Toxics

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Open AccessArticle

Developmental Neurotoxicity of 3,3',4,4'-Tetrachloroazobenzene with Thyroxine Deficit: Sensitivity of Glia and Dentate Granule Neurons in the Absence of Behavioral Changes

by G. Jean Harry, Michelle J. Hooth, Molly Vallant, Mamta Behl, Gregory S. Travlos, James L. Howard, Catherine J. Price, Sandra McBride, Ron Mervis and Peter R. Mouton

Toxics 2014, 2(3), 496-532; https://doi.org/10.3390/toxics2030496 - 24 Sep 2014

Cited by 18 | Viewed by 9649

Abstract

Thyroid hormones (TH) regulate biological processes implicated in neurodevelopmental disorders and can be altered with environmental exposures. Developmental exposure to the dioxin-like compound, 3,3',4,4'-tetrachloroazobenzene (TCAB), induced a dose response deficit in serum T4 levels with no change in 3,5,3'-triiodothyronine or thyroid stimulating hormone. [...] Read more.

Thyroid hormones (TH) regulate biological processes implicated in neurodevelopmental disorders and can be altered with environmental exposures. Developmental exposure to the dioxin-like compound, 3,3',4,4'-tetrachloroazobenzene (TCAB), induced a dose response deficit in serum T4 levels with no change in 3,5,3'-triiodothyronine or thyroid stimulating hormone. Female Sprague-Dawley rats were orally gavaged (corn oil, 0.1, 1.0, or 10 mg TCAB/kg/day) two weeks prior to cohabitation until post-partum day 3 and male offspring from post-natal day (PND) 4–21. At PND21, the high dose showed a deficit in body weight gain. Conventional neuropathology detected no neuronal death, myelin disruption, or gliosis. Astrocytes displayed thinner and less complex processes at 1.0 and 10 mg/kg/day. At 10 mg/kg/day, microglia showed less complex processes, unbiased stereology detected fewer hippocampal CA1 pyramidal neurons and dentate granule neurons (GC) and Golgi staining of the cerebellum showed diminished Purkinje cell dendritic arbor. At PND150, normal maturation of GC number and Purkinje cell branching area was not observed in the 1.0 mg/kg/day dose group with a diminished number and branching suggestive of effects initiated during developmental exposure. No effects were observed on post-weaning behavioral assessments in control, 0.1 and 1.0 mg/kg/day dose groups. The demonstrated sensitivity of hippocampal neurons and glial cells to TCAB and T4 deficit raises support for considering additional anatomical features of brain development in future DNT evaluations. Full article

(This article belongs to the Special Issue Developmental Neurotoxicology)

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453 KiB

Open AccessReview

Zebrafish as a Model for Developmental Neurotoxicity Assessment: The Application of the Zebrafish in Defining the Effects of Arsenic, Methylmercury, or Lead on Early Neurodevelopment

by Jinyoung Lee and Jennifer L. Freeman

Toxics 2014, 2(3), 464-495; https://doi.org/10.3390/toxics2030464 - 10 Sep 2014

Cited by 36 | Viewed by 9450

Abstract

Developmental exposure to neurotoxic chemicals presents significant health concerns because of the vulnerability of the developing central nervous system (CNS) and the immature brain barrier. To date, a short list of chemicals including some metals have been identified as known developmental neurotoxicants; however, [...] Read more.

Developmental exposure to neurotoxic chemicals presents significant health concerns because of the vulnerability of the developing central nervous system (CNS) and the immature brain barrier. To date, a short list of chemicals including some metals have been identified as known developmental neurotoxicants; however, there are still numerous chemicals that remain to be evaluated for their potential developmental neurotoxicity (DNT). To facilitate evaluation of chemicals for DNT, the zebrafish vertebrate model system has emerged as a promising tool. The zebrafish possesses a number of strengths as a test species in DNT studies including an abundance of embryos developing ex utero presenting ease in chemical dosing and microscopic assessment at all early developmental stages. Additionally, rapid neurodevelopment via conserved molecular pathways supports the likelihood of recapitulating neurotoxic effects observed in other vertebrates. In this review, we describe the biological relevance of zebrafish as a complementary model for assessment of DNT. We then focus on a metalloid and two metals that are known developmental neurotoxicants (arsenic, methylmercury, and lead). We summarize studies in humans and traditional vertebrate models and then detail studies defining the toxicity of these substances using the zebrafish to support application of this model system in DNT studies. Full article

(This article belongs to the Special Issue Developmental Neurotoxicology)

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Open AccessArticle

Changes in miRNA Expression Profiling during Neuronal Differentiation and Methyl Mercury-Induced Toxicity in Human in Vitro Models

by Giorgia Pallocca, Marco Fabbri, Silvia Nerini-Molteni, Francesca Pistollato, Dimitra Zagoura, Maria Grazia Sacco, Laura Gribaldo, Susanne Bremer-Hoffmann and Anna Bal-Price

Toxics 2014, 2(3), 443-463; https://doi.org/10.3390/toxics2030443 - 29 Aug 2014

Cited by 7 | Viewed by 6241

Abstract

MicroRNAs (miRNAs) are implicated in the epigenetic regulation of several brain developmental processes, such as neurogenesis, neuronal differentiation, neurite outgrowth, and synaptic plasticity. The main aim of this study was to evaluate whether miRNA expression profiling could be a useful approach to detect [...] Read more.

