VZero-Arsenic 2005
JRL; 4/05
Complexities in Arsenic Risk Assessment
Experts in the field have been addressing the complexity of establishing well-constructed risk assessment for arsenic in drinking water for years. Given that natural background levels of arsenic derive from a process that leaches the element from minerals in the ground, the existence of uncommonly high levels of arsenic in Bangladesh affords scientists with an important study environment.
However, correspondence in C&E News (Feb 11, 2002) has pointed out the lack of a clear link between the number of contaminated wells (>50 ppb arsenic) and the prevalence of people showing symptoms of arsenic poisoning. It is not unusual to find areas of Bangladesh where 50%-60% of the wells have high levels of arsenic, and the rate of population showing visible symptoms to be between 3.5 and 7 patients per 10,000 people.
In stark contrast is the area of Kachua, where 97% of all the wells tested show high levels of arsenic but the prevalence of arsenic poisoning was roughly one in 100,000 of the population, a factor of 70 below that observed elsewhere. One conclusion that can reasonably be drawn is that arsenicosis must require something beyond drinking arsenic-contaminated water. This was supported by the fact that in the course of the study, families were routinely encountered in which only one adult had symptoms of arsenic poisoning, while others showed no external symptoms, despite drinking from the same well. (The British Geological Survey has estimated that 27% of the wells in Bangladesh contain arsenic at levels exceeding 50 ppb, affecting perhaps more than 30 million people.)
Given the limited resources available for mitigation and the widespread distribution of arsenic in Bangladesh, it has been essential to support a concentrated effort to determine what specific factors contribute to the observed health effects. However, the development of data may not lead to the optimum response if risk assessment does not take into account complexities relating to human carcinogenicity.
Another correspondence in C&E News (August 6, 2001) emphasized the importance of understanding underlying mechanisms of carcinogenesis, and the need to extend the implications of those mechanisms to cancer risk evaluation. Chief among basic principles is the observation that all known human cancer risks have been faithfully reproduced in animal models. However, this is not true for inorganic arsenic compounds which, over decades of trials, have not caused tumors in animals.
Nevertheless, in various regions in Asia and South America containing arsenic at levels many times higher than found in the U.S., there is a statistical association with increased cancer risk. These data suggest the classification of arsenic as a human carcinogen; however, the picture is far more complicated.
John H. Weisburger (American Health Foundation) developed the concept that risk assessment of chemicals requires an evaluation as to whether or not they are genotoxic [Toxicol. Sciences, 57, 4(2000]. Genotoxic carcinogens react with DNA and are mutagenic. The conclusion was that virtually all human cancer risks are genotoxic, whereas there are other chemicals that enhance the risk but do so with a sharp dose-response relationship and a threshold that often is quite high.
Toby G. Rossman has done research on the mechanism of action of arsenic compounds as found in drinking water [Mutat. Res., 478, 159 (2001)]. It was demonstrated that arsenite (the likely carcinogenic form of arsenic) does not react with DNA to cause mutations and is not genotoxic in several tests. Rather, it appears to operate by inhibiting DNA repair and by increasing cell proliferation (growth). In a model of skin cancer in mice irradiated with ultraviolet light, arsenite alone in drinking water (at a concentration ten times the allowable level) caused no tumors at any site, but it enhanced the effect of solar UV.
This means that without a genotoxic carcinogenic partner, arsenite would likely have no effect at concentrations found in U.S. drinking water. In those instances where exposure to high levels of arsenic has led to cancer, the question needs to be asked as to the associated genotoxic carcinogenic partner. For skin cancer, it is likely exposure to UV light. For lung cancer, it is likely exposure to tobacco smoke. For other types of cancer, the associated genotoxic carcinogens need to be evaluated and, if possible, eliminated.
Based on these concepts, which have a solid scientific foundation, it can be suggested that the risk analysis for arsenic in drinking water should not be based on a linear extrapolation with no threshold. The data suggest that the current level of 50 ppb arsenic in water has not been proven to be a cancer risk. It is not clear that there is need to make great public expenditures to reduce naturally occurring arsenic in water in the U.S. to a level of 10 ppb.
Beyond these considerations, if domestic use of water in the U.S. occurs at around 100 gallons per day per capita, and human consumption accounts for only a fraction of a percent of this total, why should the bulk of water usage be required to meet the quality standards for potable use ? Implementing a point-of-use solution to areas of the country affected by high naturally occurring arsenic levels should not be dismissed based on issues of practicality and economics.