Joan Hardy

Long-term toxicity of sorbic acid in the rat

Abstract Groups of 48 male and 48 female rats were given diets containing 0 (control), 1·5 or 10% sorbic acid for 2 yr. There was no increase in the rate or mortality in the treated rats and no changes attributable to treatment in the haematological examinations, analyses of serum, studies of renal function or histopathological examination. The relative liver and kidney weights were increased in the rats given 10% sorbic acid. The thyroid weight was increased at the same level in males but this was not thought to be due to sorbic acid treatment. This study showed no carcinogenic effect of sorbic acid at dietary levels up to 10%. The no-effect level established by this study was 1·5% of the diet, with changes of doubtful significance at the higher level (10%).

Long-term toxicity studies of sorbic acid in mice

Abstract Sorbic acid was given to groups of 48 male and 50 female mice at dietary levels of 0 (control), 1. 5 or 10% for 80 wk. Treatment had no adverse effect on the number of deaths or the incidence of histological lesions, including tumours. Compared with the controls, there were slightly lower body weights in mice given 10% sorbic acid, increased relative kidney weights at the two higher levels and increased relative liver weights at all treatment levels. The last finding and the isolated differences in the haematological examinations were not considered to represent adverse effects. It is concluded that dietary levels of sorbic acid up to 10% did not exert any carcinogenic effect and that the no-untoward-effect level was 1% of the diet.

Long-term toxicity studies of carmoisine in mice

Abstract Carmoisine was fed to mice at dietary levels of 0 (control), 0·01, 0·05, 0·25 or 1·25% for 80 wk. There were no adverse effects on mortality, weight gain, organ weights or the incidence of histopathological findings, including tumours. There was a mild anaemia in the mice given 1·25% carmoisine. It is concluded that carmoisine has no carcinogenic potential in mice at dietary levels up to 1·25% and that the no-untoward-effect level is 0·25% (equivalent to an intake of approximately 350 mg/kg/day).

Long-term toxicity of cyclohexylamine hydrochloride in mice.

Abstract Groups of 48 male and 50 female mice were fed on diets containing 0 (control), 300, 1000 or 3000 ppm cyclohexylamine hydrochloride for 80 wk. There were no effects attributable to treatment in the number of deaths, rate of body-weight gain, food intake, water intake, haematological examinations or the incidence of tumours. The only histopathological change that could be related to treatment was an increased incidence of minor hepatic changes in the females given 3000 ppm. It is concluded that CHA exerted no carcinogenic effect at dietary levels up to 3000 ppm, while the no-untoward-effect level was 1000 ppm.

The safety testing of medical plastics. I. An assessment of methods

Abstract The toxicity of a variety of plastics medical devices used in medicine and of a number of polyvinyl chloride (PVC) samples of known constitution was evaluated by tissue culture techniques, implantation tests in rabbit muscle and rat subcutaneous tissue, and examination of the systemic effects of administering extracts of the plastics to rats and mice. PVC samples containing known concentrations of an organotin compound were used as positive controls. None of the test plastics exhibited toxicity as high as that of the positive control plastics. The tissue culture technique was the most sensitive method used and toxic effects were detected with a few of the test plastics. Implantation in rabbit sacrospinalis muscle for 7 days was the most sensitive of the implant systems tested and the results showed a good correlation with tissue culture. The systemic tests on extracts failed to demonstrate toxicity, even with the positive control plastics. In view of the high sensitivity of tissue culture, positive results should not necessarily indicate rejection of a plastics material for medical use. In such a situation, additional experimental evidence is required.

Short-term toxicity of isoamyl salicylate in rats

Abstract Isoamyl salicylate was given to groups of 15 male and 15 female rats at dietary concentrations of 0 (control), 50, 500 or 5000 ppm for 13 wk. There was a decrease in weight gain at the highest dietary level accompanied by a reduced food intake, but a paired-feeding study showed that this was due to the diets unpalatability. The females given the highest dietary level drank more water than the controls and produced slightly greater volumes of more dilute urine. The relative kidney weight was increased in rats on the 500 and 5000 ppm levels without any histopathological changes. It is concluded that isoamyl salicylate was exerting a mildly nephrotoxic effect. The relative liver weight was increased at the highest level of feeding but there were no other effects attributable to treatment. The no-untoward-effect level from this study was 50 ppm of the diet, providing a mean intake of approximately 4·7 mg/kg/day.

Short-term toxicity of furfuryl mercaptan in rats.

Abstract Groups of 15 rats of each sex were given daily doses of 0, 1, 3 or 30 mg furfuryl mercaptan/kg by stomach tube for 13 wk. No effects attributable to treatment were apparent in the analysis of urine or serum, in renal function tests or in the histological examination. At the highest dose level, a decrease in body-weight gain was associated with a reduced food intake, and there were many differences in organ weights. These consisted mainly of reduced absolute weights together with increased relative values and were thought to be associated with the lower body weights. There were some increases in haemoglobin concentration and packed cell volume at the highest dose level, but these were not considered to represent a toxic effect. The results of this study indicate a no-untoward-effect level of 3 mg/kg/day, although in view of the nature of the findings at 30 mg/kg/day, the actual level seems likely to be higher.

Short-term toxicity of dimethyl sulphide in the rat

Abstract Groups of 15 male and 15 female rats were given doses of 0 (control), 2·5, 25 or 250 mg dimethyl sulphide/kg/day for 14 wk. No effects on the rate of body-weight gain, intake of food and water, results of haematological examinations, serum-enzyme levels, urinary cell excretion, renal concentration tests, organ weights or histopathological examinations were attributable to the treatment. A no-untoward-effect level of 250 mg/kg body weight/day was therefore established.

Short-term toxicity of methylphenylcarbinyl acetate in rats

Abstract Groups of rats were given daily oral doses of 0 (control), 15, 50 or 150 mg methylphenylcarbinyl acetate/kg body weight for 13 wk. There were no effects on the rate of body-weight gain, although the food and water intakes were increased in the male rats given 150 mg/kg. The relative liver and kidney weights were increased in male rats given 50 or 150 mg/kg/day. There was an increased excretion of cells in the urine of male rats given 150 mg/kg for 6 wk. No histopathological changes were seen that could be related to treatment with methylphenylcarbinyl acetate. It was concluded that the no-untoward-effect level for methylphenylcarbinyl acetate when given to rats for 13 wk was 15 mg/kg.

Long-term feeding and reproduction studies on emulsifier YN in rats

Abstract Emulsifier YN was fed to groups of 48 male and 48 female rats at dietary levels of 0 (control), 2 or 6% for 2 yr. A similar group of rats was fed on diet containing 4% soya lecithin. These treatments did not adversely affect mortality, rate of body-weight gain, haematology, urine constituents, renal concentrating ability, serum constituents or the incidence of tumours. Thyroid weight was increased in all treated groups, but this was the result of an increased incidence of parathyroid hyperplasia, thought to be due to spontaneous renal changes combined with an elevated intake of phosphate. A slightly increased incidence of myocardial fibrosis was also associated with the parathyroid hyperplasia. The incidence and severity of other histophatological changes were not influenced by feeding YN or lecithin. A two-generation study, in which the parent animals were fed diets containing 0 or 6% YN for 13 wk before mating, revealed no effects on fertility, the number of young or the growth of young during lactation, and no abnormalities were seen. The no-untoward-effect level for YN in this study was 6%, approximately equivalent to an intake by the rat of 3 g/kg/day.