Simulation of chemical metabolism for fate and hazard assessment. V. Mammalian hazard assessment

SAR and QSAR in Environmental Research

Volumn 23, Issue 5-6, 2012, Pages 553-606

  Mekenyan, O ^a   Dimitrov, S ^a   Pavlov, T ^a   Dimitrova, G ^a   Todorov, M ^a   Petkov, P ^a   Kotov, S ^a  

^a ASSEN ZLATAROV UNIVERSITY   (Bulgaria)

Author keywords

metabolism; modelling; pathways; TIMES; toxicity

Indexed keywords

BINDING ENERGY; BIOCHEMISTRY; CHEMICAL HAZARDS; COMPUTER SOFTWARE; DETOXIFICATION; FORECASTING; MAMMALS; PHYSIOLOGY;

DETOXIFICATION PROCESS; EFFECT OF CHEMICALS; ENZYMATIC MECHANISMS; EXPOSED TO; HAZARD ASSESSMENT; METABOLIC TRANSFORMATIONS; MODELING; OXIDATION REDUCTION; PATHWAY; TIMES;

METABOLISM;

ANIMALIA; EUKARYOTA; MAMMALIA;

EID: 84864682999     PISSN: 1062936X     EISSN: 1029046X     Source Type: Journal    
DOI: 10.1080/1062936X.2012.679689     Document Type: Article

References (117)

