Application of the adverse outcome pathway (AOP) approach to inform mode of action (MOA): A case study with inorganic arsenic

References

• Ahmed, S., K. B. Ahsan, M. Kippler, A. Mily, Y. Wagatsuma, A. M. Hoque, P. T. Ngom, S. El Arifeen, R. Raqib, and M. Vahter. 2012. In utero arsenic exposure is associated with impaired thymic function in newborns possibly via oxidative stress and apoptosis. Toxicological Sciences : an Official Journal of the Society of Toxicology 129:305–14. doi:10.1093/toxsci/kfs202.
   PubMed Web of Science ®Google Scholar
• Ahmed, S., S. Mahabbat-E Khoda, R. S. Rekha, R. M. Gardner, S. S. Ameer, S. Moore, E. C. Ekstrom, M. Vahter, and R. Raqib. 2011. Arsenic-associated oxidative stress, inflammation, and immune disruption in human placenta and cord blood. Environment Health Persp 119:258–64. doi:10.1289/ehp.1002086.
   PubMed Web of Science ®Google Scholar
• Andersen, M. E., H. J. Clewell III, and K. Krishnan. 1995. Tissue dosimetry, pharmacokinetic modeling, and interspecies scaling factors. Risk Analysis : an Official Publication of the Society for Risk Analysis 15:533–37.
   PubMed Web of Science ®Google Scholar
• Ankley, G. T., R. S. Bennett, R. J. Erickson, D. J. Hoff, M. W. Hornung, R. D. Johnson, D. R. Mount, J. W. Nichols, C. L. Russom, P. K. Schmieder, J. A. Serrrano, J. E. Tietge, and D. L. Villeneuve. 2010. Adverse outcome pathways: A conceptual framework to support eco-toxicology research and risk assessment. Environmental Toxicology and Chemistry / SETAC 29:730–41. doi:10.1002/etc.v29:3.
   PubMed Web of Science ®Google Scholar
• Aposhian, H. V., B. Zheng, M. M. Aposhian, X. C. Le, M. E. Cebrian, W. Cullen, R. A. Zakharzan, M. Ma, R. C. Dart, Z. Cheng, P. Andrewes, L. Yip, G. F. O’Malley, R. M. Maiorino, W. Van Voorhies, S. M. Healy, and A. Titcomb. 2000b. DMPS-arsenic challenge test. II. Modulation of arsenic species, including monomethylarsonous acid (MMA(III)), excreted in human urine. Toxicology and Applied Pharmacology 165:74–83. doi:10.1006/taap.2000.8922.
   PubMed Web of Science ®Google Scholar
• Aposhian, H. V., E. S. Gurzau, X. C. Le, A. Gurzau, S. M. Healy, S. Lu, M. Ma, L. Yip, R. A. Zakharyan, R. M. Maiorino, R. C. Dart, M. G. Tircus, D. Gonzalez-Ramirez, D. L. Morgan, D. Avram, and M. M. Aposhian. 2000a. Occurrence of monomethylarsonous acid in urine of humans exposed to inorganic arsenic. Chemical Research in Toxicology 13:693–97. doi:10.1021/tx000114o.
   PubMed Web of Science ®Google Scholar
• Berleth, E. S., E. M. Kasperek, S. P. Grill, J. A. Braunscheidel, L. A. Graziani, and C. M. Pickart. 1992. Inhibition of ubiquitin-protein ligase (E3) by mono- and bifunctional phenylarsenoxides. Evidence for essential vicinal thiols and a proximal nucleophile. The Journal of Biological Chemistry 267:16403–11.
   PubMed Web of Science ®Google Scholar
• Boobis, A. R., J. E. Doe, B. Heinrich-Hirsch, M. E. Meek, S. Munn, M. Ruchirawat, J. Schlatter, J. Seed, and C. Vickers. 2008. IPCS framework for analyzing the relevance of a noncancer mode of action for humans. Critical Reviews in Toxicology 38:87–96. doi:10.1080/10408440701749421.
   PubMed Web of Science ®Google Scholar
• Boobis, A. R., S. M. Cohen, V. Dellarco, D. McGregor, M. E. Meek, C. Vickers, D. Willcocks, and W. Farland. 2006. IPCS framework for analyzing the relevance of a cancer mode of action for humans. Critical Reviews in Toxicology 36:781–92. doi:10.1080/10408440600977677.
   PubMed Web of Science ®Google Scholar
• Bunderson, M., D. M. Brooks, D. L. Walker, M. E. Rosenfeld, J. D. Coffin, and H. D. Beall. 2004. Arsenic exposure exacerbates atherosclerotic plaque formation and increases nitrotyrosine and leukotriene biosynthesis. Toxicology and Applied Pharmacology 201:32–39. doi:10.1016/j.taap.2004.04.008.
   PubMed Web of Science ®Google Scholar
• Bunderson, M., J. D. Coffin, and H. D. Beall. 2002. Arsenic induces peroxynitrite generation and cyclooxygenase-2 protein expression in aortic endothelial cells: Possible role in atherosclerosis. Toxicology and Applied Pharmacology 184:11–18.
