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, 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.
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 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.
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 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.
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, 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.
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 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.
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 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 (PM2.5), 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 PM2.5 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 PM2.5), 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 PM2.5, as well as with a biomarker of oxidative DNA damage.