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

MERCURY 114
2. HEALTH EFFECTS
increased urinary γ-glutamyltransferase activity was also observed. Mice given a single gavage dose of
10 mg/Hg/kg as mercuric chloride showed minor renal tubular damage and rapid regeneration of the tubular
epithelium (Nielsen et al. 1991). At 20 mg Hg/kg/day, the mice showed necrosis of the proximal tubules.
Mice given gavage doses of mercuric chloride 5 days a week for 2 weeks showed an increase in absolute and
relative kidney weights at 3.7 mg Hg/kg/day and acute renal necrosis at 59 mg Hg/kg/day (NTP 1993).
Groups of 10 female Sprague-Dawley rats were administered a single gavage dose of mercuric chloride at
7.4 or 9.2 mg Hg/kg in water and necropsied at 14 days postexposure. No effects on body weight or weights
of other organs were found. Mercury was found mainly in the kidneys (12.6 and 18.9 ppm at the low and
high doses, respectively), but trace amounts were also detected in the liver, brain, and serum. Mild-tomoderate
morphological changes, consisting of protein casts, cellular casts, and interstitial sclerosis, were
noted in the kidneys of HgCl2-treated animals in both groups (Lecavalier et al. 1994).
In a 4-week range-finding study, groups of 5 rats per sex (10 per sex for controls) received diets containing
mercuric chloride at 5, 10, or 20 mg Hg/kg/day for males and 5.5, 11.1, and 22.2 mg Hg/kg/day for females.
Nephrosis and proteinaceous casts in the kidneys were observed in all groups (males and females) fed
mercuric chloride. An increased number of epithelial cells in the urine was observed in males exposed at the
low dose; however, this effect was not observed at higher dose levels and the authors noted that the effect
could not be ascribed to treatment. The minimum-nephrotoxic-effect level (MNEL) and the no-nephrotoxiceffect
level (NNEL) for mercuric chloride in feed were determined to be 8 mg Hg/kg/day in males and
8.9 mg Hg/kg/day in females and 1 mg Hg/kg/day in males and 1.1 mg Hg/kg/day in females, respectively
(Jonker et al. 1993b). In a follow-up 4-week study, 10-week-old Wistar rats were fed mercuric chloride at
the MNEL and NNEL. In males, the MNEL resulted in the presence of ketones in urine and an increase in
the relative weight of kidneys. Effects observed in females in the MNEL group included decreased density
of urine and increased absolute and relative kidney weights. Increased absolute and relative kidney weights
were also seen in females at the NNEL. A few histopathological changes were found in the basophilic
tubules in the outer cortex of the kidneys in 5 of 5 males and 1 of 5 females exposed to the MNEL (Jonker et
al. 1993b).
Similarly, male mice receiving mercuric chloride in drinking water for 7 weeks showed slight degeneration
of the tubular epithelial cells (nuclear swelling) at 2.9 mg Hg/kg/day and minimal renal nephropathy