AOPs Including This Stressor
|Antagonist binding to PPARα leading to body-weight loss||Moderate|
Events Including This Stressor
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nuclear signaling, and have elevated binding affinity to PPARalpha, based on computational docking calculations (Gust, unpublished data).
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.