Comparison of in vitro transcriptomic points of departure with fish acute and chronic toxicity values: a case study of rainbow trout cells exposed to pesticides
Bibliographic record
Abstract
There is growing interest in transcriptomic points of departure (tPOD) values from in vitro experiments as an alternative to animal test method. The study objective was to calculate tPODs in rainbow trout gill cells (RTgill-W1 following Organisation for Economic Co-operaon and Development [OECD] 249) exposed to pesticides, and to evaluate how these values compare to fish acute and chronic toxicity data. Cells were exposed to one fungicide (chlorothalonil), 10 herbicides (atrazine, glyphosate, imazethapyr, metolachlor, diquat, s-metolachlor, aminomethylphosphonic acid, dicamba, dimethenamid-P, metribuzin), eight insecticides (chlorpyrifos, diazinon, permethrin, carbaryl, clothianidin, imidacloprid, thiamethoxam, chlorantraniliprole), and OECD 249 positive control 3,4-dichloroaniline. Pesticide concentrations in wells were modeled with IV-MBM EQP Ver. 2.1. Sequencing libraries were prepared with UPXome, and tPODs calculated with ExpressAnalyst. The method identified 14,449 unique genes, with 1,115 genes having >5 counts in the 576 samples sequenced. For all chemicals, tPODs were derived, and tPOD mode values ranged from 0.0004 to 125 µM with an average of 36 µM. There were significant correlations between tPOD mode values (x-value) and median effect concentrations from RTgill-W1 cells (y = 0.92x + 1.2, R2 = 0.9, p < 0.00001; n = 11), rainbow trout acute toxicity median lethal concentrations (y = 0.81x + 0.8, R2 = 0.63, p < 0.0001; n = 20), fish chronic sublethal effect concentrations (y = 0.53x - 0.2, R2 = 0.4, p = 0.009; n = 16), and fish chronic lethal effect concentrations (y = 0.64x - 0.023, R2 = 0.59, p = 0.0013; n = 14). Bland-Altman plot analyses of these comparisons also showed good agreement. Pathway-level benchmark doses were calculated when statistical requirements were met, and only possible for four pesticides. These findings support the notion that tPODs from short-term in vitro studies may be comparable to effect concentration data from in vivo studies of fish exposed for chronic durations.
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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 | 0.001 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 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".