Substances Included Synonyms

Therapeutic Toxic Class

A)

Specific Substances

1) Athylenglykol-monoathylather (German)
2) Cellosolve
3) Dowanol EE
4) Ektasolve EE
5) Ether monoethylique de L'ethylene-glycol (French)
6) Ethyl Cellosolve
7) Ethylene Glycol Ethyl Ether
8) Ethylene glycol monoethyl ether
9) Etoksyetylowy Alkohol (Polish)
10) Glycol ethyl ether
11) Glycol monoethyl ether
12) Hydroxy ether
13) Jeffersol EE
14) NCI-c 54853
15) Oxitol
16) Poly-solv EE
17) RCRA WASTE NUMBER: U227
18) RCRA WASTE NUMBER: U359
19) CAS 110-80-5
20) 2-ethoxyethanol
21) ETHOXYETHANOL
22) GLYCOL ETHYL ETHER (ETHYLENE GLYCOL ETHYL ETHER)

1.2.1) MOLECULAR FORMULA
1) C4-H10-O2

Available Forms Sources

A)

1) Ethylene glycol ethyl ether (EEGE) is a colorless and almost odorless liquid. It is miscible in aqueous and organic solutions, and has a low vapor pressure (Budavari, 1996).

B)

1) EEGE is prepared from ethylene oxide and ethanol (Budavari, 1996).

C)

1) Used as lacquer for nitrocellulose; agricultural chemical; detergent for automobile engine; coatings for polyester resin denatured by siloxane; carrier for printing ink; manufacture of vitamin B12; solvent for cortisone acetate; and a protective coating (Budavari, 1996; ITI, 1988).
2) 2 ethoxyethanol (EGEE) is one of the glycol ethers contained in positive photoresists used in the wafer fabrication process for semiconductor manufacturing (Paustenbach, 1988).
3) For increased stability of emulsions; used in varnish removers, cleansing solutions, dye baths (Budavari, 1996)

Overview

Life Support

A)

Clinical Effects

0.2.1)

A) USES: Ethylene glycol ethyl ether ((EGEE) also known as 2-ethoxyethanol, oxitol, ethyl cellosolve, dowanol EE, polysolve EE, hydroxyether, ethylene glycol monoethyl ether, cellosolve solvent, glycol ethyl ether) is a solvent with many commercial and industrial applications. It is a colorless liquid with a faint, sweet odor. EGEE is found in multi-purpose cleaners such as varnish removers and degreasing solutions due to its ability to dissolve oils, resins, grease, waxes, nitrocellulose, and lacquers. It is also used as an anti-icing additive in the manufacture of brake fluids, aviation fuels, and automotive anti-stall and detergent additives.
B) TOXICOLOGY: Acidosis might occur secondary to metabolism via alcohol dehydrogenase to alkoxyacids. Clinical information is very limited; however, EGEE exposure would be expected to cause CNS depression and pose a risk of aspiration pneumonitis similar to other solvents.
C) EPIDEMIOLOGY: Acute poisoning is relatively rare but this chemical is used widely in industrial settings and chronic exposure may occur in many workers among certain industries.
D) WITH POISONING/EXPOSURE

1) MILD TO MODERATE EXPOSURE: With acute inhalational exposure, eye and upper respiratory tract irritation may occur. Other symptoms that may occur include CNS symptoms such as headache, drowsiness, weakness, staggered gait, and tremor. In chronic inhalation exposures, there have been reports of dizziness, leg swelling, gynecologic disorders (benign neoplasms, cervical erosions, menstrual disorders), leukopenia, decreased sperm counts, teratogenic effects in fetuses of pregnant women, and kidney injury (hematuria, albuminuria). Direct eye contact exposure may cause immediate pain, corneal and conjunctival irritation, and tearing that usually clears after one day.
2) SEVERE EXPOSURE: Vertigo, coma, cyanosis, pulmonary edema, and repeated tonic clonic spasms have been reported after ingestion of EGEE.

0.2.4)

A) Animal studies have shown immediate discomfort along with conjunctival and corneal irritation.

0.2.7)

A) Reports of ethylene glycol ethyl ether (EGEE) toxic exposures in humans are limited. It is expected that EGEE toxic exposures may cause CNS depression.
B) Somnolence and ataxia have been observed in animals.

0.2.8)

A) Gastrointestinal hemorrhage was documented in exposed animals.

0.2.9)

A) Mild reversible liver injury was detected in apparently asymptomatic animals.

0.2.10)

A) Female enamel workers had increased incidence of benign neoplasms, cervical erosions, and menstrual disorders.
B) Renal toxicity may occur following large oral ingestions.
C) Animal studies cited severe kidney injury, hematuria, and albuminuria.

0.2.11)

A) Acidosis has not been well documented in human exposure but might occur following significant ingestion.

0.2.13)

A) Anemia and leukopenia have been observed in exposed animals.

0.2.20)

A) Birth defects, predominantly involving the heart and the skeletal system, have been reported in humans and animals.
B) Exposed male workers were demonstrated to have significantly lower sperm counts.

1) A case report of males exposed to EGME and EGEE suggested that semen quality may have been affected (Welch et al, 1988).
2) Based on an animal study, rats given EGEE had testicular degeneration with a significant depletion of haploid cells and a disproportionate ratio of diploid and tetraploid cells. Thus, the toxic effects in the male reproductive system may be related to the disproportion of testicular germ cells (Yoon et al, 2003).
3) The semen of factory workers exposed to ethylene glycol monomethyl ether was analyzed, a lower pH was noted, but no differences in sperm count or morphology were observed (Shih et al, 2000).

0.2.21)

A) At the time of this review, no studies were found on the potential carcinogenic activity of EGEE in humans.

Laboratory Monitoring

A)

B)

C)

D)

E)

Treatment Overview

0.4.2)

A) MANAGEMENT OF MILD TO MODERATE TOXICITY

1) Treatment is symptomatic and supportive.

B) MANAGEMENT OF SEVERE TOXICITY

1) Treatment is symptomatic and supportive. There is no clinical experience with severe ethylene glycol ethyl ether (EGEE) poisoning. If severe toxicity or metabolic acidosis develops, consider treatment with fomepizole or ethanol and hemodialysis. INHALATION EXPOSURE: Move patient from toxic environment to fresh air. Monitor for respiratory distress and administer oxygen as needed. Treat bronchospasms with inhaled beta-2-agonists. DERMAL EXPOSURE: Remove contaminated clothing and wash exposed areas thoroughly with soap and water. EYE EXPOSURE: Remove contact lenses and irrigate exposed eyes with normal saline or water for at least 15 minutes. If symptoms continue after irrigation, an ophthalmologic examination is indicated.

