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EC number: 216-343-6 | CAS number: 1562-00-1
Specific investigations: other studies
Administrative data
Link to relevant study record(s)
- Endpoint:
- biochemical or cellular interactions
- Type of information:
- experimental study
- Adequacy of study:
- weight of evidence
- Study period:
- 2022
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- study well documented, meets generally accepted scientific principles, acceptable for assessment
- Reason / purpose for cross-reference:
- other: Analytical dose confirmation study
- Qualifier:
- no guideline followed
- Principles of method if other than guideline:
- The developmental toxicity potential of SI was assessed by the use of Stemina's devTOX quickPredict assay. The assay was conducted on human induced pluripotent stem cells (hiPSCs) and the disturbance in cellular metabolism caused by a 48-hour exposure to SI was measured. The assessment was done by tracking two biomarkers identified as indicators of developmental toxicity: ornithine and cystine. The ornithine/cystine ratio was used to determine the concentration at which a test article disturbed the cellular metabolism, indicating developmental toxicity potential. The assay was done in accordance with Palmer J. et. al (Birth Defects Res B Dev Reprod Toxicol. 2013); Palmer J. et. al (Developmental Toxicity of Chemicals Tested in devTOXqP 2021); Zurlinden et. al (Profiling the ToxCast Library with a Pluripotent Human (H9) Stem Cell Line-Based Biomarker Assay for Developmental Toxicity, 2020).
- GLP compliance:
- no
- Type of method:
- in vitro
- Endpoint addressed:
- developmental toxicity / teratogenicity
- Details on results:
- RESULTS:
At the exposure levels evaluated, SI showed no response for the o/c ratio and cell viability.
The positive control elicited a response in the o/c ratio of 0,13 within the defined acceptance criteria, establishing that hIPSC metabolism was within assay specifications.
For figures see "Overall remarks, attachments". - Conclusions:
- In this study, the developmental toxicity potential of SI was assessed by measuring its impact on hiPSC metabolism and cell viability up to and including 1000 µM. No effects on metabolism and cell viability were detected. Therefore, SI, at the exposure levels tested, is not considered to have the potential for developmental toxicity.
- Executive summary:
Si was tested in the DevTox QuickPredict assay to assess its developmental toxicity potential across an eight-point concentration range. The prediction is based on changes in cellular metabolism in treated human induced pluripotent stem cells (hiPSCs). The ornithine and cysteine concentration in the media after exposure of hiPSCs to SI were measured. Cell viability was tested in parallel to understand whether metabolic changes occur independently of effects on cell health.
No effects on metabolism and cell viability were detected up to and including the highest dose tested. The Point of Departure was calculated from the respective dose response curves using the hiPSC developmental toxicity threshold (dTT, 0.85). The PoD for SI in this assay was found to exceed 1000 µM.
- Endpoint:
- biochemical or cellular interactions
- Type of information:
- experimental study
- Adequacy of study:
- weight of evidence
- Study period:
- 09-05-2022 - 09-08-2022
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- study well documented, meets generally accepted scientific principles, acceptable for assessment
- Reason / purpose for cross-reference:
- other: Analytical dose confirmation study
- Qualifier:
- no guideline followed
- Principles of method if other than guideline:
- This study was based on the paper of Hatherell et. al. (Identifying and Characterizing Stress Pathways of Concern for Consumer Safety in Next-Generation Risk Assessment, Toxicol Sci. 2020;176(1):11-33).
an in vitro cell stress panel study was conducted to identify concentrations associated with induction of cellular stress pathways and therefore potentially adverse health effects. First, the solubility of SI in matrix matched conditions was assessed. Then a cytotoxicity assessment utilising HepG2 cells measuring ATP & LDH content (Promega) was conducted to determine the maximum concentrations of SI to use within the cell stress panel. HepG2 cells were exposed to SI for 24h and a variety of cell stress assessments (18 assays assessing mitochondrial toxicity, cell stress, and cell health) was carried out. The BIFROST statistical model was used to analyse the concentration-response data for each biomarker and estimate a minimum effect level. Following this, a global point of departure (PoD) was calculated to represent a minimum effect level across all the cellular stress assays. - GLP compliance:
- no
- Type of method:
- in vitro
- Endpoint addressed:
- other: Mitochondrial toxicity, cell stress, and general cell health
- Details on results:
- After exposure to SI for 24 hours, of the 36 biomarkers assessed, only the Pre-Incubated Functional Mitochondrial ECAR showed a response to treatment with the PoD calculated to be 8900 µM (CDS = 0.72). From the data across all assays, a global PoD of 7300 µM was calculated.
Since only one biomarker was considered to respond to treatment with SI under the conditions of this assay, and only at very high concentrations, it is unlikely that SI will affect any of the cellular stress pathways investigated. - Conclusions:
- Based on the results of an in vitro cell stress panel study it is concluded that SI is unlikely to affect the stress pathways measured under the conditions of this assay and the global PoD is calculated to be 7300 µM.
- Executive summary:
SI was assessed in a low-tier broad-spectrum, cell stress panel in HepG2 cells consisting of 36 biomarkers representing oxidative stress, DNA damage, inflammation, endoplasmic reticulum stress, metal stress, heat shock, hypoxia as well as mitochondrial toxicity and general cellular health, measured predominantly using high content imaging. Measurements for the cell stress were analysed using Bayesian concentration-response models called BIFROST (Bayesian inference for region of signal threshold) to obtain the Point of Departure estimate in terms of the nominal concentration. The results of this in vitro cell stress panel study indicate that SI is unlikely to affect the stress pathways measured under the conditions of this assay and the global PoD is calculated to be 7300 µM.
- Endpoint:
- toxicogenomics
- Remarks:
- Transcriptomics assay
- Type of information:
- experimental study
- Adequacy of study:
- weight of evidence
- Study period:
- 23-03-2022 - 23-05-2022
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- study well documented, meets generally accepted scientific principles, acceptable for assessment
- Reason / purpose for cross-reference:
- other: Analytical dose confirmation study
- Qualifier:
- no guideline followed
- Principles of method if other than guideline:
- The objective of this study was to determine the effect of SI on RNA expression. HepG2, MCF7 and HepaRG cells were exposed to SI for 24 hours. An initial cytotoxicity study was done to determine doses for the main cell lysate generation, both LDH and cellular ATP content were assessed. Cell lysate samples were generated and analysed by transcriptomics, in addition matching cytotoxicity measurements were taken (LDH content only ). Two different models were used to interpret the transcriptomics data: (1) the global point of departure (POD) derived using the BIFROST model and (2) the minimum bench mark dose level (BMDL; the lower bound of the pathway-average Benchmark concentration) obtained using BMDexpress. The global PoD is designed to identify a gene-level ‘no observed transcriptional effect level’ (NOTEL) whereas the BMDL is intended to identify the lowest concentration that causes a perturbation of the transcriptome at the pathway level.
- GLP compliance:
- no
- Type of method:
- in vitro
- Endpoint addressed:
- other: cellular responsiveness
- Details on results:
- The full data sets for the different cell lines are attached below as full reports.
- Conclusions:
- The results indicate that, in the cell lines tested, there is no change to gene expression levels at concentrations above 150 µM.
- Executive summary:
A transcriptomics assay was performed with SI to characterise perturbations in RNA transcription across the whole genome and to provide a nontargeted approach to capture biological effects potentially undetected using the other bioactivity platforms. Multiple cell models (HepG2, HepaRG, and MCF-7) were included to increase biological coverage and two different models are used to analyse the transcriptomics data and estimate a Point of Departure (PoD): the global PoD derived using the BIFROST model, and the minimum benchmark dose lower confidence limit (BMDL) (the lower bound of the pathway-average Benchmark concentration) obtained using BMDexpress2. The global PoD is designed to identify a gene-level ‘no observed transcriptional effect level’ (NOTEL) whereas the BMDL is intended to identify the lowest concentration that causes a perturbation of the transcriptome at the pathway level. This is useful additional information because isolated changes in individual genes may not represent a meaningful biological difference, whereas changes in the expression of several genes within a pathway may be more biologically relevant. The identified PoDs for SI were 150, 2500 and 1200 µM (BIFROST) and 2660, 4210 and 1040 µM (BMDexpress) based on nominal concentrations in MCF7, HepG2 and HepaRG cells, respectively.
- Endpoint:
- mechanistic studies
- Type of information:
- experimental study
- Adequacy of study:
- weight of evidence
- Study period:
- 22/10/2020 and 30/04/2021
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- study well documented, meets generally accepted scientific principles, acceptable for assessment
- Qualifier:
- according to guideline
- Guideline:
- other: OECD, Guidance Document on Good In Vitro Method Practices (GIVIMP), OECD Series on Testing and Assessment, No. 286, OECD Publishing, Paris.
- Version / remarks:
- 2018
- Deviations:
- no
- Principles of method if other than guideline:
- The goal of this study was to assess the embryotoxicity potential of SI, by by measuring effects on differentiation of human induced pluripotent stems cells (hiPSCs) on the compounds. Differentiation of hiPSC are used to mimic early human development and perturbations of the underlying signalling events have been shown to be predictive of embryotoxic substances (Jamalpoor te al 2022).
The ReproTracker assay is based on differentiation of hiPSCs into cardiomyocytes, hepatocytes and neural rosettes, which arise from mesoderm, endoderm and ectoderm, respectively. The influence of SI on this differentiation process was determined by monitoring alterations in expression patterns of tissue specific biomarkers in a dose dependent way. To determine exposure doses, a dose rage finding study was performed first. Test concentrations for differentiation was done in twofold dilutions and concentrations where 1000, 500, 250, 125, 62.5 and 31.25 uM respectively. - GLP compliance:
- no
- Type of method:
- in vitro
- Endpoint addressed:
- developmental toxicity / teratogenicity
- Dose / conc.:
- 0 other: µM
- Remarks:
- Solvent only (dH2O)
- Dose / conc.:
- 0.32 other: µM
- Dose / conc.:
- 1.6 other: µM
- Dose / conc.:
- 8 other: µM
- Dose / conc.:
- 40 other: µM
- Dose / conc.:
- 200 other: µM
- Dose / conc.:
- 1 000 other: µM
- Details on results:
- Cytotoxicity Testing:
No cytotoxicity could be observed for SI up to the highest concentrations tested (1000uM).
Differentiation:
Differentiation of cells was as expected. Positive and negative controls showed expected behaviour either indicating embryotoxicity by downregulation of the relevant biomarkers or showing no disturbance in the differentiation process.
