Systematic review of evidence regarding potential carcinogenic mechanisms of mancozeb and ethylene thiourea (ETU)

To evaluate the carcinogenic potential of the fungicide mancozeb, we used a comprehensive and structured framework to conduct a systematic review of mechanistic data relevant to the 10 key characteristics of carcinogens (KCCs) for mancozeb and its primary metabolite, ethylene thiourea (ETU). We critically and systematically assessed the reliability, strengths, limitations, and findings of individual endpoints relevant to each KCC and integrated the mechanistic findings with the evidence for carcinogenicity from experimental animal and epidemiology evidence streams. This evaluation found that both chemicals had no more than weak overall activity for any KCC, with the exception of moderate activity for KCC5 (oxidative stress) for mancozeb. It is not likely that the moderate activity observed for KCC5 is associated with potential carcinogenicity given the lack of activity for all other KCCs, particularly those that are commonly linked to oxidative stress, and the fact that many non-carcinogenic substances can cause oxidative stress. The overall lack of support for KCCs is consistent with the general lack of carcinogenic findings in experimental animal studies of mancozeb and ETU and epidemiology studies of mancozeb, indicating that the totality of the evidence does not support mancozeb and ETU as human carcinogens.