Occupational exposure to anaesthetic gases and urinary excretion of D-glucaric acid

Abstract In order to ascertain whether the urinary excretion of D-glucaric acid (DGA) might be a suitable biomarker of effect in monitoring workers exposed to anaesthetic gases, we measured DGA before and after an operating session (and, in some workers, before and after a 2-week vacation) in 229 workers of surgical units and in 229 controls. In the former, we also measured urinary levels of nitrous oxide (N2O) and isoflurane after at least 4 h of exposure. For all subjects, information on age, smoking habits, daily intake of alcohol, coffee, and drugs, history of liver or kidney disease was collected. Study subjects were ranked according to: exposure (class 0: subjects not exposed; class 1: N2O < 27 μg 1-1 and isoflurane < 1 μg 1-1; class 2: N2O < 27 μg 1-1 and isoflurane > 1 μg 1-1; class 3: N2O >27 μg l-1 and isoflurane <1 μg l-1; class 4: N2O >27 μg l-1 and isoflurane >1 μg l-1); general habits; and DGA (two groups, below and above the arbitrary cut-off value of 3.5 mmol mol-1 creatinine). The relative risk of presenting high DGA excretion was estimated through the Odds Ratio (OR) and 95% Confidence Intervals (CI). In univariate analysis, ORs increased from class 1 (lowest exposure) to class 4 (highest exposure) and with increases in coffee and cigarette consumption. The ORs adjusted for sex, age, creatinine, and alcohol and coffee intake, conventionally 1.0 in the control group, were 0.68 (CI=0.33-1.38), 2.68 (CI=1.36-5.27), 2.68 (CI=1.21-4.90) and 3.73 (CI=1.51-9.18) respectively in exposure classes 1, 2, 3 and 4. By contrast, individual levels of DGA did not correlate with urinary concentrations of anaesthetic gases. Moreover, no significant differences in DGA levels were observed between urine samples taken before and immediately after a workshift, nor between samples collected before and after at least 2 weeks vacation. In conclusion, DGA excretion cannot be used as an individual biomarker of effect in workers exposed to anaesthetic gases. Since effects on hepatic function were not found at lower concentrations (exposure class 1), the currently adopted threshold limits (isoflurane: 1 μg 1-1; and N2O: 27 μg 1-1) appear sufficiently protective.