Top Dose Group Research Articles

Evaluation of the oral toxicity of acetaldehyde and formaldehyde in a 4-week drinking-water study in rats

A subacute oral toxicity study of acetaldehyde and formaldehyde was carried out in rats. Groups of ten male and ten female 5-wk-old rats received one of the aldehydes in the drinking-water for a period of 4 wk, acetaldehyde being given at dose levels of 25, 125 and 675 mg/kg body weight/day and formaldehyde at dose levels of 5, 25 and 125 mg/kg body weight/day. A group of 20 males and 20 females served as controls and received unsupplemented drinking-water ad lib. An additional group of ten males and ten females was given unsupplemented drinking-water in an amount equal to the amount of liquid consumed by the group given the top dose of formaldehyde. Food and liquid intake were decreased in the groups on the top dose of both acetaldehyde and formaldehyde. Hyperkeratosis of the forestomach, observed only in the top-dose rats, was the only adverse effect of acetaldehyde detected. Effects of formaldehyde, also observed only in the top-dose group, were yellow discoloration of the fur, decreased protein and albumin levels in the blood plasma, thickening of the limiting ridge and hyperkeratosis in the forestomach, and focal gastritis in the glandular stomach. It was concluded that in this study the no-observed-adverse-effect levels of acetaldehyde and formaldehyde were 125 and 25 mg/kg body weight/day, respectively.

A carcinogenicity study in mice of a ß-adrenergic antagonist, primidolol; Increased total tumour incidence without tissue specificity

The ß-adrenergic blocking agent, primidolol hydrochloride, was administered, mixed in the diet, to mice (CD-1, Charles River, France) for 18 months. Experimental groups comprised untreated controls (100/sex) and those receiving 12.5, 25 and 50 mg drug/kg body weight (50/sex). There were no non-neoplastic lesions which could be attributed to the treatment. The pattern of tumour incidence was sex-related: in females the proportion of tumour-carrying animals was significantly higher in the top dose group (48%) than in the controls (24%), whereas in males the converse was found (30% in the top dose group vs. 48% in the controls). In the top dose female group there was no one tissue in which the tumour incidence was significantly higher than in the controls. We debate whether the analysis of total tumours in the absence of a target organ is an appropriate assay for carcinogenicity. Against a background of regulatory action towards ß-blocking agents, we discuss the possibility that the results of the present study could represent either a co-carcinogenic effect of ß-blocking agents or, alternatively, a statistical contingency.