Administration-route-related difference in the micronucleus test with 7,12-dimethylbenz[a]anthracene.
The effect of route of administration on the outcome of the mouse micronucleus test was evaluated in 2 laboratories by administering a model chemical, 7,12-dimethylbenz[a]anthracene (DMBA) by intraperitoneal injection (i.p.) and oral gavage administration (p.o.) to males of 2 mouse strains, MS/Ae and CD-1. On the basis of a small-scale acute toxicity study and a pilot micronucleus test, a full-scale micronucleus test was performed with a 48-h sampling time at doses of 25, 50, 100, and 200 mg/kg by both administration routes in the 2 strains. At each dose level and in both strains, higher frequencies of micronucleated polychromatic erythrocytes (MNPCEs) were found after use of the i.p. route. In the MS/Ae strain, a linear, positive dose response was obtained by both routes. In the CD-1 strain, the maximum response was reached at 100 mg/kg and a downturn occurred at 200 mg/kg by both routes. The comparison of maximum responses indicated that MS/Ae was the higher responder for both routes of application. Although DMBA induced micronuclei more efficiently by the i.p. route than after oral administration on a mg/kg base, this route-related difference was reversed in both strains when the comparison was made on the basis of LD50 values and when the maximum responses were neglected.
Mizuhashi
F
F
Life Science Research Institute, Kumiai Chemical Industry Co., Ltd., Shizuoka, Japan.
Murata
K
K
Kitagaki
T
T
Nishitomi
T
T
Hashimoto
A
A
Kido
A
A
D015127:9,10-Dimethyl-1,2-benzanthracene / Q000008:administration & dosage* / Q000633:toxicity; D000284:Administration, Oral; D000818:Animals; D007274:Injections, Intraperitoneal; D007928:Lethal Dose 50; D008297:Male; D051379:Mice; D015162:Micronucleus Tests; D009153:Mutagens / Q000008:administration & dosage*; D010865:Pilot Projects
D009153:Mutagens; D015127:9,10-Dimethyl-1,2-benzanthracene