C) DECONTAMINATION

1) PREHOSPITAL: Gastrointestinal decontamination is contraindicated because of the risk for CNS depression and aspiration. Administer oxygen if respiratory irritation develops. Remove contaminated clothing and wash exposed skin with soap and water. Irrigate exposed eyes with water or normal saline.
2) HOSPITAL: Gastrointestinal decontamination is contraindicated because of the risk for CNS depression and aspiration. Administer oxygen if respiratory irritation develops. Remove contaminated clothing and wash exposed skin with soap and water. Irrigate exposed eyes with water or normal saline.

D) ANTIDOTE

1) There is no specific antidote for the treatment of ethylene glycol ethyl ether exposure.
2) Although ethanol and fomepizole are not approved for use in ethylene glycol ethyl ether poisoning, they may be effective in preventing formation of the acid metabolites and lessening toxicity.

a) FOMEPIZOLE: Fomepizole is administered as a 15 mg/kg loading dose, followed by four bolus doses of 10 mg/kg every 12 hours. If therapy is needed beyond this 48 hour period, the dose is then increased to 15 mg/kg every 12 hours for as long as necessary. Fomepizole is also effectively removed by hemodialysis; therefore, doses should be repeated following each round of hemodialysis.
b) ETHANOL: The in vitro affinity for ethanol is less than ethylene glycol ethyl ether for alcohol dehydrogenase, so it may be less effective. Ethanol is given to maintain a serum ethanol concentration of 100 to 150 mg/dL. This can be accomplished by using a 5% to 10% ethanol solution administered IV through a central line. Intravenous therapy dosing, which is preferred, is 0.8 g/kg as a loading dose (8 mL/kg of 10% ethanol) administered over 20 to 60 minutes as tolerated, followed by an infusion rate of 80 to 150 mg/kg/hr (for 10% ethanol, 0.8 to 1.3 mL/kg/hr for a nondrinker; 1.5 mL/kg/hr for a chronic alcoholic). During hemodialysis, either add ethanol to the dialysate to achieve 100 mg/dL concentration or increase the rate of infusion during dialysis (for 10% ethanol, 2.5 to 3.5 mL/kg/hr). Oral ethanol may be used as a temporizing measure until IV ethanol or fomepizole can be obtained, but it is more difficult to achieve the desired stable ethanol concentration. The loading dose is 0.8 grams/kg (4 mL/kg of 20% {40 proof) ethanol diluted in juice administered orally or via a nasogastric tube. Maintenance dose is 80 to 150 mg/kg/hour (of 20% {40 proof) ethanol; 0.4 to 0.7 mL/kg/hour for a nondrinker; 0.8 mL/kg/hour for a chronic alcoholic). Concentrations greater than 30% (60 proof) ethanol should be diluted. Blood ethanol levels must be monitored hourly and adjusted accordingly.

E) ENHANCED ELIMINATION

1) There is no clinical experience; however, hemodialysis might be useful to clear the parent compound and metabolites and to reverse metabolic acidosis after severe poisoning.

F) PATIENT DISPOSITION

1) HOME CRITERIA: Asymptomatic, inadvertent (taste or sip of a household product), dermal or inhalation exposures may be managed at home.
2) OBSERVATION CRITERIA: All patients with significant ingestions should be sent to the emergency department for observation. Patients with significant ingestions should be observed for at least 24 hours. Delayed symptom onset of 8 to 18 hours has been seen following ingestions of other glycol ethers. Symptomatic patients with less significant exposures may be sent home if their symptoms are clearly improving and discharge is clinically indicated.
3) ADMISSION CRITERIA: Patients with worsening symptoms should be admitted to the hospital for further treatment and evaluation. Admission to ICU may be required based on the severity of symptoms. Criteria for discharge includes clearly improving symptoms in patients who are clinically stable.
4) CONSULT CRITERIA: Consult a medical toxicologist or Poison Center for assistance in managing patients with severe toxicity or in whom diagnosis is unclear. Consult a nephrologist for severe acidosis, renal issues, or potential hemodialysis. Consultation with a critical care physician may be needed in cases of severe toxicity.

G) PITFALLS

1) Prolonged observation may be needed after ingestion of ethylene glycol ethyl ether (EGEE) due to delayed onset of symptoms. Consider the possibility of multidrug involvement when managing a suspected EGEE ingestion.

H) TOXICOKINETICS

1) Ethylene glycol ethyl ether is readily absorbed through skin, lungs and the gastrointestinal tract. It is absorbed through human skin at a rate of 0.796 mg/cm2. It is metabolized by alcohol dehydrogenase to alkoxyacids, with peak ethoxyacetic acid levels 3 to 4 hours after a 4-hour inhalational exposure. There may be accumulation of ethoxy acetic acid urine metabolites with prolonged exposure. Following inhalational exposure, an average of 23% was excreted in urine as ethoxyacetic acid. Less than 0.4% is eliminated unchanged through the lungs after inhalation. The terminal half-life of ethoxyacetic acid was 21 to 24 hours following inhalation.

I) DIFFERENTIAL DIAGNOSIS

1) Consider exposure to other glycol ethers or toxic alcohols that may cause CNS depression and/or acidosis.

Range Of Toxicity

A)

Clinical Effects

Summary Of Exposure

A)

B)

C)

D)

1) MILD TO MODERATE EXPOSURE: With acute inhalational exposure, eye and upper respiratory tract irritation may occur. Other symptoms that may occur include CNS symptoms such as headache, drowsiness, weakness, staggered gait, and tremor. In chronic inhalation exposures, there have been reports of dizziness, leg swelling, gynecologic disorders (benign neoplasms, cervical erosions, menstrual disorders), leukopenia, decreased sperm counts, teratogenic effects in fetuses of pregnant women, and kidney injury (hematuria, albuminuria). Direct eye contact exposure may cause immediate pain, corneal and conjunctival irritation, and tearing that usually clears after one day.
2) SEVERE EXPOSURE: Vertigo, coma, cyanosis, pulmonary edema, and repeated tonic clonic spasms have been reported after ingestion of EGEE.

Heent

3.4.1)

A) Animal studies have shown immediate discomfort along with conjunctival and corneal irritation.

3.4.3)

A) IRRITATION: Animal studies have shown immediate discomfort, conjunctival, and corneal irritation following ocular exposure (Grant & Schuman, 1993).

Respiratory

3.6.2)

A) ACUTE LUNG INJURY

1) WITH POISONING/EXPOSURE

a) Although not reported with ethylene glycol ethyl ether (EGEE), hyperventilation, non-cardiogenic pulmonary edema and acute respiratory distress syndrome (ARDS) has been reported following large ingestions of other glycol ethers. It is expected that similar respiratory toxicity may occur with EGEE exposures.

