Urinary excretion of phenol, catechol, hydroquinone, and muconic acid by workers occupationally exposed to benzene.

Abstract

Objectives-Animal inhalation studies and theoretical models suggest that the pattern of formation of benzene metabolites changes as exposure to benzene increases. To determine if this occurs in humans, benzene metabolites in urine samples collected as part of a cross sectional study of occupationally exposed workers in Shanghai, China were measured. Methods-With organic vapour monitoring badges, 38 subjects were monitored during their full workshift for inhalation exposure to benzene. The benzene urinary metabolites phenol, catechol, hydroquinone, and muconic acid were measured with an isotope dilution gas chromatography mass spectroscopy assay and strongly correlated with concentrations of benzene air. For the subgroup of workers (n=27) with urinary phenol >50 ng/g creatinine (above which phenol is considered to be a specific indicator of exposure to benzene), concentrations of each of the four metabolites were calculated as a ratio of the sum of the concentrations of all four metabolites (total metabolites) and were compared in workers exposed to >25 ppm v < 25 ppm. Results-The median, 8 hour time weighted average exposure to benzene was 25 ppm. Relative to the lower exposed workers, the ratio of phenol and catechol to total metabolites increased by 6.0% (p=0.04) and 22.2% (p=0.007), respectively, in the more highly exposed workers. By contrast, the ratio of hydroquinone and muconic acid to total metabolites decreased by 18.8% (p=0.04) and 26.7% (p=0.006), respectively. Similar patterns were found when metabolite ratios were analysed as a function of internal benzene dose (defined as total urinary benzene metabolites), although catechol showed a more complex, quadratic relation with increasing dose. Conclusions-These results, which are consistent with previous animal studies, show that the relative production of benzene metabolites is a function of exposure level. If the toxic benzene metabolites are assumed to be derived from hydroquinone, ring opened products, or both, these results suggests that the risk for adverse health outcomes due to exposure to benzene may have a supralinear relation with external dose, and that linear extrapolation of the toxic eVects of benzene in highly exposed workers to lower levels of exposure may underestimate risk. (Occup Environ Med 1998;55:705-711)

Hypothesis: Phenol and hydroquinone derived mainly from diet and gastrointestinal flora activity are causal factors in leukemia

“…The urinary concentrations of phenol and hydroquinone varied widely (ie 5-to 25-fold) within a given population. [49][50][51] Some studies have reported differences in phenol levels between sexes, 54 whereas others have not. 48 Variability of phenol levels among individuals appears to be greater than the difference among males and females.…”

“…The other important factors affecting reported phenol values are variation in sampling and adjustment for gravity and creatinine. Phenol levels are typically reported as a concentration, mass per mass creatinine, or total mass excreted in 24 h. Data from Refs 47,50,51,54,57,58,75,107,108. flora. Below we discuss these sources and also describe additional host and environmental factors that affect the variability of the background levels of the phenolic compounds.…”

“…However, in these and other studies, urinary phenol and hydroquinone were found to be poor predictors of lower benzene exposures. [48][49][50][51][52] For example, urinary phenol levels of workers exposed to 1 to 5 p.p.m. benzene were indistinguishable from levels in unexposed individuals.…”

“…High background concentrations of phenol, hydroquinone, catechol and 1,2,4-benzenetriol have been measured in the blood, urine and intestines of presumably unexposed humans [48][49][50][51][52][53][54][55][56][57][58][59][60][61][62] and in the blood and urine of rodents. [63][64][65] Representing measurements of hundreds of individuals in total, these studies showed that mean urinary phenol and hydroquinone levels were about 10 p.p.m.…”

Comparison of Benzene Exposure in Drivers and Petrol Stations Workers by Urinary trans,trans-Muconic Acid in West of Iran

“…The major sources of benzene in ambient air of urban areas are car exhaust and evaporation loss during the handling, distribution and storage of petrol 1,2) . Urinary metabolites that might serve as indices of occupational or environmental exposure to benzene include phenol, hydroquinone, trans, trans-muconic acid (t,t-MA), and S-phenyl mercapturic acid [3][4][5] . Of these, urinary t,t-MA concentration is recognized as a reliable biomarker which is relatively convenient to measure 6) .…”