Acetochlor is a chloroacetamide herbicide applied to various crops worldwide and is one of the top selling herbicides on the global market. Due to rain events and run-off, the potential for acetochlor-induced toxicity is a concern for aquatic species. Here we review the current state of knowledge regarding the concentrations of acetochlor in aquatic ecosystems globally and synthesize the biological impacts of acetochlor exposure to fish. We compile toxicity effects of acetochlor, outlining evidence for morphological defects, developmental toxicity, endocrine and immune system disruption, cardiotoxicity, oxidative stress, and altered behavior. To identify mechanisms of toxicity, we utilized computational toxicology and molecular docking approaches to uncover putative toxicity pathways. Using the comparative toxicogenomics database (CTD), transcripts responsive to acetochlor were captured and graphically depicted using String-DB. Gene-ontology analysis revealed that acetochlor may disrupt protein synthesis, blood coagulation, signaling pathways, and receptor activity in zebrafish. Further pathway analysis revealed potential novel targets for acetochlor disruption at the molecular level (e.g., TNF alpha, heat shock proteins), highlighting cancer, reproduction, and the immune system as biological processes associated with exposure. Highly interacting proteins in these gene networks (e.g., nuclear receptors) were selected to model binding potential of acetochlor using SWISS-MODEL. The models were used in molecular docking to strengthen evidence for the hypothesis that acetochlor acts as an endocrine disruptor, and results suggest estrogen receptor alpha and thyroid hormone receptor beta may be preferential targets for disruption. Lastly, this comprehensive review reveals that, unlike other herbicides, neither immunotoxicity nor behavioral toxicity have been fully investigated as sub-lethal endpoints for acetochlor, and such mechanisms of toxicity should be emphasized in future research investigating biological responses of fish to the herbicide.

The gradual increase in the global population has led to the rising demand for agricultural products worldwide. This required the introduction of environment- and public health-friendly advanced technologies for plant protection to guard yields from pest destruction in a sustainable way. Encapsulation technology is a promising procedure to increase the effectiveness of pesticide active ingredients while reducing human exposure and environmental impact. Despite the presumed favorable properties of encapsulated pesticide formulations on human health, it is necessary to systematically assess whether they are less harmful to human health than conventional pesticide products.
We aim to systematically review the literature to answer the question of whether micro- or nano-encapsulated pesticide formulations exert different degrees of toxicity than their conventional (not-encapsulated) counterparts in in vivo animal and in vitro (human, animal, and bacterial cell) non-target models. The answer is important to estimate the possible differences in the toxicological hazards of the two different types of pesticide formulations. Because our extracted data will come from different models, we also aim to perform subgroup analyses to investigate how toxicity varies across different models. A pooled toxicity effect estimate will also be performed by meta-analysis when appropriate.
The systematic review will follow the guidelines developed by the National Toxicology Program\'s Office of Health Assessment and Translation (NTP/OHAT). The protocol adheres to the Preferred Reporting Items for Systematic Reviews and meta-analyses Protocol (PRISMA-P) statement. PubMed (NLM), Scopus (Elsevier), Web of Science Core Collection (Clarivate), Embase (Elsevier), and Agricola (EBSCOhost) electronic databases will be comprehensively searched in September 2022 to identify eligible studies using multiple search terms of \"pesticide\", \"encapsulation\" and \"toxicity\" along with their synonyms and other words that are semantically related. The reference lists of all eligible articles and retrieved reviews will be manually screened to identify additional relevant papers.
We will include peer-reviewed experimental (non-target in vivo animal model and in vitro human, animal, and bacterial cell cultures) studies published as full-text articles in English language that simultaneously investigate the effect of any micro- or nano-encapsulated pesticide formulation, applied in all ranges of concentrations, duration, and routes of exposure, and its corresponding active ingredient(s) or its conventional non-encapsulated product formulation(s) used in the same ranges of concentrations, duration, and routes of exposure on the same pathophysiological outcome. We will exclude studies that examine pesticidal activity on target organisms, cultures of cells isolated from target organisms exposed in vivo or in vitro, and those using biological materials isolated from target organisms/cells.
Studies identified by the search will be screened and managed according to the review inclusion and exclusion criteria in the Covidence systematic review tool by two reviewers, who will also blindly extract the data and assess the risk of bias of included studies. The OHAT risk of bias tool will be applied to evaluate the quality and risk of bias in the included studies. Study findings will be synthesized narratively by important features of the study populations, design, exposure, and endpoints. If findings make it possible, a meta-analysis will be performed on identified toxicity outcomes. To rate the certainty in the body of evidence, we will use the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach.

