Chemical, pathological and toxicological studies of the effects of RICOM-1013-J of Ricinus communis var minor on women volunteers and rodents

RICOM-1013-J (Ricinus communis var minor) administered orally once to each of 12 women volunteers at a dose of 2.5-2.7 g per 8 months, protected again st pregnancy over a period of 7-8 months of study. A study of the effect of a contraceptive dose (20 mg/kg) on metabolic parameters in rat (food and w ater intake, urine and faecal output and body weight) over a period of 4 mo nths showed a slight decrease in all the parameters in the first 1-8 weeks. This effect was reversible attaining pretreatment levels from week 16. The LD50 in an acute toxicity test in mice was 63.1 +/- 16.0 g/kg s.c. Determination of blood urea, sodium (Na+), potassium (K+), chloride (Cl-) a nd bicarbonate (HCO3-) as a measure of renal function and alkaline phosphat ase (ALP), transaminases (GPT and GOT) and transpeptidases (GGT) as a measu re of liver function showed that liver function profiles in pretreated rats were not significantly different from control (p < 0.05) on day 21 to day 150. However, serum levels of ALP and GGT at day 120 to day 150 were modera tely but significantly elevated (p > 0.05) compared with the control. There were no significant changes in renal function profiles in pretreated rats (p < 0.05) compared with the control. The results of the liver and renal function profiles in women volunteers sh owed that there were no significant (p < 0.05) changes in renal functions o n day 206 following RICOM-1013-J administration. However, serum levels of A LP and GGT showed a slight rise in about 70% of volunteers, whereas bilirub in and transaminases levels were normal. The present results indicate a very high efficacy and margin of safety of R ICOM-1013-J in women volunteers. The increase in ALP and GGT in both animal and women volunteers suggest mild intrahepatic cholestatic changes which m ay be attributed to an oestrogenic effect of RICOM-1013-J. Copyright (C) 20 00 John Wiley & Sons, Ltd.