A health-based recommended occupational exposure limit for isoflurane and sevoflurane using experimental animal data based on a systematic review and dose-response analysis

Epidemiological studies have raised concerns about health risks from occupational exposure to inhalation anesthetics. This study aimed to systematically search, select and appraise the evidence from animal studies to derive occupational exposure levels (OELs) for isoflurane and sevoflurane. Twenty-four studies for isoflurane and 7 studies for sevoflurane were included, which reported on neurological and fertility outcomes. When ranking adverse outcomes by derived benchmark dose lower bounds (BDMLs), male fertility was considered as the most critical effect for both substances. Assessment factors cover uncertainties regarding interspecies and intraspecies differences. Using the BMDL as point of departure we derived 8-h time-weighted average (TWA) OELs of 0.9 mg/m³ (0.12 ppm) for isoflurane and of 0.8 mg/m³ (0.09 ppm) for sevoflurane. For peak exposures, 15-min TWA OELs of 30 mg/m³ (3.9 ppm) and 25 mg/m³ (3.0 ppm) were derived, respectively. These levels are expected to protect workers from health effects caused by these anesthetic gases.