Urinary excretion of ethoxyacetic acid after experimental human exposure to ethylene glycol monoethyl ether.

Abstract

Ten healthy male subjects were exposed to ethylene glycol monoethyl ether (EGEE) under various conditions of exposure concentration and physical workload and their urinary excretion of ethoxyacetic acid was followed up for 42 hours. Maximal excretion of ethoxyacetic acid was reached three to four hours after the end of the four hour exposure period. Afterwards, ethoxyacetic acid excretion declined slowly with a biological half life of 21-24 hours. Ethoxyacetic acid excretion increased as the uptake of EGEE increased as a consequence of higher exposure concentration or pulmonary ventilation rate during physical exercise. On average, 23 1 + 6-3% of EGEE was recovered as ethoxyacetic acid within 42 hours and the recovery did not change as the uptake of EGEE increased. Quantitative relations between ethoxyacetic acid excretion and EGEE uptake were obtained and the relevance of ethoxyacetic acid excretion as a measure for exposure to EGEE is discussed.In recent years much effort has been given to the investigation of the metabolism and disposition of ethylene glycol ethers in animals. When ['4C]-ethylene glycol ethers were given to rats or dogs, 60-80% was recovered in urine after 48 hours.' 6 Furthermore, 10-14% of the label was recovered as 14CO2 in the expired air of treated animals when the label was in the ethanol part of the molecule.' 4 When the label was in the alkoxy part, however, only 1-5% of radioactivity appeared as C02.Methoxyacetic acid was identified as the major urinary metabolite (75-90%) in rats exposed to ethylene glycol monoethyl ether (EGME).'136 Analogously, ethylene glycol monobutyl ether (EGBE) was metabolised and excreted mostly in the form of butoxyacetic acid.7 On the other hand, two major urinary metabolites were identified in rats and dogs after the administration of the ethyl (EGEE) and isopropyl (EGiPE) ether, respectively, ethoxyacetic acid and isopropoxyacetic acid (45-30%) and their glycine conjugate (30-45%).24 Both metabolites accounted for approximately 75% of the administered dose.

Field study of the urinary excretion of ethoxyacetic acid during repeated daily exposure to the ethyl ether of ethylene glycol and the ethyl ether of ethylene glycol acetate.

“…This field study on a gro up of five women da ily exposed to a mixture of EGEE and EGEE-Ac confirms the conclusions fro m our short-term experiments regarding the relatively long biological hal f-time of the main metabolite etho xyacetic acid and the expected accumu lation effect (6,7). From these experiments with single 4-h expos ure periods, a half-time of 21-24 h was estimated.…”

“…Sur veys on occupa tional exposures to these solvents and hu man epidemiologic findings are still scarce. Recently we studied the urinary excretion of ethoxyacetic acid after short-ter m (4 h) experimenta l exposures of volunteers to the ethyl ether of ethylene glycol (EGEE) and the eth yl ether of ethylene glycol acetat e (EG EE-Ac) (6,7). We established that ethox yacetic acid could be used as a specific and sensitiv e biological expos ure parameter for bo th products .…”

“…We established that ethox yacetic acid could be used as a specific and sensitiv e biological expos ure parameter for bo th products . Ho wever, in view of its relati vely long biological hal f-time in ur ine (21-24 h) (6,7), it was th ou ght that th e accumul ation of this metab olite during the work week or even over a longer period had to be conside red . Th e present field study was undertake n to investigate this ass ump tion further.…”

Hematological Follow‐up of an Intervention Program Adding Rubber Glove‐Wearing to Local Ventilation for 2‐Ethoxyethanol Acetate‐Exposed Workers

“…Our recent paper also showed that subjects recovered very quickly from the 2-ME-induced hematological effects as the airborne concentrations of 2-ME and its major toxic metabolite, MAA (2-methoxy acetic acid), were reduced 35,36) . Since the half-life of MAA in humans (77-100 h) [37][38][39] is much longer than that of EAA (23-42 h) 40,41) , we speculate that the toxic metabolite, EAA, stays in humans a shorter time than MAA, and human subjects can recover more quickly from the 2-EEA-induced hematological effects than those induced by 2-ME. Since increasing temporal trends of hemoglobin, haematocrit, and the RBC count were found in this study for the exposed workers during the followup period, these findings suggest that reducing exposures through dermal contact can lead to the gradual amelioration of the hematological effects in 2-EEAexposed workers.…”

2‐Ethoxyethanol [BAT Value Documentation in German language, 1993]

“…Die Halbwertszeiten werden in der Literatur mit Werten zwischen 21 und 42 Stunden angegeben (22,18,21,25 (22,18,21).…”