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

MERCURY 289
2. HEALTH EFFECTS
mercuric chloride in rat fibroblasts, while 5×10 -6 M mercuric chloride produced a comparable response in
C57BL/6 mouse cells; at this level, the response in CBA mouse cells was marginal. Mercuric chloride can
also bind to the chromatin of rat fibroblasts (Rozalski and Wierzbicki 1983) and Chinese hamster ovary cells
(Cantoni et al. 1984a, 1984b; Christie et al. 1984, 1985). Using the alkaline elution assay with intact
Chinese hamster ovary cells, several studies have demonstrated that mercuric chloride induces single-strand
breaks in DNA (Cantoni and Costa 1983; Cantoni et al. 1982, 1984a, 1984b; Christie et al. 1984, 1985).
Furthermore, Cantoni and Costa (1983) found that the DNA-damaging potential of mercuric chloride is
enhanced by a concurrent inhibition of DNA repair mechanisms. Methylmercuric chloride induced singlestrand
breaks in the DNA of intact rat glioblastoma cells, Chinese hamster V79 (fetal lung) cells, human lung
cells, and human nerve cells (Costa et al. 1991). Results of the Bacillus subtilis rec-assay (Kanematsu et al.
1980) and the sister chromatid exchange assay (Howard et al. 1991) provide additional support to the body
of evidence suggesting that mercuric chloride is genotoxic. However, there is no clear evidence that mercury
would cause DNA damage in vivo.
Two organic mercury compounds (methylmercury chloride at 0.08–0.4 µg Hg/mL and methoxyethyl
mercury chloride at 0.04–0.23 µg Hg/mL) induced weak but dose-related mutagenic responses in Chinese
hamster V-79 cells near the cytotoxic threshold (Fiskesjo 1979). Methylmercury was neither mutagenic nor
caused recombination in Saccharomyces cerevisiae, but it did produce a slight increase in the frequency of
chromosomal nondisjunction (Nakai and Machida 1973). Both methylmercury and phenylmercuric acetate
induced primary DNA damage in the B. subtilis rec-assay (Kanematsu et al. 1980).
In contrast, high concentrations of methylmercury (1 or 2 µm) did not increase the frequency of sister
chromatid exchanges in cultured blastocysts of early ICR mouse embryos (Matsumoto and Spindle 1982).
Severe toxicity, which was more intense in blastocysts than in morulae, consisted of cessation of
preimplantation development, blastocoel collapse, and mitotic delay.
In summary, the body of evidence showing the induction of primary DNA damage in mammalian and
bacterial cells and weak mutagenesis in mammalian cells suggests that inorganic and organic mercury
compounds have some genotoxic potential. Although the data on clastogenesis are less consistent, recent
well conducted studies suggest that mercury compounds can be clastogenic. Refer to Table 2-12 for a
further summary of these results.