Arsenic in drinking-water
Background document for development of WHO Guidelines for Drinking-water Quality
Effects on humans
A number of studies have attempted to show that arsenic is an essential element, but a biological role has not been demonstrated so far (US NRC, 1999, 2001). Arsenic has not been demonstrated to be essential in humans (IPCS, 2001).
The acute toxicity of arsenic compounds in humans is predominantly a function of their rate of removal from the body. Arsine is considered to be the most toxic form, followed by the arsenites (arsenic(III)), the arsenates (arsenic(V)) and organic arsenic compounds. Lethal doses in humans range from 1.5 mg/kg of body weight (diarsenic trioxide) to 500 mg/kg of body weight (DMA) (Buchet & Lauwerys, 1982). Acute arsenic intoxication associated with the ingestion of well water containing 1.2 and 21.0 mg of arsenic per litre has been reported (Feinglass, 1973; Wagner et al., 1979). MMA(III) and DMA(III) are more toxic than arsenate in vivo and in vitro.
Early clinical symptoms of acute intoxication include abdominal pain, vomiting, diarrhoea, muscular pain and weakness, with flushing of the skin. These symptoms are often followed by numbness and tingling of the extremities, muscular cramping and the appearance of a papular erythematous rash (Murphy et al., 1981). Within a month, symptoms may include burning paraesthesias of the extremities, palmoplantar hyperkeratosis, Mee’s lines on fingernails and progressive deterioration in motor and sensory responses (Fennell & Stacy, 1981; Murphy et al., 1981; Wesbey & Kunis, 1981).
Signs of chronic arsenicism, including dermal lesions such as hyper- and hypopigmentation, peripheral neuropathy, skin cancer, bladder and lung cancers and peripheral vascular disease, have been observed in populations ingesting arsenic-contaminated drinking-water (Tseng et al., 1968; Borgońo & Greiber, 1972; Hindmarsh et al., 1977; Tseng, 1977; Zaldivar, 1980; Zaldivar & Ghai, 1980; Valentine et al., 1982; Cebrian et al., 1983). Dermal lesions were the most commonly observed symptom, occurring after minimum exposure periods of approximately 5 years. Effects on the cardiovascular system were observed in children consuming arsenic-contaminated water (mean concentration 0.6 mg/litre) for an average of 7 years (Zaldivar, 1980; Zaldivar & Ghai, 1980).
In a large study conducted in Taiwan, a population of 40 421 was divided into three groups based on the arsenic content of their well water (high, >0.60 mg/litre; medium, 0.30–0.59 mg/litre; and low, <0.29 mg/litre) (Tseng, 1977). There was a clear dose–response relationship between exposure to arsenic and the frequency of dermal lesions, “blackfoot disease” (a peripheral vascular disorder) and skin cancer. However, several methodological weaknesses (e.g., investigators were not “blinded”) complicate the interpretation of the results. In addition, the possibility of other causes of blackfoot disease (e.g., humic acids in artesian well water) were not considered (Lu, 1990).
In Taiwan, the prevalence and mortality rates of diabetes mellitus were higher among the population of the blackfoot disease endemic area. There was also an exposure–response relationship between cumulative arsenic exposure and the prevalence of diabetes mellitus. A similar exposure–response pattern was observed in a study in Bangladesh, where prevalence of keratosis was used as a surrogate for arsenic exposure (US NRC, 1999, 2001; IPCS, 2001).
There have been numerous epidemiological studies that have examined the risk of various cancers associated with arsenic ingestion through drinking-water. Many of these studies are ecological-type studies, and many suffer from methodological flaws, particularly in the measurement of exposure. However, there is overwhelming evidence that consumption of elevated levels of arsenic through drinking-water is causally related to the development of cancer at several sites, particularly skin, bladder and lung. In several parts of the world, arsenic-induced disease, including cancer, is a significant public health problem. The studies have been reviewed in detail (US NRC, 1999, 2001; ATSDR, 2000; IPCS, 2001). Because trivalent inorganic arsenic has greater reactivity and toxicity than pentavalent inorganic arsenic, it is generally believed that the trivalent form is the carcinogen. However, there remain considerable uncertainty and controversy over both the mechanism of carcinogenicity and the shape of the dose–response curve at low intakes. Recently, the trivalent methylated metabolites, MMA(III) and DMA(III), have been found to be more genotoxic than inorganic arsenic. The role of these metabolites with regard to arsenic carcinogenicity remains unknown.
IPCS (2001) concluded that:
Long-term exposure to arsenic in drinking-water is causally related to increased risks of cancer in the skin, lungs, bladder and kidney, as well as other skin changes such as hyperkeratosis and pigmentation changes. These effects have been demonstrated in many studies using different study designs. Exposure–response relationships and high risks have been observed for each of these end-points. The effects have been most thoroughly studied in Taiwan but there is considerable evidence from studies on populations in other countries as well. Increased risks of lung and bladder cancer and of arsenic-associated skin lesions have been reported to be associated with ingestion of drinking-water at concentrations ≤50 µg arsenic/litre.