Ethylenebisdithiocarbamates (EBDCs) are a widely applied class of fungicides essential to the protection of high-value crops, including tomatoes, garlic, peppers, and grapes. Examples of these fungicides include maneb, mancozeb, and zineb, which are polymeric complexes of EBDCs and the transition metals manganese or zinc (Cocco, 2022). Annually, over 50 million pounds of EBDCs are used in agricultural practices worldwide, where they provide broad-spectrum fungal control and prevent infections such as downy mildew, blight, and rust (Rubino et al., 2014). The extensive use of these fungicides is due to their ability to inhibit and eliminate fungi and their spores, supporting high crop yields. EBDCs are applied in large quantities in both tropical and temperate agricultural zones such as Southeast Asia, South America, and Europe (Cocco, 2022).

Occupational exposure to EBDCs has raised significant health concerns, as several studies have suggested a link to carcinogenic effects (Cocco, 2022; Dall’Agnol et al., 2021; Bonner et al., 2016; EFSA, 2020). Multiple health studies have also indicated potential toxic effects of exposure to EBDCs on thyroid function and reproductive health (Omidakhsh et al., 2022; Bianchi et al., 2020; Parks et al., 2021; Runkle et al., 2017). Ethylenethiourea (ETU) is the primary metabolite of EBDCs and a biologically active chemical in humans. In 1991, the U.S. Environmental Protection Agency classified ETU as a probable human carcinogen (Group B2) (EPA, 1991). Recently, the National Toxicology Program classified ETU as, “reasonably anticipated to be a human carcinogen,” based on evidence of carcinogenicity in animal studies (NTP, 2021). Furthermore, ETU has been associated with neurological and developmental toxicity, raising additional concerns about its long-term impact on human health (Mora et al., 2018). These findings highlight the potential toxic effects of EBDCs and ETU, which underscore the need for further investigations.

Biomonitoring is a method used to assess chemical exposure by analyzing biological media (e.g. urine, blood) for biomarkers and is considered the gold standard for evaluating chemical exposure for epidemiological investigations. In the assessment of exposure to EBDCs, ETU is a reliable urinary biomarker for exposure assessment. However, there is currently a lack of comprehensive data on the human excretion profile and biological half-life of ETU. Animal studies have determined an ETU excretion half-life of 5.5 h in mice and 9.4 h in rats. (IARC, 2001; Ruddick et al., 1977). According to the findings of Kurttio et al. (1990), the estimated half-life ETU, through the kidney elimination, was close to 100 h in humans. No other human studies exist in the literature to confirm these findings. Thus, additional information concerning human excretion half-life of ETU is important for the establishment of sample collection strategies in biomonitoring and epidemiological studies aiming to investigate the associated health effects of EBDC exposure. Understanding the excretion patterns and half-life of ETU provides appropriate timing for sample collection and ensures accurate exposure estimates.

This study aimed to evaluate the excretion profile and determine the urinary half-life of ETU in farmworkers by analyzing spot urine samples collected over a 24-h period post application. The estimation of the biological half-life could provide critical data leading to better EBDC exposure estimates, improve the interpretation of exposure-effects studies, and aid in the development of physiologically based pharmacokinetic (PBPK) models involving ETU.