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Micronucleus test with methyl methanesulfonate administered by intraperitoneal injection and oral gavage
T Tsuyoshi1, M Takeuchi, H Hirono
1Research Department, Sunstar Inc., Osaka, Japan.
Abstract:
The effects of 2 routes of administration, intraperitoneal injection (i.p.) and oral gavage (p.o.), in the micronucleus test were evaluated using methyl methanesulfonate (MMS) and 2 strains of mice (MS/Ae and CD-1). A small-scale acute toxicity study and a pilot micronucleus experiment were carried out first. On the basis of the results obtained, a final micronucleus test was performed at doses of 20, 40, 80, and 160 mg/kg (i.p.) and 40, 80, 160, and 320 mg/kg (p.o.), with a 24-h sampling time. MMS induced micronucleated polychromatic erythrocytes (MNPCEs) in both routes in both mouse strains under the conditions used. At 40 and 80 mg/kg, MMS induced a higher number of MNPCEs by the i.p. route in both strains. A 160 mg/kg MMS dose induced higher numbers of MNPCEs by the p.o. route in MS/Ae mice. The route-related difference with MMS on the basis of mg/kg disappeared when the difference was determined on the basis of a ratio of the LD50. In practice, both i.p. and p.o. routes are acceptable as routes of administration in the micronucleus test using this chemical.
Insights
Methyl methanesulfonate (MMS) induces micronucleated polychromatic erythrocytes (MNPCEs) via both intraperitoneal injection and oral gavage in mice. Route-specific differences in MNPCE induction were observed, but both administration routes are acceptable for the micronucleus test.
Area of Science:
- Toxicology
- Genotoxicity Testing
Background:
- The micronucleus test is a standard genotoxicity assay.
- Evaluating different routes of administration is crucial for accurate toxicological assessments.
Purpose of the Study:
- To compare the efficacy of intraperitoneal injection (i.p.) versus oral gavage (p.o.) administration of methyl methanesulfonate (MMS) in the mouse micronucleus test.
- To determine if route-dependent differences in genotoxic effects exist.
Main Methods:
- Conducted acute toxicity and pilot micronucleus studies.
- Performed a final micronucleus test using two mouse strains (MS/Ae and CD-1) with MMS administered via i.p. and p.o. routes at various doses.
- Analyzed micronucleated polychromatic erythrocytes (MNPCEs) at a 24-h sampling time.
Main Results:
- MMS induced MNPCEs via both i.p. and p.o. routes in both mouse strains.
- Higher MNPCEs were observed with i.p. administration at lower doses (40 and 80 mg/kg) in both strains.
- At 160 mg/kg, oral gavage showed higher MNPCE induction in MS/Ae mice.
- Route-related differences in mg/kg became insignificant when normalized to LD50.
Conclusions:
- Both intraperitoneal injection and oral gavage are acceptable routes for MMS administration in the mouse micronucleus test.
- While dose-dependent route differences exist, they are not absolute and can be influenced by factors like mouse strain and specific dose.
- The findings support the flexibility in choosing administration routes for this genotoxicity assay.