Special Issue "Toxicity of Chemical Mixtures"

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

Deadline for manuscript submissions: closed (31 January 2019)

Special Issue Editor

Guest Editor
Prof. Jennifer L. Freeman

School of Health Sciences, Purdue University, West Lafayette, IN, USA
Website | E-Mail

Special Issue Information

Dear Colleagues,

In our everyday environment, we are exposed to a number of different chemical agents. However, the majority of toxicity studies involve only a single chemical presenting difficulties in chemical risk assessment. Over the past few decades, there has been a growing emphasis on studies that address various scientific questions in the evaluation of the toxicity of chemicals in a mixture. These studies are clarifying our understanding of potential toxic interactions ocurring when chemicals are present in a mixture and defining non-interactive or interactive mechanisms, including synergistic, potentiative, and antagonist interactions.

This Special Issue will focus on highlighting timely research studies addressing the toxicity of chemical mixtures. Topics are expected to include any chemical agent mixtures covering a broad base of scientific questions related to the toxicity of chemical mixtures. Studies may include, but are not limited to assessments of toxicokinetic, toxicodynamic, or metabolism interactions; molecular or epigenetic mechanisms of toxicity; phenotypic or behavioral outcomes; and/or predictive or computational toxicology approaches. Authors are invited and welcome to submit original research papers, reviews, and short communications. 

Prof. Jennifer L. Freeman
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All papers will be peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

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 quarterly 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 350 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

  • Antagonism
  • Endocrine disrupting chemicals
  • Flame retardants
  • Metals
  • Mixtures
  • Pesticides
  • Pharmaceuticals
  • Persistent Organic Pollutants
  • Potentiation
  • Synergism

Published Papers (7 papers)

