己二酸二(2-乙基己基)酯灌胃染毒对大鼠的一般生殖毒性研究

doi:10.3969/j.issn.1004-616x.2020.04.012

癌变·畸变·突变 ›› 2020, Vol. 32 ›› Issue (4): 312-316.doi: 10.3969/j.issn.1004-616x.2020.04.012

己二酸二(2-乙基己基)酯灌胃染毒对大鼠的一般生殖毒性研究

石莹, 王超, 王翀, 顾雯, 张宏伟, 段链

中国疾病预防控制中心环境与健康相关产品安全所, 北京 100021

收稿日期:2019-02-21 修回日期:2019-12-29 出版日期:2020-07-31 发布日期:2020-08-01
通讯作者: 段链,E-mail:duanlian@nieh.chinacdc.cn E-mail:duanlian@nieh.chinacdc.cn
作者简介:石莹,E-mail:shiying@nieh.chinacdc.cn。
基金资助:
国家十二五重大专项课题（2015ZX07402002）

General reproductive toxicity of DEHA on rats

SHI Ying, WANG Chao, WANG Chong, GU Wen, ZHANG Hongwei, DUAN Lian

National Institute of Environmental Health, Chinese Center for Disease Control and Prevention, Beijing 100021, China

Received:2019-02-21 Revised:2019-12-29 Online:2020-07-31 Published:2020-08-01

摘要/Abstract

摘要： 目的： 观察己二酸二（2-乙基己基）酯（DEHA）灌胃染毒对亲代大鼠的一般毒性、交配行为和对胎仔生长发育的影响。方法： 将120只成年SPF级SD大鼠按体质量随机分为4组，分别为对照组（玉米油）和低、中、高剂量[分别为28、170、1 080 mg/（kg·d）]DEHA染毒组，每组30只，雌：雄比例2：1，采用灌胃方式给予受试物，每天灌胃1次，雄鼠染毒10周、雌鼠染毒2周后同组动物合笼。各组雄鼠结束染毒后，雌鼠在交配期、妊娠期持续染毒至实验结束，测定亲代大鼠体质量、相关脏器质量及其脏器系数并进行组织病理检查，测定亲代大鼠血清生化指标。记录交配成功天数、怀孕动物数、每窝胎仔数和胎仔体质量。结果： 与对照组比较，在亲代大鼠中，高剂量DEHA染毒组亲代雄性大鼠终体质量减少（P < 0.01）、睾丸脏器系数增加（P < 0.05），谷草转氨酶（AST）水平、肌酐（CREA）水平均升高（P < 0.05）；与对照组比较，高剂量组亲代雌性大鼠肝脏和肾脏质量及肝、肾脏器系数均增加（P < 0.01或P < 0.05），低剂量组亲代雌性大鼠AST水平降低（P < 0.05）；高剂量组亲代雌性大鼠血清球蛋白（GLO）、总胆固醇（TC）水平均升高（P < 0.05）；高剂量组的胎仔体质量降低（P < 0.01）。组织病理学检查结果未见明显异常。结论： DEHA灌胃染毒可影响亲代大鼠体质量增长，对亲代大鼠肝、肾有毒性作用，引起胎仔生长发育障碍。

关键词: 己二酸二(2-乙基己基)酯, 灌胃染毒, 肝肾毒性, 胎仔发育

Abstract: OBJECTIVE: To observe the toxic effects from gavage of di(2-ethylhexyl) adipate (DEHA) on the general toxicity,mating behavior of parent and the fetal growth in rats. METHODS: 120 adult SPF SD rats were randomly divided into 4 groups according to body weight,namely control group (corn oil) and low,medium and high doses[28,170 and 1 080 mg/(kg·d) respectively]. In the DEHA group,30 animals in each group, with a female to male ratio of 2:1. The test substance was given by intragastric administration once a day. Male rats were exposed to the DEHA for 10 weeks and female rats were exposed to the DEHA for 2 weeks. Cages were closed. After the exposure,the body weight,related organ mass and organ coefficients of the parent rats were measured and pathological examinations were conducted to determine the blood biochemical indexes of the parent rats. The number of successful mating days,the number of pregnant animals,the number of litters per litter and the weight of litters were recorded. RESULTS: Among the parent rats,the final body mass of the male rats in the high-dose group decreased compared with the control group (P < 0.01),and the testicular organ coefficient increased compared with the control group (P < 0.05). The weight and liver and kidney organ coefficients increased compared with the control group (P < 0.01),and the kidney weight increased compared with the control group (P < 0.05). The levels of aspartate aminotransferase (AST) and creatinine (creatinine, CREA) in the high-dose group were higher than those in the control group (P < 0.05);the AST levels in the low-dose group were compared with the control decreased (P < 0.05); parental female rat globulin (GLO) and total cholesterol (TC) levels in the high-dose group were increased compared with the control group (P < 0.05). The weight of fetal body in the high-dose group was reduced (P < 0.01). Microscopic analyses showed no obvious pathological abnormalities. CONCLUSION: DEHA caused limited body weight gain and had toxicity in the liver and kidneys in parental rats,and might affect growth and development failure of fetuses.

