Search PubMed⌕ Search

Biomedical subjects

F J Roe

Publications and source records attributed to F J Roe.

At least 55 records · Page 3Linked to original sources
PubMed1985

Safety of nitroimidazoles.

The nitroimidazoles used in the treatment of anaerobic infection are well-tolerated by patients. With the possible exception of neurotoxic effects associated with high dosage, signs and symptoms of toxicity are transient and disappear soon after withdrawal of treatment. Teratogenicity tests in animals have given negative results in the case of metronidazole, ornidazole and tinidazole, and in the case of metronidazole no evidence of any adverse effect on the outcome of pregnancy was seen in women treated for trichomoniasis at various times during gestation, including the first trimester. The observed low general toxicity of nitroimidazoles is consistent with the non-occurrence of nitroreduction, as is the absence of chromosomal aberration in the circulating lymphocytes of patients receiving prolonged metronidazole therapy for Crohn's disease. Carcinogenicity tests involving the prolonged exposure of rats, mice and hamsters to a range of doses of metronidazole have given mixed results. In response to high doses, mice exhibited an increased risk of developing lung tumours, and female rats developed more liver tumours than controls. However, these effects may have been non-specific consequences of prolonged high dosage. No excesses of tumours were seen in response to lower doses and two tests in hamsters gave negative results. A follow-up of 771 women treated, 10 or more years previously, with metronidazole revealed no excess cancer risk. Thus the available information suggests that metronidazole, tinidazole and other 5-nitroimidazoles effective against anaerobic microorganisms are very safe both in the short-term and in the long-term.

Abnormalities, Drug-Induced↗
PubMed1984

Perspectives in carbohydrate toxicology with special reference to carcinogenicity.

All chemicals, even water and salt, can cause toxic effects if they are given to humans or laboratory animals in high enough doses. Similarly, the incidences of various kinds of neoplasm may be increased non-specifically in animals by the administration of innocent chemicals by an inappropriate route or in doses that are excessive enough to disturb normal nutritional, or hormonal status or interfere with mineral balance. High dietary concentrations of sorbitol or xylitol, if fed to laboratory rats cause enlargement of the caecum, increased absorption of calcium from the gut, increased urinary excretion of calcium, pelvic and corticomedullary nephrocalcinosis, acute tubular nephropathy, urinary calculus formation and both hyperplasia and neoplasia of the adrenal medulla. High dietary concentrations of lactose give rise to a similar spectrum of effects when given in excessive dosage to laboratory rats. Recent evidence suggesting that in the rat, but not in the mouse or in man, excessive calcium absorption stimulates the adrenal medulla is reviewed. In the mouse, but not in the rat or in man, a biologically significant amount of glycolic acid, which is a minor metabolite of xylitol in all three species, is converted to oxalate which then appears in the urine. Although the increase in urinary oxalate in the mouse is only about 20% of normal, this is enough in animals fed on diets containing 10% or 20% xylitol to predispose to bladder stone formation, and the prolonged presence of stones in the bladders, particularly of mice, in turn, predisposes to bladder tumour development. Neither bladder stones nor bladder tumours are seen in rats because biologically significant conversion of glycolate to oxalate does not occur. Studies in humans exposed up to 1 g/xylitol/kg body weight/day have revealed no evidence of increased urinary oxalate excretion. It is concluded that both the bladder tumours seen in mice, in response to 10% or 20% xylitol in the diet, and the adrenal tumours seen in rats, in response to 20% sorbitol or 20% xylitol in the diet, are laboratory artefacts. In other words, humans exposed to "normal" levels of these agents would be at no risk of developing either of these kinds of neoplasm.

Animal Nutritional Physiological Phenomena↗
PubMed1983

The carcinogenic potential of twelve refined mineral oils following long-term topical application.

