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A special issue of Toxics (ISSN 2305-6304). This special issue belongs to the section "Human Toxicology and Epidemiology".

Deadline for manuscript submissions: closed (31 July 2022) | Viewed by 25082

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Dr. Jan Korabecny

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Guest Editor

Biomedical Research Centre, University Hospital Hradec Kralove, Sokolska 581, 50005 Hradec Kralove, Czech Republic
Interests: Alzheimer’s disease; acetylcholinesterase; butyrylcholinesterase; cholinesterase; drug development; organic synthesis; medicinal chemistry; organophosphate poisoning; nerve agents; oxime reactivators; toxicology; military pharmacy; in silico methods
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Dr. Ondrej Soukup

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Guest Editor

Biomedical Research Centre, University Hospital Hradec Kralove, Sokolska 581, 50005 Hradec Kralove, Czech Republic
Interests: organophosphate poisoning; nerve agents; oxime reactivators; toxicology; military pharmacy; drug delivery Alzheimer’s disease; acetylcholinesterase; butyrylcholinesterase; cholinesterase; drug development;; in vitro testing; in vivo; toxicokinetics
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

We have issued the Special Issue of Toxics entitled, “Chemical and biological threats, hazard potential and countermeasures”. In this special issue we would like to pay attention to various aspects of toxicology specifically focused on the chemical and biological threats, which may accidentally or on purpose endanger human health. Besides the characterization of such threats and their biological consequences we will focus on the available and novel experimental countermeasures capable to protect from and/or threat such exposures.

We would like to encourage our colleagues from this field for the submission of review or original research articles that encompasses this field at different levels including chemical, biological, medical and epidemiological approaches.

Dr. Jan Korabecny
Dr. Ondrej Soukup
Guest Editors

Manuscript Submission Information

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Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Toxics is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

chemical warfare agent
organophosphorus compound
biological agent
nerve agents
novichoks
safety and health
intoxication
protection
decontamination
hazard potential
antidote
countermeasure

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Published Papers (9 papers)

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Editorial

Jump to: Research, Review

3 pages, 199 KiB

Open AccessEditorial

Chemical and Biological Threats, Hazard Potential and Countermeasures

by Ondrej Soukup and Jan Korabecny

Toxics 2022, 10(8), 444; https://doi.org/10.3390/toxics10080444 - 2 Aug 2022

Viewed by 1409

Abstract

The scope of this Special Issue is to pay attention to various aspects of toxicology specifically focused on the chemical and biological threats, which may accidentally, or on purpose, endanger human health [...] Full article

(This article belongs to the Special Issue Chemical and Biological Threats, Hazard Potential and Countermeasures)

Research

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16 pages, 2643 KiB

Open AccessArticle

Antiseizure and Neuroprotective Efficacy of Midazolam in Comparison with Tezampanel (LY293558) against Soman-Induced Status Epilepticus

by Taiza H. Figueiredo, Vassiliki Aroniadou-Anderjaska, Volodymyr I. Pidoplichko, James P. Apland and Maria F. M. Braga

Toxics 2022, 10(8), 409; https://doi.org/10.3390/toxics10080409 - 22 Jul 2022

Cited by 7 | Viewed by 1703

Abstract

Acute exposure to nerve agents induces status epilepticus (SE), which can cause death or long-term brain damage. Diazepam is approved by the FDA for the treatment of nerve agent-induced SE, and midazolam (MDZ) is currently under consideration to replace diazepam. However, animal studies have raised questions about the neuroprotective efficacy of benzodiazepines. Here, we compared the antiseizure and neuroprotective efficacy of MDZ (5 mg/kg) with that of tezampanel (LY293558; 10 mg/kg), an AMPA/GluK1 receptor antagonist, administered 1 h after injection of the nerve agent, soman (1.2 × LD₅₀), in adult male rats. Both of the anticonvulsants promptly stopped SE, with MDZ having a more rapid effect. However, SE reoccurred to a greater extent in the MDZ-treated group, resulting in a significantly longer total duration of SE within 24 h post-exposure compared with the LY293558-treated group. The neuroprotective efficacy of the two drugs was studied in the basolateral amygdala, 30 days post-exposure. Significant neuronal and inter-neuronal loss, reduced ratio of interneurons to the total number of neurons, and reduction in spontaneous inhibitory postsynaptic currents accompanied by increased anxiety were found in the MDZ-treated group. The rats treated with LY293558 did not differ from the control rats (not exposed to soman) in any of these measurements. Thus, LY293558 has significantly greater efficacy than midazolam in protecting against prolonged seizures and brain damage caused by acute nerve agent exposure. Full article

(This article belongs to the Special Issue Chemical and Biological Threats, Hazard Potential and Countermeasures)

