On October 31, 2001, Environmental Protection Agency (EPA) Administrator Christine Todd Whitman announced adoption of a final regulation aimed at reducing the public health risks caused by arsenic in drinking water. The new arsenic rule revised the drinking water standard for arsenic - a standard that hadn't been changed since 1942 - from 50 parts per billion (ppb) to 10 ppb. The new regulation brings the United States into compliance with the standard previously adopted by the World Health Organization and the European Union, and provides additional protection for 13 million Americans against the long-term effects of arsenic such as cancer, cardiovascular disease, diabetes and neurological disorders.

SRP-funded researchers at several universities played a vital role in the process leading to the new standard by contributing greatly to our knowledge of the risk and health effects of arsenic in drinking water. SRP research includes:

• studies of arsenic metabolism
• molecular epidemiological research that studied the effects of low level
• arsenic exposure on bladder cells
• traditional epidemiological studies with detailed exposure assessment that assessed the relationship between arsenic exposure and the development of cancer
• mechanistic research that shows that arsenic acts predominantly through a free radical pathway to cause cancer
• studies that demonstrate that arsenic disrupts the endocrine system
  

The 1999 and 2001 National Research Council (NRC) arsenic reports, used by the EPA as a scientific basis for lowering the drinking water standard, also cited the results of two Dartmouth SRP molecular toxicology groups. One group, led by Aaron Barchowsky, demonstrated that very low levels of arsenic (in the range equivalent to elevated United States drinking water values) affect blood vessel growth by altering critical cell signaling events of both the epithelial and endothelial cells that form the blood vessels. This has implications both for vascular disease and for metastatic cancer. The other group, led by Joshua Hamilton, made the unexpected discovery that at very low levels, arsenic disrupts the endocrine system by blocking the ability of steroid hormones such as estrogen, testosterone and corticosteroids to regulate the behavior of cells through their receptors. Such endocrine disruption could explain, at least in part, how arsenic increases the risk of various types of cancer as well as vascular disease, cardiovascular disease, diabetes, and reproductive and developmental effects. Hamilton's study was cited in a Congressional testimony by Christine Todd Whitman, as one of the key new studies that supported lowering the arsenic drinking water standard to protect the health of the U.S. population. Other SRP researchers at universities across the country have published papers concerning arsenic contamination and its human and environmental impact. Decision makers relied on several of these SRP publications; a partial list is presented at the end of this document.

SRP-funded researchers also provided technical expertise, serving on review committees during the rule making process. For example:

• Allan H. Smith (University of California, Berkeley) was a member of the NRC Subcommittee on Arsenic in Drinking Water that reviewed EPA's risk assessment for arsenic.
• Joshua Hamilton (Dartmouth College) served as an external reviewer to the NRC's 2001 Arsenic Report that was used to set the new drinking water standard, and as a reviewer for the EPA's final Arsenic in Drinking Water document.
• Margaret Karagas (Dartmouth College) served on several review panels on the health effects of arsenic including service as an External Reviewer for EPA's Provisional Toxicity Assessment for Arsenic in 2000 and most recently on the World Health Organization's International Agency for Research on Cancer (IARC) update of their monograph on arsenic and cancer.
  

On the state level, SRP researcher Joshua Hamilton is an active participant in the Healthy New Hampshire 2010 initiative and is largely responsible for ensuring that arsenic was included on the state's priority list as an environmental health concern.

Superfund Research Program researchers are deeply involved in the development and support of the New Hampshire Arsenic Consortium. This Consortium brings together university scientists and the New Hampshire Departments of Environmental Services, the Health and Human Services and the US Geological Survey. Formation of this group has led to increased communication among the agencies. It has also resulted in the design and undertaking of inter-agency projects to collect data to support risk assessments. The Arsenic Coalition has successfully raised the level of awareness of the issue of arsenic in drinking water, resulting in greater testing of private wells by the public and enhanced awareness of potential health impact.

