Acute propylene glycol ingestion

BACKGROUND: We describe a case of acute propylene glycol toxicity following ingestion of ethanol and propylene glycol-containing antifreeze in which blood lactate, serum propylene glycol, ethanol, and CO2 concentrations were serially measured. CASE REPORT: A 61-year-old man was hospitalized after acute ingestion of ethanol and automotive antifreeze. His clinical presentation and course were essentially unremarkable. Initial lab tests revealed serum ethanol concentration, 167 mg/dL, normal serum electrolytes and osmol gap, 120 mOsm/kg. Intravenous 10% ethanol infusion was begun for suspected ethylene glycol toxicity and discontinued at approximately 17 hours post-ingestion. Toxicological analysis of urine was positive for ethanol and propylene glycol, and negative for ethylene glycol, methanol, and isopropanol. Blood lactate was mildly elevated and serum CO2 concentration was normal. Gas chromatographic analysis of serial serum specimens for propylene glycol concentration revealed a maximum value of 470 mg/dL at 7 hours and a nonlinear decline to below detection limit (3 mg/dL) at 57 hours after antifreeze ingestion. The patient was discharged on hospital day 2. CONCLUSION: The propylene glycol elimination pattern, absence of significant acid-base disturbance, and minimal lactate elevation in this case are consistent with ethanol-related inhibition of propylene glycol metabolism. The effect of ethanol on clinical outcome after acute propylene glycol intoxication remains uncertain.     

Hypoglycemic coma induced by inadvertent administration of glyburide

A 79-year-old nondiabetic woman was inadvertently given a 5-mg tablet of glyburide. Blood glucose concentration was 2.6 mmol/L three hours after ingestion. The patient was discharged 9 hours after ingestion and readmitted 10 1/2 hours after ingestion, in a hypoglycemic coma (blood glucose, 0.65 mmol/L). She was treated with two bolus doses of dextrose and intravenous dextrose. Her blood glucose was abnormal until hospital day 3. On hospital day 4, she was discharged with no apparent sequelae. This patient's severe reaction may have been due to mild renal insufficiency or concurrent use of timolol. Should inadvertent administration of glyburide occur in a patient with impaired renal function, the patient should be monitored for at least 24 hours.     

Current management of ethylene glycol poisoning.

Ethylene glycol, a common antifreeze, coolant and industrial solvent, is responsible for many instances of accidental and intentional poisoning annually. Following ingestion, ethylene glycol is first hepatically metabolised to glycoaldehyde by alcohol dehydrogenase. Glycoaldehyde is then oxidised to glycolic acid, glyoxylic acid and finally oxalic acid. While ethylene glycol itself causes intoxication, the accumulation of toxic metabolites is responsible for the potentially fatal acidosis and renal failure, which characterises ethylene glycol poisoning. Treatment of ethylene glycol poisoning consists of emergent stabilisation, correction of metabolic acidosis, inhibition of further metabolism and enhancing elimination of both unmetabolised parent compound and its metabolites. The prevention of ethylene glycol metabolism is accomplished by the use of antidotes that inhibit alcohol dehydrogenase. Historically, this has been done with intoxicating doses of ethanol. At a sufficiently high concentration, ethanol saturates alcohol dehydrogenase, preventing it from acting on ethylene glycol, thus allowing the latter to be excreted unchanged by the kidneys. However, ethanol therapy is complicated by its own inherent toxicity, and the need to carefully monitor serum ethanol concentrations and adjust the rate of administration. A recent alternative to ethanol therapy is fomepizole, or 4-methylpyrazole. Like ethanol, fomepizole inhibits alcohol dehydrogenase; however it does so without producing serious adverse effects. Unlike ethanol, fomepizole is metabolised in a predictable manner, allowing for the use of a standard, validated administration regimen. Fomepizole therapy eliminates the need for the haemodialysis that is required in selected patients who are non-acidotic and have adequate renal function.     