No PoD for SI could be calculated neither for cell viability, nor in the differentiation of the cell lines.
For the figures, see "Overall remarks, attachments". - Conclusions:
- The toxicity of Isethionic acid sodium salt (SI) on the differentiation of hiPSCs to cardiomyocytes, hepatocytes and neural rosettes was assessed by a ReproTracker assay. SI did not show any alterations in biomarker gene expression, and functional and morphological characteristics of the cells.
- Executive summary:
SI was tested in the Reprotracker assay, which is a human induced pluripotent stem cells (hiPSCs)-based biomarker assay that assesses embryotoxicity. Pluripotent stem cells, under specified growth conditions, can be triggered to differentiate into all 3 germ layers (meso-, endo- and ectoderm) and further to the development of specific cell lineages, such as hepatocytes, cardiomyocytes and neuronal cells. Such differentiation processes are complex and tightly regulated and are susceptible to perturbations by teratogenic substances. By assessing the expression pattern of specific differentiation-related genes via qRT-PCR (OCT4 as a pluripotency marker, BMP4 as a mesoderm marker, FOXA2 as an endoderm marker, and MYH6, AFP, and PAX6/NESTIN as the cardiomyocyte-, hepatocyte-, and neural rosettes-specific markers, respectively), the progress of differentiation and whether a compound interferes with embryonic development can be followed.
SI did not show any alterations in biomarker gene expression, and functional and morphological characteristics of the cells. The PoD was then calculated from the qRT-PCR data using BMDexpress2. The PoD for this assay was found to exceed 1000 µM.
- Endpoint:
- biochemical or cellular interactions
- Remarks:
- In vitro test battery including binding assays, cellular and nuclear receptor functional and enzyme assays.
- Type of information:
- experimental study
- Adequacy of study:
- weight of evidence
- Study period:
- March 28, 2022 - May 11, 2022
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- study well documented, meets generally accepted scientific principles, acceptable for assessment
- Qualifier:
- according to guideline
- Guideline:
- other: ICH Topic S 7 A Safety Pharmacology Studies for Human Pharmaceuticals
- Version / remarks:
- 2001, CPMP/ICH/539/00
- Deviations:
- yes
- Remarks:
- See "Principles of method if other than guideline"
- Principles of method if other than guideline:
- This study was performed to evaluate the specific binding, enzymatic activity, coactivator recruitment of Isethionic Acid Sodium Salt (SI). An in vitro test battery was used including binding assays, cellular and nuclear receptor functional and enzyme assays.
Testing was done with a single concentration, instead of a range of concentrations as recommended in the guidance. The choice is based on the recommendations by Jenkinson et al (Journal of Pharmacological and Toxicological Methods 105 (2020)), who recommend 10 µM as a suitable concentration when only a single concentration is tested. As the solubility of SI in the test medium is expected to be high, the final test concentration was chosen at 100 µM. The assays were performed under non-GLP circumstances. The study was conducted at a Research Facility that generally works under GLP and general quality controls were applied. This implies that the non-GLP status has no further consequences for the outcome of the study. - GLP compliance:
- no
- Remarks:
- The study was conducted at a Research Facility that generally works under GLP and general quality controls were applied.
- Type of method:
- in vitro
- Endpoint addressed:
- toxicity to reproduction / fertility
- developmental toxicity / teratogenicity
- other: systemic toxicity
- Dose / conc.:
- 100 other: µM
- Remarks:
- The choice was based on the recommendations of Jenkinson et al (Journal of Pharmacological and Toxicological Methods 105 (2020)), who recommend 10 µM as a suitable concentration when only a single concentration is tested. As the solubility of SI in the test medium is high, the final test concentration was chosen at 100 µM.
- Details on results:
- Inhibition or stimulation exceeding 50% compared to the control value were considered to represent significant effects of the test compound. Such effects were not observed in any of the assays studied. One weak to moderate effect was measured for thyroperoxidase (TPO) with an inhibition of 30.9% compared to the control.
The observed in vitro effect on TPO was considered not to be toxicologically relevant based on the fact that in the repeated dose toxicity study (summarised in section 7.5) no adverse effects were found in the thyroids (absence of SI-related changes in thyroid organ weight and absence of histopathological effects after SI exposure) after exposure for 90 days up to and including 1000 mg/kg bw/day. - Conclusions:
- Isethionic acid sodium salt (SI) was tested in a battery of assays including binding assays, cellular and nuclear receptor functional assays and enzyme assays.
SI did not exhibit inhibiting or activating effects in any of the assays, except for a moderate inhibition of thyroperoxidase (TPO) compared to control values. The observed effect was considered not toxicologically relevant based on the fact that in the repeated dose toxicity study (summarised in section 7.5) no adverse effects were found in the thyroids (absence of SI-related changes in thyroid organ weight and absence of histopathological effects after SI exposure) after exposure for 90 days up to and including 1000 mg/kg bw/day. This data indicates that SI does not interfere with targets with proven links to adverse reactions in humans, including targets relevant for reproduction and development. - Executive summary:
SI was tested in an in vitro pharmacological profiling (IPP) platform contains 73 targets with known safety liabilities that were tested in binding, enzymatic, coactivator recruitment, and luciferase assays. Forty-four of the targets have been associated with in vivo adverse drug reactions by the pharmaceutical industry including: 24 G-protein-coupled receptors (GPCRs), 7 enzymes, 2 nuclear receptors, 8 ion channels, and 3 transporters. In response to the ECHA compliance check, to expand the above biological coverage, into targets implicated in DART, a further 29 targets were added to the panel, including: 5 nuclear hormone receptors, 11 basic helix-loop-helix transcription factors 11 enzymes, 1 GPCR, and 1 structural protein.
SI did not exhibit inhibiting or activating effects in any of the assays, except for a moderate inhibition of thyroperoxidase (TPO) compared to control values. The observed effect was considered not toxicologically relevant based on the fact that in the repeated dose toxicity study (summarised in section 7.5) no adverse effects were found in the thyroids (absence of SI-related changes in thyroid organ weight and absence of histopathological effects after SI exposure) after exposure for 90 days up to and including 1000 mg/kg bw/day. This data indicates that SI does not interfere with targets with proven links to adverse reactions in humans, including targets relevant for reproduction and development.
Referenceopen allclose all
Results from the controls:
Cytotoxicity assay:
the positive controls induced a response with both cellular ATP and LDH release for HepG2 cells.
Assay results:
Responses were observed for each biomarker in at least 1 positive control, in at least 2 of the 3 biological replicates where there is more than 1 positive control per assay.
Results SI:
Solubility:
A solubility assessment was performed on Isethionic Acid Sodium Salt (SI) with DMSO (data not reported). Based on data provided by the supplier and following expert review, water was selected as the final solvent for Isethionic Acid Sodium Salt (SI) in this study as higher doses could be achieved. A top concentration of 10000 μM was chosen for the cytotoxicity assay.
Cytotoxicity:
No cytotoxicity was observed when tested up to 10000 μM in HepG2 cells in either the LDH or ATP treatments.
Cell Stress Panel Test Results:
HepG2 cells were treated with various concentrations of Isethionic acid sodium salt (SI) (0.894-14650μM) for 24 h before assessment in the cell stress panel.
Isethionic acid sodium salt (SI) showed very limited activity in HepG2 cells following 24 hours incubation, and there were no indications of cytotoxicity. Effects were observed in ECAR biomarker, which is part of the Extracellular Flux Assay (also known as the Seahorse Assay) and measures mitochondrial toxicity. The OCR and Reserve capacity are measured as part of the same assay, but no response was observed with these biomarkers. A confidence score of 0.72 was reported for ECAR and responses were observed in 2 of the 3 replicates.
The global point of departure across all the measured biomarkers, based on nominal concentrations, was determined to be 7300μM.
Assay Specific results:
1. AhR Translocation Assay:
Cell Count:
Mean CDS: 0.00
Expected PoD: Mean CDS less than 0.5, value omitted.
PoD percentiles (µM) | ||||||||
Plate | CDS | 2.5th | 5th | 25th | 50th | 75th | 95th | 97.5th |
1 | 0.0084 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 |
2 | 0.0041 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 |
3 | 0.0019 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 |
Nuclear Area:
Mean CDS: 0.00
Expected PoD: Mean CDS less than 0.5, value omitted.
|
| PoD percentiles (µM) | ||||||
Plate | CDS | 2.5th | 5th | 25th | 50th | 75th | 95th | 97.5th |
1 | 0.0007 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 |
2 | 0.0018 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 |
3 | 0.0002 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 |
DNA Structure:
Mean CDS: 0.00
Expected PoD: Mean CDS less than 0.5, value omitted.
|
| PoD percentiles (µM) | ||||||
Plate | CDS | 2.5th | 5th | 25th | 50th | 75th | 95th | 97.5th |
1 | 0.0053 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 |
2 | 0.0028 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 |
3 | 0.0034 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 |
AhR Translation:
Mean CDS: 0.11
Expected PoD: Mean CDS less than 0.5, value omitted.
|
| PoD percentiles (µM) | ||||||
Plate | CDS | 2.5th | 5th | 25th | 50th | 75th | 95th | 97.5th |
1 | 0.1 | 9600 | 12000 | >15000 | >15000 | >15000 | >15000 | >15000 |
2 | 0.079 | 12000 | 13000 | >15000 | >15000 | >15000 | >15000 | >15000 |
3 | 0.15 | 7200 | 9800 | >15000 | >15000 | >15000 | >15000 | >15000 |
2. Apoptosis, Necrosis and Cell Cycle Arrest Assay:
Cell Count:
Mean CDS: 0.00
Expected PoD: Mean CDS less than 0.5, value omitted.
|
| PoD percentiles (µM) | ||||||
Plate | CDS | 2.5th | 5th | 25th | 50th | 75th | 95th | 97.5th |
1 | 0.0028 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 |
2 | 0.0015 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 |
3 | 0.0024 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 |
Nuclear Area:
Mean CDS: 0.00
Expected PoD: Mean CDS less than 0.5, value omitted.
|
| PoD percentiles (µM) | ||||||
Plate | CDS | 2.5th | 5th | 25th | 50th | 75th | 95th | 97.5th |
1 | 0.0011 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 |
2 | 0.0008 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 |
3 | 0.0009 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 |
DNA Structure:
Mean CDS: 0.00
Expected PoD: Mean CDS less than 0.5, value omitted.
