tert-dodecanethiol

Specific investigations: other studies

Link to relevant study record(s)

Reference

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, TDM was assessed for its potential to disrupt biological pathways (DNA binding, background measurement, nuclear receptor, growth factor (transforming growth factor beta), nuclear receptor (orphan, non-steroidal and steroidal), cell cycle, cyp (cytochrome P450, family 19 or 24, subfamily A, polypeptide 1), hydrolase (ATPase), cell morphology (organelle conformation)) that may result in toxicity.

Type of method:

in vitro

Vehicle:

DMSO

Remarks:

0.001 up to 200 µM

Details on study design:

See enclosed excel file

Details on results:

279 assays were performed. Tert -dodecane thiol induced a positive response in 7 assays. Nevertheless, all 7 positive assays were flaged as "Hit-call potentially confounded by overfitting" and deemed not reliable. Therefore, there is no evidence that tert-dodecane thiol could interfere with the expression of the screened genes.

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

Tert -dodecane thiol induced a positive response in 7 assays (see attached figure):

Assay Endpoint Name              Cell                  Target Family        Gene Name

ATG_ERa_TRANS_up            human liver       nuclear receptor      estrogen receptor 1

ATG_NRF2_ARE_CIS_up      human liver       DNA binding           nuclear factor, erythroid 2-like 2

ATG_PBREM_CIS_up            human liver       nuclear receptor       subfamily 1, group I, member 3

ATG_PPARg_TRANS_up       human liver       nuclear receptor       peroxisome proliferator-activated receptor gamma

ATG_PXRE_CIS_up               human liver       nuclear receptor       subfamily 1, group I, member 2

ATG_PXR_TRANS_up           human liver       nuclear receptor       subfamily 1, group I, member 2

ATG_VDRE_CIS_up               human liver       nuclear receptor       vitamin D (1,25- dihydroxyvitamin D3) receptor

All 7 positive assays were flaged as "Hit-call potentially confounded by overfitting" and deemed not reliable.

Cytotoxicity was assessed in 20 assays, no cytotoxicity was observed up to 80 µM.

Assay Component Name	time point Hr	Organism	Tissue	Cell Short Name
TOX21_AR_BLA_Antagonist_viability	24	human	kidney	HEK293T
TOX21_ARE_BLA_agonist_viability	24	human	liver	HepG2
TOX21_ERa_BLA_Antagonist_viability	24	human	kidney	HEK293T
TOX21_ESRE_BLA_viability	24	human	cervix	HeLa
TOX21_FXR_BLA_agonist_viability	24	human	kidney	HEK293T
TOX21_FXR_BLA_Antagonist_viability	24	human	kidney	HEK293T
TOX21_GR_BLA_Antagonist_viability	24	human	cervix	HeLa
TOX21_HSE_BLA_agonist_viability	24	human	cervix	HeLa
TOX21_MMP_viability	24	human	liver	HepG2
TOX21_NFkB_BLA_agonist_viability	24	human	cervix	ME-180
TOX21_p53_BLA_p1_viability	24	human	intestinal	HCT116
TOX21_p53_BLA_p2_viability	24	human	intestinal	HCT116
TOX21_p53_BLA_p3_viability	24	human	intestinal	HCT116
TOX21_p53_BLA_p4_viability	24	human	intestinal	HCT116
TOX21_p53_BLA_p5_viability	24	human	intestinal	HCT116
TOX21_PPARd_BLA_Agonist_viability	24	human	kidney	HEK293T
TOX21_PPARd_BLA_Antagonist_viability	24	human	kidney	HEK293T
TOX21_PPARg_BLA_Antagonist_viability	24	human	kidney	HEK293
TOX21_VDR_BLA_Agonist_viability	24	human	kidney	HEK293T
TOX21_VDR_BLA_Antagonist_viability	24	human	kidney	HEK293T

Executive summary:

Tert-dodecane thiol was evaluated in the ToxCast & Tox21 High-throughput Assays to evaluate the effects on a target genes like, DNA binding, nuclear receptor, growth factor (transforming growth factor beta), nuclear receptor (orphan, non-steroidal and steroidal), cell cycle, cyp (cytochrome P450, family 19 or 24, subfamily A, polypeptide 1), hydrolase (ATPase), and cell morphology (organelle conformation). 279 assays were performed at concentrations ranging from 0.001 to 200 µM. Cytotoxicity was assessed in 20 assays, no cytotoxicity was observed up to 80µM.

Tert -dodecane thiol induced a positive response in only 7 assays:

Assay Endpoint Name	Cell	Target Family
ATG_ERa_TRANS_up	human liver	nuclear receptor
ATG_NRF2_ARE_CIS_up	human liver	DNA binding
ATG_PBREM_CIS_up	human liver	nuclear receptor
ATG_PPARg_TRANS_up	human liver	nuclear receptor
ATG_PXRE_CIS_up	human liver	nuclear receptor
ATG_PXR_TRANS_up	human liver	nuclear receptor
ATG_VDRE_CIS_up	human liver	nuclear receptor

However; all 7 positive assays were flaged as "Hit-call potentially confounded by overfitting" and deemed not reliable. Therefore, there is no evidence that tert-dodecane thiol could interfere with the expression of the screened genes.

Description of key information

Tert-dodecane thiol was evaluated in the ToxCast & Tox21 High-throughput Assays to evaluate the effects on a target genes like, DNA binding, nuclear receptor, growth factor (transforming growth factor beta), nuclear receptor (orphan, non-steroidal and steroidal), cell cycle, cyp (cytochrome P450, family 19 or 24, subfamily A, polypeptide 1), hydrolase (ATPase), and cell morphology (organelle conformation). 279 assays were performed at concentrations ranging from 0.001 to 200 µM. Cytotoxicity was assessed in 20 assays, no cytotoxicity was observed up to 80µM.

Tert -dodecane thiol induced a positive response in only 7 assays:

Assay Endpoint Name	Cell	Target Family
ATG_ERa_TRANS_up	human liver	nuclear receptor
ATG_NRF2_ARE_CIS_up	human liver	DNA binding
ATG_PBREM_CIS_up	human liver	nuclear receptor
ATG_PPARg_TRANS_up	human liver	nuclear receptor
ATG_PXRE_CIS_up	human liver	nuclear receptor
ATG_PXR_TRANS_up	human liver	nuclear receptor
ATG_VDRE_CIS_up	human liver	nuclear receptor

However; all 7 positive assays were flaged as "Hit-call potentially confounded by overfitting" and deemed not reliable. Therefore, there is no evidence that tert-dodecane thiol could interfere with the expression of the screened genes.