Neurologic

3.7.1)

A) Reports of ethylene glycol ethyl ether (EGEE) toxic exposures in humans are limited. It is expected that EGEE toxic exposures may cause CNS depression.
B) Somnolence and ataxia have been observed in animals.

3.7.2)

A) CENTRAL NERVOUS SYSTEM DEFICIT

1) WITH POISONING/EXPOSURE

a) INHALATION EXPOSURES may result in the following:

1) Ataxia, tremor, somnolence, lethargy, headache, dysarthria, blurred vision, coma, and personality changes have been reported after industrial inhalation exposure to other related glycol ethers (HSDB , 2001). It is expected that exposures to ethylene glycol ethyl ether (EGEE) may also result in similar CNS signs and symptoms.

b) ORAL EXPOSURES may result in the following:

1) Ingestion of other related glycol ethers has resulted in confusion, disorientation, agitation, motor restlessness, and coma. It is expected that large oral ingestions of ethylene glycol ethyl ether (EGEE) may result in similar toxicities.

c) CASE REPORT: A 44-year-old woman drank about 40 mL of ethylene glycol ethyl ether (EGEE) by mistake and became vertiginous and unconscious shortly after exposure. On examination, she had cyanosis, pulmonary edema, repeated tonic-clonic spasms, and acetone on her breath. With oxygen and other supportive measures, she recovered completely after 44 days (Fucik, 1969).

B) DIZZINESS

1) WITH POISONING/EXPOSURE

a) Exposure to ethylene glycol monoethyl ether was studied in 32 female workers in factories manufacturing photopolymer sensitization plates and compared with 20 female subjects working in the same factories without potential exposure. Control subjects were exposed to 0.56 ppm; workers were exposed to 6.44 ppm. The most common complaints were dizziness and leg swelling, with the same frequencies seen in both groups (Wang et al, 2004).

3.7.3)

A) ANIMAL STUDIES

1) CNS DEPRESSION

a) Somnolence and ataxia were observed in rats given 185 to 380 mg/kg SC ethylene glycol ethyl ether (EGEE) for 4 weeks (Stenger et al, 1971).
b) Effects on the central nervous system were much less than those of other ethylene glycol ethers (Von Oettingen & Jirouch, 1931).

Gastrointestinal

3.8.1)

A) Gastrointestinal hemorrhage was documented in exposed animals.

3.8.3)

A) ANIMAL STUDIES

1) GI HEMORRHAGE

a) Hemorrhage of the stomach and intestines were reported in oral and inhalational studies in animals (Laug et al, 1939).

Hepatic

3.9.1)

A) Mild reversible liver injury was detected in apparently asymptomatic animals.

3.9.3)

A) ANIMAL STUDIES

1) HEPATOCELLULAR DAMAGE

a) Mild reversible liver injury was detected in the histology of apparently asymptomatic animals (Laug et al, 1939; Stenger et al, 1971).

Genitourinary

3.10.1)

A) Female enamel workers had increased incidence of benign neoplasms, cervical erosions, and menstrual disorders.
B) Renal toxicity may occur following large oral ingestions.
C) Animal studies cited severe kidney injury, hematuria, and albuminuria.

3.10.2)

A) LESION OF CERVIX

1) WITH POISONING/EXPOSURE

a) GYNECOLOGIC DISORDERS: Female enamel workers exposed to ethylene glycol monomethyl ether and other solvents had 2.5 to 9.4 times as many GYNECOLOGIC DISORDERS (benign neoplasms, cervical erosions, and menstrual disorders) than comparison groups (Syrovadko & Malsheva, 1977).

B) CRUSH SYNDROME

1) WITH POISONING/EXPOSURE

a) Renal tubular necrosis with proteinuria and hematuria has been reported following oral ingestion of other glycol ethers and ethylene glycol. However, unlike ethylene glycol, oxalate crystals have not been observed in the urine (HSDB , 1995). Similar toxicity may be expected following oral ingestions of ethylene glycol ethyl ether (EGEE).

3.10.3)

A) ANIMAL STUDIES

1) RENAL FUNCTION ABNORMAL

a) Severe kidney injury, hematuria, and albuminuria have been reported in animals following single and repeated exposure (Gross et al, 1938; Laug et al, 1939; Werner et al, 1943; Stenger et al, 1971; Kasparov et al, 1972).

Acid-Base

3.11.1)

A) Acidosis has not been well documented in human exposure but might occur following significant ingestion.

3.11.2)

A) ACIDOSIS

1) WITH POISONING/EXPOSURE

a) High anion gap metabolic acidosis has not been well documented in human exposures but might occur following significant ingestion.

Hematologic

3.13.1)

A) Anemia and leukopenia have been observed in exposed animals.

3.13.2)

A) ANEMIA

1) WITH POISONING/EXPOSURE

a) Hemoglobin, red blood cell volume, and red blood cell count were significantly lower compared to controls in male factory workers following exposure to EGEE (Shih et al, 2000).

B) LEUKOPENIA

1) WITH POISONING/EXPOSURE

a) An industrial hygiene survey was conducted to identify exposure to ethylene glycol monoethyl ether acetate (EGEEA) of two groups of shipyard painters, a low exposure group (n = 30) and a high exposure group (n = 27). Mean white blood cell counts were significantly lower in the high risk group along with an increase in leukopenia (Kim et al, 1999).

3.13.3)

A) ANIMAL STUDIES

1) LEUKOPENIA

a) Anemia and leukopenia have been observed with increased number of immature white blood cells among exposed animals (Werner et al, 1943; Stenger et al, 1971; Nagano et al, 1979).

Reproductive

3.20.1)

A) Birth defects, predominantly involving the heart and the skeletal system, have been reported in humans and animals.
B) Exposed male workers were demonstrated to have significantly lower sperm counts.

1) A case report of males exposed to EGME and EGEE suggested that semen quality may have been affected (Welch et al, 1988).
2) Based on an animal study, rats given EGEE had testicular degeneration with a significant depletion of haploid cells and a disproportionate ratio of diploid and tetraploid cells. Thus, the toxic effects in the male reproductive system may be related to the disproportion of testicular germ cells (Yoon et al, 2003).
3) The semen of factory workers exposed to ethylene glycol monomethyl ether was analyzed, a lower pH was noted, but no differences in sperm count or morphology were observed (Shih et al, 2000).

3.20.2)

A) HUMAN DATA

1) A clinical and cytologenic study of offspring of females occupationally exposed to ethylene glycol monomethyl ether demonstrated that the offspring of women exposed during pregnancy had characteristic dysmorphic features not found in the children of women who were not pregnant during the exposure. These results suggest that EGME is a teratogen, however, the study had several limitations including no controls for other possible exposures (El-Zein et al, 2002).

