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

MERCURY 234
C
2. HEALTH EFFECTS
and exhibited acute renal failure showed pale and swollen kidneys (Murphy et al. 1979). A case study
reported acute renal failure characterized by oliguria, proteinuria, hematuria, and granular casts in a woman
who ingested 30 mg Hg/kg body weight as mercuric chloride (Afonso and deAlvarez 1960). Another case
study reported a dramatic increase in urinary protein secretion by a patient who ingested a single dose of
15.8 mg Hg/kg body weight as mercuric chloride (assuming a body weight of 70 kg) (Pesce et al. 1977).
The authors of the report surmised that the increased excretion of both albumin and β2-microglobulin were
indicative of mercury-induced tubular and glomerular pathology. Acute renal failure that persisted for
10 days was also observed in a 19-month-old child who ingested an unknown amount of powdered
mercuric chloride (Samuels et al. 1982). Decreased urine was also observed in a 22-year-old who attempted
suicide by ingesting approximately 20 mg Hg/kg (Chugh et al. 1978).
An MRL of 0.002 mg Hg/kg/day has been derived for intermediate-duration oral exposure
(15–364 days) to inorganic mercury.
This MRL was based on a NOAEL of 0.23 mg Hg/kg/day for renal effects in rats administered mercuric
chloride 5 days a week for 6 months (Dieter et al. 1992; NTP 1993). This dose was duration-adjusted for a
5 day/week exposure and divided by an uncertainty factor of 100 (10 for extrapolation from animals to
humans and 10 for human variability). Increased absolute and relative kidney weights were observed in rats
exposed to 0.46 mg Hg/kg/day, the next higher treatment level. At higher doses, an increased incidence of
nephropathy (described as foci of tubular regeneration, thickened tubular basement membrane, and
scattered dilated tubules containing hyaline casts) was observed. Renal toxicity is a sensitive end point for
inorganic mercury toxicity, as seen in other intermediate-duration oral studies on rats and mice exposed to
inorganic mercury (Carmignani et al. 1992; Jonker et al. 1993a; NTP 1993), as well as case reports of
humans ingesting inorganic mercury for acute and chronic durations (Afonso and deAlvarez 1960; Davis et
al. 1974; Kang-Yum and Oransky 1992; Nielsen et al. 1991; Pesce et al. 1977).
The relatively small difference between the acute-duration MRL (0.007 mg/kg/day) and the intermediate-
duration MRL (0.002 mg/kg/day) is not meant, nor is it considered, to imply a high level of precision in the
calculation of these health guidance values. Rather, this difference of 5 µg/kg/day reflects the increased
toxicity of continued low-dose exposure for longer periods of time and is consistent with the known build­
up of mercury levels in body tissues over a prolonged course of continued exposure. The actual precision
of any derived (actually estimated) MRL is dependent upon an encompassing, but not sharply defined, area
of uncertainty based upon the database used in its determination.