Publication Details |
| Category | Text Publication |
| Reference Category | Journals |
| DOI | 10.1016/j.yrtph.2011.08.006 |
| Title (Primary) | Using the fish plasma model for comparative hazard identification for pharmaceuticals in the environment by extrapolation from human therapeutic data |
| Author | Schreiber, R.; Gündel, U.; Franz, S.; Küster, A.; Rechenberg, B.; Altenburger, R. |
| Source Titel | Regulatory Toxicology and Pharmacology |
| Year | 2011 |
| Department | BIOTOX |
| Volume | 61 |
| Issue | 3 |
| Page From | 261 |
| Page To | 275 |
| Language | englisch |
| Keywords | Drug discovery data; Toxicity assessment; Long-term ecotoxicity |
| Abstract | Thousands of drugs are currently in use, but only for a few of them
experimental chronic fish data exist. Therefore, Huggett et al. (Human Ecol Risk Assess 2003; 9:1789–1799) proposed the fish plasma model (FPM) to extrapolate the potential of unintended long-term effects in fish. The FPM compares human therapeutic plasma concentrations (HPCT) with estimated fish steady-state concentrations (FPCss),
under the assumption that biological drug targets may be conserved
across the species. In this study, the influence of using different
input parameters on the model result was characterised for 42 drugs. The
existence of structurally and functionally conserved protein targets in
zebrafish could not be refuted.
Thus, the FPM model application was not in contradiction to its basic
assumption. Further, dissociation of drugs was shown to be important in
determining the output and model robustness. As the proposed model for FPCss
estimation was considered to predict accurate values for neutral and
lipophilic chemicals only, a modified bioconcentration model was used
with DOW as predictor. Using reasonable worst case
assumptions, a hazard was indicated for one third of the selected drugs.
Our results support the notion that this approach might help to
prioritise among in use drugs to identify compounds where follow up
evidence should be considered. |
| Persistent UFZ Identifier | https://www.ufz.de/index.php?en=20939&ufzPublicationIdentifier=11807 |
| Schreiber, R., Gündel, U., Franz, S., Küster, A., Rechenberg, B., Altenburger, R. (2011): Using the fish plasma model for comparative hazard identification for pharmaceuticals in the environment by extrapolation from human therapeutic data Regul. Toxicol. Pharmacol. 61 (3), 261 - 275 10.1016/j.yrtph.2011.08.006 |
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