The Specificity of trans,trans- Muconic Acid as a Biological Indicator for Low Levels of Environmental Benzene

Abstract

trans, trans -Muconic acid (MA), a urinary ring-opened metabolite of benzene, is a newly proposed biological indicator of benzene exposure which should enable the assessment of low levels of exposure to this ubiquitous environmen tal pollutant. The presence of MA in the urine of non-occupationally exposed people is generally attributed to world-wide contamination of the environ ment by benzene (arising from such sources as smoking and other combustion, urban pollution from vehicles and maybe by food contamination). But, exami nation of the scientific literature reveals that a common food preservative and fungistatic agent, sorbic acid (SA), is also converted into MA, although in trace amounts. The permitted maximum concentration of SA in food ranges from 0.2 to 2 g·kg -1 and the acceptable daily intake (ADI-FAO/WHO) is 25 mg. kg -1 of body weight. The question, therefore, is whether the amount of MA excreted as a metabolite of SA can make a significant contribution to the total MA excreted. If so, the specificity of MA as a biological indicator for benzene exposure assessment is in doubt. Four experiments in 2 subjects were set up to try to clarify the effect on the urinary excretion of MA of the experimental ingestion of SA (2 doses of 447 and 44.7 mg); urine samples were collected, in fractions as voided, for 24 h before and 48 (or 60 h) after SA ingestion. The total amounts of MA excreted during the 24 h before ingestion of SA were respectively 79 and 34 mg in the 2 subjects; after ingestion of 447 or 44.7 mg of SA the total excretion of MA was at least respectively 20 and 2 times the background levels (when the single dose of SA was ingested) and at least 10 and 3 times (when the SA was given in divided doses). The elimination of MA after ingestion of SA was complete in 24 h; the peak concentrations always appeared in the first urine sample after the ingestion of the substance and they were more than 90 times and more than 3 times the basal levels respectively for a single ingestion of 447 and 44.7 mg of SA. The rate of biotransformation of SA into MA was, on average, 0.34 and 0.21 % in the 2 subjects; on the basis of these levels of biotransformation, it appears that 0.3-0.5 g of ingested SA would suffice to lead to excretion of 1 mg of MA, a quantity corresponding to that believed to derive from benzene exposure at levels greater than 1 ppm. Only in urine collected many hours after the last meal can a possible additive effect of MA from SA be ignored.