B) CONGENITAL ANOMALY

1) HUMAN EXPERIENCE - The rate of birth defects was 10% in offsprings of female enamel workers exposed to ethylene glycol monomethyl ethers and other solvents compared to 3.9% in controls. The predominant defects involved the heart and the foot (Syrovadko & Malsheva, 1977).

C) ANIMAL STUDIES

1) Administration by several routes to pregnant rats has caused embryonic deaths and fetal abnormalities such as skeletal defects and impaired behavioral performance (Stenger et al, 1971; Nelson et al, 1981) 1982; (Johnson, 1984).
2) Multiple defects have been similarly reported in rabbits exposed to EGEE at doses greater than 50 ppm (Andrews et al, 1981) Tinston et al, 1983).
3) Teratogenic effects observed in several animal species following inhalation exposures are reviewed in Wess (1992) and include: testicular atrophy, testicular lesions, skeletal defects, cardiovascular defects, kidney defects, and visceral malformations.
4) EGEE has reduced fertility in male experimental animals, and has also been teratogenic. It caused birth defects of the soft tissues in rabbits (Andrew & Hardin, 1984) and stunted fetal growth and caused skeletal defects in rats (Andrew & Hardin, 1984). In this latter study, EGEE was embryotoxic at doses which were also toxic to the mothers.
5) EGEE was marginally teratogenic in rabbits exposed to an airborne concentration of 175 ppm, but was not teratogenic at a concentration of 50 ppm (Doe, 1984). EGEE was fetotoxic and caused skeletal and cardiovascular defects in rats exposed by skin application (Hardin, 1982). It was teratogenic and embryotoxic in rats and rabbits exposed by inhalation (Hardin et al, 1981).
6) EGEE was not teratogenic in rabbits or mice when injected subcutaneously at doses of 25 or 100 mcL/kg/day, respectively; however, it was teratogenic in rats (Stenger et al, 1971).
7) Behavioral and neurochemical effects in the offspring of rats treated with EGEE were antagonized early, but not late, in pregnancy by ethanol (Nelson & Brightwell, 1984; Nelson et al, 1981).

3.20.3)

A) HUMANS

1) One report of menstrual disorders and birth defects was found in women exposed to EGEE and other chemicals (Syrovadko & Malysheva, 1977). These effects could not be attributed to EGEE alone because of mixed exposures.

B) ANIMAL STUDIES

1) Animal studies show minimal effects on maternal weight gain with exposure to EGEE levels of 50 ppm or less (Andrews et al, 1981) Tinston et al, 1983; (Johnson, 1984).

3.20.5)

A) ANIMAL STUDIES

1) TESTICULAR ATROPHY and DECREASED SPERM COUNT and percent normal morphology have been observed in animals following single or chronic exposures (Morris et al, 1942; Nagano et al, 1979; Oudiz & Zenick, 1986; Hurtt & Zenick, 1986; Wess, 1992; CDC, 1992).
2) Rats given EGEE were found to have testicular degeneration with a significant depletion of haploid cells as well as a disproportionate ratio of diploid and tetraploid cells. The authors concluded that the toxic effects in the male reproductive system may be related to the disproportion of testicular germ cells (Yoon et al, 2003).
3) Workers using 2EE as a binder slurry in metal casting had exposures ranging from nondetectable to 24 ppm. Their average sperm count per ejaculate was lower than that of the unexposed controls (117 vs 154 million sperm per ejaculate, p=0.05) after correcting for age, alcohol, tobacco, caffeine, urogenital disorders, and other illnesses (Ratcliffe et al, 1989).
4) Female fertility, as well as male fertility, was depressed in mice given EGEE in the drinking water; however, no histological abnormalities were apparent in the females (Lamb et al, 1984).

Carcinogenicity

3.21.1)

A) IARC Carcinogenicity Ratings for CAS110-80-5 (International Agency for Research on Cancer (IARC), 2016; International Agency for Research on Cancer, 2015; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2010; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2010a; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2008; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2007; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2006; IARC, 2004):

1) Not Listed

3.21.2)

A) At the time of this review, no studies were found on the potential carcinogenic activity of EGEE in humans.

3.21.4)

A) LACK OF EFFECTS

1) EGEE did not cause cancer in a 2-year feeding study in rats (Clayton & Clayton, 1982).

Laboratory Monitoring

Monitoring Parameters Levels

4.1.1)

A) Monitor vital signs and mental status.
B) Monitor serum electrolytes, renal function, and urinalysis in symptomatic cases or after a significant ingestion.
C) If mixed ingestion is suspected, monitor serum ethanol, methanol, and ethylene glycol concentrations as indicated.
D) In occupational exposures, obtain end of shift urine samples at the end of the work week. The metabolite 2-ethoxyacetic acid is measured in the urine and the biological exposure index is 100 mg/g creatinine.
E) In occupational exposures, determine airborne exposure of workers using charcoal tube.

4.1.2)

A) BLOOD/SERUM CHEMISTRY

1) Monitor serum electrolytes in symptomatic cases or after a significant ingestion.
2) If mixed ingestion is suspected, monitor serum ethanol, methanol, and ethylene glycol concentrations as indicated.
3) Obtain testing as indicated to monitor renal function.

4.1.3)

A) URINARY LEVELS

1) Ethoxyacetic acid in the urine indicates exposure to ethylene glycol ethyl ether (EGEE) (Smallwood et al, 1984) NIOSH, 1986).

B) URINALYSIS

1) Obtain urinalysis in symptomatic cases (look for oxalate crystals and hemoglobin).

4.1.4)

A) OTHER

1) MONITORING

a) Monitor vital signs and mental status.
b) Monitoring of occupational exposures includes direct biological monitoring by taking end of shift urine samples at the end of the work week. The metabolite 2-ethoxyacetic acid is measured in the urine and the biological exposure index is 100 mg/g creatinine (Occupational Safety & Health Administration (OSHA), 2012).
c) Determination of a worker's airborne exposure is made using a charcoal tube with samples then treated with 95:5 methylene chloride:methanol and subsequent analysis via gas chromatography using a flame ionization detector (Occupational Safety & Health Administration (OSHA), 2012).

Methods

A)

1) Using gas chromatography and alkylation with pentafluorobenzylbromide, alkoxyacetic acid concentrations in the range of 0.1 to 200 mg/L could be determined with an average imprecision of plus/minus 3.5% (Groeseneken et al, 1989).

Treatment

Life Support

A)

Patient Disposition

6.3.1)

6.3.1.1) ADMISSION CRITERIA/ORAL

A) Patients with worsening symptoms should be admitted to the hospital for further treatment and evaluation. Admission to ICU may be required based on the severity of symptoms. Criteria for discharge includes clearly improving symptoms in patients who are clinically stable.

