Inhalation Toxicity of Man-Made Mineral Fiber (MMMF)

肺沉积和肺中沉积颗粒的清除是引起尘肺病和肿瘤的重要因素。本实验选取42只雄性Wistar大鼠和45只雌性Wistar大鼠，连续6小时/天，5天/周，连续4周暴露于含SiO_2 63%的日本Advantec Toyo公司GB-100R玻璃纤维中，27只雄性Wistar大鼠连续1年进行慢性吸入毒性试验。Andersen采样器测得的质量气动直径中值为2.7 mum，扫描电镜测得的计数直径中值为0.51 mum，长度中值为5.5 mum。采用带螺旋给料机和溢流管的连续流化床控制暴露期日均暴露浓度，男、女暴露期4周分别为10.8 <正负> 3.3和9.8 <正负> 3.0 mg/m^3，暴露1年分别为2.2 <正负> 0.6 mg/m^3。采用光散射法监测曝光室内纤维颗粒浓度，并在曝光过程中保持恒定。在暴露1、2、3和4周后24小时，以及暴露4周后3.5、5.5、6和12个月的清除率后处死大鼠。对于玻璃纤维对肺沉积的慢性影响，它们在接触1年后即死亡，并在接触1年后的1年清除率后死亡。测定肺湿重和肺内二氧化硅浓度，并用等离子体asher对肺进行低温灰化（约150℃）处理。灰化后，在铂罐中加入碳酸钠熔化，用吸收分光光度法测定硅含量。通过玻璃纤维暴露大鼠肺内硅含量的测定值与对照组硅含量的差值计算出暴露大鼠肺内硅沉积量。雄性大鼠暴露4周后，玻璃纤维沉积量达300 ug，与暴露时间成正比。慢性暴露时，1年后清除后的玻璃纤维沉积量分别为1.5 mg和0.6 mg。视沉积率（即暴露期间肺内沉积量与吸入玻璃纤维量之比）在男性和女性中分别为4.5%和4.7%。雌雄大鼠的表观沉积率无显著差异。在间隙期，沉积硅含量随间隙期的增加而降低。在单室模型中，雌雄大鼠的生物学半衰期均为1.5个月；暴露4周，暴露1年9.2个月。生物半衰期随暴露时间的增加而增加。其原因可能是纤维沉积降低了清除活性，但本实验未见恶性肿瘤。10. 关键词：少

Pulmonary deposition and the clearance of deposited particles from lungs are very important factors to induce pneumoconioses and tumors.In this experiment, 42 Wistar male and 45 Wistar female rats were exposed to glass fiber (GB-100R, Advantec Toyo, Co., Japan) (content : SiO_2 63 %) for 6 hrs/day, 5 days/week for 4 weeks, and for chronic inhalation toxicity test, 27 Wistar male rats were also exposed to glass fiber for 1 year. The mass median aerodynamic diameter was 2.7 mum by an Andersen sampler, and the count median diameter and length determined by a scanning electron microscope were 0.51 mum and 5.5 mum, respectively. The daily average exposure concentration was controlled by a continuous fuluidized bed with a screw feeder and an overflow pipe at 10.8 <plus-minus> 3.3 and 9.8 <plus-minus> 3.0 mg/m^3 during the exposure period in the male group and female group for 4-week exposure, respectively and 2.2 <plus-minus> 0.6 mg/m^3 for 1-year exposure. The fibrous particle concentration … More s in the exposure chamber were monitored by a light scattering method and were constant during the exposure.The rats were sacrificed at 24 hours after 1, 2, 3 and 4 weeks exposure and after 3.5, 5.5, 6 and 12 months clearance period following a 4-week exposure. For chronic effect of glass fiber on lung deposition, they were killed just after the 1-year exposure and after 1 year clearance period following a 1-year exposure. The wet lung weight and the silica concentration in thelungs were measured and the lungs were treated for low temperature ashing (ca. 150 ﾟC) by using a plasma asher.After ashing, these samples were melted with sodium carbonate in a platinum pot to measure the silicon content by the absorption spectrophotometry.The amount of deposited silicon in rat lungs by exposure to glass fiber was calculated from the difference value of measured silicon content between the exposed rats and controls. The deposited amount of glass fiber which was observed up to 300 ug in the 4-week exposed male rats, was proportional to the exposure period. For chronic exposure, the deposited amount of glass fiber was observed 1.5 mg and 0.6 mg after the 1-year clearance just after 1-year exposure. The apparent deposition fraction which is defined as the deposited amount in the lungs to the amount of the inhaled glass fiber during the exposure, was 4.5 % and 4.7 % in male and female, respectively. There was no significant difference in the apparent deposition fraction between male and female rats.During the clearance period, the deposited silicon content decreased with the increasing of the clearance period. The biological half time in the one-compartment model was determined to be 1.5 months in male and female rats ; for 4-week exposure, but 9.2 months for 1-year exposure. The biological half time increased with the increasing of the exposure period. The cause of this may be decrease of clearance activity by fiber deposition, however, there were no malignant tumor in this experiment. 10. KEY WORDS Less