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

MERCURY 281
2. HEALTH EFFECTS
concentration resulting from injection of mercuric chloride. Furthermore, the authors reported that metallic
mercury appeared to oxidize to Hg +2 in the fetal tissues. Evidence that inhalation exposure may result in
developmental toxicity comes from a study in which neonatal rats were exposed to metallic mercury vapor
during a period of rapid brain development (this occurs postnatally in rodents but prenatally in humans),
resulting in impaired spatial learning (Fredriksson et al. 1992). Oral administration of inorganic mercury
salts to pregnant hamsters has been observed to produce an increase in the number of resorptions and small
and edematous embryos (Gale 1974). Mercury-induced embryotoxicity in one non-inbred and five inbred
stains of female hamsters was investigated by Gale and Ferm (1971). A single subcutaneous injection of
9.5 mg Hg/kg as mercuric acetate to dams on Gd 8 produced a variety of malformations, including cleft
palate, hydrocephalus, and heart defects, and statistically significant interstrain differences in the
embryotoxic response. Single doses of 1.3–2.5 mg Hg/kg as mercuric acetate injected intravenously into
pregnant hamsters on Gd 8 produced growth retardation and edema of the fetuses at all 3 dose levels, while
an increase in the number of abnormalities was detected at the two higher doses (Gale and Ferm 1971). The
relative effectiveness of different exposure routes in hamsters was compared by Gale (1974). The following
sequence of decreasing efficacy was noted for mercuric acetate: intraperitoneal > intravenous >
subcutaneous > oral. The lowest doses used (2 mg/kg for intraperitoneal and 4 mg/kg for the other 3 routes)
were all effective in causing increased resorption and an increased percentage of abnormalities. Intravenous
injection of 1.5 mg Hg/kg/day as mercuric chloride also resulted in a significant increase in the number of
abnormal preimplantation embryos (Kajiwara and Inouye 1986).
In animals, embryolethal, anatomical, and behavioral effects have been reported following oral exposure of
pregnant dams to methylmercury (Bornhausen et al. 1980; Cagiano et al. 1990; Elsner 1991; Fowler and
Woods 1977; Fuyuta et al. 1978, 1979; Guidetti et al. 1992; Gunderson et al. 1988; Hughes and Annau 1976;
Ilback et al. 1991; Inouye and Kajiwara 1988; Inouye and Murakami 1975; Inouye et al. 1985; Khera and
Tabacova 1973; Lindstrom et al. 1991; Nolen et al. 1972; Olson and Boush 1975; Reuhl et al. 1981a, 1981b;
Rice 1992; Rice and Gilbert 1990; Stoltenburg-Didinger and Markwort 1990; Yasuda et al. 1985). Thus far,
the most sensitive animal assay for developmental neurotoxicity has been a behavioral paradigm that
examined the number of rewarded responses to differential reinforcement at high rates (Bornhausen et al.
1980). At doses of 0.008 mg Hg/kg/day and above, a dose-related decrease in rewarded responses was
observed in 4-month-old offspring of rats treated on Gd 6–9. The effect was more pronounced in male
offspring than females. Foster mothers were used to preclude consumption of contaminated milk during
lactation.