化学品毒性鉴定技术规范.doc
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化学品毒性鉴定技术规范,共22.3万字282页目 录一、总则3二、试验方法（一）第一阶段试验151、急性吸入毒性试验 162、急性经皮毒性试验203、急性经口毒性试验 234、急性眼刺激性/腐蚀性试验265、皮肤刺激性/腐蚀性试验326、皮肤变态反应试验（皮肤致敏试验）36（二）第二阶段试验541、鼠伤寒沙门氏菌回复突变...
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化学品毒性鉴定技术规范
共22.3万字 282页
目 录
一、总则………………………………………………………………………………3
二、试验方法
（一）第一阶段试验…………………………………………………………………15
1、急性吸入毒性试验 ……………………………………………………………16
2、急性经皮毒性试验……………………………………………………………20
3、急性经口毒性试验 ……………………………………………………………23
4、急性眼刺激性/腐蚀性试验……………………………………………………26
5、皮肤刺激性/腐蚀性试验………………………………………………………32
6、皮肤变态反应试验（皮肤致敏试验）………………………………………36
（二）第二阶段试验………………………………………………………………54
1、鼠伤寒沙门氏菌回复突变试验（Ames试验）………………………………55
2、体外哺乳动物细胞染色体畸变试验…………………………………………62
3、体内哺乳动物骨髓细胞染色体畸变试验……………………………………68
4、体内哺乳动物骨髓嗜多染红细胞微核试验…………………………………75
5、哺乳动物精原细胞/初级精母细胞染色体畸变试验，或…………………79
精子畸形试验…………………………………………………………………87
6、啮齿类动物显性致死试验……………………………………………………90
7、免疫毒性评价试验方法………………………………………………………95
8、亚急性吸入（14/28天）毒性试验…………………………………………104
9、亚急性经皮（21/28天）毒性试验…………………………………………110
10、亚急性经口（28天）毒性试验……………………………………………115
（三）第三阶段试验………………………………………………………………121
1、亚慢性吸入毒性试验…………………………………………………………122
2、亚慢性经皮毒性试验…………………………………………………………126
3、亚慢性经口毒性试验…………………………………………………………130
4、致畸试验………………………………………………………………………136
5、两代繁殖毒性试验……………………………………………………………142
6、迟发性神经毒性试验…………………………………………………………147
（四）第四阶段试验………………………………………………………………153
1、慢性吸入毒性试验……………………………………………………………154
2、慢性经皮毒性试验……………………………………………………………160
3、慢性经口毒性试验……………………………………………………………166
4、致癌试验，或…………………………………………………………………172
慢性毒性/致癌性合并试验 ………………………………………………180
5、毒物代谢动力学试验 ………………………………………………………189
6、接触人群调查与观察（参考国内外有关专著或教科书）
（五）参考试验……………………………………………………………………196
1、皮肤变态反应试验-局部淋巴结法…………………………………………197
2、大肠杆菌回复突变试验………………………………………………………202
3、酵母菌基因突变试验………………………………………………………210
4、体外哺乳动物细胞正向基因突变试验……………………………………214
5、果蝇伴性隐性致死试验………………………………………………………220
6、枯草杆菌基因重组试验………………………………………………………224
7、体外哺乳动物细胞程序外DNA合成（UDS）试验……………………………232
8、体内哺乳动物外周血细胞微核试验…………………………………………238
9、体外哺乳动物姊妹染色单体交换（SCE）试验………………………………244
10、体内哺乳动物骨髓细胞姊妹染色体交换（SCE）试验……………………250
11、繁殖/生长发育毒性筛选试验………………………………………………256
12、亚急性毒性合并繁殖/发育毒性筛选试验…………………………………262
13、一代繁殖试验………………………………………………………………269
14、神经毒性筛选组合试验……………………………………………………274
参考文献
0. Armed Forces Institute of Pathology. Manual of Histologic Staining Methods. McGraw-Hill, NY (1968).
1. Bennet, H.S. et al. Science and art in the preparing tissues embedded in plastic for light microscopy, with special reference to glycol methacrylate, glass knives and simple stains. Stain Technology 51:71-97 (1976).
2. Di Sant Agnese, P.A. and De Mesy Jensen, K. Dibasic staining of large epoxy sections and application to surgical pathology. American Journal of Clinical Pathology 81:25-29 (1984).
3. Edwards, P.M. and Parker V.H. A simple, sensitive and objective method for early assessment of acrylamide neuropathy in rats. Toxicology and Applied Pharmacology 40:589-591 (1977).
4. Finger, F.W. Measuring behavioral activity. In: Methods in Psychobiology Vol. 2, Ed. R.D. Myers. Academic, NY. pp.1-19 (1972).
