OECD SIDS 5. TOXICITY
ID: 79-50-5 DATE: 18.01.2006
found completed cleaned up, nest Females that wer Lactation F0: De inadequate const scattered and co inadequate lacta Identification o identified by me
(i.e. memb build up e litterin ficiencies ruction or ld, physic tion or fe ffspring: ans of int
ranes, placentas and/or feeding of pups started). g were left undisturbed.
in maternal care, such as cleaning of the nest, pups left al abuse of pups or apparently eding, were recorded. The offspring was individually racutaneous injection of Indian ink.
Individual numbers assigned
F0 males F0 females
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.
Allocation to tr
per treatment group
oups: 10 F0 males and 10 F0 females
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 calculated according to the latest body weight. Observations F0 animals Mortality/Viability: Twice daily. Animals showing pain, distress or discomfort, which was considered not transient in nature or was likely to become more severe, were killed for humane reasons. The time of death was recorded as precisely as possible. Clinical signs: Once daily detailed clinical observations were made in all animals. Once prior to start of treatment and once a week thereafter, this was also performed outside the home cage in a standard arena during the pre-mating period. The time of onset, degree and duration of clinical signs were recorded. Grading of the symptoms took place according to fixed scales. The definition of gradings within these scales was as follows: Fixed scale with maximum grade 1: grade 0 = absent, grade 1 = present. Fixed scale with max. grade 3 or 4 : grade 1 = slight, grade 2 = moderate, grade 3 =
severe, grade 4 = very severe.
Cage debris of pregnant females was examined to detect potential abortions or premature births. Signs of difficult or prolonged parturition were recorded. Functional Observations: The following tests were performed in 5 males and 5 females, randomly selected from each group: hearing ability; pupillary reflex; static righting reflex; motor activity test (recording period: 12 hours during overnight for individual animals, using a computerised