Effects of pretreatment of male NMRI mice with enzyme inducers or inhibitors on clastogenicity of toluene.

Five groups of young male NMRI mice were pretreated with IP injections of three known inducers of cytochrome P450, Aroclor 1254, phenobarbital and 3-methylcholanthrene, and two inhibitors, metyrapone and alpha-naphthoflavone, 5, 3, 2, 1, and 1 day(s) before receiving toluene, respectively. Toluene was given to animals by IP injections of two similar doses 24 h apart. Increased formation of micronuclei within polychromatic erythrocytes of femoral bone marrow 30 h after the first injection of toluene was recorded. None of the treatments with an inducer or inhibitor alone gave a significant increase in the frequency of micronucleated polychromatic erythrocytes. However, pretreatment of animals with each inducer or even inhibitor resulted in an enhanced clastogenic activity of toluene. Simultaneous injections of an inhibitor and toluene clearly decreased the clastogenicities observed. Enhancement of the clastogenicity of toluene was more evident among Aroclor -pretreated animals than among the other groups. Treatment of animals with a mixture of toluene and benzene did not result in an additive clastogenic activity of benzene. IP injection of a mixture of toluene and every xylene isomer resulted in an enhanced clastogenic activity of toluene, although xylene isomers are not found to be clastogenic.

The bone marrow clastogenicity of eight halogenated benzenes in male NMRI mice.

Eight widely used halogenated benzenes, including bromobenzene (BB), chlorobenzene (CB), three isomers of dichlorobenzene (DCB) and three isomers of trichlorobenzene (TCB) were tested for acute toxicity (LD50) and clastogenicity in 8-week-old NMRI mice by intraperitoneal administration. Four doses of each chemical (up to 70% of LD50) were tested for clastogenic activity. Each compound was administered in two equal doses, 24 h apart. Increased formation of micronucleated polychromatic erythrocytes, observed in femoral bone marrow, 30 h after the first injection, was considered to be due to the clastogenic activity of the test compound. All the halogenated benzenes tested were found to be clastogenic (P less than 0.01). The highest clastogenic activities were induced by m-DCB and BB. Among the three isomers of DCB, m-DCB significantly (P less than 0.05) induced more micronuclei than o-DCB or p-DCB. No significant differences were found between the clastogenic activities of TCB isomers.