1. Dimitrov, S, Pavlov, T, Veith, G and Mekenyan, O. 2011. Simulation of chemical metabolism for fate and hazard assessment. I. Approach for simulating metabolism. SAR QSAR Environ. Res., 22: 699-718.
2. Dimitrov, S, Pavlov, T, Dimitrova, N, Georgieva, D, Nedelcheva, D, Kesova, A, Vasilev, R and Mekenyan, O. 2011. Simulation of chemical metabolism for fate and hazard assessment. II. CATALOGIC simulation of abiotic and microbial degradation. SAR QSAR Environ. Res., 22: 719-755.
3. Dimitrov, S, Dimitrova, N, Georgieva, D, Vasilev, K, Hatfield, T, Straka, J and Mekenyan, O. 2012. Simulation of chemical metabolism for fate and hazard assessment. III. New developments of BCF base-line model. SAR QSAR Environ. Res., 23: 17-36.
4. Liska, D. 1998. The detoxification enzyme systems. Altern. Med. Rev., 3: 187-197.
5. Gunaratna, C. 2000. Drug metabolism and pharmacokinetics in drug discovery: A primer for biobnalytical chemists, Part I. Curr. separations, 19: 17-23.
6. Lewis, DFV, Lake, BG, George, SG, Dickins, M, Eddershaw, PJ, Tarbit, MH, Beresford, AP, Goldfarb, PS and Guengerich, FP. 1999. Molecular modelling of CYP1 family enzymes CYP1A1, CYP1A2, CYP1A6 and CYP1B1 based on sequence homology with CYP102. Toxicology, 139: 53-79.
7. Rendic, S and DiCarlo, FJ. 1997. Human cytochrome P450 enzymes: A status report summarizing their reactions, substrates, inducers and inhibitors. Drug Metab. Rev., 29: 413-580.
8. Zanger, U, Raimundo, S and Eichelbaum, M. 2004. Cytochrome P450 2D6: Overview and update on pharmacology, genetics, biochemistry. Naunyn-Schmiedeberg's Arch. Pharmacol., 369: 23-37.
9. de Wildt, S, Kearns, G, Leeder, J and van der Anker, J. 1999. Cytochrome P450 3A: Ontogeny and drug disposition. Clin. Pharmacokinet., 37: 485-505.
10. Seliskar, M and Rozman, D. 2007. Mammalian cytochromes P450-Importance of tissue specificity. Biochim. Biophys. Acta, 1770: 458-466.
11. Hukkanen, J. Xenobiotic-metabolizing cytochrome P450 enzymes in human lung, Ph.D. thesis, Acta Univ. Oul. D 621, 2000
12. Fretland, AJ and Omiecinski, CJ. 2000. Epoxide hydrolases: Biochemistry and molecular biology. Chem.-Biol. Interact., 129: 41-59.
13. Hines, RN, Cashman, JR, Philpot, RM, Williams, DE and Ziegler, DM. 1994. The mammalian flavin-containing monooxygenases: Molecular characterization and regulation of expression. Toxicol. Appl. Pharmacol., 125: 1-6.
14. Hellgren, M. 2009. Enzymatic studies of alcohol dehydrogenase by a combination of in vitro and in silico methods, Karolinska Institutet, Stockholm, Sweden: Ph.D. thesis. p. 70
15. Haymann, E. 1980. "Carboxylesterases and amidases". In Enzymatic Bases of Detoxification, Edited by: Jakoby, W. Vol. 2, 291-323. New York: Academic Press.
16. Tipton, KF, Boyce, S, O'Sullivan, J, Davey, GP and Healy, J. 2004. Monoamine oxidases: Certainties and uncertainties. Curr. Med. Chem., 11: 1965-1982.
17. Ekins, S, Mäenpää, J and Wrighton, SA. 1999. "In vitro metabolism: Subcellular fractions". In Handbook of Drug Metabolism, Edited by: Woolf, TF. 363-400. New York: Marcel Dekker.
18. Hirom, PC, Millburn, P, Smith, RL and Williams, RT. 1972. Species variations in the threshold molecular-weight factor for the biliary excretion of organic anions. Biochem. J., 129: 1071-1077.
19. Zenser, TV, Lakshmi, VM, Hsu, FF and Davis, BB. 2002. Metabolism of N-acetylbenzidine and initiation of bladder cancer. Mutat. Res., 506-507: 29-40.
20. Dickinson, RG and King, AR. 1993. Studies on the reactivity of acyl glucuronides-V. Glucuronide-derived covalent binding of diflunisal to bladder tissue of rats and its modulation by urinary pH and β-glucuronidase. Biochem. Pharmacol., 46: 1175-1182.
21. Caldwell, J. 1982. Conjugation reaction in foreign-compound metabolism: Definition, consequences, and species variation. Drug Metab. Rev., 13: 745-777.
