Maternal age, reproduction and chromosomal aberrations in Wistar derived rats.

The fertility of rats ranges from one to 18 months. In standard teratogenicity testing young, mature females are used which may not reflect the situation in women above 35 years old. Reproduction among different age groups of Wistar ats (strain Chbb: THOM) was compared at 3, 6, 9, 12, 15 and 18 months.

Litter parameters and spontaneous abnormalities in Himalayan rabbits.

A joint study was undertaken in three testing facilities to evaluate cumulative background data of Himalayan rabbits. All litters were derived from control does. The conception rate was high (84.

Safety assessment of brotizolam.

Brotizolam (2-bromo-4-(2-chlorophenyl)-9-methyl-6H-thieno [3,2-f]-1,2,4-triazolo[4,3-a]-1,4-diazepine, We 941, Lendormin), a new hypnotic, was submitted to a comprehensive range of safety assessment tests. Acute (single dose) toxicity was very low, while in subacute and chronic studies in rodents, signs of toxicity were first seen at doses of 400 mg/kg or more. Histopathological changes were only seen in the 1 1/2-year study.

The toxicology of brotizolam.

Acute studies. Following oral or intraperitoneal administration, toxicity was very low (LD50 in rodents greater than 10,000 and greater than 900 mg/kg, respectively). Subacute and chronic studies in rodents.

Fixation-induced cyst-like spaced in the brains of rabbit foetuses.

During teratologic trials, routine investigations of 4261 brains from rabbit foetuses, fixed in Bouin's solution and sectioned by Wilson's free-hand razor blade technique, revealed cyst-like spaces in the brains of 164 foetuses (3.8%). The cyst-like spaces, characterised by the absence of an epithelial or endothelial lining, were usually solitary and occurred mainly in the massa intermedia of the thalamus.

[Reproductive toxicological investigations with ipratropiumbromide (author's transl)].

In investigations of the effect of the bronchospasmolytic (8r)-3alpha-e (ipratropiumbromide, Sch 1000, Atrovent) on the reproductive function in the mouse, rat and rabbit, no teratogenic effect was demonstrated following administration by either gavage or inhalation. Extremely high dose resulted in mortality in pregnant animals and reduction in foetal birthweight. Similarly, no evidence of impaired fertility or perinatal survival due to the substance was found.