Metformin and guanylurea reduce survival, but have limited sublethal effects in larval zebrafish ( <i>Danio rerio</i> )
Bibliographic record
Abstract
Abstract Metformin is the most common first-line oral therapeutic agent used in the treatment of type-2 diabetes, one of the most prevalent chronic diseases in North America. Post excretion, the compound enters wastewater treatment plants where it is partially bio-transformed by bacteria into guanylurea. Both metformin and guanylurea enter freshwater environments in wastewater effluent where they are available for uptake by aquatic biota. However, our understanding of the effects of metformin and guanylurea on aquatic life is limited. We tested the hypothesis that metformin and guanylurea can influence the development of zebrafish ( Danio rerio ), by assessing morphometrics, cardiac development, energetic state, and behaviour of early larvae. Embryos were exposed to environmentally relevant (0.4, 4, 40 μg·L −1 ) and supra-environmental (400 and 4000 μg·L −1 ) concentrations of metformin and guanylurea from the 4-cell stage (3 hours post fertilization; hpf), until first feed (120 hpf). Exposures to 40 μg·L −1 and higher of both metformin and guanylurea increased mortality. Metformin delayed hatching at the highest concentration tested (4000 μg·L −1 ). The incidence of spinal curvature increased with exposure to both chemicals at supra-environmental levels (400 and 4000 μg·L −1 for metformin; 400 μg·L −1 for guanylurea). Metformin and guanylurea exposure imposed slight bradycardia in early development, but did not alter oxygen consumption, ATP levels, carbohydrate levels, general swimming, light-dark movement, startle response, or thigmotaxis, irrespective of exposure concentration. The results suggest similar and low sensitivities of larval fish to both metformin and guanylurea. Apart from a small increase in mortality, these compounds impart a modest impact to the early-life stages of zebrafish that are largely limited to supra-environmental concentrations.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".