Improving Risk Assessment: Research Opportunities in Dose Response Modeling to Improve Risk Assessment

Sicherheitsfaktoren in der Risikobewertung von Chemikalien

“…In den letzten Jahren wurde mehr und mehr gefordert, die erweiterten experimentellen Möglichkeiten stärker auszuschöpfen, um mehr wissenschaftliche Aspekte in die Ableitung von sicheren Werten einzubringen.In einer internationalen Abstimmung (IPCS) sowie durch verschiedene Forschergruppen wurden Vorschläge zur Nutzung moderner Techniken mit dem Ziel einer verbesserten Risikobewertung unterbreitet [26,37].…”

Pharmacokinetic–pharmacodynamic models for categorical toxicity data

“…An improvement over standard approaches can be achieved via the used of mechanistically based dose-response models that account for the time-and dose-dependent changes in the biological system. Such models have the potential to determine reference exposure concentrations that are scientifically more credible (Zeise et al, 2002).…”

A Bayesian population PBPK model for multiroute chloroform exposure

“…Physiologically based pharmacokinetic (PBPK) modeling has been used in toxicology, epidemiology, and in exposure and risk assessment as an adjunct to studies on the toxic modes of action of xenobiotics (Gibb et al, 2002; Zeise et al, 2002; Andersen, 2003). The power of PBPK modeling is achieved at the expense of using a large number of parameters, some of which may vary significantly among individuals (e.g., tissue weights and blood flows) and few of which are known with precision (e.g., bioavailability, metabolic/excretion rates) (Zeise et al, 2002).…”

“…The power of PBPK modeling is achieved at the expense of using a large number of parameters, some of which may vary significantly among individuals (e.g., tissue weights and blood flows) and few of which are known with precision (e.g., bioavailability, metabolic/excretion rates) (Zeise et al, 2002). Therefore, every PBPK model requires some level of calibration or optimization of its parameters.…”