5. Gad, S. A neuromuscular screen for use in industrial toxicology. Journal of Toxicology and Environmental Health 9:691-704 (1982).
6. Hayat, M.A. Volume 1. Biological applications. In: Principles and Techniques of Electron Microscopy. Van Nostrand Reinhold, NY (1970).
7. Irwin, S. Comprehensive observational assessment: Ia. A systematic quantitative procedure for assessing the behavioral physiological state of the mouse. Psychopharmacologia 13:222-257 (1968).
8. Kinnard, E.J. and Watzman, N. Techniques utilized in the evaluation of psychotropic drugs on animals activity. Journal of Pharmaceutical Sciences 55:995-1012 (1966).
9. Meyer, O.A. et al. A method for the routine assessment of fore- and hindlimb grip strength of rats and mice. Neurobehavioral Toxicology 1:233-236 (1979).
10. Moser V.C. et al. Comparison of chlordimeform and carbaryl using a functional observational battery. Fundamental and Applied Toxicology 11:189-206 (1988).
11. O'Callaghan, J.P. Quantification of glial fibrillary acidic protein: comparison of slot-immunobinding assays with a novel sandwich ELISA, Neurotoxicology and Teratology, 13:275-281 (1991).
12. Palay, S.L. and Chan Palay, V. Cerebellar Cortex: Cytology and Organizatio. Springer Verlag, NY (1974).
13. Pender, M.P. A simple method for high resolution light microscopy of nervous tissue. Journal of Neuroscience Methods 15:213-218 (1985).
14. Ralis, H.M. et al. Techniques in Neurohistology, Butterworths, London (1973).
15. Reiter, L.W. Use of activity measures in behavioral toxicology. Environmental Health Perspectives 26:9-20 (1978).
16. Reiter, L.W. and MacPhail, R.C. Motor Activity: A survey of methods with potential use in toxicity testing. Neurobehavorial Toxicology 1--Suppl. 1:53-66 (1979).
17. Robbins, T.W. A critique of the methods available for the measurement of spontaneous motor activity. Handbook of Psychopharmacology Vol 7. Eds. Iversen, L.L., Iverson, D.S., Snyder, S.H. Plenum, NY. pp. 37-82 (1977).
18. Spencer, P.S., Schaumburg, H.H. Eds., Experimental and Clinical Neurotoxicology, Williams and Wilkins, Baltimore (1980).
19. World Health Organization. Principles and Methods for the Assessment of Neurotoxicity Associated with Exposure to Chemicals (Environmental Health Criteria 60), World Health Organizations Publications Center USA, Albany, NY (1986).
