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Folium Salviae
creased (X 2 , 4.05; p < 0.05). At a concentration of 100 µl/kg the terpenoid
fraction was cytotoxic. Mitomycin C, as a potent mutagen, was
(1)
used for induction of chromosome aberrations. Treatment with terpenoid
fractions (25 µl/kg and 50 µl/kg) significantly decreased the frequency
of aberrations caused by mitomycin C (X 2 , 5.42; p < 0.02: (1) X2 (1) ,
14.93; p < 0.001, respectively). There was a dose–response relationship in
which increasing concentrations of the plant extract caused decreases in
the percentage of aberrations. Nontoxic concentrations of S. officinalis
may be recommended for use as inhibitors of mutagenesis or carcinogenesis
(90).
Toxicology
The neurotoxicity of thujone has been demonstrated in rats (91). The oral
(median lethal dose LD 50
) in the rat has been reported to be 500 mg/kg
body weight (bw) (92). Thujone is much more acutely toxic after parenteral
administration and the intravenous LD 50
in rabbits is stated to be
0.031 mg/kg bw (92). The symptoms associated with acute intoxication
are epileptiform convulsions with general vasodilatation, hypotension,
retardation of the heartbeat and an increase in respiratory amplitude. In
rats, intraperitoneal injections of thujone induced electrocortical seizures
associated with myoclonic activity and the convulsant and lethal effects
occurred at similar doses of 200 mg/kg bw (93). Several studies on the
mechanism of the neurotoxicity of α-thujone indicate that it is a modulator
of the gamma-aminobutyric acid-type A receptor (94). The principal
manifestation of intoxication by thujone is epileptiform convulsions in
animals and humans. The no-observable effects limit (NOEL) for convulsions
in subchronic toxicity studies in female rats was 5 mg/kg bw
administered orally (93). The LD 50
of a methanol extract of the leaves of S.
officinalis was determined to be 4000 mg/kg (83).
The safety and antioxidant potential of an infusion of S. officinalis
leaves was assessed in vivo by measuring plasma transaminase, liver glutathione
reductase and glutathione-S-transferase activities in mice and rats.
Replacing water with the infusion for 14 days did not affect the body
weight or food consumption of the rodents. Liver toxicity was not induced
by the infusion. However, significant increases of liver glutathione-
S-transferase activity were observed in 24% of rats and 10% of mice receiving
the infusion (68).
Clinical pharmacology
The objective of a multicentre, randomized, placebo-controlled, parallel
group study was to assess the efficacy and safety of an S. officinalis ex-
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