In this study, several short-term microbial and mammalian in vitro assays w
ere used to evaluate cytotoxicity and genotoxicity of four plant volatiles
showing antifungal activity: cinnamaldehyde, carvacrol, thymol and S(+)-car
vone. All inhibited viability and proliferation of Hep-2 cells in a dose-de
pendent manner. IC50 ranged from 0.3 mM (cinnamaldehyde) to 0.7 mM (thymol)
in viability tests and from 0.2 mM (carvacrol) to 0.9 mM (carvone) in the
proliferation test. The morphological analysis suggested an involvement of
apoptosis in the cases of carvone, carvacrol and cinnamaldehyde. At nontoxi
c doses, carvacrol and thymol increased the number of revertants in the Ame
s test by 1.5-1.7 times, regardless of metabolic activation. In the SOS-chr
omotest, none of the four plant volatiles caused DNA damage at non-toxic do
ses. In the DNA repair test, a marked dose-dependent differential toxicity
was observed with carvone and, to a lesser extent, with cinnamaldehyde, whi
le with thymol and carvacrol, this effect was less pronounced. In conclusio
n, the considered in vitro cytotoxicity assays have shown to be sensitive e
nough to highlight a variety of toxic effects at the cellular level, which
can be rather different between chemically closely related compounds, such
as isomers. (C) 1999 Elsevier Science Ltd. All rights reserved.