LAUSR

The fish plasma model (FPM) 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 (Hther PC) with the postulate that no adverse toxic effects occur below the Hther PC. The present study provides several lines of evidence supporting the FPM for the beta-adrenergic agonist salbutamol, a small cationic molecule at ambient pH. Salbutamol exhibited very low acute toxicity to early and adult life stages of fish. 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 occurred also at the low mg/L range and resembled effects known from humans. This supports the FPM 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 Hther PC and approached even plasma concentrations toxic to humans. This confirms for salbutamol the FPM hypothesis that no adverse, i.e. population-relevant, toxic effects occur in fish below Hther PC. This article is protected by copyright. All rights reserved.