Unveil the toxicity induced on early life stages of zebrafish (Danio rerio) exposed to 3,4-methylenedioxymethamphetamine (MDMA) and its enantiomers.

MDMA (ecstasy) and its two mirror-image forms (enantiomers) cause distinct toxic effects in zebrafish embryos and larvae at concentrations as low as 0.02 μg/L, which are found in polluted waters. (S)-MDMA increases mortality and birth defects and disrupts the startle-habituation response, while (R)-MDMA suppresses general activity and avoidance behavior. The racemic mixture produces greater DNA damage than either enantiomer alone. Although MDMA does not accumulate in zebrafish tissues, these developmental, behavioral, and genetic effects could reduce larval survival and increase predation risk, raising concerns for wild fish populations. The findings demonstrate that enantioselective toxicity should be included in environmental risk assessments for MDMA.

Study at a glance

Abstract

The increased detection of the recreational drug 3,4-methylenedioxymethamphetamine (MDMA) in aquatic ecosystems, has raised concern worldwide about its possible negative impacts on wildlife. MDMA is produced as racemate but its enantioselective effects on non-target organisms are poorly understood. Therefore, this study aimed to provide a comprehensive study of the toxicity of MDMA and its enantiomers in the early life stages of zebrafish (Danio rerio). Zebrafish embryos (≈3 h post fertilization) were exposed to different concentrations (0.02, 0.2, 2, 20, and 200 μg/L) of (R,S)-MDMA and both pure enantiomers. Both enantiomers induced effects on embryonic development, DNA integrity, and behaviour and enantioselective effects were noted. (S)-MDMA exhibits higher toxic effects on embryonic development level with increased mortality and severity of teratogenic effects, and behavioural abnormalities in acoustic startle-habituation response. (R)-MDMA affected general activity and avoidance behaviour, showing greater inhibitory effects on behavioural activity. Additionally, (R,S)-MDMA induced higher genotoxic effects than the two isolated enantiomers. These results are of concern at populational levels since effects on mortality, development, and behaviour were observed even at environmentally relevant concentrations, which can cause a reduction of larval viability and in the number of individuals in each generation, and an increase in the risk of predation of the organisms. Yet, the bioaccumulation studies showed that MDMA is not accumulated in zebrafish. Therefore, this work demonstrated for the first time the occurrence of MDMA enantiotoxicity in the early life stages of zebrafish, which should be considered in further environmental risk assessments involving fish species or other non-target aquatic organisms.