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15 pages, 2713 KiB

Open AccessArticle

Molecular Evidence on the Inhibitory Potential of Metformin against Chlorpyrifos-Induced Neurotoxicity

by Marzieh Daniali, Maryam Baeeri, Ramtin Farhadi, Mahdi Gholami, Shokoufeh Hassani, Mona Navaei-Nigjeh, Mahban Rahimifard and Mohammad Abdollahi

Toxics 2022, 10(4), 197; https://doi.org/10.3390/toxics10040197 - 18 Apr 2022

Cited by 4 | Viewed by 2676

Abstract

Chlorpyrifos (CPF) is an organophosphorus (OP) pesticide, resulting in various health complications as the result of ingestion, inhalation, or skin absorption, and leads to DNA damage and increased oxidative stress. Metformin, derived from Galega officinalis, is reported to have anti-inflammatory and anti-apoptotic properties; thus, this study aimed to investigate the beneficial role of metformin in neurotoxicity induced by sub-acute exposure to CPF in Wistar rats. In this study, animals were divided into nine groups and were treated with different combinations of metformin and CPF. Following the 28 days of CPF and metformin administration, brain tissues were separated. The levels of inflammatory biomarkers such as tumor necrosis factor alpha (TNFα) and interleukin 1β (IL-1β), as well as the expression of 5HT1 and 5HT2 genes, were analyzed. Moreover, the levels of malondialdehyde (MDA), reactive oxygen species (ROS), and the ADP/ATP ratio, in addition to the activity of acetylcholinesterase (AChE) and superoxide dismutase (SOD), were tested through in vitro experiments. This study demonstrated the potential role of metformin in alleviating the mentioned biomarkers, which can be altered negatively as a result of CPF toxicity. Moreover, metformin showed protective potential in modulating inflammation, as well as oxidative stress, the expression of genes, and histological analysis, in a concentration-dependent manner. Full article

(This article belongs to the Special Issue Chemical and Biological Threats, Hazard Potential and Countermeasures)

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10 pages, 1229 KiB

Open AccessFeature PaperArticle

Influence of Experimental End Point on the Therapeutic Efficacy of Essential and Additional Antidotes in Organophosphorus Nerve Agent-Intoxicated Mice

by Jiri Kassa, Christopher M. Timperley, Mike Bird, A. Christopher Green and John E. H. Tattersall

Toxics 2022, 10(4), 192; https://doi.org/10.3390/toxics10040192 - 15 Apr 2022

Cited by 2 | Viewed by 2217

Abstract

The therapeutic efficacy of treatments for acute intoxication with highly toxic organophosphorus compounds, called nerve agents, usually involves determination of LD₅₀ values 24 h after nerve agent challenge without and with a single administration of the treatment. Herein, the LD₅₀ values of four nerve agents (sarin, soman, tabun and cyclosarin) for non-treated and treated intoxication were investigated in mice for experimental end points of 6 and 24 h. The LD₅₀ values of the nerve agents were evaluated by probit-logarithmical analysis of deaths within 6 and 24 h of i.m. challenge of the nerve agent at five different doses, using six mice per dose. The efficiency of atropine alone or atropine in combination with an oxime was practically the same at 6 and 24 h. The therapeutic efficacy of the higher dose of the antinicotinic compound MB327 was slightly higher at the 6 h end point compared to the 24 h end point for soman and tabun intoxication. A higher dose of MB327 increased the therapeutic efficacy of atropine alone for sarin, soman and tabun intoxication, and that of the standard antidotal treatment (atropine and oxime) for sarin and tabun intoxication. The therapeutic efficacy of MB327 was lower than the oxime-based antidotal treatment. To compare the 6 and 24 h end points, the influence of the experimental end point was not observed, with the exception of the higher dose of MB327. In addition, only a negligible beneficial impact of the compound MB327 was observed. Nevertheless, antinicotinics may offer an additional avenue for countering poisoning by nerve agents that are difficult to treat, and synthetic and biological studies towards the development of such novel drugs based on the core bispyridinium structure or other molecular scaffolds should continue. Full article

(This article belongs to the Special Issue Chemical and Biological Threats, Hazard Potential and Countermeasures)

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12 pages, 332 KiB

Open AccessArticle

Risk of Abdominal Obesity Associated with Phthalate Exposure of Nurses

by Branislav Kolena, Henrieta Hlisníková, Ľubica Kečkéšová, Miroslava Šidlovská, Tomáš Trnovec and Ida Petrovičová

