AMA Arch Indust Health
Vol 13, 1956
P 489, 497
Treatment of Lead poisoning by Edathamil Calcium-Disodium
*D.O. Shiels, M.D., B.S., D.Sc., Ph.D., F.R.I.C., F.R.A.C.I.________________________________________________________________
Edathamil tetrasodium (tetraso-diumethylene-diamine tetra-acetate) is known under the trade name of Versene. Its sodium salts have the property of forming with calcium or with lead and certain other heavy metal element compounds (the so-called chelates) in which the ionic activity of these elements is very small.
Sodium edathamil will remove calcium from body fluids and tissues and may therefore cause harmful side effects, but edathamil calcium-disodium has no such action.
From edathamil calcium-disodium the calcium is displaced by the element lead. The resulting compound is readily soluble in water and body fluids and has extremely low physiological activity so far as the lead is concerned. It is readily excreted by the by the kidney.
Present indications are that edathamil calcium-disodium has no harmful effect on bodily magnesium, iron, or trace heavy metals, such as cobalt, manganese, and copper, since in the complexes formed by these metallic elements with naturally occurring compounds in the body these elements are more tightly bound that with edathamil calcium-disodium.
PREVIOUS WORK
There have been a number of recent papers on the use of this substance in cases of lead poisoning and on its effects on other heavy metals in the human body (Belknap and Perry,1 Bessman and associates,2 Byers and Maloof,3 conference participants,4 Foreman and associates,5 Hardy and associates,6 Karpinski and associates,7 Rubin and associates,8 Sidbury and associates,9 Hamilton and Scott15).
Whereas the very marked increase in urinary lead concentrations and in the urinary lead excretion is well established, so far reports on the effects on fecal lead in cases of absorption or inorganic lead and compounds have not appeared, and the reports on the effects on blood lead have not been numerous.
When this investigation commenced, most of the papers which had appeared had stressed the use of this substance by the intravenous route.
After this present work had been almost completed, two other investigations on the oral use came to our notice. Sidbury and associates,9 contrasted the effect of oral and intravenous application. They found marked increase in urinary lead excretion due to both methods. With the oral method on the maximum excretion in the urine was not reached until the third or fourth day. These investigators found five to ten-fold increases in urinary excretion of lead follow oral administration of EDTA.
* * *
COMPARISON WITH OTHER METHODS OF TREATMENT
An interesting comparison of the effects of sodium citrate and edathamil calcium-disodium as therapeutic agents has been possible in two cases.
One patient has engaged in a battery works and the other in lead casting section of a large printing works where he was exposed to a considerable hazard during drossing. Each of these persons became poisoned on two separate occasions, with an interval or 8½ months and 11½ months between their respective poisonings. On the first occasion of each poisoning they were treated with sodium citrate orally; on the second occasion, with edathamil calcium-disodium.
* * *
The increase in the excretion of lead in urine is very much greater with this method than with the sodium citrate treatment in an equal period of time.
* * *
SUMMARY
Edathamil calcium-disodium taken orally in doses of 2gm twice a day for adults caused from fivefold to thirty-five-fold increases in urinary lead concentration and from fivefold to twenty-two-fold increases in urinary lead excretion. In some instances this occurred on the first day of treatment.
This method of treatment caused very considerable increase in fecal lead excretion.
It caused immediate falls and subsequent rises in blood lead concentration in some cases and in another case a steady fall.
In most instances the amounts excreted in the urine alone greatly exceeded the amount circulating in the blood prior to treatment.
[Emphasis added.]
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