ABSTRACT
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.
Subject(s)
Butylamines/chemistry , Epoxy Compounds/toxicity , Skin/drug effects , Alkylation , Animals , Epoxy Compounds/chemistry , Guinea Pigs , Magnetic Resonance Spectroscopy , Predictive Value of Tests , ProtonsABSTRACT
Male Fischer 344 rats were given eight daily doses of 0, 30, 100 or 300 mg/kg methoxyacetic acid by gavage. The high dose resulted in decreased body weight, severe degeneration of testicular germinal epithelium, decreased size of the thymus with depletion of thymic cortical lymphoid elements, and reductions in bone marrow cellularity resulting in depressions of red blood cell counts, hemoglobin concentration, packed cell volume, and white blood cell counts. Some of these observations were apparent to a lesser degree in rats given 100 mg/kg. The low dose produced no apparent effects during the course of the study. These toxicological properties of methoxyacetic acid are remarkably similar to ethylene glycol monomethyl ether (EGME), and the adverse effects of EGME in rats are probably the result of in vivo bioactivation of EGME to methoxyacetic acid.