Brazil is the third largest exporter of fruits and vegetables in the world and, consequently, uses large amounts of pesticides. Food contamination with pesticide residues (PRs) is a serious concern, especially in developing countries. Several research reports revealed that some Brazilian farmers spray pesticides on fruits and vegetables in large quantities, generating PRs after harvest. Thus, ingestion of food contaminated with PRs can cause adverse health effects. Based on information obtained through a systematic review of essential information from 33 articles, we studied the assessment of potential health risks associated with fruit and vegetable consumption in children and adults from Brazilian states. This study identified 111 PRs belonging to different chemical groups, mainly organophosphates and organochlorines, in 26 fruit and vegetable samples consumed and exported by Brazil. Sixteen of these PRs were above the Maximum Residue Limit (MRL) established by local and international legislation. We did not identify severe acute and chronic dietary risks, but the highest risk values were observed in São Paulo and Santa Catarina, associated with the consumption of tomatoes and sweet peppers due to the high concentrations of organophosphates. A high long-term health risk is associated with the consumption of oranges in São Paulo and grapes in Bahia due to chlorothalonil and procymidone. We also identified that 26 PRs are considered carcinogenic by the United States Environmental Protection Agency (US EPA), and the carcinogenic risk analysis revealed no severe risk in any Brazilian state investigated due to the cumulative hazard index (HI) < 1. However, the highest HI values were in São Paulo due to acephate and carbaryl in sweet pepper and in Bahia due to dichlorvos. This information can help regulatory authorities define new guidelines for pesticide residue limits in fruits and vegetables commonly consumed and exported from Brazil and monitor the quality of commercial formulations.

The use of agrochemicals has grown in recent years following the increase in agricultural productivity, to eliminate weeds that can compromise crop yields. The intensive use of these products combined with the lack of treatment of agricultural wastewater is causing contamination of the natural environments, especially the aquatics. Glyphosate [N-(phosphonomethyl) glycine] is the most commonly used herbicide in agriculture worldwide. Studies have shown that this compound is toxic to a variety of fish species at the concentrations of environmental relevance. Glyphosate-based herbicides can affect fish biochemical, physiological, endocrine, and behavioral pathways. Changes in behaviors such as foraging, escaping from predators, and courtship can compromise the survival of species and even communities. The behavior patterns of fish has been shown to be a sensitive tool for risk assessment. In this sense, this review summarizes and discusses the toxic effects of glyphosate and its formulations on the behavior of fish in different life stages. Additionally, behavioral impairments were associated with other negative effects of glyphosate such as energy imbalance, stress responses, AChE inhibition, and physiological and endocrine disturbances, which are evidenced and described in the literature. Graphical abstract.

Azole fungicides are widely used chemicals in agriculture and medicine. Their antifungal activity involves inhibition of steroid biosynthesis via inhibition of several cytochrome p450 enzymes. Evidence is accumulating in fish species to suggest azole fungicides perturb multiple hormone signaling pathways. The objective of this review was to comprehensively review data for azole-mediated impacts on the teleost endocrine system. We emphasize aspects of azole-induced endocrine disruption in several fish species, with special focus on the hypothalamic-pituitary-gonadal (HPG), hypothalamus-pituitary-thyroid (HPT) and hypothalamic-pituitary-adrenal (HPA) axis. Histopathological, physiological, and molecular data suggest azole fungicides at environmentally relevant concentrations and above are endocrine disruptors in fish. Endocrine disruption has been well documented for some azoles (e.g., difenconazole, fadrozole, ketoconazole, tebuconazole, triadimefon), but there are little data for others (e.g., cyproconazole, expoxiconazole, imidazole, metoconazole, nocodazole) in fish, revealing a knowledge gap in our understanding of azole toxicity. Based upon literature, computational analyses of transcriptome responses revealed progesterone-mediated oocyte maturation, insulin signaling pathway, adrenergic signaling, and metabolism of angiotensinogen may be processes disrupted by azoles. However, hormonal regulation of the sympathetic nervous system and the cardiovascular system in response to azole exposure has yet to be investigated in fish. Recommendations for studies moving forward include focus on non-steroid endocrine pathways, mechanisms of neuroendocrine disruption, and transgenerational effects of azoles on fish. This critical review identifies knowledge gaps and future directions for environmental studies focused on the effects of azoles in aquatic species.

