Monitoring human dose comparisons

Human dose comparisons utilizing biomonitoring and passive monitoring of an exposure environment following surface treatment with an insecticide... 

The pharmacokinetics of hyperforin have been studied in rats and humans (Biber et ai. 1998). In rats, after a 300 mg/kg orai dose of hypericum extract (WS 5572, containing 5% hyperforin), maximum piasma ieveis of 370 ng/mi (690 nM) are achieved at 3 hours. The haif-iife of hyperforin is 6 hours. Humans given a 300 mg tabiet of hypericum (containing 14.8 mg hyperforin) showed maximum piasma ieveis of 150 ng/mi (280 nM) at 3.5 hours. The haif-iife is 9 hours, and mean residence time is 12 hours. Pharmacokinetics of hyperforin are iinear up to 600 mg, and no accumuiation occurs after repeated doses. By comparison, effective and safe piasma ieveis of paroxetine and fluoxetine vary between 40 and 200 ng/mi (Preskorn 1997). The effective piasma concentration of hyperforin predicted from computer-fit data is approximateiy 97 ng/mi (180 nM), which couid be easiiy monitored (Biber et ai. 1998). There is a iinear correiation between orai dose of hyperforin and piasma ieveis, and steady-state concentrations of 100 ng/mi (180 nM) couid be achieved with three-times-daiiy dosing. 

In vitro SCE assays are routinely conducted in cultured Chinese hamster ovary (CHO) cells or human lymphocytes, and assessments of SCEs in human lymphocytes have been used for human population monitoring. Following in vivo exposure, SCEs are usually visualized in bone marrow cells from mice implanted with BrdU-containing tablets (or pumps). Such SCE assays have been used to test several hundred chemicals and have been shown to be highly sensitive and, in comparison to conventional assays for chromosomal aberrations, to be more rapid, less subjective, and capable of detecting effects at lower dose levels. 

The external dose to the critical population group in conditions of chronic (prolonged) exposure should be determined on the basis of environmental monitoring data by the use of a simple calculation model in which account is taken of the partial shielding of the human environment in comparison with an open area, human occupation, the ratio between the dose in air and the effective dose, and the seasonal variation of relevant parameters. 

---