Time for Re-Evaluating the Human Carcinogenicity of Ethylenedithiocarbamate Fungicides? A Systematic Review

Abstract

Background. In January 2021, the European Union ended the license of Mancozeb, the bestselling ethylenedithiocarbamate (EBDC) fungicide, because of some properties typical of human carcinogens. This decision contrasts the IARC classification of EBDC fungicides (Group 3, not classifiable as to human carcinogenicity). A systematic review of the scientific literature was conducted to explore the current evidence. Methods. Human and experimental studies of cancer and exposure to EBDC fungicides (Mancozeb, Maneb, Zineb, and others) and ethylene thiourea (ETU), their major metabolite, published in English as of December 2021, were retrieved using PubMed, the list of references of the relevant reports, and grey literature. Results. The epidemiological evidence of EBDC carcinogenicity is inadequate, with two studies each suggesting an association with melanoma and brain cancer and inconsistent findings for thyroid cancer. Experimental animal studies point at thyroid cancer in rats and liver cancer in mice, while multiple organs were affected following the long-term oral administration of Mancozeb. The mechanism of thyroid carcinogenesis in rats has also been shown to occur in humans. Genotoxic effects have been reported. Conclusions. The results of this systematic review suggest inadequate evidence for the carcinogenicity of EBDC fungicides from human studies and sufficient evidence from animal studies, with positive results on three out of ten key characteristics of carcinogens applying to humans as well. An IARC re-evaluation of the human carcinogenicity of EBDC fungicides is warranted.

Comparative omics analysis for novel target discovery in plant pathogens: A case study for Magnaporthe oryzae

“…Among the 13 pathways that remained, 10 exhibited resemblances to those of rice. These overlapping pathways may shed light on the concerns surrounding multisite fungicides such as mancozeb (Gullino et al., 2010), whose widespread use has been met with reported adverse effects on both human health (Cocco, 2022) and plants (Fatma et al., 2018). These revelations prompt a deeper scrutiny of other members within the realm of multisite fungicides, especially those without clearly defined targets yet endorsed by the Fungicide Resistance Action Committee (FRAC) for combating fungal plant pathogens (Corkley et al., 2022).…”

“…This quantity could otherwise sustain 60 million people (Nalley et al., 2016). In 2021, the European Union banned mancozeb (Cocco, 2022), a compound once deemed safe for human use over several decades (Gullino et al., 2010). This underscores the importance of evaluating future safety beyond a purely chemical perspective.…”

Assessment of Mancozeb Exposure, Absorbed Dose, and Oxidative Damage in Greenhouse Farmers

“…The general population is passively exposed to fungicides through the environment, soil, water, consumption of contaminated wine and food (particularly tomatoes, citrus fruits, and potatoes), as well as cigarette smoking (because MNZ is largely used in tobacco cultivation) [ 7 , 8 ]. The professional exposure to MNZ especially occurs in the agriculture and farming industries, key sectors of MNZ production and application, either through the inhalation route or direct skin contact, although the dermal route represents the main route of exposure [ 9 , 10 ]. For such reasons, agricultural workers represent a subpopulation at higher risk of exposure to pesticides, including DTCs [ 11 ].…”

“…Nonetheless, the International Agency for Research on Cancer (IARC) classified MNZ as a Class 3 carcinogen given the limited evidence in humans, although teratogenic and carcinogenic effects have been observed in animal studies [ 5 , 21 ]. Additionally, DTC and/or ETU exposure has been associated with neurodevelopmental damage due to the well-known crucial role of thyroid function in brain development [ 9 , 22 ]. Recent studies suggest possible disrupted neurobehavioral outcomes and neurotoxicity with Parkinson-like neuronal damage upon MNZ exposure [ 23 , 24 ].…”

Efecto inhibitorio in vitro de extractos de hojas de ricino (Ricinus communis) sobre el crecimiento de Alternaria tenuissima

“…En esta línea, algunos de los fungicidas recomendados para combatir alternariosis, como el mancozeb (ditiocarbamato) y el iprodione (dicarboximida), están siendo objeto de reevaluaciones de toxicidad debido a la creciente evidencia de su potencial como cancerígenos para los seres humanos. De hecho, recientemente la Unión Europea ha suspendido el uso del mancozeb y ha disminuido el límite máximo de residuos de iprodione permitido en los alimentos (EFSA, 2016;Cocco, 2022). Adicionalmente, el uso recurrente de estos compuestos ha derivado en el origen de cepas fitopatógenas resistentes (Tripathi & Dubey, 2004).…”