OECD SIDS 5. TOXICITY
ID: 79-50-5 DATE: 18.01.2006
Rat: male and female Wistar rats Crl: (WI) BR (outbred, SPF-Quality). Untreated animals and virgin females were used at initiation of the studied test system. Source: Charles River Deutschland, Sulzfeld, Germany. Age at start F0-treatment: Approximately 10 weeks. Number of F0-animals: 40 females and 40 males. Acclimatisation F0: 5 days prior to start of treatment. Health check F0: A health inspection was performed prior to commencement of treatment to ensure that the animals were in a good state of health. Randomisation F0: 5 days before study start, by computer-generated random algorithm according to body weight, with all animals within ± 20% of the sex mean. Identification F0: By tattoo on the tail. Mating procedures F0: Females were paired on a one-to-one-basis with males from the same treatment group. Each morning following pairing, the trays under the cages were checked for ejected copulation plugs. The day on which a copulation plug was found was designated day 0 of gestation (=day 0 post-coitum). Once mating had occurred, the males and females were separated. - Mating had not been detected for females 53, 56, 57 (group 2), and 78 (group 4) after one week of pairing. On 14 October 2002, these females were paired with proven males of the same treatment group. Parturition F0: The females were allowed to litter normally. Day 1 of lactation was defined as the day when a litter was found completed (i.e. membranes, placentas cleaned up, nest build up and/or feeding of pups started). Females that were littering were left undisturbed. Lactation F0: Deficiencies in maternal care, such as inadequate construction or cleaning of the nest, pups left scattered and cold, physical abuse of pups or apparently inadequate lactation or feeding, were recorded. Identification offspring: The offspring was individually identified by means of intracutaneous injection of Indian ink.
Individual numbers assigned
F0 males F0 females
Allocation to treatment groups: 10 F0 males and 10 F0 females
per treatment group
These dose levels were chosen based on the results of a dose range finding study (NOTOX Project 359325). Dose level Group 1: vehicle (milli-Q water) only.
Treatment F0 animals Method: Oral gavage, using a rubber catheter attached to a plastic disposable syringe. Frequency: Once daily, at approximately the same time each day. Exposure period: The males were exposed for 2 weeks prior to mating, during mating and up to termination (28 days for all males). The females were exposed for 2 weeks prior to mating, during mating, during post-coitum and at least 4 days of lactation. The mean duration of treatment of females was 43 days, with a minimum of 28 days and a maximum of 56 days. Dose volume: 5 ml/kg body weight. Actual dose volumes were