   PubMed Web of Science ®Google Scholar
• Burgess, J. L., M. Kurzius-Spencer, G. S. Poplin, S. R. Littau, M. J. Kopplin, S. Stürup, S. Boitano, and R. Clark Lantz. 2014. Environmental arsenic exposure, selenium and sputum alpha-1 antitrypsin. Journal of Exposure Science & Environmental Epidemiology 24:150–55. doi:10.1038/jes.2013.35.
   PubMed Web of Science ®Google Scholar
• Chen, Y., P. Factor-Litvak, G. R. Howe, J. H. Graziano, P. Brandt-Rauf, F. Parvez, A. Van Geen, and H. Ahsan. 2007. Arsenic exposure from drinking water, dietary intakes of B vitamins and folate, and risk of high blood pressure in Bangladesh: A population-based, cross-sectional study. American Journal of Epidemiology 165:541–52. doi:10.1093/aje/kwk037.
   PubMed Web of Science ®Google Scholar
• Clewell, H. J., H. J. Andersen, and B. J. Blaauboer. 2008. On the incorporation of chemical-specific information in risk assessment. Toxicology Letters 180:100–09. doi:10.1016/j.toxlet.2008.06.002.
   PubMed Web of Science ®Google Scholar
• Clewell, H. J., P. R. Gentry, H. A. Barton, A. M. Shipp, J. W. Yager, and M. E. Anderson. 1999. Requirements for a biologically realistic cancer risk assessment for inorganic arsenic. International Journal of Toxicology 18:131–47. doi:10.1080/109158199225701.
   Web of Science ®Google Scholar
• Clewell, H. J., R. S. Thomas, E. M. Kenyon, M. F. Hughes, B. M. Adair, P. R. Gentry, and J. W. Yager. 2011. Concentration- and time-dependent genomic changes in the mouse urinary bladder following exposure to arsenate in drinking water for up to 12 weeks. Toxicological Sciences : an Official Journal of the Society of Toxicology 123:421–32. doi:10.1093/toxsci/kfr199.
   PubMed Web of Science ®Google Scholar
• Cohen, S. M., A. Chowdhury, and L. L. Arnold. 2016. Inorganic arsenic: A non-genotoxic carcinogen. Journal Environment Sciences 49:28–37. doi:10.1016/j.jes.2016.04.015.
   Web of Science ®Google Scholar
• Cohen, S. M., L. L. Arnold, B. D. Beck, A. S. Lewis, and M. Eldan. 2013. Evaluation of the carcinogenicity of inorganic arsenic. Critical Reviews in Toxicology 43:711–52. doi:10.3109/10408444.2013.827152.
   PubMed Web of Science ®Google Scholar
• Dangleben, N., C. F. Skibol, and M. T. Smith. 2013. Arsenic immunotoxicity: A review. Environmental Health : a Global Access Science Source 12:73. doi:10.1186/1476-069X-12-73.
   PubMed Web of Science ®Google Scholar
• Ding, W., W. Liu, K. L. Cooper, X. J. Qin, P. L. De Souza Bergo, L. G. Hudson, and K. J. Liu. 2009. Inhibition of poly(ADP-ribose)polymerase-1 by arsenite interferes with repair of oxidative damage. The Journal of Biological Chemistry 284:6809–17. doi:10.1074/jbc.M805566200.
   PubMed Web of Science ®Google Scholar
• Dodmane, P. R., L. L. Arnold, K. L. Pennington, D. J. Thomas, and S. M. Cohen. 2013. Effect of dietary treatment with dimethylarsinous acid (DMAIII) on the urinary bladder epithelium of arsenic (+3 oxidation state) methyltransferase (As3mt) knockout and C57BL/6 wild type female mice. Toxicology 305:130–35. doi:10.1016/j.tox.2013.01.015.
   PubMed Web of Science ®Google Scholar
• Dybing, E. 2002. Development and implementation of the IPCS conceptual framework for evaluating mode of action of chemical carcinogens. Toxicology 181-182:121–25.
   PubMed Web of Science ®Google Scholar
• Farzan, S. F., S. Korrick, Z. Li, R. Enelow, A. J. Gandolfi, J. Madan, K. Nadeau, and M. R. Karagas. 2013. In utero arsenic exposure and infant infection in a United States cohort: A prospective study. Environmental Research 126:24–30. doi:10.1016/j.envres.2013.05.001.
   PubMed Web of Science ®Google Scholar
• Felix, K., S. K. Manna, K. Wise, J. Barr, and G. T. Ramesh. 2005. Low levels of arsenite activates nuclear factor-kappaB and activator protein-1 in immortalized mesencephalic cells. Journal of Biochemical and Molecular Toxicology 19:67–77. doi:10.1002/jbt.20062.
