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of Validation and Acceptance Criteria for Alternative Toxicological Test Methods. Held în Solna, Sweden, 22 - 24 January 1996 (http://www.oecd.org/ehs/test/background.htm). (2) OECD (1998) Harmonized Integrated Hazard Classification System for Human Health and Environmental Effects of Chemical Substances, aș endorsed by the 28th Joint Meeting of the Chemicals Committee and the Working Party on Chemicals, November 1998 (http://www.oecd.org/ehs/Class/HCL6.htm). (3) Worth, A.P. and Fentem J.H. (1999). A General Approach for

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A General Approach for Evaluating Stepwise Testing Strategies. ATLA 27, 161-177. (4) Metodă de testare B.4. Toxicitate acută: iritație/coroziune dermica. (5) Young, J.R., How, M.J., Walker, A.P., Worth W.M.H. (1988) Classification aș Corrosive or Irritant to Skin of Preparations Containing Acidic or Alkaline Substance Without Testing on Animals. Toxicol. In Vitro, 2, 19 - 26. (6) Neun, D.J. (1993) Effects of Alkalinity on the Eye Irritation Potențial of Solutions Prepared at a Single pH. J. Toxicol. Cut. Ocular Toxicol

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Worth W.M.H. (1988) Classification aș Corrosive or Irritant to Skin of Preparations Containing Acidic or Alkaline Substance Without Testing on Animals. Toxicol. In Vitro, 2, 19 - 26. (6) Neun, D.J. (1993) Effects of Alkalinity on the Eye Irritation Potențial of Solutions Prepared at a Single pH. J. Toxicol. Cut. Ocular Toxicol. 12, 227 - 231. (7) Fentem, J.H., Archer, G.E.B., Balls, M., Botham, P.A., Curren, R.D., Earl, L.K., Edsail, D.J., Holzhutter, H.G. and Liebsch, M. (1998) The ECVAM internațional validation study

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Skeleton în Rât Foetuses. Congenital Anomalies 32; :381-391. (9) Kimmel, C.A. et al. (1993) Skeletal Development Following Heat Exposure în the Rât. Teratology 47:229-242. (10) Marr, M.C. et al. (1988) Comparison of Single and Double Staining for Evaluation of Skeletal Development: The Effects of Ethylene Glycol (EG) în CD Rats. Teratology 37; 476. (11) Barrow, M.V. and Taylor, W.J. (1969) A Rapid Method for Detecting Malformations în Rât Foetuses. Journal of Morphology 127:291-306. (12) Fritz, H. (1974

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Anomalies 32; :381-391. (9) Kimmel, C.A. et al. (1993) Skeletal Development Following Heat Exposure în the Rât. Teratology 47:229-242. (10) Marr, M.C. et al. (1988) Comparison of Single and Double Staining for Evaluation of Skeletal Development: The Effects of Ethylene Glycol (EG) în CD Rats. Teratology 37; 476. (11) Barrow, M.V. and Taylor, W.J. (1969) A Rapid Method for Detecting Malformations în Rât Foetuses. Journal of Morphology 127:291-306. (12) Fritz, H. (1974) Prenatal Ossification în Rabbits ss

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Glycol (EG) în CD Rats. Teratology 37; 476. (11) Barrow, M.V. and Taylor, W.J. (1969) A Rapid Method for Detecting Malformations în Rât Foetuses. Journal of Morphology 127:291-306. (12) Fritz, H. (1974) Prenatal Ossification în Rabbits ss Indicative of Foetal Maturity. Teratology 11; 313-320. (13) Gibson, J.P. et al. (1966) Use of the Rabbit în Teratogenicity Studies. Toxicology and Applied Pharmacology 9; :398-408. (14) Kimmel, C.A. and Wilson, J.G. (1973) Skeletal Deviation în Rats: Malformations or Variations? Teratology

