Acute exposure to acrylamide (ACR), a type-2 alkene, may lead to a ataxia, skeletal muscles weakness and numbness of the extremities in human and laboratory animals. In the present manuscript, ACR acute neurotoxicity has been characterized in adult zebrafish, a vertebrate model increasingly used in human neuropharmacology and toxicology research. At behavioral level, ACR-treated animals exhibited “depression-like” phenotype comorbid with anxiety behavior. At transcriptional level, ACR induced down-regulation of regeneration-associated genes and up-regulation of oligodendrocytes and reactive astrocytes markers, altering also the expression of genes involved in the presynaptic vesicle cycling. ACR induced also significant changes in zebrafish brain proteome and formed adducts with selected cysteine residues of specific proteins, some of them essential for the presynaptic function. Finally, the metabolomics analysis shows a depletion in the monoamine neurotransmitters, consistent with the comorbid depression and anxiety disorder, in the brain of the exposed fish.

In this study, the simultaneous presence of eight polybrominated diphenyl ethers (PBDEs), nine new brominated flame retardants (NBFRs) and ten organophosphorus flame retardants (OPFRs) was investigated in dust samples collected from different indoor environments (homes, schools, theatres, a university and a Research Institute) in Barcelona, Spain. OPFRs were detected at the highest concentrations followed by PBDEs. ∑OPFRs ranged from 2053 to 72,090ngg(-1) and tris(2-chloroisopropyl) phosphate (TCIPP) was the most abundant compound. BDE-209 was the main PBDE congener detected (up to 14,990ngg(-1)), while other PBDEs ranged from 2.6 to 118ngg(-1). Among the studied NBFRs, decabromodiphenyl ethane (DBDPE - up to 4432ngg(-1)) followed by bis(2-ethylhexyl) tetrabromophthalate (BEH-TEBP - up to 508ngg(-1)) were detected at the highest concentration, whereas a lower detection frequency was observed for 2-ethylhexyl 2,3,4,5-tetrabromobenzoate (EH-TBB), 1,2-bis(2,4,6-tribromophenoxy)ethane (BTBPE), pentabromotoluene (PBT) and hexabromobenzene (HBB). The levels and profile of flame retardants (FRs) were characteristic of each environment, where theatres followed by homes presented the highest concentrations and schools had the lowest levels. Principal Component Analysis permitted to identify the main sources and distribution of all FRs, according to specific uses in each environment. The simultaneous presence of all FR families in indoor dust points to the need to monitor these compounds to minimize human exposure.

No abstract

Acrylamide (ACR), a type-2 alkene, may lead to a synaptopathy characterized by ataxia, skeletal muscles weakness and numbness of the extremities in exposed human and laboratory animals. Currently, only the mildly affected patients undergo complete recovery, and identification of new molecules with therapeutic bioactivity against ACR acute neurotoxicity is urgently needed. Here, we have generated a zebrafish model for ACR neurotoxicity by exposing 5 days post-fertilization zebrafish larvae to 1 mM ACR for 3 days. Our results show that zebrafish mimics most of the pathophysiological processes described in humans and mammalian models. Motor function was altered, and specific effects were found on the presynaptic nerve terminals at the neuromuscular junction level, but not on the axonal tracts or myelin sheath integrity. Transcriptional markers of proteins involved in synaptic vesicle cycle were selectively altered, and the proteomic analysis showed that ACR-adducts were formed on cysteine residues of some synaptic proteins. Finally, analysis of neurotransmitters profile showed a significant effect on cholinergic and dopaminergic systems. These data support the suitability of the developed zebrafish model for screening of molecules with therapeutic value against this toxic neuropathy.

The present paper describes the Vibrational Startle Response Assay (VSRA), a new robust, simple and automated in vivo medium-to high-throughput procedure for assessment of the escape response and its habituation in zebrafish larvae. Such behaviors enable fish larvae to escape from predator strikes in aquatic ecosystems. The assay is based on measuring the distance moved by each larva during the startle response evoked by repetitive vibrational stimuli. The iterative reduction observed in the response to a series of tapping stimulus in VSRA met the main criteria of habituation. Subsequently, the analysis of concordance using a battery of neuroactive compounds modulating different neurotransmitter systems demonstrated that the results of VSRA are highly predictive of the effects on other vertebrates. Finally, as a proof of concept, VSRA was used to test two relevant environmental pollutants at different concentrations. The results demonstrated that VSRA is suitable for concentration-response analysis of environmental pollutants, opening the possibility to determine the potency and the associated hazard of impaired escape response for the different compounds. Therefore, we suggest that VSRA could be a valuable tool for screening of chemical compounds capable of compromising predator avoidance behavior.

No abstract

The results obtained in this study demonstrate the capability of LC-Orbitrap-MS for accurate trace analysis of these very polar contaminants. This method permitted to identify cyclophosphamide and epirubicin in wastewaters and influents of WWTP, but no traces were detected in WWTP effluents. The methodology herein developed is sensitive and robust and applicable for screening of a large number of samples since no preconcentration is needed.

The effects of pharmaceuticals and personal care products (PPCPs) on aquatic organisms represent a significant current concern. Herein, a targeted metabolomics approach using liquid chromatography-high resolution mass spectrometry (LC-HRMS) is presented to characterise concentration changes in 29 selected metabolites following exposures of aquatic invertebrates, Gammarus pulex, to pharmaceuticals. Method performance revealed excellent linearity (R2 > 0.99), precision (0.1–19%) and lower instrumental limits of detection (0.002–0.20 ng) for all metabolites studied. Three pharmaceuticals were selected representing the low, middle and high range of measured acute measured toxicities (of a total of 26 compounds). Gammarids were exposed to both the no-observed-adverse-effect-level (NOAEL) and the lowest-observed-adverse-effect-level (LOAEL) of triclosan (0.1 and 0.3 mg L− 1), nimesulide (0.5 and 1.4 mg L− 1) and propranolol (100 and 153 mg L− 1) over 24 h. Quantitative metabolite profiling was then performed. Significant changes in metabolite concentrations relative to controls are presented and display distinct clustered trends for each pharmaceutical. Approximately 37% (triclosan), 33% (nimesulide) and 46% (propranolol) of metabolites showed statistically significant time-related effects. Observed changes are also discussed with respect to internal concentrations of the three pharmaceuticals measured using a method based on pulverised liquid extraction, solid phase extraction and LC-MS/MS. Potential metabolic pathways that may be affected by such exposures are also discussed. This represents the first study focussing on quantitative, targeted metabolomics of this lower trophic level benthic invertebrate that may elucidate biomarkers for future risk assessment.