OECD SIDS 5. TOXICITY
ID: 79-50-5 DATE: 18.01.2006
and in Milli-U water adjusted to pH 4 were stable for 4 hours at room temperature. Formulations in Milli-U water adjusted to pH 4 are stable for 8 days at 37°C (27 September 2002). The results of 17 October 2002 confirmed stability for 8 days at 37°C for Group 2. However for Group 4, stability was not confirmed. Therefore, it was decided to repeat stability testing for Group 4. Results of these analyses (31 October 2002) showed an increase of 33% over 8 days at 37°C. This was due to the low values at t=0. The values at t=8 days were very close to the target (200 mg/g). Based on this it was concluded that the Group 4 formulations were stable over 8 days at 37°C and thus confirmed the results of 27 September 2002. Conclusion: Taking the analytical problems into account, it could be concluded that formulations were prepared accurately and homogeneously. Furthermore, it could be concluded th at formulations in Milli-U water were stable for 4 hours at room temperature and that formulations in Milli-U water adjusted to pH 4 were stable for 4 hours at room temperature and for 8 days at 37°C.
Mortality No unscheduled deaths occurred during the study period.
Clinical signs Females of the highest dose group showed aggressive and restless behaviour during days 5 to 15 of treatment. Incidental findings that were noted included scabs, wound, hunched posture, piloerection, broken upper incisors, broken tail apex, and alopecia at several parts of the body. These findings are commonly noted in rats of this age and strain which are housed and treated under the conditions in this study. At the incidence observed, these were considered signs of no toxicological significance.
Functional observations No changes were observed in hearing ability, pupillary reflex, static righting reflex and grip strength in the animals treated with dl-lactone, when compared to control animals. The variation in motor activity did not indicate a relation with treatment. Females of the highest dose group showed a decreased motor activity at the low sensors when compared to the control group. Since this change occurred in the absence of similar changes of the high sensors, they were considered to be of no toxicological relevance.
Body weight Body weights and body weight gain were unaffected by treatment up to and including 1000 mg/kg bw/d. Males of the 200 mg/kg bw/d dose group showed statistically significant decreased body weights on day 1 of the mating period. In the absence of a clear dose response relationship, this finding was considered to be of no toxicological relevance. On day 8 of the pre-mating period, males of the highest dose group showed a statistically significant increased body weight gain. As this finding was very slight and not considered to be adverse, it was considered to be of no toxicological significance.