6.3.1.2) HOME CRITERIA/ORAL

A) Asymptomatic, inadvertent ingestion (taste or sip of a household product) , dermal or inhalation exposures may be managed at home.

6.3.1.3) CONSULT CRITERIA/ORAL

A) Consult a medical toxicologist or Poison Center for assistance in managing patients with severe toxicity or in whom diagnosis is unclear. Consult a nephrologist for severe acidosis, renal issues, or potential hemodialysis. Consultation with a critical care physician may be needed in cases of severe toxicity.

6.3.1.5) OBSERVATION CRITERIA/ORAL

A) All patients with significant ingestions should be sent to the emergency department for observation. Patients with significant ingestions should be observed for at least 24 hours. Delayed symptom onset of 8 to 18 hours has been seen following ingestion of other glycol ethers. Symptomatic patients with less significant exposures may be sent home if their symptoms are clearly improving and discharge is clinically indicated.

Monitoring

A)

B)

C)

D)

E)

Oral Exposure

6.5.1)

A) Gastrointestinal decontamination is contraindicated because of the risk for CNS depression and aspiration.

6.5.2)

A) Gastrointestinal decontamination is contraindicated because of the risk for CNS depression and aspiration.
B) NASOGASTRIC TUBE

1) Consider simple nasogastric tube aspiration for recent large ingestions, if the airway is protected.

6.5.3)

A) SUPPORT

1) Treatment is symptomatic and supportive. There is no clinical experience with severe ethylene glycol ethyl ether (EGEE) poisoning. If severe toxicity or metabolic acidosis develops, consider treatment with fomepizole or ethanol and hemodialysis.

B) MONITORING OF PATIENT

1) Monitor vital signs and mental status.
2) Monitor serum electrolytes, renal function, and urinalysis in symptomatic cases or after a significant ingestion.
3) If mixed ingestion is suspected, monitor serum ethanol, methanol, and ethylene glycol concentrations as indicated.
4) In occupational exposures, obtain end of shift urine samples at the end of the work week. The metabolite 2-ethoxyacetic acid is measured in the urine and the biological exposure index is 100 mg/g creatinine.

C) ACUTE LUNG INJURY

1) ONSET: Onset of acute lung injury after toxic exposure may be delayed up to 24 to 72 hours after exposure in some cases.
2) NON-PHARMACOLOGIC TREATMENT: The treatment of acute lung injury is primarily supportive (Cataletto, 2012). Maintain adequate ventilation and oxygenation with frequent monitoring of arterial blood gases and/or pulse oximetry. If a high FIO2 is required to maintain adequate oxygenation, mechanical ventilation and positive-end-expiratory pressure (PEEP) may be required; ventilation with small tidal volumes (6 mL/kg) is preferred if ARDS develops (Haas, 2011; Stolbach & Hoffman, 2011).

a) To minimize barotrauma and other complications, use the lowest amount of PEEP possible while maintaining adequate oxygenation. Use of smaller tidal volumes (6 mL/kg) and lower plateau pressures (30 cm water or less) has been associated with decreased mortality and more rapid weaning from mechanical ventilation in patients with ARDS (Brower et al, 2000). More treatment information may be obtained from ARDS Clinical Network website, NIH NHLBI ARDS Clinical Network Mechanical Ventilation Protocol Summary, http://www.ardsnet.org/node/77791 (NHLBI ARDS Network, 2008)

3) FLUIDS: Crystalloid solutions must be administered judiciously. Pulmonary artery monitoring may help. In general the pulmonary artery wedge pressure should be kept relatively low while still maintaining adequate cardiac output, blood pressure and urine output (Stolbach & Hoffman, 2011).
4) ANTIBIOTICS: Indicated only when there is evidence of infection (Artigas et al, 1998).
5) EXPERIMENTAL THERAPY: Partial liquid ventilation has shown promise in preliminary studies (Kollef & Schuster, 1995).
6) CALFACTANT: In a multicenter, randomized, blinded trial, endotracheal instillation of 2 doses of 80 mL/m(2) calfactant (35 mg/mL of phospholipid suspension in saline) in infants, children, and adolescents with acute lung injury resulted in acute improvement in oxygenation and lower mortality; however, no significant decrease in the course of respiratory failure measured by duration of ventilator therapy, intensive care unit, or hospital stay was noted. Adverse effects (transient hypoxia and hypotension) were more frequent in calfactant patients, but these effects were mild and did not require withdrawal from the study (Wilson et al, 2005).
7) However, in a multicenter, randomized, controlled, and masked trial, endotracheal instillation of up to 3 doses of calfactant (30 mg) in adults only with acute lung injury/ARDS due to direct lung injury was not associated with improved oxygenation and longer term benefits compared to the placebo group. It was also associated with significant increases in hypoxia and hypotension (Willson et al, 2015).

D) ACIDOSIS

1) METABOLIC ACIDOSIS: Treat severe metabolic acidosis (pH less than 7.1) with sodium bicarbonate, 1 to 2 mEq/kg is a reasonable starting dose(Kraut & Madias, 2010). Monitor serum electrolytes and arterial or venous blood gases to guide further therapy.

E) FOMEPIZOLE

1) Fomepizole (4-MP) is not FDA approved for glycol ether poisoning and there are no published reports describing its use in humans with glycol ether poisoning. Theoretically, it should be as useful as ethanol. Fomepizole is a specific antagonist of alcohol dehydrogenase, and has been demonstrated to be highly effective in the treatment of ethylene glycol poisoning (Battistella, 2002; Druteika et al, 2002; Sivilotti et al, 2000; Borron et al, 1999; Brent et al, 1999).
2) DOSE

a) An initial loading dose of 15 mg/kg is intravenously infused over 30 minutes followed by doses of 10 mg/kg/every 12 hours for 4 doses, then 15 mg/kg every 12 hours until ethylene glycol concentrations are below 20 mg/dL (Prod Info ANTIZOL(R) IV injection, 2006).
b) HEMODIALYSIS: The frequency of dosing should be increased during dialysis. If dialysis is begun 6 hours or more since the last fomepizole dose the next scheduled dose should be administered. Dosing during dialysis should be increased to every 4 hours (Prod Info ANTIZOL(R) IV injection, 2006).

1) If the last fomepizole dose was administered one to three hours before completion of dialysis, half of the next scheduled dose should be administered at the completion of dialysis. If the last fomepizole dose was administered more than 3 hours before completion of hemodialysis, the next scheduled dose should be administered when dialysis is completed.