   PubMed Web of Science ®Google Scholar
• Foley, T. D., S. L. Melideo, A. E. Healey, E. J. Lucas, and J. A. Koval. 2011. Phenylarsine oxide binding reveals redox-active and potential vicinal thiols on the catalytic subunit of protein phosphatase 2A. Neurochemical Research 36:232–40. doi:10.1007/s11064-010-0310-4.
   PubMed Web of Science ®Google Scholar
• Ganapathy, S., S. Xiao, S. J. Seo, R. Lall, M. Yang, T. Xu, H. Su, M. Shadfan, C. S. Ha, and Z. M. Yuan. 2014. Low-dose arsenic induces chemotherapy protection via p53/nf-kb-mediated metabolic regulation. Oncogene 33:1359–66. doi:10.1038/onc.2013.81.
   PubMed Web of Science ®Google Scholar
• Gentry, P. R., H. J. Clewell III, T. B. Greene, A. C. Franzen, and J. W. Yager. 2014a. The impact of recent advances in research on arsenic cancer risk assessment. Reg Toxicogical Pharmacology 69:91–104. doi:10.1016/j.yrtph.2014.02.006.
   PubMed Web of Science ®Google Scholar
• Gentry, P. R., J. W. Yager, R. A. Clewell, and H. J. Clewell III. 2014b. Use of mode of action data to inform a dose-response assessment for bladder cancer following exposure to inorganic arsenic. Toxicology in Vitro : an International Journal Published in Association with BIBRA 28:1196–205. doi:10.1016/j.tiv.2014.05.011.
   PubMed Web of Science ®Google Scholar
• Gentry, P. R., T. B. McDonald, D. E. Sullivan, A. M. Shipp, J. W. Yager, and H. J. Clewell III. 2010. Analysis of genomic dose-response information on arsenic to inform key events in a mode of action for carcinogenicity. Environmental and Molecular Mutagenesis 51:1–14. doi:10.1002/em.20505.
   PubMed Web of Science ®Google Scholar
• Gu, L., Y. Okada, S. K. Clinton, C. Gerard, G. K. Sukhova, P. Libby, and B. J. Rollins. 1998. Absence of monocyte chemoattractant protein-1 reduces atherosclerosis in low density lipoprotein receptor–Deficient mice. Molecular Cell 2:275–81.
   PubMed Web of Science ®Google Scholar
• Harmon, M. E., J. Lewis, C. Miller, J. Hoover, A. S. Ali, C. Shuey, M. Cajero, S. Lucas, B. Pacheco, E. Erdei, S. Ramone, T. Nez, M. J. Campen, and M. Gonzales. 2018. Arsenic association with circulating oxidized Low-density lipoprotein in a Native American community. Journal of Toxicology and Environmental Health. Part A 81:535–48. doi:10.1080/15287394.2018.1443860.
   PubMed Web of Science ®Google Scholar
• Hernandez-Zavala, A., E. Cordova, L. M. Del Razo, M. E. Cebrian, and E. Garrido. 2005. Effects of arsenite on cell cycle progression in a human bladder cancer cell line. Toxicology 207:49–57. doi:10.1016/j.tox.2004.08.013.
   PubMed Web of Science ®Google Scholar
• Hershko, D. D., B. W. Robb, E. S. Hungness, G. Luo, and P. O. Hasselgren. 2002. Arsenite stabilizes IκBα and prevents NF-κB activation in IL-1 β-stimulated caco-2 cells independent of the heat shock response. Journal of Cellular Biochemistry 84:687–98.
   PubMed Web of Science ®Google Scholar
• Holsapple, M. P., H. C. Pitot, S. M. Cohen, A. R. Boobis, J. E. Klaunig, T. Pastoor, V. L. Dellarco, and Y. P. Dragan. 2006. Mode of action in relevance of rodent liver tumors to human cancer risk. Toxicological Sciences : an Official Journal of the Society of Toxicology 89:51–56. doi:10.1093/toxsci/kfj001.
   PubMed Web of Science ®Google Scholar
• Hsueh, Y.-M., P. Lin, H. W. Chen, H. S. Shiue, C. J. Chung, C. T. Tsai, Y. K. Huang, H. Y. Chiou, and C. J. Chen. 2005. Genetic polymorphisms of oxidative and antioxidant enzymes and arsenic-related hypertension. Journal of Toxicology and Environmental Health. Part A 68:1471–84. doi:10.1080/15287390590967414.
   PubMed Web of Science ®Google Scholar
• Hu, Y., L. Su, and E. T. Snow. 1998. Arsenic toxicity is enzyme specific and its effects on ligation are not caused by the direct inhibition of DNA repair enzymes. Mutation Research 408:203–18.
   PubMed Web of Science ®Google Scholar
• James, K. A., T. Byers, J. E. Hokanson, J. R. Meliker, G. O. Zerbe, and J. A. Marshall. 2015. Association between lifetime exposure to inorganic arsenic in drinking water and coronary heart disease in Colorado residents. Environment Health Persp 123:128–34. doi:10.1289/ehp.1307839.
