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

MERCURY 345
2. HEALTH EFFECTS
Additional chronic-duration oral exposure information in animals concerning renal effects following
inorganic mercury exposure is needed to evaluate the threshold of this effect in humans following chronic
exposure. The data would be useful if populations living near hazardous waste sites were to be exposed
chronically to inorganic mercury that leached into near-by wells or water supplies.
Forestomach squamous cell papillomas and thyroid follicular cell carcinomas have been observed in rats
and renal tubule tumors have been observed in mice following oral exposure to mercuric chloride (NTP
1993). Renal tumors have also been observed in rats and mice after oral exposure to organic mercury
(Hirano et al. 1986; Mitsumori et al. 1981, 1990; Solecki et al. 1991). These results suggest the potential
carcinogenicity of mercury to humans. Therefore, additional chronic-duration animal studies on metallic,
inorganic, and organic mercury are needed to confirm the findings of the NTP study. Additional longterm
follow-up studies examining carcinogenicity in highly exposed populations (i.e., those involved in
mercury mining, or the exposed Iraqi or Japanese populations) are needed to evaluate the likelihood of
tumors appearing in humans.
Genotoxicity. Although there are data from several in vivo studies on rats (oral exposure) and mice
(intraperitoneal) indicating that inorganic and organic mercury compounds can cause clastogenic effects
in mammalian germinal cells, the differences in species sensitivity, and in some cases strain sensitivity,
do not permit the use of these findings for predicting a potential hazard to human genetic material (Suter
1975; Zasukhina et al. 1983). Epidemiological studies of humans occupationally or accidentally exposed
to mercurials were inconclusive, but the combined results from these studies did not suggest that metallic
mercury and organic mercury are clastogens for human somatic cells (Anwar and Gabal 1991; Barregard
et al. 1991; Mabille et al. 1984; Popescu et al. 1979; Verschaeve et al. 1976, 1979; Wulf et al. 1986).
There is, however, convincing evidence that inorganic and organic mercury compounds can interact with
and damage DNA in vitro (Williams et al. 1987). The outcome of this damage has not been
characterized, but there is some indication that mercury compounds are weak mutagens for cultured
mammalian cells. In addition, in vitro results with human cells (Betti et al. 1992) and animal cells
(Howard et al. 1991) and in vivo data in mice (Ghosh et al. 1991) suggest that mercury compounds can
cause clastogenic effects in somatic cells. Considering the problems stated above in using the whole
animal data, and the apparent species- and strain-specific responses noted in the DNA damage tests with
cultured mammalian cells, the in vitro data, while of interest, are probably not reliable indicators of
potential adverse effects in humans exposed to mercury. Well controlled human epidemiological studies
are needed to determine the genetic hazard of mercury compounds to humans.