Short-term transcriptomic points-of-departure are consistent with chronic points-of departure for three organophosphate pesticides across mouse and fathead minnow.
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1005574 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR25644400.fastq.gz | Fastqsanger.gz | |||
| SRR25644401.fastq.gz | Fastqsanger.gz | |||
| SRR25644402.fastq.gz | Fastqsanger.gz | |||
| SRR25644403.fastq.gz | Fastqsanger.gz | |||
| SRR25644404.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 84 |
Similar Datasets
Project description:New approach methods (NAMs) can reduce the need for chronic, animal-based toxicity and carcinogenicity bioassays. Here, we apply benchmark dose (BMD) response modeling (BMDExpress 2.3) to transcriptomic data after short-term exposures to three organophosphate pesticides (OPPs) to estimate chronic adverse effect levels in mouse. Specifically, mouse-liver were collected for RNA sequencing after 7-days of exposure, respectively, to several dose-levels of well-known OPPs: fenthion, methidathion and parathion. Transcriptional points-of-departure (TPODs) were compared to chronic, apical points-of-departures (APOD) for each OPP to inform more efficient means of estimating chemical potency and risk. The mouse-liver TPODs for fenthion, methidathion, and parathion were 0.009, 0.093, and 0.046 mg/Kg-day, respectively. These short-term TPODs reflected the relative potencies of the most sensitive, apical effects from the chronic studies with fenthion identified as the most potent OPP. Moreover, the TPODs were 2.3 to 17-fold more sensitive than the chronic APODs for mouse, suggesting utility in using short-term gene response for estimating long-term chemical risk. Further investigation into OPPs’ modes of action identified significant impacts on acetylcholinesterase mRNA abundance (FDR p-value <0.05, |FC|>2) as well as enrichment of canonical pathways (IPA, z-score>|2|) associated with organism death and neurological and immune dysfunctions, which have been known to be affected by OPPs. Despite bioassay-related differences, our results indicate the conservation of key events potentially important to OPPs biological activity and potency across species. While additional research is needed, these results build confidence in using short-term, molecular-based assays for the characterization of toxicity and risk, thereby reducing reliance on chronic, rodent-based studies.
2023-11-13 | GSE240853 | GEO
Project description:It is postulated that below a transcriptomic-based point of departure, adverse effects are unlikely to occur, thereby providing a chemical concentration to use in screening level hazard assessment. The present study extends previous work describing a high throughput fathead minnow assay that can provide full transcriptomic data after exposure to a test chemical. One day post-hatch fathead minnows were exposed to ten concentrations of three representatives of four chemical modes of action: organophosphates, ecdysone receptor agonists, plant photosystem II inhibitors, and estrogen receptor agonists for 24 hours. Concentration response modeling was performed on whole body gene expression data from each exposure, using measured chemical concentrations when available. Transcriptomic points of departure in larval fathead minnow were lower than apical effect concentrations across fish species but not always lower than toxic effect concentrations in other aquatic taxa like crustaceans and insects. The point of departure was highly dependent on measured chemical concentration which were often lower than the nominal concentration. Differentially expressed genes between chemicals within modes of action were compared and often showed statistically significant overlap. In addition, reproducibility between identical exposures using a positive control chemical (CuSO4) and variability associated with the transcriptomic point of departure using in-silico sampling were considered. Results extend a transcriptomic-compatible fathead minnow high throughput assay for possible use in ecological hazard screening.
2024-10-18 | GSE252223 | GEO
Project description:RNA-seq expression assays were done in larval Pimephales promelas (Fathead minnow, FHM) exposed to 10 chemicals (3 metals, 4 Neonicotinoids, and 3 pharmaceuticals) over a range of concentrations to derive relatively short term transcriptomics based points of departure (tPODs). tPODs were compared to apical points of departures (aPODs) to investigate the potential use of the FHM tPODS as part of a high throughput approach that might be used in a regulatory context.
