The use of proton nuclear magnetic resonance spectrometry (1H NMR) for monitoring the reaction of epoxides with butylamine and predictive capabilities of the relative alkylation index (RAI) for skin sensitization by epoxides.

A group of alkyl epoxides was compared for their guinea pig sensitization capacity and reactivities towards a protein-surrogate substrate, n-butylamine. Instead of the previously reported use of a titration method for determination of alkylation rate, proton nuclear magnetic resonance spectrometry (1H NMR) was used. The resulting relative alkylation indices (RAIs) were calculated in order to correlate these indices with the results of the guinea pig sensitization test data. The use of 1H NMR was determined to be a useful tool for collection of in vitro reaction rates, but there was no correlation between the RAIs and guinea pig sensitization score for this group of epoxides.

Hazard communication: the case for category IV "cancer information".

Chemical hazard labeling is changing in order to convey information to a broad spectrum of the public. In addition to standard hazard warnings, supplemental information which includes the enumeration of a wide range of possible adverse effects which may occur under conditions of overexposure is also appropriate. With regard to cancer hazard warnings, known human carcinogens and even confirmed animal carcinogens are fairly easy to identify. The new American National Standards Institute, Inc., guidelines are recommending that cancer hazard warnings be limited to these known human and animal carcinogens. It seems appropriate, however, to extend cancer label statements to encompass information about certain animal tests which are indicative of some degree of carcinogenic activity, but which are not believed to be relevant to human risk in the classical sense when consideration is given to all of the data. This information concerning carcinogenicity test results and their relevance to humans can be added to label text but need not be in the form of a warning.

A collection of guinea pig sensitization test results--grouped by chemical class.

Various chemical groups were evaluated for their skin sensitization potential in the guinea pig. In general, amines, acetanilides, pyridines, piperidines, and sulfones were positive in the guinea pig test. Since these tests were done over a period of years, any further structural-related correlations or predictions should be made with caution due to variability of sample purity or differences in methodology. It is important to realize that every chemical which is positive in the guinea pig should not be construed as definitive evidence of human skin sensitization.