Arsenic risk assessment scope and planning.

Arsenic – Stakeholder recommendations regarding US EPA’s Toxicological Review of Inorganic Arsenic – Scoping and Planning

These recommendations are respectfully submitted to the US EPA and NAS Arsenic Toxicology Review Panel by the following: Dr Kathleen Burns and Dr Micheal Harbut

Our written comments submitted at the January 8-9 US EPA arsenic stakeholder meeting titled “Toxicological Review of Arsenic Must Include Consideration of Disproportionately High Rates of Cardiovascular Disease in African Americans” are being submitted with these recommendations. The following recommendations are brief summaries on issues we consider important to the arsenic risk assessment scope and planning.  Most are also more broadly relevant to the IRIS evaluations of all hazardous chemicals. We make these recommendations based on our experience in toxicology, epidemiology, risk assessment, public health, and medicine, with the goal of obtaining more informative, public health-oriented, and scientifically current toxicological reviews from US EPA. We will provide additional technical information and citations related to these issues when we submit recommendations regarding technical aspects that are scheduled by US EPA to be addressed in the near future.

 Recognition of the Use of EPA’s IRIS assessments worldwide & the implications for scope  IRIS evaluations are used across the US and in other countries as a key source of information on qualitative and quantitative aspects of hazardous chemicals. They are relied upon by public health, occupational and environmental agencies, scientists and health professionals, and industry and advocates. Information that is not included regarding health may not be considered. 

A common misconception is that IRIS files list all potential human health effects, which was neither the intent nor the actual content of such documents. However, the current use of IRIS files suggests that specific language and technical content could substantially improve the utility and appropriate use of IRIS assessments^[1].  This is especially true for arsenic, which is of high national and international concern.  EPA’s arsenic assessment will inevitably be widely relied upon as being highly authoritative.

Inclusion of Information Explicit information on the types of information that are included and excluded should be offered upfront, with links to other sources for information that is not included (e.g., medical guidance, clinical testing for identified health problems, susceptibility aspects that aren’t covered).  Since the sources of such information will be largely consistent across chemicals, this would impose a minimal time burden.

It is important that IRIS evaluations provide a scientifically complete picture of the range of adverse health effects and related science for all impacts that may be relevant to public health and regulatory actions.  This should include discussions and citations for well-established adverse effects and a summary of emerging scientific evidence on likely or potentially relevant effects.  In the specific case of arsenic, the rapid acceleration in the publication of epidemiological, toxicological, and mechanistic science has resulted in many new health concerns since 2000, especially in the last 5 years.  It has also confirmed previously “suspected” effects and provided extensive supporting mechanistic and other evidence.

We expect the IRIS assessment will provide detail on a single or few sensitive noncancer endpoints for quantification (e.g., hypertension).  Recent scientific evidence supports examination and discussion of the issue of when exposure occurs, and that should include an emphasis on protections required during particular life stages.  For example, a review of the impacts of arsenic on early-life exposure by Boekelheide et al (2012) found an association with increased risk of cardiovascular disease later in life.^[2] The study authors suggest that their data and approaches can inform risk assessment and we recommend that this be carefully evaluated, with reliance on this and other information.

In addition to those health endpoints chosen for quantitative evaluation, it is important that the IRIS evaluation include discussions of other health effects and physiological perturbations with potential public health impacts (e.g., neurotoxicity, developmental harm, endocrine disruption, adverse impacts on male reproductive capacity).  A general discussion of the ranges of exposure that may incur such effects, appropriately caveated, would be valuable to the public health and scientific communities, even in the absence of the ability to provide definitive quantification of exposure and outcome.

Acute exposure considerations & use of normative assumptions.  In some cases, inclusion of acute toxicity information may be warranted.  Due to the prevalence of arsenic and some other naturally occurring hazards, oral, inhalation and dermal exposure at elevated levels are possible, and may occur in individuals with considerable susceptibility (e.g., newborns, people with existing diseases related to those caused by arsenic, or other chemicals with toxic effects similar to those of arsenic).  Toxicological reviews do not explicitly address exposure, but must consider it to determine if acute exposure effects are possible in highly exposed susceptible populations.

Reliance on the 95^th percentile for exposure assessment must be revisited to address its potential for exclusion of substantial numbers of people.  Normative assumptions and reliance on a “normal” distribution inherently ignore exposures of up to 5% of a population of over 300 million people, thereby “accepting” serious health risks to a very large number of people.

People highly exposed to waterborne contaminants are often in poorer communities.  Infants who receive the least costly formula – powdered milk mixed with tap water – are in the highest exposure groups for water contaminants, as are infants with health problems, low birth weight, or who suffer dehydration due to common illnesses.  They consume far more water in relation to their body weight than is accounted for in normative approaches to exposure and their consumption could incur acute toxicity at water contamination levels considered “acceptable” for a healthy adult.  They easily exceed a reference dose calculated based on normative assumptions.

Likewise people who work in jobs involving manual labor or outdoor work or who lack air conditioning in hot climates consumer more water, but cannot elect to consume less water.  They are placed in jeopardy by insufficient risk calculations and inadequately protective standards.  We recommend that the IRIS assessments include: 1) explicit discussion of the range of exposures under plausible worst case scenarios, 2) discussion of the potential health effects that may occur as a result of those elevated exposures, and 3) directions on accessing appropriate health guidance if acute exposure is suspected.

 Mixtures of Chemicals  EPA has discussed and provided some guidance on this difficult problem.  There are potentially an infinite number of combinations of chemicals.  However, it is common to have multiple toxic heavy metals in soil, air, or water, due to their natural and anthropogenic sources (e.g., fuel combustion).  Consequently, it is necessary to have specific guidance on methods to address the assessment of toxicity when multiple heavy metals and/or other hazardous chemicals are present in order to prevent underestimation of effects or insufficiently protective policies.

Consideration of the combination of toxic heavy metals that are likely to occur in combination with arsenic is especially important for noncarcinogenic effects because the current risk assessment paradigm does not easily adapt to consideration of mixtures.  Most toxic heavy metals target the same organ systems, though their potency varies by organ and cell type, and the nature of the evidence varies (i.e., the outcomes being measured).  In spite of the difficult, it is clear that a health-protective approach to this is essential.  The combined exposures impacting the nervous system, liver, kidneys, and other organ systems at ostensibly “safe” levels may pose serious health risks.

We recommend that the IRIS assessment explicitly point out the need to evaluate concurrent exposures to other toxic heavy metals (and possibly other commonly encountered chemicals with similar target organs) when determining appropriate public policies and public health responses.  EPA should quickly incorporate a simple mathematical model in IRIS assessments to assist users in making prudent public health judgments, due to the prevalence of multiple heavy metal contamination across the US.

Use of existing public health data to inform toxicological reviews. As noted in our submission for the January 8-9 meeting, health sciences are sophisticated in their elucidation of both at risk populations and the underlying mechanisms for those increased risks.  Health statistics should be used to inform toxicological reviews and quantitative risk assessments when it suggests fundamental elevated-risk populations that are likely to be impacted by exposure to an agent. Epidemiological studies, health databases, and other sources documenting pre-existing elevated risks should be utilized to modify the qualitative evaluations of chemicals that are likely to exacerbate those risks.  Morbidity distributions can be used to inform the likelihood of reaching an adverse tipping point and adjust estimates of safe exposure, rather than reliance on simplistic “safety factors”.

The extensive health documentation on cardiovascular disease in African Americans and the unequivocal literature on arsenic’s cardiovascular impacts make this chemical an ideal candidate for the development of such an approach (see citations and brief discussion in our January 8^th submission to US EPA for the stakeholders meeting).  We highly recommend work on this issue due to both the critical public health need and the strong potential for improving the quality and length of life among a substantial portion of the US population through high quality scientific work to develop a scientifically-based approach to the problem.

 Database Review  Considerable concern was raised by US EPA staff at the January 8-9 meeting regarding the extensive nature of the arsenic database on health and related scientific issues.  The use of various systematics options was presented as “necessary”.  Two days later the NAS had an excellent two day meeting: “Integrating Environmental Health Data to Advance Discovery”.  The keynote and subsequent speakers emphasized the limited understanding we currently have of health and biology, the need to avoid over-simplification because so many fundamental dynamics are not understood, and some ways in which the challenge of extensive scientific data is being addressed.  EPA and other staff spoke at the meeting, which covered epidemiology, toxicology, clinical medicine, and other issues.  These fields and the meeting content were highly relevant to how the evaluation of arsenic is approached.

The juxtaposition of the approaches recommended by the two meetings could not be more strikingly different.  We believe the second is far more appropriate when approaching a complex chemical such as arsenic.  Many of the health hazards of arsenic that are well established were not being consider 20 years ago, and many new concerns are being substantiated by carefully designed experimental work.  More advances are expected.  Many connections across the evidence from different studies, fields of inquiry, and methods can be obtained through careful review of the health-related data on arsenic.  It is onerous, and we have provided a compilation of most of the studies from 2012 in Appendix A.  This was done to 1) illustrate the wide range of new information being generated and 2) emphasize the need for careful review.

Systematics as presented on January 8^th by US EPA relied on key words and other tricks-of-the-trade that sound logical, but have limited value in accessing the breadth of relevant science.  Investigation of chemical toxicity is an iterative process that requires considerable attention to detail, and the skills of well-trained toxicologists, epidemiologists, geneticists, and others to identify both the relevant information and make the connections between important related concepts.  This simply cannot be done by a computer model, no matter how carefully designed.

Our group includes people charged with reviewing all of the chemical toxicity data for US EPA’s 500 Toxics Release Inventory Chemicals.  Others carried out reviews of all of the published corporate and grey literature on chemicals comprising tens of thousands of pages.   So we do not recommend a human versus computer selection of key papers without understanding the difficulty of the task.  However, we believe that there is simply no replacement for well trained scientists’ selection of studies from the entire range of potentially relevant information.