MicroRNAs (miRNAs) are implicated in the epigenetic regulation of several brain developmental processes, such as neurogenesis, neuronal differentiation, neurite outgrowth, and synaptic plasticity. The main aim of this study was to evaluate whether miRNA expression profiling could be a useful approach to detect in vitro developmental neurotoxicity. For this purpose, we assessed the changes in miRNA expression caused by methyl mercury chloride (MeHgCl), a well-known developmental neurotoxicant, comparing carcinoma pluripotent stem cells (NT-2) with human embryonic stem cells (H9), both analyzed during the early stage of neural progenitor commitment into neuronal lineage. The data indicate the activation of two distinct miRNA signatures, one activated upon neuronal differentiation and another upon MeHgCl-induced toxicity. Particularly, exposure to MeHgCl elicited, in both neural models, the down-regulation of the same six out of the ten most up-regulated neuronal pathways, as shown by the up-regulation of the corresponding miRNAs and further assessment of gene ontology (GO) term and pathway enrichment analysis. Importantly, some of these common miRNA-targeted pathways defined in both cell lines are known to play a role in critical developmental processes, specific for neuronal differentiation, such as axon guidance and neurotrophin-regulated signaling. The obtained results indicate that miRNAs expression profiling could be a promising tool to assess developmental neurotoxicity pathway perturbation, contributing towards improved predictive human toxicity testing. Full article

(This article belongs to the Special Issue Developmental Neurotoxicology)

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Open AccessReview

Cd, Pb and Hg Biomonitoring in Fish of the Mediterranean Region and Risk Estimations on Fish Consumption

by Elisavet A. Renieri, Athanasios K. Alegakis, Michalis Kiriakakis, Marco Vinceti, Eren Ozcagli, Martin F. Wilks and Aristidis M. Tsatsakis

Toxics 2014, 2(3), 417-442; https://doi.org/10.3390/toxics2030417 - 18 Aug 2014

Cited by 60 | Viewed by 9999

Abstract

Cadmium (Cd), lead (Pb) and mercury (Hg) are toxic metals with increasing interest due to their tendency to bioaccumulate in fish tissue which may pose a threat to human health via fish consumption. This review of the recent literature on Cd, Pb, Hg [...] Read more.

Cadmium (Cd), lead (Pb) and mercury (Hg) are toxic metals with increasing interest due to their tendency to bioaccumulate in fish tissue which may pose a threat to human health via fish consumption. This review of the recent literature on Cd, Pb, Hg levels summarizes data of fish biomonitoring studies in the Mediterranean Sea in order to determine potential risks due to dietary intake of metals. The analytical methods applied are described, with Atomic Absorption Spectroscopy and Inductively Coupled Plasma Mass Spectroscopy being the most popular. Most of the literature reviewed is focused on the Eastern Mediterranean. Results from the studies indicate that metals mostly accumulate in liver, followed by muscle. Although there are few studies reporting metal levels in fish exceeding the maximum residue levels (MRLs), the bulk of the studies cite levels below the MRLs. The hazard index (HI) of fish consumption, namely the ratio of estimated weekly intake to provisional tolerable weekly intake (EWI/PTWI) was estimated for adult consumers and no risk emerged. The EWI/PTWI ratios of lead and mercury for Italy (0.14 and 0.22 respectively) represent the highest HI levels estimated. In view of maximizing the benefits while minimizing the risks of fish consumption, a more detailed fish-specific database on intakes for consumers is required and extended bimonitoring in as many regions as possible. Full article

(This article belongs to the Collection Heavy Metals Toxicology)

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Open AccessReview

An Update and Review of Unconventional Metals Testing and Treatment

by Diana J. Felton, Stefanos N. Kales and Rose H. Goldman

Toxics 2014, 2(3), 403-416; https://doi.org/10.3390/toxics2030403 - 11 Aug 2014

Cited by 6 | Viewed by 12648

Abstract

Most patients who receive unconventional testing for metals do not have any remarkable exposure history and typically lack symptoms or objective findings compatible with classic heavy metal intoxication. Unconventional tests results are usually promoted by alternative practitioners as the basis for recommending, promoting, [...] Read more.