   PubMed Web of Science ®Google Scholar
• Josyula, A. B., G. S. Poplin, M. Kurzius-Spencer, H. E. McClellen, M. J. Kopplin, S. Sturup, R. C. Lantz, and J. L. Burgess. 2006. Environmental arsenic exposure and sputum metalloproteinase concentrations. Environmental Research 102:283–90. doi:10.1016/j.envres.2006.01.003.
   PubMed Web of Science ®Google Scholar
• Kapahi, P., T. Takahashi, G. Natoli, S. R. Adams, Y. Chen, R. Y. Tsien, and M. Karin. 2000. Inhibition of NF-κB activation by arsenite through reaction with a critical cysteine in the activation loop of IκB kinase. The Journal of Biological Chemistry 275:36062–66. doi:10.1074/jbc.M007204200.
   PubMed Web of Science ®Google Scholar
• Karin, M., T. Takahashi, P. Kapahi, M. Delhase, Y. Chen, C. Makris, D. Rothwarf, V. Baud, G. Natoli, F. Guido, and N. Li. 2001. Oxidative stress and gene expression: The AP-1 and NF-κB connections. BioFactors (Oxford, England) 15:87–89.
   PubMed Web of Science ®Google Scholar
• Kenyon, E. M., M. F. Hughes, B. M. Adair, J. H. Highfill, E. A. Crecelius, H. J. Clewell III, and J. W. Yager. 2008. Tissue distribution and urinary excretion of inorganic arsenic and its methylated metabolites in C57BL6 mice following subchronic exposure to arsenate in drinking water. Toxicology and Applied Pharmacology 232:448–55. doi:10.1016/j.taap.2008.07.018.
   PubMed Web of Science ®Google Scholar
• Kitchin, K. T. 2001. Recent advances in arsenic carcinogenesis: Modes of action, animal model systems, and methylated arsenic metabolites. Toxicology and Applied Pharmacology 172:249–61. doi:10.1006/taap.2001.9157.
   PubMed Web of Science ®Google Scholar
• Kitchin, K. T., and K. Wallace. 2005. Arsenite binding to synthetic peptides based on the Zn finger region and the estrogen binding region of the human estrogen receptor-alpha. Toxicology and Applied Pharmacology 206:66–72. doi:10.1016/j.taap.2004.12.010.
   PubMed Web of Science ®Google Scholar
• Kitchin, K. T., and K. Wallace. 2008. The role of protein binding of trivalent arsenicals in arsenic carcinogenesis and toxicity. J Inorganic Biochem 102:532–39. doi:10.1016/j.jinorgbio.2007.10.021.
   PubMed Web of Science ®Google Scholar
• Laden, B. P., and T. D. Porter. 2001. Inhibition of human squalene monooxygenase by tellurium compounds: Evidence of interaction with vicinal sulfhydryls. Journal of Lipid Research 42:235–40.
   PubMed Web of Science ®Google Scholar
• Le, X. C., M. Ma, X. Lu, W. R. Cullen, H. V. Aposhian, and B. Zheng. 2000. Determination of monomethylarsonous acid, a key arsenic methylation intermediate, in human urine. Environment Health Persp 108:1015–18. doi:10.1289/ehp.001081015.
   PubMed Web of Science ®Google Scholar
• Lee, P. C., I. C. Ho, and T. C. Lee. 2005. Oxidative stress mediates sodium arsenite-induced expression of heme oxygenase-1, monocyte chemoattractant protein-1, and interleukin-6 in vascular smooth muscle cells. Toxicological Sciences : an Official Journal of the Society of Toxicology 85:541–50. doi:10.1093/toxsci/kfi101.
   PubMed Web of Science ®Google Scholar
• Li, J. H., and T. G. Rossman. 1989. Inhibition of DNA ligase activity by arsenite: A possible mechanism of its comutagenesis. Molecular Toxicology 2:1–9.
   PubMedGoogle Scholar
• Ling, M., Y. Li, Y. Xu, Y. Pang, L. Shen, R. Jiang, Y. Zhao, X. Yang, J. Zhang, J. Zhou, X. Wang, and Q. Liu. 2012. Regulation of miRNA-21 by reactive oxygen species-activated ERK/NF-κB in arsenite-induced cell transformation. Free Radical Biology & Medicine 52:1508–18. doi:10.1016/j.freeradbiomed.2012.02.020.
   PubMed Web of Science ®Google Scholar
• Lynch, H. N., K. Zu, E. M. Kennedy, T. Lam, X. Liu, D. M. Pizzurro, C. T. Loftus, and L. R. Rhomberg. 2017. Quantitative assessment of lung and bladder cancer risk and oral exposure to inorganic arsenic: Meta-regression analyses of epidemiological data. Environment International 106:178–206. doi:10.1016/j.envint.2017.04.008.
   PubMed Web of Science ®Google Scholar
• Lynn, S., H. T. Lai, J. R. Gurr, and K. Y. Jan. 1997. Arsenite retards DNA break rejoining by inhibiting DNA ligation. Mutagenesis 12:353–58.
