The following study was conducted by the Beijing Guoyi Biomedicine Application Technology Research Institute in October, 1997.
Long-Term Oral Toxicity Study
The study took 60 healthy Wistar white mice (30 male and 30 female) with weights between 60-95 grams. They were divided into 3 groups (20 in each group). The test substance (Liver No. 1™) was given orally once a day with a dosages of 3g/kg (equivalent to 40 times of the maximum recommended daily dosage of adults) to testing group I, and 6g/kg (equivalent to 80 times of the maximum recommended daily dosage of adults) to testing group II. The comparison group was fed with sugar dissolution of the same amount daily. The experiment lasted 12 weeks. All groups were observed for their conditions daily, and their weights, amount of food and water intake were measured during the experiment period.
Various indexes of hematology and hemabiochemistry were measured through tail-vein sampling for each mouse before the intake of the test substance. Half of randomly selected mice from each group were measured with the same above indexes at 24 hours after the last intake of the test substance and 2 weeks after stopping taking-in the test article. The results were summarized as follows:
• Effects upon general appearance and weight:
During the course of the experiment which referred to as before, during, and after taking-in the test articles, there were no differences in outward appearances and behaviors, food-taking and water-drinking among various groups. Weight increasing rates of various groups were quite similar and there were no statistically significant differences.• Effects upon indexes of hematology:
Results indicated that there were no statistically significant differences among the classifications of red blood cells, white blood cells, hemoglobin, and platelets in the comparison made among large dosage group, small dosage group and comparison group, also in comparisons of the same group in their different stages. Fluctuations were within normal ranges.• Effects upon indexes of hematological biochemistry:
The results showed that the contents of AST, ALP, CHO, TP, AIB, T.B:1 and BUN were in the normal range for both the mice in large dosage group and small dosage group, before intake of the test article, during the 12 weeks while taking in the test article, and after quitting the test article. There were no significant differences among the comparison groups. Also, there were no remarkable differences among various groups before and after taking-in test article.• Effects upon internal organs histology:
Half of the mice of various groups were tested for their hearts, livers, lungs, spleens and suprarenal glands, and weighed them to calculate their weight per 100g when they have taken in test article for 12 weeks, and later after quitting for 2 weeks. The results showed that there was no significant difference among each group while taking-in test article and after quitting test article.
They were observed with naked eyes and conducted histopathology examinations to the hearts, livers, kidneys, spermaries, ovaries, brains and large intestines. The results proved that no pathological changes concerning toxicity happened. Hepatic cells hepatin appeared in 2-4 cases each group. It might be concerned with nourishment and was normal.
Therefore, the period of long-term toxicity experiment was 12 weeks. Test articles were taken in at dosages of 3g/kg and 6g/kg once a day. No testing animals died of medical toxicity. No abnormal phenomena occurred in blood pictures, various indexes of hematological biochemistry and histopathological examination. Thus it concluded that Liver No. 1™ is safe to take in.