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al. (1992) Developmental Stages of the CD (Sprague-Dawley) Rât Skeleton after Maternal Exposure to Ethylene Glycol. Teratology 46; 169-181. (16) Monie, I.W. et al. (1965) Dissection Procedures for Rât Foetuses Permitting Alizarin Red Staining of Skeleton and Histological Study of Viscera. Supplement to Teratology Workshop Manual, pp. 163-173. (17) Spark, C. and Dawson, A.B. (1928) The Order and Time of appearance of Centers of Ossification în the Fore and Hind Limbs of the Albino Rât, with Special Reference to

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în Teratology. În Teratology: Principles and Techniques, Wilson J.G. and Warkany J. (eds). University of Chicago, Chicago, ÎL, pp 251-277. (23) Wilson, J.G. and Fraser, F.C. (eds). (1977) Handbook of Teratology, Vol. 4. Plenum, NY. (24) Varnagy, L. (1980) Use of Recent Fetal Bone Staining Techniques în the Evaluation of Pesticide Teratogenicity. Acta Vet. Acad. Sci. Hung. 28; 233-239. (25) Staples, R.E. (1974) Detection of visceral Alterations în Mammalian Foetuses. Teratology 9; 37-38. (26) Van Julsingha, E.B. and C.G. Bennett (1977

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Fraser, F.C. (eds). (1977) Handbook of Teratology, Vol. 4. Plenum, NY. (24) Varnagy, L. (1980) Use of Recent Fetal Bone Staining Techniques în the Evaluation of Pesticide Teratogenicity. Acta Vet. Acad. Sci. Hung. 28; 233-239. (25) Staples, R.E. (1974) Detection of visceral Alterations în Mammalian Foetuses. Teratology 9; 37-38. (26) Van Julsingha, E.B. and C.G. Bennett (1977) A Dissecting Procedure for the Detection of Anomalies în the Rabbit Foetal Head. În: Methods în Prenatal Toxicology Neubert, D., Merker, H.J. and Kwasigroch

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femelelor gestante și descendenți. 4. REFERINȚE BIBLIOGRAFICE: (1) Sadleir, R.M.F.S. (1979). Cycles and Seasons, În: Reproduction în Mammals: I. Germ Cells and Fertilization, C.R. Auston and R.V. Short (eds.), Cambridge, New York. (2) Gray, L.E. et al., (1989). A Dose-Response Analysis of Methoxychlor-Induced Alterations of Reproductive Development and Function în the Rât. Fundamental and Applied Toxicology 12:92-108. (3) Robb, G.W. et al., (1978). Daily Sperm Production and Epididymal Sperm Reserves of Pubertal and Adult Rats. Journal of Reproduction and Fertility

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Fundamental and Applied Toxicology 12:92-108. (3) Robb, G.W. et al., (1978). Daily Sperm Production and Epididymal Sperm Reserves of Pubertal and Adult Rats. Journal of Reproduction and Fertility 54:103-107. (4) Klinefelter, G.R. et al., (1991). The Method of Sperm Collection Significantly Influences Sperm Motion Parameters Following Ethane Dimethanesulfonate Administration în the Rât. Reproductive Toxicology 5:39-44 (5) Seed, J. et al. (1996). Methods for Assessing Sperm Motility, Morphology, and Counts în the Rât, Rabbit, and Dog: a Consensus

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Counts în the Rât, Rabbit, and Dog: a Consensus Report. Reproductive Toxicology 10(3):237- 244. (6) Chapin, R.E. et al., (1992). Methods for Assessing Rât Sperm Motility. Reproductive Toxicology 6:267-273 (7) Klinefelter, G.R. et al., (1992). Direct Effects of Ethane Dimethanesulphonate on Epididymal Function în Adult Rats: an In Vitro Demonstration. Journal of Andrology 13:409-421. (8) Slott, V.L. et al., (1991). Rât Sperm Motility Analysis: Methodologic Considerations. Reproductive Toxicology 5:449-458. (9) Slott, V.L. and Perreault, S.D., (1993

