Accorsi Antonio, Valenti Simona, Barbieri Anna, Raffi Giovanni Battista, Violante Francesco Saverio
Laboratorio di Tossicologia, Servizio di Sicurezza, Igiene e Medicina del Lavoro, Università degli Studi di Bologna, Via Palagi 9, 40138 Bologna, Italy.
Int Arch Occup Environ Health. 2003 Mar;76(2):129-36. doi: 10.1007/s00420-002-0379-4. Epub 2002 Sep 24.
Assessment of individual exposures to sevoflurane plus nitrous oxide (N(2)O) by biological monitoring of unmodified analytes in post-shift urine of exposed personnel.
Anaesthetics in urine and breathing area were monitored in 124 subjects in 11 operating theatres. Passive samplers were collected after 2.5-7 h of exposure, at the same time as post-shift urinary samples, to evaluate the individual time-weighted average (TWA) exposures to sevoflurane and N(2)O. A static headspace sampler coupled with a gas chromatograph mass spectrometer was used for analytical determinations (sensitivity sufficient to reveal biological/environmental exposures of 0.1 microg/l(urine) and 50 ppb for sevoflurane, and 1 microg/l(urine) and 80 ppb for N(2)O).
Median (range) post-shift urinary and environmental values were 1.2 microg/l(urine) (0.1-5.0) and 0.4 ppm (0.05-3.0) for sevoflurane ( n=107) and 10.9 microg/l(urine) (0.5-74.9) and 8.6 ppm (0.2-123.4) for N(2)O ( n=121) (all low-exposure range). At log-log regression, urinary levels closely correlated with environmental data (sevoflurane, r(2)=0.7538; N(2)O, r(2)=0.8749). Biological equivalent limits (BELs) based on National Institute for Occupational Safety and Health (NIOSH) TWA exposure limits, calculated as means of regression slope and y-intercept, were 3.6 microg/l(urine) for sevoflurane (corresponding to 2 ppm) and 22.3 microg/l(urine) for N(2)O (corresponding to 25 ppm). Individual "mixture BELs", which we calculated by applying the American Conference of Governmental Industrial Hygienists (ACGIH) threshold limit value (TLV) mix formula to biomarker values and using the obtained NIOSH-based BELs as a reference, closely correlated with mixture TLVs (rho=0.816, Lin's concordance test). CONCLUSIONS. We propose urinary sevoflurane as a new, specific, internal dose biomarker for routine biological monitoring of personal exposures among operating-theatre personnel, and use of reliable "mixture BELs" to provide safer levels of internal exposure for workers exposed to mixtures of sevoflurane and N(2)O, and conceivably also to other mixtures of toxicants with possible additive effects.
通过对暴露人员下班时尿液中未修饰分析物进行生物监测，评估个体对七氟醚加氧化亚氮（N₂O）的暴露情况。
对11个手术室的124名受试者的尿液和呼吸区域的麻醉剂进行监测。在暴露2.5 - 7小时后，与下班时的尿液样本同时收集被动采样器，以评估个体对七氟醚和N₂O的时间加权平均（TWA）暴露量。使用与气相色谱质谱仪联用的静态顶空采样器进行分析测定（灵敏度足以检测出七氟醚在尿液中的生物学/环境暴露量为0.1微克/升，在空气中为50 ppb；N₂O在尿液中的暴露量为1微克/升，在空气中为80 ppb）。
七氟醚（n = 107）下班时尿液和环境中的中位数（范围）分别为1.2微克/升（尿液）（0.1 - 5.0）和0.4 ppm（0.05 - 3.0）；N₂O（n = 121）下班时尿液和环境中的中位数（范围）分别为10.9微克/升（尿液）（0.5 - 74.9）和8.6 ppm（0.2 - 123.4）（均处于低暴露范围）。在对数-对数回归分析中，尿液水平与环境数据密切相关（七氟醚，r² = 0.7538；N₂O，r² = 0.8749）。根据美国国家职业安全与健康研究所（NIOSH）的TWA暴露限值计算的生物等效限值（BELs），以回归斜率和y轴截距的平均值计算，七氟醚为3.6微克/升（尿液）（相当于2 ppm），N₂O为22.3微克/升（尿液）（相当于25 ppm）。我们通过将美国政府工业卫生学家会议（ACGIH）的阈限值（TLV）混合公式应用于生物标志物值，并以基于NIOSH的BELs作为参考来计算个体“混合BELs”，其与混合TLV密切相关（rho = 0.816，林氏一致性检验）。结论：我们建议将尿液中的七氟醚作为一种新的、特异性的内部剂量生物标志物，用于对手术室人员个人暴露情况进行常规生物监测，并使用可靠的“混合BELs”为暴露于七氟醚和N₂O混合物（可能还包括其他具有潜在相加作用的毒物混合物）的工人提供更安全的内部暴露水平。