|
| PoD percentiles (µM) | ||||||
Plate | CDS | 2.5th | 5th | 25th | 50th | 75th | 95th | 97.5th |
1 | 0 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 |
2 | 0.0016 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 |
3 | 0 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 |
Membrane permeability:
Mean CDS: 0.00
Expected PoD: Mean CDS less than 0.5, value omitted.
|
| PoD percentiles (µM) | ||||||
Plate | CDS | 2.5th | 5th | 25th | 50th | 75th | 95th | 97.5th |
1 | 0.0003 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 |
2 | 0.0024 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 |
3 | 0.0005 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 |
Caspase 3/7 intensity:
Mean CDS: 0.01
Expected PoD: Mean CDS less than 0.5, value omitted.
|
| PoD percentiles (µM) | ||||||
Plate | CDS | 2.5th | 5th | 25th | 50th | 75th | 95th | 97.5th |
1 | 0.0001 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 |
2 | 0.0012 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 |
3 | 0.0001 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 |
3. DNA damage (phospho-p53 & pH2AX) assay:
Cell Count:
Mean CDS: 0.01
Expected PoD: Mean CDS less than 0.5, value omitted.
|
| PoD percentiles (µM) | ||||||
Plate | CDS | 2.5th | 5th | 25th | 50th | 75th | 95th | 97.5th |
1 | 0.0008 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 |
2 | 0.0042 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 |
3 | 0.0014 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 |
Nuclear Area:
Mean CDS: 0.00
Expected PoD: Mean CDS less than 0.5, value omitted.
|
| PoD percentiles (µM) | ||||||
Plate | CDS | 2.5th | 5th | 25th | 50th | 75th | 95th | 97.5th |
1 | 0.0003 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 |
2 | 0.0004 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 |
3 | 0.0004 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 |
DNA Structure:
Mean CDS: 0.00
Expected PoD: Mean CDS less than 0.5, value omitted.
|
| PoD percentiles (µM) | ||||||
Plate | CDS | 2.5th | 5th | 25th | 50th | 75th | 95th | 97.5th |
1 | 0 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 |
2 | 0.0003 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 |
3 | 0.0004 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 |
DNA Damage (pH2AX):
Mean CDS: 0.01
Expected PoD: Mean CDS less than 0.5, value omitted.
|
| PoD percentiles (µM) | ||||||
Plate | CDS | 2.5th | 5th | 25th | 50th | 75th | 95th | 97.5th |
1 | 0.027 | 14000 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 |
2 | 0.0035 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 |
3 | 0.0044 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 |
Phospho-p53:
Mean CDS: 0.00
Expected PoD: Mean CDS less than 0.5, value omitted.
|
| PoD percentiles (µM) | ||||||
Plate | CDS | 2.5th | 5th | 25th | 50th | 75th | 95th | 97.5th |
1 | 0.0004 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 |
2 | 0.0005 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 |
3 | 0 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 |
4. ER Stress Assay Panel 1:
Cell count:
Mean CDS: 0.00
Expected PoD: Mean CDS less than 0.5, value omitted.
|
| PoD percentiles (µM) | ||||||
Plate | CDS | 2.5th | 5th | 25th | 50th | 75th | 95th | 97.5th |
1 | 0.0004 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 |
2 | 0.002 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 |
3 | 0.0018 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 |
Nuclear Area:
Mean CDS: 0.00
Expected PoD: Mean CDS less than 0.5, value omitted.
|
| PoD percentiles (µM) | ||||||
Plate | CDS | 2.5th | 5th | 25th | 50th | 75th | 95th | 97.5th |
1 | 0.0003 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 |
2 | 0.0003 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 |
3 | 0.001 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 |
DNA Structure:
Mean CDS: 0.01
Expected PoD: Mean CDS less than 0.5, value omitted.
|
| PoD percentiles (µM) | ||||||
Plate | CDS | 2.5th | 5th | 25th | 50th | 75th | 95th | 97.5th |
1 | 0.0093 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 |
2 | 0.0007 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 |
3 | 0.006 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 |
Endoplasmic reticulum:
Mean CDS: 0.01
Expected PoD: Mean CDS less than 0.5, value omitted.
|
| PoD percentiles (µM) | ||||||
Plate | CDS | 2.5th | 5th | 25th | 50th | 75th | 95th | 97.5th |
1 | 0.0074 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 |
2 | 0.0033 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 |
3 | 0.0092 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 |
BiP:
Mean CDS: 0.01
Expected PoD: Mean CDS less than 0.5, value omitted.
|
| PoD percentiles (µM) | ||||||
Plate | CDS | 2.5th | 5th | 25th | 50th | 75th | 95th | 97.5th |
1 | 0.0049 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 |
2 | 0.0034 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 |
3 | 0.0091 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 |
5. ER Stress Assay Panel 2:
Cell Count:
Mean CDS: 0.02
Expected PoD: Mean CDS less than 0.5, value omitted.
|
| PoD percentiles (µM) | ||||||
Plate | CDS | 2.5th | 5th | 25th | 50th | 75th | 95th | 97.5th |
1 | 0.0061 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 |
2 | 0.015 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 |
3 | 0.04 | 13000 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 |
Nuclear Area:
Mean CDS: 0.00
Expected PoD: Mean CDS less than 0.5, value omitted.
|
| PoD percentiles (µM) | ||||||
Plate | CDS | 2.5th | 5th | 25th | 50th | 75th | 95th | 97.5th |
1 | 0.001 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 |
2 | 0.0027 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 |
3 | 0.0005 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 |
DNA Structure:
Mean CDS: 0.00
Expected PoD: Mean CDS less than 0.5, value omitted.
|
| PoD percentiles (µM) | ||||||
Plate | CDS | 2.5th | 5th | 25th | 50th | 75th | 95th | 97.5th |
1 | 0.0027 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 |
2 | 0.0019 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 |
3 | 0.0007 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 |
ATF4:
Mean CDS: 0.00
Expected PoD: Mean CDS less than 0.5, value omitted.
|
| PoD percentiles (µM) | ||||||
Plate | CDS | 2.5th | 5th | 25th | 50th | 75th | 95th | 97.5th |
1 | 0.0038 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 |
2 | 0.0055 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 |
3 | 0.0014 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 |
PERK:
Mean CDS: 0.02
Expected PoD: Mean CDS less than 0.5, value omitted.
|
| PoD percentiles (µM) | ||||||
Plate | CDS | 2.5th | 5th | 25th | 50th | 75th | 95th | 97.5th |
1 | 0.026 | 15000 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 |
2 | 0.0098 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 |
3 | 0.016 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 |
CHOP:
Mean CDS: 0.01
Expected PoD: Mean CDS less than 0.5, value omitted.
|
| PoD percentiles (µM) | ||||||
Plate | CDS | 2.5th | 5th | 25th | 50th | 75th | 95th | 97.5th |
1 | 0.0035 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 |
2 | 0.0056 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 |
3 | 0.0098 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 |
6. HCS GSH, ROS, MMP & ATP Assay
Cell count:
Mean CDS: 0.01
Expected PoD: Mean CDS less than 0.5, value omitted.
|
| PoD percentiles (µM) | ||||||
Plate | CDS | 2.5th | 5th | 25th | 50th | 75th | 95th | 97.5th |
1 | 0.0078 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 |
2 | 0.0067 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 |
3 | 0.0072 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 |
Nuclear Area:
Mean CDS: 0.01
Expected PoD: Mean CDS less than 0.5, value omitted.
|
| PoD percentiles (µM) | ||||||
Plate | CDS | 2.5th | 5th | 25th | 50th | 75th | 95th | 97.5th |
1 | 0.02 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 |
2 | 0.0042 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 |
3 | 0.0054 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 |
DNA Structure:
Mean CDS: 0.02
Expected PoD: Mean CDS less than 0.5, value omitted.
|
| PoD percentiles (µM) | ||||||
Plate | CDS | 2.5th | 5th | 25th | 50th | 75th | 95th | 97.5th |
1 | 0.0093 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 |
2 | 0.024 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 |
3 | 0.019 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 |
Mitochondrial mass:
Mean CDS: 0.00
Expected PoD: Mean CDS less than 0.5, value omitted.
|
| PoD percentiles (µM) | ||||||
Plate | CDS | 2.5th | 5th | 25th | 50th | 75th | 95th | 97.5th |
1 | 0.001 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 |
2 | 0.0008 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 |
3 | 0.0018 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 |
Mitochondrial membrane potential:
Mean CDS: 0.01
Expected PoD: Mean CDS less than 0.5, value omitted.
|
| PoD percentiles (µM) | ||||||
Plate | CDS | 2.5th | 5th | 25th | 50th | 75th | 95th | 97.5th |
1 | 0.0097 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 |
2 | 0.0078 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 |
3 | 0.011 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 |
Oxidative stress (DHE):
Mean CDS: 0.00
Expected PoD: Mean CDS less than 0.5, value omitted.
|
| PoD percentiles (µM) | ||||||
Plate | CDS | 2.5th | 5th | 25th | 50th | 75th | 95th | 97.5th |
1 | 0.0012 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 |
2 | 0.0003 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 |
3 | 0.0013 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 |
GSH content:
Mean CDS: 0.00
Expected PoD: Mean CDS less than 0.5, value omitted.
|
| PoD percentiles (µM) | ||||||
Plate | CDS | 2.5th | 5th | 25th | 50th | 75th | 95th | 97.5th |
1 | 0.0029 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 |
2 | 0.0073 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 |
3 | 0.0011 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 |
Cellular ATP:
Mean CDS: 0.01
Expected PoD: Mean CDS less than 0.5, value omitted.
|
| PoD percentiles (µM) | ||||||
Plate | CDS | 2.5th | 5th | 25th | 50th | 75th | 95th | 97.5th |
1 | 0.0079 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 |
2 | 0.017 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 |
3 | 0.016 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 |
7. HCS MMP and ATP (TMRE)
Cell count:
Mean CDS: 0.00
Expected PoD: Mean CDS less than 0.5, value omitted.
|
| PoD percentiles (µM) | ||||||
Plate | CDS | 2.5th | 5th | 25th | 50th | 75th | 95th | 97.5th |
1 | 0.0015 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 |
2 | 0.0017 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 |
3 | 0.0007 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 |
Nuclear Area:
Mean CDS: 0.82
Expected PoD: 9100 µM
|
| PoD percentiles (µM) | ||||||
Plate | CDS | 2.5th | 5th | 25th | 50th | 75th | 95th | 97.5th |
1 | 1 | 4300 | 4900 | 7100 | 8800 | 10000 | 12000 | 13000 |
2 | 0.48 | 7700 | 9000 | 12000 | >15000 | >15000 | >15000 | >15000 |
3 | 0.99 | 3600 | 4200 | 6400 | 8300 | 10000 | 12000 | 13000 |
DNA structure:
Mean CDS: 0.23
Expected PoD: Mean CDS less than 0.5, value omitted.
