A model for the metabolism of sulfite in mammals

The distribution of sulfite in the rabbit fits a two-compartmental open-system model ( Riegelman et al., 1968 ) characterized by rapid distribution and elimination with the rate constants of the order 0.1 to 1.0 min −1. Sulfite clearance can be calculated from this model using plasma decay data obtained after a single iv injection of sulfite, and the theoretical rate thus calculated is in satisfactory agreement with clearance determined at steady state conditions. Measurement of urinary sulfite following iv sulfite administration and demonstration of mass balance in the conversion of the remaining sulfite to sulfate using a mathematical model show that sulfite clearance occurs predominantly by metabolism to sulfate. It is concluded that sulfite clearance is primarily dependent upon the efficiency of sulfite oxidase, the enzyme catalyzing the oxidation of sulfite to sulfate. The results indicate that the efficiency of this enzyme decreases as sulfite dose increases. Preliminary experiments with one rhesus monkey suggest that the pattern of sulfite distribution and elimination is similar to that in rabbits but that the kinetics of the removal mechanisms are different. It is felt that meaningful inter- and intraspecific comparisons can be made using the technique presented, and that these comparisons would provide a quantitative basis for predictions of risks of systemic sulfite toxicity.