3) INDICATIONS

a) Anion gap metabolic acidosis associated with a history of ethylene glycol ethyl ether ingestion.
b) Any symptomatic patient with a history of ethylene glycol ethyl ether ingestion.
c) A good history of substantial ethylene glycol ethyl ether ingestion.
d) Keep in mind that EGEE serum levels are not routinely available, and interpretation is difficult since a toxic range has not been established. Thus, the endpoint of therapy will often be arbitrary.

F) ETHANOL

1) EFFICACY

a) The role of ethanol therapy in preventing toxicity of ethoxyethanol is uncertain. No human studies evaluating efficacy in poisoned patients are available.
b) In vivo experiments in animals have shown marked inhibition of elimination of ethoxyethanol (EE) during ethanol administration, an indication that ethanol competes with alcohol dehydrogenase (ADH) for metabolism (Romer et al, 1985).
c) The presence of the ethoxyacetic acid metabolite, presumably via metabolism by alcohol dehydrogenase, provides a theoretical mechanism for benefit of ethanol.
d) However, the in vitro affinity of EE for ADH is higher than the affinity of ethanol for ADH.

2) INDICATIONS

a) Anion gap metabolic acidosis associated with a history of ethylene glycol ethyl ether ingestion.
b) Any symptomatic patient with a history of ethylene glycol ethyl ether ingestion.
c) A good history of substantial ethylene glycol ethyl ether ingestion.
d) Keep in mind that EGEE serum levels are not routinely available, and interpretation is difficult since a toxic range has not been established. Thus, the endpoint of ethanol therapy will often be arbitrary.

3) ETHANOL THERAPY

a) CONCENTRATIONS AVAILABLE (V/V)

1) In the United States, 5% or 10% (V/V) ethanol in 5% dextrose for intravenous infusion is no longer available commercially (Howland, 2011). Ethanol 10% (V/V) contains approximately 0.08 gram ethanol/mL.
2) ABSOLUTE ETHANOL or dehydrated ethanol, USP contains no less than 99.5% volume/volume or 99.2% weight/weight of ethanol with a specific gravity of not more than 0.7964 at 15.56 degrees C. Absolute ethanol is hygroscopic (absorbs water from the atmosphere) and when exposed to air may be less than 99.5% ethanol by volume (S Sweetman , 2002).

b) PREPARATION OF 10% V/V ETHANOL IN A 5% DEXTROSE SOLUTION

1) A 10% (V/V) solution can be prepared by the following method (Howland, 2011):

a) If available, use sterile ethanol USP (absolute ethanol). Add 55 mL of the absolute ethanol to 500 mL of 5% dextrose in water for infusion. This yields a total volume of 555 mL. This produces an approximate solution of 10% ethanol in 5% dextrose for intravenous infusion (Howland, 2011).

4) PRECAUTIONS

a) HYPOGLYCEMIA

1) Hypoglycemia may occur, especially in children. Monitor blood glucose frequently (Howland, 2011; Barceloux et al, 2002).

b) CONCURRENT ETHANOL

1) If the patient concurrently has ingested ethanol, then the ethanol loading dose must be modified so that the blood ethanol level does not exceed 100 to 150 mg/dL (Barceloux et al, 2002).

c) DISULFIRAM

1) Fomepizole is preferred as an alcohol dehydrogenase inhibitor in patients taking disulfiram. If fomepizole is not available, ethanol therapy should be initiated in those patients with signs or symptoms of severe poisoning (acidemia, toxic blood level) despite a history of recent disulfiram (Antabuse(R)) ingestion.
2) The risk of not treating these patients is excessive, especially if hemodialysis is not immediately available.
3) Administer the ethanol cautiously with special attention to the severity of the "Antabuse reaction" (flushing, sweating, severe hypotension, and cardiac dysrhythmias).
4) Be prepared to treat hypotension with fluids and pressor agents (norepinephrine or dopamine). Monitor ECG and vital signs carefully. Hemodialysis should be performed as soon as adequate vital signs are established, and every effort should be made to obtain fomepizole.

5) LOADING DOSE

a) INTRAVENOUS LOADING DOSE

1) Ethanol is given to maintain a patient’s serum ethanol concentration at 100 to 150 mg/dL. This can be accomplished by using a 5% or 10% ethanol solution administered intravenously through a central line (10% ethanol is generally preferred due to the large volumes required for 5%). Intravenous therapy dosing, which is preferred, is 0.8 g/kg as a loading dose (8 mL/kg of 10% ethanol) administered over 20 to 60 minutes as tolerated. Begin the maintenance infusion as soon as the loading dose is infused (Howland, 2011).

b) ORAL LOADING DOSE

1) Oral ethanol may be used as a temporizing measure until intravenous ethanol or fomepizole can be obtained, but it is more difficult to achieve the desired stable ethanol concentrations. The loading dose is 0.8 g/kg (4 mL/kg) of 20% (40 proof) ethanol diluted in juice administered orally or via a nasogastric tube(Howland, 2011).

6) MAINTENANCE DOSE

a) MAINTENANCE DOSE

1) Maintain a serum ethanol concentration of 100 to 150 mg/dL. Intravenous administration is preferred, but oral ethanol may be used if intravenous is unavailable(Howland, 2011; Barceloux et al, 2002).

INTRAVENOUS ADMINISTRATION OF 10% ETHANOL
Non-drinker to moderate drinker	80 to 130 mg/kg/hr (0.8 to 1.3 mL/kg/hr)
Chronic drinker	150 mg/kg/hr (1.5 mL/kg/hr)
ORAL ADMINISTRATION OF 20% (40 proof) ETHANOL*
Non-drinker to moderate drinker	80 to 130 mg/kg/hr (0.4 to 0.7 mL/kg/hr) orally or via nasogastric tube
Chronic drinker	150 mg/kg/hr (0.8 mL/kg/hr) orally or via nasogastric tube
*Diluted in juice

b) MAINTENANCE DOSE/ETHANOL DIALYSATE

1) During hemodialysis maintenance doses of ethanol should be increased in accordance with the recommendation given below, or ethanol should be added to the dialysate to achieve a concentration of 100 milligrams/deciliter (Pappas & Silverman, 1982).

c) MAINTENANCE DOSE/ETHANOL-FREE DIALYSATE

1) Maintain a serum ethanol concentration of 100 to 150 mg/dL(Howland, 2011; Barceloux et al, 2002):

INTRAVENOUS ADMINISTRATION OF 10% ETHANOL - 250 to 350 mg/kg/hr (2.5 to 3.5 mL/kg/hr)
ORAL ADMINISTRATION OF 20% (40 proof) ETHANOL* - 250 to 350 mg/kg/hr (1.3 to 1.8 mL/kg/hr) orally or via nasogastric tube
*Diluted in juice

