Workplace environmental exposure level guide: n-Methyl-2-pyrrolidone

Abstract

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 in vitro and in vivo 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/m3) causing only minor effects in males (slightly reduced mean body weight) at 100 ppm (400 mg/m3). 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/m3) 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/m3) was derived, and a skin notation is assigned because of the contribution of dermal absorption to the systemic toxicity of NMP.