Study on the embryofeto-toxicity of citral in the rat

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 household products, as a fragrance in cosmetics, and as a food flavouring additive. This study was undertaken to investigate the embryofeto-toxic potential of citral in the rat. Citral (60; 125; 250; 500 and 1000 mg/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. Fetuses were weighed, examined for external malformations, and fixed for 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 citral was maternally toxic over the dose range tested. A slight but statistically significant increase in the ratio of resorptions per implantations was observed with 60 and 125 mg/kg body weight. Doses higher than 125 mg/kg reduced dose-dependently the ratio of pregnant per mated female. Signs of fetal growth retardation and a higher incidence of minor skeletal abnormalities were found in doses higher than 60 mg/kg. No increase in the frequency of visceral anomalies was found at any dose level, but an increase in fetal spleen weight was observed in doses higher than 125 mg/kg. Therefore, data presented in this paper indicate that the no-observed adverse effect level for embryofeto-toxicity is lower than 60 mg citral/kg body weight p.o.