revised final - Agency for Toxic Substances and Disease Registry ...

MERCURY 333
2. HEALTH EFFECTS
metabolism is slight in humans. Penicillamine is removed though the kidneys (Florentine and Sanfilippo
1991). However, acute allergic reactions to penicillamine may occur (Goldfrank et al. 1990). An
experimental drug, N-acetyl-D,L-penicillamine (NAP), is very similar to its analog, penicillamine, in its
properties of absorption, metabolism, and excretion; however, it may be more mercury-specific in its
chelating abilities and less toxic (Goldfrank et al. 1990; Haddad and Winchester 1990). A high success
rate (88%) has been reported by investigators using NAP to treat victims of mercury inhalation (Florentine
and Sanfilippo 1991).
2,3-Dimercaptosuccoinic acid (DMSA), an analogue of BAL, is another experimental chelating agent.
DMSA can be given orally and is primarily excreted through the kidneys (Aposhian et al. 1992b). It has
been shown to be an effective chelator for both inorganic and methylmercury (Magos 1967). Comparative
studies have demonstrated that DMSA is as effective, if not more so, as dimercaprol, penicillamine, and
NAP. Data also suggest that this chelating drug produces fewer adverse effects than NAP (Florentine and
Sanfilippo 1991). 2,3-Dimercaptopropane-1-sulfonate (DMPS) is another BAL analogue that is an orally
effective chelator for mercury. Reports differ with respect to which of these analogues is less toxic
(Ellenhorn and Barceloux 1988; Goldfrank et al. 1990; Jones 1991; Karagacin and Kostial 1991). Better
results were obtained in rats with DMPS than with DMSA when the chelating agent was administered at
least 24 hours following exposure to mercuric chloride. However, early oral administration of DMPS
(within 24 hours) resulted in increased mercury retention (Karagacin and Kostial 1991). In contrast,
DMSA resulted in decreased mercury retention irrespective of when it was administered.
Hemodialysis with infusion of a chelator (cysteine, N-acetylcysteine, NAP) has been reported to be
effective in some severe cases of poisoning where renal failure is a complication (Berlin 1986; Goldfrank
et al. 1990; Haddad and Winchester 1990). It has been reported to be advantageous to begin the
hemodialysis before substantial renal damage has occurred (Haddad and Winchester 1990).
Because methylmercury undergoes enterohepatic recirculation, nonabsorbable agents have been used to
"trap" methylmercury excreted into the bile (Lund et al. 1984). A polystyrene resin containing sulfhydryl
groups added to food at a concentration of 1% doubled the elimination rate of methylmercuric chloride
when administered to mice. The elimination half-life decreased from 65 to 20 days (Clarkson et al. 1973).
Excretion of methylmercury may also be enhanced by bile drainage either through catheterization and
drainage of the choledochal duct or by surgical establishment of gallbladder drainage (Berlin 1986).
However, this method has not been used therapeutically.