Ethylene glycol poisoning: experiences from an epidemic in Sweden.

In 1987 two lethal adult cases of accidental ethylene glycol poisoning were given spectacular attention in the Swedish mass media. This resulted in an epidemic of intentional ethylene glycol poisonings. In addition to six cases related to alcohol abuse, another 30 severe suicidal poisonings were reported to the Swedish Poison Information Centre in five months. The clinical course and outcome in these 36 severe cases are reviewed. The primary clinical manifestations were metabolic acidosis, CNS disturbances and kidney damage with circulatory failure in the most severe cases. Mortality was 17%. Fragmentation of the normal striation in heart cells was found in two of the fatal cases and severe brain damage in all fatal poisonings. The degree of acidosis but not the serum ethylene glycol level correlated with both kidney damage and outcome. Treatment included ethanol, correction of the metabolic acidosis and dialysis. Four patients with serum ethylene glycol concentrations of 10-20 mmol/L (620-1240 mg/L) but with no or minimal metabolic acidosis were treated with ethanol alone; none of these patients developed renal damage.     

急性乙二醇中毒3例报告及文献回顾

乙二醇为防冻剂的主要成分。乙二醇主要在肝脏内先后代谢为羟乙醛、乙醇醛、乙醇酸及草酸。这些代谢特可导致代谢性酸中毒。典型临床表现通常为3个阶段：第1阶段在摄入后12h内，乙二醇致中枢神经系统抑制；第2阶段在摄入12～24h后，出现代谢性酸中毒和心肺疾病；第3阶段在摄入后24～72h。出现肾小管坏死和肾衰竭。乙二醇致死量为1．4-1．6ml／kg[成人（70kg）约为100m1]。一旦怀疑乙二醇中毒，应尽快测定乙二醇和乙醇酸血浓度明确诊断。中毒治疗原则包括早期及时洗胃，给予乙醇或甲吡唑解毒剂，血液透析，碳酸氢钠vitB6等。大多数乙二醇中毒患者经早期诊断治疗后可恢复正常。本文报告3例急性乙醇中毒，3例患者均为男性（48岁），每人服用防冻液约为150ml。2倒出现头痛有，1例出现上腹不适、兴奋、躁动。3倒患者在摄入乙醇后12～18h出现代谢性酸中毒，24h出现血尿。经洗胃和血液透析，给予法莫替丁40mg，10％葡萄糖酸钙20ml。4％碳酸氢钠静脉注射，38％白酒200ml口服。2倒治愈，1例于摄入乙二醇后29h死亡。     

Fomepizole (4-methylpyrazole) in fatal methanol poisoning with early CT scan cerebral lesions

BACKGROUND: Methanol poisoning, potentially fatal, is generally treated with the combination of ethanol as antidote, and hemodialysis. Fomepizole, a competitive inhibitor of alcohol dehydrogenase, has more recently been used, and is capable of blocking the toxic metabolism of methanol. To our knowledge, its use has never been reported as an antidote in severe methanol poisoning requiring hemodialysis. CASE REPORT: We report a case of fatal methanol poisoning (1.9 g/L on admission) suspected due to the combined presence of coma and severe metabolic acidosis with normokalaemia. CONCLUSION: The fomepizole treatment protocol (10 mg/kg by i.v. infusion over 1 hour before dialysis, repeated 12 hours later in combination with 1.5 mg/kg/h during dialysis) was simple to use and appeared effective in eliminating methanol in combination with hemodialysis. The case is also unusual in terms of severity and the early onset of cerebral lesions demonstrated by computed tomography (CT) scan.     

