Publication related to RSI or an RSI staff member
Pharmacokinetics of methylmercury in the blood of monkeys (Macaca fascicularis).
Statistical analysis of the blood mercury profiles of groups of two and four adult female cynomolgus monkeys (Macaca fascicularis) given single oral doses of 500 micrograms and 50 microCi (25.3 micrograms) methylmercury/kg body wt, respectively, indicates that a two-compartment model best describes the absorption and elimination of methylmercury in blood. Absorption was largely complete within 6 hr, and the half-time of methylmercury during the terminal elimination phase ranged from 10 to 15 days. In addition, three groups of five adult female cynomolgus monkeys were dosed with methylmercury every Monday, Wednesday, and Friday for periods up to 2 years at effective doses of 10, 25, or 50 micrograms methylmercury/kg body wt/day. The average blood levels at steady state were estimated to be 0.27 +/- 0.02, 0.69 +/- 0.03, and 1.51 +/- 0.08 ppm, respectively, with average time taken to achieve 95% of the steady-state blood level being about 92 days. The steady-state blood levels obtained via extrapolation of the results from the two single-dose experiments were significantly different from those actually achieved, indicating that the average steady-state blood levels under chronic dosing conditions may not be accurately estimated on the basis of short-term experiments. The data were also used to examine the impact of different dosing intervals on variation in blood mercury levels.
Authors
- Rice, D C, Rice DC, Health Protection Branch, Health & Welfare Canada, Ottawa, Ontario.
- Krewski, D, Krewski D,
- Collins, B T, Collins BT,
- Willes, R F, Willes RF,
Statistical analysis of the blood mercury profiles of groups of two and four adult female cynomolgus monkeys (Macaca fascicularis) given single oral doses of 500 micrograms and 50 microCi (25.3 micrograms) methylmercury/kg body wt, respectively, indicates that a two-compartment model best describes the absorption and elimination of methylmercury in blood. Absorption was largely complete within 6 hr, and the half-time of methylmercury during the terminal elimination phase ranged from 10 to 15 days. In addition, three groups of five adult female cynomolgus monkeys were dosed with methylmercury every Monday, Wednesday, and Friday for periods up to 2 years at effective doses of 10, 25, or 50 micrograms methylmercury/kg body wt/day. The average blood levels at steady state were estimated to be 0.27 +/- 0.02, 0.69 +/- 0.03, and 1.51 +/- 0.08 ppm, respectively, with average time taken to achieve 95% of the steady-state blood level being about 92 days. The steady-state blood levels obtained via extrapolation of the results from the two single-dose experiments were significantly different from those actually achieved, indicating that the average steady-state blood levels under chronic dosing conditions may not be accurately estimated on the basis of short-term experiments. The data were also used to examine the impact of different dosing intervals on variation in blood mercury levels.
