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

MERCURY 325
2. HEALTH EFFECTS
the reduction of the mercuric ion to metallic mercury, thereby making it more favorable for permeating
the placenta (Khayat and Dencker 1982).
Ethanol also potentiates the toxicity of methylmercury (Rumbeiha et al. 1992; Tamashiro et al. 1986;
Turner et al. 1981). Studies in animals have shown increased mortality (Tamashiro et al. 1986), increased
severity and decreased time to onset of neurotoxicity (hind-limb ataxia) (Tamashiro et al. 1986; Turner et
al. 1981), and increased renal toxicity (increased hematuria, renal weight, blood urea nitrogen, and
oliguria) (Rumbeiha et al. 1992; Tamashiro et al. 1986) when methylmercury exposure occurred
concomitant with ethanol ingestion. Although increased mercury concentrations were observed in the
brain and kidneys, the changes in mercury content were insufficient to fully explain the observed
potentiation of toxicity (Tamashiro et al. 1986), suggesting that ethanol may enhance the toxic
mechanisms of methylmercury. The mechanism for this enhancement is unknown.
Atrazine and potassium dichromate have also been demonstrated to enhance the toxicity of inorganic
mercury. Administration of atrazine, a widely used herbicide, with methylmercury in the diet resulted in
a higher deposition of mercury in the liver and an earlier onset of neurotoxicity (Meydani and Hathcock
1984). The mechanism underlying this interaction was unclear. Parenteral administration of minimally
toxic doses of potassium dichromate and mercuric chloride resulted in a synergistic inhibition of the renal
transport of organic ions p-aminohippurate and tetraethylammonium (Baggett and Berndt 1984).
Although the mechanism underlying this interaction was not examined, it may be associated with the fact
that both mercury and potassium dichromate are both toxic to the renal proximal tubule (Biber et al.
1968).
Agents that deplete nonprotein sulfhydryls may increase the toxicity of mercury. Depletion of
glutathione levels with diethylmaleate in rats resulted in greatly increased renal toxicity of mercury
chloride (Girardi and Elias 1991). Greater decreases in glomerular filtration and increases in fractional
excretion of sodium and lithium, urinary γ-glutamyltransferase, and lipid peroxidation were observed.
Conversely, chemicals that protect against oxidative damage may decrease the toxic effects of mercury.
Increased survival and decreased toxicity were observed in rats given vitamin E (α-tocopherol) during
treatment with methylmercury (Welsh 1979). It is probable that the mechanism for the protection
involved the antioxidant properties of vitamin E.
The exogenous application of the monothiols glutathione or its, precursor N-acetyl-DL-homocysteine
thiolactone (NAHT), or B-complex and E vitamins to mice exposed to methylmercuric chloride injected