Environmental risk assessment of psychoactive drugs in the aquatic environment

Cunha, Deivisson Lopes; Mendes, Maíra P.; Marques, Márcia

doi:10.1007/s11356-018-3556-z

Cited by 73 publications

(28 citation statements)

References 80 publications

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“…Zebrafish is well known as a sensitive bioindicator since it is able to respond to a large variety of chemicals [ 71 ]. Furthermore, this animal model has been used to assess psychoactive drug consequences in behavioral context [ 23 , 72 , 73 ]. In this study, the adverse effects of antidepressants were examined in the locomotor activity assay in zebrafish larvae.…”

Section: Discussionmentioning

confidence: 99%

Antidepressant Screening Demonstrated Non-Monotonic Responses to Amitriptyline, Amoxapine and Sertraline in Locomotor Activity Assay in Larval Zebrafish

Suryanto

Audira

Uapipatanakul

et al. 2021

Cells

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Antidepressants are well-known drugs to treat depression and major depressive disorder for humans. However, the misuse and abuse of antidepressants keep increasing with several side effects reported. The aim of this study was to assess the potential adverse effects of 18 antidepressants by monitoring zebrafish larval locomotor activity performance based on the total distance traveled, burst movement count, and total rotation count at four dark-light intercalated phases. In general, zebrafish larvae displayed sedative effects after antidepressant exposure by showing a significant reduction in all of the locomotor activity-related endpoints. However, three antidepressants i.e., amitriptyline, amoxapine, and sertraline were able to trigger a significantly high locomotor activity in zebrafish larvae during the light cycle. These differences might be due to the pharmacologic differences among the antidepressants. In addition, since each antidepressant possesses a different dosage range from the other, overdoses of these antidepressants might also be the causes of these differences. Furthermore, based on these results, a further study was conducted to observe the effect of these three antidepressants in lower concentrations. From the results, biphasic effects in terms of zebrafish larval locomotor activity were demonstrated by these drugs. Even though further studies are still required to validate the mechanism, these findings indicate that these antidepressants might share a common mechanism responsible for their effects on zebrafish larval locomotor activity although there were some differences in potency of these effects.

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Section: Discussionmentioning

confidence: 99%

Antidepressant Screening Demonstrated Non-Monotonic Responses to Amitriptyline, Amoxapine and Sertraline in Locomotor Activity Assay in Larval Zebrafish

Suryanto

Audira

Uapipatanakul

et al. 2021

Cells

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“…While previous publications have mainly reviewed and assessed data that is publicly available, e.g. in scientific literature or European public assessment reports [23][24][25][26], our evaluation is focussed on data available to regulatory authorities, originating from the authorisation process of human medicinal products. Therefore, our analysis provides an evaluation based on an extensive set of standardised and quality-checked data.…”

Section: Evaluation Of Regulatory Datamentioning

confidence: 99%

Environmental fate and effects assessment of human pharmaceuticals: lessons learnt from regulatory data

et al. 2021

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Human pharmaceuticals are extensively studied and assessed before marketing approval. Since 2006, this also includes an assessment of environmental risks. In the European Union, this is based on the guideline on the environmental risk assessment of medicinal products for human use (EMEA/CHMP/SWP/4447/00 corr 2), which is currently under revision. For Germany, the German Environment Agency (UBA) is tasked with the evaluation of environmental risks of human pharmaceuticals. Applicants seeking approval of medicinal products need to submit fate and effect data, in case predicted environmental concentrations (PECs) exceed 10 ng/L in surface waters, or the substance is of specific concern through its mode of action or physico-chemical characteristics.Over the last decade, this regulatory work resulted in an internal agency database containing effect data on approximately 300 active pharmaceutical ingredients (APIs). A considerable part of this data is currently not publicly available due to property rights held by the respective applicants. The database was evaluated to draw conclusions on how the current assessment approach may be improved.The evaluation of aquatic effect data shows considerable variation in ecotoxic effect concentrations, but supports the current use of 10 ng/L as PEC action limit. For endocrine-active substances and antibiotics, a clear sensitivity profile was observed, which allows a more targeted assessment in the future. The conclusions drawn from terrestrial effect data are less clear, as the database itself is biased because information is only available for substances with high sorption. Further adaptations of the terrestrial assessment strategy, including action triggers, appear necessary. Fate data show a high persistence of many APIs: approximately 43% of all APIs are classified as very persistent; 12% of these show DT50 values in a range where abiotic or biotic degradation is not expected.Overall, the evaluation has shown that improvements of the current guideline are possible.

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“…Stock solutions of both compounds (concentration of 10 mg L −1 ) were prepared using ultra-pure water (AquaMax Basic 360 Series and Ultra 370 Series instrument, Young Lin, Anyang, Republic of Korea) and were stored at 4 • C. The exposure solutions of 1 µg L −1 were prepared by dilution of the stock solution in aged tap water. Concentration testing was utilized to evaluate reported [29] environmentally relevant concentrations.…”

Section: Chemicalsmentioning

confidence: 99%

Oxazepam Alters the Behavior of Crayfish at Diluted Concentrations, Venlafaxine Does Not

Kubec

Hossain

Grabicová

et al. 2019

Water

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Pharmaceutically active compounds are only partially removed from wastewaters and hence may be major contaminants of freshwaters. Direct and indirect effects on aquatic organisms are reported at dilute concentrations. This study was focused on the possible effects of environmentally relevant concentrations (~1 µg L−1) of two psychoactive compounds on the behavior of freshwater crayfish. Experimental animals exposed to venlafaxine did not show any behavioral alteration. Crayfish exposed to the benzodiazepine oxazepam exhibited a significant alteration in the distance moved and activity, and the effects were different when individuals were ready for reproduction. Results suggested that even the low concentration of selected psychoactive pharmaceuticals could alter the behavioral patterns of crayfish, as reported for other pharmaceuticals. These results provide new information about the possible adverse effects of pharmaceuticals at dilute concentrations. From previous knowledge and our results, it is obvious that different compounds have different effects and the effects are even specific for different taxa. Detailed studies are therefore needed to assess the possible ecological consequences of particular substances, as well as for their mixtures.

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Environmental risk assessment of psychoactive drugs in the aquatic environment

Cited by 73 publications

References 80 publications

Antidepressant Screening Demonstrated Non-Monotonic Responses to Amitriptyline, Amoxapine and Sertraline in Locomotor Activity Assay in Larval Zebrafish

Antidepressant Screening Demonstrated Non-Monotonic Responses to Amitriptyline, Amoxapine and Sertraline in Locomotor Activity Assay in Larval Zebrafish

Environmental fate and effects assessment of human pharmaceuticals: lessons learnt from regulatory data

Oxazepam Alters the Behavior of Crayfish at Diluted Concentrations, Venlafaxine Does Not

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