Experimental Study On The Acute Toxicity, Subchronic Toxicity By Oral Exposure And Mutagenicity Of Tebuconazole TC

Objective: Acute toxicity test, subchronic toxicity test by oral in SD rats and a set of mutagenicity tests were adopted to ascertain the acute oral LD₅₀, subchronic toxic characteristic and main target organs, and to provide definite toxicological data for comprehensive safety evaluation and the further study on Tebuconazole TC.Method: According to rules from "Toxicological Test Methods of Pesticides for Registration" (GB15670-1995 of PRC), acute oral LD₅₀ of Tebuconazole TC was determined by Horn's methods, the subchronic toxic signs and symptoms, changes of routine detective indicators in hematology, blood biochemistry and pathomorphologic changes in main organs induced by Tebuconazole TC was measured by 90-d subchronic oral (by gavage) toxicity test. Mutagenicity of Tebuconazole TC was detected by Ames assay, mice bone marrow polychromatic erythrocytes micronucleus test and mice testicle cell chromosome aberration test.Results: 1. The acute oral LD50 of Tebuconazole TC to females and males were 1470 mg/kg,2150 mg/kg respectively and then it was classified as low toxicity pesticide. 2. Compare with the negative groups, there were no significant increases (P>0.05) in the bacterial colony counts of reverse mutation in all S. typhimurium test strains in all treated groups (62.5～2500μg/plate with Tebuconazole TC, which indicated Ames test were negative. 3. Micronucleus rate and PCE/NCE ratio that was induced by of Tebuconazole TC at dosage from 14.7 to 294 mg/kg.bw did not show significant difference in comparison with the negative control, which means Tebuconazole TC couldn't induce micronucleus formation and inhibit bone marrow cell-cleavage at certain dosages ranges. 4. At the dosage from 36.8 to 147 mg/kg, types and rates of chromosome aberration in mice testicle cell induced by Tebuconazole had no significant difference comparing with the negative group, which mean Tebuconazole TC did not induce chromosomal aberration of male mice germ cells at certain dosages ranges. 5 Results from subchronic toxicity test showed that male rats treated with high dosage (71.7mg/kg.bw/d) appeared obvious clinical symptoms such as poor spirit, blowzy fur, filth in perineal region and so on which beginning from the seventh weeks until to the exposure end. At the same time the body weight of male rats treated with high and middle dosage also decreased obviously on one occasion at the exposure middle stage and there was a significant difference(p<0.05) compare with the negative group. At termination, it was observed that some hematological changes had been appeared in the male rats treated with the high dosage group, such as increase in platelet count (PLT )and plateletocrit (PCT), decrease in haemoglobin (Hb) and hematocrit (HCT). PLT was also increased in female rats treated with Tebuconazole TC at the high dosage(49.0mg/ kg.bw/d ). Liver coefficient was obvious increased in male rats treated with middle and high dosage. At the same time it was showed that fatty degenerescence and focal or local necrosis can be found in 4 animals (4/20) treated with the high dose by histopathologic examination, while only one animal (1/20) appeared fatty degenerescence in control group. It was not observed any changes of toxicological significance and any relations between dose and effects appeared in blood biochemistry. There were also no any obvious changes in urinalysis parameters.Conclusion: 1. The acute oral LD50 of Tebuconazole TC to females and males SD rats were 1470 mg/kg,2150 mg/kg respectively, then it was classified as low toxicity pesticide and a lesser hazard for inducing acute poisoning by food in general population 2. All results from Ames assay, mice bone marrow polychromatic erythrocytes micronucleus test and mice testicle cell chromosome aberration test were negative, which indicated that Tebuconazole TC does not induce obviously mutagenic effect. 3. Tebuconazole TC may have some cumulative toxicity and could provoke potential chronic toxicity, the main target organs were liver and hematological system. 4. The no-observable-adverse-effect level(NOVEL) of Tebuconazole TC in subchronic toxicity test by oral were 8.0mg/kg/d and 16.3mg/kg/d respectively.