Zebrafish Embryo Neonicotinoid Developmental Neurotoxicity in the FET Test and Behavioral Assays

The need for reliable, sensitive (developmental) neurotoxicity testing of chemicals has steadily increased. Given the limited capacities for routine testing according to accepted regulatory guidelines, there is potential risk to human health and the environment. Most toxicity studies are based on mammalian test systems, which have been questioned for low sensitivity, limited relevance for humans, and animal welfare considerations. This increased the need for alternative models, one of which is the zebrafish (Danio rerio) embryo. This study assessed selected neonicotinoids at sub-lethal concentrations for their effects on embryonic development and behavior. The fish embryo acute toxicity test (OECD TG 236) determined the lowest observable effective concentrations, which were used as the highest test concentrations in subsequent behav-ioral assays. In the FET test, no severe compound-induced sublethal effects were seen at < 100 mu M. In the coiling assay, exposure to >= 1.25 mu M nicotine (positive control) affected both the burst duration and burst count per minute, whereas >= 50 mu M thiacloprid affected the mean burst duration. Exposure to >= 50 mu M acetamiprid and imidacloprid induced sig-nificant alterations in both mean burst duration and burst count per minute. In the swimming assay, 100 mu M acetamiprid induced alterations in the frequency and extent of movements, whilst nicotine exposure only induced non-significant changes. All behavioral changes could be correlated to findings in mammalian studies. Given the quest for alternative test methods of (developmental) neurotoxicity, zebrafish embryo behavior testing could be integrated into a future tiered testing scheme.

Automated summary

The demand for reliable and sensitive (developmental) neurotoxicity testing of chemicals is increasing. However, the limitations of current mammalian test systems have led to the need for alternative models. This study evaluated the effects of neonicotinoids on zebrafish embryo development and behavior and found that the behavioral changes observed in the zebrafish were consistent with findings from mammalian studies. As a result, zebrafish embryo behavior testing could be integrated into future tiered testing schemes.