On the basis of in vivo toxicological long-term tests performed on rodents, the
herbicide Linuron [3-(3,4-dichlorophenyl)-1-methoxy-1-
methylurea] has been classified by the U.S. Environmental Protection Agency (EPA) (1988) as a class C
carcinogen (possibly carcinogenic to humans). However, when
Linuron was analyzed for genotoxicity, negative results were obtained. An epigenetic,
tumor-promoting potential was hence suspected to be responsible for the oncogenic activity of the molecule. In the absence of in vivo data concerning the
tumor-promoting activity of the
herbicide and being well established that
tumor promoters interfere with the cell growth rate and gap-junctional permeability, the effects of technical grade
Linuron and of its trade formulation (
Linuron 50) on these parameters were investigated. This is especially important in the case of the formulated preparation for a correct estimate of the health hazard to humans. Cytotoxicity and gap-junctional intercellular communication (GJIC) assays were performed on the endothelial cell line F-BAE GM 7373, an in vitro cell system known to be responsive to the
biological effects of
tumor promoters. A time- and dose-related cytotoxic effect was found for both
Linuron and
Linuron 50, the latter being the far more cytotoxic of the two. However, when tested at noncytotoxic concentrations over a period of 48 h, neither
Linuron nor
Linuron 50 altered the capacity of F-BAE GM 7373 cells to intercommunicate. On the basis of the results obtained, the possibility that
Linuron and
Linuron 50 are endowed with
tumor-promoting activity is discussed. In vivo studies on
tumor-promoting and genotoxic activity are in progress to
complement the information available on the toxicological properties of
Linuron and its trade preparation.