Stressor: 237

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

Nitrotoluenes (hypothesized binding)

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
Antagonist binding to PPARα leading to body-weight loss	Moderate

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

Antagonist binding to PPARα leading to body-weight loss

Nitrotoluenes (hypothesized binding) - Recent observations of PPARalpha antagonism by nitrotoluenes (including: 2,4-dinitrotoluene and 2-amino-4,6-dinitrotoluene) have demonstrated dose-response relationships for PPARalpha nuclear signaling inhibition in in vitro investigations which corresponded with dose-responsive decreases in transcriptional expression of genes for which PPARalpha acts as a transcriptional regulator, including various lipid metabolism pathways (Wilbanks et al 2014, Gust et al 2015). There is additional evidence that multiple nitrotoluenes including the base structure, 2,4,6-trinitrotoluene and molecules with various substitutions of the nitro groups around that base structure inhibit PPARalpha nuclear signaling, and have elevated binding affinity to PPARalpha, based on computational docking calculations (Gust, unpublished data).

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

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

Nitrotoluenes represent a class of industrial compounds that can be used as explosives and / or propellants in the manufacture of military munitions. The core structure of the molecules is a toluene where one to three hydrogen groups around the ring are substituted with nitro groups. Environmental degradation of nitrotoluenes can reduce the nitro groups to amino groups, which are found in addition to the parent compounds in industrial facilities and on training ranges where munitions are made / used (Talmage et al 1999).

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

Environmental exposures to nitrotoluenes may occur via inhalation, ingestion by contaminated ground water, consumption by wildlife on training ranges and exposure to aquatic organisms in contaminated surface water (Talmage et al 1999).

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

Talmage, S.S., Opresko, D.M., Maxwell, C.J., Welsh, C.J., Cretella, F.M., Reno, P.H., Daniel, F.B., 1999. Nitroaromatic munition compounds: environmental effects and screening values. Rev. Environ. Contam. Toxicol. 161, 1-156.