摘要
目的研究溴氯海因泡腾片通过皮肤途径的急性和亚急性毒性,了解其实际应用的安全性。方法采用动物试验和生化检验方法对急性和亚急性毒性进行评价。结果在本实验室条件下,溴氯海因泡腾片对二种性别的SD大鼠急性经皮LD50均大于2 000 mg·kg~(-1);在亚急性经皮毒性试验期间,各试验组动物无死亡。试验末,动物体质量及其增长值、血清生化检测项目均在本检测单位正常值范围内,与对照组比较差异无统计学意义(P>0.05)。血常规检测发现,高剂量组雄鼠白细胞总数显著升高,雌鼠白细胞中淋巴细胞占比均显著增加,与对照组比较差异有统计学意义(P<0.05)。此外,高剂量组雄鼠的肝体比值显著升高,同时组织病理学观察发现高剂量组有部分动物肝细胞出现病变。附加组动物停止染毒观察2周后,各项指标未见明显异常。结论溴氯海因泡腾片急性经皮毒性属低毒,其对雌、雄SD大鼠的亚急性(21 d)经皮无可见有害作用水平(NOAEL)为500 mg·kg~(-1)。
Objective To study acute and subacute dermal toxicity of a disinfectant for hospital sewage which contained 1-bromo-3-chloro-5,5-dimethylhydantoin(BCDMH) in order to know about its application safety.Methods Animal test and biochemical examination methods were adopted to evaluate its acute and subacute toxicities.Results In our lab,the acute dermal LD50 values were more than 2 000 mg·kg~(-1) for both male and female SD rats.During the subacute toxicity test,none of the rats died.At the end of the experiment,animals' bodymass and weight gain,serum biochemical examinations were in the normal ranges,there were no difference compared with the control(P > 0.05).On the other side,the proportion of lymphocytes in female as well as WBC in male SD rats of the high dose group were increased obviously which compared with the control(P < 0.05).Besides,the value of liver/weight in male SD rats of the high dose group was increased obviously,and some pathological changes of liver cells were found during the pathological examination.There were no obvious abnormalities in the additional group during 2 weeks of the termination.Conclusion The BCDMH effervescent tablet is classified as low toxicity.And its no-observed-adverse-effect-level(NOAEL) of subacute dermal toxicity(21 d) is 500 mg·kg~(-1) for both male and female SD rats.
引文
[1]马云,高艳玲,陈丽春,等.中国医院污水处理现状及前景分析[J].环境科学与管理,2007,32(3):128-130,164.
[2]蔡荣华,张家凯,高春娟.溴氯海因杀生剂的合成研究[J].盐业与化工,2008,37(6):9-17.
[3]DALMAU G,MARTINEZ-ESCALA ME,GZQUEZ V,et al.Swimming pool contact dermatitis caused by 1-bromo-3-chloro-5,5-dimethylhydantoin[J].Contact Dermatitis,2012,66(6):335-339.
[4]金满平,王康,郭璐.溴氯海因的爆炸性、氧化性及腐蚀性试验观察[J].安全健康和环境,2011,11(5):39-41,48.
[5]王娟,马征,夏声贤.医院污水消毒剂溴氯海因泡腾片亚急性经口毒性研究[J].现代医院,2015,15(4):7-10.
[6]中华人民共和国卫生部.化学品毒理学评价程序和试验方法[EB/OL].(2011-08-19)[2015-03-13].http://www.nhfpc.gov.cn/zhuz/pyl/201201/53857/files/3be0500aea6043b2b26a7ff06dad6c66.pdf.
[7]张金梅,霍明甲,金满平,等.卤代海因的危险特性实验研究[J].中国安全生产科学技术,2011,7(11):121-125.
[8]CALIFORNIA ENVIRONMENTAL PROTECTION AGENCY DEPARTMENT OF PESTICIDE REGULATION MEDICAL TOXICOLOGY BRANCH.Summary of Toxicology Data 1-Bromo-3-Chloro-5,5-Dimethylhydantoin(5,5-Dimethylhydantoin)[EB/OL].(2017-10-12)http://www.cdpr.ca.gov/docs/risk/toxsums/pdfs/2080.pdf.
[9]张桥.卫生毒理学基础[M].3版.北京:人民卫生出版社,2000:91.
[10]方华,上官小来,岑江杰,等.避蚊胺原药对大鼠亚急性经皮毒性研究[J].浙江化工,2008,39(6):26-30.
[11]陈贵秋,庄世峰,李世康,等.一种含氯烟雾消毒剂消毒相关性能研究[J].中国消毒学杂志,2011,28(1):3-6.
