Principles for the safety evaluation of flavouring substances.

This paper reviews efforts by various organizations to develop principles and procedures for the safety evaluation of flavouring substances. Critical factors considered in safety evaluation of these substances include their level of human intake, ease of metabolism to innocuous end-products and the margin of safety between no-observed-effect levels in animal studies and human intakes. These factors form the basis for the principles and criteria laid out in this paper.

Granulomas in the livers of humans and Fischer rats associated with the ingestion of mineral hydrocarbons: a comparison.

Ninety-day feeding studies were conducted in Fischer 344 rats using a series of highly refined mineral hydrocarbons which included mineral oils and waxes representative of those used in consumer products and food applications. The series included materials which had been refined by oleum or hydrogenation. The materials tested were representative of the range of carbon chain lengths, molecular weights, and viscosities which are currently in use.

Granulomas in the livers of humans and fischer rats associated with the ingestion of mineral hydrocarbons: A comparison.

Ninety-day feeding studies were conducted in Fischer 344 rats using a series of highly refined mineral hydrocarbons which included mineral oils and waxes representative of those used in consumer products and food applications. The series included materials which had been refined by oleum or hydrogenation. The materials tested were representative of the range of carbon chain lengths, molecular weights, and viscosities which are currently in use.

Chemical carcinogens and human cancer.

The minor role of the cancer research community in efforts to control human cancer by testing chemicals in rote bioassays and empirical "carcinogen" labelling is discussed. Although the causation of certain cancers by chemical carcinogens was a prominent segment of cancer research for many years this is no longer the case. The field has become the province of governmental regulators and little evidence suggests that an impact on the incidence of human cancer has resulted.

Toxicology, disappointments and promise.

The development of toxicology during the past 50 years is traced, with particular reference to chronic testing and carcinogenesis. The increasing dichotomy between the study of human disease and the accumulation of routine experimental data is examined. It is suggested that a drastic change is needed in toxicological approaches that replaces rote testing with more thoughtful scientific research.

Carcinogenicity of methapyrilene hydrochloride, mepyramine hydrochloride, thenyldiamine hydrochloride, and pyribenzamine hydrochloride in Sprague-Dawley rats.

Four histamine antagonists, methapyrilene, thenyldiamine, mepyramine and pyribenzamine were tested for carcinogenicity in rats by continuous application in drinking water. Only methapyrilene displayed significant carcinogenic effects, inducing liver tumors in a dose-related pattern. Analogues not containing a thiophene ring (mepyramine, pyribenzamine) did not exhibit neoplastic effects under the experimental conditions.

Carcinogenic activity of hexachlorobenzene in mice and hamsters.

Hexachlorobenzene (HCB) has been used as a fungicide, is a contaminant of various pesticides and is a by-product in the manufacture of many other chlorinated hydrocarbons. In Turkey, HCB caused an epidemic of toxic porphyria involving several thousand people between 1955 and 1959. The aim of the present studies was to determine the chronic toxicity of HCB after prolonged oral administration and we report here that HCB is carcinogenic in mice and hamsters.

Evaluation of the toxicity and carcinogenicity of hair dyes in Swiss mice.

The chronic toxicologic and carcinogenic potential of two oxidative and twelve non-oxidative hair dyes has been evaluated. The dyes were skin painted up to 3 times weekly on groups of 60 male and 60 female Eppley Swiss mice. Treatments were carried out for 20 months followed by terminal sacrifice.