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Caffeine is a contaminant frequently detected in water bodies. Growth trends in both human population and caffeine consumption per capita are expected to exacerbate the occurrence of caffeine in freshwaters. Yet the effects of caffeine on native fish fauna are poorly understood. We exposed larvae of an endemic Neotropical catfish (
Rhamdia quelen
) to a range of caffeine concentrations for 30 days. We found that larvae exposed to the highest concentration (16 mg L
−1
) showed skeletal deformations and reduced growth. We further compiled measured environmental concentrations of caffeine in surface freshwater globally and performed a risk assessment. Our analysis points to a low risk to
R. quelen
and equally sensitive fish species in ~90% of the freshwater ecosystems considered in our analysis. The risk quotient is higher in freshwater ecosystems of South and Central America, where
R. quelen
is endemic. Although the ecotoxicological risk is currently low in most places, increased caffeine consumption, exacerbated by the lack of sanitation, is expected to increase caffeine concentrations in many parts of the world, posing a threat of sublethal morphological effects to local fish species.