Toxics 2022, 10(3), 143; https://doi.org/10.3390/toxics10030143 - 18 Mar 2022

Cited by 5 | Viewed by 2601

Abstract

Background: Occupational health hazards associated with phthalate exposure among nurses are still not well understood. Methods: We used high-performance liquid chromatography and tandem mass spectrometry to analyze phthalates. Anthropometric measurements and questionnaires were conducted. Results: We observed associations between mono-benzyl phthalate (MBzP) and body mass index (BMI), hip circumference (HC), waist circumference (WC), waist to height ratio (WHtR), and fat mass index (FMI), visceral fat content, BMI risk and hip index risk (HIrisk), adjusted to consumer behavior and consumer practices (r = 0.36–0.61; p ≤ 0.046). In the same model, we detected an association between mono-n-butyl phthalate (MnBP) and waist to hip ratio (WHR; r = 0.36; p = 0.046), mono-carboxy-isononyl phthalate (cx-MiNP) and BMI (r = 0.37; p = 0.043), HC (r = 0.4; p = 0.026) and WHtR (r = 0.38; p = 0.037), between mono-oxo-isononyl phthalate oxo (MiNP) and HC (r = 0.36; p = 0.045), mono-2-ethylhexyl phthalate (MEHP), mono(2-ethyl-5-oxohexyl) phthalate (oxo-MEHP) and HIrisk (r = 0.38–0.41; p ≤ 0.036), between oxo-MEHP and Anthropometric Risk Index (ARI risk; r = 0.4; p = 0.028). We detected a relationship between BMI and MBzP (β = 0.655; p < 0.001) and mono-2-ethylhexyl phthalate (MEHP; β = −0.365; p = 0.003), between hip circumference and MBzP (β = 0.486; p < 0.001), MEHP (β = −0.402; p = 0.001), and sum of secondary metabolites of diisononyl phthalate (∑DiNP; β = 0.307; p = 0.016). We observed a relationship between fat content and MBzP (β = 0.302; p = 0.033), OH-MnBP (β = −0.736; p = 0.006) and MiBP (β = 0.547; p = 0.046), visceral fat content and MBzP (β = 0.307; p = 0.030), HI-risk and MBzP (β = 0.444; p = 0.001), ARI-risk and sum of di-n-butyl phthalate metabolites (∑DnBP; β = 0.337; p = 0.018). We observed an association between the use of protective equipment with cx-MiNP. Conclusions: Occupational exposure to phthalates may induce abdominal obesity and result in obesity-related metabolic disorders. Full article

(This article belongs to the Special Issue Chemical and Biological Threats, Hazard Potential and Countermeasures)

13 pages, 2524 KiB

Open AccessArticle

Diacetyl Vapor Inhalation Induces Mixed, Granulocytic Lung Inflammation with Increased CD4⁺CD25⁺ T Cells in the Rat

by Emma L. House, So-Young Kim, Carl J. Johnston, Angela M. Groves, Eric Hernady, Ravi S. Misra and Matthew D. McGraw

Toxics 2021, 9(12), 359; https://doi.org/10.3390/toxics9120359 - 20 Dec 2021

Cited by 5 | Viewed by 3352

Abstract

Diacetyl (DA) is a highly reactive alpha diketone associated with flavoring-related lung disease. In rodents, acute DA vapor exposure can initiate an airway-centric, inflammatory response. However, this immune response has yet to be fully characterized in the context of flavoring-related lung disease progression. The following studies were designed to characterize the different T cell populations within the lung following repetitive DA vapor exposures. Sprague-Dawley rats were exposed to 200 parts-per-million DA vapor for 5 consecutive days × 6 h/day. Lung tissue and bronchoalveolar lavage fluid (BALF) were analyzed for changes in histology by H&E and Trichrome stain, T cell markers by flow cytometry, total BALF cell counts and differentials, BALF IL17a and total protein immediately, 1 and 2 weeks post-exposure. Lung histology and BALF cell composition demonstrated mixed, granulocytic lung inflammation with bronchial lymphoid aggregates at all time points in DA-exposed lungs compared to air controls. While no significant change was seen in percent lung CD3⁺, CD4⁺, or CD8⁺ T cells, a significant increase in lung CD4⁺CD25⁺ T cells developed at 1 week that persisted at 2 weeks post-exposure. Further characterization of this CD4⁺CD25⁺ T cell population identified Foxp3⁺ T cells at 1 week that failed to persist at 2 weeks. Conversely, BALF IL-17a increased significantly at 2 weeks in DA-exposed rats compared to air controls. Lung CD4⁺CD25⁺ T cells and BALF IL17a correlated directly with BALF total protein and inversely with rat oxygen saturations. Repetitive DA vapor exposure at occupationally relevant concentrations induced mixed, granulocytic lung inflammation with increased CD4⁺CD25⁺ T cells in the rat lung. Full article

(This article belongs to the Special Issue Chemical and Biological Threats, Hazard Potential and Countermeasures)

