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Biomedical subjects

B L Oser

Publications and source records attributed to B L Oser.

At least 19 recordsLinked to original sources
PubMed1987

Toxicology then and now.

A review of the history of the evolution of the science of toxicology from the original concepts of Paracelsus through the early development of analytical chemistry and its contributions to the detection of toxic substances in foods and drugs as these have led to modern regulatory rules for public protection is presented. The legal actions taken to protect against adulteration of food prior to the early steps by the U.S. Department of Agriculture that concluded with the passage of the 1906 Food and Drug Act are systematically documented. The history is reviewed of the Food and Drug Administration's role in the use of animal toxicity studies to develop reasonable criteria for safety of foods and drugs for man. Modern concepts of molecular distribution, metabolism, and excretion of substances in the animal body are discussed as these impinge on the so-called "protection index." The legal and often litigious controversies over the claimed carcinogenicity of chemical substances is documented with comments on the Delaney dilemma and the role of in vitro tests in toxicology. The review concludes with a discussion of the hazards of use of stochastic mathematical models to assess carcinogenicity and suggests that the criteria employed in the report of the Scientific Committee of the Food Safety Council are properly structured to give a contemporary evaluation of all the currently available data. References give documentation of events over the past 200 years that explain the present state of toxicology as a discipline.

Europe↗
PubMed1976

Long-term and multigeneration toxicity studies with cyclohexylamine hydrochloride.

Cyclohexylamine (CHA), the metabolite of cyclamate produced in varying degree by gastrointestinal microorganisms, was subjected to a 2-year multi-generation feeding study in rats, at dosages of 15, 50, 100, and 150 mg/kg/d. Observations included growth, feed efficiency, clinical and hematological tests, reproduction, teratology, mortality and gross and microscopic pathology. Rats from the first litters of each generation from F0 through F4 were mated to produce the next succeeding generation. Those from the second litters of F1 through F4 were also mated, half the dams being delivered by hysterotomy for teratological examination, while litters from the other half were raised to maturity. Except for some non-progressive growth retardation in the higher dosage groups, due to lower food consumption, the physical and clinical observations in the test groups fell substantially within normal limits and were not significantly different from the untreated controls. Reproduction rates were normal in all groups but at the higher dosages the size of the litters and their weaning weights were slightly reduced. At the 150 mg/kg level, histopathological examination revealed mucosal thickening of the bladder walls and evidence of renal calcification; however, no bladder tumors were seen, such as occurred in the chronic feeding study in which rats received 2500 mg/kg of a cyclamate: saccharin (10 : 1) mixture. A significantly higher incidence of testicular atrophy, characteristic of aged rats, was observed in the F0 group at the highest dosage level; however, these males continued to be fertile, in two cases up to 6 consecutive matings.

Animals↗
PubMed1975

Chronic toxicity study of cyclamate: saccharin (10: 1) in rats.

Chronic rat feeding studies were conducted on a 10: 1 cyclamate/saccharin (C/S) mixture to supplement previous investigations which had established the safety of the individual components. The test mixture was fed at dietary levels designed to furnish 500, 1120, and 2500 mg/kg body weight to groups of 35 male and 45 female rats. The protocol included observations of physical condition, growth response, food efficiency, blood, urine, and postmortem pathology. Reproduction and lactation performance was examined through 2 litters. Teratology was also investigated. Since conversion to cyclohexylamine (CHA) was found to occur in many of the rats, particularly in the higher dosage groups, it was included as an added insult in the diets of about half the animals during the last quarter of the 2-year test period. The only positive finding in these studies which proved to have crucial significance was the occurrence of papillary carcinomas in the bladders of 12 of the 70 rats fed the maximum dietary level of the mixture (equivalent to about 2500 mg/kg body weight) for periods ranging from 78 to 105 weeks (except for one earlier death). This finding was the principal reason for the removal of cyclamates from the "generally recognized as safe" (GRAS) group of non-nutritive sweeteners by the U.S. Department of Health, Education and Welfare. In the opinion of the authors, the sequelae following this precipitate ban on cyclamates, prompted by a verbal report of the preliminary findings, warrant placing the study on record for the information of toxicologists and regulatory agencies throughout the world.

Animals↗
PubMed1970

Bladder tumors in rats fed cyclohexylamine or high doses of a mixture of cyclamate and saccharin.

Papillary transitional cell tumors were found in the urinary bladders in 8 rats out of 80 that received 2600 milligrams per kilogram of body weight per day of a mixture of sodium cyclamate and sodium saccharin (10:1) for up to 105 weeks. From week 79 on, several of these rats received cyclohexylamine hydrochloride (125 milligrams per kilogram per day, the molecular equivalent of the conversion of about 10 percent of the cyclamate dosage to cyclohexylamine) in addition to the sodium cyclamate and sodium saccharin. In another study in which 50 rats were fed daily 15 milligrams of cyclohexylamine sulfate per kilogram of body weight for 2 years, eight males and nine females survived. One of the eight males had a tumor of the urinary bladder. In neither study were bladder tumors found in the control rats or in rats treated with lower doses of the compounds.

Amines↗