   PubMed Web of Science ®Google Scholar
• Mahieu, P., J. P. Buchet, H. Roels, and R. Lauwerys. 1981. The metabolism of arsenic in humans acutely intoxicated by As2O3: Its significance for the duration of BAL therapy. Clinical Toxicology 18:1067–75. doi:10.3109/15563658108990336.
   PubMed Web of Science ®Google Scholar
• Mathas, S., A. Lietz, M. Janz, M. Hinz, F. Jundt, C. Scheidereit, K. Bommert, and B. Dorken. 2003. Inhibition of NF-κB essentially contributes to arsenic-induced apoptosis. American Social Hematology 102:1028–34.
   Google Scholar
• Meek, M. E., A. Boobis, I. Cote, V. Dellarco, G. Fotakis, S. Munn, J. Seed, and C. Vickers. 2014. New developments in the evolution and application of the WHO/IPCS framework on mode of action/species concordance analysis. Journal of Applied Toxicology : JAT 34:1–18. doi:10.1002/jat.2949.
   PubMed Web of Science ®Google Scholar
• Meek, M. E., J. R. Bucher, S. M. Cohen, V. Dellarco, R. N. Hill, L. D. Lehman-McKeeman, D. G. Longfellow, T. Pastoor, J. Seed, and D. E. Patton. 2003. A framework for human relevance analysis of information on carcinogenic modes of action. Critical Reviews in Toxicology 33:591–653. doi:10.1080/713608373.
   PubMed Web of Science ®Google Scholar
• Moon, K. A., E. Guallar, J. G. Umans, R. B. Devereux, L. G. Best, K. A. Francesconi, W. Goessler, J. Pollak, E. K. Silbergeld, B. V. Howard, and A. Navas-Acien. 2013. Association between exposure to low to moderate arsenic levels and incident cardiovascular disease: A prospective cohort study. Annals of Internal Medicine 159:649–59. doi:10.7326/0003-4819-159-10-201311190-00719.
   PubMed Web of Science ®Google Scholar
• NRC. 2013. Critical Aspects of EPA’s IRIS Assessment of Inorganic Arsenic: Interim Report. Washington, DC: National Research Council. National Academy Press.
   Google Scholar
• O’Bryant, S. E., M. Edwards, C. V. Menon, G. Gong, and R. Barber. 2011. Long-term low-level arsenic exposure is associated with poorer neuropsychological functioning: A Project FRONTIER study. International Journal of Environmental Research and Public Health 8:861–74. doi:10.3390/ijerph8030861.
   PubMed Web of Science ®Google Scholar
• OECD. 2013. Guidance document on developing and accessing adverse outcome pathways. In Series on Testing and Assessment, No. 184, Vol. ENV/JM/MONO (20136, p. 45. Organization for Economic Cooperation and Development, Environment Directorate Paris, France.
   Google Scholar
• OECD. 2018. Users’ handbook supplement to the guidance document developing and accessing AOPs. Series on Testing & Assessment No. 233. Series on Adverse Outcome Pathways No.1. Organization for Economic Cooperation and Development, Environment Directorate Paris, France. ENV/JM/MONO(2016)12.
   Google Scholar
• Parrish, A. R., X. H. Zheng, K. D. Turney, H. S. Younis, and A. J. Gandolfi. 1999. Enhanced transcription factor DNA binding and gene expression induced by arsenite or arsenate in renal slices. Toxicological Sciences : an Official Journal of the Society of Toxicology 50:98–105.
   PubMed Web of Science ®Google Scholar
• Pesola, G. R., F. Parvez, Y. Chen, A. Ahmed, R. Hasan, and H. Ahsan. 2012. Arsenic exposure from drinking water and dyspnoea risk in Araihazar, Bangladesh: A population-based study. The European Respiratory Journal 39:1076–83. doi:10.1183/09031936.00042611.
   PubMed Web of Science ®Google Scholar
• Pi, J., B. A. Diwan, Y. Sun, J. Liu, W. Qu, Y. He, M. Styblo, and M. P. Waalkes. 2008. Arsenic-induced malignant transformation of human keratinocytes: Involvement of Nrf2. Free Radical Biology & Medicine 45:651–58. doi:10.1016/j.freeradbiomed.2008.05.020.
   PubMed Web of Science ®Google Scholar
• Qin, X. J., W. Liu, Y. N. Li, X. Sun, C. X. Hai, L. G. Hudson, and K. J. Liu. 2012. Poly(ADPribose)polymerase-1 inhibition by arsenite promotes the survival of cells with unrepaired DNA lesions induced by UV exposure. Toxicological Sciences : an Official Journal of the Society of Toxicology 127:120–29. doi:10.1093/toxsci/kfs099.
   PubMed Web of Science ®Google Scholar
• Rahman, A., M. Vahter, E. C. Ekström, and L. A. Persson. 2011. Arsenic exposure in pregnancy increases the risk of lower respiratory tract infection and diarrhea during infancy in Bangladesh. Environment Health Persp 119:719–24. doi:10.1289/ehp.1002265.
