Suchergebnisse

Although analysis of in vivo pharmacokinetic data necessitates use of time‐dependent physiologically‐based pharmacokinetic (PBPK) models, risk assessment applications are often driven primarily by steady‐state and/or integrated (e.g., AUC) dosimetry. To that end, we present an analysis of steady‐state solutions to a PBPK model for a generic volatile chemical metabolized in the liver. We derive an equivalent model that is much simpler and contains many fewer parameters than the full PBPK model. The state of the system can be specified by two state variables—the rate of metabolism and the rate of clearance by exhalation. For a given oral dose rate or inhalation exposure concentration, the system state only depends on the blood‐air partition coefficient, metabolic constants, and the rates of blood flow to the liver and of alveolar ventilation. At exposures where metabolism is close to linear, only the effective first‐order metabolic rate is needed. Furthermore, in this case, the relationship between cumulative exposure and average internal dose (e.g., AUCs) remains the same for time‐varying exposures. We apply our analysis to oral‐inhalation route extrapolation, showing that for any dose metric, route equivalence only depends on the parameters that determine the system state. Even if the appropriate dose metric is unknown, bounds can be placed on the route‐to‐route equivalence with very limited data. We illustrate this analysis by showing that it reproduces exactly the PBPK‐model‐based route‐to‐route extrapolation in EPA's 2000 risk assessment for vinyl chloride. Overall, we find that in many cases, steady‐state solutions exactly reproduce or closely approximate the solutions using the full PBPK model, while being substantially more transparent. Subsequent work will examine the utility of steady‐state solutions for analyzing cross‐species extrapolation and intraspecies variability.

Research on Asian migration flows to and community creation in Great Britain has neglected the case of Sri Lankans. In fact Sri Lankans by 1991 constituted the sixth biggest Asian community, with over 39,000 residents of Britain having been born in Sri Lanka. An estimate of the population of Sri Lankan origins by the end of the 1990s suggests around 65,000 residents, including British-born offspring. Using information on country of birth from the 1991 British census, this paper discusses the characteristics of the Sri Lankan community. It is shown to be markedly different from other South Asian groups in a number of respects, most particularly through its extreme, and growing, geographical concentration in the South East and Greater London.

SummaryThis paper considers three main issues. First, it deals with the underlying structural causes of international migration, especially labour migration, and the way they are liable to create ethnically distinct sub-populations. In achieving this it presents a typology of forms and characteristics of ethnic migration streams. Secondly, and by way of contrast, the case is argued for the need to consider ethnic migration from the behavioural perspective. Thirdly, reasons are described and suggested for the position of relative disadvantage in which many migrant ethnic minorities find themselves placed.