Troup C M, Dodd D E, Fowler E H, Frank F R
Environ Health Perspect. 1987 Jun;72:21-8. doi: 10.1289/ehp.877221.
Human, rat, and guinea pig packed erythrocytes exposed to 100, 500, or 1000 ppm of methyl isocyanate (MIC) vapor in vitro showed a concentration-related inhibition of cholinesterase (ChE) activity. Rat and guinea pig packed erythrocytes showed an almost complete inhibition of ChE activity at 2000 ppm. In vitro exposures of human and guinea pig blood to 1000 or 2000 ppm of MIC vapor resulted in qualitative alterations in the electrophoretic mobility of hemoglobin (Hb) as measured by citrated agar electrophoresis. In rats and guinea pigs, neither IV injection of liquid MIC nor in vivo exposure to 1000 ppm of MIC by inhalation resulted in any inhibition of erythrocyte ChE activity or alteration in Hb electrophoretic mobility. As a result of these observations, it was concluded that neither ChE inhibition nor structural alteration of Hb were major contributing factors to death resulting from MIC exposure. Rats and guinea pigs receiving IV injections of liquid MIC showed an increase in creatine kinase (CK) levels. This increase could not be attributed to a specific isoenzyme of CK by ion exchange chromatography. Rats exposed to 100, 600, or 1000 ppm of MIC and guinea pigs exposed to 25, 125, or 225 ppm of MIC and bled immediately following a 15-min exposure or at 1, 2, 4, or 16 hr postexposure had the following alterations in blood parameters: an increase in CK, increases in hemoglobin concentration and hematocrit, reticulocytosis (rats only), neutrophilia, a decrease in blood pH and PO2, and an increase in blood PCO2.(ABSTRACT TRUNCATED AT 250 WORDS)
在体外,将人、大鼠和豚鼠的浓缩红细胞暴露于浓度为100、500或1000 ppm的异氰酸甲酯(MIC)蒸气中,胆碱酯酶(ChE)活性呈现出与浓度相关的抑制作用。在2000 ppm时,大鼠和豚鼠的浓缩红细胞ChE活性几乎完全被抑制。通过枸橼酸琼脂电泳测定,将人和豚鼠的血液在体外暴露于1000或2000 ppm的MIC蒸气中,会导致血红蛋白(Hb)电泳迁移率发生定性改变。在大鼠和豚鼠中,静脉注射液态MIC或吸入1000 ppm的MIC进行体内暴露,均未导致红细胞ChE活性受到抑制或Hb电泳迁移率发生改变。基于这些观察结果,得出结论:ChE抑制和Hb结构改变均不是MIC暴露导致死亡的主要因素。静脉注射液态MIC的大鼠和豚鼠肌酸激酶(CK)水平升高。通过离子交换色谱法无法将这种升高归因于CK的特定同工酶。暴露于100、600或1000 ppm MIC的大鼠以及暴露于25、125或225 ppm MIC的豚鼠,在暴露15分钟后或暴露后1、2、4或16小时立即采血,血液参数有以下变化:CK升高、血红蛋白浓度和血细胞比容增加、网织红细胞增多(仅大鼠)、中性粒细胞增多、血液pH值和PO2降低以及血液PCO2升高。(摘要截短于250字)