Phthalates and non-phthalates plasticizers disrupt lipid metabolism
Why this work is in the frame
A frame that forgets how it found something cannot be audited. These are the routes that admitted this work.
Bibliographic record
Abstract
Plasticizers are synthetic organic chemicals that are used in different products to make them flexible, elastic, and durable. Plasticizers are not attached to the products by covalent bonds, as a result, they leach out from the products leading to environmental contamination. The most widely used plasticizer, Di-(2-ethyl hexyl) phthalate (DEHP), have been restricted from general use in the EU, Canada, and the USA due to their reported toxicity. The alternative plasticizer, Di-(isononyl) cyclohexane-1,2-dicarboxylate (DINCH), was introduced to the European market as a safer alternative for endocrine-disrupting phthalates such as DEHP, and diisononyl phthalate (DINP). According to the current toxicological data, DINCH is neither an endocrine disruptor and nor a reproductive toxicant. Thus, DINCH was approved for use in food contact containers, and in children’s toys. The increase in global demand for alternative plasticizers led to their buildup in the environment and an increase in DINCH exposure. The lack of toxicity data and safety assessment of DINCH has raised the concern to human and animal health. Due to the similar structure of DEHP, DINP, and DINCH, we suggest that DINCH can be classified as a metabolic disruptor that alters fat metabolism and induces adipogenesis. In this study, we investigated the negatives effects of DINCH (at concentrations ranging from 0.01 to 10 μM) compared it to phthalates DINP, DEHP, Dibutyl phthalate (DBP), and Diethyl phthalate (DEP) at the early developmental stages of zebrafish. We further analyzed DINCH and DINP using the mouse preadipocyte cells 3T3L1. We found that DINCH and DEHP caused hatching delay in a dose-dependent manner. Behavioral analysis of larvae demonstrated that DEHP, DBP, DEP, and DINCH impair motor activity. The Oil Red O lipid staining showed a slight lipid accumulation in larval zebrafish at different DINP and DINCH concentrations. To further confirm the findings, qPCR was performed to analyze lipid metabolism genes. DINCH and DINP altered lipid metabolism genes including, fasn, srebp, pparg etc. The oxidative stress state imposed by DINCH exposure was shown by a slight increase in superoxide dismutase enzymatic activity and the alteration on stress-related genes. In 3T3L1 cells, 10 and 100 μM of DINCH and DINP exposure induced lipid droplets formation like that induced by 100 nM rosiglitazone. Genes associated with lipid metabolism and lipid transport were altered by DINCH and DINP. These results indicate that DINCH exposure could induce physiological and metabolic toxicity. The data presented in this thesis could provide crucial information for further toxicological assessment.
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Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.001 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.002 | 0.001 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.001 | 0.001 |
| 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 it