OECD SIDS 5. TOXICITY
ID: 79-50-5 DATE: 18.01.2006
Species: Sex: Strain: Route of administration: Exposure Period:
Frequency of treatment: Premating Exposure Period
rat male/female other: Wistar Crl: (WI) BR (outbred, SPF quality) gavage males: 2 weeks prior to mating, during mating and up to termination (28 days for all males) females: 2 weeks prior to mating, during mating, during gestation and at least 4 days of lactation; mean treatment duration for females was 43 days once daily
14 days 14 days
No. of generation studies: 1
Control Group: NOAEL Parental: NOAEL F1 Offspring: Result:
(controls, vehicle only = milli-U water), 40, 200
and 1000 mg/kg bw/d yes, concurrent vehicle = 1000 mg/kg bw = 1000 mg/kg bw no reprotoxic effects noted up to the highest dose of 1000 mg/kg bw/d
other: OECD Guideline 422, "Combined repeated dose toxicity study with the reproduction/developmental toxicity screening test", 22-Mar-1996 2003 yes as prescribed by 1.1 - 1.4
Year: GLP: Test substance:
Test substance formulation Vehicle Water (Milli-Q) of 37ºC adjusted to pH 4. Acetic acid was added to milli-Q water to obtain pH 4. Rationale for vehicle: Based on trial formulations performed at NOTOX and on information provided by the sponsor. During NOTOX Project 257568 (Determination of the hydrolysis of dl-lactone as a function of pH) it was determined that dllactone was hydrolytically stable at pH 4 and 50ºC. Formulations in Milli-Q water are stable for 4 hours at room temperature and formulations in Milli-Q water adjusted to pH 4 are stable for 4 hours at room temperature and for 8 days at 37°C (determined during this project).
Animal husbandry Conditions. A controlled environment was maintained in the room with optimal conditions of approximately 15 air changes per hour, a temperature of 17.1-24.2°C, a relative humidity of 33-76% and a 12 hour light/12 hour dark cycle. Temporary deviations from the maximum level for relative humidity (with a maximum of 6%) and light/dark cycle (with a maximum of 1 hour) occurred due to cleaning procedures or performance of functional observations in the room. Based on laboratory historical data these deviations are considered not to affect the study integrity.
Accommodation Upon arrival, animals were housed in groups of 5 animals/sex/cage in suspended stainless steel cages. During the mating procedures, females were caged together with males on a one-to-one-basis in suspended stainless steel cages with wire mesh floors. Mated females and males were individually