AOPs Including This Stressor
|Antagonist binding to PPARα leading to body-weight loss||Moderate|
Events Including This StressorThis table is automatically generated and lists KE’s including this stressor.
Chemical TableThe 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. Instructions 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 “CAS- preferred name” “JChem InChIKey – preferred name” or “Indigo InChIKey- preferred name” depending on which field you perform the search. 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.
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nuclear signaling, and have elevated binding affinity to PPARalpha, based on computational docking calculations (Gust, unpublished data).
This table is automatically generated and includes the Events with this associated stressor as well as the evidence text from this Event Stressor.
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
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).
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.