Age of Exposed Population

Current biokinetic models differ in their flexibility for use in other than stable, (near) steady-state Pb exposures of human risk populations. The lEUBK is only operative in cases where Pb exposures are stable and long term. By contrast, the O Haherty PB-PK model is constructed to reflect acute or episodic Pb exposures. Current biokinetic models also differ in the age ranges of exposed populations to be modeled. The lEUBK model is for children up to 84 months old. The PB-PK models are basically hfetime in their application. 

In order to determine the effective dose of a given agent to the population at risk, evaluators need to take into account such variables as the duration and intensity of exposure, the age distribution of exposed persons at the time of their exposure, their sex, state of disease or health, and the estimated concentrations of the agent and its metabolic derivatives in various tissues of the body. Also, insofar as possible, the mode of action of the agent should be characterized in order to enable selection of the appropriate dose-incidence model for use in risk estimation. 

Arterial hypertension is very common. Approximately 40% of the population over the age of 40 exhibit elevations of blood pressure, more than 140 mm. of mercury systolic and 90 mm. diastolic (64). The incidence increases with advancing years. It appears to be greater in negroes (2, 3, 23), the obese (33), and those exposed to higher degrees of civilization (16). 

Fisher 1998 demonstrates that the more that is learned about the biomarker (half-life, time course in blood or urine, and development of PBPK model) and the exposed population (age, body weight, pharmacoge-netic traits, behavioral factors that affect exposure, and time between exposure and sample measurement), the more refined dose estimates can become. Without such information, a highly transient metabolite like TCE is not a reliable marker of exposure, unless exposure is nearly continuous and uniform. That may not be the case in the general population, so TCE in blood may not be a good biomarker for assessment of general-population exposure, although PBPK models are available to extrapolate from biomarker concentration to external dose in both animals and humans (Clewell et al. 2000). 

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