|
| PoD percentiles (µM) | ||||||
Plate | CDS | 2.5th | 5th | 25th | 50th | 75th | 95th | 97.5th |
1 | 0.23 | 8200 | 10000 | >15000 | >15000 | >15000 | >15000 | >15000 |
2 | 0.18 | 9500 | 11000 | >15000 | >15000 | >15000 | >15000 | >15000 |
3 | 0.29 | 4500 | 6500 | 13000 | >15000 | >15000 | >15000 | >15000 |
Mitochondrial mass:
Mean CDS: 0.16
Expected PoD: Mean CDS less than 0.5, value omitted.
|
| PoD percentiles (µM) | ||||||
Plate | CDS | 2.5th | 5th | 25th | 50th | 75th | 95th | 97.5th |
1 | 0.18 | 9600 | 11000 | >15000 | >15000 | >15000 | >15000 | >15000 |
2 | 0.11 | 11000 | 12000 | >15000 | >15000 | >15000 | >15000 | >15000 |
3 | 0.2 | 8800 | 10000 | >15000 | >15000 | >15000 | >15000 | >15000 |
Mitochondrial membrane potential:
Mean CDS: 0.03
Expected PoD: Mean CDS less than 0.5, value omitted.
|
| PoD percentiles (µM) | ||||||
Plate | CDS | 2.5th | 5th | 25th | 50th | 75th | 95th | 97.5th |
1 | 0.028 | 14000 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 |
2 | 0.014 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 |
3 | 0.042 | 13000 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 |
Cellular ATP:
Mean CDS: 0.00
Expected PoD: Mean CDS less than 0.5, value omitted.
|
| PoD percentiles (µM) | ||||||
Plate | CDS | 2.5th | 5th | 25th | 50th | 75th | 95th | 97.5th |
1 | 0.0027 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 |
2 | 0.0017 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 |
3 | 0.0025 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 |
8. Inflammation & pH Assay:
Cell count:
Mean CDS: 0.00
Expected PoD: Mean CDS less than 0.5, value omitted.
|
| PoD percentiles (µM) | ||||||
Plate | CDS | 2.5th | 5th | 25th | 50th | 75th | 95th | 97.5th |
1 | 0.0001 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 |
2 | 0.0004 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 |
3 | 0.0003 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 |
Nuclear Area:
Mean CDS: 0.00
Expected PoD: Mean CDS less than 0.5, value omitted.
|
| PoD percentiles (µM) | ||||||
Plate | CDS | 2.5th | 5th | 25th | 50th | 75th | 95th | 97.5th |
1 | 0.0009 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 |
2 | 0.0005 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 |
3 | 0.0016 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 |
DNA structure:
Mean CDS: 0.01
Expected PoD: Mean CDS less than 0.5, value omitted.
|
| PoD percentiles (µM) | ||||||
Plate | CDS | 2.5th | 5th | 25th | 50th | 75th | 95th | 97.5th |
1 | 0.0041 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 |
2 | 0.0004 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 |
3 | 0.023 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 |
Intracellular pH:
Mean CDS: 0.00
Expected PoD: Mean CDS less than 0.5, value omitted.
|
| PoD percentiles (µM) | ||||||
Plate | CDS | 2.5th | 5th | 25th | 50th | 75th | 95th | 97.5th |
1 | 0.0008 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 |
2 | 0.0011 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 |
3 | 0.0011 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 |
HIF1alpha:
Mean CDS: 0.01
Expected PoD: Mean CDS less than 0.5, value omitted.
|
| PoD percentiles (µM) | ||||||
Plate | CDS | 2.5th | 5th | 25th | 50th | 75th | 95th | 97.5th |
1 | 0.0095 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 |
2 | 0.0031 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 |
3 | 0.0024 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 |
ICAM1:
Mean CDS: 0.00
Expected PoD: Mean CDS less than 0.5, value omitted.
|
| PoD percentiles (µM) | ||||||
Plate | CDS | 2.5th | 5th | 25th | 50th | 75th | 95th | 97.5th |
1 | 0.0002 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 |
2 | 0.0011 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 |
3 | 0.0009 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 |
9. Inflammatory Response ELISA (Flow Cytometry) IL8 only
Cell count:
Mean CDS: 0.01
Expected PoD: Mean CDS less than 0.5, value omitted.
|
| PoD percentiles (µM) | ||||||
Plate | CDS | 2.5th | 5th | 25th | 50th | 75th | 95th | 97.5th |
1 | 0.0036 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 |
2 | 0.0057 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 |
3 | 0.0066 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 |
IL-8:
Mean CDS: 0.01
Expected PoD: Mean CDS less than 0.5, value omitted.
|
| PoD percentiles (µM) | ||||||
Plate | CDS | 2.5th | 5th | 25th | 50th | 75th | 95th | 97.5th |
1 | 0.0054 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 |
2 | 0.013 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 |
3 | 0.0065 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 |
10. LDH Assay:
LDH release:
Mean CDS: 0.01
Expected PoD: Mean CDS less than 0.5, value omitted.
|
| PoD percentiles (µM) | ||||||
Plate | CDS | 2.5th | 5th | 25th | 50th | 75th | 95th | 97.5th |
1 | 0.0033 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 |
2 | 0.0028 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 |
3 | 0.012 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 |
11. Metal Stress Assay:
Cell count:
Mean CDS: 0.01
Expected PoD: Mean CDS less than 0.5, value omitted.
|
| PoD percentiles (µM) | ||||||
Plate | CDS | 2.5th | 5th | 25th | 50th | 75th | 95th | 97.5th |
1 | 0.0018 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 |
2 | 0.011 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 |
3 | 0.002 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 |
Nuclear Area:
Mean CDS: 0.00
Expected PoD: Mean CDS less than 0.5, value omitted.
|
| PoD percentiles (µM) | ||||||
Plate | CDS | 2.5th | 5th | 25th | 50th | 75th | 95th | 97.5th |
1 | 0.0003 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 |
2 | 0.0014 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 |
3 | 0.001 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 |
DNA structure:
Mean CDS: 0.00
Expected PoD: Mean CDS less than 0.5, value omitted.
|
| PoD percentiles (µM) | ||||||
Plate | CDS | 2.5th | 5th | 25th | 50th | 75th | 95th | 97.5th |
1 | 0.0012 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 |
2 | 0.0003 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 |
3 | 0.0001 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 |
Metallothionein:
Mean CDS: 0.00
Expected PoD: Mean CDS less than 0.5, value omitted.
|
| PoD percentiles (µM) | ||||||
Plate | CDS | 2.5th | 5th | 25th | 50th | 75th | 95th | 97.5th |
1 | 0.0035 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 |
2 | 0.0016 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 |
3 | 0.0019 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 |
MTF1:
Mean CDS: 0.00
Expected PoD: Mean CDS less than 0.5, value omitted.
|
| PoD percentiles (µM) | ||||||
Plate | CDS | 2.5th | 5th | 25th | 50th | 75th | 95th | 97.5th |
1 | 0.0014 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 |
2 | 0.0015 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 |
3 | 0.0011 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 |
12. Mitochondrial Oxidative Stress Assay (PGC1alpha)
Cell count:
Mean CDS: 0.01
Expected PoD: Mean CDS less than 0.5, value omitted.
|
| PoD percentiles (µM) | ||||||
Plate | CDS | 2.5th | 5th | 25th | 50th | 75th | 95th | 97.5th |
1 | 0.0019 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 |
2 | 0.0038 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 |
3 | 0.0068 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 |
Nuclear Area:
Mean CDS: 0.00
Expected PoD: Mean CDS less than 0.5, value omitted.
|
| PoD percentiles (µM) | ||||||
Plate | CDS | 2.5th | 5th | 25th | 50th | 75th | 95th | 97.5th |
1 | 0.0007 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 |
2 | 0.0007 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 |
3 | 0.0029 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 |
DNA structure:
Mean CDS: 0.00
Expected PoD: Mean CDS less than 0.5, value omitted.
|
| PoD percentiles (µM) | ||||||
Plate | CDS | 2.5th | 5th | 25th | 50th | 75th | 95th | 97.5th |
1 | 0.0021 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 |
2 | 0.0005 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 |
3 | 0.0008 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 |
Mitochondrial ROS:
Mean CDS: 0.02
Expected PoD: Mean CDS less than 0.5, value omitted.
|
| PoD percentiles (µM) | ||||||
Plate | CDS | 2.5th | 5th | 25th | 50th | 75th | 95th | 97.5th |
1 | 0.034 | 14000 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 |
2 | 0.013 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 |
3 | 0.026 | 14000 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 |
PGC1alpha:
Mean CDS: 0.00
Expected PoD: Mean CDS less than 0.5, value omitted.
|
| PoD percentiles (µM) | ||||||
Plate | CDS | 2.5th | 5th | 25th | 50th | 75th | 95th | 97.5th |
1 | 0.0006 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 |
2 | 0.0004 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 |
3 | 0.0016 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 |
13. Osmotic & Heat Shock Stress Assay:
Cell count:
Mean CDS: 0.00
Expected PoD: Mean CDS less than 0.5, value omitted.
|
| PoD percentiles (µM) | ||||||
Plate | CDS | 2.5th | 5th | 25th | 50th | 75th | 95th | 97.5th |
1 | 0.0004 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 |
2 | 0.0005 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 |
3 | 0.0014 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 |
Nuclear Area:
Mean CDS: 0.00
Expected PoD: Mean CDS less than 0.5, value omitted.
|
| PoD percentiles (µM) | ||||||
Plate | CDS | 2.5th | 5th | 25th | 50th | 75th | 95th | 97.5th |
1 | 0.0027 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 |
2 | 0.0029 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 |
3 | 0.0019 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 |
DNA structure:
Mean CDS: 0.00
Expected PoD: Mean CDS less than 0.5, value omitted.
|
| PoD percentiles (µM) | ||||||
Plate | CDS | 2.5th | 5th | 25th | 50th | 75th | 95th | 97.5th |
1 | 0.0048 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 |
2 | 0.0007 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 |
3 | 0.0016 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 |
Heat Shock Response (Hsp70):
Mean CDS: 0.00
Expected PoD: Mean CDS less than 0.5, value omitted.