Given the new arenas of knowledge in arsenic toxicity, especially at the subcellular level where new nomenclature is prevalent, it is very important to have scientists carrying out such work.  If US EPA requires additional time to be careful and comprehensive, then that should be provided, since the quality of the science matters far more than the month in which the evaluation is completed.

Genotoxicity Although these recommendations are largely on scoping and planning, the issue of genotoxicity was raised at the January 8-9 meeting.  Based on a review of the extensive scientific evidence available on inorganic arsenic, there is no doubt that arsenic is genotoxic.  It may be that past US EPA concerns regarding the implications for IRIS cancer potency values impacted their evaluation of the science, enabling them to avoid a protection factor for early life exposures which is necessary in this case. A positive genotoxicity conclusion is therefore likely to result in a higher cancer potency estimate and lower public health exposure limits (e.g., drinking water standards).  However, the scientific evidence is overwhelming at this point and should not be suppressed to achieve more politically palatable results. The implications of health science for policy should be deliberated outside of the IRIS process, after the best possible scientific evaluation is conducted.

We look forward to hearing what the NAS panel has to contribute regarding US EPA’s evaluation of arsenic and hope that our recommendations will be considered.

Disclosure: We did not receive any funding to develop these recommendations and have no financial conflicts of interest.  We each have conducted scientific and/or medical work related to arsenic and the assessment of health risks over many years.

Appendix A.  Health-relevant Studies of Arsenic Published in Peer Reviewed Journals in 2012.

This Appendix contains all potentially health-relevant publications that were retrieved during January 2013 from the National Library of Medicine via PubMed through a search with a single term: “arsenic”.  All papers were printed or published via e-pub during 2012.  Papers were excluded if they did not appear to be health related or focused primarily on the use of arsenic in cancer therapy, though the latter may be useful in IRIS evaluation. The wide ranging information on health and related scientific concepts that address arsenic’s toxicological actions are clear from a quick review of the paper topics.

In chronological order based on National Library of Medicine publication date.

Kunrath J, Gurzau E, Gurzau A, et al Blood pressure hyperreactivity: an early cardiovascular risk in normotensive men exposed to low-to-moderate inorganic arsenic in drinking water.  J Hypertens. 2013 Feb;31(2):361-9.

Lamm SH, Robbins SA, Zhou C, et al. Bladder/lung cancer mortality in Blackfoot-disease (BFD)-endemic area villages with low (<150μg/L) well water arsenic levels – An exploration of the dose-response Poisson analysis. Regul Toxicol Pharmacol. 2013 Feb;65(1):147-56.

Yadav S, Anbalagan M, Shi Y, et al. Arsenic inhibits the adipogenic  differentiation of mesenchymal stem cells by down-regulating peroxisome proliferator-activated receptor gamma and CCAAT enhancer-binding proteins. Toxicol In Vitro. 2013 Feb;27(1):211-9.

Stamatelos SK, Androulakis IP, Kong AN, et al A semi-mechanistic integrated toxicokinetic-toxicodynamic (TK/TD) model for arsenic(III) in hepatocytes. J Theor Biol. 2013 Jan 21;317:244-56.

Vitela-Rodriguez AV, Rangel-Mendez JR. Arsenic removal by modified activated  carbons with iron hydro(oxide) nanoparticles. J Environ Manage. 2013 Jan 15;114:225-31.

Macoch M, Morzadec C, Fardel O, et al. Inorganic arsenic impairs differentiation and functions of human dendritic cells. Toxicol Appl Pharmacol. 2013 Jan 15;266(2):204-13.

Chung CJ, Huang CY, Pu YS, et al. The effect of cigarette smoke and arsenic exposure on urothelial carcinoma risk is modified by glutathione S-transferase M1 gene null genotype. Toxicol Appl Pharmacol 2013 Jan 15;266(2):254-9.

Shiue I. Urinary environmental chemical concentrations and vitamin D are associated with vision, hearing, and balance disorders in the elderly. Environ Int. 2013 Jan 9;53C:41-46.

Bhattacharjee P, Banerjee M, Giri AK. Role of genomic instability in arsenic-induced carcinogenicity. A review. Environ Int. 2013 Jan 8;53C:29-40.

Wang Y, Zhao F, Liao Y, et al. Effects of arsenite in astrocytes on neuronal signaling transduction. Toxicology. 2013 Jan 7;303C:43-53.

Pogribny IP, Rusyn I. Environmental toxicants, epigenetics, and cancer. Adv Exp Med Biol. 2013;754:215-32.

Kathirgamanathan K, Angaran P, Lazo-Langner A, et al. Cardiac conduction block at multiple levels caused by arsenic trioxide therapy. Can J Cardiol. 2013  Jan;29(1):130.

Khan PK, Kesari VP, Kumar A. Mouse micronucleus assay as a surrogate to assess genotoxic potential of arsenic at its human reference dose. Chemosphere. 2013 Jan;90(3):993-7. Epub 2012 Aug 18.

Wu S, Deng F, Huang J, et al. Blood Pressure Changes and Chemical Constituents of Particulate Air Pollution: Results from the Healthy Volunteer Natural Relocation Study. Env Health Persp 2013 Jan;121(1):66-72. Epub Oct

Schlebusch, C; Lewis C; Vahter, M. et al. Possible positive selection for an arsenic-protective haplotype in humans. Environ Health Perspect. 2013 Jan;121(1):53-8. Epub 2012 Oct 16.

Amaya E, Gil F, Freire C. Placental concentrations of heavy metals in a mother-child cohort. Environ Res. 2013 Jan;120:63-70. Epub 2012 Nov 9.

Andra SS, Makris KC, Christophi CA . Delineating the degree of association between biomarkers of arsenic exposure and type-2 diabetes mellitus.  Int J Hyg Environ Health. 2013 Jan;216(1):35-49.

Kossowska B, Dudka I, Gancarz R. Application of classic epidemiological studies and proteomics in research of occupational and environmental exposure to lead, cadmium and arsenic. Int J Hyg Environ Health. 2013 Jan;216(1):1-7. Epub 2012 Apr 8

Jovanovic D, Rasic-Milutinovic Z, Paunovic K,. Low levels of arsenic in drinking water and type 2 diabetes in Middle Banat region, Serbia. Int J Hyg Environ Health. 2013 Jan;216(1):50-5. Epub 2012 Feb 11

Jin L, Zhang L, Li Z, Liu JM, Ye R, Ren A. Placental concentrations of mercury, lead, cadmium, and arsenic and the risk of neural tube defects in a Chinese population. Reprod Toxicol. 2013 Jan;35:25-31.EPub:  2012 Nov 16.

Pei Q, Ma N, Zhang J. Oxidative DNA damage of peripheral blood polymorphonuclear leukocytes, selectively induced by chronic arsenic exposure, is associated with extent of arsenic-related skin lesions. Toxicol Appl Pharmacol. 2013 Jan 1;266(1):143-9.  Epub 2012 Nov 8.

Samadder A, Das J, Das S.  Poly(lactic-co-glycolic) acid loaded nano-insulin has greater potentials of combating arsenic induced hyperglycemia in mice: Some novel findings. Toxicol Appl Pharmacol. 2012 Dec 29.

Chung CJ, Huang YL, Huang YK. Urinary arsenic profiles and the risks of cancer mortality: A population-based 20-year follow-up study in arseniasis-endemic areas in Taiwan. Environ Res. 2012 Dec 28.

Gupta DK, Inouhe M, Rodríguez-Serrano M. Oxidative stress and arsenic toxicity: Role of NADPH oxidases. Chemosphere. 2012  Dec 21

Douillet C, Currier J, Saunders J. Methylated trivalent arsenicals are potent inhibitors of glucose stimulated insulin secretion by murine pancreatic islets. Toxicol Appl Pharmacol. 2012 Dec 20;267(1):11-15.

Chen B, Liu J, Chang Q. JNK and STAT3 signaling pathways converge on Akt-mediated phosphorylation of EZH2 in bronchial epithelial cells induced by arsenic. Cell Cycle. 2012 Dec 19;12(1).

Liu Y, Hock JM, Van Beneden RJ et al. Aberrant overexpression of FOXM1 transcription factor plays a critical role in lung carcinogenesis induced by low  doses of arsenic. Mol Carcinog. 2012 Dec 19

Calatayud M, Vázquez M, Devesa V et al. In Vitro Study of Intestinal Transport of Inorganic and Methylated Arsenic Species by Caco-2/HT29-MTX Cocultures. Chem Res Toxicol. 2012 Dec 17;25(12):2654-62.

Saunders JE, Jastrzembski BG, Buckey JC. Hearing Loss and Heavy Metal Toxicity in a Nicaraguan Mining Community: Audiological Results and Case Reports. Audiol Neurootol. 2012 Dec 15;18(2):101-113.

Zheng Y, Tao S, Lian F.  Sulforaphane prevents pulmonary damage in response to inhaled arsenic by activating the Nrf2-defense response. Toxicol Appl Pharmacol. 2012 Dec 15;265(3):292-9.

Ljung Björklund K, Vahter M. Metals and trace element concentrations in breast milk of first time healthy mothers: a biological monitoring study. Environ Health. 2012 Dec 14;11(1):92.

Hawkesworth S, Wagatsuma Y, Kippler M. Early exposure to toxic metals has a limited effect on blood  pressure or kidney function in later childhood, rural Bangladesh. Int J Epidemiol. 2012 Dec 14.

Burgess J, Kurzius-Spencer M, O’Rourke M. Environmental arsenic exposure and serum matrix metalloproteinase-9. J Expo Sci Environ Epidemiol. 2012 Dec 12.

Wang X, Zhang J, Zhao L et al. Effect of subchronic exposure to arsenic on levels of essential trace elements in mice brain and its gender difference. Biometals. 2012 Dec 9.

Islam MR, Khan I, Attia J. Association between Hypertension and Chronic  Arsenic Exposure in Drinking Water: A Cross-Sectional Study in Bangladesh. Int J  Environ Res Public Health. 2012 Dec 7;9(12):4522-36.

