Abstract

Dinitroanisole (DNAN), 3-nitro-1,2,4-triazol-5-one (NTO), and nitroguanidine (NQ) are constituents of insensitive munitions being developed to minimize the acute hazards associated with non-intentional detonation of warheads. Although a reference dose (RfD) has been established for NQ and occupational exposure levels have been developed for all three compounds, current state-of-the science methods were not used. Here we present the latest toxicity data and interpretations for NTO, DNAN, and NQ and use Bayesian Benchmark Dose modeling and a Bayesian approach to applying uncertainty factors to derive tolerable daily intake (TDI) values. A TDI of 0.02 mg/kg-d was calculated for DNAN based on extramedullary hematopoiesis in female rats. A TDI of 2.4 mg/kg-d was derived for NTO based on testicular toxicity in male rats. A TDI of 4.0 mg/kg-d was derived for NQ based on increased fetal resorptions in rabbits. These TDIs are generally an order of magnitude higher than previously developed reference values. These values can be used to inform public health, occupational safety, and product acquisition and stewardship decisions. Drinking water, soil, and tap water screening levels were derived for residential and worker exposure scenarios to help inform risk assessment decisions.

摘要

二硝基苯甲醚 (DNAN)、3-硝基-1,2,4-三唑-5-酮 (NTO) 和硝基胍 (NQ) 是正在开发的钝感弹药的成分，以尽量减少与弹头非故意引爆相关的急性危害。尽管已经为 NQ 建立了参考剂量 (RfD)，并且已经为所有三种化合物制定了职业暴露水平，但并未使用当前的科学方法。在这里，我们展示了 NTO、DNAN 和 NQ 的最新毒性数据和解释，并使用贝叶斯基准剂量建模和贝叶斯方法来应用不确定因素来推导出每日可耐受摄入量 (TDI) 值。基于雌性大鼠的髓外造血，计算出 DNAN 的 TDI 为 0.02 mg/kg-d。根据雄性大鼠的睾丸毒性，推导出 NTO 的 TDI 为 2.4 mg/kg-d。TDI 为 4。0 mg/kg-d 是基于兔中增加的胎儿吸收得出的 NQ。这些 TDI 通常比以前制定的参考值高一个数量级。这些值可用于为公共卫生、职业安全以及产品采购和管理决策提供信息。饮用水、土壤和自来水筛选水平是针对住宅和工人暴露场景得出的，以帮助为风险评估决策提供信息。