Twelve mineral oils, originating from naphthenic and paraffinic stocks and variously refined, were evaluated for their potential to induce cutaneous neoplasia in female CF1 mice. The oils were applied to the shorn dorsal skin for up to 78 weeks, using several different treatment regimes. The sole acid/earth refined naphthenic spindle oil was a moderately potent cutaneous carcinogen. By comparison, the 11 oils, processed by other refining routes, were less carcinogenic or non-carcinogenic to murine skin. Two of the 11 oils were weak cutaneous carcinogens viz, a naphthenic spindle oil refined only by mild hydrotreatment and a paraffinic spindle oil refined by mild solvent extraction and 'Ferrofining'. All 9 remaining oils had been solvent-extracted as part of the secondary refining process; none induced malignant tumours, although solitary benign tumours of the treated site were recorded after exposure to 3 oils. The cutaneous carcinogenic potential of the test oils did not correlate well with their potential to induce epidermal hyperplasia at the treated site. Consequently, hyperplasia caused after short term exposure is of little value for distinguishing between carcinogenic and non-carcinogenic oils.

Administration, Topical↗
PubMed1983

Toxicologic evaluation of metronidazole with particular reference to carcinogenic, mutagenic, and teratogenic potential.

The gastrointestinal tract and nervous system are the main targets for metronidazole toxicity. With the possible exception of certain neurotoxic effects in a few heavily treated patients, all the toxic effects of metronidazole are transient and reversible on withdrawal of the drug. Properly designed tests for embryotoxicity and teratogenicity in rats, rabbits, and mice have produced convincingly negative results, and no adverse effects on the fetus have been observed in women given the drug for trichomoniasis during various stages of pregnancy. The antimicrobial activity of metronidazole is thought to depend on its nitroreduction to form short-lived cytotoxic metabolites capable of reacting with deoxyribonucleic acid. It is therefore perhaps not surprising that metronidazole has been reported to be mutagenic for certain strains of Salmonella typhimurium. Metronidazole gave negative results in the mouse micronucleus test and no increase in sister chromatid exchanges or chromosomal aberrations in cultured human lymphocytes. Prolonged exposure to metronidazole in the treatment of patients with Crohn's disease was not associated with any increase in the frequency of chromosomal aberrations. Prolonged high-dose exposure of mice to metronidazole led to an increased incidence of lung tumors in three separate studies and to a suggestive increase in lymphoreticular neoplasia in female animals in one of the studies. These effects are probably nonspecific, since major effects on the incidence of neoplasms of the same and other kinds have been produced by merely varying the amount of a standard diet that mice consume. A reported excess of liver tumors in rats exposed to metronidazole can be explained by the fact that the authors failed to age standardize their data despite a big and highly significant beneficial effect of the drug on survival. Two carcinogenicity studies in hamsters have given entirely negative results. The follow-up for 10 or more years of 771 women first treated with metronidazole between 1960 and 1969 for trichomoniasis revealed no excess of any form of cancer attributable to treatment, and no excess cancer risk has so far come to light in the Kaiser-Permanente follow-up of nearly 2500 patients given at least one prescription of metronidazole between 1969 and 1973. At the present time it is reasonable to conclude that this highly useful, and sometimes life-saving, drug is essentially free of cancer risk or other serious toxic side effects.

Abnormalities, Drug-Induced↗
PubMed1982

The effect of dose and vehicle on early tissue damage and regenerative activity after chloroform administration to mice.

The relationship between the acute toxicity of orally-administered chloroform and its long-term tumorigenic potential was studied in male mice of the CFLP outbred Swiss albino mouse strain. A single dose of approximately 18 mg CHCl3/kg had no detectable acute toxic effect on the liver or kidneys and did not stimulate regenerative activity, whereas both toxicity and subsequent tissue regeneration were observed with single doses of about 60 mg/kg or higher. The severity of the toxic effects and regenerative changes was greater when corn oil was used as a vehicle for chloroform than when the vehicle was a toothpaste base. In earlier long-term studies in mice of the same strain, kidney tumours occurred in males given 60 mg/kg/day throughout life but not in mice given 17 mg/kg/day. The tumour response was greater when the 60-mg/kg/day dose was given in an oily vehicle than when it was given in toothpaste. The findings are consistent with the hypothesis that early acute toxic change and subsequent repair are a sine qua non for tumorigenesis in the kidney and liver in response to chloroform.

