Arsenic methylation saturable

From a practical point of view, saturation of elimination has important consequences. If the metabolism becomes saturated, the duration of the action of the compound is prolonged. In such a case, correct timing for collection of biological monitoring samples also becomes difficult to assess. Furthermore, saturation of metabolism may also have qualitative effects. For example, it has been argued (but not yet proved) that arsenic compounds cause cancer at high doses at which methylation of inorganic arsenic becomes saturated. ... 

When all the dimethyl sulphate has been added, the flask is fitted with a reflux condenser and the contents boiled for 2 hours. The sodium salt of methyl arsenic acid is obtained. It is allowed to cool and a small amount of potassium iodide is added, after which a current of sulphur dioxide is passed through the liquid until it is saturated (about 6 hours). The mixture is again boiled under reflux for about an hour during this period, an oily substance consisting of methyl arsenious oxide deposits at the bottom of the flask, where it is saturated with a current of gaseous hydrochloric acid, while the flask is cooled externally. On attaining complete saturation, the flask is connected with a Liebig s condenser and the liquid distilled. Much hydrochloric acid is evolved at first later a mixture of hydrochloric acid and methyl dichloroarsine distils over. The distillation is continued until no more oily liquid condenses. The distillate is placed in a separatory funnel and the oily layer separated and distilled. 

The separation of traces is done in a closed system and involves absorbing the traces in a suitable sorbent, for example hydrogen sulphide in a zinc acetate solution, ammonia in dilute HCl, and methyl borate in dilute NaOH. In the Gutzeit method traces of arsenic, liberated in the form of AsHa, are absorbed by a strip of paper saturated with a reagent giving a colour effect with AsHa. In all such procedures a carrier gas, such as hydrogen, nitrogen, chlorine, or steam is indispensable... 

Inorganic arsenic, MMA, and DMA were found to be the only metabolic forms of As in urine of volunteers who ingested 125, 250, 500, or 1000//g sodium As daily for 5 days (Buchet et al. 1981a). The amounts of iAs, MMA, and DMA excreted in urine on day 5 (taken separately or together) correlated significantly with daily ingested dose. As noted above, this study provided equivocal evidence that the capacity for methylation of As could be saturated at high levels of iAs intake. 

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