Ethoxyquin distribution in rats: Skaare, J. U. & Nafstad, I. (1979). The distribution of 14C-ethoxyquin in rat. Acta pharmac. tox. 1979, 44, 303

Abstract

Arsenic in the environment occurs in both organic and inorganic compounds in its trivalent or pentavalent state. Certain fish and crustaceans contain very high levels of organic arsenic, often as arsenobetaine. In most other foodstuffs, levels of arsenic are low and the form is not known. The total daily intake of arsenic in the general population is reported to be approximately a few tenths of a milligram, but varies to a great extent depending on the amount of fish consumed.Both organic arsenic in seafood and inorganic arsenic in water, beverages, and drugs have been shown to be readily absorbed (70-90%) by the gastrointestinal tract. Some reports also indicate a fairly high degree of absorption after the inhalation of arsenic.Absorbed arsenic, irrespective of form, is widely distributed in the body. After exposure to inorganic arsenic, clearance of arsenic from the skin, upper gastrointestinal tract, epididymis, thyroid, and skeleton is slower than from other organs. The highest levels of arsenic in humans are normally found in the hair, nails, and skin. The main route of excretion is through the kidneys. After ingestion of arsenite or arsenate, approximately 35% of the dose is excreted within 2 days. From animal experiments it seems that insoluble inorganic arsenic inhaled through the airway is deposited and retained in lung tissue for a relatively long time. Animal data indicate arsenobetaine accumulation in cartilage, testes, epididymis, and muscle. Of ingested arsenobetaine, 50-80% is excreted in the urine within 2 days.Biotransformation of inorganic arsenic has been shown to occur in both animals and humans. Methylated compounds, such as methylarsonic acid and dimethylarsinic acid, have been detected in the urine after ingestion or inhalation of inorganic arsenic. Reduction of arsenate and oxidation of arsenite in vivo have been demonstrated in experimental animals. Recently, a human arsenic methyltransferase has been identified.Medications, contaminated food, beverages, and drinking water have given rise to a number of episodes of arsenic poisoning.Inorganic arsenic-induced skin lesions such as dermatoses, which may include eruption, pigmentation, or leukodermal hyperkeratosis, may ultimately lead to the development of skin cancer and Bowen disease. Effects on the nervous system (e.g. peripheral nervous disturbance), as well as on the heart and circulatory system (e.g. abnormal electrocardiograms, peripheral vascular disturbances with gangrene of the extremities, ischemic heart disease, cerebral infarction, and erectile dysfunction), have also been reported after chronic exposure to inorganic arsenic. Hematological changes after inorganic arsenic exposure are characterized by anemia and leukopenia. Chronic oral ingestion of inorganic arsenic in drinking water has also been reported to cause internal cancers (of the lung, bladder, kidney, and liver), diabetes, hypertension, cataract, pterygium, and developmental retardation.Arsenic poisoning among industrial workers is characterized by perforation of the nasal septum, skin changes, and peripheral neuritis. There is substantial epidemiological evidence of an excessive risk of lung cancer among workers exposed to arsenic.Arsine gas is a powerful hemolytic poison encountered under some industrial conditions. Arsine poisoning is characterized by nausea, vomiting, headache, shortness of breath, and hemoglobinuria. Literature on the toxicology and environmental aspects of arsenicals has been reviewed by the World Health Organization (WHO (World Health Organization), 1981, WHO., 2001), in monographs by the International Agency for Research on Cancer (IARC (International Agency for Research on Cancer), 1982, IARC., 2004, IARC., 2006, IARC, 2012), Fowler (1983), and by the National Research Council (NRC) (1999).