Animals↗
PubMed1982

Bacterial mutagenicity studies on chloroform in vitro.

Chloroform was tested for mutagenicity in the Salmonella/microsome assay using five strains of Salmonella typhimurium. In view of previous reports describing the development of liver and kidney tumours in some experiments involving long-term administration of chloroform to rats and mice, the mutagenicity tests were carried out in the absence of any S-9 microsomal-enzyme preparation and in the presence of S-9 microsomal-enzyme preparations derived from (a) livers and (b) kidneys of rats and mice previously exposed to the microsomal-enzyme inducer Aroclor 1254. No evidence of potential mutagenicity was observed under any of the test conditions. To determine whether the findings might have been influenced by the volatility of the chloroform, the test organisms were exposed to chloroform vapour, but again chloroform gave no indication of potential mutagenicity. Taken in conjunction with already published data from mutagenicity studies with chloroform, it appears unlikely that the tumours observed in some long-term rodent studies are attributable to a genotoxic action of the compound.

Animals↗
PubMed1982

A comparison of the effects of lactose and of two chemically modified waxy maize starches on mineral metabolism in the rat.

Diets containing 30% by weight of waxy maize starch, lactose monohydrate, acetylated distarch phosphate (EEC No. 1414) or acetylated distarch adipate (EEC No. 1422) were fed to weanling female Specified Pathogen-Free Sprague-Dawley rats for 1 yr and to similar 9-month-old rats for 34 wk. Behaviour and general health were unaffected by the different diets and there were no diet-related differences in food consumption. AT the end of the experiment with 9-month-old rats the mean body weight of the animals receiving lactose was significantly lower than that of the controls receiving starch. The animals receiving the modified starches were slightly but not significantly heavier than the controls at the end of both experiments. The main treatment-related changes in rats on the three test diets were (1) caecal enlargement, (2) increased urinary excretion of calcium, (3) increased renal calcification as measured by chemical analysis of renal tissue obtained at autopsy and (4) increased medullary and pelvic nephrocalcinosis as assessed histopathologically. Acetylated distarch adipate had a slightly greater effect on the above parameters than acetylated distarch phosphate but both modified starches had less effect than lactose. The calcium content of the kidneys, as measured by chemical analysis or histopathology, increased with age, even in the animals receiving the control diet. This change may be due to excessively high concentrations of calcium and phosphorus in all the diets, including the control diet. Cortico-medullary mineral deposits were not a feature in these studies possibly because the diets were not deficient in magnesium. The importance of correct dietary formulation in long-term toxicity studies is emphasized.

Animals↗
PubMed1981

Safety evaluation of cimetidine: 54 month interim report on long-term study in dogs.

Cimetidine [N"-cyano-N-methyl-N'-2[(5-methylimidazol-4-yl)methylthio]ethyl guanidine] was administered orally to eight male and four female beagle dogs at a dose level of 144 mg per kg bodyweight per day. Four males and two females received placebo tablets. Dosing began in March 1976. During the first 26 months of dosing the animals became obese--the control animals more so than the cimetidine-treated. Since month 27 feeding time was restricted and there has been an overall weight loss. Some control animals are still obese. One control male and one dosed female have been killed because they developed convulsions. No treatment-related effects on haematology, clinical biochemistry, urinalysis, electrocardiography or clinical condition have been seen. Three out of the five surviving control animals but none of the 11 surviving cimetidine-dosed animals have developed cataracts. Biopsies of gastric mucosa taken during endoscopy in months 41, 47 and 53 have shown no changes attributable to cimetidine treatment.

Administration, Oral↗