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

MERCURY A-8
APPENDIX A
MINIMAL RISK LEVEL (MRL) WORKSHEET
Chemical name(s): Mercury (inorganic)
CAS number(s): 7439-97-6
Date: June 15, 2001
Profile status: Final Draft
Route: [ ] Inhalation [X] Oral
Duration: [ ] Acute [ X ] Intermediate [ ] Chronic
Key to figure: 17
Species: Rat
Minimal Risk Level: 0.002 [ X ] mg/kg/day [ ] ppm
Reference: NTP. 1993. NTP technical report on the toxicology and carcinogenesis studies of mercuric
chloride (CAS no. 7487-94-7) in F344/N rats and B6C3F 1 mice (gavage studies). NTP TR408.
Experimental design: Fischer 344 rats (10/sex/group) were administered 0, 0.23, 0.46, 0.93, 1.9, or 3.7 mg
Hg/kg/day as mercuric chloride in deionized water by oral gavage once daily 5 days per week for 26 weeks.
Body weights were recorded weekly. Surviving animals were sacrificed and necropsied. Organ weights
were determined for the brain, heart, liver, lung, kidney, thymus, and testes. Histopathological
examinations were performed.
Effects noted in study and corresponding doses: The relative and absolute kidney weights were
significantly increased for dosed males and for females exposed to at least 0.46 mg/kg/day. At the two
low-dose groups and the control group, minimal nephropathy was observed in nearly all the males. At 0.93
mg/kg/day level, renal tubule necrosis became more severe (moderate) and was statistically significant and
remained at this severity at the higher dose groups. The female rats had a significant increased incidence at
the high dose only, and severity was minimal. Nephropathy was characterized by foci of tubular
regeneration, thickened tubular basement membrane, and scattered dilated tubules containing hyaline casts.
Macroscopic changes included granular kidneys in dosed males. After 4 months of exposure, urinary levels
of alkaline phosphatase, aspartate aminotransferase, lactate dehydrogenase, and gamma-glutamyl
transferase were significantly elevated in both sexes at 3.7 mg Hg/kg/day, but at 6 months control levels had
increased such that enzyme levels in males were no longer statistically significant and only levels of
alkaline phosphatase and gamma-glutamyl transferase were significantly elevated in females.
Dose end point used for MRL derivation: 0.23 mg Hg/kg/day; no renal effects
[X ] NOAEL [ ]LOAEL
Uncertainty and modifying factors used in MRL derivation: 100
[ ] 1 [ ] 3 [ ] 10 (for use of a LOAEL)
[ ] 1 [ ] 3 [ X ] 10 (for extrapolation from animals to humans)
[ ] 1 [ ] 3 [ X ] 10 (for human variability)
Was a conversion factor used from ppm in food or water to a mg/body weight dose?
If so explain: No conversion factor used.
Was a conversion used from intermittent to continuous exposure?