The fish plasma model predicts the fish blood plasma concentration of a pharmaceutical from the water concentration to which the fish is exposed and compares it to the human therapeutic plasma concentration with the postulate that no adverse toxic effects occur below this concentration. The present study provides several lines of evidence supporting the fish plasma model for the beta‐adrenergic agonist salbutamol, a small, at ambient pH cationic molecule. Salbutamol exhibited very low acute toxicity to early and adult life stages of fathead minnows (Pimephales promelas). Biomass reduction in fish early life stages was the most sensitive apical endpoint, with no observed effect concentrations (NOECs) in the low mg/L range upon continuous exposure for up to 120 days. Given that predicted and measured environmental concentrations are at least 1000‐fold lower, the risk of salbutamol in freshwater is deemed very low. Increase of heart beat rate and decrease of total triglyceride content in fish also occurred in the low mg/L range and resembled effects known from humans. This supports the fish plasma model assumption of conserved targets in fish with similar functionality. Plasma concentrations measured in adult and juvenile fish exposed to water concentrations around the NOECs exceeded the human therapeutic plasma concentration and approached plasma concentrations toxic to humans. This confirms for salbutamol the fish plasma model hypothesis that no adverse, i.e. population‐relevant, toxic effects occur in fish below the human therapeutic plasma concentration.
For additional information, see the publication in Environmental Toxicology and Chemistry:
Weil, M., Falkenhain, A.-M., Scheurer, M., Ryan, J.J., Coors, A. (2019). Uptake and effects of the beta‐adrenergic agonist salbutamol in fish: supporting evidence for the fish plasma model. Environmental Toxicology and Chemistry in press.
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