Abstract |
Meta-Phenylenediamine (CAS No. 108-45-2) was evaluated for clastogenic effects in male and female Crl:CDBR mice (5-6/sex/treatment group) following gavage dosing (2 doses, 24 hours apart) at concentrations of 0, 16, 33 and 65 mg/kg bodyweight. Five animals/sex/group were sacrificed for harvest of femur bone marrow and 1000 polychromatic erythrocytes/animal at 24 hours (all treatment groups) and 48 hours (0 and 65 mg/kg/day groups) after a second dose. Bone marrow smears were analyzed for treatment-related incidence of micronuclei in polychromatic erythrocytes. Among the in vivo observations included lethargy, half-closed eyes, and labored and/or rapid breathing at all dosage levels, persisting to 3-4 hours after 65 mg/kg treatments. Initial gasping, face pawing, spasms, and tremors were associated with 65 mg/kg doses, as was brown urine 24 hours after administration of a final dose. A solitary 65 mg/kg/day male found dead 24 hours after a second dose comprised the study mortality and weight loss in 33 and 65 mg/kg/day treatment groups was statistically significant. Upon cytogenetic evaluation, there was no statistically significant increase in micronucleated polychromatic erythrocytes in any treatment group relative to vehicle control (deionized water). The only statistically significant (p < 0.05; Dunnett's test) finding from all bone marrow smears was a reduction in young, polychromatic erythrocytes. |