"- Storage condition of test material: at room temperature, protected from moisture

- Stability under test conditions: stable

- Solubility and stability of the test substance in the solvent/vehicle: Formulations of the test item in paraffin oil were found to be homogenous at both concentrations tested (12.5 mg/mL and 250 mg/ mL). Formulations at 12.5 mg/mL and 250 mg/mL were also found to be stable under all conditions investigated (6 hours at room temperature, 10 days at room temperature, at 2-8 °C and at -15 to -35 °C)."

"- Treatment of test material prior to testing: The test item was weighed into a tared plastic vial on a suitable precision balance and the vehicle was added to give the appropriate final concentration of the test item and further vortexed for 2-3 minutes. To protect from hydrolysis by humidity, the test item and formulation containers were purged with argon after the preparation before closing.

- Preliminary purification step (if any): none"

"The test item or vehicle were administered at a single dose daily to the animals by oral gavage. The application volume for all groups was 4 mL/kg body weight. For each animal the individual dosing volume was calculated on the basis of the body weight most recently measured. The test item formulation was prepared at least once every ten days based on available stability data. The prepared formulation was stored at room temperature under argon.

VEHICLE

- Justification for use and choice of vehicle (if other than water): The vehicle light liquid paraffin was selected based on the test item’s characteristics, dose range -finding study and testing guideline after consultation with the sponsor.

- Concentration in vehicle: not specified

- Amount of vehicle (if gavage): not specified

- Lot/batch no. (if required): 0000720349 / 0000855509

- Purity: not specified"

"Samples were collected for the investigation of homogeneity and substance concentration. Samples were taken from the top, middle and bottom of prepared formulations from all dose groups and from the middle of the control group in study week 1 (pre-mating period), 3 (rst week of mating), 5 (gestation) and in the last week of the study (gestation/lactation) from all groups (40 samples)."

Duration of treatment/exposure: females, up to 54 days; males, 28 days

Frequency of treatment: 7 days a week

Duration of test: up to 54 days

Regarding the high-dose group: The high-dose group dose level was initially 150 mg/kg bw/day. At the end of the 2nd week of the pre-mating period, the animals of the high-dose group were not administered with the test item for 2 to 3 days due to observed morbidity and mortality. From the respective pre-mating day 14/mating day 1 onwards, surviving high-dose animals were treated with a reduced dose level of of 125 mg/kg bw/day.

Dose selection rationale: The doses were selected according to the results of a previous dose range-finding study and in consultation with the sponsor.

Concentration and homogeneity of the test item in the vehicle were analysed in formulations of all dose groups in study weeks 1, 3, 5 and the last week. Nominal concentrations were confirmed for all dose groups, as measured mean concentrations were within acceptance criterion of 10 %. All samples were homogenous, as COV was below or equal 10 %.

F1 Rats