   PubMed Web of Science ®Google Scholar
• Raqib, R., S. Ahmed, R. Sultana, Y. Wagatsuma, D. Mondal, A. M. Hoque, B. Nermell, M. Yunus, S. Roy, L. A. Persson, S. E. Arifeen, S. Moore, and M. Vahter. 2009. Effects of in utero arsenic exposure on child immunity and morbidity in rural Bangladesh. Toxicology Letters 185:197–202. doi:10.1016/j.toxlet.2009.01.001.
   PubMed Web of Science ®Google Scholar
• Rippa, M., T. Bellini, M. Signorini, and F. Dallocchio. 1981. Evidence for multiple pairs of vicinal thiols in some proteins. The Journal of Biological Chemistry 256:451–55.
   PubMed Web of Science ®Google Scholar
• Rossman, T. G., A. N. Uddin, F. J. Burns, and M. C. Bosland. 2002. Arsenite cocarcinogenesis: An animal model derived from genetic toxicology studies. Environment Health Persp 110:749–52. doi:10.1289/ehp.02110s5749.
   PubMed Web of Science ®Google Scholar
• Sarkozi, K., A. Papp, E. Horvath, Z. Mate, A. Ferencz, E. Hermesz, J. Krisch, E. Paulik, and A. Szabo. 2016. Green tea and vitamin C ameliorate some neurofunctional and biochemical signs of arsenic toxicity in rats. Nutritional Neuroscience 19:102–09. doi:10.1179/1476830514Y.0000000151.
   PubMed Web of Science ®Google Scholar
• Sasaki, A., Y. Oshima, and A. Fujimura. 2007. An approach to elucidate potential mechanism of renal toxicity of arsenic trioxide. Experimental Hematology 35:252–62. doi:10.1016/j.exphem.2006.10.004.
   PubMed Web of Science ®Google Scholar
• Schieffer, B., T. Selle, A. Hilfiker, D. Hilfiker-Kleiner, K. Grote, U. J. F. Tietge, C. Trautwein, M. Luchtefeld, M. S. Schmittkamp, S. Heeneman, M. J. A. P. Daemen, and H. Drexler. 2004. Impact of Interleukin-6 on plaque development and morphology in experimental atherosclerosis. Circulation 110:3493–500. doi:10.1161/01.CIR.0000148135.08582.97.
   PubMed Web of Science ®Google Scholar
• Smith, A. H., G. Marshall, Y. Yuan, C. Ferreccio, J. Liaw, O. Von Ehrenstein, C. Steinmaus, M. N. Bates, and S. Selvin. 2006. Increased mortality from lung cancer and bronchiectasis in young adults after exposure to arsenic in utero and in early childhood. Environment Health Persp 114:1293–96. doi:10.1289/ehp.8832.
   PubMed Web of Science ®Google Scholar
• Snow, E., M. Shuliga, S. Chouchane, and Y. Hu. 2001. Sub-toxic arsenite induces a multi-component protective response against oxidative stress in human cells. Jun. 18-22, 2000 San Diego, California: 265–75. Elsevier Science Ltd.
   Google Scholar
• Snow, E. T., P. Sykora, T. R. Durham, and C. B. Klein. 2005. Arsenic, mode of action at biologically plausible low doses: What are the implications for low dose cancer risk?. Toxicology and Applied Pharmacology 207 (2 Suppl):557–64. doi:10.1016/j.taap.2005.01.048.
   PubMedGoogle Scholar
• Sonich-Mullin, C., R. Fielder, J. Wiltse, K. Baetcke, J. Dempsey, P. Fenner-Crisp, D. Grant, M. Hartley, A. Knaap, D. Kroese, I. Mangelsdorf, E. Meek, J. M. Rice, and M. Younes, the International Programme on Chemical Safety. 2001. IPCS conceptual framework for evaluating a mode of action for chemical carcinogenesis. Reg Toxicogical Pharmacology 34: 146–52. doi: 10.1006/rtph.2001.1493.
   PubMed Web of Science ®Google Scholar
• States, J. C., S. Srivastava, Y. Chen, and M. Barchowsky. 2009. Arsenic and cardiovascular disease. Toxicological Sciences : an Official Journal of the Society of Toxicology 107:312–23. doi:10.1093/toxsci/kfn236.
   PubMed Web of Science ®Google Scholar
• Sykora, P., and E. T. Snow. 2008. Modulation of DNA polymerase beta-dependent base excision repair in cultured human cells after low dose exposure to arsenite. Toxicology and Applied Pharmacology 228:385–94. doi:10.1016/j.taap.2007.12.019.
   PubMed Web of Science ®Google Scholar
• Thompson, D. J. 1993. A chemical hypothesis for arsenic methylation in mammals. Chem-Biol Interact 88:89–114.