22. Wang, M and Dickinson, RG. 1998. Disposition and covalent binding of diflunisal and diflunisal acyl glucuronide in the isolated perfused rat liver. Drug Metab. Dispos., 26: 98-104.
23. Brown, SA. 2001. "Pharmacokinetics: Disposition and fate of drugs in the body". In Veterinary Pharmacology and Therapeutics, 8, Edited by: Adams, HR. 15-56. Ames, Iowa, USA: Iowa State University Press.
24. Bartlet, AL and Kirinya, LM. 1976. Activities of mixed function oxidases, UDP-glucuronyl transferase and sulphate conjugation enzymes in Aalliformes and Anseriformes. Exp. Physiol., 61: 105-119.
25. Sallustio, BC, Sabordo, L, Evans, AM and Nation, RL. 2000. Hepatic disposition of electrophilic acyl glucuronide conjugates. Curr. Drug. Metab., 1: 163-180.
26. Bailey, MJ and Dickinson, RG. 2003. Acyl glucuronide reactivity in perspective: Biological consequences. Chem. Biol. Interact., 145: 117-137.
27. Soars, MG, Burchell, B and Riley, RJ. 2002. In vitro analysis of human drug glucuronidation and prediction of in vivo metabolic clearance. J. Pharmacol. Exp. Ther., 301: 382-390.
28. Nakamura, A, Nakajima, M, Yamanaka, H, Fujiwara, R and Yokoi, T. 2008. Expression of UGT1A and UGT2B mRNA in human normal tissues and various cell lines. Drug. Metab. Dispos., 36: 1461-1464.
29. Shiratani, H, Katoh, M, Nakajima, M and Yokoi, T. 2008. Species differences in UDP-glucuronosyltransferase activities in mice and rats. Drug. Metab. Dispos., 36: 1745-1752.
30. Parke, DV. 1968. The Biochemistry of Foreign Compounds, Oxford, England: Pergamon Press.
31. van Iersel, MLPS, Ploemen, J-PHTM, Bello, ML, Federici, G and van Bladeren, PJ. 1997. Interactions of α, β-unsaturated aldehydes and ketones with human glutathione S-transferase, P1-1. Chem-Biol. Interact., 108: 67-78.
32. Koob, M and Dekant, W. 1991. Bioactivation of xenobiotics by formation of toxic glutathione conjugates. Chem-Biol. Interact., 77(2): 107-136.
33. Husain, A, Zhang, X, Doll, MA, States, JC, Barker, DF and Hein, DW. 2007. Identification of N-Acetyltransferase 2 (NAT2) transcription start sites and quantitation of NAT2-specific mRNA in human tissues. Drug Metab. Dispos., 35: 721-727.
34. Liu, Y, Norton, JT, Witschi, MA, Lou, QXG, Wa, C, Appella, DH, Chen, Z and Huang, S. 2011. Methoxyethylamino-numonafide Is an efficacious and minimally toxic amonafide derivative in murine models of human cancer. Neoplasia, 13: 453-460.
35. Gibson, G and Skett, P. 2001. Introduction to Drug Metabolism, 21Cheltenham, UK: Nelson Thornes Publishers.
36. Shimoi, K, Okada, H, Furugori, M, Goda, T, Takase, S, Suzuki, M, Hara, Y, Yamamoto, H and Kinae, N. 1998. Intestinal absorption of luteolin and luteolin 7-O-beta-glucoside in rats and humans. FEBS Lett., 438: 220-224.
37. Manach, C, Texier, O, Régérat, F, Agullo, G, Demigné, C and Rémésy, C. 1996. Dietary quercetin is recovered in rat plasma as conjugated derivatives of isorhamnetin and quercetin. Nutr. Biochem., 7: 375-380.
38. Ellis, RJ. 2001. Macromolecular crowding: Obvious but underappreciated. Trends Biochem. Sci., 26: 597-604.
39. Schnell, S and Turner, TE. 2004. Reaction kinetics in intracellular environments with macromolecular crowding: Simulations and rate laws. Prog. Biophys. Mol. Biol., 85: 235-260.
40. Conrado, RJ, Varner, JD and DeLisa, MP. 2008. Engineering the spatial organization of metabolic enzymes: Mimicking nature's synergy. Curr. Opin. Biotechnol., 19: 492-499.
41. Srere, PA and Ovádi, J. 1990. Enzyme-enzyme interaction and their metabolic role. FEBS Lett., 268: 360-364.
42. Spivey, HO and Ovádi, J. 1999. Substrate Channeling. Methods, 19: 306-321.
43. Jørgensen, K, Rasmussen, AV, Morant, M, Nielsen, AH, Bjarnholt, N, Zagrobelny, M, Bak, S and Møller, BL. 2005. Metabolon formation and metabolic channeling in the biosynthesis of plant natural products. Curr. Opin. Plant Biol., 8: 280-291.
