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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possibly because of exposure to manganese, rather than the dithiocarbamate (111), and this fungicide has been recently withdrawn from the U.S. market (112).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).
Pesticides and Chronic Diseases
Published in William J. Rea, Kalpana D. Patel, Reversibility of Chronic Disease and Hypersensitivity, Volume 4, 2017
William J. Rea, Kalpana D. Patel
The ethylene bisdithiocarbamate class includes maneb, zineb, mancozeb, metiram, and nabam. According to the EPA, a common contaminant ethylene thiourea (ET) is a carcinogen in rats and has specific effects on the thyroid in three animal types. ET accumulates in processed and cooled foods. These thiocarbamates are all complexed with minerals, zinc, manganese, iron, and sodium. We have seen one farmer who worked with maneb who had extremely high levels of manganese and was extremely ill with chemical sensitivity.171
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
A comparison of no restraint, collaring only, or collaring plus wrapping was made on the teratogenicity of dermally applied ethylene thiourea (ETU) or ethylene glycol monoethyl ether (EGEE) in rats.44 When maternal grooming and presumably ingestion were prevented by collaring or collaring and wrapping, no teratogenicity was observed for dermal ETU exposure; in the absence of wrapping and/or collaring, ETU resulted in developmental toxicity including teratogenicity. The implication is that the teratogenicity of ETU applied dermally without occlusion may be due to ingestional exposure and not to true dermal exposure. EGEE resulted in teratogenicity in the presence of collaring and wrapping. This study included a sham control group (collared and wrapped, no material applied) and a vehicle control group (collared and wrapped with the DMSO vehicle applied) but no untreated control group so the effects of the procedures per se could not be evaluated for all parameters. However, the authors did wrap and/or collar dams on gestational day 5 and began application of the test materials on day 6; a slight reduction in body weight was observed in the dams on day 6 which were collared or collared and wrapped relative to their weights on day 5 (which was not observed in the group which received neither collar nor wrapping).
Pre-imaginal exposure to mancozeb induces morphological and behavioral deficits and oxidative damage in Drosophila melanogaster
Published in Drug and Chemical Toxicology, 2023
Cynthia Camila Ziech, Nathane Rosa Rodrigues, Giulianna Echeverria Macedo, Karen Kich Gomes, Illana Kemmerich Martins, Jeferson Luis Franco, Thaís Posser
The toxicological effects of MZ are attributed to the presence of metals manganese and zinc in its formulation, which could lead to metal accumulation in tissues like the brain (Costa-Silva et al. 2018). Together with the presence of metal, the main MZ degradation byproduct ethylene thiourea (ETU), which demonstrated genotoxic potential (Deardfield 1994) has been implied in MZ toxicity. The mechanisms of action underlying MZ toxicity are not entirely known; however, oxidative stress (OS) is recognized as a primary factor in MZ. Oxidative stress (OS) results from an imbalance between the levels of reactive oxygen species (ROS) and antioxidant defense acting in the neutralization of those species (Davies 2000). In addition, a cellular pro-oxidant environment may damage biomolecules like proteins, lipids, and nucleic acids and has been implied in the etiology of pathologies like tumors and neurodegenerative disorders (Valko et al. 2006, Uttara et al. 2009, Phom et al. 2014). In this context, inhibition of mitochondrial complexes, NADPH oxidase, and xanthine oxidase induction and modulation in the activity of the antioxidant enzymes were reported to MZ (Zhang et al. 2003, Hogarth 2012, Todt et al. 2016, Costa-Silva et al. 2018).
An examination of historical control histopathology metadata from 51 Amphibian Metamorphosis Assays
Published in Critical Reviews in Toxicology, 2021
Jeffrey C. Wolf, Adriana C. Bejarano, Douglas J. Fort, James R. Wheeler
Although the OGD considers FC hypertrophy, FC hyperplasia, thyroid hypertrophy, and thyroid atrophy to be the core diagnoses of the AMA, other types of morphologic findings may be the key determinants of endocrine activity in certain studies. For example, Opitz et al. 2006 found differences in follicle size and colloid depletion to be particularly sensitive for detecting the goitrogenic effects of ethylenethiourea (ETU) in X. laevis tadpoles. However, to minimize the potential for creating false-positive or -negative outcomes, and to maintain the integrity of the historical control data, it is recommended that non-core and ad hoc diagnoses be employed sparingly and judiciously. As stated earlier, such diagnoses should be clearly definable, capable of being applied consistently, and plausibly linked to some type of pathological or physiological process.
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
Farmers, especially those who make use of DTCs, are the individuals who are most occupationally exposed to these fungicides, since application is followed by air contamination. Thus, in addition to workers who deal with these substances, other people who live nearby are also exposed to them through inhaled air and skin contact (Sammartano et al. 2020). It is important to note that EBDCs are unstable in the presence of oxygen, moisture and biological systems. For that reason, they undergo rapid decomposition producing the ethylenethiourea (ETU) compound, which is responsible for toxicity, since it is stable (IPCS 1988; Sammartano et al. 2020).