Citral, 3,7-dimethyl-2,6-octadien-1-al, found in the essential oils of
a large variety of useful plants, is used as a scenting agent in hous
ehold products, as a fragrance in cosmetics, and as a food flavouring
additive. This study was undertaken to investigate the embryofeto-toxi
c potential of citral in the rat. Citral (60; 125; 250; 500 and 1000 m
g/kg) in corn oil was given orally to Wistar rats from day 6 to 15 of
pregnancy. Caesarean sections were carried out on day 21 of pregnancy,
and the number of resorptions and implantation sites were recorded. F
etuses were weighed, examined for external malformations, and fixed fo
r visceral examination, or cleared and stained with Alizarin Red S for
skeleton evaluation. A transient decrease in weight gain from days 6
to 11 of gestation at the lowest doses, and a reduction in body weight
minus uterine weight at term at the highest doses, indicated that cit
ral was maternally toxic over the dose range tested. A slight but stat
istically significant increase in the ratio of resorptions per implant
ations was observed with 60 and 125 mg/kg body weight. Doses higher th
an 125 mg/kg reduced dose-dependently the ratio of pregnant per mated
female. Signs of fetal growth retardation and a higher incidence of mi
nor skeletal abnormalities were found in doses higher than 60 mg/kg. N
o increase in the frequency of visceral anomalies was found at any dos
e level, but an increase in fetal spleen weight was observed in doses
higher than 125 mg/kg. Therefore, data presented in this paper indicat
e that the no-observed adverse effect level for embryofeto-toxicity is
lower than 60 mg citral/kg body weight p.o.