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Over the last decades, new psychoactive substances (NPSs) have established a new pattern of drug synthesis and distribution. These compounds brought with them several challenges, including their analytical determination by known methodologies, the uncertainty of their toxicological effects, and the possible approaches used for control. In Brazil, the control of NPS started with a nominal list of proscribed compounds. But the variety of substances was so large that other strategies were implemented. Generic legislation was created as several groups began to emerge, such as phenethylamines, synthetic cathinones, and synthetic cannabinoids. The legislation also began to include salts and isomers of all listed substances and precursor chemical ingredients or plants that may be used to produce them. Those substances are known for the unpredictability of their effects, causing a wide range of symptoms, including seizures, aggression, and acute psychosis. Users under effect represent a high risk for themselves and others. In this study, we present an overview of the timeline in which NPSs were detected in Brazilian territory and the legislative approaches. A complete literature search was performed using PubMed, Scopus, the World Wide Web and Brazilian governmental websites employing relevant keywords such as NPS, legislation, and Brazil. Even with the high volume of legislative measures, the race against NPS intoxication cases and apprehensions continues to be fierce. There are limitations in the process of detection, identification, and prohibition of the substances in the country that demand a multifactorial approach, stronger public health measures, scientific research, as well as harm reduction strategies. Nevertheless, the Brazilian scenario on NPS arrival reflects a worldwide problem faced by many countries. In conclusion, it is stated that the use of multiple legislative strategies such as prohibition lists and generic controls can provide for better regulation of the NPS problem. However, this issue needs to be addressed by multiple organizations, including police departments and the public health system, and that effort needs to be coordinated and standardized for all Brazilian Federal states. [ABSTRACT FROM AUTHOR]

The neonicotinoid imidacloprid was promoted in the market because of widespread resistance to other insecticides, plus its low mammalian impact and higher specific toxicity towards insects. This study aimed to evaluate the immunomodulatory effect of imidacloprid on macrophages. RAW 264.7 cells were incubated to 0–4000 mg/L of imidacloprid for 24 and 96 h. Imidacloprid presented a concentration-dependent cytotoxicity after 24 h and 96 h incubation for MTT reduction (3-(4,5-dimethyl-thiazol-2-yl)− 2,5-diphenyltetrazolium bromide) (EC 50 519.6 and 324.6 mg/L, respectively) and Neutral Red (3-amino-7-dimethylamino-2-methylphenazine hydrochloride) assays (EC 50 1139.0 and 324.2 mg/L, respectively). Moreover, imidacloprid decreased the cells' inflammatory response and promoted a mitochondrial depolarization. The complex II and succinate dehydrogenase (SDH) activities in RAW 264.7 cells incubated with imidacloprid increased more at 24 h. These results suggest that imidacloprid exerts an immunomodulatory effect and mitochondria can act as regulator of innate immune responses in the cytotoxicity mediated by the insecticide in RAW 264.7 cells. [Display omitted] • A commercial formulation of imidacloprid impaired the inflammatory response in RAW 264.7 cells; • The immunotoxic effects were associated with long term exposure to imidacloprid; • The mitochondria is a primary target of imidacloprid cytotoxicity. [ABSTRACT FROM AUTHOR]

Imidacloprid (IMI) is a neonicotinoid insecticide employed worldwide for crop protection. IMI's mode of action occurs through the agonism of postsynaptic nicotinic acetylcholine receptors (nAChRs), with high specificity for insect nAChRs although there are reports of mammals' toxicity. Studies on IMI's neurotoxicity are not conclusive; therefore, the aim of this study was to evaluate the subchronic toxic effects of an IMI based commercial pesticide on rats. Adult male Wistar rats received an IMI suspension via the oral route at doses of 1.5, 5, and 15 mg/kg for 45 consecutive days. IMI caused an increase in rearing and time spent at the periphery in the locomotor activity test and a decrease in time spent to finish the OX maze task (p < 0.05; ANOVA/Bonferroni). In blood, there was a decrease in mean corpuscular hemoglobin and mean corpuscular hemoglobin concentration (p < 0.05; ANOVA/Bonferroni) and an increase in serum butyrylcholinesterase activity (p < 0.001; ANOVA/Bonferroni). Therefore, subchronic administration of an IMI-based-pesticide caused behavioral and systemic impairments in rats. • Imidacloprid increased rearing in rats. • Imidacloprid increased time spent at the periphery in the locomotor activity test. • Imidacloprid decreased the time spent to finish the OX maze task. • Imidacloprid decreased mean corpuscular hemoglobin in rats. • Imidacloprid increased serum butyrylcholinesterase in rats. [ABSTRACT FROM AUTHOR]

Environmental exposure to manganese (Mn) results in several toxic effects, mainly neurotoxicity. This study investigated associations among Mn exposure, neuropsychological performance, biomarkers of oxidative damage and early kidney dysfunction in children aged 6–12 years old. Sixty-three children were enrolled in this study, being 43 from a rural area and 20 from an urban area. Manganese was quantified in blood (B-Mn), hair (H-Mn) and drinking water using inductively coupled plasma mass spectrometry (ICP-MS). The neuropsychological functions assessed were attention, perception, working memory, phonological awareness and executive functions – inhibition. The Intelligence quotient (IQ) was also evaluated. The biomarkers malondialdehyde (MDA), protein carbonyls (PCO), δ-aminolevulinate dehydratase (ALA-D), reactivation indexes with dithiothreitol (ALA-RE/DTT) and ZnCl 2 (ALA-RE/ZnCl 2 ), non-protein thiol groups, as well as microalbuminuria (mALB) level and N-acetyl-β-D-glucosaminidase (NAG) activity were assessed. The results demonstrated that Mn levels in blood, hair and drinking water were higher in rural children than in urban children ( p <0.01). Adjusted for potential confounding factors, IQ, age, gender and parents' education, significant associations were observed mainly between B-Mn and visual attention (β=0.649; p <0.001). Moreover, B-Mn was negatively associated with visual perception and phonological awareness. H-Mn was inversely associated with working memory, and Mn levels from drinking water with written language and executive functions – inhibition. Rural children showed a significant increase in oxidative damage to proteins and lipids, as well as alteration in kidney function biomarkers ( p <0.05). Moreover, significant associations were found between B-Mn, H-Mn and Mn levels in drinking water and biomarkers of oxidative damage and kidney function, besides between some oxidative stress biomarkers and neuropsychological tasks ( p <0.05). The findings of this study suggest an important association between environmental exposure to Mn and toxic effects on neuropsychological function, oxidative damage and kidney function in children. [ABSTRACT FROM AUTHOR]