Studies On Acute Toxicity,Chronic Toxicity,F₁ Reproductive And Developmental Toxicity Of Aspirin Eugenol Ester In Rats

Aspirin eugenol ester?AEE?,a novel colorless transparent crystal compounds,was independently produced by the condensation between free carboxyl of aspirin and free hydroxyl of eugenol under at Lanzhou Institute of Husbandry and Pharmaceutical Sciences of Chinese Academy of Agricultural Sciences?CAAS?.This study was mainly to explore the acute toxicity,150-day toxicity and reproductive and developmental toxicity of AEE and provide the references for safety evaluation of AEE on the basis of previous studies.1.Acute toxicity of aspirin eugenol ester in Sprague-Dawley ratsThe acute toxicity study was carried out to evaluate the toxic characteristics and target organs of aspirin eugenol ester.The experiment was designed in accordance with the method provided by the K?rber arithmetic method.According to the pre-test results to calculate LD₁₀₀ and LD₀,7 groups of different doses of AEE and control group of CMC-Na were,male and female half,divided into 8 groups.After treatment 14 days,death time and rate of rats were counted at the end of the experiment.The microscopic pathology of mild damages on organs was conducted.The results showed that the LD50 of AEE in rats was 5.95 g/kg upon oral administration and its 95%confidence interval calculation was5.30g/kg⁶.68 g/kg.The death time of rats were centralized at 48⁹6 h after exposing to AEE more than 4.03 g/mg by the analysis of the cumulative mortality–time of AEE in each group.Significant decreases in body weights were noted after treatment of AEE 3 days,after that body weights gradually grow and recover at the 5 day.Remarkable damages on livers and gastrointestinal tract were found at AEE dosage of more than 5.00 g/kg.The results indicated that AEE was classified as practically non-toxic compound according to WHO.The target organs of AEE were liver,kidney and gastrointestinal tract.2.A 150-day oral dose toxicity study of aspirin eugenol ester in Wistar ratsThis study was to validate adverse effect level and target organs of AEE on rats.This can provide guidelines for reproductive and developmental test.240 rats aged 5 weeks,female and male half,were randomly divided into 6 groups.The chronic toxicity of AEE was evaluated in rats with three different doses?4.5 mg/kg/d,18.0 mg/kg/d,683 mg/kg/d respectively?.Three additional groups of rats were orally administrated with aspirin?10 mg/kg/d?,eugenol?9 mg/kg/d?and carboxyl methyl cellulose sodium as the control treatments,respectively.The results showed that the rats of AEE high dose group have significant differences in body weight,blood index and organ coefficient.There were some significant differences in the AEE middle dose group,the aspirin group and the eugenol group.There was no significant difference in low AEE group.The results indicated that the toxic target organs of AEE might be liver and kidney.AEE was safe at 18 mg/kg/day for chronic repeating.Moreover,aspirin and eugenol had stronger toxicity than AEE on blood at equal mole3.One-Generation Reproductive and Developmental Toxicity of Orally Administrated Aspirin Eugenol Ester.This study was to investigate whether AEE could influence on reproduction and development of rats.360 rats aged 6 weeks,female and male half,were randomly divided into 6 groups.The dosages of AEE?498.0 mg/kg/d,124.5 mg/kg/d,31.1 mg/kg/d,respectively?were administrated.Three additional groups of rats were orally administrated with eugenol?246.0 mg/kg/d?,aspirin?68.4 mg/kg/d?and blank control group.After the administration,rats administrated HAEE and aspirin were significant differences in reproductive and developmental defferences compared to blank group.Testis and epididymis indexes of rats in high dose AEE group were significant differences.Testis and epididymis indexes of rats in aspirin and eugenol groups were significant differences.Under the experimental condition,no observed adverse effect level?NOAEL?of AEE was 31.1 mg/kg/d.Low observed adverse effect level?LOAEL?was 124.5 mg/kg/d.To sum up,the toxicity of AEE is low.However,AEE can damage the liver,kidney and gastrointestinal tracts,moreover,have bad influence on rats about reproductive and developmental aspect along the long-term exposure to high dose.