   PubMed Web of Science ®Google Scholar
• Tokar, E. J., B. A. Diwan, J. M. Ward, D. A. Delker, and M. P. Waalkes. 2011. Carcinogenic effects of whole life exposure to inorganic arsenic in CD1 mice. Toxicological Sciences : an Official Journal of the Society of Toxicology 119:73–83. doi:10.1093/toxsci/kfq315.
   PubMed Web of Science ®Google Scholar
• Tsai, S.-M., T. N. Wang, and Y. C. Ko. 1998. Cancer mortality trends in a blackfoot disease endemic community of Taiwan following water source replacement. Journal of Toxicology and Environmental Health. Part A 55:389–404. doi:10.1080/009841098158322.
   PubMed Web of Science ®Google Scholar
• Tseng, H. P., Y. H. Wang, M. M. Wu, H. W. The, H. Y. Chiou, and C. J. Chen. 2006. Association between chronic exposure to arsenic and slow nerve conduction velocity among adolescents in Taiwan. Journal Health, Population, Nutritional 24:182–89.
   PubMed Web of Science ®Google Scholar
• Tsou, T. C., F. Y. Tsai, M. C. Wu, and L. W. Chang. 2003. The protective role of NF-κB and AP-1 in arsenite-induced apoptosis in aortic endothelial cells. Toxicology and Applied Pharmacology 191:177–87.
   PubMed Web of Science ®Google Scholar
• Tsuda, T., A. Babazono, E. Yamamoto, N. Kurumatani, Y. Mino, T. Ogawa, Y. Kishi, and H. Aoyama. 1995. Ingested arsenic and internal cancer: A historical cohort study followed for 33 years. American Journal of Epidemiology 141:198–209.
   PubMed Web of Science ®Google Scholar
• USEPA. 2005. Guidelines for Carcinogen Risk Assessment. EPA/630/P-03/001B. Washington, DC: United States Forum.
   Google Scholar
• USEPA. 2018. Arsenic, inorganic CASRN 7440- 28-2.United States Environmental Protection Agency. https://cfpub.epa.gov/ncea/iris2/chemicalLanding.cfm?substance_nmbr=278#tab-2 Accessed on: July 2018
   Google Scholar
• Vahter, M. 1994. Species differences in the metabolism of arsenic. In Arsenic Exposure and Health, eds W. R. Chappell, C. O. Abernathy, and C. R. Cothern, 171–80. Northwood, United Kingdom: Science and Technology Letters.
   Google Scholar
• Vahter, M., and J. Envall. 1983. In vivo reduction of arsenate in mice and rabbits. Environmental Research 32:14–24.
   PubMed Web of Science ®Google Scholar
• Villeneuve, D. L., D. Crump, N. Garcia-Reyero, M. Hecker, T. H. Hutchinson, C. A. LaLone, B. Landesmann, T. Lettieri, S. Munn, M. Nepelska, M. A. Ottinger, L. Vergauwen, and M. Whelan. 2014a. Adverse outcome pathway (AOP) development I: Strategies and principles. Toxicological Sciences : an Official Journal of the Society of Toxicology 142:312–20. doi:10.1093/toxsci/kfu199.
   PubMed Web of Science ®Google Scholar
• Villeneuve, D. L., D. Crump, N. Garcia-Reyero, M. Hecker, T. H. Hutchinson, C. A. LaLone, B. Landesmann, T. Lettieri, S. Munn, M. Nepelska, M. A. Ottinger, L. Vergauwen, and M. Whelan. 2014b. Adverse outcome pathway development II: Best practices. Toxicological Sciences : an Official Journal of the Society of Toxicology 142:321–30. doi:10.1093/toxsci/kfu200.
   PubMed Web of Science ®Google Scholar
• Walter, I., T. Schwerdtle, C. Thuy, J. L. Parsons, G. L. Dianov, and A. Hartwig. 2007. Impact of arsenite and its methylated metabolites on PARP-1 activity, PARP-1 gene expression and poly (ADP-Ribsoyl)ation in cultured human cells. DNA Repair 6:61–70. doi:10.1016/j.dnarep.2006.08.008.
   PubMed Web of Science ®Google Scholar
• Wang, X. J., Z. Sun, W. Chen, Y. Li, N. F. Villeneuve, and D. D. Zhang. 2008. Activation of Nrf2 by arsenite and monomethylarsonous acid is independent of Keap1-C151: Enhanced Keap1-Cul3 interaction. Toxicology and Applied Pharmacology 230:383–89. doi:10.1016/j.taap.2008.03.003.
   PubMed Web of Science ®Google Scholar
• Wasserman, G. A., X. Liu, N. J. Loiacono, J. Kline, P. Factor-Litvak, A. Van Geen, J. L. Mey, D. Levy, R. Abramson, A. Schwartz, and J. H. Graziano. 2014. A cross-sectional study of well water arsenic and child IQ in Maine schoolchildren. Environmental Health : a Global Access Science Source 13:23. doi:10.1186/1476-069X-13-23.
