Shindo Y, Toyoda Y, Kawamura K, Kurebe M, Shimada H, Hattori C, Satake S
Pharmacology and Toxicology Laboratories, Meiji Seika Kaisha Ltd., Yokohama, Japan.
Mutat Res. 1989 Aug;223(4):403-6. doi: 10.1016/0165-1218(89)90096-7.
The effect of route of administration, intraperitoneal (i.p.) or oral gavage (p.o.), in the mouse micronucleus test was studied with K2CrO4 in 2 mouse strains (MS/Ae and CD-1). A simplified acute toxicity test to estimate the toxic dose levels of K2CrO4 showed that the LD50S were 50 mg/kg i.p. and 300 mg/kg p.o. for MS/Ae and 32 mg/kg i.p. and 180 mg/kg p.o. for CD-1. Based on results of a pilot micronucleus test to determine appropriate dose levels and the optimal sampling time, it was decided to sample bone marrow cells of both strains of mice 24 h after i.p. doses of 10-80 mg/kg and p.o. doses ranging from 20 to 320 mg/kg. K2CrO4 administered i.p. induced micronucleated polychromatic erythrocytes (MNPCEs) dose-dependently in both strains. In contrast, when administered p.o. the chemical failed to induce MNPCEs. These results suggest that this difference between i.p. and p.o. routes is related to a difference of absorption or metabolic fate of chromate in vivo.
在2个小鼠品系（MS/Ae和CD-1）中，研究了腹腔注射（i.p.）或灌胃（p.o.）给药途径对小鼠微核试验中重铬酸钾（K2CrO4）效应的影响。一项用于估计K2CrO4毒性剂量水平的简化急性毒性试验表明，MS/Ae品系腹腔注射的半数致死量（LD50）为50 mg/kg，灌胃为300 mg/kg；CD-1品系腹腔注射为32 mg/kg，灌胃为180 mg/kg。根据初步微核试验结果确定合适的剂量水平和最佳采样时间，决定对2个品系小鼠腹腔注射10 - 80 mg/kg剂量、灌胃20 - 320 mg/kg剂量24小时后采集骨髓细胞。腹腔注射K2CrO4在2个品系中均剂量依赖性地诱导产生微核多染红细胞（MNPCEs）。相比之下，灌胃给药时该化学物质未能诱导产生MNPCEs。这些结果表明，腹腔注射和灌胃给药途径之间的这种差异与体内铬酸盐的吸收或代谢命运差异有关。
