Toxicol Ind Health. 2022 Jun;38(6):309-329. doi: 10.1177/07482337221093838.
n-Methyl-2-pyrrolidone (NMP) is a widely used solvent with a mild amine-like odor that can exist in a vapor or aerosol at moderate temperatures. In humans, NMP was reported to induce weak and transient eye irritation and headache. NMP was not a dermal sensitizer and has a low acute toxicity via oral, dermal, and inhalation routes. NMP was not genotoxic/mutagenic in a battery of and studies. Furthermore, NMP was not carcinogenic in rats although species-specific liver tumors were identified in mice. Chronic studies in the rat provided a NOAEL of 10 ppm (40 mg/m) causing only minor effects in males (slightly reduced mean body weight) at 100 ppm (400 mg/m). Developmental toxicity was considered the critical endpoint (decreased fetal body weights at non-maternally toxic doses). Benchmark dose and PBPK models were utilized to derive an internal dose of 350-470 mg·h/L as a NOAEL for this response and a human equivalent air concentration of 350-490 ppm. With the application of adjustment factors, an 8-h time-weighted average WEEL value of 15 ppm (60 mg/m) was derived and is expected to provide a significant margin of safety against any potential adverse health effects in workers. To address the potential for respiratory irritation, a short-term exposure level of 30 ppm (120 mg/m) was derived, and a skin notation is assigned because of the contribution of dermal absorption to the systemic toxicity of NMP.
N-甲基-2-吡咯烷酮(NMP)是一种用途广泛的溶剂,具有温和的胺样气味,在中等温度下可以以蒸气或气溶胶形式存在。在人类中,据报道 NMP 会引起轻微和短暂的眼睛刺激和头痛。NMP 不是皮肤致敏剂,经口服、皮肤和吸入途径具有低急性毒性。在一系列和研究中,NMP 没有遗传毒性/致突变性。此外,NMP 对大鼠没有致癌性,尽管在小鼠中发现了种特异性肝肿瘤。大鼠的慢性研究提供了 10ppm(40mg/m)的无观察到不良作用水平(NOAEL),在 100ppm(400mg/m)时仅对雄性造成轻微影响(平均体重略有降低)。发育毒性被认为是关键终点(在非母体毒性剂量下降低胎儿体重)。基准剂量和 PBPK 模型被用于推导 350-470mg·h/L 的内部剂量作为该反应的 NOAEL 和 350-490ppm 的人类等效空气浓度。应用调整因子,推导出 15ppm(60mg/m)的 8 小时时间加权平均 WEEL 值,预计将为工人提供对任何潜在健康影响的显著安全边际。为了解决呼吸刺激的潜在问题,推导出 30ppm(120mg/m)的短期暴露水平,并由于皮肤吸收对 NMP 的全身毒性的贡献,分配了皮肤标注。