44. Huthmacher, C, Gille, C and Holzhütter, H-G. 2008. A computational analysis of protein interactions in metabolic networks reveals novel enzyme pairs potentially involved in metabolic channeling. J. Theor. Biol., 252: 456-464.
45. Eisenbrand, G, Pool-Zobel, B, Baker, V, Balls, M, Blaauboer, BJ, Boobis, A, Carere, A, Kevekordes, S, Lhuguenot, JC, Pieters, R and Kleiner, J. 2002. Methods of in vitro toxicology. Food Chem. Toxicol., 40(2-3): 193-236.
46. Brandon, EFA, Raap, CD, Meijerman, I, Beijnen, JH and Schellens, JHM. 2003. An update on in vitro test methods in human hepatic drug biotransformation research: Pros and cons. Toxicol. Appl. Pharmacol., 189: 233-246.
47. Kolanczyk, RC, Schmieder, P, Jones, WJ, Mekenyan, OG, Chapkanov, A, Kotov, S, Velikova, M, Kamenska, V, Vasilev, K and Veith, GD. 2012. MetaPath: An electronic knowledge base for collating, exchanging and modeling case studies of xenobiotic metabolism. Regul. Toxicol. Pharm., 63: 84-96 [Epub ahead of print].
48. Council Directive of 27 July 1976 on the approximation of the laws of the Member States relating to cosmetic products, OJ L. 262, 27.9.1976, p. 169
49. Basketter, DA, Scholes, EW and Kimber, I. 1994. The performance of the local lymph node assay with chemicals identified as contact allergens in the human maximization test. Food Chem. Toxicol., 32: 543-547.
50. Magnusson, B and Kligman, AM. 1969. The identification of contact allergens by animal assay. The guinea pig maximization test. J. Investig. Dermatol., 52: 268-276.
51. Magnusson, B and Kligman, AM. 1970. Allergic contact dermatitis in the guinea pig. Identification of contact allergens, Springfield, IL: Charles C Thomas.
52. Kayser, D and Schlede, E. (eds.), Chemikalien und Kontagtalergie-eine bewertende Zusammenstellung, Medizin & Wissen Verlagges, Munchen, 2001
53. Schlede, E, Aberer, W, Fuchs, T, Gerner, I, Lessmann, H, Maurer, T, Rossbacher, R, Stropp, G, Wagner, E and Kayser, D. 2003. Chemical substances and contact allergy-244 substances ranked according to allergenic potency. Toxicol., 193: 219-259.
54. Bergstrom, MA, Anderson, SI, Broo, K, Luthman, K and Karlberg, A-T. 2008. Oximes: Metabolic activation and structure-allergenic activity relationships. J. Med. Chem., 51: 2541-2550.
55. Gerberick, GF, Vassallo, JD, Bailey, RE, Chaney, JG, Morrall, SW and Lepoittevin, JP. 2004. Development of a peptide reactivity assay for screening contact allergens. Toxicol. Sci., 81: 332-343.
56. Gerberick, GF, Ryan, CA, Kern, PS, Schlatter, H, Dearman, RJ, Kimber, I, Patlewicz, GY and Basketter, DA. 2005. Compilation of historical Local Lymph Node data for the evaluation of skin sensitization alternative methods. Dermatitis, 16: 1-46.
57. Kern, PS, Gerberick, F, Ryan, CA, Kimber, I, Aptula, A and Basketter, DA. 2010. Local lymph node data for the evaluation of skin sensitization alternatives: A second compilation. Dermatitis, 21: 8-32.
58. Natsch, A, Gfeller, H, Rothaupt, M and Ellis, G. 2007. Utility and limitations of a peptide reactivity assay to predict fragrance allergens in vitro. Toxicol. in Vitro, 21: 1220-1226.
59. Patlewicz, GY, Basketter, DA, Pease, CK, Wilson, K, Wright, ZM, Roberts, DW, Bernard, G, Arnau, EG and Lepoittevin, JP. 2004. Further evaluation of quantitative structure-activity relationship models for the prediction of the skin sensitization potency of selected fragrance allergens. Contact Dermatitis, 50: 91-97.
60. Patlewicz, G, Dimitrov, SD, Low, LK, Kern, PS, Dimitrova, GD, Comber, MI, Aptula, AO, Phillips, RD, Niemelä, J, Madsen, C, Wedebye, EB, Roberts, DW, Bailey, PT and Mekenyan, OG. 2007. TIMES-SS-A promising tool for the assessment of skin sensitization hazard. A characterization with respect to the OECD validation principles for (Q)SARs and an external evaluation for predictivity. Reg. Toxicol. Pharmacol., 48: 225-239.
