Subacute toxicity of oral 2,6‐dinitrotoluene and 1,3,5‐trinitro‐1,3,5‐triazine (RDX) exposure to the northern bobwhite (Colinus virginianus)

Abstract

Military activities associated with training have resulted in soil residues of munition compounds and their breakdown products. Often, these areas are valuable habitats used by birds. To evaluate the possibility of adverse effects in birds, the effects from oral exposures of 2,6-dinitrotoluene (2,6-DNT) and 1,3,5-trinitro-1,3,5-triazine (RDX) were tested using a controlled dosing regime in northern bobwhite (Colinus virginianus). Nine groups of birds of mixed sex received either corn oil or 50, 100, 190, or 350 mg 2,6-DNT/kg body weight/d or 20, 80, 125, or 180 mg RDX/kg body weight/d mixed in corn oil via gavage for 14 d. Etiology of disease was markedly different between compounds. Increased RDX exposure caused an inverse relationship to time of death, symptoms including clonic followed by tonic convulsions, and death shortly thereafter. Brain concentrations of RDX postmortem, however, were relatively consistent (mean +/- standard error, 20.5 +/- 2.9 mg/kg tissue). Observations of 2,6-DNT effects included gastrointestinal distress, dehydration, and a reduction in body mass and feed consumption. Together, these data suggest that RDX is more toxic from short, repeated exposures than 2,6-DNT, resulting in central nervous system-related effects, whereas 2,6-DNT causes gastrointestinal disturbances at higher exposures.

Investigations of transcript expression in fathead minnow (Pimephales promelas) brain tissue reveal toxicological impacts of RDX exposure

“…Seizures have been observed in rats (Meyer et al, 2005), miniature swine (Schneider et al, 1977), mice (Dilley et al, 1978), Northern bobwhite quail (Johnson et al, 2007) and humans (Stone et al, 1969;Woody et al, 1986) within hours after exposure to RDX. Gust et al (2009) hypothesized that the mode of action underlying RDX-induced seizures in Northern bobwhite is the inhibition of neuronal membrane depolarization back to the baseline voltage after an action potential thereby resulting in hyper-excitation.…”

“…Observed effects of RDX exposure in the ecotoxicological model species fathead minnow include lethality, impaired growth and reduced reproduction (Burton et al, 1994;Talmage et al, 1999). Evidence that the central nervous system is the primary toxicological target for RDX include observation of RDX-induced convulsions in rats (Meyer et al, 2005), miniature swine (Schneider et al, 1977), mice (Dilley et al, 1978), Northern bobwhite (Johnson et al, 2007;Quinn et al, 2009;Gust et al, 2009) and humans (Stone et al, 1969;Woody et al, 1986). Neurotoxicogenomic investigations in rat and Northern bobwhite indicate that RDX-induced seizures are likely driven by various impacts on genes and pathways involved in the neurophysiology of brain tissue (Bannon et al, 2009;Gust et al, 2009 Given that RDX may accumulate in surface waters, the potential for impacts on CNS in fish is of concern.…”

Genomic investigation of year‐long and multigenerational exposures of fathead minnow to the munitions compound RDX

“…A critical tissue residue of approximately 20 mg/g in brain tissue has been observed to correspond with seizure activity and subsequent mortality in the Northern bobwhite [22], with brain tissue residues below this level having little impact on transcript expression [24]. Mortality in fathead minnow exposed in the 96-h challenge experiment also corresponded with whole body tissue concentrations of approximately 20 mg/g (Figs.…”

“…Each diluted extract was then added into a 200 ml glass insert placed in a 1.5-ml amber vial (Agilent Technologies). Samples were analyzed for RDX using methods as described by Johnson et al [22].…”

“…Reductions in survival and reproduction were observed at !5 mg/L for all fish species tested with limited sublethal impacts observed below that concentration. In addition, RDX has been observed to elicit neurotoxic effects [22][23][24][25][26] and hepatotoxicity [22,26] in a wide phylogenetic spectrum of animal species. We therefore focused our investigations on the effects of RDX exposure on transcript expression in fathead minnow brain and liver tissues.…”