4-Methylpyrazole may be an alternative to ethanol therapy for ethylene glycol intoxication in man

4-Methylpyrazole (4 MP) is a strong inhibitor of alcohol dehydrogenase. Its use in acute ethylene glycol (EG) or methanol intoxication has been suggested in experimental studies about its efficacy and safety. We report three cases of accidental intoxication with ethylene glycol in man treated orally with 20 mg/kg/day of 4 MP. The treatment was maintained until plasma EG concentrations became unmeasurable. The patients were admitted early during the course of the poisoning. Their neurological status was good. A slight metabolic acidosis observed in two cases was easily corrected and did not recur. Renal function remained normal in all cases. No patient underwent hemodialysis. On admission plasma EG concentrations were 24.2 mmol/l, 13 mmol/l and 9.7 mmol/l respectively. Plasma EG half-lives were 14.5, 11.5 and 14.75 hours respectively. Plasma oxalate concentrations and the rate of urine oxalate elimination, determined in two patients, were high on admission but quickly returned to normal. Concerning possible side effects of 4 MP, a skin rash was observed in one patient and a possible eosinophilia in the others. These three cases suggest that 4 MP may decrease the metabolic consequences of EG poisoning in man and may be of therapeutic value when administered early during the course of the intoxication before coma, seizures and organic renal failure have occurred.     

American Academy of Clinical Toxicology Practice Guidelines on the Treatment of Ethylene Glycol Poisoning. Ad Hoc Committee.

Fomepizole (4-methylpyrazole, 4-MP, Antizol) is a potent inhibitor of alcohol dehydrogenase that was approved recently by the US Food and Drug Administration (FDA) for the treatment of ethylene glycol poisoning. Although ethanol is the traditional antidote for ethylene glycol poisoning, it has not been studied prospectively. Furthermore, the FDA has not approved the use of ethanol for this purpose. Case reports and a prospective case series indicate that the intravenous (i.v.) administration of fomepizole every 12 hours prevents renal damage and metabolic abnormalities associated with the conversion of ethylene glycol to toxic metabolites. Currently, there are insufficient data to define the relative role of fomepizole and ethanol in the treatment of ethylene glycol poisoning. Fomepizole has clear advantages over ethanol in terms of validated efficacy, predictable pharmacokinetics, ease of administration, and lack of adverse effects, whereas ethanol has clear advantages over fomepizole in terms of long-term clinical experience and acquisition cost. The overall comparative cost of medical treatment using each antidote requires further study.     

Role of fomepizole in the management of ethylene glycol toxicity

OBJECTIVE: To systematically review English-language articles on fomepizole administration in patients with ethylene glycol poisoning. DATA SOURCES: MEDLINE, EMBASE, Current Contents, and PubMed. Search terms were fomepizole, 4-methylpyrazole, and ethylene glycol. The search was supplemented with a bibliographic review of all relevant articles. STUDY SELECTION: All published reports of fomepizole administration in patients with ethylene glycol poisoning were reviewed, irrespective of study design. We identified one clinical trial and subsequent pharmacokinetic study, one case series, and 13 case reports. RESULTS: Fomepizole has been investigated in 70 patients in open, unblinded studies. Most patients received an intravenous loading dose, with subsequent variable maintenance doses every 12 hours until plasma ethylene glycol levels became undetectable. Additional hemodialysis treatment generally was administered when patients had renal insufficiency or ethylene glycol levels above 50 mg/dl. Many patients had detectable ethanol levels either because of coadministration or as a result of adjunctive treatment at a referring center. Poorer patient outcomes, such as death and renal insufficiency, were associated with later clinical presentation time after ingestion. At therapeutic fomepizole levels (> 8.6 mg/ml), the half-life of ethylene glycol was prolonged to over 19 hours. Fomepizole appeared to be well tolerated by most patients. CONCLUSION: Fomepizole is an effective alcohol dehydrogenase inhibitor that decreases production of ethylene glycol metabolites. Reduced mortality and morbidity are undetermined because of the small number of patients evaluated to date. Data on comparative efficacy of fomepizole versus ethanol and data on administration of fomepizole in children are limited.     