|
| PoD percentiles (µM) | ||||||
Plate | CDS | 2.5th | 5th | 25th | 50th | 75th | 95th | 97.5th |
1 | 0.0005 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 |
2 | 0.0004 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 |
3 | 0.0006 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 |
Osmotic stress (NFAT):
Mean CDS: 0.01
Expected PoD: Mean CDS less than 0.5, value omitted.
|
| PoD percentiles (µM) | ||||||
Plate | CDS | 2.5th | 5th | 25th | 50th | 75th | 95th | 97.5th |
1 | 0.011 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 |
2 | 0.0035 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 |
3 | 0.013 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 |
14. Oxidative Stress Assay (Heme oxygenase 1 and NRF2):
Cell count:
Mean CDS: 0.00
Expected PoD: Mean CDS less than 0.5, value omitted.
|
| PoD percentiles (µM) | ||||||
Plate | CDS | 2.5th | 5th | 25th | 50th | 75th | 95th | 97.5th |
1 | 0.0018 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 |
2 | 0.0062 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 |
3 | 0.0037 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 |
Nuclear area:
Mean CDS: 0.00
Expected PoD: Mean CDS less than 0.5, value omitted.
|
| PoD percentiles (µM) | ||||||
Plate | CDS | 2.5th | 5th | 25th | 50th | 75th | 95th | 97.5th |
1 | 0.0011 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 |
2 | 0.0043 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 |
3 | 0.0015 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 |
DNA structure:
Mean CDS: 0.00
Expected PoD: Mean CDS less than 0.5, value omitted.
|
| PoD percentiles (µM) | ||||||
Plate | CDS | 2.5th | 5th | 25th | 50th | 75th | 95th | 97.5th |
1 | 0.0004 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 |
2 | 0.0013 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 |
3 | 0.0013 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 |
NRF2:
Mean CDS: 0.02
Expected PoD: Mean CDS less than 0.5, value omitted.
|
| PoD percentiles (µM) | ||||||
Plate | CDS | 2.5th | 5th | 25th | 50th | 75th | 95th | 97.5th |
1 | 0.027 | 15000 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 |
2 | 0.013 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 |
3 | 0.032 | 14000 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 |
Heme oxygenase:
Mean CDS: 0.01
Expected PoD: Mean CDS less than 0.5, value omitted.
|
| PoD percentiles (µM) | ||||||
Plate | CDS | 2.5th | 5th | 25th | 50th | 75th | 95th | 97.5th |
1 | 0.0044 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 |
2 | 0.0041 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 |
3 | 0.011 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 |
15. Oxidative Stress Assay (SRXN1 Only):
Cell count:
Mean CDS: 0.00
Expected PoD: Mean CDS less than 0.5, value omitted.
|
| PoD percentiles (µM) | ||||||
Plate | CDS | 2.5th | 5th | 25th | 50th | 75th | 95th | 97.5th |
1 | 0.0033 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 |
2 | 0.0058 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 |
3 | 0.0025 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 |
Nuclear Area:
Mean CDS: 0.00
Expected PoD: Mean CDS less than 0.5, value omitted.
|
| PoD percentiles (µM) | ||||||
Plate | CDS | 2.5th | 5th | 25th | 50th | 75th | 95th | 97.5th |
1 | 0.002 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 |
2 | 0.0044 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 |
3 | 0.0005 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 |
DNA structure:
Mean CDS: 0.00
Expected PoD: Mean CDS less than 0.5, value omitted.
|
| PoD percentiles (µM) | ||||||
Plate | CDS | 2.5th | 5th | 25th | 50th | 75th | 95th | 97.5th |
1 | 0.0014 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 |
2 | 0.0016 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 |
3 | 0.0019 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 |
SRXN1:
Mean CDS: 0.01
Expected PoD: Mean CDS less than 0.5, value omitted.
|
| PoD percentiles (µM) | ||||||
Plate | CDS | 2.5th | 5th | 25th | 50th | 75th | 95th | 97.5th |
1 | 0.0095 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 |
2 | 0.0059 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 |
3 | 0.0038 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 |
16. Phospholipidosis and Steatosis Assay:
Cell count:
Mean CDS: 0.00
Expected PoD: Mean CDS less than 0.5, value omitted.
|
| PoD percentiles (µM) | ||||||
Plate | CDS | 2.5th | 5th | 25th | 50th | 75th | 95th | 97.5th |
1 | 0.0015 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 |
2 | 0.0011 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 |
3 | 0.002 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 |
Nuclear Area:
Mean CDS: 0.01
Expected PoD: Mean CDS less than 0.5, value omitted.
|
| PoD percentiles (µM) | ||||||
Plate | CDS | 2.5th | 5th | 25th | 50th | 75th | 95th | 97.5th |
1 | 0.006 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 |
2 | 0.0072 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 |
3 | 0.014 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 |
DNA structrure:
Mean CDS: 0.00
Expected PoD: Mean CDS less than 0.5, value omitted.
|
| PoD percentiles (µM) | ||||||
Plate | CDS | 2.5th | 5th | 25th | 50th | 75th | 95th | 97.5th |
1 | 0.0026 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 |
2 | 0.0055 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 |
3 | 0.0029 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 |
Phospholipidosis:
Mean CDS: 0.00
Expected PoD: Mean CDS less than 0.5, value omitted.
|
| PoD percentiles (µM) | ||||||
Plate | CDS | 2.5th | 5th | 25th | 50th | 75th | 95th | 97.5th |
1 | 0.0013 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 |
2 | 0.001 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 |
3 | 0.0035 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 |
Steatosis:
Mean CDS: 0.01
Expected PoD: Mean CDS less than 0.5, value omitted.
|
| PoD percentiles (µM) | ||||||
Plate | CDS | 2.5th | 5th | 25th | 50th | 75th | 95th | 97.5th |
1 | 0.0023 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 |
2 | 0.013 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 |
3 | 0.0062 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 |
17. Seahorse Mitochondrial toxicity assay with pre-incubation:
Pre-incubated Func Mito:
Mean CDS: 0.00
Expected PoD: Mean CDS less than 0.5, value omitted.
|
| PoD percentiles (µM) | ||||||
Plate | CDS | 2.5th | 5th | 25th | 50th | 75th | 95th | 97.5th |
1 | 0.0004 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 |
2 | 0.002 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 |
3 | 0.0044 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 |
Pre-incubated Func Mito Reserve Capacity:
Mean CDS: 0.01
Expected PoD: Mean CDS less than 0.5, value omitted.
|
| PoD percentiles (µM) | ||||||
Plate | CDS | 2.5th | 5th | 25th | 50th | 75th | 95th | 97.5th |
1 | 0.0008 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 |
2 | 0.014 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 |
3 | 0.018 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 |
Pre-incubated Func Mito ECAR:
Mean CDS: 0.72
Expected PoD: 8900 μM
|
| PoD percentiles (µM) | ||||||
Plate | CDS | 2.5th | 5th | 25th | 50th | 75th | 95th | 97.5th |
1 | 0.86 | 2700 | 3900 | 9500 | 12000 | 13000 | >15000 | >15000 |
2 | 0.95 | 1300 | 2200 | 7100 | 9600 | 11000 | >15000 | >15000 |
3 | 0.36 | 2300 | 5200 | 13000 | >15000 | >15000 | >15000 | >15000 |
18. XBP1 Assay:
Cell count:
Mean CDS: 0.00
Expected PoD: Mean CDS less than 0.5, value omitted.
|
| PoD percentiles (µM) | ||||||
Plate | CDS | 2.5th | 5th | 25th | 50th | 75th | 95th | 97.5th |
1 | 0.0009 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 |
2 | 0.0009 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 |
3 | 0.0004 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 |
Nuclear Area:
Mean CDS: 0.00
Expected PoD: Mean CDS less than 0.5, value omitted.
|
| PoD percentiles (µM) | ||||||
Plate | CDS | 2.5th | 5th | 25th | 50th | 75th | 95th | 97.5th |
1 | 0.0002 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 |
2 | 0 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 |
3 | 0.0001 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 |
DNA structure:
Mean CDS: 0.17
Expected PoD: Mean CDS less than 0.5, value omitted.
|
| PoD percentiles (µM) | ||||||
Plate | CDS | 2.5th | 5th | 25th | 50th | 75th | 95th | 97.5th |
1 | 0.25 | 8400 | 10000 | 15000 | >15000 | >15000 | >15000 | >15000 |
2 | 0.21 | 10000 | 11000 | >15000 | >15000 | >15000 | >15000 | >15000 |
3 | 0.06 | 13000 | 14000 | >15000 | >15000 | >15000 | >15000 | >15000 |
XBP1:
Mean CDS: 0.01
Expected PoD: Mean CDS less than 0.5, value omitted.
|
| PoD percentiles (µM) | ||||||
Plate | CDS | 2.5th | 5th | 25th | 50th | 75th | 95th | 97.5th |
1 | 0.013 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 |
2 | 0.011 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 |
3 | 0.0013 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 | >15000 |
CONTROL RESULTS
Cell Lysate Generation
Chlorpromazine induced a response with both cellular ATP and LDH release in all three cell lines, CCCP induced a dose response for cellular ATP in all three cell lines and for LDH in HepaRG and HepG2 cell lines.HepG2, HepaRG and MCF7 Cells were treated with Chlorpromazine at doses of 0.064 – 1000 μM for 24h before assessment of LDH leakage (Promega) was performed. Chlorpromazine demonstrated a positive response in the LDH assay in all three cell lines across the plates subsequently sequenced. MRM’s for the transcriptomics controls were assessed in all the cell models. Results demonstrated that the controls were in the correct positions on all plates (data not shown). No cytotoxicity was observed when tested up to 10,000 μM in any of the three cell lines for either LDH or ATP measurements.
Sequencing – TempO-Seq
Principle Component Analysis (PCA) showed that samples and controls cluster in a generally expected way (figure attached below in "Overall remarks, Attachments"), indicating proper functioning of the assay.
Samples from each cell line (MCF7, HepG2 or HepaRG) cluster together. And the bulk lysate controls, which were generated using MCF7 cells, cluster with the MCF7 samples.
BMDExpress2 - MCF-7
The final number of replicates per concentration group was 3-4 (143 for the negative control group). Normalised and rlog transformed data is then inputted into BMDExpress2 for dose response modelling.