2) Variations in blood flow rate and the ethanol extraction efficiency of the dialyzer will affect the dialysance(McCoy et al, 1979).
3) If the ethanol dialysance ((CL)D) is calculated, the infusion rate during dialysis (Kod) can be individually adjusted using the following expression (McCoy et al, 1979):

Kod = Vmax x   Cp   + (CL)D x Cp
             -------
             Km + Cp
where Cp = desired blood ethanol level
*  Vmax = 175 mg/kg/hr in chronic ethanol drinkers 
*  Vmax = 75 mg/kg/hr in non-chronic drinkers
*  Km = 13.8 mg/dL

7) PEDIATRIC DOSE

a) There is very little information on ethanol dosing in the pediatric patient (Barceloux et al, 2002). The loading dose and maintenance infusion should be the same as for an adult non-drinker. Loading dose is 0.8 g/kg (8 mL/kg) of 10% ethanol infused over 1 hour, maintenance dose is 80 mg/kg/hr (0.8 mL/kg/hr) of 10% ethanol (Howland, 2011).
b) Blood ethanol concentration should be initially monitored hourly and the infusion rate should be adjusted to obtain an ethanol concentration of 100 to 150 mg/dL (Howland, 2011; Barceloux et al, 2002).

1) Monitor blood glucose and mental status frequently during therapy (Howland, 2011). Ethanol-induced hypoglycemia is more common in children (Barceloux et al, 2002) and children may develop more significant CNS depression.

8) MONITORING PARAMETERS

a) ETHANOL CONCENTRATION

1) Blood ethanol concentrations should be determined every 1 to 2 hours until concentrations are maintained within the therapeutic range (100 - 150 mg/dL). Thereafter concentrations should be monitored every 2 to 4 hours. Any change in infusion rate will require monitoring every 1 to 2 hours until the therapeutic range is reached and maintained (Barceloux et al, 2002).

b) ADDITIONAL MONITORING

1) Monitor serum electrolytes and blood glucose, monitor for CNS depression (Howland, 2011).

9) DURATION OF THERAPY

a) SERUM CONCENTRATIONS AVAILABLE: Ethanol therapy should be continued until the following criteria are met:

1) Glycol ether blood concentration, measured by a reliable technique, is no longer detectable.
2) Glycol ether-induced acidosis (pH, blood gases), clinical findings (CNS, hyperventilation), electrolyte abnormalities (calcium, potassium), and osmolal gap have resolved.
3) Glycol ether serum concentrations are not routinely available and a toxic range has not been established.

b) NO SERUM CONCENTRATIONS AVAILABLE: There is no data to guide the decision to terminate therapy. Treat until the patient's clinical findings resolve. Observe closely for recurrent toxicity after ethanol is discontinued.

1) If the clinical findings have not resolved, it may indicate the continued presence of glycol ether, metabolites, or both or some other etiology.

c) Metabolite concentrations have not been studied in blood (Rambourg-Schepens et al, 1988; Groeseneken et al, 1986b). The biological half-life of ethoxyacetic acid (ethylene glycol monoethyl ether metabolite) in man following inhalation exposure is 21 to 24 hours (Groeseneken et al, 1986a).
d) Serum osmolality may not be indicative of exposure (Lund et al, 1983).

10) MONITORING OF PATIENT

a) ETHANOL/ETHYLENE GLYCOL ETHYL ETHER INGESTION: Patients who have concurrently ingested ethanol and ethylene glycol ethyl ether may have a normal acid-base profile and urinalysis. Consider implementing the ethanol treatment regimen in these patients. Determine blood ETOH level before beginning ETOH therapy and modify loading dose accordingly.
b) ETHANOL DOSING: (Concurrent ingested ethanol)

1) To modify the loading dose for the patients who have concurrently ingested ethanol use the following equation to calculate the loading dose:

1) LD = {100 mg/dL - existing ethanol plasma concentration(mg/dL)} x (apparent Vd)

2) Note the loading dose obtained by this method is the amount of pure ethanol in milligrams/kilogram. It must be converted for intravenous and oral use to milliliters/kilogram. This can be accomplished by using the relationship:

1) LD(mL/kg) = LD(mg/kg) / {(specific gravity of ethanol) x (concentration as a fraction)}

3) Ten percent (V/V) ethanol for intravenous infusion:

1) LD(mL/kg) = LD(mg/kg) / {790 mg/mL x (10/100)}

4) 95 percent (V/V) ethanol for oral use:

1) LD(mL/kg) = LD(mg/kg) / {790 mg/mL x (95/100)}

5) Calculation of loading dose assumes instantaneous absorption.

Inhalation Exposure

6.7.1)

A) Move patient from the toxic environment to fresh air. Monitor for respiratory distress. If cough or difficulty in breathing develops, evaluate for hypoxia, respiratory tract irritation, bronchitis, or pneumonitis.
B) OBSERVATION: Carefully observe patients with inhalation exposure for the development of any systemic signs or symptoms and administer symptomatic treatment as necessary.
C) INITIAL TREATMENT: Administer 100% humidified supplemental oxygen, perform endotracheal intubation and provide assisted ventilation as required. Administer inhaled beta-2 adrenergic agonists, if bronchospasm develops. Consider systemic corticosteroids in patients with significant bronchospasm (National Heart,Lung,and Blood Institute, 2007). Exposed skin and eyes should be flushed with copious amounts of water.

Eye Exposure

6.8.1)

A) EYE IRRIGATION, ROUTINE: Remove contact lenses and irrigate exposed eyes with copious amounts of room temperature 0.9% saline or water for at least 15 minutes. If irritation, pain, swelling, lacrimation, or photophobia persist after 15 minutes of irrigation, an ophthalmologic examination should be performed (Peate, 2007; Naradzay & Barish, 2006).

Dermal Exposure

6.9.1)

A) DERMAL DECONTAMINATION

1) DECONTAMINATION: Remove contaminated clothing and wash exposed area thoroughly with soap and water for 10 to 15 minutes. A physician may need to examine the area if irritation or pain persists (Burgess et al, 1999).

Enhanced Elimination

A)

1) There is no clinical experience; however, hemodialysis might be useful to clear the parent compound and metabolites and to reverse metabolic acidosis after severe poisoning.

Abstracts

Case Reports

A)

1) INHALATION: Examination of workers employed in the manufacture of lacquers and paint revealed very little evidence of any injury to health from the use of this material (Browning, 1965).

a) It was observed that operators applying ethylene glycol monoethyl ether with a spray gun can work all day without discomfort or ill effects.

