Jump to: Editorial, Review, Other

22 pages, 1724 KiB

Open AccessArticle

Associations between Urinary Phthalate Metabolites with BDNF and Behavioral Function among European Children from Five HBM4EU Aligned Studies

by Elena Salamanca-Fernández, Lydia Espín-Moreno, Alicia Olivas-Martínez, Ainhoa Pérez-Cantero, José L. Martín-Rodríguez, Rafael M. Poyatos, Fabio Barbone, Valentina Rosolen, Marika Mariuz, Luca Ronfani, Ľubica Palkovičová Murínová, Lucia Fábelová, Tamás Szigeti, Réka Kakucs, Amrit K. Sakhi, Line S. Haug, Birgitte Lindeman, Janja Snoj Tratnik, Tina Kosjek, Griet Jacobs, Stefan Voorspoels, Helena Jurdáková, Renáta Górová, Ida Petrovičová, Branislav Kolena, Marta Esteban, Susana Pedraza-Díaz, Marike Kolossa-Gehring, Sylvie Remy, Eva Govarts, Greet Schoeters, Mariana F. Fernández and Vicente Mustieles Show full author list Hide full author list

Toxics 2024, 12(9), 642; https://doi.org/10.3390/toxics12090642 - 31 Aug 2024

Viewed by 949

Abstract

Based on toxicological evidence, children’s exposure to phthalates may contribute to altered neurodevelopment and abnormal regulation of brain-derived neurotrophic factor (BDNF). We analyzed data from five aligned studies of the Human Biomonitoring for Europe (HBM4EU) project. Ten phthalate metabolites and protein BDNF levels were measured in the urine samples of 1148 children aged 6–12 years from Italy (NACII-IT cohort), Slovakia (PCB-SK cohort), Hungary (InAirQ-HU cohort) and Norway (NEBII-NO). Serum BDNF was also available in 124 Slovenian children (CRP-SLO cohort). Children’s total, externalizing and internalizing behavioral problems were assessed using the Child Behavior Checklist at 7 years of age (only available in the NACII-IT cohort). Adjusted linear and negative binomial regression models were fitted, together with weighted quantile sum (WQS) regression models to assess phthalate mixture associations. Results showed that, in boys but not girls of the NACII-IT cohort, each natural-log-unit increase in mono-n-butyl phthalate (MnBP) and Mono(2-ethyl-5-oxohexyl) phthalate (MEOHP) was cross-sectionally associated with higher externalizing problems [incidence rate ratio (IRR): 1.20; 95% CI: 1.02, 1.42 and 1.26; 95% CI: 1.03, 1.55, respectively]. A suggestive mixture association with externalizing problems was also observed per each tertile mixture increase in the whole population (WQS—IRR = 1.15; 95% CI: 0.97, 1.36) and boys (IRR = 1.20; 95% CI: 0.96, 1.49). In NACII-IT, PCB-SK, InAirQ-HU and NEBII-NO cohorts together, urinary phthalate metabolites were strongly associated with higher urinary BDNF levels, with WQS regression confirming a mixture association in the whole population (percent change (PC) = 25.9%; 95% CI: 17.6, 34.7), in girls (PC = 18.6%; 95% CI: 7.92, 30.5) and mainly among boys (PC = 36.0%; 95% CI: 24.3, 48.9). Among CRP-SLO boys, each natural-log-unit increase in ∑DINCH concentration was associated with lower serum BDNF levels (PC: −8.8%; 95% CI: −16.7, −0.3). In the NACII-IT cohort, each natural-log-unit increase in urinary BDNF levels predicted worse internalizing scores among all children (IRR: 1.15; 95% CI: 1.00, 1.32). Results suggest that (1) children’s exposure to di-n-butyl phthalate (DnBP) and di(2-ethylhexyl) phthalate (DEHP) metabolites is associated with more externalizing problems in boys, (2) higher exposure to DINCH may associate with lower systemic BDNF levels in boys, (3) higher phthalate exposure is associated with higher urinary BDNF concentrations (although caution is needed since the possibility of a “urine concentration bias” that could also explain these associations in noncausal terms was identified) and (4) higher urinary BDNF concentrations may predict internalizing problems. Given this is the first study to examine the relationship between phthalate metabolite exposure and BDNF biomarkers, future studies are needed to validate the observed associations. Full article

