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

MERCURY 354
2. HEALTH EFFECTS
initially distributed in a similar manner to methylmercury; however, the distribution eventually resembles
that of inorganic mercury.
The available evidence suggests that feces and urine constitute the main excretory pathways of metallic
mercury and inorganic mercury compounds in both humans and animals. Additional excretory routes
following metallic and inorganic mercury exposure include exhalation and secretion in saliva, sweat, bile,
and breast milk (Joselow et al. 1968b; Lovejoy et al. 1974; Rothstein and Hayes 1964; Sundberg and
Oskarsson 1992; Yoshida et al. 1992). Excretion following exposure to organic mercury is considered to
be predominantly through the fecal route in humans. Evidence from studies in humans and animals (mice,
rats) suggests that exposure to methylmercury leads primarily to biliary secretion, while excretion is
initially through the bile; it then shifts to the urine following phenylmercury exposure (Berlin and Ullberg
1963; Berlin et al. 1975; Gotelli et al. 1985; Norseth and Clarkson 1971). No further comparative studies
on excretion are warranted because there is no apparent difference in the excretion of mercury in any form
in humans and animals.
Two PBPK models have recently been published on the pharmacokinetics of methylmercury in rats (Farris
et al. 1993; Gray 1995). Additional PBPK studies are needed to support species and dose extrapolations,
and a better understanding of the underlying toxic and kinetic mechanisms is needed in support of human
risk assessments.
Validation of in vitro data is a major need. Much of the data from in vitro experimentation is based on
unrealistic concentrations of the toxicant or is derived from studies using non-physiological designs. In
particular, more validation is needed for immunotoxicity studies and biochemical studies.
Methods for Reducing Toxic Effects. Nonspecific methods or treatments for reducing absorption
following mercury exposure include the administration of chelators or protein solutions to neutralize and
bind to inorganic mercury compounds (Bronstein and Currance 1988; Florentine and Sanfilippo 1991;
Gossel and Bricker 1984). The use of a particular chelator is dependent upon the type of mercury
exposure (Gossel and Bricker 1984). Chelation therapy is the treatment of choice for reducing the body
burden of mercury (Florentine and Sanfilippo 1991; Gossel and Bricker 1984; Haddad and Winchester
1990). However, chelation releases mercury from soft tissues that can then be redistributed to the brain.
Additional research is needed to elucidate the mechanisms of absorption and distribution of inorganic and
organic mercury. Animal studies suggest that antioxidants may be useful for decreasing the toxicity of