d'Alessandro A, Osterloh J D, Chuwers P, Quinlan P J, Kelly T J, Becker C E
Istituto di Medicina del Lavoro e Tossicologia Ambientale, University of Perugia, Italy.
Environ Health Perspect. 1994 Feb;102(2):178-81. doi: 10.1289/ehp.94102178.
Methanol will be present as a new air pollutant when methanol-powered vehicles are introduced in the United States. Little is known about the effect of low-dose methanol exposure. It is controversial whether or not formate, the main metabolite responsible for methanol's acute toxicity, is a sensitive biological marker of toxicity or exposure. We studied the effect of a 4-hr exposure at rest to 200 ppm of methanol vapors on endogenous serum formate and on urinary formic acid excretion. A randomized, double-blind study of human exposure to a constant concentration of methanol was performed in a whole-body exposure chamber. Twenty-six healthy volunteers, each serving as his or her own control, participated in sham and methanol exposures. Urine (at 0, 4, 8 hr) and serum specimens (15 time points over 8 hr) collected before, during, and after the exposure were measured for formate. We found no significant differences in serum formate concentration between exposure and control conditions either at any time point or for area under the curve. Mean concentrations at the end of the exposure were: exposed 14.28 +/- 8.90 mg/l and control 12.68 +/- 6.43 mg/l. A slight, but nonsignificant (p = 0.08), increase in urine formate excretion rate was found at 4 hr (exposed 2.17 +/- 1.69 mg/4 hr and control 1.67 +/- 1.02 mg/4 hr). Age, sex, folic acid level, and smoking were not significant covariates. At 200 ppm, methanol exposure does not contribute substantially to endogenous formate quantities. Serum and urine formate determinations are not sensitive biological markers of methanol exposure at the threshold limit value.
在美国引入甲醇动力汽车后,甲醇将成为一种新的空气污染物。关于低剂量甲醇暴露的影响,人们知之甚少。负责甲醇急性毒性的主要代谢产物甲酸是否是毒性或暴露的敏感生物标志物,这一点存在争议。我们研究了在静息状态下暴露于200 ppm甲醇蒸气4小时对内源性血清甲酸和尿中甲酸排泄的影响。在全身暴露舱中进行了一项关于人体暴露于恒定浓度甲醇的随机、双盲研究。26名健康志愿者,每人都作为自己的对照,参与了假暴露和甲醇暴露。在暴露前、暴露期间和暴露后收集的尿液(0、4、8小时)和血清样本(8小时内15个时间点)进行甲酸测定。我们发现,在任何时间点或曲线下面积方面,暴露组和对照组的血清甲酸浓度均无显著差异。暴露结束时的平均浓度为:暴露组14.28±8.90 mg/l,对照组12.68±6.43 mg/l。在4小时时发现尿甲酸排泄率有轻微但不显著(p = 0.08)的增加(暴露组2.17±1.69 mg/4小时,对照组1.67±1.02 mg/4小时)。年龄、性别、叶酸水平和吸烟不是显著的协变量。在200 ppm时,甲醇暴露对内源性甲酸量的贡献不大。血清和尿甲酸测定在阈限值时不是甲醇暴露的敏感生物标志物。