Arsenic Exposure and Toxicology: A Historical Perspective

Arsenic toxicity is a global health problem affecting many millions of people. Contamination is caused by arsenic from natural geological sources leaching into aquifers, contaminating drinking water and may also occur from mining and other industrial processes. Arsenic is present as a contaminant in many traditional remedies. Arsenic trioxide is now used to treat acute promyelocytic leukaemia. Absorption occurs predominantly from ingestion from the small intestine, though minimal absorption occurs from skin contact and inhalation. Arsenic exerts its toxicity by inactivating up to 200 enzymes, especially those involved in cellular energy pathways and DNA synthesis and repair. Acute arsenic poisoning is associated initially with nausea, vomiting, abdominal pain, and severe diarrhoea. Encephalopathy and peripheral neuropathy are reported. Chronic arsenic toxicity results in multisystem disease. Arsenic is a well documented human carcinogen affecting numerous organs. There are no evidence based treatment regimens to treat chronic arsenic poisoning but antioxidants have been advocated, though benefit is not proven. The focus of management is to reduce arsenic ingestion from drinking water and there is increasing emphasis on using alternative supplies of water.

https://pmj.bmj.com/content/postgradmedj/79/933/391.full.pdf

Acute and chronic arsenic toxicity

Toxicological profile for arsenic

The urinary elimination of the metabolites of arsenic has been followed up as a function of time in volunteers who ingested a single oral dose of arsenic (500 μg As) either as sodium arsenite (Asi), monomethylarsonate (MMA), or cacodylate (DMA). The excretion rate increased in the order Asi < DMA < MMA. After 4 days, the amount of arsenic excreted in urine represents 46, 78, and 75% of the ingested dose in the case of Asi, MMA and DMA, respectively. With regard to the in vivo biotransformations, it is concluded that DMA is excreted unchanged; MMA is slightly (13%) methylated into DMA while roughly 75% of the arsenic excreted after ingestion of Asi is methylated arsenic (about 1/3 as MMA and about 2/3 as DMA).

Comparison of the Urinary-excretion of Arsenic Metabolites After a Single Oral Dose of Sodium Arsenite, Monomethylarsonate, Or Dimethylarsinate in Man

This is the first of two articles reviewing the epidemiologic research on cardiovascular diseases (CVD) and the work environment. It deals with a number of nonchemical factors, ie, physical inactivity at work, stressors at work, shift work, noise, cold, heat, and electromagnetic fields and waves. First the methodological quality of each of the empirical studies is assessed on the basis of epidemiologic criteria. Then the research literature on each of the aforementioned factors of the work environment is evaluated. It is concluded that the hypothesis of a causal relationship between physical inactivity at work and risk of CVD is substantially supported by the literature. As regards work stressors and shift work, several good studies have been published during the last 10 years strongly suggesting a causal relationship. Other studies have shown a relationship between noise and elevated blood pressure, but the quality of this literature is low. Heat and cold appear to have an acute effect on the incidence of CVD, but the possible chronic effect has seldom been investigated. Concerning electromagnetic fields and waves, it is concluded that more research is needed. The study of CVD and work ought to play a bigger role in research in the fields of occupational medicine and cardiovascular epidemiology in the future.

Cardiovascular diseases and the work environment. A critical review of the epidemiologic literature on nonchemical factors.

This report examines the mortality experience of 527 men who retired from a copper smelter where they were exposed to airborne arsenic trioxide. Urinary arsenic values of all plant employees were d...

Mortality experience in relation to a measured arsenic trioxide exposure.

1. A study of 24 smelter workers routinely exposed to arsenic trioxide was conducted to evaluate some characteristics of its absorption and excretion. A statistically significant correlation was found between airborne arsenic trioxide concentrations below 300 mug/m3 and urinary arsenic values below 500 mug/liter. These men wore personal monitors for five consecutive work days and were determined to have been exposed to average airborne arsenic concentrations of 53 mug/m3 (70 mug/m3 of arsenic trioxide) which increased their urinary arsenic values from 152 mug/liter to 200 mug/liter (an average gain on 32%). 2. The background average urinary arsenic value for adult males not exposed to arsenic trioxide in industry was determined to be 52.6 mug/liter for 204 men during preemployment examinations. 3. After removal from industrial arsenic trioxide exposure, the rate of fall in urinary arsenic values varies with the magnitude of the urinary arsenic level. An initial decrease of 9.5% per day was measured for workers having urinary arsenic values below 200 mug/liter. The initial decrease is about 21% per day for workers with urinary arsenic values over 600 mug/liter. 4. It was determined that arsenic in seafood can alter, in a dramatic fashion, the urinary arsenic values determined for smelter workers within 24 hours following consumption. It is recommended, therefore, that the absorption of arsenic trioxide due to industrial exposure is best evaluated from urine samples collected at least two days after seafood has been eaten.

Sherman S. Pinto

Papers

Mortality experience in relation to a measured arsenic trioxide exposure.

Arsenic trioxide absorption and excretion in industry.