Tolylfluanid, a phenylsulfamide fungicide, is one of the many pesticides that are frequently detected in crops. Therefore, its health risk is a concern. Micromolar concentrations of
tolylfluanid induce
chromosomal aberrations and micronuclei in mammalian lymphocytes. The findings prompted us to study the cellular actions of
tolylfluanid and another frequently detected
pesticide,
dichlofluanid, at submicromolar and micromolar concentrations. Of the cellular actions of chemicals, the action on cellular Ca(2+) homeostasis is important since Ca(2+) is involved in cell signaling and death. Consequently, in this study, the effects of phenylsulfamide fungicides were examined on rat thymocytes by using
fluorescent probes in order to further characterize the cellular actions of phenylsulfamide fungicides. Both phenylsulfamide fungicides exhibited biphasic, early and late, increase in intracellular Ca(2+) levels. The early phase was dependent on intracellular Ca(2+) release and increased membrane Ca(2+) permeability. The late phase was owing to Ca(2+) influx via activation of store-operated Ca(2+) channels and the further increase of membrane ionic permeability. Voltage-dependent Ca(2+) channels were not involved. The increases in intracellular Ca(2+) levels by phenylsulfamide fungicides were observed at
drug concentrations of 0.1 μM or more (up to 10 μM). Thus, it is plausible that micromolar concentrations of phenylsulfamide fungicides deregulate intracellular Ca(2+) homeostasis in rat thymocytes. Both phenylsulfamide fungicides
at 10 μM promoted the transition from intact living cells to living cells with
phosphatidylserine-exposed membranes. This was not the case for phenylsulfamide fungicides at 3 μM. The potency of
tolylfluanid was similar to that of
dichlofluanid. Although the information on residual concentrations of
tolylfluanid and
dichlofluanid is very limited, their residual concentrations do not reach micromolar levels. It is unlikely that humans will develop adverse effects on exposure to phenylsulfamide fungicides under present environmental conditions.