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Epididymal Function în Adult Rats: an In Vitro Demonstration. Journal of Andrology 13:409-421. (8) Slott, V.L. et al., (1991). Rât Sperm Motility Analysis: Methodologic Considerations. Reproductive Toxicology 5:449-458. (9) Slott, V.L. and Perreault, S.D., (1993). Computer-Assisted Sperm Analysis of Rodent Epididymal Sperm Motility Using the Hamilton-Thorn Motility Analyzer. În: Methods în Toxicology, Part A., Academic, Orlando, Florida, pp. 319-333. (10) Toth, G.P. et al. (1989). The Automated Analysis of Rât Sperm Motility Following Subchronic Epichlorhydrin Administration: Methodologic and Statistical

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of Andrology 8:330-337. (12) Linder, R.E. et al., (1992). Endpoints of Spermatoxicity în the Rât After Short Duration Exposures to Fourteen Reproductive Toxicants. Reproductive Toxicology 6:491-505. (13) Korenbrot, C.C. et al., (1977). Preputial Separation aș an External Sign of Pubertal Development în the Male Rât. Biological Reproduction 17:298303. (14) Russell, L.D. et al., (1990). Histological and Histopathological Evaluation of the Testis, Cache River Press, Clearwater, Florida. (15) Heindel, J.J. and R.E. Chapin, (eds.) (1993). Part B. Female Reproductive

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1990). Histological and Histopathological Evaluation of the Testis, Cache River Press, Clearwater, Florida. (15) Heindel, J.J. and R.E. Chapin, (eds.) (1993). Part B. Female Reproductive Systems, Methods în Toxicology, Academic, Orlando, Florida. (16) Heindel, J.J. et al., (1989) Histological Assessment of Ovarian Follicle Number în Mice Aș a Screen of Ovarian Toxicity. În: Growth Factors and the Ovary, A.N. Hirshfield (ed.), Plenum, New York, pp. 421-426. (17) Manșon, J.M. and Y.J. Kang, (1989). Test Methods for Assessing Female Reproductive and

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River Press, Clearwater, Florida. (15) Heindel, J.J. and R.E. Chapin, (eds.) (1993). Part B. Female Reproductive Systems, Methods în Toxicology, Academic, Orlando, Florida. (16) Heindel, J.J. et al., (1989) Histological Assessment of Ovarian Follicle Number în Mice Aș a Screen of Ovarian Toxicity. În: Growth Factors and the Ovary, A.N. Hirshfield (ed.), Plenum, New York, pp. 421-426. (17) Manșon, J.M. and Y.J. Kang, (1989). Test Methods for Assessing Female Reproductive and Developmental Toxicology. În: Principles and Methods of Toxicology, A

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and Y.J. Kang, (1989). Test Methods for Assessing Female Reproductive and Developmental Toxicology. În: Principles and Methods of Toxicology, A.W. Hayes (ed.), Raven, New York. (18) Smith, B.J. et al,. (1991). Comparison of Random and Serial Sections în Assessment of Ovarian Toxicity. Reproductive Toxicology 5:379-383. (19) Heindel, J.J. (1999). Oocyte Quantitation and Ovarian Histology. În: An Evaluation and Interpretation of Reproductive Endpoints for Human Health Risk Assessment, G. Daston,. and C.A. Kimmel, (eds.), ILSI Press, Washington, DC. (20

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node assay: developments and applications. Toxicology, 93, 13-31. 3 Kimber, I., Hilton, J., Dearman, R.J., Gerberick, G.F., Ryan, C.A., Basketter, D.A., Lea, L., House, R.V., Ladies, G.S., Loveless, S.E., Hastings, K .L. (1998). Assessment of the skin sensitisation potențial of topical medicaments using the local lymph node assay: An inter laboratory exercise. Journal of Toxicology and Environmental Health, 53, 563-79. 4 Metodă de testare B.6. 5 Chamberlain, M. and Basketter, D.A. (1996). The local lymph node assay: status of

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of topical medicaments using the local lymph node assay: An inter laboratory exercise. Journal of Toxicology and Environmental Health, 53, 563-79. 4 Metodă de testare B.6. 5 Chamberlain, M. and Basketter, D.A. (1996). The local lymph node assay: status of validation. Food and Chemical Toxicology 34, 999-1002. 6 Basketter, D.A., Gerberick, G.F., Kimber, Ț. and Loveless, S.E (1 996). The local lymph node assay- A viable alternative to currently accepted skin sensitisation tests. Food and Chemical Toxicology, 34, 985-997