Geier DA, Kern JK, King P. Hair toxic metal concentrations and autism spectrum disorder severity in young children. Int J Environ Res Public Health. 2012 Dec 6;9(12):4486-97.

Hou Y, Xue P, Woods C et al. Association between Arsenic Suppression of Adipogenesis and Induction of CHOP10 via the Endoplasmic Reticulum Stress Response. Environ Health Perspect. 2012 Dec 5.

Ivanov VN, Hei TK. Induction of apoptotic death and retardation of neuronal  differentiation of human neural stem cells by sodium arsenite treatment. Exp Cell Res. 2012 Dec 5.

Ramsey KA, Bosco A, McKenna K et al. In Utero Exposure to Arsenic Alters Lung Development and Genes Related to Immune and Mucociliary Function in Mice. Environ Health Perspect. 2012 Dec 4.

Rasmussen PE, Levesque C, Chénier M et al.  Canadian House Dust Study: Population-based concentrations, loads and loading rates of arsenic, cadmium, chromium, copper, nickel, lead, and zinc inside urban  homes. Sci Total Environ. 2012 Dec 4;443C:520-529.

Bhattacharya A, Dhar P, Mehra RD. Preliminary morphological and biochemical  changes in rat liver following postnatal exposure to sodium arsenite. Anat Cell Biol. 2012 Dec;45(4):229-40.

Yildiz D, Cakir Y. Efflux of glutathione and glutathione complexes from human erythrocytes in response to inorganic arsenic exposure. Biol Trace Elem Res. 2012 Dec;150(1-3):451-9.

Jain A, Flora GJ, Bhargava R, et al. Influence of age on arsenic-induced  oxidative stress in rat. Biol Trace Elem Res. 2012 Dec;149(3):382-90.

Falnoga I, Zelenik Pevec A, Šlejkovec Z et al. Arsenic trioxide (ATO) influences the gene expression of metallothioneins in human glioblastoma cells. Biol Trace Elem Res. 2012 Dec;149(3):331-9.

Xu ZP, Huo JM, Sang YL, et al. Effects of arsenic trioxide (As(2)O(3)) on airway remodeling in a murine model of bronchial asthma. Can J Physiol Pharmacol. 2012 Dec;90(12):1576-84.

Chervona Y, Hall MN, Arita A, et al. Associations between Arsenic Exposure and Global  Posttranslational Histone Modifications among Adults in Bangladesh. Cancer Epidemiol Biomarkers Prev. 2012 Dec;21(12):2252-60.

Liang YH, Li P, Zhao JX, et al. Arsenic trioxide regulates the production and activities of matrix metalloproteinases-1, -2, and -9 in fibroblasts and THP-1. Chin Med J (Engl). 2012 Dec;125(24):4481-7.

Moon K, Guallar E, Navas-Acien A. Arsenic exposure and cardiovascular disease: an updated systematic review. Curr Atheroscler Rep. 2012 Dec;14(6):542-55.

Maull EA, Ahsan H, Edwards J, et al. Evaluation of the Association between Arsenic and Diabetes: A National Toxicology Program Workshop Review. Environ Health Perspect. 2012 Dec;120(12):1658-70.

Zhao F, Wang Y, Jin Y, et al. Effects of exogenous methionine on arsenic burden and NO metabolism in brain of mice exposed to arsenite through drinking water. Environ Toxicol. 2012 Dec;27(12):700-6.

Selvaraj V, Yeager-Armstead M, Murray E. Protective and antioxidant role of  selenium on arsenic trioxide-induced oxidative stress and genotoxicity in the fish hepatoma cell line PLHC-1. Env Tox Chem. 2012 Dec;31(12):2861-9.

Song G, Cui Y, Han ZJ, et al. Effects of choline on sodium arsenite-induced neural tube defects in chick embryos. Food Chem Toxicol. 2012 Dec;50(12):4364-74.

Thomas-Schoemann A, Batteux F, Mongaret C, et al. Arsenic trioxide exerts  antitumor activity through regulatory T cell depletion mediated by oxidative stress in a murine model of colon cancer. J Immun. 2012. 189(11):5171-7.

Melkonian S, Argos M, Chen Y,et al. Intakes of several nutrients are associated with incidence of arsenic-related keratotic skin lesions in bangladesh. J Nutr. 2012 Dec;142(12):2128-34.

Prabu SM, Muthumani M. Silibinin ameliorates arsenic induced nephrotoxicity  by abrogation of oxidative stress, inflammation and apoptosis in rats. Mol Biol Rep. 2012 Dec;39(12):11201-16.

Kippler M, Wagatsuma Y, Rahman A, et al.  Environmental exposure to arsenic and cadmium during pregnancy and fetal size: A  longitudinal study in rural Bangladesh. Reprod Toxicol. 2012 Dec;34(4):504-11.

Liu C, Huang C, Huang C. Occupational neurotoxic diseases in Taiwan. Saf  Health Work. 2012 Dec;3(4):257-67.

Zhang T, Qi Y, Liao M, et al. Autophagy is a cell self-protective mechanism against arsenic-induced cell transformation. Toxicol Sci. 2012 Dec;130(2):298-308.

Anwar-Mohamed A, El-Sherbeni A, Kim S, et al. Acute arsenic toxicity alters cytochrome P450 and soluble epoxide hydrolase and their associated arachidonic acid metabolism in C57Bl/6 mouse heart. Xenobiotica 2012

Dec;42(12):1235-47.

Lee JY, Eom M, Yang J et al. Acute Kidney Injury by Arsine Poisoning: The Ultrastructural Pathology of the Kidney. Ren Fail. 2012 Nov 30.

Ríos R, Santoyo ME, Cruz D, et al. Methyl group balance in brain and liver: role of choline on increased S-adenosyl  methionine (SAM) demand by chronic arsenic exposure. Toxicol Lett. 2012 Nov 30;215(2):110-8.

Sherwood CL, Lantz RC, Boitano S. Chronic arsenic exposure in nanomolar concentrations compromises wound response and intercellular signaling in airway epithelial cells. Toxicol Sci. 2012 Nov 30.

Yager JW, Gentry PR, Thomas R, et al. Evaluation of gene expression changes in human primary uroepithelial cells following 24-Hr exposures to inorganic arsenic and its methylated metabolites. Environ Mol Mutagen. 2012 Nov 29.

Begum M, Horowitz J, Hossain MI. Low-Dose Risk Assessment for Arsenic: A Meta-Analysis Approach. Asia Pac J Public Health. 2012 Nov 27.

Feki-Tounsi M, Olmedo P, Gil F, et al. Low-level arsenic exposure is associated with bladder cancer risk and cigarette smoking: a case-control study among men in Tunisia. Environ Sci Pollut  Res Int. 2012 Nov 27.

Lau A, Whitman SA, Jaramillo MC, et al. Arsenic-Mediated Activation of the Nrf2-Keap1 Antioxidant Pathway. J Biochem Mol Toxicol. 2012 Nov 27.

Deb D, Biswas A, Ghose A, et al. Nutritional  deficiency and arsenical manifestations: a perspective study in an arsenic-endemic region of West Bengal, India. Public Health Nutr. 2012 Nov 27:1-12.

Hartwig A. Metal interaction with redox regulation: an integrating concept in metal carcinogenesis? Free Radic Biol Med. 2012 Nov 23;55C:63-72.

Wu CH, Tseng YS, Kao Y, et al. Low concentration of arsenic induced aberrant mitosis in keratinocytes through E2F1 transcriptionally regulated Aurora-A. Toxicol Sci. 2012 Nov 22.

Vineetha VP, Prathapan A, Soumya R, et al. Arsenic Trioxide Toxicity in  H9c2 Myoblasts-Damage to Cell Organelles and Possible Amelioration with Boerhavia diffusa. Cardiovasc Toxicol. 2012 Nov 19.

Tokar EJ, Person RJ, Sun Y, et al. Chronic Exposure of Renal Stem Cells to Inorganic Arsenic Induces a Cancer Phenotype. Chem Res Toxicol. 2012 Nov 19.

Calatayud M, Vélez D, Devesa V. Metabolism of inorganic arsenic in intestinal epithelial cell lines. Chem Res Toxicol. 2012 Nov 19;25(11):2402-11.

Li H, Engström K, Vahter M, et al. Arsenic exposure through drinking water is associated with longer telomeres in peripheral blood. Chem Res Toxicol.  2012 Nov 19;25(11):2333-9.

Parajuli RP, Fujiwara T, Umezaki M, et al. Association of cord blood levels of lead, arsenic, and zinc with neuro-developmental indicators in newborns: A birth cohort study in Chitwan Valley, Nepal. Environ Res. 2012 Nov 16.

Gribble MO, Howard BV, Umans JG, et al. Arsenic exposure, diabetes prevalence, and diabetes control in the strong heart study. Am J Epidemiol. 2012 Nov 15;176(10):865-74.

Klei LR, Garciafigueroa DY, Barchowsky A. Arsenic activates endothelin-1 Gi  protein-coupled receptor signaling to inhibit stem cell differentiation in adipogenesis. Toxicol Sci. 2012 Nov 14.

Zheng LY, Umans J, Tellez-Plaza M, et al. Urine Arsenic and  Prevalent Albuminuria: Evidence From a Population-Based Study. Am J Kidney Dis. 2012 Nov 9.

Ahern, A. Exploring links between arsenic and diabetes with Ana Navas-Acien. Environ Health Perspect. 2012 Nov;120(11)

Smith AH, Marshall G, Liaw J, et al. Mortality in young adults following in utero and childhood exposure to arsenic in drinking water. Environ Health Perspect. 2012 Nov;120(11):1527-31.

Amaral AF, Porta M, Silverman D, et al. Pancreatic cancer risk and levels of trace elements. Gut. 2012 Nov;61(11):1583-8.

