Sugiyama C, Kobayashi H, Kishi M
Shiseido Toxicological and Analytical Research Center, Yokohama-shi, Japan.
Mutat Res. 1989 Aug;223(4):361-4. doi: 10.1016/0165-1218(89)90086-4.
The effect of route of administration on the outcome of the mouse micronucleus test was evaluated in 2 laboratories by administering 2-acetylaminofluorene (2-AAF) by intraperitoneal injection (i.p.) and oral gavage (p.o.) to 2 mouse strains, MS/Ae and CD-1. On the basis of a small-scale acute toxicity study and a pilot micronucleus test, the full-scale experiment was performed with a 24-h sampling time at doses ranging from 75 to 600 mg/kg by both routes. The results indicated that 2-AAF induced micronucleated polychromatic erythrocytes (MNPCEs) at all doses tested by both routes. In the MS/Ae strain, higher doses were required by p.o. than by i.p. to reach a similar level of MNPCE incidence. On the other hand, similar responses were recorded by both administration routes with CD-1 mice. Since the LD50 for the p.o. route was higher than that for the i.p. route in both strains, the route-related difference with MS/Ae mice became small when the comparison between i.p. and p.o. was made on the basis of the LD50. Thus both i.p. and p.o. routes are acceptable in the micronucleus test of this chemical.
在2个实验室中，通过对MS/Ae和CD-1这2种小鼠品系腹腔注射（i.p.）和灌胃（p.o.）给予2-乙酰氨基芴（2-AAF），评估给药途径对小鼠微核试验结果的影响。根据小规模急性毒性研究和预试验微核试验，以24小时采样时间，通过两种途径在75至600mg/kg的剂量范围内进行了全面实验。结果表明，两种途径在所有测试剂量下2-AAF均诱导产生了微核多染红细胞（MNPCEs）。在MS/Ae品系中，口服给药比腹腔注射需要更高的剂量才能达到相似水平的MNPCE发生率。另一方面，两种给药途径在CD-1小鼠中记录到相似的反应。由于两种品系中口服途径的半数致死量（LD50）均高于腹腔注射途径，因此当基于LD50对腹腔注射和口服进行比较时，MS/Ae小鼠与给药途径相关的差异变小。因此，在该化学品的微核试验中，腹腔注射和口服途径均是可接受的。