Most patients who receive unconventional testing for metals do not have any remarkable exposure history and typically lack symptoms or objective findings compatible with classic heavy metal intoxication. Unconventional tests results are usually promoted by alternative practitioners as the basis for recommending, promoting, and selling to the patient questionable and often inappropriate therapies/interventions supposedly aimed at “detoxification”. Most of these patients will have no evidence of overexposure to metals on the basis of a thorough history and will have levels of metals on conventional tests performed at reliable laboratories that are undetectable, within population background ranges or above population background, but well below levels associated with toxicity. Full article

(This article belongs to the Collection Heavy Metals Toxicology)

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Open AccessReview

The Use of Chemical Weapons in the Syrian Conflict

by René Pita and Juan Domingo

Toxics 2014, 2(3), 391-402; https://doi.org/10.3390/toxics2030391 - 30 Jul 2014

Cited by 80 | Viewed by 20955

Abstract

This paper aims at explaining the lessons learned from the chemical attacks that took place in 2013 in the Syrian military conflict, especially the sarin attacks on the Ghouta area of Damascus on August 21. Despite the limitations the UN Mission found while [...] Read more.

This paper aims at explaining the lessons learned from the chemical attacks that took place in 2013 in the Syrian military conflict, especially the sarin attacks on the Ghouta area of Damascus on August 21. Despite the limitations the UN Mission found while investigating the use of chemical weapons (CW) in Syria, some interesting conclusions for the scientific and medical community can be obtained from its reports. These include the advantages of the Chemical Weapons Convention procedure for the investigation of alleged CW use, when compared with the United Nations mechanism for similar investigations, the difficulties of differential diagnosis based only on clinical signs and symptoms and the impact of secondary contamination when responding to a CW attack. Full article

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Open AccessArticle

Short-Term Traffic-Related Exposures and Biomarkers of Nitro-PAH Exposure and Oxidative DNA Damage

by Andreas M. Neophytou, Jaime E. Hart, Yan Chang, Junfeng Zhang, Thomas J. Smith, Eric Garshick and Francine Laden

Toxics 2014, 2(3), 377-390; https://doi.org/10.3390/toxics2030377 - 22 Jul 2014

Cited by 25 | Viewed by 6317

Abstract

Exposure to vehicle exhaust has been associated with cardiac and respiratory disease, lung cancer and greater overall mortality. We investigated whether amino-polycyclic aromatic hydrocarbon (amino-PAH) metabolites of nitro-PAHs could be used as biomarkers of these exposures. Pre- and post-shift urine samples were collected [...] Read more.

Exposure to vehicle exhaust has been associated with cardiac and respiratory disease, lung cancer and greater overall mortality. We investigated whether amino-polycyclic aromatic hydrocarbon (amino-PAH) metabolites of nitro-PAHs could be used as biomarkers of these exposures. Pre- and post-shift urine samples were collected at the beginning and end of a work week from 82 male U.S. trucking industry workers. We used repeated-measures analysis to examine associations of total 1- and 2-aminonaphthalene (1 & 2-AN) and 1-aminopyrene (1-AP) urinary concentrations with microenvironment exposures to particulate matter (PM_2.5), elemental and organic carbon and between 1 & 2-AN and 1-AP with urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG). There was an association between work week mean PM_2.5 levels and post-shift 1 & 2-AN (141.8 pg/mL increase (95% CI: 53.3, 230.2) for each IQR increase (5.54 µg/m³) in PM_2.5), but no associations with other exposure measures. There was a statistically significant increase in 8-OHdG concentrations with 1 & 2-AN (2.38 µg/mg creatinine (95% CI: 0.19, 4.58) per 242.85 pg/mg creatinine increase in 1 & 2-AN) and suggestive associations with all other exposure measures. Our findings suggest associations between urinary amino-PAHs with vehicle exhaust-related PM_2.5, as well as with a biomarker of oxidative DNA damage. Full article

(This article belongs to the Special Issue Exposure to Airborne Toxics in Biological Populations and Implications for Health)

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485 KiB

Open AccessReview

The Alchemist’s Approach to Metal Poisoning: Transforming the Metal Burden

by Wayne Briner

Toxics 2014, 2(3), 364-376; https://doi.org/10.3390/toxics2030364 - 25 Jun 2014

Cited by 6 | Viewed by 4845

Abstract

Metal poisoning is a global problem with humans being exposed to a wide range of metals in varying doses and varying time frames. Traditionally, treatment involves removal of the toxic source or chelation therapy. An intermediate approach is needed. This review outlines the [...] Read more.

Metal poisoning is a global problem with humans being exposed to a wide range of metals in varying doses and varying time frames. Traditionally, treatment involves removal of the toxic source or chelation therapy. An intermediate approach is needed. This review outlines the argument for the use of essential metal supplementation as a strategy to induce metallothionein expression and displace the toxic metal from important biological systems, improving the metal burden of the patient. Specific recommendations are given for supplementation with calcium, zinc and vitamin E as a broad strategy to improve the status of those exposed to toxic metals. Full article

(This article belongs to the Collection Heavy Metals Toxicology)

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Toxics, Volume 2, Issue 3 (September 2014) – 8 articles , Pages 364-532

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