BMS 233110-01

Specific investigations: other studies

Administrative data

Endpoint:

specific investigations: other studies

Remarks:

additional toxicological test

Type of information:

experimental study

Data source

Reference

Reference Type:

other: Body responsible for the test

Title:

Unnamed

Materials and methods

Principles of method if other than guideline:

Test procedure:
Following an initial toxicity range-finder study, 900mg/kg
BW was chosen as the maximum tolerated dose. A lower dose level of 360mg/kg was also selected.

Groups of 5 male rats were treated once by oral gavage at a dose volume of 10ml/kg with the vehicle, arachis oil, the
test substance or the appropriate positive control, 2- acetamidofluorene (2-AAF) or dimethylnitrosamine (DMN). Approx 12-14 hours (expt 1) or 2-4 hours (expt 2) after dosing, animals were sacrificed and the livers perfused with

collagenase to provide a primary culture of hepatocytes. Cultures were prepared from 3 animals in each dose group and treated with [3H] thymidine. 3 out of 6 slides from each animal were dipped in photographic emulsion to prepare autoradiograms. Slides were examined after development of emulsion and staining and the net grain count (NNG) was determined for each of at least 2 of the 3 slides for each animal and dose group.

Results and discussion

Details on results:

The test substance did not induce UDS in isolated hepatocytes under the test conditions employed.

Any other information on results incl. tables

Clinical signs observed at 900mg/kg BW included lethargy, piloerection, eye closure and an unsteady gait. Piloerection was also observed at 360mg/kg BW.