Massive Ethylene Glycol Ingestion Treated with Fomepizole Alone—A Viable Therapeutic Option

Fomepizole is used to treat and prevent toxicity from ethylene glycol poisoning. Treatment with fomepizole without hemodialysis in massive ethylene glycol ingestion has been rarely reported in the literature; however, published literature and practice guidelines recommend considering dialysis for ethylene glycol levels >50 mg/dL. We report a case of massive ethylene glycol ingestion resulting in the highest serum ethylene glycol concentration in a patient without ethanol co-ingestion who was treated with fomepizole and was not hemodialyzed. A 48-year-old male presented to the emergency department after reportedly ingesting >1liter of antifreeze in an attempt at self-harm. He denied concomitant ethanol consumption. His initial presenting serum ethylene glycol level was 700 mg/dL, with normal renal function, and a metabolic acidosis with a high anion gap. One hour after presentation, he was started on intravenous fomepizole. Treatment with fomepizole continued until the patient's plasma ethylene glycol concentration was 16 mg/dL. His metabolic acidosis quickly resolved, he had no adverse reactions to the treatment, and his renal function remained normal. Ultimately, he was discharged to a psychiatric unit without sequelae. Published literature and practice guidelines suggests considering hemodialysis initiation in patients with an ethylene glycol level >50 mg/dL. This recommendation is anecdotally, rather than evidence, based. With the potential risks inherent in hemodialysis, our case provides evidence that treatment with fomepizole without hemodialysis appears to be a viable alternative option in patients with even extremely high plasma ethylene glycol concentrations as long as their renal function is intact.     

Considerations for the treatment of ethylene glycol poisoning based on analysis of two cases

The clinical picture as well as the principles of treatment in ethylene glycol poisoning differ with the time after ingestion. These time-related differences are illustrated by two case reports. During the first hours of ethylene glycol poisoning, the patient suffers from drunkenness, vomiting and somnolence due to the intoxicant effect of ethylene glycol on the central nervous system. In the following hours a poisoning with glycolate and oxalate develops, with increasing acidosis, renal and brain damage. A patient admitted within a few hours of an overdose, with no or only slight metabolic acidosis, may be successfully treated with ethanol. If the serum concentration of ethylene glycol is very high, hemodialysis may be deferred until the necessary staff and equipment are available. If the patient is admitted with severe metabolic acidosis, hemodialysis must be started immediately. The need for ethanol administration during hemodialysis merits reevaluation.     

万古霉素致肾衰竭死亡2例

2例精神病患者因肺部感染静脉滴汪万古霉素致肾衰竭死亡。 例1为84岁男性精神病患者，因肺部感染和呼吸衰竭行气管切开。给予患者糖皮质激素、头孢他啶及依替米星治疗，后改为万古霉素1g，2次／d，静脉滴注。患者的Cr和BUN水平用药前为分别为71μmol／L和7．3mmol／L；治疗第9天分别升至223μmol／L和27.3mmol／L。患者尿量由1930ml（治疗第6天）减少至650ml（治疗第8天）。患者出现肺栓塞、急性肾衰竭、代谢性酸中毒、心律失常及浅昏迷，最后经抢救无效死亡。例2为58岁女性精神病患者，因肺部感染给予头孢吡肟、亚胺培南-西司他丁及低分子肝素钙，后改为万古霉素1g，2次／d，静脉滴注。患者的Cr和BUN水平用药前分别为87μmol／L和7．5mmol／L，用药第3天分别升至124μmol／L和14．7mmol／L，用药第6天分别升至436μmol／L和30．1mmol／L。患者尿量自用药第3天下降至900ml，用药第6天下降至200ml，并出现腹泻。诊断为急性肾衰竭，停用万古霉素，经抢救无效，于停用万古霉素第3天死亡。     

Alkyldiol antidotes to ethylene glycol toxicity in mice.

