Results of Long‐Term Experimental Studies on the Carcinogenicity of Ethylene‐bis‐Dithiocarbamate (Mancozeb) in Rats

Abstract

Mancozeb, an ethylene-bis-dithiocarbamate (EBDC), has been one of the most commonly used fungicides in commercial use for several decades. Nevertheless, up to now, no adequate published experimental studies on the carcinogenicity of Mancozeb have been published. Because of the importance of the compound and of the number of people potentially exposed (workers engaged in the production and use of the fungicide, people living in agricultural areas where the compound is sprayed, and people consuming polluted products), a long-term experimental study of Mancozeb was begun at the Cancer Research Center of the Ramazzini Foundation. Groups of 150 male and female Sprague-Dawley rats, 8 weeks old at the start of the treatment, were administered Mancozeb at the concentration of 1000, 500, 100, 10, and 0 ppm in feed supplied ad libitum for 104 weeks. At the end of the treatment, animals were kept under controlled conditions until spontaneous death. Mancozeb caused an increase in (1) total malignant tumors, (2) malignant mammary tumors, (3) Zymbal gland and ear duct carcinomas, (4) hepatocarcinomas, (5) malignant tumors of the pancreas, (6) malignant tumors of the thyroid gland, (7) osteosarcomas of the bones of the head, and (8) hemolymphoreticular neoplasias. On the basis of these data, Mancozeb must be considered a multipotent carcinogenic agent.

Phytotoxicity: An Overview of the Physiological Responses of Plants Exposed to Fungicides

“…These multisite inhibitors have several kinds of toxic action in fungal cells such as metal chelation, mixed disulfide formation, and transport of heavy metals across membranes. Dialkyldithiocarbamates inhibit a wide range of fungal enzymes, but the pyruvic dehydrogenase system is particularly sensitive to these fungicides [4]. Another group of organic contact fungicide widely used is the ethylenebisdithiocarbamates, which include zineb, maneb, metiram, and mancozeb.…”

“…Within the organic contact fungicides, for example, dialkyldithiocarbamates, which include the fungicides thiram, ferbam, and ziram, are a group of fungicides with a high role in the worldwide control of plant diseases since they are generally more effective and less toxic than the inorganic compounds (e.g., sulfur and copper fungicides) [4,17]. These multisite inhibitors have several kinds of toxic action in fungal cells such as metal chelation, mixed disulfide formation, and transport of heavy metals across membranes.…”

“…Fungicide toxicity is not always restricted to the target pest organism, having also been demonstrated in mammals [4] including humans [5]. The extensive use of fungicides in plant protection against fungal disease generates longterm residues in food and in the environment [6,7].…”

Biomonitoring of Contemporary Pesticides: Ethylenethiourea in Occupational Settings

“…Besides the thyroid gland, the major site of ETU-induced carcinogenicity, the liver is also a target. Chronic ETU admistration produces hepatocellular carcinoma in mouse and rats (Innes et al, 1969;Belpoggi et al, 2002). However, ETU had mostly negative mutagenic effects in mammalian test systems Teramoto et al, 1977) and did not induce DNA damage in cultured rat liver cells (Althaus et al, 1982).…”

Dissipation Behavior of a Mancozeb Residue (Dithiocarbamate Fungicide) in Tomato Under South Moroccan Climatic Condition

“…In addition, Fungicides of the dithiocarbamate group are much better at controlling fungal pathogens of Solanaceous crops and vegetables [8]. To sustain the quality and productivity of the crops mancozeb, the ethylene-bis-dithiocarbamate (EBDC), is recommended but it was considered to be a multipotent carcinogenic agent in a long-term rat study [9].…”