61. Barratt, MD, Basketter, DA, Chamberlain, M, Admans, GD and Langowski, JJ. 1994. An expert system rulebase for identifying contact allergens. Toxicol. in Vitro, 8: 1053-1060.
62. Cronin, MT and Basketter, DA. 1994. Multivariate QSAR analysis of a skin sensitization database. SAR QSAR Environ. Res., 2: 159-179.
63. ECETOC [European Centre for Ecotoxicology and Toxicology of Chemicals], Contact Sensitization: Classification According to Potency, Tech. Rep. No. 87, 4 Avenue E. Van Nieuwenhuyse (Bte 6), B-1160 Brussels, Belgium, 2003
64. Dimitrov, SD, Low, LK, Patlewicz, GY, Kern, PS, Dimitrova, GD, Comber, MHI, Philips, RD, Niemela, J, Bailey, PT and Mekenyan, OG. 2005. Skin sensitization: Modeling based on skin metabolism simulation and formation of protein conjugates. Int. J. Toxicol., 24: 189-204.
65. Mekenyan, OG, Ivanov, JM, Karabunarliev, SH, Bradbury, SP, Ankley, GT and Karcher, W. 1997. A computationally-based hazard identification algorithm that incorporates ligand flexibility. 1. Identification of potential androgen receptor ligands. Environ. Sci. Technol., 31: 3702-3711.
66. Bradbury, SP, Mekenyan, OG, Kamenska, VB, Schmieder, P and Ankley, GT. 2000. A computationally-based identification algorithm for estrogen receptor ligands. Part I. Predicting hER" binding affinity. Toxicol. Sci., 58: 253-269.
67. Mekenyan, O, Nikolova, N, Schmieder, P and Veith, G. 2004. COREPA-M: A multi-dimentional formulation of COREPA. QSAR Comb. Sci., 23: 5-18.
68. Smith, CK and Hotchkiss, SAM. 2001. Allergic Contact Dermatitis: Chemical and Metabolic Mechanisms, London, UK: Taylor & Francis Ltd.
69. Enoch, SJ, Ellison, CM, Schultz, TW and Cronin, MTD. 2011. A review of the electrophilic reaction chemistry involved in covalent protein binding relevant to toxicity. Crit. Rev. Toxicol., 41: 783-802.
70. Dimitrov, S, Dimitrova, G, Pavlov, T, Dimitrova, N, Patlewicz, G, Niemela, J and Mekenyan, O. 2005. A stepwise approach for defining the applicability domain of SAR and QSAR models. J. Chem. Inf. Model., 45: 839-849.
71. Version, EPI Suite. 4.00, 2009, software Available athttp://www.epa.gov/opptintr/exposure/pubs/episuitedl.thm
72. Roberts, DW, Patlewicz, G, Dimitrov, SD, Low, LK, Aptula, AO, Kern, PS, Dimitrova, GD, Comber, MIH, Phillips, RD, Niemelä, J, Madsen, C, Wedebye, EB, Bailey, PT and Mekenyan, OG. 2007. TIMES-SS-A mechanistic evaluation of an external validation study using reaction chemistry principles. Chem. Res. Toxicol., 48: 225-239.
73. Aptula, AO, Patlewicz, G and Roberts, DW. 2005. Skin sensitization: Reaction mechanistic applicability domains for structure-activity relationship. Chem. Res. Toxicol., 18: 1420-1426.
74. Enoch, SJ, Madden, JC and Cronin, MT. 2008. Identification of mechanisms of toxic action for skin sensitisation using a SMARTS pattern based approach. SAR QSAR Environ. Res., 19: 555-578.
75. Patlewicz, GY, Wright, ZM, Basketter, DA, Pease, CK, Lepoittevin, J-P and Gimenez, AE. 2002. Structure-activity relationships for selected fragrance allergens. Contact Derm., 47: 219-226.
76. European Medicines Agency, Genotoxicity: A standard battery for genotoxicity testing of pharmaceuticals, ICH Topic S2B, Ref. No. CPMP/ICH/174/95, International Conference on Harmonization, London, 1997
77. OECD, Final Report of the Sixth Meeting of the Task Force on Endocrine Disrupters Testing and Assessment (EDTA 6), ENV/JM/TG/EDTA/M, (2003) 4
78. Ames, B, McCann, J and Yamasaki, E. 1975. Methods for detecting carcinogens and mutagens with the Salmonella/mammalian-microsome mutagenicity test. Mutat. Res., 31: 347-364.
79. Wright, AS. 1980. The role of metabolism in chemical mutagenesis and chemical carcinogenesis. Mutat Res., 75: 215-241.
