OO-tert-butyl O-(2-ethylhexyl) peroxycarbonate

Specific investigations: other studies

Link to relevant study record(s)

Reference

Reference 1

Endpoint:

biochemical or cellular interactions

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: data from iCSS CompTox Dashboard. Data Quality 100%. Data manually curated with highest confidence

Principles of method if other than guideline:

Using a high-throughput robotic screening system, TBEC was assessed for its potential to disrupt biological pathways (DNA binding, growth factor, nuclear receptor (non-steroidal and steroidal), cell cycle, cytochrome P450, hydrolase and cell morphology) that may result in toxicity.

Type of method:

in vitro

Specific details on test material used for the study:

DSSTOX GSID: 44921

Remarks:

0.0006 to 90µM

Details on study design:

See enclosed excel file

Details on results:

113 assays were performed. TBEC was inactive in all assays, therefore, there is no evidence that TBEC could interfere with the expression of the screened genes.

113 assays were performed, all results are displayed in the enclosed excel file.

TBEC was inactive in all assay (see attached figure).

 

Executive summary:

Using a high-throughput robotic screening system, TBEC was assessed for its potential to disrupt biological pathways (DNA binding, growth factor, nuclear receptor (non-steroidal and steroidal), cell cycle, cytochrome P450, hydrolase and cell morphology) that may result in toxicity. 113 assays were performed. TBEC was inactive in all assays, therefore, there is no evidence that TBEC could interfere with the expression of the screened genes.

Reference 2

Endpoint:

biochemical or cellular interactions

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Principles of method if other than guideline:

The PubChem BioAssay database was searched for chemogenomic, medicinal chemistry and functional genomics biological activities

Type of method:

in vivo

Specific details on test material used for the study:

PubChem CID: 61931
PubChem SID: 144211602

Details on results:

150 bioassays with 150 bioactivity outcomes were retrieved from the PubChem BioAssay data base. TBEC was reported as inactive in 137 biossays, inconclusive in 12 bioassays and active in 1 cytotoxicity bioassay. Nevertheless, according to the detailed results of this cytotoxicity assay, there was no demonstration of a toxicological activity.

The list of all the assays performed is displayed in the enclosed excel file.

Detailed data on the assay reported as positive are displayed below and in the attached figure.

Activity Value [µM]	Substance SID	BioAssay AID	BioAssay Name
48.9662	144211602	743209	qHTS assay for small molecule activators of the heat shock response signaling pathway - cell viability counter screen

Data for SID 144211602 in AID 743209

Phenotype-Replicate_1	Cytotoxic
Potency-Replicate_1 [uM]*	48.9662
Efficacy-Replicate_1 [%]	80.4056
Analysis Comment-Replicate_1
Activity_Score-Replicate_1	41
Curve_Description-Replicate_1	Partial curve; high efficacy
Fit_LogAC50-Replicate_1	-4.3101
Fit_HillSlope-Replicate_1	2.9023
Fit_R2-Replicate_1	0.9315
Fit_InfiniteActivity-Replicate_1 [%]	-79.6205
Fit_ZeroActivity-Replicate_1 [%]	0.7851
Fit_CurveClass-Replicate_1	-2.1
Excluded_Points-Replicate_1	0 0 0 0 0 0 0 0 0 0 0 0 0 0 0
Max_Response-Replicate_1 [%]	-62.9701
Activity at 0.00107 uM-Replicate_1 [%]	-3.289
Activity at 0.00238 uM-Replicate_1 [%]	-0.5705
Activity at 0.00531 uM-Replicate_1 [%]	1.9899
Activity at 0.012 uM-Replicate_1 [%]	-4.3088
Activity at 0.026 uM-Replicate_1 [%]	9.1788
Activity at 0.059 uM-Replicate_1 [%]	3.3052
Activity at 0.132 uM-Replicate_1 [%]	-6.3236
Activity at 0.275 uM-Replicate_1 [%]	-5.0525
Activity at 0.550 uM-Replicate_1 [%]	3.6889
Activity at 1.225 uM-Replicate_1 [%]	8.459
Activity at 2.701 uM-Replicate_1 [%]	0.678
Activity at 5.947 uM-Replicate_1 [%]	1.6567
Activity at 13.22 uM-Replicate_1 [%]	-4.8617
Activity at 29.14 uM-Replicate_1 [%]	-18.3784
Activity at 62.57 uM-Replicate_1 [%]	-62.9701
Compound QC-Replicate_1	QC'd by SIGMA
Phenotype-Replicate_2	Inactive
Max_Response-Replicate_2 [%]	15.201
Activity at 0.00107 uM-Replicate_2 [%]	26.1066
Activity at 0.00238 uM-Replicate_2 [%]	1.123
Activity at 0.00531 uM-Replicate_2 [%]	-0.4973
Activity at 0.012 uM-Replicate_2 [%]	18.7334
Activity at 0.026 uM-Replicate_2 [%]	12.6056
Activity at 0.059 uM-Replicate_2 [%]	12.5507
Activity at 0.132 uM-Replicate_2 [%]	0.7704
Activity at 0.275 uM-Replicate_2 [%]	2.2138
Activity at 0.550 uM-Replicate_2 [%]	19.2095
Activity at 1.225 uM-Replicate_2 [%]	2.6449
Activity at 2.701 uM-Replicate_2 [%]	8.3207
Activity at 5.947 uM-Replicate_2 [%]	24.1029
Activity at 13.22 uM-Replicate_2 [%]	1.1825
Activity at 29.14 uM-Replicate_2 [%]	10.9219
Activity at 62.57 uM-Replicate_2 [%]	15.201
Phenotype-Replicate_3	Inactive
Max_Response-Replicate_3 [%]	-16.9007
Activity at 0.00107 uM-Replicate_3 [%]	-20.298
Activity at 0.00238 uM-Replicate_3 [%]	-23.115
Activity at 0.00531 uM-Replicate_3 [%]	0
Activity at 0.012 uM-Replicate_3 [%]	-30.2343
Activity at 0.026 uM-Replicate_3 [%]	0
Activity at 0.059 uM-Replicate_3 [%]	-7.8363
Activity at 0.132 uM-Replicate_3 [%]	-4.6272
Activity at 0.275 uM-Replicate_3 [%]	-11.0875
Activity at 0.550 uM-Replicate_3 [%]	-13.2885
Activity at 1.225 uM-Replicate_3 [%]	-9.6367
Activity at 2.701 uM-Replicate_3 [%]	1.2267
Activity at 5.947 uM-Replicate_3 [%]	-20.8329
Activity at 13.22 uM-Replicate_3 [%]	-8.8938
Activity at 29.14 uM-Replicate_3 [%]	-1.869
Activity at 62.57 uM-Replicate_3 [%]	-16.9007