A series of alkyldiols were compared to ethanol or pyrazole as antidotes in ethylene glycol toxicity. Mouse liver alcohol dehydrogenase oxidized ethanol and a series of alkyldiols. The K_m values in millimoles per liter determined from the assays were 0.4 with ethanol, 53 with ethylene glycol, 14 with propylene glycol, 5.4 with 1,3-propanediol, 3.8 with 1,2-butanediol, 1.5 with 1,3-butanediol, 0.5 with 1,4-butanediol, 56 with 2,3-butanediol, 0.23 with 1,5-pentanediol, and 0.031 with 1,6-hexanediol. These data indicated that ethanol and the alkyldiols, with the exception of 2,3-butanediol, had higher affinities for mouse liver alcohol dehydrogenase than ethylene glycol. Propylene glycol (27.2 mmol/kg), 1,2-butanediol (11.2 mmol/kg), and 1,3-butanediol (22.3 mmol/kg) were the only alkyldiols found to protect mice. Acute and delayed toxicity and hexobarbital sleeping time studies indicated that the alkyldiols which protected the mice were, in general, the least toxic and least hypnotic of the alkyldiols. Therapeutic ratios found by dividing the 144 hr LD50 of an antidote by the dose which produced the maximum antidotal effect were 3.17 for ethanol, 2.56 for pyrazole, 6.16 for propylene glycol, 4.15 for 1.2-butanediol, and 5.11 for 1,3-butanediol. These data suggest that the alkyldiol antidotes are effective and may be safter than either ethanol or pyrazole.     

Kinetic disposition of ethanol in the neonatal piglet and hemodynamic effects in the presence and absence of 4-methylpyrazole

The hemodynamic effects of acute ethanol intoxication and the kinetic disposition of ethanol are reported for the first time in neonatal piglets under nitrous oxide anesthesia. Two hours after a single dose of ethanol (1.4 g/kg), blood pressure decreased from 76 +/- 4 to 71 +/- 4 mm Hg (p less than 0.05) and heart rate increased from 194 +/- 10 to 227 +/- 8 beats/min (p less than 0.05; means +/- SE). By 5 hr, blood pressure dropped to 67.5 +/- 4 mm Hg and heart rate increased to 239 +/- 8 beats/min. In piglets pretreated with 4-methylpyrazole, an alcohol dehydrogenase inhibitor, there was a transient increase in blood pressure (p less than 0.05) and a decrease in heart rate (p less than 0.05) immediately after the end of the ethanol infusion. However, the hemodynamic alterations observed 2 hr after ethanol treatment alone were prevented with 4-methylpyrazole. These findings indicate that ethanol metabolites play a significant role in hemodynamic alterations observed after acute ethanol intoxication. The mean ethanol metabolic rate derived from plasma data was 94 +/- 9 mg/liter/hr. This corresponded to an apparent Km of 68 +/- 3 mg/liter and a Vm of 123 +/- 11 mg/liter/hr. The Vd was 0.966 +/- 0.031 liter/kg. The metabolic rate for ethanol, derived from plasma data, correlated with in vitro alcohol dehydrogenase activity at pH 7.4 and 25 and 37 degrees C. The optimum pH for hepatic alcohol dehydrogenase activity was 9.9.     

Polyuria, Acidosis, and Coma Following Massive Ibuprofen Ingestion

Ibuprofen was the first over-the-counter nonsteroidal anti-inflammatory drug available in the United States. Despite being a common agent of ingestion, significant toxicity in overdose is rare. We report a case of a massive ibuprofen ingestion who developed polyuria, acidosis, and coma but survived, despite having a serum ibuprofen concentration greater than previous fatal cases. A 19-year-old man ingested 90 g (1,200 mg/kg) ibuprofen. He was initially awake and alert, but his level of consciousness deteriorated over several hours. Seven hours following the ingestion, he was intubated and mechanically ventilated secondary to loss of airway reflexes. He developed a lactic acidosis and polyuria, which lasted for nearly 24 h. His serum creatinine peaked at 1.12 mg/dL. An ibuprofen level drawn 7 h postingestion was 739.2 mg/L (therapeutic 5–49 mg/L). We describe a case of a massive ibuprofen overdose characterized by metabolic acidosis, coma, and a state of high urine output who survived with aggressive supportive care. This case is unique in several ways. First, ibuprofen levels this high have only rarely been described. Second, polyuria is very poorly described following ibuprofen ingestions.     