80. Serafimova, R, Todorov, M, Pavlov, T, Kotov, S, Jacob, E, Aptula, A and Mekenyan, O. 2007. Identification of the structural requirements for mutagencitiy, by incorporating molecular flexibility and metabolic activation of chemicals. II. General Ames mutagenicity model. Chem. Res. Toxicol., 20: 662-676.
81. Connoly, M. 1983. Analytical molecular surface calculation. J. Apll. Cryst., 16: 548-558.
82. Sawatari, K, Nakanishi, Y and Matsushima, T. 2001. Relationships between chemical structures and mutagenicity: A preliminary survey for a database of mutagenicity test results of New Work place chemicals. Ind. Health, 39: 341-345.
83. International Agency for Research on Cancer (IARC), IARC Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Humans-Views and Expert Opinions of an IARC Working Group, Lyon, France, 1987 (Russian Ed.)
84. National Toxicology Program, software available at:http://ntp-apps.niehs.nih.gov/ntp_tox/index.cfm
85. Therman, E and Susman, M. 1993. Human Chromosomes: Structure, Behavior, and Effects, 3rd, Berlin: Springer-Verlag.
86. Obe, G, Pfeiffer, P, Savage, JR, Johannes, C, Goedecke, W, Jeppesen, P, Natarajan, AT, Martínez-López, W, Folle, GA and Drets, ME. 2002. Chromosomal aberrations: Formation, identification and distribution. Mutat. Res., 504: 17-36.
87. Degrassi, F, Fiore, M and Palitti, F. 2004. Chromosomal aberrations and genomic instability induced by topoisomerase-targeted antitumour drugs. Curr. Med. Chem.-Anti-Cancer Agents, 4: 317-325.
88. Ishidate, M Dr, Miura, KF and Sofuni, T. 1998. Chromosome aberration assays in genetic testing in vitro. Mutat. Res., 404: 167-172.
89. OECD. 1997. Guideline for the Testing of Chemicals: No. 473, In Vitro Mammalian Chromosomal Aberration Test, Paris: Organization for Economic Cooperation and Development.
90. Sofuni, T. (ed.), Data Book of Chromosomal Aberration Test In Vitro, Life-Science Information Center, Tokyo, Japan, Revised Edition, 1998
91. Mekenyan, O, Todorov, M, Serafimova, R, Stoeva, S, Aptula, A, Finking, R and Jacob, E. 2007. Identifying the structural requirements for chromosomal aberration by incorporating molecular flexibility and metabolic activation of chemicals. Chem. Res. Toxicol., 20: 1927-1941.
92. Hutt, AM and Kalf, GF. 1996. Inhibition of human DNA topoisomerase II by hydroquinone and p-benzoquinone, reactive metabolites of benzene. Environ. Health Perspect., 104: 1265-1269.
93. Freidig, AP, Verhaar, HJM and Hermens, JLM. 1999. Quantitative structure-property relationships for the chemical reactivity of acrylates and methacrylate. Environ. Toxicol. Chem., 18: 1133-1139.
94. Metz, B, Kersten, GFA, Hoogerhout, P, Brugghe, HF, Timmermans, HAM, de Jong, A, Meiring, H, ten Hove, J, Hennink, WE, Crommelin, DJA and Jiskoot, W. 2004. Identification of formaldehyde-induced modifications in proteins reactions with model peptides. J. Biol. Chem., 279: 6235-6243.
95. Gatto, B, Capranico, G and Palumbo, M. 1999. Drugs acting on DNA topoisomerases: Recent advances and future perspectives. Curr. Pharm. Des., 5: 195-215.
96. IRIS, Environmental Protection Agency, Methyl Acrylate (CASRN 96-33-3), 1990. Available athttp://www.epa.gov/iris/subst/0441.htm
97. RoC Background Document, Ethyl Acrylate, 1998. Available athttp://ntp.niehs.nih.gov/files/EthylAcryl.pdf
98. SIDS Initial Assessment Report. n-Butyl Acrylate, 2002. Available at http://www.inchem.org/documents/sids/sids/141322.pdf
99. Moore, MM, Amtower, A, Doerr, CL, Brock, KH and Dearfield, KL. 1988. Genotoxicity of acrylic acid, methyl acrylate, ethyl acrylate, methyl methacrylate, and ethyl methacrylate in L5178Y mouse lymphoma cells. Environ. Mol. Mutagen., 11: 49-63.