Alyea RA, Moore NP, Lebaron M, et al. Is the current  product safety assessment paradigm protective for epigenetic mechanisms? J Pharmacol Toxicol Methods. 2012 Nov;66(3):207-14.

Wu C, Su C, Lee H. et al. Joint effect of arsenic methylation profile and NNK metabolites on urothelial carcinoma. J Urol. 2012 Nov;188(5):1701-5.  

 

Stein EM, Tallman MS. Does arsenic trioxide impact fertility? Leuk Lymphoma. 2012 Nov;53(11):2099-100.

Gupta S, Bagel B, Gujral S, et al. Parenthood in patients with acute promyelocytic leukemia after treatment with arsenic trioxide: a case series. Leuk Lymphoma. 2012 Nov;53(11):2192-4.   

 

Hossain M, Vahter M, Concha G, et al. Environmental arsenic exposure and DNA methylation of tumor suppressor gene p16 and DNA repair gene MLH1: effect of arsenic metabolism and genotype. Metallomics 2012 Nov;4(11):1167-75   

 

Patlolla AK, Todorov TI, et al. Arsenic-induced biochemical and genotoxic effects and distribution in tissues of  Sprague-Dawley rats. Microchem J. 2012 Nov 1;105:101-107.

Erraguntla N, Sielken R, Valdez-Flores C, et al.An updated inhalation unit risk factor for arsenic & inorganic arsenic compounds based on  a combined analysis of epidemiology studies. Reg Tox Pharm. 2012 Nov;64(2):329-41.   

 

Yang B, Fu J, Zheng H, et al. Deficiency in the nuclear factor E2-related factor 2 renders pancreatic β-cells vulnerable to arsenic-induced cell damage. Toxicol Appl Pharmacol. 2012 Nov 1;264(3):315-23.  

Tsang V, Fry RC, Niculescu M, et al. The epigenetic effects of a high prenatal folate  intake in male mouse fetuses exposed in utero to arsenic. Toxicol Appl Pharmacol. 2012 Nov 1;264(3):439-50.   

 

Martín-Pardillos A, Sosa C, Sorribas V. Arsenic increases Pi-mediated vascular calcification and induces premature senescence in vascular smooth muscle cells. Toxicol Sci. 2012 Oct 27.

Kumasaka MY, Yamanoshita O, Shimizu S, et al. Enhanced carcinogenicity by coexposure to arsenic and iron and a novel remediation system for the elements in well drinking water. Arch Toxicol. 2012 Oct 26.

Drobná Z, Del Razo LM, García-Vargas G, et al Environmental exposure to arsenic, AS3MT polymorphism and  prevalence of diabetes in Mexico. J Expo Sci Environ Epidemiol. 2012 Oct 24.  

 

Mathews V, Paul MS, Abhilash M, et al. Mitigation of hepatotoxic effects of arsenic trioxide through omega-3 fatty acid in rats. Toxicol Ind Health. 2012 Oct 18.

Jiang R, Li Y, Xu Y, et al. EMT and CSC-like properties mediated by the IKKβ/IκBα/RelA signal pathway via the transcriptional regulator, Snail, are involved in the arsenite-induced neoplastic transformation of human keratinocytes. Arch Toxicol.  2012 Oct 16.

Morzadec C, Bouezzedine F, Macoch M, et al. Inorganic arsenic  impairs proliferation and cytokine expression in human primary T lymphocytes. Toxicology. 2012 Oct 9;300(1-2):46-56.

Pastoret A, Marcos R, Sampayo-Reyes A, et al. Inhibition of hepatocyte nuclear factor 1 and 4 alpha (HNF1α and HNF4α) as a mechanism of arsenic carcinogenesis. Arch Toxicol. 2012 Oct 5.

Guan H, Piao F, Zhang X, et al. Prenatal exposure to arsenic and its effects on fetal development in the general population of Dalian. Biol Trace Elem Res. 2012 Oct;149(1):10-5.   

 

Neslund-Dudas C, Mitra B, Kandegedara A, et al. Association of metals and proteasome activity in erythrocytes of prostate cancer patients and controls. Biol Trace Elem Res. 2012 Oct;149(1):5-9.   

Chu W, Li C, Qu X, et al. Arsenic-induced interstitial myocardial fibrosis reveals a new insight into drug-induced long QT syndrome. Cardiovasc Res. 2012 Oct 1;96(1):90-8.   

 

Sakamoto M, Chan H, Domingo J, et al. Changes in body burden  of mercury, lead, arsenic, cadmium and selenium in infants during early lactation in comparison with placental transfer. Ecotoxicol Environ Saf. 2012 Oct;84:179-84.  

 

Maity JP, Nath B, Kar S, et al. Arsenic-induced health crisis in peri-urban  Moyna and Ardebok villages, West Bengal, India: an exposure assessment study. Environ Geochem Health. 2012 Oct;34(5):563-74.  

 

Davis MA, Mackenzie TA, Cottingham KL, et al. Rice consumption and urinary arsenic concentrations in U.S. children. Environ Health Perspect. 2012 Oct;120(10):1418-24.  

 

Boekelheide K, Blumberg B, Chapin RE, et al.. Predicting  later-life outcomes of early-life exposures. Environ Health Perspect. 2012 Oct;120(10):1353-61.  

 

Uccello M, Malaguarnera G, Corriere T, et al. Risk of hepatocellular carcinoma in workers exposed to chemicals. Hepat Mon. 2012 Oct;12(10 HCC):e5943.

 

Goggin SL, Labrecque MT, Allan AM. Perinatal exposure to 50 ppb sodium arsenate induces hypothalamic-pituitary-adrenal axis dysregulation in male C57BL/6 mice. Neurotoxicology. 2012 Oct;33(5):1338-45.

 

Jing J, Zheng G, Liu M, et al. Changes in the synaptic structure of hippocampal neurons and impairment of spatial memory in a rat model caused by chronic arsenite exposure. Neurotoxicology. 2012 Oct;33(5):1230-8.

 

Liu S, Piao F, Sun X. et al. Arsenic-induced inhibition of hippocampal neurogenesis and its reversibility. Neurotoxicology. 2012 Oct;33(5):1033-9.

 

Bomhard EM, Cohen SM, Gelbke HP, et al. Evaluation of the male reproductive toxicity of gallium arsenide. Regul Toxicol Pharmacol. 2012 Oct;64(1):77-86.

 

Ding L, Saunders RJ, Drobná Z, et al. Methylation of arsenic by recombinant human wild-type arsenic (+3 oxidation state) methyltransferase and its methionine 287 threonine (M287T) polymorph: Role of glutathione. Toxicol Appl Pharmacol. 2012 Oct 1;264(1):121-30.

 

Liu XP, Huang YC, Hung W, et al. Sodium arsenite-induced  abnormalities in expressions of Caveolin-1, eNOS, IKKβ, and COX-2 in SV-40 immortalized human uroepithelial cells and in urothelial carcinomas. Toxicol In Vitro. 2012 Oct;26(7):1098-105.

 

Bengleil M, Hassaneen S, Fry J. Induction of anoikis by sodium arsenite in  rat hepatoma FGC4 cells: comparison with cadmium chloride and implications for assessment of regulation of heat shock protein 70. Toxicol Mech Methods. 2012 Oct;22(8):611-6.

 

Ahmed S, Ahsan KB, Kippler M, et al. In utero arsenic exposure is associated with impaired thymic function in newborns possibly via oxidative stress and apoptosis. Toxicol Sci. 2012 Oct;129(2):305-14.

 

Nohara K, Tateishi Y, Suzuki T, et al. Late-onset increases in oxidative stress and other  tumorigenic activities and tumors with a Ha-ras mutation in the liver of adult male C3H mice gestationally exposed to arsenic. Toxicol Sci. 2012 Oct;129(2):293-304.

 

Liu J, Chen B, Lu Y, et al. JNK-dependent Stat3 phosphorylation contributes to Akt activation in response to arsenic exposure. Toxicol Sci. 2012  Oct;129(2):363-71.

 

Zhang C, Mao G, He S, et al. Relationship between long-term exposure to low-level arsenic in drinking water and the prevalence of abnormal blood pressure. J Hazard Mater. 2012 Sep 26.

 

Aung KH, Kurihara R, Nakashima S, et al. Inhibition of neurite outgrowth and alteration of cytoskeletal gene  expression by sodium arsenite. Neurotoxicology. 2012 Sep 25.

Paul S, Das N, Bhattacharjee P, et al. Arsenic-induced toxicity and carcinogenicity: a two-wave cross-sectional study in arsenicosis individuals in West Bengal, India. J Expo Sci Environ Epidemiol. 2012 Sep 19.

Kim HG, Kim DJ, Li S, et al. Polycomb (PcG) proteins, BMI1 and SUZ12, regulate arsenic-induced cell transformation. J Biol Chem. 2012 Sep 14;287(38):31920-8.

Chen CJ. Comparing the joint effect of arsenic exposure, cigarette smoking and risk genotypes of vascular endothelial growth factor on upper urinary tract urothelial carcinoma & bladder cancer. J Hazard Mater. 2012 Sep 7.

Canet MJ, Hardwick RN, Lake A, et al. Altered arsenic disposition in experimental nonalcoholic Fatty liver disease. Drug Metab Dispos. 2012 Sep;40(9):1817-24.

Wang J, Zhang W, Sun D, et al. Analysis of neuroglobin mRNA expression in rat brain due to arsenite-induced oxidative stress. Environ Toxicol. 2012 Sep;27(9):503-9.

Li X, Shi Y, Wei Y, et al.  Altered expression profiles of microRNAs upon arsenic exposure of human umbilical vein endothelial cells. Environ Toxicol Pharmacol. 2012 Sep;34(2):381-7.

Lambrou A, Baccarelli A, Wright RO, et al. Arsenic exposure and DNA methylation among elderly men. Epidemiology. 2012 Sep;23(5):668-76.