20. Zeman, W. and Innes, J.R. Craigie's Neuroanatomy of the Rat, Academic, NY (1963).
共22.3万字 282页
目 录
一、总则………………………………………………………………………………3
二、试验方法
（一）第一阶段试验…………………………………………………………………15
1、急性吸入毒性试验 ……………………………………………………………16
2、急性经皮毒性试验……………………………………………………………20
3、急性经口毒性试验 ……………………………………………………………23
4、急性眼刺激性/腐蚀性试验……………………………………………………26
5、皮肤刺激性/腐蚀性试验………………………………………………………32
6、皮肤变态反应试验（皮肤致敏试验）………………………………………36
（二）第二阶段试验………………………………………………………………54
1、鼠伤寒沙门氏菌回复突变试验（Ames试验）………………………………55
2、体外哺乳动物细胞染色体畸变试验…………………………………………62
3、体内哺乳动物骨髓细胞染色体畸变试验……………………………………68
4、体内哺乳动物骨髓嗜多染红细胞微核试验…………………………………75
5、哺乳动物精原细胞/初级精母细胞染色体畸变试验，或…………………79
精子畸形试验…………………………………………………………………87
6、啮齿类动物显性致死试验……………………………………………………90
7、免疫毒性评价试验方法………………………………………………………95
8、亚急性吸入（14/28天）毒性试验…………………………………………104
9、亚急性经皮（21/28天）毒性试验…………………………………………110
10、亚急性经口（28天）毒性试验……………………………………………115
（三）第三阶段试验………………………………………………………………121
1、亚慢性吸入毒性试验…………………………………………………………122
2、亚慢性经皮毒性试验…………………………………………………………126
3、亚慢性经口毒性试验…………………………………………………………130
4、致畸试验………………………………………………………………………136
5、两代繁殖毒性试验……………………………………………………………142
6、迟发性神经毒性试验…………………………………………………………147
（四）第四阶段试验………………………………………………………………153
1、慢性吸入毒性试验……………………………………………………………154
2、慢性经皮毒性试验……………………………………………………………160
3、慢性经口毒性试验……………………………………………………………166
4、致癌试验，或…………………………………………………………………172
慢性毒性/致癌性合并试验 ………………………………………………180
5、毒物代谢动力学试验 ………………………………………………………189
6、接触人群调查与观察（参考国内外有关专著或教科书）
（五）参考试验……………………………………………………………………196
1、皮肤变态反应试验-局部淋巴结法…………………………………………197
2、大肠杆菌回复突变试验………………………………………………………202
3、酵母菌基因突变试验………………………………………………………210
4、体外哺乳动物细胞正向基因突变试验……………………………………214
5、果蝇伴性隐性致死试验………………………………………………………220
6、枯草杆菌基因重组试验………………………………………………………224
7、体外哺乳动物细胞程序外DNA合成（UDS）试验……………………………232
8、体内哺乳动物外周血细胞微核试验…………………………………………238
9、体外哺乳动物姊妹染色单体交换（SCE）试验………………………………244
10、体内哺乳动物骨髓细胞姊妹染色体交换（SCE）试验……………………250
11、繁殖/生长发育毒性筛选试验………………………………………………256
12、亚急性毒性合并繁殖/发育毒性筛选试验…………………………………262
13、一代繁殖试验………………………………………………………………269
14、神经毒性筛选组合试验……………………………………………………274
参考文献
0. Armed Forces Institute of Pathology. Manual of Histologic Staining Methods. McGraw-Hill, NY (1968).
1. Bennet, H.S. et al. Science and art in the preparing tissues embedded in plastic for light microscopy, with special reference to glycol methacrylate, glass knives and simple stains. Stain Technology 51:71-97 (1976).
2. Di Sant Agnese, P.A. and De Mesy Jensen, K. Dibasic staining of large epoxy sections and application to surgical pathology. American Journal of Clinical Pathology 81:25-29 (1984).
3. Edwards, P.M. and Parker V.H. A simple, sensitive and objective method for early assessment of acrylamide neuropathy in rats. Toxicology and Applied Pharmacology 40:589-591 (1977).
4. Finger, F.W. Measuring behavioral activity. In: Methods in Psychobiology Vol. 2, Ed. R.D. Myers. Academic, NY. pp.1-19 (1972).
5. Gad, S. A neuromuscular screen for use in industrial toxicology. Journal of Toxicology and Environmental Health 9:691-704 (1982).
6. Hayat, M.A. Volume 1. Biological applications. In: Principles and Techniques of Electron Microscopy. Van Nostrand Reinhold, NY (1970).
7. Irwin, S. Comprehensive observational assessment: Ia. A systematic quantitative procedure for assessing the behavioral physiological state of the mouse. Psychopharmacologia 13:222-257 (1968).
8. Kinnard, E.J. and Watzman, N. Techniques utilized in the evaluation of psychotropic drugs on animals activity. Journal of Pharmaceutical Sciences 55:995-1012 (1966).
9. Meyer, O.A. et al. A method for the routine assessment of fore- and hindlimb grip strength of rats and mice. Neurobehavioral Toxicology 1:233-236 (1979).
10. Moser V.C. et al. Comparison of chlordimeform and carbaryl using a functional observational battery. Fundamental and Applied Toxicology 11:189-206 (1988).
11. O'Callaghan, J.P. Quantification of glial fibrillary acidic protein: comparison of slot-immunobinding assays with a novel sandwich ELISA, Neurotoxicology and Teratology, 13:275-281 (1991).
12. Palay, S.L. and Chan Palay, V. Cerebellar Cortex: Cytology and Organizatio. Springer Verlag, NY (1974).
13. Pender, M.P. A simple method for high resolution light microscopy of nervous tissue. Journal of Neuroscience Methods 15:213-218 (1985).
14. Ralis, H.M. et al. Techniques in Neurohistology, Butterworths, London (1973).
15. Reiter, L.W. Use of activity measures in behavioral toxicology. Environmental Health Perspectives 26:9-20 (1978).
16. Reiter, L.W. and MacPhail, R.C. Motor Activity: A survey of methods with potential use in toxicity testing. Neurobehavorial Toxicology 1--Suppl. 1:53-66 (1979).
17. Robbins, T.W. A critique of the methods available for the measurement of spontaneous motor activity. Handbook of Psychopharmacology Vol 7. Eds. Iversen, L.L., Iverson, D.S., Snyder, S.H. Plenum, NY. pp. 37-82 (1977).
18. Spencer, P.S., Schaumburg, H.H. Eds., Experimental and Clinical Neurotoxicology, Williams and Wilkins, Baltimore (1980).
19. World Health Organization. Principles and Methods for the Assessment of Neurotoxicity Associated with Exposure to Chemicals (Environmental Health Criteria 60), World Health Organizations Publications Center USA, Albany, NY (1986).
20. Zeman, W. and Innes, J.R. Craigie's Neuroanatomy of the Rat, Academic, NY (1963).