Key SRP publications in relation to the EPA decision to lower the arsenic drinking water standard:

• Kaltreider, R.C., A.M. Davis, J.P. Lariviere and J.W. Hamilton. 2001. Arsenic Alters the Function of the Glucocorticoid Receptor as a Transcription Factor. Environmental Health Perspectives 109(3):245-51.
• Karagas, M.R., T. Stukel, J.S. Morris, T.D. Tosteson, S.K. Spencer and E.R. Greenberg. 2001. Skin cancer risk in relation to toenail arsenic concentrations in a US population-based case-control study. American Journal of Epidemiology 153:559-65.
• Ferreccio, C., C. Gonzalez, V. Milosavjlevic, G. Marshall, A.M. Sancha and A.H. Smith. 2000. Lung cancer and arsenic concentrations in drinking water in Chile. Epidemiology 11:673-79.
• Smith, A.H., M.L. Biggs, L.E. Moore, R. Haque, C. Steinmaus, J. Chung, A.L. Hernandez and P. Lopipero. 1999. Cancer risks from arsenic in drinking water: implications for drinking water standards. In: Proceedings of the Third International Conference on Arsenic Exposure and Health Effects, July 12-15, 1998, San Diego, California. Elsevier Science, LTD. pp 191-99.
• Barchowsky, A., R. Roussel, L.R. Klei, P.E. James, N. Ganju, K.R. Smith, E.J. Dudek. 1999. Low levels of arsenic trioxide stimulate proliferative signals in primary vascular cells without activating stress effector pathways. Toxicology and Applied Pharmacology 159: 65-75.
• Hopenhayn-Rich, C., M.L. Biggs and A.H. Smith. 1998. Lung and kidney cancer mortality associated with arsenic in drinking water in Cordoba, Argentina. International Journal of Epidemiology 27:561-69.
• Smith, A.H., M. Goycolea, R. Haque, M.L. Biggs. 1998. Marked increase in bladder and lung cancer mortality in a region of Northern Chile due to arsenic in drinking water. American Journal of Epidemiology 147:660-669.
• Moore, L.E., A.H. Smith, C. Hopenhayn-Rich, M.L. Biggs, D.A. Kalman and M.T. Smith. 1997. Decrease in bladder cell micronucleus prevalence after intervention to lower the concentration of arsenic in drinking water. Cancer Epidemiology, Biomarkers, & Prevention 6:1051-6.
• Hopenhayn-Rich, C., M.L. Biggs, D.A. Kalman, L.E. Moore, A.H. Smith. 1996. Arsenic methylation patterns before and after changing from higher to lower concentrations of arsenic in drinking water. Environmental Health Perspectives 104:1200-1207.
• Hopenhayn-Rich, C., M.L. Biggs, A. Fuchs, R. Bergoglio, E. Tello, H. Nicolli and A.H. Smith. 1996. Bladder cancer mortality associated with arsenic in drinking water in Argentina. Epidemiology 7:117-124.
• Moore, L., A.H. Smith, C. Hopenhayn-Rich, M.L. Biggs, M.L. Warner, D. Kalman and M.T. Smith. 1995. Increased bladder cell micronuclei found in two populations environmentally exposed to arsenic in drinking water. Clinical Chemistry 41:1915-1917.
• Bates, M.N., A.H. Smith and K.P. Cantor. 1995. Case-control studies of bladder cancer and arsenic in drinking water. American Journal of Epidemiology 141:523-530.
• Bates, M.N., A.H. Smith and C. Hopenhayn-Rich. 1992. Arsenic ingestion and internal cancers: a review. American Journal of Epidemiology 135:462-476.
• Smith, A.H., C. Hopenhayn-Rich, M.N. Bates, H.M. Goeden, I. Hertz-Picciotto, H.M. Duggan, R. Wood, M.T. Smith and M.J. Kosnett. 1992. Cancer risks from arsenic in drinking water. Environmental Health Perspectives 97:259-267.