Stressor: 218

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

metofluthrin

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

AOP Name	Evidence
Constitutive androstane receptor activation leading to hepatocellular adenomas and carcinomas in the mouse and the rat	High

Events Including This Stressor

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

Event Name
Activation, Constitutive androstane receptor
Altered gene expression specific to CAR activation, Hepatocytes

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

User term	DTXID	Preferred name	Casrn	jchem_inchi_key	indigo_inchi_key
metofluthrin	DTXSID4034738	Metofluthrin	240494-70-6	KVIZNNVXXNFLMU-DUVUQDDDSA-N	KVIZNNVXXNFLMU-DUVUQDDDSA-N

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

Constitutive androstane receptor activation leading to hepatocellular adenomas and carcinomas in the mouse and the rat

Metofluthrin produced increased liver tumors in male and female Wistar rats at dose levels of 900 and 1800 ppm in the diet for 2 years (Deguchi et al., 2009). As shown in Table 5 of the AOP for CAR-mediated rodent liver tumors, dose-concordant data supporting all of the Key Events and/or Associative Events in the AOP for CAR have been demonstrated with metofluthrin (Deguchi et al., 2009; Yamada et al., 2009). Therefore, there is Strong evidence for metofluthrin as an AOP stressor for the CAR-mediated formation of rat liver tumors.

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

Metofluthrin

1. The hepatic gene expression profiles of male rats administered 3600 ppm metofluthrin in the diet for one week had similar gene expression profiles to those of male rats administered 1000 ppm NaPB (a known CAR activator) for one week, including the modulation of xenobiotic metabolism genes. For example, a statistically-significant, dose-dependent induction of the mRNA levels of Cyp2b1/2 and Cyp3a1 was observed in the livers of male and female rats administered metofluthrin in the diet for one week (Deguchi et al., 2009; Yamada et al., 2009). Additional experiments used RNA interference (RNAi) where CAR-specific small interfering RNA (siRNA) was co-incubated along with metofluthrin. Exposure of rat hepatocytes to metofluthrin plus the CAR siRNA in vitro resulted in a statistically significant reduction in the Cyp2b1 mRNA levels compared to hepatocytes treated with metofluthrin without CAR knockdown (Deguchi et al., 2009).

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