(This article belongs to the Special Issue Environmental and Occupational Exposure to Chemical Agents and Health Challenges)

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15 pages, 1782 KiB

Open AccessArticle

Analysis of Mercury in Aquifers in Gold Mining Areas in the Ecuadorian Amazon and Its Associated Risk for Human Health

by Irene Passarelli, Michelle Vanessa Villacis Verdesoto, Samantha Jiménez-Oyola, Ana Gabriela Flores Huilcapi, Demmy Mora-Silva, Giorgio Anfuso, Jose Fernando Esparza Parra, Mirian Jimenez-Gutierrez, Luis Santiago Carrera Almendáriz, Victor Gabriel Avalos Peñafiel, Salvatore Straface and Carlos Mestanza-Ramón

Toxics 2024, 12(2), 162; https://doi.org/10.3390/toxics12020162 - 19 Feb 2024

Cited by 2 | Viewed by 2455

Abstract

Gold mining activity is a source of supply in many areas of the world, and especially in developing countries, it is practiced illegally and by applying unsafe techniques. Particularly in Ecuador, artisanal and small-scale gold mining (ASGM) is widespread, and it is based on the use of toxic substances, such as mercury (Hg), in gold recovery. Hg is a heavy metal that is water-insoluble, which, once mobilized, poses a threat to both the environment and human health. This study analyzes Hg concentrations in the six provinces of Napo, Sucumbíos, Orellana, Pastaza, Morona Santiago, and Zamora Chinchipe of the Ecuadorian Amazon region to conduct a human health risk assessment. Significant differences in Hg levels were found between provinces, but concentrations were below MPL imposed by Ecuadorian regulations everywhere. Nevertheless, a worrisome picture emerges, especially with regard to the most vulnerable receptors represented by the child population. There are multiple factors of incidence that may affect the possible future development of the phenomenon, and with reference to the social, economic, and environmental context of the region, it can be concluded that it may be appropriate to plan further investigation to arrive at a more comprehensive assessment. The results of this study can be used by decision makers to plan further investigation and to implement monitoring networks, risk mitigation strategies, and groundwater protection measures. Full article

(This article belongs to the Special Issue Environmental and Occupational Exposure to Chemical Agents and Health Challenges)

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16 pages, 4711 KiB

Open AccessArticle

K252a Prevents Microglial Activation Induced by Anoxic Stimulation of Carotid Bodies in Rats

by Ricardo Cuéllar-Pérez, Fernando Jauregui-Huerta, Yaveth Ruvalcaba-Delgadillo, Sergio Montero, Mónica Lemus, Elena Roces de Álvarez-Buylla, Joaquín García-Estrada and Sonia Luquín

Toxics 2023, 11(10), 871; https://doi.org/10.3390/toxics11100871 - 20 Oct 2023

Cited by 1 | Viewed by 1521

Abstract

Inducing carotid body anoxia through the administration of cyanide can result in oxygen deprivation. The lack of oxygen activates cellular responses in specific regions of the central nervous system, including the Nucleus Tractus Solitarius, hypothalamus, hippocampus, and amygdala, which are regulated by afferent pathways from chemosensitive receptors. These receptors are modulated by the brain-derived neurotrophic factor receptor TrkB. Oxygen deprivation can cause neuroinflammation in the brain regions that are activated by the afferent pathways from the chemosensitive carotid body. To investigate how microglia, a type of immune cell in the brain, respond to an anoxic environment resulting from the administration of NaCN, we studied the effects of blocking the TrkB receptor on this cell-type response. Male Wistar rats were anesthetized, and a dose of NaCN was injected into their carotid sinus to induce anoxia. Prior to the anoxic stimulus, the rats were given an intracerebroventricular (icv) infusion of either K252a, a TrkB receptor inhibitor, BDNF, or an artificial cerebrospinal fluid (aCSF). After the anoxic stimulus, the rats were perfused with paraformaldehyde, and their brains were processed for microglia immunohistochemistry. The results indicated that the anoxic stimulation caused an increase in the number of reactive microglial cells in the hypothalamic arcuate, basolateral amygdala, and dentate gyrus of the hippocampus. However, the infusion of the K252a TrkB receptor inhibitor prevented microglial activation in these regions. Full article