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25 pages, 10388 KiB

Open AccessArticle

Reactive Organic Suspensions Comprising ZnO, TiO₂, and Zeolite Nanosized Adsorbents: Evaluation of Decontamination Efficiency on Soman and Sulfur Mustard

by Raluca Elena Ginghina, Adriana Elena Bratu, Gabriela Toader, Andreea Elena Moldovan, Tudor Viorel Tiganescu, Ramona Elena Oncioiu, Panaghia Deliu, Razvan Petre, Gabriel Epure and Munizer Purica

Toxics 2021, 9(12), 334; https://doi.org/10.3390/toxics9120334 - 3 Dec 2021

Cited by 5 | Viewed by 3215

Abstract

This paper comprises an extensive study on the evaluation of decontamination efficiency of three types of reactive organic suspensions (based on nanosized adsorbents) on two real chemical warfare agents: soman (GD) and sulfur mustard (HD). Three types of nanoparticles (ZnO, TiO₂, and zeolite) were employed in the decontamination formulations, for enhancing the degradation of the toxic agents. The efficacy of each decontamination solution was investigated by means of GC-MS analysis, considering the initial concentration of toxic agent and the residual toxic concentration, measured at different time intervals, until the completion of the decontamination process. The conversion of the two chemical warfare agents (HD and GD) into their decontamination products was also monitored for 24 h. Full article

(This article belongs to the Special Issue Chemical and Biological Threats, Hazard Potential and Countermeasures)

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20 pages, 9340 KiB

Open AccessFeature PaperArticle

Synthesis and Decontamination Effect on Chemical and Biological Agents of Benzoxonium-Like Salts

by Aneta Markova, Michaela Hympanova, Marek Matula, Lukas Prchal, Radek Sleha, Marketa Benkova, Lenka Pulkrabkova, Ondrej Soukup, Zuzana Krocova, Daniel Jun and Jan Marek

Toxics 2021, 9(9), 222; https://doi.org/10.3390/toxics9090222 - 15 Sep 2021

Cited by 5 | Viewed by 2816

Abstract

Benzoxonium chloride belongs to the group of quaternary ammonium salts, which have been widely used for decades as disinfectants because of their high efficacy, low toxicity, and thermal stability. In this study, we have prepared the C₁₀-C₁₈ set of benzoxonium-like salts to evaluate the effect of their chemical and biological decontamination capabilities. In particular, biocidal activity against a panel of bacterial strains including Staphylococcus aureus in biofilm form was screened. In addition, the most promising compounds were successfully tested against Francisella tularensis as a representative of potential biological warfare agents. From a point of view of chemical warfare protection, the efficiency of BOC-like compounds to degrade the organophosphate simulant fenitrothion was examined. Notwithstanding that no single compound with universal effectiveness was identified, a mixture of only two compounds from this group would be able to satisfactorily cover the proposed decontamination spectrum. In addition, the compounds were evaluated for their cytotoxicity as a basic safety parameter for potential use in practice. In summary, the dual effect on chemical and biological agents of benzoxonium-like salts offer attractive potential as active components of decontamination mixtures in the case of a terrorist threat or chemical or biological accidents. Full article

(This article belongs to the Special Issue Chemical and Biological Threats, Hazard Potential and Countermeasures)

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Review

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10 pages, 738 KiB

Open AccessReview

Scientific Evidence about the Risks of Micro and Nanoplastics (MNPLs) to Human Health and Their Exposure Routes through the Environment

by Ana Clara Bastos Rodrigues, Gabriel Pereira de Jesus, Dunia Waked, Gabriel Leandro Gomes, Thamires Moraes Silva, Victor Yuji Yariwake, Mariane Paula da Silva, Antônio José Magaldi and Mariana Matera Veras

Toxics 2022, 10(6), 308; https://doi.org/10.3390/toxics10060308 - 8 Jun 2022

Cited by 31 | Viewed by 3910

Abstract

Nowadays, a large amount and variety of plastic is being produced and consumed by human beings on an enormous scale. Microplastics and nanoplastics (MNPLs) have become ubiquitous since they can be found in many ecosystem components. Plastic particles can be found in soil, water, and air. The routes of human exposure are numerous, mainly involving ingestion and inhalation. Once ingested, these particles interact with the gastrointestinal tract and digestive fluids. They can adsorb substances such as additives, heavy metals, proteins, or even microorganisms on their surface, which can cause toxicity. During inhalation, they can be inhaled according to their respective sizes. Studies have reported that exposure to MNPLs can cause damage to the respiratory tract, creating problems such as bronchitis, asthma, fibrosis, and pneumothorax. The reports of boards and committees indicate that there is little data published and available on the toxicity of MNPLs as well as the exposure levels in humans. Despite the well-established concept of MNPLs, their characteristics, and presence in the environment, little is known about their real effects on human health and the environment. Full article

(This article belongs to the Special Issue Chemical and Biological Threats, Hazard Potential and Countermeasures)

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