OECD SIDS 5. TOXICITY
ID: 79-50-5 DATE: 18.01.2006
both kidneys, yellowish soft nodule at the tail of the left epididymis, dark red discolouration of the right clitoral gland, watery-clear cyst at the right ovary, haemorrhagic/clotted blood in the right uterus horn, enlarged spleen, many dark red foci on the right clitoral gland, uterus enlarged with greenish contents, hard and dark red discolouration of the papillary process of the liver, alopecia and gray-white discolouration of the medulla of the kidney. These findings are occasionally seen among rats used in these types of studies and in the absence of correlated microscopic findings they were considered changes of no toxicological significance.
Organ weights No treatment-related changes were present. Males of the 200 mg/kg bw/d dose group showed statistically significantly decreased absolute and relative adrenals weight and females of the 40 mg/kg bw/d dose group showed statistically significantly increased relative adrenals weight. In the absence of a dose-response relationship, these findings were considered to be caused by chance and not related to treatment.
Microscopic examination Microscopic findings: There were no treatment-related findings. Staging of spermatogenesis: The assessment of the integrity of the spermatogenetic cycle did not provide any evidence of impaired spermatogenesis.
Reproduction Reproduction parameters were unaffected by treatment up to 1000 mg/kg bw/d. Of the control group, two females were non-pregnant. Of the 40 mg/kg bw/d dose group, one female did not mate and two females mated in the second mating period. Of the 200 mg/kg bw/d dose group, two females were non-pregnant. And of the 1000 mg/kg bw/d dose group, one female was non-pregnant. Mating performance, duration of gestation, fertility parameters and number of pups at birth were similar for the control and treated groups.
Breeding data Breeding parameters were unaffected by treatment up to 1000 mg/kg bw/d. The number of dead and living pups at first litter check, postnatal loss between days 0-4 post-partum,
living pups similar for
at day 4 post-partum and the viability index were control and treated groups.
Pups Development mg/kg bw/d. and treated
of pups was unaffected by treatment up to 1000 Mean body weights of pups were similar for control groups. Incidental clinical symptoms consisted of
(very) small pups, little or no milk and bruise on the head or snout. Macroscopic examination of the pups revealed tip of tail missing, tip of tail discoloured dark red, autolysis, small appearance and no milk. No relationship with treatment was established for these observations or they were considered to be within the normal biological variation for rats of this age and strain. dl-Lactone from Roche Dalry, batch BX226, purity 99.8% as per