|| Harvard/MIT Faculty
|| CHRONIC HEALTH EFFECTS
absorption is also believed to lead to vascular
disease. A medical
glossary also lists symptoms. Other comments upon
chronic health effects
come from the University
Estimate of Deaths in Bangladesh
There are a
of interesting scientific questions that can be raised and may be
at some time in the future. For other chemicals,
animals have often given indications on what we should expect, but
it has proven hard to persuade laboratory animals to get cancer or
lesions at equivalent doses, the applicability of animal tests is
(1) Are dyspigmentation, keratoses, skin cancers, and internal cancers all different distinct medical end points or is there a natural progression from dyspigmentation, through keratoses to skin cancer? There are indications that Dyspigmentation in its early stages can be reversed on provision of pure water, but that keratoses may be irreversible. Also that skin cancers appear at locations on the skin where there has been some skin damage.
(2) Is there a threshold below which arsenic damage to people does not occur? Is such a threshold the same for all lesions, or is it just for skin lesions, or for the uncommon cancers such as bladder cancer? This is a difficult question to answer. This was discussed in the framework of arsenic induced lesions by Wilson in a poster at the 4th International Arsenic Conference in San Diego (and introduced to EPA) There are a number of subsidiary questions which this discussion raises.
(2a) Is the induction of any or all arsenic lesions a deterministic or a stochastic response? Not all members of a population exposed to a moderate level of arsenic develop lesions. Attempts to understand any differences between individuals that could explain differences in response seem to have had no success. Therefore it is usually assumed that the induction of these lesions is a stochastic rather than deterministic. Yet some evidence from Inner Mongolia presented by Tucker et al. in posters at the 5th International Arsenic Conference suggest that there may be more determinism than often assumed. Using the criteria for dyspigmentation employed by the Huhhot Anti-Epidemic Station the data suggest a threshold in response at about 75 ppb. Yet when Tucker's more sensitive method is used dyspigmentation is seen below 75 ppb suggesting that any level of arsenic produces an effect that develops deterministically into more serious effects.
(2b) Does arsenic act indirectly, and differently from background, on a stage of the process with a non linear process? The general default argument for low dose linearity depends upon the usual assumption, that cancer is caused by a multistage process, and arsenic is assumed to act directly on one stage in that process in the same way that natural, background, processes act. Then, as shown by many authors over the years (Doll, Peto, Crump. Crawford, Wilson, Garwin) low dose linearity becomes a simple mathematical consequence (Taylor's theorem). Is that a correct assumption? Moreover the linearity suggested by Taylor's theorem is only at low doses. Common sense suggest that low means appreciably less than the natural processes. It might well apply at the doses of concern for lung cancers which are common, especially among smokers, but does it apply for bladder cancer whose incidence at 500 ppb seems 10-50 times more than the natural incidence?
(2c) Arsenic is not a genotoxic agent. Does this fact make any difference to the discussion of linearity in question (2b)? Clearly only a genotoxic agent is expecte to act at the first, initiating, stage of the cancer process. But all agents, can act at later stages. It is noteworthy that several non-genotoxic agents, asbestos, benzene and dioxin are not genotoxic yet are assumed for regulatory purposes to have a linear dose response. Should arsenic be treated any differently from these, and if so, why?
(2d) Can studies of large populations exposed at low levels tell us much? Many people say no. There are too many problems that lead to variations between groups larger than statistical fluctuations suggesting that even taking a larger study will not give a significant effect. But in spite of the well known probelsm with ecological studies, Lamm et al. presented at the 5th International Arsenic Conference a study of the variation of bladder cancer across seveal US counties with different arsenic levels. Up to 50 ppb in the water no relation with arsenic level was seen, and the largest effects considered possible by the US National Academy studies could be excluded. The variation between counties was large (with a fluctuation of 23%) which suggests that if we could understand the reasons (or some of them) for the variation, a much stronger statement could be made.
(3) Are there any remedial actions that can cure arsenic poisoning or alleviate its symptoms? Answering this question is a major aim of several epidemiological studies including the one being carried out by Professor Christiani at the Harvard School of Public Health. From general considerations one might expect, for example, that arsenic related cancer incidence could be reduced a factor of two by a good diet (fresh fruit and vegetables) as compared to a bad diet. Even cigarette related lung cancers are so reduced in US studies. As of summer 2005 it has been shown (PhD thesis from HSPH) that ingestion of betel nuts increases the sensitivity by a factor of 2. It has been recently claimed that the medical algae Spirulina helps the treatment of of patients with chronic arsenic poisoning. Selenium is a chemical antagonist of arsenic and many people have suggested that it be used. But over doses of selenium can cause troubles themselves and there is general agreement that the use of selenium requires close supervision.
An abstract of this article and abstract (in
another article (in French) commenting upon it are available here.
The work of Dr Toby Rossman seems to be one of those that may
illuminate the problem. In particular she has shown that
works as a co-carcinogen
with ultraviolet light in causing skin cancers. This
has also been shown by Tucker and collaborators.