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Research

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Open AccessArticle Comparison of the Respiratory Toxicity and Total Cholinesterase Activities in Dimethyl Versus Diethyl Paraoxon-Poisoned Rats
Received: 26 February 2019 / Revised: 11 April 2019 / Accepted: 13 April 2019 / Published: 16 April 2019
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Abstract
The chemical structure of organophosphate compounds (OPs) is a well-known factor which modifies the acute toxicity of these compounds. We compared ventilation at rest and cholinesterase activities in male Sprague-Dawley rats poisoned with dimethyl paraoxon (DMPO) and diethyl paraoxon (DEPO) at a subcutaneous [...] Read more.
The chemical structure of organophosphate compounds (OPs) is a well-known factor which modifies the acute toxicity of these compounds. We compared ventilation at rest and cholinesterase activities in male Sprague-Dawley rats poisoned with dimethyl paraoxon (DMPO) and diethyl paraoxon (DEPO) at a subcutaneous dose corresponding to 50% of the median lethal dose (MLD). Ventilation at rest was recorded by whole body plethysmography. Total cholinesterase activities were determined by radiometric assay. Both organophosphates decreased significantly the respiratory rate, resulting from an increase in expiratory time. Dimethyl-induced respiratory toxicity spontaneously reversed within 120 min post-injection. Diethyl-induced respiratory toxicity was long-lasting, more than 180 min post-injection. Both organophosphates decreased cholinesterase activities from 10 to 180 min post-injection with the same degree of inhibition of total cholinesterase within an onset at the same times after injection. There were no significant differences in residual cholinesterase activities between dimethyl and diethyl paraoxon groups at any time. The structure of the alkoxy-group is a determinant factor of the late phase of poisoning, conditioning duration of toxicity without significant effects on the magnitude of alteration of respiratory parameters. For same duration and magnitude of cholinesterase inhibition, there was a strong discrepancy in the time-course of effects between the two compounds. Full article
(This article belongs to the Special Issue Toxicity of Chemical Mixtures)
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Open AccessArticle Protective Effects of Centella asiatica on Cognitive Deficits Induced by D-gal/AlCl3 via Inhibition of Oxidative Stress and Attenuation of Acetylcholinesterase Level
Received: 19 January 2019 / Revised: 6 March 2019 / Accepted: 8 March 2019 / Published: 30 March 2019
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Abstract
Alzheimer’s disease (AD) is a progressive neurodegenerative disorder with cholinergic dysfunctions and impaired redox homeostasis. The plant Centella asiatica (CA) is renowned for its nutritional benefits and herbal formulas for promoting health, enhancing cognition, and its neuroprotective effects. The present study aims to [...] Read more.
Alzheimer’s disease (AD) is a progressive neurodegenerative disorder with cholinergic dysfunctions and impaired redox homeostasis. The plant Centella asiatica (CA) is renowned for its nutritional benefits and herbal formulas for promoting health, enhancing cognition, and its neuroprotective effects. The present study aims to investigate the protective role of CA on D-gal/AlCl3-induced cognitive deficits in rats. The rats were divided into six groups and administered with donepezil 1 mg/kg/day, CA (200, 400, and 800 mg/kg/day) and D-gal 60 mg/kg/day + AlCl3 200 mg/kg/day for 10 weeks. The ethology of the rats was evaluated by the Morris water maze test. The levels of acetylcholinesterase (AChE), phosphorylated tau (P-tau), malondialdehyde (MDA) and activities of superoxide dismutase (SOD), in the hippocampus and cerebral cortex were estimated by enzyme-linked immunosorbent assay (ELISA). Additionally, the ultrastructure of the prefrontal cortex of the rats’ was observed using transmission electron microscopy (TEM). Rats administered with D-gal/AlCl3 exhibited cognitive deficits, decreased activities of SOD, and marked increase in AChE and MDA levels. Further, prominent alterations in the ultrastructure of the prefrontal cortex were observed. Conversely, co-administration of CA with D-gal/AlCl3 improved cognitive impairment, decreased AChE levels, attenuated the oxidative stress in hippocampus and cerebral cortex, and prevented ultrastructural alteration of neurons in the prefrontal cortex. Irrespective of the dose of CA administered, the protective effects were comparable to donepezil. In conclusion, this study suggests that CA attenuated the cognitive deficits in rats by restoring cholinergic function, attenuating oxidative stress, and preventing the morphological aberrations. Full article
(This article belongs to the Special Issue Toxicity of Chemical Mixtures)
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Open AccessArticle Early, Subclinical Hematological Changes Associated with Occupational Exposure to High Levels of Nitrous Oxide
Received: 9 October 2018 / Revised: 14 November 2018 / Accepted: 16 November 2018 / Published: 21 November 2018
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Abstract
This study was undertaken to determine whether exposure of operating room personnel to inhalation anesthetics, nitrous oxide, isoflurane, and sevoflurane was associated with any hematological changes. This historical cohort study was performed in 2018 at a large public hospital in Shiraz, where 52 [...] Read more.
This study was undertaken to determine whether exposure of operating room personnel to inhalation anesthetics, nitrous oxide, isoflurane, and sevoflurane was associated with any hematological changes. This historical cohort study was performed in 2018 at a large public hospital in Shiraz, where 52 operating room personnel and 52 administrative staff were investigated. The blood sample was taken from all individuals for Complete Blood Count. Furthermore, demographic information was collected through questionnaires. Mean atmospheric concentrations of nitrous oxide, isoflurane, and sevoflurane, to which subjects were exposed, were 850.92, 2.40, and 0.18 ppm, respectively. The hematological parameters were within the normal range in both groups. However, the mean values of hemoglobin, hematocrit, mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration, and red blood cell count in the exposed group were significantly lower than the control group. No significant differences were noted between the two groups as far as other hematological factors were concerned. These findings provide circumstantial evidence to further substantiate the notion that occupational exposure to inhalation anesthetics, under the exposure scenario explained in this study, is associated with subtle, subclinical, prepathologic hematological changes. Long-term consequence and ramifications of these effects require further investigation. The range of exposure levels to anesthetic gases in operating rooms. Full article
(This article belongs to the Special Issue Toxicity of Chemical Mixtures)
Open AccessArticle Evaluating the Joint Toxicity of Two Benzophenone-Type UV Filters on the Green Alga Chlamydomonas reinhardtii with Response Surface Methodology
Received: 24 October 2017 / Revised: 8 January 2018 / Accepted: 9 January 2018 / Published: 10 January 2018
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Abstract
The widespread occurrence of benzophenone-type ultraviolet (UV) filter has raised the public concerns over the ecotoxicological effects of these chemicals. The present study assessed the joint toxicity of two representative benzophenones, benzophenone-1 (BP-1) and benzophenone-3 (BP-3), on the green alga Chlamydomonas reinhardtii using [...] Read more.
The widespread occurrence of benzophenone-type ultraviolet (UV) filter has raised the public concerns over the ecotoxicological effects of these chemicals. The present study assessed the joint toxicity of two representative benzophenones, benzophenone-1 (BP-1) and benzophenone-3 (BP-3), on the green alga Chlamydomonas reinhardtii using response surface methodologies (RSM). Specific growth rate and photosynthetic pigments were used as endpoints to evaluate the toxic effects. Generally, exposure to the combined BP-1 and BP-3 negatively affected cell growth and pigments production, with higher inhibitions at higher exposure concentrations. The simultaneous reduction in growth rate and pigments contents indicated that BP-1 and BP-3 regulated the growth of the tested alga by affecting the photosynthesis process. Results also showed that second order polynomial regression models fitted well with experimental results for all endpoints. The obtained regression models further indicated that the effects of the combination stemmed significantly from the linear concentration of BP-1 and BP-3. The overall results demonstrated that RSM could be a useful tool in ecotoxicological studies. Full article
(This article belongs to the Special Issue Toxicity of Chemical Mixtures)
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Review

