Reproductive toxicity studies of D-camphor in rats and rabbits.

The embryotoxicity of D-Camphor (CAS 76-22-2), orally employed for the treatment of hypotonic circulatory dysregulations, was investigated in rats and rabbits. D-Camphor elicited no evidence of teratogenicity when administered orally during the fetal period of organogenesis to pregnant rats at doses up to 1000 mg/kg b.w./day, and to pregnant rabbits at doses up to 681 mg/kg b.w./day. The no-observed-effect level for the fetal organism for the rat was above 1000 mg/kg b.w., and for the rabbit above 681 mg/kg b.w. In rat dams a dose-dependent reduction in food intake and salivation was noted from 464 mg/kg b.w./p.o. onwards. The high dose of 1000 mg/kg b.w./d p.o. resulted in fairly pronounced signs of toxicity such as clonic convulsion, pilo-erection, reduced motility and reduced body weight gain. In rabbit dams the high dose level of 681 mg/kg b.w./d p.o. resulted in reduced body weight gain and food consumption. No increased incidence in variations, retardations or malformations were observed at any of the treated dose levels not even at the highest tested dose level (rat: 1000 mg/kg b.w./d p.o.; rabbit: 681 mg/kg b.w./d p.o.). The daily maximum human therapeutic camphor dose is approximately 1.43 mg/kg b.w. Hence, under the present test conditions the therapeutic ratio is above 450 for the endpoint embryotoxicity reflecting a wide margin of safety.

Anti-inflammatory, spasmolytic and diuretic effects of a commercially available Solidago gigantea Herb. extract.

The evaluation of a commercially available Solidago gigantea Herb. extract (Urol mono) revealed pronounced anti-inflammatory properties in the rat with respect to a reduction of the carrageenin-induced rat paw oedema. A direct comparison with diclofenac-Na (3 mg/kg b.w. p.o.) revealed that a high dose of Solidago gigantea Herb. extract possesses the same anti-inflammatory efficacy as diclofenac-Na. In addition, the Solidago gigantea Herb. extract exhibited moderate spasmolytic and diuretic properties.

Reproductive toxicity studies of benzalazine in rats and rabbits.

Embryotoxicity studies of benzalazine (2-hydroxy-5-[(4-carboxyphenyl) azo]benzoic acid, CAS 64896-26-0), a new agent for the treatment of ulcerative colitis and Crohn's disease of the large intestine, were performed in rats and rabbits. Benzalazine elicited no evidence of teratogenicity when administered orally during the fetal organogenesis period to pregnant rats at doses up to 2000 mg/kg b.w./d, or to pregnant rabbits at doses up to 1000 mg/kg b.w./d. Rat fetuses in the 400 and 2000 mg/kg groups exhibited decreased body weights; the placentae weights were decreased in these dose groups, too. Rabbit fetuses in the high-dose group (1000 mg/kg b.w./d p.o.) also showed decreased body weights. Decreased body weight gain and reduced food intake were seen in rat dams in the high-dose group (2000 mg/kg b.w./d p.o.). In rabbit dams a decrease in body weight gain in the high-dose group (1000 mg/kg b.w./d p.o.) and a dose-dependent reduction in food intake from 200 mg/kg b.w./d p.o. onwards were noted. No further disturbances were observed in the behaviour of the rat and rabbit dams. External appearance, faeces, consumption of drinking water and macroscopical inspection during autopsy did not indicate any influence of the test compound. No retardations or malformations were seen even at the highest tested dose levels (rat: 2000 mg/kg b.w./d p.o.; rabbit: 1000 mg/kg b.w./d p.o.).

Oncogenicity studies of benzalazine in mice and rats.

Oncogenicity studies of benzalazine (2-hydroxy-5-[(4-carboxyphenyl) azo]benzoic acid, CAS 64896-26-0), a new agent for the treatment of ulcerative colitis and Crohn's disease of the large intestine, were carried out in male and female mice and rats. The compound was administered in the diet for 119 weeks (rats) and 120 weeks (mice) at dose levels of 100, 300 and 900/1800 mg/kg b.w./d for mice and of 300, 900 and 2700/1800 mg/kg b.w./d for rats. The administration of benzalazine produced no effects on survival, appearance or behaviour. Body weights of the high-dosed male mice and rats (both sexes) were occasionally significantly decreased when compared to the controls. A slight but in most cases statistically significant reduction of the relative food consumption of the female mice of all treated groups was observed between test weeks 6 and 12. In the high-dosed rats a statistically significant increase of the relative food consumption was found between test weeks 17 and 109. At necropsy, there was no evidence of treatment-related changes, nor were these seen on histopathological examination. All microscopic changes seen in mice and rats were of the usual type commonly occurring in untreated aged NMRI mice and Sprague-Dawley rats. However, an increased incidence of thyroid cystic hyperplasia was found in the rats of the high dose-level group. In addition, an increased incidence of thyroid adenomas was found in the male rats of the high-dosed group only as compared to the control groups. This increased tumour incidence is regarded as a marginal finding and may be of a spontaneous nature within the normal range of the background data. However, a substance-related influence cannot completely be excluded. In conclusion, the administration of benzalazine for more than 24 months to NMRI mice and Sprague-Dawley rats produced only slight effects on body weight in the high-dosed male mice and in rats (both sexes) with a no-effect level of 300 mg/kg b.w./d in the diet for mice or 900 mg/kg b.w./d in the diet for rats. There was no evidence of an oncogenic effect of benzalazine.

Characterisation of the central nervous depressant activity of a commercially available valerian root extract.

The evaluation of a commercially available valerian root extract (Valdispert) revealed pronounced sedative properties in the mouse with respect to a reduction in motility and an increase in the thiopental sleeping-time. A direct comparison with diazepam and chlorpromazine revealed a moderate sedative activity for the tested extract. The extract showed only weak anticonvulsive properties.

Antinociceptive properties of thiamine, pyridoxine and cyanocobalamin following repeated oral administration to mice.

Following repeated oral administration for 7 days thiamine (thiamine nitrate, CAS 532-43-4), pyridoxine (pyridoxol hydrochloride, CAS 58-56-0), and cyanocobalamin (CAS 68-19-9) exhibited at high dose levels alone or in combination dose-related antinociceptive properties in the writhing test in the mouse. Cyanocobalamin exerted a potentiating effect in the combination of the 3 vitamins.