Kinetics of Methyl Mercury in Blood and Brain During Chronic Exposure in the Monkey Macaca fascicularis

Abstract

The disposition parameters derived from a compartmental model kinetic analysis of blood Hg levels in nonpregnant, adult female Macaca fascicularis given daily doses of MeHg did not vary with either dosage level (50, 70 or 90 micrograms MeHg/kg b.wt.day) or duration of exposure (up to 507 day). In contrast, blood clearance of Hg in pregnant females was dose-dependent; it being higher at the 90 micrograms MeHg/kg b.wt.day than at the lower dosage levels. Hg levels in the brain of adult fascicularis relative to blood Hg also increased at the highest level of exposure. Blood Hg half-life in neonate fascicularis was similar to half-life in their mothers (adults). Finally, the regional distribution of mercury in the brains of adult and neonate fascicularis exposed to low and intermediate levels of MeHg resembles the reported distribution of mercury in the brains of adult and neonate humans environmentally exposed to MeHg. Consequently, M. fascicularis may be an especially appropriate animal model for studying the neurotoxic mechanisms of chronic methyl mercury exposure.

Comparison of Blood and Brain Mercury Levels in Infant Monkeys Exposed to Methylmercury or Vaccines Containing Thimerosal

“…Nonhuman primates have been used extensively in previous studies of MeHg toxicokinetics and developmental neurotoxicity (Burbacher et al 1986, 1990b; Gunderson et al 1986, 1988; Rice and Gilbert 1982, 1990, 1995; Stinson et al 1989; Vahter et al 1994, 1995). The routes of administration (oral for MeHg and im injection for thimerosal-containing vaccines) were chosen to mimic the two routes of Hg exposure for humans.…”

Assessing the neurotoxicological risk of methylmercury exposure for beluga whales (delphinapterus leucas) harvested in the Mackenzie Delta Estuary.

“…Mercury concentrations in brain tissue from the harvested whales were below the lowest observable adverse effects levels documented for primates (Berlin et al, 1975b;Evans et al, 1977;Luschei et al, 1977;Stinson et al, 1989). We would expect clinical symptoms of Hg intoxication to include the loss o f motor coordination (Bellum et al, 2012), abnormal movements and convulsions (Takeuchi et al, 1977), loss of balance (Farina et al, 2005), and reduced passive avoidance.…”

“…The lethal concentration ofH gT in human brain tissue was 16.8 mg kg'1 ww in the cerebellum o f one individual (Eto et al, 1999). Dietary MeHg dosing studies on primate species indicated that Hg intoxication was associated with brain HgT concentrations between 6.0 and 12.0 mg kg"1 ww (Berlin et al, 1975a;Evans et al, 1977;Luschei et al, 1977;Stinson et al, 1989). Furthermore, concentrations below ~2 to 5 mg kg'1 ww were likely below thresholds o f overt MeHg intoxication in mink (Suzuki, 1979;Wobeser et al, 1976).…”

“…Biochemical changes may be an indicator o f early-stage effects before the manifestation o f disease . If beluga whales are equally sensitive to Hg toxicity as primates and mink, we would expect clinical symptoms to arise when total Hg concentrations in brain tissue exceeded 6.0 to 12.0 mg kg'1 wet weight (ww; Berlin et al, 1975b;Evans et al, 1977;Luschei et al, 1977;Stinson et al, 1989).…”

“…The median Hg concentration in the cerebellar cortex was 0.77 mg kg'1 ww, and ranged from 0.32 to 3.27 mg kg'1 ww; therefore, none exceeded threshold levels for clinical symptoms from primate studies, which are between 6.0 and 12.0 mg kg'1 ww (Berlin et al, 1975b;Evans et al, 1977;Luschei et al, 1977;Stinson et al, 1989). Five beluga whales had Hg concentrations between 1.0 and 4.0 mg kg'1 ww, which is the range in which we would expect to observe biochemical changes but not clinical symptoms (Basu et al, 2007a;Basu et al, 2008;Suzuki, 1979;Wobeser et al, 1976).…”