Toxicological responses of red-backed salamanders (Plethodon cinereus) to subchronic soil exposures of 2,4-dinitrotoluene
ABSTRACT Dinitrotoluenes are used as propellants and in explosives by the military and as such have been found at relatively high concentrations in the soil. To determine whether concentrations of 2,4-dinitrotoluene (2,4-DNT) in soil are toxic to amphibians, 100 red-backed salamanders (Plethodon cinereus) were exposed to either 1500, 800, 200, 75 or 0mg 2,4-DNT/kg soil for 28 days and evaluated for indicators of toxicity. Concentrations of 2,4-DNT were less than targets and varied with time. Most salamanders exposed to concentrations exceeding 1050 mg/kg died or were moribund within the first week. Salamanders exposed to soil concentrations exceeding 345 mg/kg lost >6% of their body mass though no mortality occurred. Overt effects included a reduction in feed consumption and an increase in bucco-pharyngeal oscillations in salamanders. These results suggest that only high soil concentrations of 2,4-DNT have the potential to cause overtly toxic effects in terrestrial salamanders.
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ABSTRACT: 2,4-dinitrotoluene (2,4-DNT) is a nitroaromatic used in industrial dyes and explosives manufacturing processes that is found as a contaminant in the environment. Previous studies have implicated antagonism of PPARα signaling as a principal process affected by 2,4-DNT. Here, we test the hypothesis that 2,4-DNT-induced perturbations in PPARα signaling and resultant downstream deficits in energy metabolism, especially from lipids, cause organism-level impacts on exercise endurance. PPAR nuclear activation bioassays demonstrated inhibition of PPARα signaling by 2,4-DNT whereas PPARγ signaling increased. PPARα (-/-) and wild-type (WT) female mice were exposed for 14 days to vehicle or 2,4-DNT (134 mg/kg/day), and performed a forced swim to exhaustion one day after the last dose. 2,4-DNT significantly decreased body weights and swim times in WTs, but effects were significantly mitigated in PPARα (-/-) mice. 2,4-DNT decreased transcript expression for genes downstream in the PPARα signaling pathway, principally genes involved in fatty acid transport. Results indicate that PPARγ signaling increased resulting in enhanced cycling of lipid and carbohydrate substrates into glycolytic/gluconeogenic pathways favoring energy production versus storage in 2,4-DNT-exposed WT and PPARα (-/-) mice. PPARα (-/-) mice appear to have compensated for the loss of PPARα by shifting energy metabolism to PPARα-independent pathways resulting in lower sensitivity to 2,4-DNT when compared to WT mice. Our results validate 2,4-DNT-induced perturbation of PPARα signaling as the molecular initiating event (MIE) for impaired energy metabolism, weight loss and decreased exercise performance.Toxicological Sciences 06/2014; 141(1). DOI:10.1093/toxsci/kfu104 · 4.48 Impact Factor
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ABSTRACT: The development of media-specific ecological values for risk assessment includes the derivation of acceptable levels of exposure for terrestrial wildlife (e.g., birds, mammals, reptiles, and amphibians). Though the derivation and subsequent application of these values can be used for screening purposes, there is a need to identify toxicological effects thresholds specifically for making remedial decisions at individual contaminated sites. A workshop was held in the fall of 2012 to evaluate existing methods and recent scientific developments for refining ecological soil screening levels (Eco-SSLs) and improving the derivation of site-specific ecological soil cleanup values (Eco-SCVs). This included a focused session on the development and derivation of toxicity reference values (TRVs) for terrestrial wildlife. Topics that were examined included: methods for toxicological endpoint selection, techniques for dose-response assessment, approaches for cross-species extrapolation, and tools to incorporate environmental factors (e.g., metal bioavailability and chemistry) into a reference value. The workgroup also made recommendations to risk assessors and regulators on how to incorporate site-specific wildlife life history and toxicity information into the derivation of TRVs to be used in the further development of soil cleanup levels. Integr Environ Assess Manag © 2013 SETAC.Integrated Environmental Assessment and Management 07/2014; 10(3). DOI:10.1002/ieam.1474