   PubMed Web of Science ®Google Scholar
• Wiencke, J. K., and J. W. Yager. 1992. Specificity of arsenite in potentiating cytogenetic damage induced by the DNA crosslinking agent diepoxybutane. Environmental and Molecular Mutagenesis 19:195–200.
   PubMed Web of Science ®Google Scholar
• Wu, M. M., H. Y. Chiou, I. C. Ho, C. J. Chen, and T. C. Lee. 2003. Gene expression of inflammatory molecules in circulating lymphocytes from arsenic-exposed human subjects. Environment Health Persp 111:1429–38. doi:10.1289/txg.6396.
   PubMed Web of Science ®Google Scholar
• Xue, P., Y. Hou, Q. Zhang, C. G. Woods, K. Yarborough, H. Liu, G. Sun, M. E. Andersen, and J. Pi. 2011. Prolonged inorganic arsenite exposure suppresses insulin-stimulated AKT S473 phosphorylation and glucose uptake in 3T3-L1 adipocytes: Involvement of the adaptive antioxidant response. Biochemical and Biophysical Research Communications 407:360–65. doi:10.1016/j.bbrc.2011.02.138.
   PubMed Web of Science ®Google Scholar
• Yadav, R. S., R. K. Shukla, M. L. Sankhwar, D. K. Patel, R. W. Ansari, A. B. Pant, F. Islam, and V. K. Khanna. 2010. Neuroprotective effect of curcumin in arsenic-induced neurotoxicity in rats. Neurotoxicology 31:533–39. doi:10.1016/j.neuro.2010.05.001.
   PubMed Web of Science ®Google Scholar
• Yager, J. W., and J. K. Wiencke. 1993. Enhancement of chromosomal damage by arsenic: Implications for mechanism. Environment Health Persp 101 (Suppl 3):79–82. doi:10.1289/ehp.93101s379.
   PubMedGoogle Scholar
• Yager, J. W., and J. K. Wiencke. 1997. Inhibition of poly (ADP-ribose) polymerase by arsenite. Mutation Research 386:345–51.
   PubMed Web of Science ®Google Scholar
• Yager, J. W., P. R. Gentry, R. S. Thomas, L. Pluta, A. Efremenko, M. Black, A. Arnold, J. McKim, P. Wilga, G. Gill, K. Y. Choe, and H. J. Clewell III. 2013. Evaluation of gene expression changes in human primary uroepithelial cells following 24-hr exposures to inorganic arsenic and its methylated metabolites. Environmental and Molecular Mutagenesis 54:82–98. doi:10.1002/em.21749.
   PubMed Web of Science ®Google Scholar
• Yang, C-Y., C-C. Chang, S-C. Ho, and H-F. Chiu. 2008. Is colon cancer mortality related to arsenic exposure?. Journal Of Toxicology and Environmental Health, Part A 71 (8):533–538. doi:10.1080/15287390801907509.
   PubMed Web of Science ®Google Scholar
• Yuan, L., X. Yuan, M. Ling, Y. Yang, S. Wang, Z. Li, J. Zhou, X. Wang, and Q. Liu. 2010. Mot-2-mediated cross talk between nuclear factor-κB and p53 is involved in arsenite-induced tumorgenesis of human embryo lung fibroblast cells. Environment Health Persp 118:936–42. doi:10.1289/ehp.0901677.
   PubMed Web of Science ®Google Scholar
• Zhan, L., H. Zhang, Q. Zhang, C. G. Woods, Y. Chen, P. Xue, J. Dong, E. J. Tokar, Y. Xu, Y. Hou, J. Fu, K. Yarhorough, A. Wang, W. Qu, M. P. Waalkes, M. E. Anderson, and J. Pi. 2012. Regulatory role of KEAP1 and NRF2 in PPARγ expression and chemoresistance in human non-small-cell lung carcinoma cells. Free Radical Biology & Medicine 53:758–68. doi:10.1016/j.freeradbiomed.2012.05.041.
   PubMed Web of Science ®Google Scholar
• Zhao, L., S. Chen, L. Jia, S. Shu, P. Zhu, and Y. Liu. 2012. Selectivity of arsenite interaction with zinc finger proteins. Metallomics 4:988–94. doi:10.1039/c2mt20090b.
   PubMed Web of Science ®Google Scholar
• Zhou, L. F., Y. Zhu, X. F. Cui, W. P. Xie, A. H. Hu, and K. S. Yin. 2006. Arsenic trioxide, a potent inhibitor of NF-κB, abrogates allergen-induced airway hyperresponsiveness and inflammation. Resp Researcher 7:146. doi:10.1186/1465-9921-7-146.
   PubMed Web of Science ®Google Scholar
• Zhou, X., X. Sun, K. L. Cooper, F. Wang, K. J. Liu, and L. G. Hudson. 2011. Arsenite interacts selectively with zinc finger proteins containing C3H1 or C4 motifs. The Journal of Biological Chemistry 286:22855–63. doi:10.1074/jbc.M111.232926.
   PubMed Web of Science ®Google Scholar