Probe Level Dose Response:
After the Williams Trend Test pre-filter (using a 1.5 fold change (FC) and p < 0.05 filter), 77 probes are seen to have a significant monotonic dose response with treatment of Isethionic acid sodium salt across the concentrations tested. Out of those 77 probes, 21 probes had a significant modeland BMDL fit to them. Significant model fits were defined as those which had a fit p filter >0.1 and BMDLs are deemed significant if both the BMDL/BMDU ratio <40 and BMD <the highest tested concentration. Please see Figure 6 and 7 in "Overall remarks, Attachments".
Probe level PODs and statistics:
| PoD (μM) | |
| Avg of 20 BMDLs with highest FC | 6920 |
| Avg of 20 BMDLs with highest FC | 8630 |
The accumulation plot of significant pathway mean BMDLs and accumulation plots of signigicant probes with marked probes in the pathway, can be found in the report attached below.
Pathway level PoDs and statistics:
| PoD(μM) | |
| Avg of 20 lowest pathway BMDLs | 6260 |
| The lowest pathway BMDL | 2860 |
| Avg of 20 pathway BMDLs with lowest 2-tail fisher P values | 6260 |
BMDExpress2 - HepG2
The final number of replicates per concentration group was 3-4 (181 for the negative control group). Normalised and rlog transformed data is then inputted into BMDExpress2 for dose response modelling.
Probe Level Dose Response:
After the Williams Trend Test pre-filter (using a 1.5 fold change (FC) and p < 0.05 filter), 171 probes are seen to have a significant monotonic dose response with treatment of Isethionic acid sodium salt across the concentrations tested. Out of those 171 probes, 19 probes had a significant model and BMDL fit to them. Significant model fits were defined as those which had a fit p filter >0.1 and BMDLs are deemed significant if both the BMDL/BMDU ratio <40 and BMD <the highest tested concentration. Please see Figure 11 and 12 in "Overall remarks, Attachments".
Probe level PODs and statistics:
| PoD (μM) | |
| Avg of 20 BMDLs with highest FC | 5580 |
| Avg of 25th-75th percentile of BMDLs | 9670 |
The accumulation plot of significant pathway mean BMDLs and accumulation plots of signigicant probes with marked probes in the pathway, can be found in the report attached below.
Pathway level PoDs and statistics:
| PoD(μM) | |
| Avg of 20 lowest pathway BMDLs | 8110 |
| The lowest pathway BMDL | 4210 |
| Avg of 20 pathway BMDLs with lowest 2-tail fisher P values | 8110 |
BMDExpress2 - HepaRG
The final number of replicates per concentration group was 3-5 (184 for the negative control group). Normalised and rlog transformed data is then inputted into BMDExpress2 for dose response modelling.
Probe Level Dose Response:
After the Williams Trend Test pre-filter (using a 1.5 fold change (FC) and p < 0.05 filter), 165 probes are seen to have a significant monotonic dose response with treatment of Isethionic acid sodium salt across the concentrations tested. Out of those 165 probes, 67 probes had a significant model and BMDL fit to them.
Significant model fits were defined as those which had a fit p filter >0.1 and BMDLs are deemed significant if both the BMDL/BMDU ratio <40 and BMD <the highest tested concentration.
Probe level PODs and statistics:
| PoD (μM) | |
| Avg of 20 BMDLs with highest FC | 2990 |
| Avg of 25th-75th percentile of BMDLs | 8660 |
The accumulation plot of significant pathway mean BMDLs and accumulation plots of signigicant probes with marked probes in the pathway, can be found in the report attached below.
Pathway level PoDs and statistics:
| PoD(μM) | |
| Avg of 20 lowest pathway BMDLs | 3330 |
| The lowest pathway BMDL | 1040 |
| Avg of 20 pathway BMDLs with lowest 2-tail fisher P values | 3590 |
BIFROST- MCF 7
Summary results:
Global PoD (µM): 150
Num. probes analysed: 12764
Num. CDS>0.5: 151
Num. CDS=1.0: 0
Lowest responding probe (50th percentile): EMCN_14104
Second lowest responding probe (50th percentile): C3orf33_23050
Third lowest responding probe (50th percentile): CBFA2T3_26969
Probe with largest fold-increase in expression: SOCS2_6660
Probe with largest fold-decrease in expression: DNAJC30_14685
BIFROST- HepG2
Global PoD (µM): 2500
Num. probes analysed: 11907
Num. CDS>0.5: 38
Num. CDS=1.0: 0
Lowest responding probe (50th percentile): CYP3A7-CYP3A51P_24430
Second lowest responding probe (50th percentile): HVCN1_15252
Third lowest responding probe (50th percentile): CYP3A43_28477
Probe with largest fold-increase in expression: CYP3A43_28477
Probe with largest fold-decrease in expression: DKK4_89471
BIFROST- HepaRG
Global PoD (µM): 1200
Num. probes analysed: 13023
Num. CDS>0.5: 37
Num. CDS=1.0: 0
Lowest responding probe (50th percentile): HSD11B1_21451
Second lowest responding probe (50th percentile): FAH_2303
Third lowest responding probe (50th percentile): HSDL2_23982
Probe with largest fold-increase in expression: PERM1_24905
Probe with largest fold-decrease in expression: GNMT_16770
Study 1: Binding Assays (including receptors, ion channels, transporters and other enzymes)
Binding Assays - SI Results:
| Assay Name | Test Compound | Test Concentration | % Inhibition of Control Specific Binding | ||
| 1st | 2nd | mean | |||
| A2A(h) (agonist radioligand) | SI | 1.0E-04 M | -16.6 | -6.8 | -11.7 |
| α1A(h) (antagonist radioligand) | SI | 1.0E-04 M | 7.7 | 4.5 | 6.1 |
| α2A(h) (antagonist radioligand) | SI | 1.0E-04 M | -11.2 | -13.0 | -12.1 |
| β1(h) (agonist radioligand) | SI | 1.0E-04 M | 7.7 | 4.6 | 6.1 |
| β2(h) (antagonist radioligand) | SI | 1.0E-04 M | -0.7 | 0.3 | -0.2 |
| AT1 (h) (antagonist radioligand) | SI | 1.0E-04 M | 6.7 | 4.1 | 5.4 |
| BZD (central) (agonist radioligand) | SI | 1.0E-04 M | -19.9 | -9.4 | -14.7 |
| CB1(h) (agonist radioligand) | SI | 1.0E-04 M | -45.8 | -1.8 | -23.8 |
| CB2(h) (agonist radioligand) | SI | 1.0E-04 M | -17.1 | -6.1 | -11.6 |
| CCK1 (CCKA) (h) (agonist radioligand) | SI | 1.0E-04 M | 4.9 | -15.1 | -5.1 |
| D1(h) (antagonist radioligand) | SI | 1.0E-04 M | -0.1 | -2.6 | -1.4 |
| D2S(h) (agonist radioligand) | SI | 1.0E-04 M | -27.1 | -26.8 | -27.0 |
| ETA(h) (agonist radioligand) | SI | 1.0E-04 M | -10.1 | -22.0 | -16.1 |
| NMDA (antagonist radioligand) | SI | 1.0E-04 M | 5.3 | 6.9 | 6.1 |
| H1(h) (antagonist radioligand) | SI | 1.0E-04 M | -8.3 | -10.3 | -9.3 |
| H2(h) (antagonist radioligand) | SI | 1.0E-04 M | -4.8 | -7.4 | -6.1 |
| MAO-A (antagonist radioligand) | SI | 1.0E-04 M | 0.2 | -5.7 | -2.8 |
| M1(h) (antagonist radioligand) | SI | 1.0E-04 M | 1.9 | 2.3 | 2.1 |
| M2 (h) (antagonist radioligand) | SI | 1.0E-04 M | 0.5 | -3.4 | -1.4 |
| M3(h) (antagonist radioligand) | SI | 1.0E-04 M | -3.9 | 0.8 | -1.6 |
| N neuronal α4β2 (h) (agonist radioligand) | SI | 1.0E-04 M | -5.9 | -2.3 | -4.1 |
| δ (DOP) (h) (agonist radioligand) | SI | 1.0E-04 M | -1.8 | 3.0 | 0.6 |
| kappa (h) (KOP) (agonist radioligand) | SI | 1.0E-04 M | 8.9 | -2.7 | 3.1 |
| μ (MOP) (h) (agonist radioligand) | SI | 1.0E-04 M | -4.3 | -1.2 | -2.8 |
| 5-HT1A(h) (agonist radioligand) | SI | 1.0E-04 M | 11.0 | 2.7 | 6.9 |
| 5-HT1B (h) (antagonist radioligand) | SI | 1.0E-04 M | -14.4 | -7.0 | -10.7 |
| 5-HT2A(h) (agonist radioligand) | SI | 1.0E-04 M | -4.7 | 6.9 | 1.1 |
| 5-HT2B(h) (agonist radioligand) | SI | 1.0E-04 M | -7.6 | -4.2 | -5.9 |
| 5-HT3(h) (antagonist radioligand) | SI | 1.0E-04 M | 15.3 | 12.8 | 14.1 |
| GR (h) (agonist radioligand) | SI | 1.0E-04 M | -11.1 | -10.7 | -10.9 |
| AR(h) (agonist radioligand) | SI | 1.0E-04 M | -16.1 | -19.7 | -17.9 |
| V1a(h) (agonist radioligand) | SI | 1.0E-04 M | 8.9 | 7.1 | 8.0 |