In this critical review, we synthesize data from peer-reviewed literature reporting on triazole fungicide exposures in the zebrafish model. Based on their mode of action in plants (potent inhibitors of ergosterol synthesis), we focused attention on mechanisms related to cellular, lipid, and steroid metabolism. Evidence from several studies reveals that zebrafish exposed to triazoles present with impaired mitochondrial oxidative phosphorylation and oxidative stress, as well as dysregulation of lipid metabolism. Such metabolic disruptions are expected to underscore developmental delays, deformity, and aberrant locomotor activity and behaviors often observed following exposure. We begin by summarizing physiological and behavioral effects observed with triazole fungicide exposure in zebrafish. We then discuss mechanisms that may underlie adverse apical effects, focusing on mitochondrial bioenergetics and metabolism. Using computational approaches, we also identify novel biomarkers of triazole fungicide exposure. Extracting and analyzing data contained in the Comparative Toxicogenomics Database (CTD) revealed that transcriptional signatures responsive to different triazoles are related to metabolism of lipids and lipoproteins, biological oxidations, and fatty acid, triacylglycerol, and ketone body metabolism among other processes. Pathway and sub-network analysis identified several transcripts that are responsive in organisms exposed to triazole fungicides, several of which include lipid-related genes. Knowledge gaps and recommendations for future investigations include; (1) targeted metabolomics for metabolites in glycolysis, Krebs cycle, and the electron transport chain; (2) additional studies conducted at environmentally relevant concentrations to characterize the potential for endocrine disruption, given that studies point to altered cholesterol (precursor for steroid hormones), as well as altered estrogen receptor alpha and thyroid hormone expression; (3) studies into the potential role for lipid peroxidation and oxidation of lipid biomolecules as a mechanism of triazole-induced toxicity, given the strong evidence for oxidative damage in zebrafish following exposure to triazole fungicides.

Agriculture accountsfor an important economic activity worldwide and the search for the increased productivity incorporated the use of pesticides in this practice. Such compounds have significant environmental and human health effects, especially for workers exposed to them. Among the main health problems caused by pesticides are the renal alterations, which in more advanced stages comprise an important public health problem. For this reason, this systematic review aimed at gathering evidence of the risk of renal changes induced by occupational exposure to pesticides. The search was made in PubMed, Scopus, Lilacs and Scielo in December 2017, using keywords as pesticides, poisoning, kidney, renal insufficiency. After the application of inclusion criteria, 11 studies were selected. It was possible to gather evidence on the prevalence and risk (3.12-6.71) of renal injury from the occupational exposure of agricultural workers and its association with the exposure to agrichemicals, as organophosphates and herbicides.

Herbicides are an important asset in ensuring food security, especially when faced with an ever-increasing demand on food production to feed the global population. The current selection of herbicides is increasingly encountering resistance in agricultural weeds they once targeted effectively. It is imperative that new compounds or more effective modes of action are discovered in order to overcome this resistance. This cheminformatics review looks at current herbicides and evaluates their physiochemical properties on a class-by-class basis. We focus in particular on the synthetic auxin herbicides, Herbicide Resistance Action Committee class O, analyzing these against herbicides more generally and for class-specific features such as mobility in plant vasculature. We summarise the physiochemical properties of all 24 compounds used commercially as auxins and relate these results to ongoing approaches to novel auxin discovery. We introduce an interactive, open source cheminformatics tool known as DataWarrior for herbicide discovery, complete with records for over 300 herbicidal compounds. We hope this tool helps researchers as part of a rational approach to not only auxin discovery but agrochemical discovery in general.