Toxicity Assessment in C. elegans

Overview

This source page is a mechanical bulk-ingest record for a PDF in the research-pulls corpus. It preserves source-level identity, routeable product/analyte scope, and exact extracted numeric lines for later human or fresh-context audit. It does not derive HMTc thresholds, percentiles, or brand-by-brand comparisons.

Key numbers

The worker extracted the full PDF text with layout preservation twice and compared extraction hashes before commit. The following lines are copied from numeric/table-bearing regions of the PDF and retain the source units and wording where legible:

• variation of 1–5% for developmental endpoints and 6–17% for reproductive-related endpoints,
• embryo count, body size, or viability. Importantly, worms remained > 97% viable and motile across all
• humans, rodent data alone are only 43% predictive of human toxicity outcomes (3). The concordance
• improves to 71% when combined with a non-rodent species, supporting a multi-tier approach. With over
• extensive conservation with mammals, with up to 60–80% and ~ 83% homology to the human genome
• Developmental toxicity endpoints demonstrate ~ 53% balanced accuracy for predicting mammalian
• embryos achieved 69% balanced accuracy in predicting mammalian reproductive toxicity (23). Acute
• toxicity studies of 17 non-acidic chemicals reported 88.5% concordance with rat lethal dose predictions,
• working dilutions, ensuing a final DMSO concentration of 1.0% (v/v) in each well. Solvent control wells
• received DMSO at the same final concentration (1.0% v/v).
• received 5 µl of DMSO solvent (1% v/v). The 24-well culture plates were sealed with airtight films (Cat#
• For each chemical tested, we first performed a range-finding assay using at least 20 concentrations
• Table 1). Time-lapse images were inspected to count all worms within the 10,744 x 6,290 µm2 field of
• larger worms, wells containing populations younger than L4 were filled with molten 2% agarose gel to
• Mean phenotype scores were calculated per well and used to fit concentration-response curves from 3
• mean CV% and standard error of mean (SEM) across all 10 combinations were reported for each
• endpoint. To measure the strengths of the difference between 1% DMSO and methylmercury-treated
• worms, we calculated the Strictly Standardized Mean Difference (SSMD) for all 6 endpoints using 3
• Assay power was estimated using the mean and standard deviations obtained from all 60 possible
• combinations (10 combinations per well position × 6 well positions with 1% DMSO) for all endpoints
• from repeatability experiments. Power calculations were performed for a fixed value of n = 3 technical
• replicates and a series of hypothetical treatment group means representing 2.5% − 50% effect sizes
• possible values of 0 embryos for Reproductive endpoints and estimated mean L1 body dimensions
• estimate, the 95% confidence interval (CI) bands were calculated and plotted. Two concentration-
• concentration (EC50) values with high confidence and low coefficient of variance (CV%).
• 98.3%. The segmentation model was evaluated on a separate test set of 439 full worm images,
• because of its wide applicability to a range of chemicals. Four DMSO concentrations (0.0, 0.2, 0.5, and
• 1.0%) were tested to characterize baseline phenotypes under solvent only control conditions. Each
• variability in addition to inter-experimental variability (Fig. 3A). We selected a 1% DMSO concentration as
• including 1% DMSO (Fig. 3B). To examine variability across both biological and technical replicates, we
• representative biological replicate, the mean body parameters for 0% DMSO were 1,522 ± 8 µm (length,
• embryos (Fig. 3H and Supplementary Fig. 10F), whereas for 1% DMSO, averages were 29.2 ± 0.5 (p-
• = 0.24) total embryos. Although, there were significant differences between 0% and 1% DMSO conditions
• Although body length and volume showed statistically significant changes (+ 4.9% and − 7.3%,
• (Supplementary Fig. 11). DMSO concentrations ≥ 1% has previously been reported to affect worm
• between 0% and 1% DMSO for early-stage, late-stage, and total embryo counts (Supplementary
• variation (CV%) between 6 technical replicates (Columns 1 to 6 in vivoChip-24x) for each condition. For
• 1% DMSO condition, the mean CV% values between the technical replicates were < 3.8% for
• developmental endpoints and < 12.5% for embryonic endpoints (Fig. 4). This data suggests high
• To assess inter-experimental repeatability, we calculated the coefficient of variation (CV%) between 3
• calculation for all 10 possible combinations of the 5 experiments (Figs. 5A-B). For the 0% DMSO
• populations, the mean CV% values across different experiments and 60 total combinations were 1.5 ±

Methods (brief)

• substantial housing infrastructures, and complex experimental design. High costs also restrict sample
• reached adulthood. Adult F1 worms were collected by washing both plates with M9 buffer and treated
• and worms with measurements outside these fences were excluded. Inspection of excluded samples
• below the control means (one-sample, one-tailed t test, α = 0.05) using GraphPad Prism (version 10.6.1).
• imaging speed. Prior to chip imaging, videos of the culture plates were collected to analyze worm
• based models are implemented. Across these studies, we collected and annotated data from over ~
• 22. Widmayer, S. J. et al. C. elegans toxicant responses vary among genetically diverse individuals.

Implications

This page makes the source discoverable for category-level evidence routing. Values remain source-native and should be used only with the stated matrix, species, basis, geography, and censoring context from the paper. The page does not convert total mercury to methylmercury or use total arsenic as inorganic arsenic.

Wiki pages this source may touch

• Fish — marine, non-predatory (sardines, anchovies, salmon, cod)
• Shellfish (shrimp, crab, lobster, clams, oysters, mussels)
• Mercury
• Mercury
• Cadmium
• Lead
• Arsenic

Verification notes

• Identity check: DOI, raw handle, candidate cite-key, and SHA-256 were compared against existing wiki/sources/ pages before creation.
• Full-PDF read: pdftotext -layout was run on the full PDF twice; extracted text hashes matched before the page was written.
• Numeric verification: numeric/table-bearing lines were selected mechanically from the verified extraction and preserved without unit conversion or rounding.
• Brand firewall: the worker skips PDFs when extracted numeric lines appear brand/manufacturer-sensitive; this page contains category-level or species-level evidence only.
• HMTc firewall: no threshold, percentile, pass/fail, clean/dirty, or certification math is stated.

Update history

The five most recent substantive edits to this page, classified major (evidence or structure moved), correction (a published value or statement was wrong and has been fixed), or minor (narrative rewritten without changing the underlying evidence). Each description is derived from what the edit did to this page; the linked commit is the authoritative record, routine regeneration passes are excluded, and the full version history lives in git. When DOI minting comes online (see schema docs), each entry below will also link to a version-pinned DataCite DOI.