In Vitro Interactions of Biological Nucleophiles with Fluorotelomer Unsaturated Acids and Aldehydes: Fate and Consequences
Bibliographic record
Abstract
Fluorotelomer unsaturated aldehydes and acids (FTUALs and FTUCAs) are intermediate metabolites that form from the biotransformation of fluorotelomer-based chemicals. FTUALs and FTUCAs have been previously suggested to contribute to the toxicity associated with human exposure to fluorotelomer compounds by covalently binding to biological nucleophiles. However, the extent of their reactivity has only been assessed with glutathione. The purpose of the present study was to assess the reactivity of these intermediate metabolites with a series of nucleophilic amino acids and model proteins. In vitro experiments were carried out in an aqueous buffer system to determine the reactivity of nucleophilic amino acids with FTUCAs and FTUALs having varying fluorinated chain lengths. Using (19)F NMR spectroscopy to monitor the disappearance of the FTUCAs and FTUAL signals and the production of a fluoride signal, reaction rate constants were determined under pseudo-first-order conditions. The FTUCAs reacted only with cysteine with the following second order rate constants: 3.63 (± 1.37) × 10(-5) min(-1) mM(-1) (4:2 FTUCA), 1.19 (± 0.91) × 10(-5) min(-1) mM(-1) (6:2 FTUCA), and 4.56 (± 0.94) × 10(-5) min(-1) mM(-1) (8:2 FTUCA). The FTUALs were significantly more reactive than any of the FTUCAs with reactivity decreasing in the following order: cysteine >> histidine > lysine >> arginine. The following second-order rate constants were obtained: 5.7 (± 4.2) × 10(-4) min(-1) mM(-1) (histidine), 4.3 (± 1.4) × 10(-4) min(-1) mM(-1) (lysine), and 1.4 (± 0.73) × 10(-4) min(-1) mM(-1) (arginine). FTUCAs and FTUALs were also reacted with model proteins to assess their potential for forming covalent adducts. Electrospray ionization mass spectrometry (ESI-MS) was used to investigate the stoichiometry of FTUCAs and FTUALs covalently bound to apomyoglobin (ApoMg) and human serum albumin (HSA). FTUCAs were not reactive, whereas two measurable FTUAL adducts were formed with both ApoMg and HSA at each of the FTUAL chain lengths (6:2, 8:2, and 10:2). This is the first study to probe the reactivity of FTUALs and FTUCAs with nucleophiles other than glutathione, further elucidating possible FTUAL and FTUCA fate within biological systems.
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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 | 0.001 | 0.001 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 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 | 0.001 | 0.001 |
| 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".