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Toxicology. 36, 327-33. 8 Van Och, F.M.M, Slob, W., De Jong, W.H., Vandebriel, R.J., Van Loveren, H. (2000). A quantitative method for assessing the sensitising potency of low molecular weight chemicals using a local lymph node assay: employement of a regression method that includes determination of uncertainty margins. Toxicology, 146, 49-59. 9 Dearman, R.J., Hilton, J., Evans, P., Harvey, P., Basketter, D.A. and Kimber, I. (1998). Temporal stability of local lymph node assay responses to hexyl cinnamic aldehyde. Journal

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molecular weight chemicals using a local lymph node assay: employement of a regression method that includes determination of uncertainty margins. Toxicology, 146, 49-59. 9 Dearman, R.J., Hilton, J., Evans, P., Harvey, P., Basketter, D.A. and Kimber, I. (1998). Temporal stability of local lymph node assay responses to hexyl cinnamic aldehyde. Journal of Applied Toxicology, 18, 281-4. 10 Național Institute of Environmental Health Sciences (1999). The Murine Local Lymph Node Assay: A Test Method for Assessing the Allergic Contact Dermatitis Potențial of

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margins. Toxicology, 146, 49-59. 9 Dearman, R.J., Hilton, J., Evans, P., Harvey, P., Basketter, D.A. and Kimber, I. (1998). Temporal stability of local lymph node assay responses to hexyl cinnamic aldehyde. Journal of Applied Toxicology, 18, 281-4. 10 Național Institute of Environmental Health Sciences (1999). The Murine Local Lymph Node Assay: A Test Method for Assessing the Allergic Contact Dermatitis Potențial of Chemicals/Compounds: The Results of an Independent Peer Review Evaluation Coordinated by the Interagency Coordinating Committee on the Validation

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of local lymph node assay responses to hexyl cinnamic aldehyde. Journal of Applied Toxicology, 18, 281-4. 10 Național Institute of Environmental Health Sciences (1999). The Murine Local Lymph Node Assay: A Test Method for Assessing the Allergic Contact Dermatitis Potențial of Chemicals/Compounds: The Results of an Independent Peer Review Evaluation Coordinated by the Interagency Coordinating Committee on the Validation of Alternative Methods (ICCVAM) and the Național Toxicology Program Center for the Evaluation of Alternative Toxicological Methods (NICETAM). NIH Publication No

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13. Moser, V.C., Anthony, D.C., Sette, W.F. and MacPhail, R.C. (1992). Comparison of Subchronic Neurotoxicity of 2-Hydroxyethyl Acrylate and Acrylamide în Rats. Fund. Appl.Toxicol., 18, 343-352. 14. O'Callaghan J.P. (1988). Neurotypic and Gliotypic Proteins aș Biochemical Markers of Neurotoxicity. Eurotoxicol. Teratol., 10, 445-452. 15. O'Callaghan J.P. and Miller, D.B. (1988). Acute Exposure of the Neonatal Rut to Triethyltin Rcsults în Persistent Changes în Neurotypic and Gliotypic Proteins. J. Pharmacol. Exp. Ther., 244, 368-378. 16. Fox. D.A., Lowndes

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pp. 299-335. 17. Johnson, B.L. (1980). Electrophysiological Methods în Neurotoxicity Testing. În: Experimental and Clinical Neurotoxicology. Spencer, P.S. and Schaumburg, H.H. eds., Williams and Wilkins Co.,. Baltimore/London, pp. 726-742. 18. Bancroft, J.D. and Steven A. (1990). Theory and Practice of Histological Techniques, Chapter 17, Neuropathological Techniques, Lowe, James and Cox, Gordon eds. Churchill Livingstone. Tabelul 1: Numărul minim de animale necesare pe grup pentru studiile de neurotoxicitate realizate separat sau în combinație cu alte studii STUDIU DE NEUROTOXICITATE REALIZAT: Separat

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