Report No DWI0710

Nov 1995

This study was designed to assess the potential induction of micronuclei by bromoform in bone marrow cells of mice. Mice were treated with a single acute oral administration of the test substance by intragastric gavage at a dose levels of 250, 500 and 1 000 mg/kg. A preliminary toxicity test had previous]y shown 1000 mg/kg to be approximately the maximum tolerated dose.

Negative and positive control groups were dosed in an identical manner, orally by intragastric gavage. The negative control group received the vehicle, aqueous 1 % methylcellulose. The positive control group was treated with mitomycin C at 12 mg/kg bodyweight.

Bone marrow smears were obtained from five male and five female animals in the negative control and test substance groups at 2 sampling times; these being 24 or 48 hours after dosing. Bone marrow smears were obtained from the positive control group 24 hours after dosing. One smear from each animal was examined for the presence of micronuclei in 2000 polychromatic erythrocytes. The ratio of polychromatic to normochromatic erythrocytes was assessed by examination of at least 1000 erythrocytes from each animal. A record of the incidence of micronucleated normochromatic erythrocytes was also kept

Mice treated with bromoform did not show any significant increase in the frequency of micronucleated polychromatic erythrocytes at either sampling time.

There was no significant decrease in the ratio of polychromatic to normochromatic erythrocytes after treatment of the animals with bromoform.

The positive control compound, mitomycin C, produced large, highly significant increases in the frequency of micronucleated polychromaic erythrocytes together with decreases in the ratio of polychromatic to normochromatic erythrocytes.

It is concluded that bromoform has not shown any evidence of causing chromosome damage in this in vivo test

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