 

Executive summary:

The PubChem BioAssay database was searched for chemogenomic, medicinal chemistry and functional genomics biological activities. 150 bioassays with 150 bioactivity outcomes were retrieved. TBEC was reported as inactive in 137 biossays, inconclusive in 12 bioassays and active in 1 cytotoxicity bioassay. Nevertheless, according to the detailed results of this cytotoxicity assay, there was no demonstration of a toxicological activity. Therefore, TBEC is devoied of activity in cell viability assays, and of agonist and/or antagonist activities on the peroxisome proliferator-activated receptor alpha (PPARa), delta (PPARd) and gamma (PPARg), antioxidant response element (ARE), androgen receptor (AR), estrogen receptor alpha (ER-alpha), thyroid receptor (TR) and glucocorticoid receptor (GR), p53, vitamin D receptor, retinoic acid receptor (RAR), farnesoid-X-receptor (FXR), hypoxia (HIF-1), NFkB, RXR, retinoid-related orphan receptor gamma (ROR-gamma) and aryl hydrocarbon receptor (AhR) signaling pathways.

Description of key information

Using a high-throughput robotic screening system (US EPA, 2017), TBEC was assessed for its potential to disrupt biological pathways (DNA binding, growth factor, nuclear receptor (non-steroidal and steroidal), cell cycle, cytochrome P450, hydrolase and cell morphology) that may result in toxicity. 113 assays were performed. TBEC was inactive in all assays, therefore, there is no evidence that TBEC could interfere with the expression of the screened genes.

The PubChem BioAssay database was searched for chemogenomic, medicinal chemistry and functional genomics biological activities (NCBI, 2017). 150 bioassays with 150 bioactivity outcomes were retrieved. TBEC was reported as inactive in 137 biossays, inconclusive in 12 bioassays and active in 1 cytotoxicity bioassay. Nevertheless, according to the detailed results of this cytotoxicity assay, there was no demonstration of a toxicological activity. Therefore, TBEC is devoied of activity in cell viability assays, and of agonist and/or antagonist activities on the peroxisome proliferator-activated receptor alpha (PPARa), delta (PPARd) and gamma (PPARg), antioxidant response element (ARE), androgen receptor (AR), estrogen receptor alpha (ER-alpha), thyroid receptor (TR) and glucocorticoid receptor (GR), p53, vitamin D receptor, retinoic acid receptor (RAR), farnesoid-X-receptor (FXR), hypoxia (HIF-1), NFkB, RXR, retinoid-related orphan receptor gamma (ROR-gamma) and aryl hydrocarbon receptor (AhR) signaling pathways.