100. Benigni, R, Bossa, C and Worth, A. 2010. Structural analysis and predictive value of the rodent in vivo micronucleus assay results. Mutagenesis, 25: 335-341.
101. Patlewicz, G, Mekenyan, O, Dimitrova, G, Kuseva, C, Todorov, M, Kotov, S, Stoeva, S and Donner, EM. 2010. Can mutagenicity information be useful in an Integrated Testing Strategy (ITS) for skin sensitization?. SAR QSAR Environ. Res., 21: 619-656.
102. Furuya, K, Durie, P, Roberts, E and Soldin, S. 1995. Glycine Conjugation of Para-Aminobenzoic Acid (PABA): A Quantitative Test of Liver Function. Clin. Biochem., 28: 531-540.
103. Benigni, R, Bossa, C, Tcheremenskaia, O and Worth, A. Development of Structural Alerts for the in vivo Micronucleus Assay in Rodents, JRC Scientific and Tech. Rep. EUR 23844 EN-2009, 2009,pp. 1-42
104. WHO International Programme on Chemical Safety. Geneva, Epichlorohydrin, Environ. Health Criteria 33, 1984
105. Rossi, A, Migliore, L, Lascialfari, D, Sbrana, I, Loprieno, N, Tortoreto, M, Bidoli, F and Pantarotto, C. 1983. Genotoxicity, metabolism and blood kinetics of epichlorohydrin in mice. Mutat. Res., 118: 213-226.
106. Wirnitzer, U. 4-Amino-2-Hydroxytoluene (WR 23032)-Comet Assay in vivo in liver, stomach and urinary bladder epithelium male rat, BAYER AG, 2005 as cited in Opinion on SCIENTIFIC COMMITTEE ON CONSUMER PRODUCTS (SCCP) on 4-Amino-2-hydroxytoluene, COLIPA N° A27, 9th plenary meeting of 10 October 2006
107. Witt, K, Livanos, E, Kissling, G, Torous, D, Caspary, W, Tice, R and Recio, L. 2008. Comparison of flow cytometry- and microscopy-based methods for measuring micronucleated reticulocyte frequencies in rodents treated with nongenotoxic and genotoxic chemicals. Mutat. Res., 649: 101-113.
108. Hedtke, B, Gao, Z, Chen, L, Weber, W and Dix, K. 2008. Metabolism and disposition of 5-amino o-cresol in female F344 rats and B6C3F1 mice. Xenobiotica, 38: 171-184.
109. Daston, GP, Gooch, JW, Breslin, WJ, Shuey, DL, Nikiforov, AI, Fico, TA and Gorsuch, JW. 1997. Environmental estrogens and reproductive health: A discussion of the human and environmental data. Reprod. Toxicol., 11: 465-481.
110. Ing, N and O'Malley, B. 1995. "The steroid hormone receptor superfamily-Molecular mechanisms of action". In Molecular Endocrinology: Basic Concepts and Clinical Correlations, Edited by: Weintraub, B. 195-215. New York: Raven Press.
111. ICCVAM Final Report: ICCVAM Evaluation of In Vitro Test Methods for Detecting Potential Endocrine Disruptors: Estrogen receptor and androgen receptor binding and transcriptional activation assays, NIH Publication No: 03-4503, 2003
112. Serafimova, R, Todorov, M, Nedelcheva, D, Pavlov, T, Akahori, Y, Nakai, M and Mekenyan, O. 2007. QSAR and mechanistic interpretation of estrogen receptor binding. SAR QSAR Environ. Res., 18: 1-33.
113. Shelby, M, Newbold, R, Tully, D, Chae, K and Davis, V. 1996. Assessing environmental chemicals for estrogenicity using a combination of in vitro and in vivo assays. Environ. Health Perspect., 104: 1296-1300.
114. Mekenyan, O and Serafimova, R. 2009. "Mechanism based modeling of ER binding affinity: A COREPA implementation". In Endocrine Disruption Modeling, Edited by: Devillers, J. 259-294. France: CRC Press.
115. Katzenellenbogen, J. Effectiveness of QSAR for prescreening of endocrine disruptor hazard, SCOPE/IUPAC International Symposium on Endocrine Active Substances, Yokohama, Japan, 2002
116. Paterson, P and Fry, J. 1985. Influence of cytochrome P-450 type on the pattern of conjugation of 4-hydroxybiphenyl generated from biphenyl or 4-methoxybiphenyl. Xenobiotica, 15(6): 493-502.
117. OECD, The Report from the Expert Group on (Quantitative) Structure-Activity Relationships [(Q)SARs] on the Principles for the Validation of (Q)SARs, ENV/JM/TG(2004)27/REV, Organisation for Economic Cooperation and Development, Paris, 2004