Outcomes following abuse of methanol-containing carburetor cleaners

INTRODUCTION: Carbureter cleaners may contain methanol and are abused via inhalation. Toxicity resulting from the methanol component of these products is poorly described. METHODS: We conducted a retrospective poison center chart review over a four-year period (3/98-3/02) of outcomes following methanol-containing carbureter cleaners (MCC) exposure. Inclusion criteria were: (1) use of MCC, (2) evaluation in health care facility (HCF), (3) no known co-ingestion exposure and (4) at least 12 hour follow-up. RESULTS: 33 cases were reviewed with 11 cases excluded because of significant co-ingestions. Of the remaining 22 cases the mean age was 17 [range: 14-41] years old with 90% of cases between 14 and 17 years old. Six women and 16 men were in the study. Six of 22 cases had acidosis (serum bicarbonate < or =22 mmol/L or pH < or =7.35), 100% of patients had neurological symptoms (ataxia, etc.) and 14/22 had vomiting on presentation. Three patients received treatment with ethanol (1) and fomepizole (2). All others received intravenous fluids (15) or no treatment (4). Mean serum methanol concentration was 28mg/dl [range: 0-341 with 17/22 developing acidosis. Serum methanol was obtained at a mean of 3.5 hours [range 1-7 hours] post use. All metabolic disturbances resolved within 24 hours except in one patient (41 years old) in which her disturbances resolved within 72 hours. No patient developed visual disturbances or neurological sequealae. CONCLUSIONS: Significant toxicity following inhalation of MCC was rare with symptoms improving without aggressive care (dialysis, alcohol dehydrogenase blockade).     

静脉应用伏立康唑致急性肾损伤及肾小管性酸中毒

1例80岁男性患者因术后感染给予亚胺培南西司他汀钠、万古霉素、卡泊芬净、米卡芬净及美罗培南,效果不佳,后治疗改为联用美罗培南1.0 g,1次/8 h静脉滴注及伏立康唑200 mg(首日剂量400 mg,1次/12 h),1次/12 h静脉滴注。第5～9天,实验室检查示血清肌酐(SCr)154～208μmol/L,尿素氮(BUN)24.3～35.9 mmol/L,血清胱抑素C 4.54～5.44 mg/L;血pH值7.18～7.34,氯离子122～130 mmol/L,钾离子3.4～4.1 mmol/L,标准碳酸氢盐波动于12～15 mmol/L,实际碳酸氢盐13～14 mmol/L,阴离子间隙13～14 mmol/L。尿分析示红细胞3.8～4.8个/HP,蛋白±,pH值保持在5.5。诊断为肾小管性酸中毒、急性肾损伤。第9天,伏立康唑用法改为每晨静脉滴注200 mg,每晚鼻饲给药200 mg。调整用法后第3天患者出现高氯性酸中毒、低钾血症,第11天停用伏立康唑,美罗培南继续应用。停药2 d后,患者血清SCr及BUN水平升至最高,分别达282μmol/L及49.4 mmol/L,随后逐渐降低,分别于停药后第25天和停药后34天降至正常,血气分析各项指标于停药后第25天基本恢复正常。     

Butoxyethanol ingestion with prolonged hyperchloremic metabolic acidosis treated with ethanol therapy

