Ethylenebisdithiocarbamic acid, salts and esters (EBDCs)

Ethylenebisdithiocarbamate (EBDC) fungicides were developed in the 1940s by Rohm and Haas and DuPont as a new class of protective fungicides. [1] The major EBDCs — maneb (manganese ethylenebisdithiocarbamate), zineb (zinc EBDC), mancozeb (manganese/zinc EBDC mixture), and metiram — work by disrupting multiple enzyme systems in fungal cells (the multi-site mechanism that prevents resistance development). They became the dominant protective fungicides in world agriculture, applied to potatoes for late blight control (the same disease that triggered the Irish famine of the 1840s), grapes for downy mildew, tomatoes for early and late blight, and dozens of other crops. [2] Annual global use of mancozeb alone exceeds 50,000 tons. The regulatory concern that emerged in the 1970s is not with the EBDCs themselves but with their principal metabolite, ethylenethiourea (ETU, CAS 96-45-7). ETU is formed when EBDCs degrade in the environment (in treated crops, in processed food from treated crops, and in the human body after consumption). ETU is a potent thyroid toxicant — it inhibits thyroid peroxidase, suppressing thyroid hormone synthesis and causing compensatory thyroid enlargement (goiter) and thyroid tumors in animals at doses achievable through dietary exposure from treated food. [3] The EPA classified ETU and EBDCs as probable human carcinogens. The EU has restricted or banned several EBDCs on the basis of ETU concerns. Mancozeb's EU approval expired in 2020 without renewal due to concerns about ETU residues in food and environmental persistence.

Agricultural workers applying EBDC fungicides face inhalation of spray and dust and dermal exposure. The general public is exposed primarily through dietary residues of EBDCs and ETU in food — particularly potatoes, wine grapes, tomatoes, and processed tomato products. ETU survives cooking and food processing better than the parent EBDCs. Washing produce reduces EBDC surface residues but has limited effect on ETU within the food.

ETU's mechanism of thyroid disruption is well-established: it inhibits thyroid peroxidase, the enzyme that incorporates iodine into thyroid hormones, causing hypothyroidism and compensatory TSH elevation, which drives thyroid cell proliferation and ultimately thyroid adenomas and carcinomas in rodents. [3] Developing fetuses and infants are particularly sensitive because thyroid hormones are critical for brain development — ETU exposure during pregnancy raises concerns about neurodevelopmental effects. The EPA classified both EBDCs and ETU as Group B2 probable human carcinogens, with ETU designated as a developmental/reproductive toxicant.

Agricultural workers applying EBDC fungicides are most occupationally exposed. The general population is exposed through diet; pregnant women and infants are the most sensitive subpopulations because of thyroid hormone-dependent fetal and neonatal brain development. People with borderline hypothyroidism may be more susceptible to ETU's thyroid effects.

1. Wash all produce thoroughly before eating — EBDCs are primarily surface residues and washing significantly reduces dietary exposure. 2. Peeling potatoes and vegetables removes surface EBDC deposits. 3. Choose organically grown potatoes, tomatoes, and grapes where EBDC use is prohibited. 4. Agricultural applicators must wear chemical-resistant gloves, respiratory protection, and protective clothing during mixing and application. 5. Pregnant women should be especially attentive to choosing low-EBDC-residue foods given the thyroid disruption and potential fetal neurodevelopmental concerns.