Chervona Y, Costa M. The control of histone methylation and gene expression  by oxidative stress, hypoxia, and metals. Free Radic Biol Med. 2012 Sep 1;53(5):1041-7.

Cheng TF, Choudhuri S, Muldoon-Jacobs K. Epigenetic targets of some toxicologically relevant metals: a review of the literature. J Appl Toxicol. 2012 Sep;32(9):643-53.
Syed EH, Poudel KC, Sakisaka K, et al. Quality of life and mental health status of arsenic-affected patients in a Bangladeshi population. J Health Popul Nutr. 2012 Sep;30(3):262-9.

Lu H, Vlaminckx E, Cools F, et al. Direct effects of arsenic trioxide on action potentials in isolated cardiac tissues: importance of choice of species, type of cardiac tissue & perfusion time. J Pharm Tox Meth 2012 Sep;66(2):135-44

Rahbar M, Samms-Vaughan M, Ardjomand-Hessabi M, et al. The role of drinking water sources, consumption of vegetables and seafood in relation to blood arsenic concentrations of Jamaican children with and without Autism Spectrum Disorders. Sci Total Environ. 2012 Sep 1;433:362-70. 

Tandon N, Roy M, Roy S, et al. Protective Effect of Psidium guajava in Arsenic-induced Oxidative Stress and Cytological Damage in Rats. Toxicol Int. 2012 Sep;19(3):245-9.

Hong GM, Bain LJ. Arsenic exposure inhibits myogenesis and neurogenesis in P19 stem cells through repression of the β-catenin signaling pathway. Toxicol Sci. 2012 Sep;129(1):146-56.

Sinha D, Biswas J, Bishayee A. Nrf2-mediated redox signaling in arsenic carcinogenesis: a review. Arch Toxicol. 2012 Aug 23

Lu C, Zhao F, Sun D, et al. Comparison of  speciated arsenic levels in the liver and brain of mice between arsenate and arsenite exposure at the early life. Environ Toxicol. 2012 Aug 21.

Das N, Paul S, Chatterjee D, et al. Arsenic exposure through drinking water increases the risk of liver and cardiovascular diseases in the population of West Bengal, India. BMC Public Health. 2012 Aug 10;12:639.

Shan H, Zhang Y, Cai B, et al. Upregulation of microRNA-1 and microRNA-133 contributes to arsenic-induced cardiac electrical remodeling. Int J Cardiol. 2012 Aug 10.

Palacios J, Roman D, Cifuentes F. Exposure to low level of arsenic and lead  in drinking water from Antofagasta city induces gender differences in glucose homeostasis in rats. Biol Trace Elem Res. 2012 Aug;148(2):224-31.

Saha KK, Engström A, Hamadani J, et al. Pre- and postnatal arsenic exposure and body size to 2 years of age: a cohort study in rural bangladesh. Environ Health Perspect. 2012 Aug;120(8):1208-14.

Jovanović DD, Paunović K, Manojlović D, et al. Arsenic in drinking water and acute coronary syndrome in Zrenjanin municipality, Serbia. Environ Res. 2012 Aug;117:75-82.

Ciarrocca M, Tomei F, Caciari T, et al. Exposure to arsenic in urban and rural areas and effects on thyroid hormones. Inhal Toxicol. 2012 Aug;24(9):589-98.

 

Baek D, Kim T, Lim H, et al. Embryotoxicity assessment of developmental neurotoxicants using a neuronal endpoint in the embryonic stem cell test. J Appl  Toxicol. 2012 Aug;32(8):617-26.

Mondal B, Chatterjee D, Bhattacharyya M. Structure-function alteration of hemoglobin in arsenicosis patients: a probable pathway to exert toxicity. J Appl  Toxicol. 2012 Aug;32(8):581-9.

Clancy HA, Sun H, Passantino L, et al. Gene expression changes in human lung cells exposed to arsenic, chromium, nickel or vanadium indicate the first steps in cancer. Metallomics. 2012 Aug;4(8):784-93.

You BR, Park WH. Arsenic trioxide induces human pulmonary fibroblast cell death via increasing ROS levels and GSH depletion. Oncol Rep. 2012 Aug;28(2):749-57.

Huang C, Su C, Chung C, et al. Urinary  total arsenic and 8-hydroxydeoxyguanosine are associated with renal cell carcinoma in an area without obvious arsenic exposure. Toxicol Appl Pharmacol. 2012 Aug 1;262(3):349-54.

Liao YT, Chen CJ, Li W, et al. Elevated lactate dehydrogenase activity and increased cardiovascular mortality in the arsenic-endemic areas of southwestern Taiwan. Toxicol Appl Pharmacol. 2012 Aug 1;262(3):232-7.
 Li Y, Wang M, Piao F, et al. Subchronic exposure to arsenic inhibits spermatogenesis and downregulates the expression of ddx3y in testis and epididymis  of mice. Toxicol Sci. 2012 Aug;128(2):482-9.

Gadhia SR, Calabro AR, Barile FA. Trace metals alter DNA repair and histone  modification pathways concurrently in mouse embryonic stem cells. Toxicol Lett. 2012 Jul 20;212(2):169-79.

Watanabe T, Hirano S. Metabolism of arsenic and its toxicological relevance. Arch Toxicol. 2012 Jul 19.

Kong AP, Xiao K, Choi K, et al. Associations between microRNA (miR-21, 126, 155 and 221), albuminuria and heavy metals in Hong Kong Chinese adolescents. Clin Chim Acta. 2012 Jul 11;413(13-14):1053-7.

Ajees AA, Marapakala K, Packianathan C, et al. . Structure of an As(III) S-adenosylmethionine methyltransferase: insights into the mechanism of arsenic biotransformation. Biochemistry. 2012 Jul 10;51(27):5476-85.

Xu W, Bao H, Liu F, et al. Environmental exposure to arsenic may reduce human semen quality: associations derived from a Chinese cross-sectional study. Environ Health. 2012 Jul 9;11:46.

Makris KC, Christophi C, Paisi M, et al. A preliminary assessment of  low level arsenic exposure and diabetes mellitus in Cyprus. BMC Public Health. 2012 Jul 4;12:334.

Li P, Zhong Y, Jiang X, et al. Seminal plasma metals concentration with respect to semen quality. Biol Trace Elem Res. 2012 Jul;148(1):1-6.

Chen JW, Wang SL, Wang Y, et al. Arsenic methylation, GSTO1 polymorphisms, and metabolic syndrome in an arseniasis endemic area of southwestern Taiwan. Chemosphere. 2012 Jul;88(4):432-8.

Kile ML, Baccarelli A, Hoffman E, et a;. Prenatal arsenic exposure and DNA methylation in maternal and umbilical cord blood leukocytes. Environ Health Perspect. 2012 Jul;120(7):1061-6.

Liu G, Liu M, Kim EH, et al. periplasmic arsenite-binding protein involved in regulating arsenite oxidation. Environ Microbiol. 2012 Jul;14(7):1624-34.

Aelion C, Davis H, Lawson AB, et al. Associations of estimated residential soil arsenic and lead concentrations and community-level environmental measures with mother-child health conditions in South Carolina. Health Place. 2012 Jul;18(4):774-81.

Chervona Y, Arita A, Costa M. Carcinogenic metals and the epigenome: understanding the effect of nickel, arsenic, and chromium. Metallomics. 2012 Jul;4(7):619-27.

Gardner RM, Engström K, Bottai M, et al. Pregnancy and the methyltransferase genotype independently influence the arsenic  methylation phenotype. Pharmacogenet Genomics. 2012 Jul;22(7):508-16.

McClintock TR, Chen Y, Bundschuh J, et al. Arsenic exposure in Latin America: biomarkers, risk assessments and related health effects. Sci Total Environ. 2012 Jul 1;429:76-91. 

Wang X, Mandal A, Saito H, et al Arsenic and chromium in drinking  water promote tumorigenesis in a mouse colitis-associated colorectal cancer model and the potential mechanism is ROS-mediated Wnt/β-catenin signaling pathway. Toxicol Appl Pharmacol. 2012 Jul 1;262(1):11-21.

Lin TS, Wu CC, Wu J, et al. Oxidative DNA damage estimated by urinary 8-hydroxy-2′-deoxyguanosine and arsenic in glass production workers. Toxicol Ind  Health. 2012 Jul;28(6):513-21.

Yih LH, Hsu N, Kuo H, et al. Inhibition of the heat shock response by PI103 enhances the cytotoxicity of arsenic trioxide. Toxicol Sci. 2012 Jul;128(1):126-36.

Yih LH, Wu YC, Hsu N, et al. Arsenic trioxide induces abnormal mitotic spindles through a PIP4KIIγ/Rho pathway. Toxicol Sci. 2012 Jul;128(1):115-25.

Beebe-Dimmer JL, Iyer PT, Nriagu J, et al . Genetic variation in glutathione S-transferase omega-1, arsenic methyltransferase and methylene-tetrahydrofolate reductase, arsenic exposure and bladder cancer: a case-control study. Environ Health. 2012 Jun 29;11:43.

Letašiová S, Medve’ová A, Šovčíková A, et al. Bladder cancer, a review of the environmental risk factors. Environ  Health. 2012 Jun 28;11 Suppl 1:S11.

Suzuki T, Nohara K. Long-term arsenic exposure induces histone H3 Lys9 dimethylation without altering DNA methylation in the promoter region of p16(INK4a) and down-regulates its expression in the liver of mice. J Appl Toxicol. 2012 Jun 25:1-8.

Antonio Garcia MT, Herrera Dueñas A, Pineda Pampliega J. Hematological effects of arsenic in rats after sub-chronical exposure during pregnancy & lactation:The protective role of antioxidants. Exp Toxicol Path 2012 Jun 22.

Wu F, Jasmine F, Kibriya M, et al.  Association between arsenic exposure from drinking  water and plasma levels of cardiovascular markers. Am J Epidemiol. 2012 Jun 15;175(12):1252-61.

