Chronic Arsenic Poisoning: History, Study and Remediation

Arsenic has been used for many years for medicinal purposes. It used to be used as a cure for diseases such as syphilis and has been shown to assist in curing some leukemias. It was taken as a medicine in Fowler's Solution for well over a century. That arsenic at low levels is safe seemed to be reinforced by animal studies that seemed to show that arsenic is beneficial (to animals) at low doses. Indeed, the fact that laboratory animals could not be persuaded to develop cancer misled toxicologists throughout the world and greatly contributed to the present catastrophe. Others have written about other possible beneficial effects at very low levels. It is important to note that the beneficial effects are for different medical outcomes (end points) than either the acute or chronic adverse effects and that both beneficial and adverse effects can be observed simultaneously (as is well known for alcohol ingestion). Another detailed article about beneficial uses of arsenic can be found here. Mineral hot springs in the USA still advertise arsenic pools and their users, including this webmaster, are convinced that the effects are beneficial! (But arsenic penetrates the skin only slowly)

Chronic Adverse Effects
.

Chronic effects of prolonged low level exposure have recently showed up. Among various summaries we link to an information site run by ASTDR. Skin pigmentation, keratoses and skin cancers were found by Tseng in Taiwan in 1966 among people who drank from arsenic contaminated wells (but no effect was seen below about 150 parts per billion (ppb), which might therefore be a biological threshold) and a very high incidence of lung, bladder and other cancers was found in Taiwan by Dr Chien-Jen Chen in 1986 and by Dr Allan Smith and collaborators in Chile in 1993. These convinced WHO to recommend lowering the regulatory level from 50 ppb to 10 ppb for arsenic in water. It appears that there are no data on humans to contest the idea that prolonged exposure to low doses is dangerous. Although arsenic was used medicinally in "Fowler's Solution" (1% arsenite), prolonged use had led to these chronic skin effects. This was observed as early as 1888 by Hutchinson. A follow up of a number of English patients treated with Fowler's Solution has been reported by Dr Susan Evans in published literature, in a report at the February 1998 conference in Dhaka and in a presidential address by Susan Evans to the Liverpool Medical Institute, which is available for download in PDF format. This shows that the use of "Fowler's solution" (which is primarily medicinal arsenic) in the UK is probably responsible for 5 bladder cancer cases among the patients among whom only 1.6 were expected from natural causes. The arsenic dose was equivalent to an average lifetime dose that would come from drinking water with about 25 ppb of arsenic therein.

After several years of low level arsenic exposure, various skin lesions appear. These are manifested by hyperpigmentation (dark spots), hypopigmentation (white spots) and keratoses of the hands and feet. After a dozen or so years skin cancers are expected. Twenty or thirty years after exposure to 500 ppb of arsenic, internal cancers (lung, kidney, liver and bladder) appear among 10% of all exposed. Moreover, the dose-response relationship for these internal cancers is consistent with being linear with no threshold. Photographs of a number of victims of this poisoning are available both from Bangladesh and from Inner Mongolia.

Although the most dramatic effect was the observation of internal cancers in Tawian, the most extensive epidemiological studies have come from the work in Chile, in which Dr Allan Smith of UC Berkeley has been heavily involved. They find the extraordinarily surprizing result that ingested arsenic in Chile has produced lung cancer at a rate greater than that of a heavy cigarette smoker! Recently, the group identified an effect of arsenic exposure to chldren - who have developing lungs -. Children exposed to arsenic have ten times the normal lung cancer incidence.

. .
The Effect of Diet

An important issue for coping with arsenic exposure is the effect of diet. A general issue can be stated: there is frequently more than one cause of a cancer or a lesion. For example lung cancer can be caused by cigarette smoking or asbestos or both together, in a synergistic way such that the risks multiply (rather than add) when both are present. In the USA it has been found that people who have a good diet of fresh fruit and vegetables (5 servings per day) have half the risk of many cancers, including lung cancers caused by cigarettes, as those without a good diet. By analogy, one might expect that the lung cancer risk from arsenic will be less among those with a good diet. Anecdotal indications from Bangladesh suggests that a good diet reduces skin lesions, and the effect is seen in West Bengal , but the effect is small and the authors recommend that effort is better spent on obtaining pure water. Nonetheless epidemiological studies to confirm this are highly desirable. Khaliquzzaman and Khan have calculated the "Arsenic Exposure of Bangladesh Population through Food Chain" using known amounts in food, in an unpublished World Bank report. The amount is less than from drinking water but not much less.

There are several specific chemicals that have been suggested that would either (i) help to prevent arsenic lesions by rapid removal of arsenic from the body or (ii) help to cure arsenic lesions. Encouragement of methylation of the arsenic probably accelerates methylation, but the methylation has been suggested as a cause of internal cancers. The specific chemical that has come to the mind of many health experts is selenium. It was noted in the 1930s that effects of excess selenium can be counteracted by adding arsenic to the diet because As and Se combine. Does the inverse take place? It is reported that areas with high incidence of arsenical lesions have low selenium in the water. Some victims have low selenium levels. Does adding selenium to the diet really help, either to prevent the lesions from forming (likely), or to treat them afterwards (less likely)? We have, with help from others, compiled a list of references and a recent paper on the subject. Professor Zuberi of Rajshashi University has suggested methionine to reduce the arsenic lesions. Dr. OGB Nambiar has suggested that ferrous sulphate, after conversion to sulfide by bacteria in the colon, absorbs arsenic and assists safe excretion. The evidence for these remains indirect, and there may be (as suggested above) competing adverse effects. Only good epidemiology can tell and this is under way in several places.

This is the subject of a whole issue of the journal Applied Geochemistry:
Bhattacharya, P., A. H. Welch, K. M. Ahmed, G. Jacks and R. Naidu (Eds.)