China
Africa
Explore chapters and articles related to this topic
Agrochemicals: A Brief Overview
Published in Dongyou Liu, Handbook of Foodborne Diseases, 2018
Dithiocarbamates are a family of fungicides widely used since the 1940s to control fungal pathogens in a variety of crops. Compounds in this class include Maneb and Zineb (which include a metal moiety, manganese, and zinc, respectively) and Thiram (which does not have a metal moiety). These compounds have low acute toxicity, but chronic exposure is associated with adverse effects that may be due to the dithiocarbamate acid or the metal moiety. An important common metabolite of dithiocarbamates is ethylenethiourea, which is responsible for their effects on the thyroid (alterations of thyroid hormone levels, thyroid hypertrophy, and tumors) (110). Chronic exposure to Maneb has been associated with parkinsonism, possibly because of exposure to manganese, rather than the dithiocarbamate (111), and this fungicide has been recently withdrawn from the U.S. market (112). Interestingly, the structure of dithiocarbamate fungicides resembles that of disulfiram, an inhibitor of aldehyde dehydrogenase used in the treatment of alcoholism; for this reason, dithiocarbamates may interact with alcohol, leading to elevation in acetaldehyde levels (109). In addition, inhibition of aldehyde dehydrogenase, which also metabolizes DOPAL (3,4-dihydroxy phenyl acetaldehyde), a toxic metabolite of dopamine, is emerging as an important mechanism for a pesticidal etiology of Parkinson disease (113).
Environmental toxicants on Leydig cell function
Published in C. Yan Cheng, Spermatogenesis, 2018
Leping Ye, Xiaoheng Li, Xiaomin Chen, Qingquan Lian, Ren-Shan Ge
Carbamates are used as insecticides and fungicides. Maneb is a widely used fungicide in agriculture. Exposure of maneb (1 and 4 mg/kg BW/day, i.p.) for 9–18 days to male rats reduced testosterone production and CYP11A1 activity in Leydig cells.192 Carbendazim is a metabolite of benomyl, one of the most widespread environmental contaminants. Exposure to carbendazim (25 mg/kg BW/day) to male rats for 48 days significantly reduced testosterone levels and 3β-HSD and 17β-HSD3 activities without affecting serum LH levels.193 Exposure to carbendazim to rats also caused an increase in ROS production and the downregulation of Star mRNA levels. The addition of a flavonoid can prevent this, suggesting an ROS-inducing mechanism.194
Reproductive and Developmental Toxicity Studies by Cutaneous Administration
Published in Rhoda G. M. Wang, James B. Knaak, Howard I. Maibach, Health Risk Assessment, 2017
Rochelle W. Tyl, Raymond G. York, James L. Schardein
Imidazolidinethione, a fungicide degradation product of maneb, induced polymorphic malformations and other developmental toxicity when administered topically to rats at only 50 mg/kg on gestation days 10 and 11 or 12 and 13.” The developmental toxicity elicited was similar to that observed following oral administration in the rat,126 whereas the single inhalation exposure study reported in this species did not report developmental toxicity.127 The chemical is developmentally hazardous, producing developmental effects at a fraction of the dosage eliciting maternal toxicity.
Manganese-induced neurodegenerative diseases and possible therapeutic approaches
Published in Expert Review of Neurotherapeutics, 2020
Airton C. Martins, Priscila Gubert, Gustavo R. Villas Boas, Marina Meirelles Paes, Abel Santamaría, Eunsook Lee, Alexey A. Tinkov, Aaron B. Bowman, Michael Aschner
Human exposure to Mn mainly occurs via intake of contaminated food and water, by occupational sources (inhalation of industrial applications, dust, mist, or fumes with Mn), and by environmental sources which include pesticides containing Mn [101]. Maneb (ethylenebis-dithiocarbamate) is a Mn-containing fungicide whose chronic exposure may produce symptoms and signs of central nervous system (CNS) Mn poisoning. Maneb exposure in rats caused a reduction in fertility and testosterone levels. In contrast, its co-administration with Basella alba L. (Basellaceae) extract minimized such changes in reproductive function [153]. B. alba showed efficacy in restoring the antioxidant system in the testicular tissue likely due to the presence of various antioxidant compounds, including phenolic compounds, carotenoids, ascorbic acid, saponins, coumarins and limonoids [154]. Finally, beyond the pharmacological advantages of plants usage, an extensive historical background of their consumption is available, thus reducing toxicological risks and adverse effects when compared to newly synthesized molecules.
Bioactivation of herbal constituents: mechanisms and toxicological relevance
Published in Drug Metabolism Reviews, 2019
Silymarin (Figure 12(a)), a flavonoid mixture extracted from the seeds of the plant Silybum marianum (milk thistle), possesses anti-inflammatory, antioxidant, immunomodulatory, antifibrotic, antiproliferative and antiviral properties (Surai 2015). Silymarin extracts typically contain 65%-80% flavonolignans (namely silybins A and B, isosilybins A and B, silychristins A and B, and silydianin) with silybins as the predominant bioactive components (Křen et al. 2013). Due to its antioxidant and chemopreventive effects, silymarin has been used as ‘liver tonics’ for centuries to treat liver disorders of different etiologies in traditional herbal remedies (Federico et al. 2017). It has been shown that silymarin protected against maneb- and paraquat-induced hepatotoxicity in rats via modulation of xenobiotic metabolizing enzymes and inhibition of inflammatory response (Ahmad et al. 2013). Silybin, the major silymarin flavonolignan, was demonstrated to alleviate hepatic steatosis and fibrosis in a NASH mouse model via activation of Nrf2 and inhibition of NF-κB pathways (Ou et al. 2018). Silymarin flavonolignans undergo CYP-mediated hydroxylations on ring A followed by two-electron oxidation to ortho- or papa-quinones leading to formation of GSH conjugates (Chen et al. 2018) (Figure 12(a)). Meantime, O-demethylation of ring E yields a catechol which can be oxidized to electrophilic ortho-quinone. These electrophilic quinones are proposed as mediators of mechanism-based inactivation of CYP3A4 and CYP2C9 (Sridar et al. 2004). Likewise, these quinone metabolites may contribute to the antioxidant and anti-inflammatory effects of silymarin via covalent modification of the cysteine thiols of Keap1 protein leading to activation of the Keap1/Nrf2/ARE pathway (Surai 2015).
Analytical and toxicological aspects of dithiocarbamates: an overview of the last 10 years
Published in Toxicology Mechanisms and Methods, 2022
Jéssica Cristina Romoli, Deborah Thais Palma Scarferla, Raul Gomes Aguera, Renata Sano Lini, Giseli Cristina Pante, Carlos Roberto Bueno Junior, Juliana Cristina Castro, Simone Aparecida Galerani Mossini, Camila Marchioni, Miguel Machinski Junior
Our literature search comprised Pubmed, Science Direct and Web of Science databases, covering the period from 2010 to 2020. The descriptors used were: “dithiocarbamate fungicide”, “dithiocarbamate pesticides”, “chromatography”, “liquid chromatography”, “gas chromatography”, “biological monitoring”, “biological samples”, “carbon disulfide”, “2-thiazolidinethione-4-carboxylic acid”, “propylenethiourea”, “ethylenethiourea”, “mancozeb”, “maneb”, “zineb” and “metiram”.