Druwe IL, Sollome J, Sanchez-Soria P, et al. Arsenite activates NFκB through induction of C-reactive protein. Toxicol Appl Pharmacol. 2012 Jun 15;261(3):263-70.

Islam R, Khan I, Hassan S, et al. Association between type 2 diabetes and chronic arsenic exposure in drinking water: a cross sectional study in Bangladesh. Environ Health. 2012 Jun 7;11:38.

Ma Y, Zhang C, Chen X, et al. The influence of modified pluronic F127 copolymers with higher phase transition temperature on arsenic trioxide-releasing properties and toxicity in a subcutaneous model of rats. AAPS PharmSciTech. 2012 Jun;13(2):441-7.

 

Yen YP, Tsai KS, Chen Y, et al. Arsenic induces apoptosis in myoblasts through a reactive oxygen species-induced endoplasmic reticulum stress and mitochondrial dysfunction pathway. Arch Toxicol. 2012 Jun;86(6):923-33.

Anwar-Mohamed A, Abdelhamid G, Amara IE, et al. Differential modulation of aryl hydrocarbon receptor regulated enzymes by arsenite in the kidney, lung, and heart of C57BL/6 mice. Arch Toxicol. 2012 Jun;86(6):897-910.

Tseng HY, Liu ZM, Huang HS. NADPH oxidase-produced superoxide mediates EGFR  transactivation by c-Src in arsenic trioxide-stimulated human keratinocytes. Arch Toxicol. 2012 Jun;86(6):935-45.

Yajima I, Uemura N, Nizam S, et al. Barium inhibits arsenic-mediated apoptotic cell death in human squamous cell carcinoma cells. Arch Toxicol. 2012 Jun;86(6):961-73.

Wang L, Kou M, Weng C, et al. Arsenic modulates heme oxygenase-1, interleukin-6 and vascular endothelial growth factor expression in endothelial cells: roles of ROS, NF-κB, and MAPK pathways. Arch Toxicol. 2012 Jun;86(6):879-96.

Xu Y, Li Y, Pang Y, et al.  Blockade of p53 by HIF-2α, but not HIF-1α, is involved in arsenite-induced malignant transformation of human bronchial epithelial cells. Arch Toxicol. 2012  Jun;86(6):947-59.

Chang Y, Kuo T, Hsu C, et al. Characterization of the  role of protein-cysteine residues in the binding with sodium arsenite. Arch Toxicol. 2012 Jun;86(6):911-22.

Ma Y, Niu R, Sun Z, et al. Inflammatory responses induced by fluoride and arsenic at toxic concentration in rabbit aorta. Arch Toxicol. 2012 Jun;86(6):849-56.

Tokar J, Diwan B, Thomas D, et al. Tumors and proliferative lesions  in adult offspring after maternal exposure to methylarsonous acid during gestation in CD1 mice. Arch Toxicol. 2012 Jun;86(6):975-82.

 

Escobar-García D, Del Razo L, Sanchez-Peña L, et al. Association of glutathione S-transferase Ω 1-1 polymorph-isms (A140D and E208K) with expression of interleukin-8 (IL-8), transforming growth factor beta (TGF-β), and apoptotic protease-activating factor 1 (Apaf-1) in humans chronically exposed to arsenic in drinking water. Arch Toxicol. 2012 Jun;86(6):857-68.

Chen S, Chen C, Kuo C, et al . Elevated risk of hypertension induced by arsenic exposure in Taiwanese rural residents: possible effects of manganese superoxide dismutase (MnSOD) and 8-oxoguanine DNA glycosylase (OGG1) genes. Arch Toxicol. 2012 Jun;86(6):869-78.

Németi B, Anderson ME, Gregus Z. Glutathione synthetase promotes the reduction of arsenate via arsenolysis of glutathione. Biochimie. 2012 Jun;94(6):1327-33.

Tang C, Li A, Guan Y et al. Influence of polluted SY River on child growth and sex hormones. Biomed Environ Sci. 2012 Jun;25(3):291-6.

Hu YC, Cheng H, Hsieh B, et al. Arsenic trioxide affects bone remodeling by effects on osteoblast differentiation and function. Bone. 2012 Jun;50(6):1406-15.

 

Goineau S, Legrand C, Froget G. Whole-cell configuration of patch-clamp technique in the hERG channel assay to predict the ability of a compound to prolong QT interval. Curr Protoc Pharmacol. 2012 Jun;Ch 10:Unit 10.15.

Kesari V, Kumar A, Khan P. Genotoxic potential of arsenic at its reference dose. Ecotoxicol Environ Saf. 2012 Jun;80:126-31.

Barrett JR. Bad neighbors: arsenic-induced tumor cells convert normal stem cells into a cancerous phenotype. Environ Health Perspect. 2012 Jun;120(6):A244. 

Xu Y, Tokar E, Sun Y, et al. Arsenic-transformed malignant prostate epithelia can convert noncontiguous normal stem cells into an oncogenic phenotype. Environ Health Perspect. 2012 Jun;120(6):865-71.

Thayer KA, Heindel JJ, Bucher JR, et al. Role of environmental chemicals  in diabetes and obesity: a National Toxicology Program workshop review. Environ Health Perspect. 2012 Jun;120(6):779-89.

Negishi T, Takahashi M, Matsunaga Y, et al. Diphenylarsinic acid increased the synthesis and release of neuroactive and vasoactive peptides in rat cerebellar astrocytes. J Neuropathol Exp Neurol. 2012 Jun;71(6):468-79.

 

Arita A, Shamy MY, Chervona Y, et al The effect of exposure to carcinogenic metals on histone tail modifications and gene expression in human subjects. J Trace Elem Med Biol. 2012  Jun;26(2-3):174-8.

Nordberg G, Jin T, Wu X, et al. Kidney dysfunction and cadmium exposure–factors influencing dose-response relationships. J Trace Elem Med Biol. 2012 Jun;26(2-3):197-200.

Stueckle T, Lu Y, Davis M, et al. Chronic occupational exposure to arsenic induces carcinogenic gene signaling networks and neoplastic transformation in human lung  epithelial cells. Tox Appl Pharm. 2012 Jun 1;261(2):204-16.

Goodrich JM, Basu N. Variants of glutathione s-transferase pi 1 exhibit differential enzymatic activity and inhibition by heavy metals. Toxicol In Vitro. 2012 Jun;26(4):630-5.   

Kim S, Takeuchi A, Kawasumi Y, et al. Guillain-Barré Syndrome-like Neuropathy Associated with Arsenic Exposure. J Occup Health. 2012 May 29.

Luo JH, Qiu Z, Zhang L, et al. Arsenite exposure altered the expression of NMDA receptor and postsynaptic signaling proteins in rat hippocampus. Toxicol Lett. 2012 May 20;211(1):39-44.

Bomberger J, Coutermarsh B, Barnaby R, et al. Arsenic promotes ubiquitinylation and lysosomal degradation of cystic fibrosis transmembrane conductance regulator (CFTR) chloride channels in human airway epithelial cells.  J Biol Chem. 2012 May 18;287(21):17130-9.

Alava P, Tack F, Laing G, et al. Arsenic undergoes significant speciation changes upon incubation of contaminated rice with human colon micro biota. J Hazard Mater. 2012 May 17.

Martinez VD, Vucic E, Lam S, et al. Arsenic and lung cancer in never-smokers: lessons from Chile. Am J Respir Crit Care Med. 2012 May 15;185(10):1131-2.

Echaniz-Laguna A, Benoilid A, Vinzio S, et al. Mitochondrial myopathy caused by arsenic trioxide therapy. Blood. 2012 May 3;119(18):4272-4.

Chen Y, McClintock T, Segers S, et al. Prospective investigation of major dietary patterns and risk of cardiovascular mortality in Bangladesh. Int J Cardiol. 2012  May 3.

Intarasunanont P, Navasumrit P, Waraprasit S, et al. Effects of arsenic exposure on DNA methylation in cord blood samples from newborn babies and in a human lymphoblast cell line. Environ Health. 2012 May 2;11:31.

Bharti VK, Srivastava R, Sharma B, et al. Buffalo (Bubalus bubalis) epiphyseal proteins counteract arsenic-induced oxidative stress in brain, heart,  and liver of female rats. Biol Trace Elem Res. 2012 May;146(2):224-9.

Jasso-Pineda Y, Díaz-Barriga F, Calderón J, et al. DNA damage & decreased DNA repair in peripheral blood mono-nuclear cells in individuals exposed to arsenic & lead in a mining site. Biol Trace Elem Res 2012May;146(2):141-9.

Rodrigues E, Kile M, Hoffman E, et al. GSTO and AS3MT genetic polymorphisms and differences in urinary arsenic concentrations among residents in Bangladesh. Biomarkers. 2012 May;17(3):240-7.

Zhang X, Su Y, Zhang M, et al. Opposite effects of arsenic trioxide on the Nrf2 pathway in oral squamous cell carcinoma in vitro and in vivo. Cancer Lett. 2012 May 1;318(1):93-8.

Leonardi G, Vahter M, Clemens F, et al. Inorganic arsenic and basal cell carcinoma in areas of Hungary, Romania, and Slovakia: a case-control study.  Environ Health Perspect. 2012 May;120(5):721-6.

Maiti S, Chattopadhyay S, Deb B, et al. Antioxidant and metabolic impairment result in DNA damage in arsenic-exposed individuals with severe dermatological manifestations in Eastern India. Env Tox. 2012 May;27(6):342-50.

Pesola GR, Parvez F, Chen Y, et al. Arsenic exposure from drinking water and dyspnoea risk in Araihazar, Bangladesh: a population-based study. Eur Respir J. 2012 May;39(5):1076-83.

Pearce DC, Dowling K, Sim MR. Cancer incidence and soil arsenic exposure in  a historical gold mining area in Victoria, Australia: a geospatial analysis. J Expo Sci Environ Epidemiol. 2012 May-Jun;22(3):248-57.