BACKGROUND: Severe toxic ingestions of butoxyethanol (CAS No. 111-76-2) are rare despite the prevalence of this glycol ether in products such as glass and surface cleaners. Manifestations of acute butoxyethanol toxicity include metabolic acidosis, hemolysis, hepatorenal dysfunction, and coma, but vary widely in reported cases. Furthermore, the optimal therapeutic approach is not yet established. Much of the toxicity of butoxyethanol has been ascribed to its aldehyde and acid metabolites which are similar to those produced by oxidative metabolism of methanol and ethylene glycol. Although the roles of alcohol dehydrogenase inhibition with ethanol or fomepizole and hemodialysis are clear in the case of toxic ingestions of methanol and ethylene glycol, they remain poorly defined for butoxyethanol poisoning. CASE REPORT: We report the case of a 51-year-old female who ingested up to 8 ounces of Sanford Expo White Board Cleaner (butoxyethanol and isopropanol). She developed prolonged hyperchloremic metabolic acidosis and mental status depression and was treated with ethanol therapy but not hemodialysis. This patient recovered without apparent sequelae. The kinetics of butoxyethanol metabolism in this case are described and the potential therapeutic options are discussed.     

Predictors of Ethylene Glycol Ingestion Cases Called into a Regional Poison Center

Poison center consultations for potential toxic alcohol poisonings are challenging because blood levels are typically not immediately available. The primary objective of this study was to determine whether readily obtainable laboratory values can be used to accurately and rapidly diagnose these poisonings. Over a 15-month period, patients with a history of toxic alcohol ingestion or a metabolic acidemia (pH?≤?7.30 or serum bicarbonate ≤?18 mEq/L) that prompted a poison center consultation were enrolled. A predictive logistic regression model was used to assess the combined ability of serum pH, calcium, osmolar gap, and anion gap levels to predict a final diagnosis of toxic alcohol poisoning. There were 102 subjects included in the analysis. A total of 44% (45/102) patients had a final diagnosis of ethylene glycol (EG) poisoning. Higher levels of calcium, osmolar gap, and anion gap were independently associated with statistically significant or marginally significant increases in the odds of a final diagnosis of EG poisoning. The c-index was estimated at 0.81, indicating that the model showed a reasonable ability to discriminate EG cases from others. The final model had a sensitivity and specificity of 78% and 89%, respectively, and positive and negative predictive values of 84% and 83% respectively. The combination of elevated calcium, osmolar gap, and anion gap is associated with a high likelihood of EG poisoning, but clinician gestalt is still essential for its diagnosis. Further refinement of the model is needed.     

Ethanol-induced accumulation of ethylene glycol monoalkyl ethers in rats

In adult female SPF Sprague-Dawley rats, exposed for 2 hours to 2-methoxy-ethanol (ME, 1600 ppm), 1-acetoxy-2-methoxy-ethane (AME, 800 ppm), 2-ethoxy-ethanol (EE, 420 ppm), or 1-acetoxy-2-ethoxy-ethane (AEE, 170 ppm) the blood level of ME (after ME or AME) or EE (after EE or AEE) was considerably increased after pretreatment with ethanol (20 mmol/kg b.w. i.p.). (ME and EE are metabolites of AME and AEE, respectively.) After i.p. co-administration of ME (10 mmol/kg), EE (10 mmol/kg) or butoxy-ethanol (BE, 2.5 mmol/kg) with ethanol (20 mmol/kg) the blood level of ME, EE, and BE remained nearly constant as long as ethanol levels in blood were above 3 mmol/l. Repeated i.p. dosing (5 times one injection per hour) with EE (4 mmol/kg) or ME (5 mmol/kg) plus ethanol (8 or 10 mmol/kg) each resulted in an almost complete accumulation of both ether compounds in the blood. Blood levels of ethanol were increased significantly after EE, but only slightly after ME administration. The prolonged retention of ME, EE, or BE is due to an inhibition of the degradation of these compounds following the competition with ethanol at the alcohol dehydrogenase, the common metabolizing enzyme. This study has demonstrated that glycol ether derivatives are extremely accumulated as long as only very low levels of ethanol are present in blood. Therefore, it is concluded that the elimination of the investigated glycol ethers after occupational exposure can be retarded in alcoholized employees causing an increased health risk of these chemicals following the consumption of alcoholic beverages.