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

MERCURY 348
2. HEALTH EFFECTS
might affect the response to other forms or other routes of exposure (e.g., how an adverse immune effect
induced by inhalation of mercury vapor from dental amalgam might effect the dose-response from
exposure to ingested methylmercury). Therefore, the potential for immunotoxic effects from exposure to
mercury vapor, mercury salts, or methylmercury separately or in combination is of considerable
importance and warrants further research, especially from low level chronic exposures.
Neurotoxicity. The nervous system is the major target organ for metallic and organic mercury
through inhalation and oral routes, respectively. In humans, the neurological effects of metallic mercury
have been observed primarily after acute high-concentration exposures (accidental) to intermediate and
chronic low-concentration exposures (occupational). Tremors and irritability are the most prominent
symptoms of inhaled metallic mercury in humans (Albers et al. 1988; Bidstrup et al. 1951; Fawer et al.
1983; Piikivi et al. 1984). Information on effects in humans from oral exposure includes case histories, for
example, a chronic oral exposure to a laxative containing mercurous chloride (Davis et al. 1974), acute to
intermediate duration ingestion of high levels of methylmercury-contaminated food (Bakir et al. 1973;
Kutsuna 1968), or to chronic low-level exposures from fish or marine mammals containing methylmercury
(Davidson et al. 1995aa, 1995b; Grandjean et al. 1997b, 1998). Case histories of dermal exposure to
inorganic mercury cite similar neurological effects from acute (Bourgeois et al. 1986; DeBont et al. 1986)
or chronic exposures (Dyall-Smith and Scurry 1990).
The neurotoxicity of inhaled metallic mercury has been studied in animals for acute and intermediate
exposures (Ashe et al. 1953; Ganser and Kirschner 1985; Kishi et al. 1978). Behavioral, motor, and
cognitive effects, as well as histopathological changes in the brain, were reported in rats, rabbits, and mice.
Neurological disturbances in rats and mice resulted from acute, intermediate, and chronic oral exposures to
mercuric mercury (Chang and Hartmann 1972b; Ganser and Kirschner 1985). Oral exposure to organic
mercury in animals produced a range of neurological changes (Charbonneau et al. 1976; Evans et al. 1977;
Magos and Butler 1972; Rice and Gilbert 1982; Sharma et al. 1982; Tsuzuki 1981). A chronic inhalation
MRL was derived for metallic mercury. Additional animal studies are needed, however, to evaluate the
neurotoxicity of inorganic mercuric salts to resolve some of the conflicting findings from pervious work
(Chang and Hartmann 1972b; Ganser and Kirschner 1985; Goldman and Blackburn 1979; NTP 1993). In
vivo studies are needed to evaluate the mechanisms of neurotoxic effects seen in in vitro studies, i.e., the
lipoperoxidation and cell injury in methylmercury-exposed cerebellar granule cells (Sarafian and Verity
1991). Further evaluation is needed in humans and animal models of the potential for neurological effects
and delayed neurotoxicity from chronic low level exposures to organic and inorganic mercury, especially