Sung TI, Wang YJ, Chen C, et al. Increased serum level of epidermal growth factor receptor in liver cancer patients and its association with exposure to arsenic. Sci Total Environ. 2012 May 1;424:74-8.

Hong GM, Bain LJ. Sodium arsenite represses the expression of myogenin in C2C12 mouse myoblast cells through histone modifications and altered expression of Ezh2, Glp, and Igf-1. Tox Appl Pharm. 2012 May 1;260(3):250-9.

Naranmandura H, Xu S, Koike S, et al. The endoplasmic reticulum is a target organelle for trivalent dimethylarsinic acid (DMAIII)-induced cytotoxicity. Toxicol Appl Pharmacol. 2012  May 1;260(3):241-9.

Qin X, Liu W, Li Y, et al. Poly(ADP-ribose) polymerase-1 inhibition by arsenite promotes the survival of cells with unrepaired DNA lesions induced by UV exposure. Toxicol Sci. 2012 May;127(1):120-9.

Xu Y, Ma B, Nussinov R. Structural and Functional Consequences of Phosphate-Arsenate Substitutions in Selected Nucleotides: DNA, RNA, and ATP. J Phys Chem B. 2012 Apr 17.

Zangi R, Filella M. Transport routes of metalloids into and out of the cell: a review of the current knowledge. Chem Biol Interact. 2012 Apr 15;197(1):47-57. 

Bacigalupo C, Hale B. Human health risks of Pb and As exposure via consumption of home garden vegetables and incidental soil and dust ingestion: a probabilistic screening tool. Sci Total Environ. 2012 Apr 15;423:27-38.

Wang J, Gu J, Leszczynski J. Could hydrolysis of arsenic substituted DNA be  prevented? Protection arises from stacking interactions. Chem Commun (Camb). 2012 Apr 14;48(30):3626-8.

Lesseur C, Gilbert-Diamond D, Andrew A, et al. A case-control study of polymorphisms in xenobiotic and arsenic metabolism genes and arsenic-related bladder cancer in New Hampshire. Toxicol Lett. 2012 Apr 5;210(1):100-6.

Alava P, Tack F, Laing GD, et al. HPLC-ICP-MS method development to monitor arsenic speciation changes by human gut microbiota. Biomed Chromatogr. 2012 Apr;26(4):524-33.

 

Qi H, Chen B, Le X, et al. Concomitant induction of heme oxygenase-1 attenuates the cytotoxicity of arsenic species from lumbricus extract in human liver HepG2 cells. Chem Biodivers. 2012 Apr;9(4):739-54.

Zhao R, Hou Y, Zhang Q, et al. Cross-regulations among NRFs & KEAP1 and effects of their silencing on arsenic-induced antioxidant response and cytotoxicity in human keratinocytes. Env Health Perspect. 2012 Apr;120(4):583-9.

Gamble MV, Hall MN. Relationship of creatinine and nutrition with arsenic metabolism. Environ Health Perspect. 2012 Apr;120(4):A145-6.

Abhyankar LN, Jones MR, Guallar E, et al. Arsenic exposure and hypertension: a systematic review. Environ Health Perspect. 2012 Apr;120(4):494-500.

Carbonell-Barrachina AA, Wu X, Ramírez-Gandolfo A, et al. Inorganic arsenic contents in rice-based infant foods from Spain, UK, China and USA. Environ Pollut. 2012 Apr;163:77-83.

Noreault-Conti T, Fellows A, Jacobs J, et al. Arsenic decreases RXRα-dependent transcription of CYP3A and suppresses immune regulators in hepatocytes. Int Immunopharmacol. 2012 Apr;12(4):651-6.

Suriyo T, Watcharasit P, Thiantanawat A, et al. Arsenite promotes apoptosis and dysfunction in microvascular endothelial cells via an alteration of intracellular calcium homeostasis. Toxicol In Vitro. 2012 Apr;26(3):386-95.

Sanchez-Soria P, Broka D, Monks SL, et al. Chronic low-level arsenite exposure through drinking water increases blood pressure & promotes concentric left ventricular hypertrophy in female miceTox Pathol 2012 Apr;40(3):504-12

Gu J, Wang J, Xie Y, Leszczynski J, et al. Structural and electronic property responses to the arsenic/phosphorus exchange in GC-related DNA of the B-form. J Comput Chem. 2012 Mar 30;33(8):817-21.

Nriagu J, Lin TS, Mazumder D, et al. E-cadherin polymorphisms and susceptibility to arsenic-related skin lesions in West Bengal, India. Sci Total Environ. 2012 Mar 15;420:65-72.

Tokar E, Diwan B, Waalkes M. Renal, hepatic, pulmonary and adrenal tumors induced by prenatal inorganic arsenic followed by dimethylarsinic acid in  adulthood in CD1 mice. Toxicol Lett. 2012 Mar 7;209(2):179-85.

Nain S, Smits JE. Pathological, immunological and biochemical markers of subchronic arsenic toxicity in rats. Environ Toxicol. 2012 Mar;27(4):244-54.

Ahmad W, Prawez S, Chanderashekara H, et al. Subacute arsenic exposure through drinking water reduces the pharmacodynamic effects of ketoprofen in male rats. Environ Toxicol Pharmacol. 2012 Mar;33(2):267-76.

Messarah M, Klibet F, Boumendjel A et al. epatoprotective role and antioxidant capacity of selenium on arsenic-induced liver injury in rats. Exp Toxicol Pathol. 2012 Mar;64(3):167-74. 

Ferreira M, Matos RC, Oliveira H, et al. Impairment of mice spermatogenesis by sodium arsenite. Hum Exp Toxicol. 2012 Mar;31(3):290-302.

Karagas MR, Andrew AS, Nelson H et al. SLC39A2 and FSIP1 polymorphisms as potential modifiers of arsenic-related bladder cancer. Hum Genet. 2012 Mar;131(3):453-61.

Somé IT, Sakira AK, Ouédraogo M, et al. Arsenic levels in tube-wells water, food, residents’ urine and the prevalence of skin lesions in Yatenga province, Burkina Faso. Interdiscip Toxicol. 2012 Mar;5(1):38-41.

Rana T, Bera AK, Das S et al. Metabolic adaptations to arsenic-induced oxidative stress in male wistar rats. J Biochem Mol Toxicol. 2012 Mar;26(3):109-16.

Sanchez-Rodas D, de la Campa AS, Oliveira V et al. Health implications of the distribution of arsenic species in airborne particulate matter. J Inorg Biochem. 2012 Mar;108:112-4.

Chen PC, Chen WC, Chao SC, et al. Six primary cancers in one Lynch syndrome patient with chronic arsenic exposure. J Surg Oncol. 2012 Mar;105(3):329-30.

Fernández MI, López JF, Vivaldi B, et al. Long-term impact of arsenic in drinking water on bladder cancer health care and mortality rates 20 years after end of exposure. J Urol. 2012 Mar;187(3):856-61.

Bornhorst J, Ebert F, Lohren H, et al. Effects of manganese and arsenic species on the level of energy related nucleotides in human cells. Metallomics. 2012 Mar;4(3):297-306.

Markowski VP, Reeve EA, Onos K, et al. Effects of prenatal exposure to sodium arsenite on motor and food-motivated behaviors from birth to adulthood in C57BL6/J mice. Neurotoxicol Teratol. 2012 Mar;34(2):221-31.

Hossain E, Islam K, Yeasmin F, et al. Elevated levels of plasma Big endothelin-1 and its relation to hypertension and skin lesions in individuals exposed to arsenic. Toxicol Appl Pharmacol. 2012 Mar 1;259(2):187-94.

Calatayud M, Barrios J, et al. In vitro study of transporters  involved in intestinal absorption of inorganic arsenic. Chem Res Toxicol. 2012 Feb 20;25(2):446-53.

Fraser B. Cancer cluster in Chile linked to arsenic contamination. Lancet.  2012 Feb 18;379(9816):603.

Oh R, Pan W, Yalcin A, et al. Functional RNA interference (RNAi) screen identifies system A neutral amino acid transporter 2 (SNAT2) as a mediator of arsenic-induced endoplasmic reticulum stress. J Biol Chem. 2012 Feb 17;287(8):6025-34.

Li Y, Gao Y, Zhao L, et al. Changes in serum thioredoxin among individuals chronically exposed to arsenic in drinking water. Toxicol Appl Pharmacol. 2012 Feb 15;259(1):124-32.

Lin PY, Lin YL, Huang C, et al. Inorganic arsenic in drinking water accelerates N-butyl-N-(4-hydroxybutyl) nitrosamine-induced bladder tissue damage in mice. Toxicol Appl Pharmacol. 2012 Feb 15;259(1):27-37.

Cho Y, Ahn KH, Back M, et al. Age-related effects of sodium arsenite on splenocyte proliferation and Th1/Th2 cytokine production. Arch Pharm Res. 2012 Feb;35(2):375-82.

Yassine H, Kimzey MJ, Galligan M, et al. Adjusting for Urinary Creatinine Overestimates Arsenic Concentrations in Diabetics. Cardiorenal Med. 2012 Feb;2(1):26-32. Epub 2011 Dec 23.

Yannone SM, Hartung S, Menon A, et al. Metals in biology: defining metalloproteomes. Curr Opin Biotechnol. 2012 Feb;23(1):89-95.

Gong G, O’Bryant SE. Low-level arsenic exposure, AS3MT gene polymorphism and cardiovascular diseases in rural Texas counties. Environ Res. 2012 Feb;113:52-7.

Gandhi DN, Panchal GM, Patel KG. Developmental and neurobehavioural toxicity study of arsenic on rats following gestational exposure. Indian J Exp Biol. 2012 Feb;50(2):147-55.

Zhao Y, Toselli P, Li W. Microtubules as a critical target for arsenic toxicity in lung cells in vitro and in vivo. Int J Environ Res Public Health. 2012 Feb;9(2):474-95.