| Ca2+ channel (L, dihydropyridine site) (antagonist radioligand) | SI | 1.0E-04 M | -22.7 | -33.2 | -27.9 |
| Potassium Channel hERG (human)- [3H] Dofetilide | SI | 1.0E-04 M | -4.1 | -2.3 | -3.2 |
| KV channel (antagonist radioligand) | SI | 1.0E-04 M | 4.7 | -3.6 | 0.6 |
| Na+ channel (site 2) (antagonist radioligand) | SI | 1.0E-04 M | -5.6 | -0.6 | -3.1 |
| norepinephrine transporter(h) (antagonist radioligand) | SI | 1.0E-04 M | -4.7 | -0.6 | -2.7 |
| dopamine transporter(h) (antagonist radioligand) | SI | 1.0E-04 M | -0.3 | -2.7 | -1.5 |
| 5-HT transporter (h) (antagonist radioligand) | SI | 1.0E-04 M | -1.2 | 0.0 | -0.6 |
Binding Assays - Reference Compound Results:
| Assay Name + Compound I.D. | IC50(M) | Ki(M) | nH |
| A2A(h) (agonist radioligand) | |||
| NECA | 4.6E-08 M | 3.8E-08 M | 1.0 |
| α1A(h) (antagonist radioligand) | |||
| WB 4101 | 5.3E-10 M | 2.7E-10 M | 1.2 |
| α2A(h) (antagonist radioligand) | |||
| yohimbine | 7.7E-09 M | 3.4E-09 M | 2.0 |
| β1(h) (agonist radioligand) | |||
| atenolol | 2.9E-07 M | 1.6E-07 M | 1.2 |
| β2(h) (antagonist radioligand) | |||
| ICI 118551 | 9.8E-10 M | 3.3E-10 M | 1.0 |
| AT1 (h) (antagonist radioligand) | |||
| saralasin | 9.3E-10 M | 4.7E-10 M | 0.9 |
| BZD (central) (agonist radioligand) | |||
| diazepam | 9.1E-09 M | 7.7E-09 M | 1.4 |
| CB1(h) (agonist radioligand) | |||
| CP 55940 | 3.0E-09 M | 9.2E-10 M | 1.2 |
| CB2(h) (agonist radioligand) | |||
| WIN 55212-2 | 1.4E-09 M | 9.3E-10 M | 1.2 |
| CCK1 (CCKA) (h) (agonist radioligand) | |||
| CCK-8s | 1.2E-10 M | 9.3E-11 M | 1.6 |
| D1(h) (antagonist radioligand) | |||
| SCH 23390 | 3.2E-10 M | 1.3E-10 M | 1.3 |
| D2S(h) (agonist radioligand) | |||
| 7-OH-DPAT | 2.5E-09 M | 9.9E-10 M | >3 |
| ETA(h) (agonist radioligand) | |||
| endothelin-1 | 2.3E-11 M | 1.1E-11 M | 1.1 |
| NMDA (antagonist radioligand) | |||
| CGS 19755 | 2.6E-07 M | 2.1E-07 M | 0.8 |
| H1(h) (antagonist radioligand) | |||
| pyrilamine | 2.5E-09 M | 1.5E-09 M | 1.3 |
| H2(h) (antagonist radioligand) | |||
| cimetidine | 5.5E-07 M | 5.4E-07 M | 1.1 |
| MAO-A (antagonist radioligand) | |||
| clorgyline | 1.3E-09 M | 7.7E-10 M | 1.6 |
| M1 (h) (antagonist radioligand) | |||
| pirenzepine | 2.8E-08 M | 2.4E-08 M | 1.6 |
| M2 (h) (antagonist radioligand) | |||
| methoctramine | 5.1E-08 M | 3.6E-08 M | 1.2 |
| M3 (h) (antagonist radioligand) | |||
| 4-DAMP | 8.6E-10 M | 6.1E-10 M | 1.8 |
| N neuronal α4β2 (h) (agonist radioligand) | |||
| nicotine | 3.8E-09 M | 1.3E-09 M | 0.9 |
| δ (DOP) (h) (agonist radioligand) | |||
| DPDPE | 2.1E-09 M | 1.2E-09 M | 1.0 |
| kappa (h) (KOP) (agonist radioligand) | |||
| U50488 | 3.8E-10 M | 2.1E-10 M | 1.3 |
| μ (MOP) (h) (agonist radioligand) | |||
| DAMGO | 9.1E-10 M | 3.8E-10 M | 1.0 |
| 5-HT1A(h) (agonist radioligand) | |||
| 8-OH-DPAT | 5.4E-10 M | 2.7E-10 M | 0.8 |
| 5-HT1B (h) (antagonist radioligand) | |||
| Serotonine | 1.5E-07 M | 6.6E-08 M | 0.9 |
| 5-HT2A(h) (agonist radioligand) | |||
| (±)DOI | 4.4E-10 M | 3.3E-10 M | 0.7 |
| 5-HT2B(h) (agonist radioligand) | |||
| (±)DOI | 2.6E-09 M | 1.3E-09 M | 0.9 |
| 5-HT3(h) (antagonist radioligand) | |||
| MDL 72222 | 1.2E-08 M | 8.2E-09 M | 1.5 |
| GR (h) (agonist radioligand) | |||
| dexamethasone | 5.9E-09 M | 3.0E-09 M | 1.2 |
| AR(h) (agonist radioligand) | |||
| testosterone | 8.7E-09 M | 3.9E-09 M | 1.0 |
| V1a(h) (agonist radioligand) | |||
| [d(CH2)51,Tyr(Me)2]-AVP | 7.9E-10 M | 5.0E-10 M | 1.2 |
| Ca2+ channel (L, dihydropyridine site) (antagonist radioligand) | |||
| nitrendipine | 2.8E-10 M | 1.8E-10 M | 1.1 |
| Potassium Channel hERG (human)- [3H] Dofetilide | |||
| Terfenadine | 9.4E-08 M | 6.5E-08 M | 1.1 |
| KV channel (antagonist radioligand) | |||
| α-dendrotoxin | 2.7E-10 M | 2.1E-10 M | 1.2 |
| Na+ channel (site 2) (antagonist radioligand) | |||
| veratridine | 9.4E-06 M | 8.5E-06 M | 1.0 |
| norepinephrine transporter(h) (antagonist radioligand) | |||
| protriptyline | 3.9E-09 M | 2.9E-09 M | 1.3 |
| dopamine transporter(h) (antagonist radioligand) | |||
| BTCP | 1.8E-08 M | 9.6E-09 M | 1.0 |
| 5-HT transporter (h) (antagonist radioligand) | |||
| imipramine | 3.4E-09 M | 1.5E-09 M | 1.2 |
Cellular and Nuclear Receptor Functional Assays:
Agonist Effect - SI Results:
| Assay Name | Test Compound | Test Concentration | % of Control Agonist Response | ||
| 1st | 2nd | Mean | |||
| LXR alpha (h) (agonist effect) | SI | 1.0E-04 M | -0.2 | -0.2 | -0.2 |
| CAR (h) (agonist effect) | SI | 1.0E-04 M | -1.2 | -4.4 | -2.8 |
| PPARα (h) (agonist effect) | SI | 1.0E-04 M | -0.2 | -0.5 | -0.3 |
| PPARδ (h) (agonist effect) | SI | 1.0E-04 M | 1.1 | 0.7 | 0.9 |
| PPARγ (h) (agonist effect) | SI | 1.0E-04 M | 0.0 | 0.1 | 0.1 |
| PXR (h) (agonist effect) | SI | 1.0E-04 M | -4.6 | -5.2 | -4.9 |
| PR (h) (agonist effect) | SI | 1.0E-04 M | 0.1 | 0.2 | 0.1 |
| VDR (h) (agonist effect) | SI | 1.0E-04 M | -0.1 | 0.0 | -0.1 |
Agonist Effect - Reference Compound Results:
| Assay Name + Compound I.D. | EC50(M) | nH |
| LXR alpha (h) (agonist effect) | ||
| T0901317 | 2.0E-06 M | n/a |
| CAR (h) (agonist effect) | ||
| CITCO | 1.4E-07 M | n/a |
| PPARα (h) (agonist effect) | ||
| GW 7647 | 4.9E-09 M | n/a |
| PPARδ (h) (agonist effect) | ||
| GW 0742 | 3.8E-09 M | n/a |
| PPARγ (h) (agonist effect) | ||
| rosiglitazone | 1.8E-07 M | n/a |
| PXR (h) (agonist effect) | ||
| T0901317 | 1.5E-08 M | n/a |
| PR (h) (agonist effect) | ||
| progesterone | 1.2E-08 M | n/a |
| VDR (h) (agonist effect) | ||
| calcitriol | 3.0E-09 M | n/a |
Antagonist Effect - SI Results:
| Assay Name | Test Compound | Test Concentration | % Inhibition of Control Agonist Response | ||
| 1st | 2nd | Mean | |||
| LXR alpha (h) (antagonist effect) | SI | 1.0E-04 M | -2.6 | -5.7 | -4.1 |
| CAR (h) (antagonist effect) | SI | 1.0E-04 M | 4.0 | 6.3 | 5.1 |
| PPARα (h) (antagonist effect) | SI | 1.0E-04 M | -5.5 | -2.7 | -4.1 |
| PPARδ (h) (antagonist effect) | SI | 1.0E-04 M | 5.1 | 18.1 | 11.6 |
| PPARγ (h) (antagonist effect) | SI | 1.0E-04 M | 16.9 | 3.0 | 9.9 |
| PXR (h) (antagonist effect) | SI | 1.0E-04 M | -4.8 | -8.7 | -6.7 |
| PR (h) (antagonist effect) | SI | 1.0E-04 M | 6.7 | 5.5 | 6.1 |
| VDR (h) (antagonist effect) | SI | 1.0E-04 M | 5.1 | 0.2 | 2.6 |
Antagonist Effect - Reference Compound Results:
| Assay Name + Compound I.D. | IC50(M) | KB(M) | nH |
| CAR (h) (antagonist effect) | |||
| Clotrimazole | 4.1E-06 M | 4.4E-07 M | n/a |
| PPARα (h) (antagonist effect) | |||
| GW 9662 | 5.3E-07 M | 2.0E-08 M | n/a |
| PPARδ (h) (antagonist effect) | |||
| GSK 0660 | 4.5E-06 M | 6.9E-07 M | n/a |
| PPARγ (h) (antagonist effect) | |||
| GW 9662 | 4.2E-08 M | 1.0E-08 M | n/a |
| PXR (h) (antagonist effect) | |||
| clotrimazole | 1.1E-05 M | 9.2E-07 M | n/a |
| PR (h) (antagonist effect) | |||
| mifepristone | 4.3E-09 M | 5.3E-10 M | n/a |
Enzyme and Assays - SI Results:
| Assay Name | Test Compound | Test Concentration | % Inhibition of Control Values | ||
| 1st | 2nd | Mean | |||
| COX1(h) | SI | 1.0E-04 M | 5.5 | -7.8 | -1.2 |
| COX2(h) | SI | 1.0E-04 M | 10.3 | 19.8 | 15.0 |
| PDE3A (h) | SI | 1.0E-04 M | -0.9 | -20.0 | -10.4 |
| PDE4D2 (h) | SI | 1.0E-04 M | -7.0 | -10.7 | -8.9 |
| ACE (h) | SI | 1.0E-04 M | 5.4 | 1.3 | 3.4 |
| ACE-2 (h) | SI | 1.0E-04 M | 0.1 | 1.3 | 0.7 |
| Lck kinase (h) | SI | 1.0E-04 M | 5.6 | 10.4 | 8.0 |
| acetylcholinesterase (h) | SI | 1.0E-04 M | 4.5 | 5.6 | 5.0 |
| carbonic anhydrase II (h) | SI | 1.0E-04 M | 0.6 | 11.1 | 5.9 |
| HDAC1 (h) | SI | 1.0E-04 M | 20.4 | -5.1 | 7.6 |
| Aromatase / CYP19A1 | SI | 1.0E-04 M | 2.9 | 3.6 | 3.3 |
Enzyme and Assays - Reference Compound Results:
| Assay Name + Compound I.D. | IC50(M) | nH |
| COX1(h) | ||
| Diclofenac | 2.0E-08 M | 1.6 |
| COX2(h) | ||
| NS398 | 1.0E-07 M | 1.5 |
| PDE3A (h) | ||
| milrinone | 3.4E-07 M | 0.8 |
| PDE4D2 (h) | ||
| Ro 20-1724 | 1.4E-07 M | 0.9 |
| ACE (h) | ||
| captopril | 7.4E-10 M | 1.2 |
| ACE-2 (h) | ||
| Ac-GG-26-NH2 | 7.2E-07 M | 1.3 |
| Lck kinase (h) | ||
| staurosporine | 3.0E-08 M | 2.6 |
| acetylcholinesterase (h) | ||
| galanthamine | 6.8E-07 M | 1.0 |
| carbonic anhydrase II (h) | ||
| acetazolamide | 3.7E-08 M | 1.4 |
| HDAC1 (h) | ||
| trichostatin A | 3.0E-09 M | 1.1 |
| Aromatase / CYP19A1 | ||
| Letrozole | 1.4E-09 M | 2.0 |
Remaining results - SI Results:
| Assay Name | Test Compound | Test Concentration | % Inhibition of Control Values | ||
| 1st | 2nd | Mean | |||
| DNMT1 Human DNA Methyltransferase Enzymatic Assay, Cerep | SI | 1.0E-04 M | 4.2 | -7.2 | -1.5 |
| Thyroperoxidase | SI | 1.0E-04 M | 32.0 | 29.9 | 30.9 |
Remaining results - Reference Compound Results:
| Assay Name + Compound I.D. | IC50(M) | nH |
| DNMT1 Human DNA Methyltransferase Enzymatic Assay, Cerep | ||
| SAH | 1.0E-07 M | 1.5 |
| Thyroperoxidase | ||
| Methimazole (MMI) | 1.1E-08 M | 1.0 |
Study 2:
Experimental (complete) Results:
| Assay Name | Batch* | Spec. | Rep. | Conc. | % Inh. | IC50* | Ki | nH | R |
| Compound: Isethionic acid sodium salt (SI) | |||||||||
| 11-beta-Hydroxysteroid Dehydrogenase 1 (11-beta-HSD1) | 487004 | hum | 2 | 100 μM | 3 | ||||
| HMG-CoA Reductase | 487003 | hum | 2 | 100 μM | -20 | ||||
| Steroid 5α-Reductase | 487006 | rat | 2 | 100 μM | 1 | ||||
| Colchicine | 487058 | rat | 2 | 100 μM | 6 | ||||
* Batch: Represents compounds tested concurrently in the same assay(s).
hum=Human
| Assay Name | Batch* | Spec. | Tissue | Rep. | Conc. | Criteria | Resp. | Ag. | Ant. | R |
| Compound: Isethionic acid sodium salt (SI) | ||||||||||
| Estrogen Receptor alpha (ERα) Coactivator | 487218 | hum | Insect cells | 2 | 100 µM | ≥± 50% | 2% | ND | ||
| Estrogen Receptor alpha (ERα) Coactivator | 487219 | hum | Insect cells | 2 | 100 µM | ≥± 50% | ND | -12% | ||
| Estrogen Receptor beta (ERβ) Coactivator | 487220 | hum | Insect cells | 2 | 100 µM | ≥± 50% | 1% | ND | ||
| Estrogen Receptor beta (ERβ) Coactivator | 487221 | hum | Insect cells | 2 | 100 µM | ≥± 50% | ND | 20% | ||
| Retinoic Acid Receptor, RARA (RARα) | 487674 | hum | E. coli | 2 | 100 µM | ≥± 50% | 0% | ND | ||
| Retinoic Acid Receptor, RARA (RARα) | 487785 | hum | E. coli | 2 | 100 µM | ≥± 50% | ND | -6% | ||
| Retinoid X Receptor Alpha (RXRα) Coactivator | 486987 | hum | Insect cells | 2 | 100 µM | ≥± 50% | 0% | ND | ||
| Retinoid X Receptor Alpha (RXRα) Coactivator | 486990 | hum | Insect cells | 2 | 100 µM | ≥± 50% | ND | -1% | ||
| Retinoid X Receptor Beta (RXRβ) Coactivator | 486991 | hum | Insect cells | 2 | 100 µM | ≥± 50% | -2% | ND | ||
| Retinoid X Receptor Beta (RXRβ) Coactivator | 486992 | hum | Insect cells | 2 | 100 µM | ≥± 50% | ND | 6% | ||
| Thyroid Receptor Alpha Coactivator | 486551 | hum | Insect cells | 2 | 100 µM | ≥± 50% | 4% | ND | ||
| Thyroid Receptor Beta Coactivator | 486552 | hum | Insect cells | 2 | 100 µM | ≥± 50% | 1% | ND | ||
* Batch: Represents compounds tested concurrently in the same assay(s). Ag.=Agonist; Ant.=Antagonist; Resp.=Response; ND=Assay Test Not Done hum=Human
Reference Compound results:
| Assay Name | Reference Compound | Historical | Concurrent | |||
| IC50* | Ki | nH | Batch * | IC50* | ||
| 11-beta-Hydroxysteroid Dehydrogenase 1 (11-beta-HSD1) | PF 915275 | 0.041 μM | 487004 | 0.035 μM | ||
| HMG-CoA Reductase | Lovastatin | 0.074 μM | 487003 | 0.13 μM | ||
| Steroid 5α-Reductase | Finasteride | 0.036 μM | 487006 | 0.036 μM | ||
| Colchicine | Colchicine | 2.80 μM | 2.80 μM | 1.30 | 487058 | 2.38 μM |
* Batch: Represents compounds tested concurrently in the same assay(s).
| Historical | Concurrent ‡ | |||
| Assay Name | Reference Compound | IC50/EC50* | Batch* | IC50/EC50 |
| Estrogen Receptor alpha (ERα) Coactivator - Ag. | Estriol | 3.0 nM | 487218 | 3.17 nM |
| Estrogen Receptor alpha (ERα) Coactivator - Ant. | ICI182780 | 13.0 nM | 487219 | 8.38 nM |
| Estrogen Receptor beta (ERβ) Coactivator - Ag. | Estriol | 3.10 nM | 487220 | 4.67 nM |
| Estrogen Receptor beta (ERβ) Coactivator - Ant. | ICI182780 | 7.30 nM | 487221 | 2.64 nM |
| Retinoic Acid Receptor, RARA (RARα) - Ag. | TTNPB | 0.88 nM | 487674 | 0.34 nM |
| Retinoic Acid Receptor, RARA (RARα) - Ant. | Ro-415253 | 4.10 nM | 487785 | 2.32 nM |
| Retinoid X Receptor Alpha (RXRα) Coactivator - Ag. | Fluorobexarotene | 3.60 nM | 486987 | 4.55 nM |
| Retinoid X Receptor Alpha (RXRα) Coactivator - Ant. | UVI3003 | 0.055 μM | 486990 | 0.039 μM |
| Retinoid X Receptor Beta (RXRβ) Coactivator - Ag. | Fluorobexarotene | 9.90 nM | 486991 | 4.18 nM |
| Retinoid X Receptor Beta (RXRβ) Coactivator - Ant. | HX531 | 6.30 μM | 486992 | 5.77 μM |
| Thyroid Receptor Alpha Coactivator - Ag. | T3 | 0.12 nM | 486551 | 0.19 nM |
| Thyroid Receptor Beta Coactivator - Ag. | T3 | 0.37 nM | 486552 | 0.73 nM |
* Batch: Represents compounds tested concurrently in the same assay(s).
‡ For some assays only a single concentration of reference compound is tested.
Study 3:
ATP Concentration: 90 µM
| Sample | Counts | Mean (Counts - Blanks) | Activity (% Control) | Mean | SD* |
| Isethionic acid sodium salt (SI) @ 100µM | 17737 | 16936 | 106 | 104 | 4 |
| 16893 | 101 | ||||
| Control | 17673 | 16323 | 106 | 100 | 5 |
| 15738 | 94 | ||||
| 16799 | 101 | ||||
| 16596 | 99 | ||||
| Blank | 398 | / | / | / | / |
| 360 | / |
* NB. Where n = 2, the value reported here is actually range / √ 2
Description of key information
The bioactivity of SI was assessed in a battery of in vitro tests relevant to systemic, reproductive, and developmental toxicity. Concentration-response curves were derived for 40 cell stress markers measured in HepG2 Cells and High Throughput Transcriptomics was conducted in HepG2, HepaRG and MCF7 cells (cell stress panel; Transcriptomics). Pharmacological profiling of SI against 79 targets was conducted (IPP) as well as specific assays relating to developmental toxicity (Reprotracker, devTOXqp). Dose response modelling of this in vitro data was used to derive Points of Departure (PoDs) where a biological response was obtained. PoDs for SI in these assays ranged from 146-7300 µM. Analytical chemistry approaches were used to study the stability and achieved concentrations of SI in these in vitro assays (summarized in Section 8. Analytical methods). PoDs were adjusted to correct for achieved concentrations of SI.
This data is used in a Next Generation Safety Assessment (NGSA), which is an exposure-led approach to safety assessment that employs the use of these New Approach Methodologies (NAMs).
An overview of this approach can be found in section 13 (narrative document).
Additional information
Information on Registered Substances comes from registration dossiers which have been assigned a registration number. The assignment of a registration number does however not guarantee that the information in the dossier is correct or that the dossier is compliant with Regulation (EC) No 1907/2006 (the REACH Regulation). This information has not been reviewed or verified by the Agency or any other authority. The content is subject to change without prior notice.
Reproduction or further distribution of this information may be subject to copyright protection. Use of the information without obtaining the permission from the owner(s) of the respective information might violate the rights of the owner.