(This article belongs to the Special Issue Environmental and Occupational Exposure to Chemical Agents and Health Challenges)

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11 pages, 725 KiB

Open AccessArticle

The Hematological and Biochemical Effects from Pesticide Exposure on Thai Vegetable Farmers

by Siriphan Bunsri, Nutnichawan Muenchamnan, Warangkana Naksen and Parichat Ong-Artborirak

Toxics 2023, 11(8), 707; https://doi.org/10.3390/toxics11080707 - 17 Aug 2023

Cited by 2 | Viewed by 2204

Abstract

Pesticide-related health concerns are a global public health issue. Few studies in Thailand have explored the hematological and biochemical effects of occupational pesticide exposure. The goal of this study was to investigate the effects of pesticides on the hematology, hepatic, and renal function of Thai vegetable farmers. A cross-sectional study was carried out in Chiang Mai, northern Thailand. A total of 124 apparently healthy vegetable farmers were interviewed about their lifetime exposure to agricultural pesticides. Blood samples were collected via venipuncture to be tested for complete blood count (CBC), liver function, and kidney function. Approximately 46% of the farmers were pesticide users who reported a history of pesticide use for their crops, while 54% were non-pesticide users. In the male farmers, the activities of aspartate aminotransferase (AST), mean corpuscular hemoglobin (MCH), and mean corpuscular hemoglobin concentration (MCHC) were significantly higher in the pesticide users compared to the non-pesticide users, while the estimated glomerular filtration rate (eGFR), hematocrit (HCT), and red blood cells (RBC) were significantly lower (p < 0.05). In the females, the pesticide users had significantly higher levels of alanine aminotransferase (ALT), alkaline phosphatase (ALP), and MCHC than the non-pesticide users (p < 0.05). Pesticide use among Thai vegetable farmers may cause hematological alterations and increase the risk of hepatic and renal dysfunction. Some hematological and biochemical parameters may be used for monitoring to protect them from the adverse health effects of occupational exposure to pesticides. Full article

(This article belongs to the Special Issue Environmental and Occupational Exposure to Chemical Agents and Health Challenges)

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11 pages, 1143 KiB

Open AccessEditor’s ChoiceArticle

Kinetics of Excretion of the Perfluoroalkyl Surfactant cC₆O₄ in Humans

by Silvia Fustinoni, Rosa Mercadante, Giorgia Lainati, Simone Cafagna and Dario Consonni

