Comparative urinary excretion of ethoxyacetic acid in man and rat after single low doses of ethylene glycol monoethyl ether.
Male rats were given a single oral dose of ethylene glycol monoethyl ether (EGEE), the dose ranging from plausible human exposures (0.5-1 mg/kg) to doses reported in the literature (100 mg/kg). Urinary excretion of ethoxyacetic acid (EAA) and its glycine conjugate was followed up to 60 h after dosing and compared to data of experimentally exposed human volunteers. In rats, the mean elimination half-life of free as well as conjugated EAA was 7.2 h for all doses. EAA was excreted partly as a glycine conjugate (on average 27%), the extent of conjugation being independent of the dose. The conjugation with glycine showed a clearly diurnal variation, the lowest extent being found during the night. The relative amount of EGEE recovered in urine as EAA was only 13.4% for the lowest dose, but increased as the administered dose of EGEE was higher, indicating that EGEE was metabolised at least in two parallel pathways of which one pathway becomes saturated at relatively low doses. In man, urinary excretion of EAA for equivalent low doses of EGEE differed from that in the rat by a longer elimination half-life (mean 42 h), by the absence of EAA conjugates and by a higher recovery.
Groeseneken
D
D
Department of Occupational and Insurance Medicine, K.U. Leuven, Louvain, Belgium.
Veulemans
H
H
Masschelein
R
R
Van Vlem
E
E
D000085:Acetates / Q000652:urine*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D005026:Ethylene Glycols / Q000378:metabolism*; D005998:Glycine / Q000378:metabolism; D006207:Half-Life; D006801:Humans; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D013045:Species Specificity
D000085:Acetates; D005026:Ethylene Glycols; C034096:ethoxyacetic acid; C021296:2-ethoxyethanol; D005998:Glycine