2) INHALATION: A man developed slight bilirubinemia and albuminuria after 13 years of chronic exposure. ORAL: A 44-year-old woman drank about 40 mL of ethylene glycol ethyl ether by mistake and became vertiginous and unconscious shortly after exposure. On examination, she had cyanosis, pulmonary edema, repeated tonic-clonic spasms, and acetone on her breath. With oxygen and other supportive measures, she recovered completely after 44 days (Fucik, 1969).

Range Of Toxicity

Summary

A)

Maximum Tolerated Exposure

A)

B)

C)

1) A 44-year-old woman ingested 40 mL of 2-Ethoxyethanol, developing vertigo, unconsciousness, cyanosis, tachypneumonary edema, and tonic-clonic spasms (Occupational Safety & Health Administration (OSHA), 2012).

D)

E)

Workplace Standards

A)

1) Editor's Note: The listed values are recommendations or guidelines developed by ACGIH(R) to assist in the control of health hazards. They should only be used, interpreted and applied by individuals trained in industrial hygiene. Before applying these values, it is imperative to read the introduction to each section in the current TLVs(R) and BEI(R) Book and become familiar with the constraints and limitations to their use. Always consult the Documentation of the TLVs(R) and BEIs(R) before applying these recommendations and guidelines.

a) Adopted Value

1) 2-Ethoxyethanol (EGEE)

a) TLV:

1) TLV-TWA: 5 ppm
2) TLV-STEL:
3) TLV-Ceiling:

b) Notations and Endnotes:

1) Carcinogenicity Category: Not Listed
2) Codes: BEI, Skin
3) Definitions:

a) BEI: The BEI notation is listed when a BEI is also recommended for the substance listed. Biological monitoring should be instituted for such substances to evaluate the total exposure from all sources, including dermal, ingestion, or non-occupational.
b) Skin: This refers to the potential significant contribution to the overall exposure by the cutaneous route, including mucous membranes and the eyes, either by contact with vapors or, of likely greater significance, by direct skin contact with the substance. It should be noted that although some materials are capable of causing irritation, dermatitis, and sensitization in workers, these properties are not considered relevant when assigning a skin notation. Rather, data from acute dermal studies and repeated dose dermal studies in animals or humans, along with the ability of the chemical to be absorbed, are integrated in the decision-making toward assignment of the skin designation. Use of the skin designation provides an alert that air sampling would not be sufficient by itself in quantifying exposure from the substance and that measures to prevent significant cutaneous absorption may be warranted. Please see "Definitions and Notations" (in TLV booklet) for full definition.

c) TLV Basis - Critical Effect(s): Male repro dam; embryo/fetal dam
d) Molecular Weight: 90.12

1) For gases and vapors, to convert the TLV from ppm to mg/m(3):

a) [(TLV in ppm)(gram molecular weight of substance)]/24.45

2) For gases and vapors, to convert the TLV from mg/m(3) to ppm:

a) [(TLV in mg/m(3))(24.45)]/gram molecular weight of substance

e) Additional information:

B) NIOSH REL and IDLH Values for CAS110-80-5 (National Institute for Occupational Safety and Health, 2007):

1) Listed as: 2-Ethoxyethanol
2) REL:

a) TWA: 0.5 ppm (1.8 mg/m(3))
b) STEL:
c) Ceiling:
d) Carcinogen Listing: (Not Listed) Not Listed
e) Skin Designation: [skin]

1) Indicates the potential for dermal absorption; skin exposure should be prevented as necessary through the use of good work practices and gloves, coveralls, goggles, and other appropriate equipment.

f) Note(s):

3) IDLH:

a) IDLH: 500 ppm
b) Note(s): Not Listed

C) Carcinogenicity Ratings for CAS110-80-5 :

1) ACGIH (American Conference of Governmental Industrial Hygienists, 2010): Not Listed ; Listed as: 2-Ethoxyethanol (EGEE)
2) EPA (U.S. Environmental Protection Agency, 2011): Not Assessed under the IRIS program. ; Listed as: 2-Ethoxyethanol
3) IARC (International Agency for Research on Cancer (IARC), 2016; International Agency for Research on Cancer, 2015; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2010; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2010a; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2008; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2007; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2006; IARC, 2004): Not Listed
4) NIOSH (National Institute for Occupational Safety and Health, 2007): Not Listed ; Listed as: 2-Ethoxyethanol
5) MAK (DFG, 2002): Not Listed
6) NTP (U.S. Department of Health and Human Services, Public Health Service, National Toxicology Project ): Not Listed

D) OSHA PEL Values for CAS110-80-5 (U.S. Occupational Safety, and Health Administration (OSHA), 2010):

1) Listed as: 2-Ethoxyethanol (Cellosolve)
2) Table Z-1 for 2-Ethoxyethanol (Cellosolve):

a) 8-hour TWA:

1) ppm: 200

a) Parts of vapor or gas per million parts of contaminated air by volume at 25 degrees C and 760 torr.

2) mg/m3: 740

a) Milligrams of substances per cubic meter of air. When entry is in this column only, the value is exact; when listed with a ppm entry, it is approximate.

3) Ceiling Value:
4) Skin Designation: Yes
5) Notation(s): Not Listed

Toxicity Information

7.7.1)

A) References: RTECS, 1991 Sax & Lewis, 1989 OHM/TADS, 1991

1) LD50- (INTRAPERITONEAL)MOUSE:

a) 1710 mg/kg

2) LD50- (ORAL)MOUSE:

a) 4310 mg/kg

3) LD50- (ORAL)RAT:

a) 3000 mg/kg
b) 3460 mg/kg

4) LD50- (SUBCUTANEOUS)RAT:

a) 3160 mg/kg

Pharmacology Toxicology

Toxicologic Mechanism

A)

Physicochemical

Physical Characteristics

A)

B)

C)

Molecular Weight

A)

Other

A)

1) Currently not available (CHRIS , 2002)

Animal Toxicology

References

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ETHYLENE GLYCOL ETHYL ETHER

Classification | Detailed evidence-based information

Therapeutic Toxic Class

Specific Substances

Available Forms Sources

Life Support

Clinical Effects

Laboratory Monitoring

Treatment Overview

Range Of Toxicity

Summary Of Exposure

Heent

Respiratory

Neurologic

Gastrointestinal

Hepatic

Genitourinary

Acid-Base

Hematologic

Reproductive

Carcinogenicity

Monitoring Parameters Levels

Methods

Life Support

Patient Disposition

Monitoring

Oral Exposure

Inhalation Exposure

Eye Exposure

Dermal Exposure

Enhanced Elimination

Case Reports

Summary

Maximum Tolerated Exposure

Workplace Standards

Toxicity Information

Toxicologic Mechanism

Physical Characteristics

Molecular Weight

Other

General Bibliography