Stressor: 251

Title

To create a new stressor, from the Listing Stressors page at https://aopwiki.org/stressors click ‘New stressor.’ This will bring you to a page entitled “New Stressor” where a stressor title can be entered. Click ‘Create stressor’ to create a new Stressor page listing the stressor title at the top. More help

TCPOBOP

Stressor Overview

The stressor field is a structured data field that can be used to annotate an AOP with standardised terms identifying stressors known to trigger the MIE/AOP. Most often these are chemical names selected from established chemical ontologies. However, depending on the information available, this could also refer to chemical categories (i.e., groups of chemicals with defined structural features known to trigger the MIE). It can also include non-chemical stressors such as genetic or environmental factors. More help

AOPs Including This Stressor

This table is automatically generated and lists the AOPs associated with this Stressor. More help

Events Including This Stressor

This table is automatically generated and lists the Key Events associated with this Stressor. More help

Chemical Table

The Chemical Table lists chemicals associated with a stressor. This table contains information about the User’s term for a chemical, the DTXID, Preferred name, CAS number, JChem InChIKey, and Indigo InChIKey.To add a chemical associated with a particular stressor, next to the Chemical Table click ‘Add chemical.’ This will redirect you to a page entitled “New Stressor Chemical.’ The dialog box can be used to search for chemical by name, CAS number, JChem InChIKey, and Indigo InChIKey. Searching by these fields will bring forward a drop down list of existing stressor chemicals formatted as  Preferred name, “CAS- preferred name,” “JChem InChIKey – preferred name,” or “Indigo InChIKey- preferred name,” depending on by which field you perform the search. It may take several moments for the drop down list to display. Select an entity from the drop down list and click ‘Add chemical.’ This will return you to the Stressor Page, where the new record should be in the ‘Chemical Table’ on the page.To remove a chemical associated with a particular stressor, in the Chemical Table next to the chemical you wish to delete, click ‘Remove’ and then click 'OK.' The chemical should no longer be visible in the Chemical table. More help

AOP Evidence

This table is automatically generated and includes the AOPs with this associated stressor as well as the evidence term and evidence text from this AOP Stressor. More help

Event Evidence

This table is automatically generated and includes the Events with this associated stressor as well as the evidence text from this Event Stressor. More help
Activation, Constitutive androstane receptor

There is no evidence text for this event.

Altered gene expression specific to CAR activation, Hepatocytes

TCPOBOP (1,4-bis[2-(3,5-dichloropyridyloxy)]benzene)

1.         Hepatic CAR-dependent genes were identified by comparing the gene expression profiles of wild-type and CAR/PXR single and double-knockout mice after intraperitoneal (i.p.)  injection with TCPOBOP and/or  PCN (pregnenolone 16alpha-carbonitrile; PXR activator) for 12 h prior to sacrifice (3 mg/kg body weight) (Tojima et al., 2012). Both common and unique gene target genes for CAR and PXR were identified. CAR-dependent gene targets included those involved in xenobiotic metabolism, apoptosis, cholesterol metabolism and lipid metabolism. A similar experiment in wild-type C57BL/6N mice administered TCPOBOP (i.p., 3 mg/kg) or PCN once daily for four days identified common and unique CAR- and PXR-target genes (Cui and Klaassen, 2016).

2.         The hepatic gene expression profiles of CAR-null, PXR-null, and PXR/CAR-null and WT rats after single treatment (i.p.; 16 h after injection) with vehicle (corn oil), PXR agonist PCN (100 mg/kg) and/or TCPOBOP (12.5 mg/kg) were compared. The results identified that PXR and CAR are involved in the regulation and expression of both common and different drug metabolizing genes in the rat liver (Forbes et al., 2017). As an example, induction of rat Cyp2b2 expression was avidly expressed in wild-type and PXR-null rats, but was blocked in the CAR-null and PXR/CAR-null rats.

3.         Comparison of gene expression profiles of wild-type and CAR null mice exposed to TCPOBOP (i.p.; 3 mg/kg bw/day) for 3 consecutive days and seven weeks revealed that TCPOBOP induced the expression of prototypical CAR-responsive genes (e.g. Cyp2b10) and lipogenic genes such as Fasn, Elovl6, Gpat and Pnpla3 (Marmugi et al., 2016).

Stressor Info

Text sections under this subheading include the Chemical/Category Description and Characterization of Exposure. More help
Chemical/Category Description
To edit the Chemical/Category Description” section, on a KER page, in the upper right hand menu, click ‘Edit.’ This brings you to a page entitled, “Editing Stressor.”  Scroll down to the “Chemical/Category Description” section, where a text entry box allows you to submit text. Click ‘Update’ to save your changes and return to the Stressor page.  The new text should appear under the “Chemical/Category Description”  section on the page. More help
Characterization of Exposure
To edit the “Characterization of Exposure” section, on a Stressor page, in the upper right hand menu, click ‘Edit.’ This brings you to a page entitled, “Editing Stressor.”  Scroll down to the “Characterization of Exposure”  section, where a text entry box allows you to submit text. Click ‘Update’ to save your changes and return to the Stressor page.  The new text should appear under the “Characterization of Exposure” section on the page. More help

References

List of the literature that was cited for this Stressor description. Ideally, the list of references, should conform, to the extent possible, with the OECD Style Guide (https://www.oecd.org/about/publishing/OECD-Style-Guide-Third-Edition.pdf) (OECD, 2015).To edit the “References” section, on a Stressor page, in the upper right hand menu, click ‘Edit.’ This brings you to a page entitled, “Editing Stressor.”  Scroll down to the “References” section, where a text entry box allows you to submit text. Click ‘Update’ to save your changes and return to the Stressor page.  The new text should appear under the “References” section on the page. More help