Carcinogenicity of EBDCs.

In 1997 we published an article in EHP on cytogenetic and thyroid hormonal changes in 49 heavily exposed workers applying ethylene bisdithiocarbamate (EBDC) fungicide to tomatoes, based on a collaborative study done by the U.S. National Institute for Occupational Safety and Health and the Institute of Public Health in Mexico (Steenland et al. 1997). EBDCs are a common class of fungicides (e.g., mancozeb, maneb) that are metabolized to ethylene thiourea (ETU) in workers after primarily dermal absorption. In experiments in rats, ETU caused decreased thyroid hormone [thyroxine (T4)], increased thyroid-stimulating hormone (TSH), and thyroid tumors. We sought to determine whether workers exposed to ETU showed thyroid hormone changes compared to a nonexposed comparison group (n = 31). We also looked at sister chromatid exchange (SCE) and chromosomal translocations (balanced chromosomal aberrations that are not cell lethal) in the lymphocytes of exposed workers and nonexposed controls. In this study (Steenland et al. 1997), we found a mean urinary ETU level in the exposed applicators of 58 ppb, although 34% had levels below the limit of detection (most ETU is excreted within 24 hr). All 31 nonexposed controls had levels below the limit of detection. We found a significant increase in TSH (p = 0.05) in applicators versus nonexposed controls, suggesting that increased TSH compensated for a thyroid hormone decrease (altered homeostasis). We also found increased SCEs (p = 0.03) and chromosomal translocations (p = 0.05) in the applicators versus the nonexposed population, suggesting cytogenetic damage due to ETU. Subsequently, in 2001 the International Agency for Research on Cancer (IARC) downgraded ETU from group 2B (possibly carcinogenic to humans) to group 3 (not classifiable as to carcinogenicity in humans) (IARC 2001). Although IARC recognized that ETU was carcinogenic in animals, it judged that the mechanism by which cancer occurred in animals was not relevant to humans. Specifically, IARC (2001) stated that cancer occurred via a