Toxics 2023, 11(3), 284; https://doi.org/10.3390/toxics11030284 - 20 Mar 2023

Cited by 4 | Viewed by 2125

Abstract

cC₆O₄ is a new-generation perfluoroalkyl surfactant used in the chemical industry for the synthesis of perfluoroalkyl polymers. It was introduced as a less biopersistent substitute of traditional perfluoroalkyl surfactants such as PFOA, but its kinetics in humans was never investigated. This work is aimed to investigate the kinetics of elimination of cC₆O₄ in exposed workers. Eighteen male individuals occupationally exposed to cC₆O₄ in the production of fluoropolymers volunteered for the study. Blood and urine samples were collected from the end of a work-shift for the following 5 days off work. Serum and urinary cC₆O₄ were measured by LC-MS/MS. Seventy-two samples with serum cC₆O₄ ranging from 0.38 to 11.29 µg/L were obtained; mean levels were 3.07, 2.82, 2.67 and 2.01 µg/L at times 0, 18, 42 and 114 h. Two hundred and fifty-four urine samples with cC₆O₄ ranging from 0.19 to 5.92 µg/L were obtained. A random-intercept multiple regression model was applied to serum data and a half-life of 184 (95% CI 162–213) h for a first-order kinetics elimination was calculated; a mean distribution volume of 80 mL/kg was also estimated. Pearson’s correlation between ln-transformed serum and daily urine concentrations was good, with r ranging from 0.802 to 0.838. The amount of cC₆O₄ excreted daily in urine was about 20% of the amount present in serum. The study allowed calculating a half-life for cC₆O₄ in blood of about 8 days in humans, supporting its much shorter biopersistence in comparison with legacy PFAS. The good correlation between urine and serum cC₆O₄ suggests urine as a possible non-invasive matrix for biomonitoring. The amount of cC₆O₄ excreted daily in urine suggests urine as the sole elimination route. Full article

(This article belongs to the Special Issue Environmental and Occupational Exposure to Chemical Agents and Health Challenges)

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11 pages, 743 KiB

Open AccessArticle

Using Urinary Biomarkers to Estimate the Benzene Exposure Levels in Individuals Exposed to Benzene

by Shiwei Cui, Bo Pang, Huifang Yan, Bo Wu, Ming Li, Caihong Xing and Juan Li

Toxics 2022, 10(11), 636; https://doi.org/10.3390/toxics10110636 - 23 Oct 2022

Cited by 4 | Viewed by 2391

Abstract

Urinary benzene metabolites trans, trans-muconic acid (t, t-MA), and S-phenyl mercapturic acid (S-PMA) are often used as biomarkers of internal exposure to benzene. However, there are few reports on using urinary benzene metabolites to estimate airborne benzene concentrations in individuals exposed to benzene. In this study, t, t-MA, and S-PMA were analyzed by UPLC-MS/MS, and a simple pharmacokinetic model was used to calculate the daily intake (DI) of benzene based on the levels of urinary t, t-MA, and S-PMA in occupational individuals. The back-calculated airborne benzene levels (BCABL) were obtained from the DI of benzene. Among the exposed subjects (n = 84), the median BCABL (3.67 mg/m³) based on t, t-MA was very close to the median level of measured airborne benzene (3.27 mg/m³, p = 0.171), and there was no effect of smoking or dietary habits on t, t-MA-based BCABL. In the control subjects (n = 49), the levels of measured airborne benzene were all below the quantitation limit (0.024 mg/m³), and the BCABL (0.002–0.25 mg/m³) calculated by S-PMA was close to this background level. Our study suggests that the t, t-MA-based BCABL can reflect the actual airborne benzene level in a range of 1.10–86.91 mg/m³ and that the S-PMA-based BCABL is more reliable for non-professional benzene exposure. Full article

(This article belongs to the Special Issue Environmental and Occupational Exposure to Chemical Agents and Health Challenges)

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Review

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111 pages, 4013 KiB

Open AccessEditor’s ChoiceReview

The Comet Assay as a Tool in Human Biomonitoring Studies of Environmental and Occupational Exposure to Chemicals—A Systematic Scoping Review

by Carina Ladeira, Peter Møller, Lisa Giovannelli, Goran Gajski, Anja Haveric, Ezgi Eyluel Bankoglu, Amaya Azqueta, Marko Gerić, Helga Stopper, José Cabêda, Fernanda S. Tonin and Andrew Collins

