Urinary alkoxyacetic acids and renal effects of exposure to ethylene glycol ethers

Abstract

Objectives - Ethylene glycol ethers and their acetates are widely used in industry, because of their hydrophilic and simultaneously lipophilic properties. Ethylene glycol ethers and their acetates are mainly metabolised to alkoxyacetic acids, but there is also a minor pathway through ethylene glycol to oxalic acid. The main pathway of ethylene glycol ethers is associated with significant clinical or experimental health effects and the minor pathway is also interesting because formation of urinary stones depends principally upon the urinary concentration of oxalate and calcium. Methods - Excretion of alkoxyacetic and oxalic acids was examined among silkscreen printers for an entire working week. The aim of the study was to evaluate alkoxyacetic acids as early indicators of exposure to glycol ethers and to evaluate their toxicity to kidneys. The load of alkoxyacetic and oxalic acids was compared with the excretion of calcium, chloride, ammonia, and glycosaminoglycans (GAG). Morning urine was chosen for the main analysis, as the overall metabolite, ethoxyacetic acid (EAA), has a long elimination time from the body. Results - The excretion of calcium increased according to the urinary alkoxyacetic acid load. The excretion of ammonia and chloride was higher among the exposed workers than among the controls. The highest urinary alkoxyacetic acid loan was also associated with increased excretion of GAG, which may reflect the toxicity of metabolites of ethylene glycol ether. The excretion of GAG correlated positively with that of calcium in the printers with highest exposure. The tendency to form urinary stones was 2.4-fold higher among silkscreen printers than among office workers. Conclusion - On the basis of renal effects our study indicates the need for establishing a new biological exposure limit before a workshift that is clearly below 100 mmol ethoxyacetic acids per mol creatinine in morning urine or people occupationally exposed to ethylene glycol ethers.