Respiratory uptake and elimination of ethylene glycol monoethyl ether after experimental human exposure.

Abstract

Ten male volunteers were exposed to ethylene glycol monoethyl ether (EGEE) under various conditions of exposure concentration and physical workload. Steady state levels of retention, atmospheric clearance, and rate of uptake were reached immediately after the start of the exposure period for all experimental conditions. Retention was high (64% in resting condition) and increased as physical exercise was performed during exposure. Atmospheric clearance increased as the pulmonary ventilation rate increased. The rate of uptake was higher as exposure concentration or pulmonary ventilation rate, or both, increased. Individual uptake appeared to be governed mainly by transport mechanisms (pulmonary ventilation or cardiac output or both) and not by anthropometric factors. Respiratory elimination of unchanged EGEE accounted for < 0 4% of the total body uptake. Postexposure breath concentrations declined rapidly during the first minutes after cessation of exposure, after which a much slower decrease was observed. This slow decrease could be described by a regression equation containing two exponential terms indicating that at least two pharmacological compartments are concerned.In recent years much evidence has become available on the toxicity of ethylene glycol ethers and this has been recently reviewed.12 By contrast, data on the toxicokinetics and disposition of glycol ethers are scant. When beagle dogs were exposed to ethylene glycol monoethyl ether acetate (EGEEAc), approximately 70% of the inhaled vapour was retained at equilibrium (ca 3 h). Postexposure breath concentrations declined rapidly indicating a rapid removal of the component from the blood.3 When rats were orally dosed with "4C-labelled ethylene glycol monomethyl ether (EGME), 50-70% of the radiolabel was excreted in the urine within 48 hours, mostly in the form of methoxyacetic acid,4" whereas 15% of the radioactivity was identified as the parent compound.5Analogously, when rats were exposed to the ethylether (EGEE), the major urinary metabolite was ethoxyacetic acid and its glycine conjugate.6Depending on the position of the radiolabel, different amounts of "4C were recovered in expired air as '4CO2: when the label was in the ethanol part of the molecule, 5% appeared as exhaled '4CO2 in the first 10 hours, whereas 12-14% were recovered as "4C02 when the label appeared in the ether group.Only minor fractions in the expired air (04-3%) were identified as the parent compound and there was no indication for the presence of volatile metabolites other than C02.4-6

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, 2‐Ethoxyethyl acetate [MAK Value Documentation, 1998]

“…Physical activity also led to increased uptake. With equivalent doses, retention of 2-ethoxyethyl acetate was always somewhat lower than retention of 2-ethoxyethanol (Groeseneken et al 1986a); this was attributed to the slightly lower water solubility of the acetate. The amount of unmetabolized 2-ethoxyethyl acetate exhaled was < 0.5 % of the total amount absorbed.…”

“…A maximum of 0.4 % of the absorbed dose was exhaled unchanged. Apart from 2-ethoxyethanol, no other volatile organic compounds were detected in the exhaled air (Groeseneken et al 1986a).…”

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

“…Dies bedeutet, daß die im Körper verbleibende Menge an 2-Ethoxyethanol allein eine Funktion der Raumluftkonzentration, des Atemzeitvolumens, des Hautkontaktes und der Dauer der Exposition ist und daß eine Sättigung der Kompartimente des menschlichen Körpers durch Ethoxyethanol nicht eintritt (17). Dies ist eine Folge des Verteilungsgleichgewichtes des 2-Ethoxyethanols zwischen Blut und Luft, das ganz auf der Seite des Blutes liegt.…”

“…In diesem Zusammenhang kommt der Arbeit von Groeseneken und Mitarbeitern (17,18) besondere Bedeutung zu. Diese Autoren haben fünf Probanden bei gleichzeitiger unterschiedlicher körperlicher Belastung definierten Ethoxyethanol-Konzentrationen ausgesetzt.…”