Toxics 2024, 12(4), 270; https://doi.org/10.3390/toxics12040270 - 5 Apr 2024

Cited by 4 | Viewed by 3294

Abstract

Biomonitoring of human populations exposed to chemical substances that can act as potential mutagens or carcinogens, may enable the detection of damage and early disease prevention. In recent years, the comet assay has become an important tool for assessing DNA damage, both in environmental and occupational exposure contexts. To evidence the role of the comet assay in human biomonitoring, we have analysed original research studies of environmental or occupational exposure that used the comet assay in their assessments, following the PRISMA-ScR method (preferred reporting items for systematic reviews and meta-analyses extension for scoping reviews). Groups of chemicals were designated according to a broad classification, and the results obtained from over 300 original studies (n = 123 on air pollutants, n = 14 on anaesthetics, n = 18 on antineoplastic drugs, n = 57 on heavy metals, n = 59 on pesticides, and n = 49 on solvents) showed overall higher values of DNA strand breaks in the exposed subjects in comparison with the unexposed. In summary, our systematic scoping review strengthens the relevance of the use of the comet assay in assessing DNA damage in human biomonitoring studies. Full article

(This article belongs to the Special Issue Environmental and Occupational Exposure to Chemical Agents and Health Challenges)

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17 pages, 3411 KiB

Open AccessEditor’s ChoiceReview

Hand Sanitizer Gels: Classification, Challenges, and the Future of Multipurpose Hand Hygiene Products

by Yilei Ma, Jia Yi, Jiahui Ma, Haiyang Yu, Li Luo, Wei Wu, Libo Jin, Qinsi Yang, Ting Lou, Da Sun and Min Cao

Toxics 2023, 11(8), 687; https://doi.org/10.3390/toxics11080687 - 10 Aug 2023

Cited by 4 | Viewed by 4852

Abstract

Hand hygiene is a crucial measure in the prevention and control of infections, and there is a growing awareness among individuals who are making a conscious effort to maintain hand cleanliness. With the advent of the SARS-CoV-2 outbreak, the demand for hand hygiene products has also gradually shifted towards those with antimicrobial properties. Among these products, hand sanitizer gels (HSGs) have gained considerable popularity as an efficient method of hand cleaning, due to their rapid drying and sustained antimicrobial efficacy. Concurrently, there has been a growing interest in novel HSGs that offer additional functions such as skin whitening, moisturizing, and anti-inflammatory effects. These novel HSGs effectively address concerns associated with the ingestion of antimicrobial ingredients and demonstrate reduced skin irritation, thereby alleviating hand dermatological issues. This review provides an extensive overview of the application scenarios, classification, and challenges associated with HSGs while emphasizing the emergence of novel components with biological functions, aiming to contribute to the advancement of hand hygiene practices and offer novel insights for the development of novel HSGs with outstanding antimicrobial properties with other multiple biological functions and desirable biosafety profiles. Full article

(This article belongs to the Special Issue Environmental and Occupational Exposure to Chemical Agents and Health Challenges)

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Other

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13 pages, 1218 KiB

Open AccessEditor’s ChoicePerspective

Inhalation of Microplastics—A Toxicological Complexity

by Myriam Borgatta and Florian Breider

Toxics 2024, 12(5), 358; https://doi.org/10.3390/toxics12050358 - 11 May 2024

Cited by 4 | Viewed by 1684

Abstract

Humans are chronically exposed to airborne microplastics (MPs) by inhalation. Various types of polymer particles have been detected in lung samples, which could pose a threat to human health. Inhalation toxicological studies are crucial for assessing the effects of airborne MPs and for exposure-reduction measures. This communication paper addresses important health concerns related to MPs, taking into consideration three levels of complexity, i.e., the particles themselves, the additives present in the plastics, and the exogenous substances adsorbed onto them. This approach aims to obtain a comprehensive toxicological profile of deposited MPs in the lungs, encompassing local and systemic effects. The physicochemical characteristics of MPs may play a pivotal role in lung toxicity. Although evidence suggests toxic effects of MPs in animal and cell models, no established causal link with pulmonary or systemic diseases in humans has been established. The transfer of MPs and associated chemicals from the lungs into the bloodstream and/or pulmonary circulation remains to be confirmed in humans. Understanding the toxicity of MPs requires a multidisciplinary investigation using a One Health approach. Full article

(This article belongs to the Special Issue Environmental and Occupational Exposure to Chemical Agents and Health Challenges)

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