Cui Y, Han Z, Hu Y, et al. MicroRNA-181b and microRNA-9 mediate arsenic-induced angiogenesis via NRP1. J Cell Physiol. 2012 Feb;227(2):772-83.

Zhao F, Liao Y, Jin Y, et al. Effects of arsenite on glutamate  metabolism in primary cultured astrocytes. Toxicol In Vitro. 2012 Feb;26(1):24-31.

Medeiros M, Zheng X, Novak P, et al. Global gene expression changes in human urothelial cells exposed to  low-level monomethylarsonous acid. Toxicology. 2012 Jan 27;291(1-3):102-12.

Huo T, Chang B, Zhang Y, et al. Alteration of amino acid neurotransmitters in brain tissues of immature rats treated with realgar. J Pharm Biomed Anal. 2012 Jan 5;57:120-4.

Chhabra D, Oda K, Jagannath P, et al. Chronic heavy metal exposure and gallbladder cancer risk in India, a comparative study with Japan. Asian Pac J Cancer Prev. 2012;13(1):187-90.

Sumi D, Himeno S. Role of arsenic (+3 oxidation state) methyltransferase in arsenic metabolism and toxicity. Biol Pharm Bull. 2012;35(11):1870-5.

Isokpehi RD, Udensi UK, Anyanwu M, et al. Knowledge building insights on biomarkers of arsenic toxicity to keratinocytes and melanocytes. Biomark Insights. 2012;7:127-41.

Kolachi NF, Kazi TG, Afridi H, et al. Interaction between selenium and arsenic in biological samples of psoriasis patients. Clin Lab. 2012;58(3-4):233-43.

Caciari T, Capozzella A, Tomei F, et al. Arsenic and peripheral blood count in workers exposed to urban stressors. Clin Ter. 2012;163(5):e293-302.

Chattopadhyay S, Deb B, Maiti S. Hepatoprotective role of vitamin B(12) and folic acid in arsenic intoxicated rats. Drug Chem Toxicol. 2012 Jan;35(1):81-8.

 

Mordukhovich I, Wright RO, Hu H, et al. Associations of toenail arsenic, cadmium, mercury, manganese, and lead with blood pressure in the normative aging study. Environ Health Perspect. 2012 Jan;120(1):98-104.

Sanders AP, Messier KP, Shehee M, et al Arsenic in North Carolina: public health implications. Environ Int. 2012 Jan;38(1):10-6.

Molin M, Ulven SM, Dahl L,et al. Humans seem to produce arsenobetaine and dimethylarsinate after a bolus dose  of seafood. Environ Res. 2012 Jan;112:28-39.

Dávila-Esqueda ME, Jiménez-Capdeville ME, Delgado JM, et al. Effects of arsenic exposure during the pre- and postnatal development on the puberty of female offspring. Exp Toxicol Pathol. 2012 Jan;64(1-2):25-30.

IARC Working Group on the Evaluation of Carcinogenic Risks to Humans. Arsenic, metals, fibres, and dusts. IARC Monogr Eval Carcinog Risks Hum. 2012;100(Pt C):11-465.

Cherry N, McDonald C, Chowdhury Z. Zinc in well water and infant mortality  in bangladesh: a report from gonoshasthaya kendra. Int J Environ Res Public Health. 2012 Jan;9(1):171-7.

Yuan XH, Lu CL, Yao N, et al. Arsenic induced progesterone production in a caspase-3-dependent manner and changed redox status  in preovulatory granulosa cells. J Cell Physiol. 2012 Jan;227(1):194-203.

Guha Mazumder D, Purkayastha I, Ghose A, et al. Hypertension in chronic arsenic exposure: A case control study in West Bengal. J Environ Sci Health A Tox Hazard Subst Environ Eng. 2012;47(11):1514-20.

Islam LN, Zahid MS, Nabi AH, et al. Function of serum complement in drinking water arsenic toxicity. J Toxicol. 2012;2012:302817.

Hall MN, Gamble MV. Nutritional manipulation of one-carbon metabolism: effects on arsenic methylation and toxicity. J Toxicol. 2012;2012:595307.

Abir T, Rahman B, D’Este C, et al. The Association between Chronic Arsenic Exposure and Hypertension: A Meta-Analysis. J Toxicol. 2012;2012:198793. 

Gomez-Rubio P, Klimentidis YC, Cantu-Soto E, et al. Indigenous American ancestry is associated with arsenic methylation efficiency in an admixed population of northwest Mexico. J Tox Environ Health A. 2012;75(1):36-49.

Fujiwara Y, Yamamoto C, Inagaki T, et al. Bismuth protects against arsenite-induced inhibition of proteoglycan synthesis in cultured vascular endothelial cells. J Toxicol Sci. 2012;37(4):837-43.

Vykhovanets EV, MacLennan GT, Vykhovanets O, et al. Molecular imaging of nuclear factor-κB in bladder as a primary regulator of inflammatory response. J Urol. 2012 Jan;187(1):330-7.

Sengupta A, Saha K, Jash D, et al. Pulmonary Cavity due to Chronic Eosinophilic Pneumonia Associated with Arsenicosis. JNMA J Nepal Med Assoc. 2012 Jan-Mar;52(185):29-32.

Blaurock-Busch E, Amin OR, et al. Toxic Metals and Essential  Elements in Hair and Severity of Symptoms among Children with Autism. Maedica (Buchar). 2012 Jan;7(1):38-48.

Agusa T, Kunito T, Tue N, et al. Individual variations in arsenic metabolism in Vietnamese: the association with arsenic exposure and GSTP1 genetic polymorphism. Metallomics. 2012 Jan;4(1):91-100.

Flora SJ, Mittal M, Pachauri V, et al. A possible mechanism for combined arsenic and fluoride induced cellular and DNA damage in mice. Metallomics. 2012 Jan;4(1):78-90.

Pierce BL, Kibriya M, Tong L, et al. Genome-wide association study identifies chromosome 10q24.32 variants associated  with arsenic metabolism and toxicity phenotypes in Bangladesh. PLoS Genet. 2012;8(2):e1002522.

Matulis SM, Morales A, Yehiayan L, et al. Alterations in glutathione levels and apoptotic regulators are associated with acquisition of arsenic trioxide resistance in multiple myeloma. PLoS One. 2012;7(12):e52662.

Aravena C, Beltrán AR, Cornejo M, et al. Potential Role of Sodium-Proton Exchangers in the Low Concentration Arsenic Trioxide-Increased Intracellular pH and Cell Proliferation. PLoS One. 2012;7(12):e51451.

Zhang L, Wang K, Zhao F, et al. Near infrared imaging of EGFR of oral squamous cell carcinoma in mice administered arsenic trioxide. PLoS One. 2012;7(9):e46255.

Treas JN, Tyagi T, Singh KP. Effects of chronic exposure to arsenic and estrogen on epigenetic regulatory genes expression and epigenetic code in human prostate epithelial cells. PLoS One. 2012;7(8):e43880.

States JC, Singh AV, Knudsen TB, et al. Prenatal arsenic exposure alters gene expression in the adult liver to a proinflammatory state contributing to accelerated atherosclerosis. PLoS One. 2012;7(6):e38713.

Kozul-Horvath CD, Zandbergen F, Jackson B et al. Effects of low-dose drinking water arsenic on mouse fetal and postnatal growth and development. PLoS One. 2012;7(5):e38249.

Xu Y, Li Y, Pang Y, Ling M, et al. EMT and stem cell-like properties associated with HIF-2α are involved in arsenite-induced transformation of human bronchial epithelial cells. PLoS One. 2012;7(5):e37765.

Pilsner J, Hall M, Liu X, et al. Influence of prenatal arsenic exposure and newborn sex on global methylation of cord blood DNA. PLoS One. 2012;7(5):e37147.

Du J, Zhou N, Liu H, et al. Arsenic induces functional re-expression of estrogen receptor α by demethylation  of DNA in estrogen receptor-negative human breast cancer. PLoS One. 2012;7(4):e35957.

Sanders AP, Flood K, Chiang S,et al. Towards prenatal biomonitoring in North Carolina: assessing arsenic, cadmium, mercury, and lead levels in pregnant women. PLoS One. 2012;7(3):e31354.

Jackson BP, Taylor VF, et al. Arsenic concentration and  speciation in infant formulas and first foods. Pure Appl Chem. 2012;84(2):215-223. Epub 2012 Jan 16.

Su CT, Lin HC, Choy CS, et al. The relationship between obesity, insulin and arsenic methylation capability in Taiwan adolescents. Sci Total Environ. 2012 Jan 1;414:152-8.

Escudero-Lourdes C, Wu T, Camarillo J. et al. Interleukin-8 over-production and autocrine cell activation are key factors in monomethylarsonous acid-induced malignant transformation of urothelial cells. Tox Appl Phar. 2012 Jan 1;258(1):10-8.

Ngalame NN, Micciche AF, Feil ME, et al. Delayed Temporal Increase of Hepatic Hsp70 in ApoE Knockout Mice After Prenatal Arsenic Exposure. Toxicol Sci. 2012 Jan;131(1):225-33.

Sun Y, Tokar EJ, Waalkes MP. Overabundance of putative cancer stem cells in human skin keratinocyte cells malignantly transformed by arsenic. Toxicol Sci. 2012 Jan;125(1):20-9.

Huang NC, Wann SR, Chang H, et al. Arsenic, vinyl chloride, viral hepatitis, and hepatic angiosarcoma: a hospital-based study and review of literature in Taiwan. BMC Gastroenterol. 2011 Dec 26;11:142.

El-Ghor A, Noshy M, Eid E. Lead acetate and arsenic trioxide induce instability of microsatellites at three different

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[1] The IRIS assessments and toxicological reviews are not identical, but both are the subject of the ongoing meetings and deliberations. For simplicity, they are both referred to simply as “IRIS assessment” in these recommendations.

[2] Boekelheide K et al. 2012. Predicting Later-life Outcomes of Early-life Exposures. Environ Health Persp. 120(10):1353-1361.