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Open AccessReview Exploration of Computational Approaches to Predict the Toxicity of Chemical Mixtures
Received: 22 January 2019 / Revised: 10 March 2019 / Accepted: 14 March 2019 / Published: 19 March 2019
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Abstract
Industrial advances have led to generation of multi-component chemicals, materials and pharmaceuticals which are directly or indirectly affecting the environment. Although toxicity data are available for individual chemicals, generally there is no toxicity data of chemical mixtures. Most importantly, the nature of toxicity [...] Read more.
Industrial advances have led to generation of multi-component chemicals, materials and pharmaceuticals which are directly or indirectly affecting the environment. Although toxicity data are available for individual chemicals, generally there is no toxicity data of chemical mixtures. Most importantly, the nature of toxicity of these studied mixtures is completely different to the single components, which makes the toxicity evaluation of mixtures more critical and challenging. Interactions of individual chemicals in a mixture can result in multifaceted and considerable deviations in the apparent properties of its ingredients. It results in synergistic or antagonistic effects as opposed to the ideal case of additive behavior i.e., concentration addition (CA) and independent action (IA). The CA and IA are leading models for the assessment of joint activity supported by pharmacology literature. Animal models for toxicity testing are time- and money-consuming as well as unethical. Thus, computational approaches are already proven efficient alternatives for assessing the toxicity of chemicals by regulatory authorities followed by industries. In silico methods are capable of predicting toxicity, prioritizing chemicals, identifying risk and assessing, followed by managing, the risk. In many cases, the mechanism behind the toxicity from species to species can be understood by in silico methods. Until today most of the computational approaches have been employed for single chemical’s toxicity. Thus, only a handful of works in the literature and methods are available for a mixture’s toxicity prediction employing computational or in silico approaches. Therefore, the present review explains the importance of evaluation of a mixture’s toxicity, the role of computational approaches to assess the toxicity, followed by types of in silico methods. Additionally, successful application of in silico tools in a mixture’s toxicity predictions is explained in detail. Finally, future avenues towards the role and application of computational approaches in a mixture’s toxicity are discussed. Full article
(This article belongs to the Special Issue Toxicity of Chemical Mixtures)
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Open AccessFeature PaperReview Comparative Assessment of Tungsten Toxicity in the Absence or Presence of Other Metals
Received: 17 October 2018 / Revised: 3 November 2018 / Accepted: 6 November 2018 / Published: 9 November 2018
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Abstract
Tungsten is a refractory metal that is used in a wide range of applications. It was initially perceived that tungsten was immobile in the environment, supporting tungsten as an alternative for lead and uranium in munition and military applications. Recent studies report movement [...] Read more.
Tungsten is a refractory metal that is used in a wide range of applications. It was initially perceived that tungsten was immobile in the environment, supporting tungsten as an alternative for lead and uranium in munition and military applications. Recent studies report movement and detection of tungsten in soil and potable water sources, increasing the risk of human exposure. In addition, experimental research studies observed adverse health effects associated with exposure to tungsten alloys, raising concerns on tungsten toxicity with questions surrounding the safety of exposure to tungsten alone or in mixtures with other metals. Tungsten is commonly used as an alloy with nickel and cobalt in many applications to adjust hardness and thermal and electrical conductivity. This review addresses the current state of knowledge in regard to the mechanisms of toxicity of tungsten in the absence or presence of other metals with a specific focus on mixtures containing nickel and cobalt, the most common components of tungsten alloy. Full article
(This article belongs to the Special Issue Toxicity of Chemical Mixtures)
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Open AccessReview Heavy Metal Mixture Exposure and Effects in Developing Nations: An Update
Received: 21 September 2018 / Revised: 17 October 2018 / Accepted: 23 October 2018 / Published: 2 November 2018
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Abstract
The drive for development and modernization has come at great cost. Various human activities in developed and developing countries, particularly in sub-Saharan Africa (SSA) have given rise to environmental safety concerns. Increased artisanal mining activities, illegal refining, use of leaded petrol, airborne dust, [...] Read more.
The drive for development and modernization has come at great cost. Various human activities in developed and developing countries, particularly in sub-Saharan Africa (SSA) have given rise to environmental safety concerns. Increased artisanal mining activities, illegal refining, use of leaded petrol, airborne dust, arbitrary discarding and burning of toxic waste, absorption of production industries in inhabited areas, inadequate environmental legislation, and weak implementation of policies, have given rise to the incomparable contamination and pollution associated with heavy metals in recent decades. This review evaluates the public health effects of heavy metals and their mixtures in SSA. This shows the extent and size of the problem posed by exposure to heavy metal mixtures in regard to public health. Full article
(This article belongs to the Special Issue Toxicity of Chemical Mixtures)
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