Key words: di(2-ethylhexyl)adipate, oral exposure, liver and kidney toxicity, fetal development

中图分类号:

R994.6

石莹, 王超, 王翀, 顾雯, 张宏伟, 段链. 己二酸二(2-乙基己基)酯灌胃染毒对大鼠的一般生殖毒性研究[J]. 癌变·畸变·突变, 2020, 32(4): 312-316.

SHI Ying, WANG Chao, WANG Chong, GU Wen, ZHANG Hongwei, DUAN Lian. General reproductive toxicity of DEHA on rats[J]. Carcinogenesis, Teratogenesis & Mutagenesis, 2020, 32(4): 312-316.

参考文献

[1] CHARLES A S, PETERSON D R, PARKERTON T F, et al. The environmental fate of phthalate esters:a literature review[J]. Chemosphere, 1997, 35(4):667-749.
[2] 龚丽雯, 王成云, 李京会, 等. PVC包装膜中己二酸酯类增塑剂在水中的迁移行为研究[J]. 聚氯乙烯, 2006, 9(1):31-35.
[3] 单晓梅, 黄发源, 张兵, 等. 合肥市水源水与出厂水中增塑剂污染特征及其水环境健康风险评估[J]. 环境与职业医学, 2013, 30(10):741-747.
[4] 陈丽, 周颖, 吴毅凌, 等. 以黄浦江为水源的管网末梢水中微量有机物污染现状[J]. 卫生研究, 2008, 37(2):137-143.
[5] OECD. OECD Guideline for Testing of Chemicals No 415:One-generation reproduction toxicity study[S/OL].[2019-02-20]. https://www.oecdilibrary.org/docserver/9789264070844-en.pdf?expires=1591261892&id=id&accname=guest&checksum=7176C7EA22A16B9DF5146D1E87C2D865
[6] US EPA. Final drinking water criteria document for di(2-ethylhexyl)adipate[R]. Washington, DC:Health and Ecological Crteria Division Office of Science and Technology Office Water, 1992.
[7] WATO E, ASAHIYAMA M, SUZUKI A, et al. Effects of 2-or 4-week repeated dose studies and fertility study of di(2-ethylhexyl) adipate (DEHA) in female rats[J].J Toxicol Sci, 2009, 34(Sup 1):101-109.
[8] ARRINGTON L R, KLING J M. Introductory laboratory animal science[M]. Interstate Printers and Publishers, Inc., 1978:9-11.
[9] SMYTH H F, CARPENTER C P, WEIL C S. Range-finding toxicity data, list IV[J]. AMA Arch Ind Hyg, 1957, 4:119.
[10] LAKE B G, PRICE R J, CUNNINGHAME M E, et al. Comparison of the effects of di-(2-ethylhexyl) adipate on hepatic peroxisome proliferation and cell replication in the rat and mouse[J]. Toxicology, 1997, 123(3):217-226.
[11] DALGAARD M, HASS U, VINGGAARD A M, et al. Di(2-ethylhexyl) adipate (DEHA) induced developmental toxicity but not antiandrogenic effects in pre-and postnatally exposed Wistar rats[J]. Reprod Toxicol, 2003, 17(2):163-170.

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己二酸二(2-乙基己基)酯灌胃染毒对大鼠的一般生殖毒性研究

General reproductive toxicity of DEHA on rats

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