2023-01-01 | GSE207231 | GEO
Project description:Traditional toxicity testing has been unable to keep pace with the introduction of new chemicals into commerce. Consequently, there are limited or no toxicity data upon which to base a risk assessment for many chemicals to which fish and wildlife may be exposed. Per- and polyfluoroalkyl substances (PFAS) are emblematic of this issue in that most the ecological hazards of most PFAS remain uncharacterized. The present study employed a high throughput assay to identify the concentration at which 20 PFAS, with diverse properties, elicited a concerted gene expression response in larval fathead minnows (Pimephales promelas, 5-6 days post-fertilization) exposed for 24 h. Based on a reduced transcriptome approach that measured whole body expression of 1832 genes, the median transcriptomic point of departure (tPOD) for the 20 PFAS tested was 10 µM. Longer chain carboxylic acids (12-13 C-F) and an eight C-F di-alcohol, N-alkyl sulfonamide, and telomer sulfonic acid were among the most potent PFAS, eliciting gene expression responses at concentrations below 1 µM. With a few exceptions, larval fathead minnow tPODs were concordant with those based on whole transcriptome response in human cell lines. However, larval fathead minnow tPODs were often greater than those for Daphnia magna exposed to the same PFAS. The tPODs overlapped concentrations at which other sub-lethal effects have been reported in fish (available for 10 PFAS; including a range of species, life stages, and study designs). Nonetheless, fathead minnow tPODs were all orders of magnitude higher than aqueous PFAS concentrations detected in tributaries of the North American Great Lakes suggesting a substantial margin of safety in those systems, even for PFAS with significant potential for bioaccumulation. Overall, results broadly support the use of a fathead minnow larval transcriptomics assay to derive screening level potency estimates for use in ecological risk-based prioritization. Traditional toxicity testing has been unable to keep pace with the introduction of new chemicals into commerce. Consequently, there are limited or no toxicity data upon which to base a risk assessment for many chemicals to which fish and wildlife may be exposed. Per- and polyfluoroalkyl substances (PFAS) are emblematic of this issue in that most the ecological hazards of most PFAS remain uncharacterized. The present study employed a high throughput assay to identify the concentration at which 20 PFAS, with diverse properties, elicited a concerted gene expression response in larval fathead minnows (Pimephales promelas, 5-6 days post-fertilization) exposed for 24 h. Based on a reduced transcriptome approach that measured whole body expression of 1832 genes, the median transcriptomic point of departure (tPOD) for the 20 PFAS tested was 10 µM. Longer chain carboxylic acids (12-13 C-F) and an eight C-F di-alcohol, N-alkyl sulfonamide, and telomer sulfonic acid were among the most potent PFAS, eliciting gene expression responses at concentrations below 1 µM. With a few exceptions, larval fathead minnow tPODs were concordant with those based on whole transcriptome response in human cell lines. However, larval fathead minnow tPODs were often greater than those for Daphnia magna exposed to the same PFAS. The tPODs overlapped concentrations at which other sub-lethal effects have been reported in fish (available for 10 PFAS; including a range of species, life stages, and study designs). Nonetheless, fathead minnow tPODs were all orders of magnitude higher than aqueous PFAS concentrations detected in tributaries of the North American Great Lakes suggesting a substantial margin of safety in those systems, even for PFAS with significant potential for bioaccumulation. Overall, results broadly support the use of a fathead minnow larval transcriptomics assay to derive screening level potency estimates for use in ecological risk-based prioritization.
2024-10-23 | GSE246120 | GEO
Project description:Comparative analysis of transcriptomic points-of-departure (tPODs) and adverse apical responses in embryo-larval fathead minnows exposed to fluoxetine
| PRJNA742771 | ENA
Project description:Current methods to support chemical hazard assessment face significant challenges given the rapidly growing number of compounds of emerging concern (CEC) requiring assessment. Standard testing strategies rely upon live animal testing, which are time-consuming, expensive, and ethically questionable. These concerns serve as an impetus to develop new approach methodologies (NAMs) that do not rely on live animal tests. This study explored the application of the molecular benchmark dose (BMD) approach in a 7-day embryo-larval fathead minnow (FHM) assay to derive determine transcriptomic points-of-departure (tPODs) which can be useds to predict apical BMDs of fluoxetine (FLX), a highly prescribed and potent selective serotonin reuptake inhibitor frequently detected in surface waters. Fertilized FHM embryos were exposed to graded concentrations of FLX (confirmed at <LOD, 0.19, 0.74, 3.38, 10.2, 47.5 µg/L) for 32 days. Subsets of fish were subjected to omics and locomotor analyses at 7 days post-fertilization (dpf) and to histological and biometric measurements at 32 dpf. Enrichment analyses of transcriptomics and proteomics data revealed significant perturbations in gene sets associated with serotonergic and axonal functions. BMD analysis resulted in tPOD values of 0.56 µg/L (median of the 20 most sensitive gene-level BMDs), 5.0 µg/L (tenth percentile of all gene-level BMDs), 7.51 µg/L (mode of the first peak of all gene-level BMDs) , and 5.66 µg/L (pathway-level BMD). These tPODs are protective of apical locomotor and reduced weight effects (LOEC of 10.2 µg/L) observed in this study and are well within the range of chronic apical BMDs of FLX reported in the literature. Furthermore, the distribution of gene-level BMDs followed a bimodal pattern, revealing disruption of sensitive neurotoxic pathways at low concentrations and metabolic pathway perturbations at higher concentrations. This is one of the first studies to derive tPODs for FLX using a short-term embryo assay at a life stage not considered to be a live animal under current legislations.
2021-12-12 | GSE179232 | GEO
Project description:Tricresyl Phosphate (TCP) is an organophosphate flame retardant currently on the market and used as a replacement for phased-out polybrominated diphenyl ethers. Toxicity information on this class of chemicals is inadequate. Herein, the NTP use short-term, in vivo transcriptomic studies to inform potential points of departure for TCP.
2022-07-01 | GSE123433 | GEO
Project description:Triphenyl phosphate (TPHP) is an organophosphate flame retardant currently on the market and used as a replacement for phased-out polybrominated diphenyl ethers. Toxicity information on this class of chemicals is inadequate. Herein, the NTP use short-term, in vivo transcriptomic studies to inform potential points of departure for TPHP.
2018-10-23 | GSE121134 | GEO
Project description:Isopropylated Phenol Phosphate (IPP) is an organophosphate flame retardant currently on the market and used as a replacement for phased-out polybrominated diphenyl ethers. Toxicity information on this class of chemicals is inadequate. Herein, the NTP use short-term, in vivo transcriptomic studies to inform potential points of departure for IPP.
2022-07-01 | GSE123432 | GEO
Project description:Isodecyl Diphenyl Phosphate (IDDP) is an organophosphate flame retardant currently on the market and used as a replacement for phased-out polybrominated diphenyl ethers. Toxicity information on this class of chemicals is inadequate. Herein, the NTP use short-term, in vivo transcriptomic studies to inform potential points of departure for IDDP.
2022-07-01 | GSE123431 | GEO