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

MERCURY 283
2. HEALTH EFFECTS
The above information clearly indicates the possibility of developmental toxicity in offspring of mothers that
ingest sufficient amounts of organic mercury. The animal data also suggest that exposure to sufficient
amounts of inorganic mercury by inhalation of metallic mercury vapor or ingestion of inorganic mercury
may result in developmental toxicity.
Genotoxic Effects. The overall findings from cytogenetic monitoring studies of workers occupationally
exposed to mercury compounds by inhalation (Anwar and Gabal 1991; Barregard et al. 1991; Mabille et al.
1984; Popescu et al. 1979; Verschaeve et al. 1976, 1979) or accidentally exposed through ingestion (Wulf et
al. 1986) provided no convincing evidence that mercury adversely affects the number or structure of
chromosomes in human somatic cells. Studies reporting a positive result (Anwar and Gabal 1991; Barregard
et al. 1991; Popescu et al. 1979; Skerfving et al. 1970, 1974; Verschaeve et al. 1976; Wulf et al. 1986) were
compromised either by technical problems, a lack of consideration of confounding factors, or a failure to
demonstrate a relationship between mercury exposure and induced aberrations. Therefore, none of these
studies can be used to predict the potential genetic hazard to humans associated with exposure to mercury or
mercury compounds.
A dose-related increase in chromosome aberrations was observed in the bone marrow of mice administered a
single oral dose of mercuric chloride at levels of at least 4.4 mg Hg/kg (Ghosh et al. 1991). By contrast,
there was no valid evidence of a genotoxic effect on somatic cells of cats chronically exposed to methylmercury
orally (Miller et al. 1979). However, only minimal toxicity was observed at the high dose
(0.046 mg Hg/kg/day) in this study. Doses of 0.86, 1.7, or 3.4 mg Hg/kg as methylmercury hydroxide
administered once by intraperitoneal injection to groups of 2 male CBA mice did not cause an increase in
micronucleated polychromatic erythrocytes harvested from bone marrow cells 24 hours after treatment
(Jenssen and Ramel 1980). Similarly, there was no increase in structural chromosome aberrations in bone
marrow cells collected from male Swiss OF1 mice (3–4/group) 12, 24, 36, or 48 hours postexposure to single
intraperitoneal doses of 0.7, 1.5, 3.0, or 4.4 mg Hg/kg as mercuric chloride (Poma et al. 1981). The lack of a
clastogenic response, particularly with mercuric chloride, should not be viewed as a possible inability of this
compound to penetrate somatic cell membranes. There are data from the study of Bryan et al. (1974)
indicating that mercuric chloride can bind to chromatin in the livers of mice challenged with 38 mg
Hg/kg/day as mercuric chloride for 1 month. Although the overall data are mixed, the findings from a well
conducted study using oral dosing suggests that mercury can be clastogenic for somatic cells (Ghosh et al.
1991).