摘要
目的探讨邻苯二甲酸二丁酯(di-n-butyl phthalate,DBP)对青春期雄性大鼠的系统毒性。方法用DBP灌胃染毒雄性Wistar大鼠8周,剂量分别为250、5001、000 mg/(kg.d)。观察临床症状,动物体重增长,血常规,血清生化,血Zn,解剖及组织病理学等指标。通过剂量-效应关系的分析,求出基准反应(benchmark response,BMR)为10%的基准剂量(benchmark dose,BMD)及95%可信限的下限值(benchmark dose lower bound,BMDL)。结果研究发现具有剂量相关的效应终点有体重、血清尿素氮含量,血清Zn含量,睾丸系数,肾脏系数和肝脏系数,其BMDL分别为408.2,57.7,99.0,263.3,103.1,24.3 mg/(kg.d)。结论DBP对雄性青春期大鼠具有一般毒性。DBP对雄性青春期大鼠一般毒性的最低可观察毒性作用剂量水平(lowest observed adverse effect level,LOAEL)为250 mg/(kg.d),BMD和BMDL分别为42.4和24.3 mg/(kg.d)(根据肝脏系数),同时肝脏系数为最敏感效应指标。研究结果显示,BMDL评价方法较LOAEL方法更为敏感。
Objective To evaluate the effects of general toxicity of di-n-butyl phthalate (DBP) in puberty male rats. Methods Male Wistar rats(at age of 4 wks after birth)were administrated with DBP (250, 500, or 1 000 mg/(kg·d)), and with corn oil (as control), respectively, for 8 wks. The clinical symptoms, body weight, hematological, clinical chemical, serum zinc levels, morphology, and histomorphology examinations were taken. Evaluation consisted of dose-response analysis with calculation of a benchmark dose (BMD), and benchmark dose at the lower 95% one-sided confidence bound (BMDL) at predefined critical effect sizes (CESs) of 10% .Results It was found in this study that the dosage related endpoints were body weights, serum urea nitrogen, serum zinc, and parameters of testis, kidney and liver with the BMDLs of 408.2,57.7,99.0,263.3,103.1,24.3 mg/(kg·d), respectively. Conclusion The DBP has obvious general toxicities to puberty male rats. The lowest observed adverse effect level (LOAEL) of DBP is 250 mg/(kg·d). Theresponses of BMD and BMDL was 42.4 and 24.3 mg/(kg·d), respectively, based on liver parameter, which was the most sensitive parameter in the sequence of events. This result suggested that BMDL be more sensitive than LOAEL analysis.
出处
《毒理学杂志》
CAS
CSCD
北大核心
2007年第3期194-197,共4页
Journal of Toxicology
基金
国家自然科学基金资助项目(30150003)
科技部社会公益研究项目(2001DIB0059)
教育部留学回国人员科研启动基金(2001年)
关键词
邻苯二甲酸二丁酯
系统毒性
基准剂量法
Di-n-butyl phthalate
general toxicity
Benchmark dose analysis