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Trends in the urinary concentrations of the four arsenic species, pentavalent [As (V)] and trivalent [As (III)] inorganic arsenic, monomethylarsonic acid (MMAA) and dimethylarsinic acid (DMAA), were followed for several days subsequent to the acute intoxication of two human subjects by arsenic trioxide [As (III)2O3] and sodium orthoarsenate [Na2HAs(V)O4.7H2O], respectively, in unsuccessful suicide attempts. Total arsenic concentrations ranged from 1.6 to 18.7 mg/l. The increasing predominance of the less toxic methylated species, especially DMAA, after 3 or 4 days supports the concept of methylation as a natural detoxification mechanism as part of an overall reduction/methylation sequence involved in the biotransformation of inorganic arsenic by the human body. However, the additional possibility of oxidation of As(III) to As(V) in vivo under extreme immediate postingestion conditions is suggested by initial high urinary As(V) after arsenic trioxide intoxication. Relative proportions of As(V), As(III), MMAA and DMAA in both cases probably reflect species-dependent differences in rates of direct elimination and reactivity with tissues as well as the efficiency of methylation.

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In arsenic exposure studies based on analysis of urine, it is important to distinguish inorganic arsenic (As(V), As(III)) and its methylated metabolites (monomethylarsonic acid, MMAA; dimethylarsinic acid, DMAA) from the rapidly excreted inert organoarsenicals, such as arsenobetaine, commonly ingested via seafood LoveU and Farmer, 1983). The recognised order of toxicity of these arsenicals, i.e. As(III) > As(V) >> MMAA, DMAA >> arsenobetaine, is reflected in the reduction/ methylation sequences As(V) ---> As(III) ---> MMAA ---> DMAA in the biotransformation of inorganic arsenic by the human body, as exemplified by analytical speciation of urinary arsenic in cases of acute arsenic poisoning (Lovell and Farmer, 1985). Using Vichy mineral water as a convenient source of inorganic arsenic (As(V)) (Farmer and Johnson, 1985), this natural detoxification mechanism was confirmed by controlled metabolic studies which also demonstrated that 40%-60% of the daily intake of inorganic arsenic is excreted, predominantly as DMAA, each day in urine (Johnson and Farmer, 1989b).On the basis of this observation and urinary X As(V), As(III), MMAA, DMAA concentrations, itwas determined that the daily inorganic arsenic intake of Glasgow adult controls (11-16.5 lxg) is comparable to MAFF dietary estimates, well within the FAO/WHO provisional tolerable daily intake of 2 lxg kg 1 body weight. Similar calculations showed that for adults from Cornwall in the mineralised south-west of England the additional average daily intake of inorganic arsenic is only 4.25-6.4 lxg, a surprisingly low increment in view of their arsenic-contaminated environment. A few noticeably elevated urinary Z As(V), As(III), MMAA, DMAA concentrations, up to a maximum of 48.7 gg g-1 creatinine, were found for pre-school children living in sight of a working tin mine (Johnson and Farmer, 1989a).In a comparative study of workers occupationally exposed, via inhalation and ingestion, to inorganic arsenic compounds, mean urinary !; As(V), As(III), MMAA, DMAA concentrations for Glasgow and Cornwall adults of 4.4 I.tg g-1 and 6.1 Ixg g-1 respectively, were markedly exceeded by workers involved in arsenical manufacture (245 ~tg g-l), glass manufacture (79.4 lxg g-l) and timber treatment (47.9 gg g-l). For these groups, the average urinary arsenic speciation pattern (1-6% As(V), 11-14% As(III), 14-18% MMAA and 63-70% DMAA), with notable As(V) and As(III) contributions, reflects an exposure to inorganic arsenic which is considerably enhanced relative to that of controls, for whom DMAA typically exceeds 80% of the sum. The urinary arsenic concentrations (maximum 956 ~tg g-l) for a significant proportion of the chemical workers, in particular, correspond to calculated intakes of inorganic arsenic in excess of recommended limits and Similar to those associated with increased incidence of lung cancer and other inorganic arsenic related diseases reported elsewhere in the world (Farmer and Johnson, 1989 Analytical Proceedings, 20, 274. Lovell, M.A. and Farmer, LG. 1985. Arsenic s...

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