Comparative Toxicological Evaluation of UV-Degraded versus Parent-Insensitive Munition Compound 1-Methyl-3-Nitroguanidine in Fathead Minnow.

The US Army is replacing traditional munitions with insensitive munitions resistant to accidental detonation. Although the parent insensitive munition compound nitroguanidine (NQ) is generally not acutely toxic at concentrations >1000 mg/L in aquatic exposures, products formed by intensive ultraviolet (UV) degradation resulted in multiple-order of magnitude increases in toxicity. A methylated congener of NQ, 1-methyl-3-nitroguanidine (MeNQ), is also being assessed for potential use in insensitive munition explosive formulations; therefore, the present study investigated the hazard of parent versus UV-degraded MeNQ using fathead minnows (Pimephales promelas). Although up to 716 mg/L parent MeNQ caused no significant mortality or effects on growth in larval P. promelas fish in 7-d exposures, a similar concentration of MeNQ subjected to UV treatment resulted in 85% mortality. The UV treatment degraded only 3.3% of the MeNQ (5800 mg/L stock, UV-treated for 6 h), indicating that MeNQ degradation products have potentially high toxicity. The parent MeNQ exposure caused significantly decreased transcriptional expression of genes within the significantly enriched insulin metabolic pathway, suggesting antagonism of bioenergetics pathways, which complements observed, although nonsignificant, decreases in body weight. Significant differential transcriptional expression in the UV-degraded MeNQ treatments resulted in significant enrichment of pathways and functions related to the cell cycle, as well as erythrocyte function involved in O /CO exchange. These functions represent potential mechanistic sources of increased toxicity observed in the UV-degraded MeNQ exposures, which are distinct from previously observed mechanisms underlying increased toxicity of UV-degraded NQ in fish. Environ Toxicol Chem 2020;39:612-622. © 2019 SETAC.