Human Health Effects:

Toxicity Summary:

IDENTIFICATION: 2-Butoxyethanol is a high production volume glycol ether. It is a colorless liquid that is miscible in water and soluble in most organic solvents. 2-Butoxyethanol is used widely as a solvent in surface coatings, such as spray lacquers, quick dry lacquers, enamels, varnishes, varnish removers and latex paint. HUMAN EXPOSURE: Based on limited data, ambient exposures in air are generally in the ug/cu m range. Industrial exposure of the general population to this chemical is most likely from inhalation and dermal absorption during the use of products containing 2-butoxyethanol. Levels of airborne 2-butoxyethanol in occupational settings are typically in the mg/cu m range. The results of in vitro studies indicate that human red blood cells are not as sensitive to the hemolytic effects of 2-butoxyethanol and 2-butoxyacetic acid and also that red blood cells are more sensitive to hemolysis by 2-butoxyacetic acid than to hemolysis by 2-butoxyethanol. ANIMAL STUDIES: 2-Butoxyethanol is readily absorbed following inhalation, oral or dermal exposure. The chemical is metabolized via alcohol and aldehyde dehydrogenases, with the formation of 2-butoxyacetaldehyde and 2-butoxyacetic acid, the principal metabolite, although other metabolic pathways have also been identified. This chemical has moderate acute toxicity and it is irritating to the eyes and skin; it is not a skin sensitizer. The principal effect exerted by 2-butoxyethanol and its metabolite 2-butoxyacetic acid is hematotoxicity, with the rat being the most sensitive species. In rats, adverse effects on the central nervous system, kidneys and liver occur at higher exposure concentrations than do the hemolytic effects. In animals, adverse effects on reproduction and development have not been observed at less than toxic doses. Although the results of in vitro tests for mutagenicity of 2-butoxyethanol were inconsistent, the absence of structural alerts and the negative findings from in vivo studies indicate that 2-butoxyethanol is not mutagenic.
[World Health Organization/International Programme on Chemical Safety. Concise International Chemical Assessment Document No. 10. 2-Butoxyethanol p.4 (1998)]**QC REVIEWED**

Evidence for Carcinogenicity:

WEIGHT-OF-EVIDENCE CHARACTERIZATION: No reliable human epidemiological studies are available that address the potential carcinogenicity of EGBE. ... NTP /the National Toxicology Program/ (1988) reported no evidence of carcinogenic activity in male F344/N rats, and equivocal evidence of carcinogenic activity in female F344/N rats on the basis of increased combined incidences of benign and malignant pheochromocytoma (mainly benign) of the adrenal medulla. They also reported some evidence of carcinogenic activity in male B6C3F1 mice on the basis of increased incidences of hemangiosarcoma of the liver, and some evidence of carcinoma (mainly papilloma). ... because of the uncertain relevance of these tumor increases to humans, the fact that EGBE is generally negative in genotoxic tests and the lack of human data to support the findings in rodents, the human carcinogenic potential of EGBE, in accordance with the recently proposed Guidelines for Carcinogen Risk Assessment (USEPA, 1996), cannot be determined at this time, but suggestive evidence exists from rodent studies. Under existing EPA guidelines (USEPA, 1986), EGBE is judged to be a possible human carcinogen, Group C. HUMAN CARCINOGENICITY DATA: There are currently no human epidemiological studies addressing the potential carcinogenicity of EGBE.
[U.S. Environmental Protection Agency's Integrated Risk Information System (IRIS) for ethylene glycol monobutyl ether (111-76-2) Available from: http://www.epa.gov/ngispgm3/iris on the Substance File List as of March 15, 2000]**QC REVIEWED**

Human Toxicity Excerpts:

SYMPTOMATOLOGY: 1. Central nervous depression, although probably less prominent than with ethylene glycol. 2. No hypocalcemic tetany or metabolic acidosis with the possible exception of poisonings due to ethylene glycol monomethyl ether. 3. Nausea, vomiting, and sometimes diarrhea. 4. Prominent headache. Later abdominal and lumbar pain and costovertebral angle tenderness. 5. Transient polyuria & then oliguria, progressing to anuria. 6. Acute renal failure ... 7. Less critical pathological lesions may appear in brain, lung, liver, meninges and heart. 8. Observations in animals suggest the remote possibility of pulmonary edema, intravascular hemolysis & bone marrow depression, at least with some ether derivatives of ethylene and diethylene glycols. ... /Ethylene glycol (Group B compounds)/
[Gosselin, R.E., R.P. Smith, H.C. Hodge. Clinical Toxicology of Commercial Products. 5th ed. Baltimore: Williams and Wilkins, 1984.,p. II-176]**PEER REVIEWED**

EXPOSURE ... TO HIGH CONCN ... OF ... VAPORS, PROBABLY IN RANGE OF 300-600 PPM FOR SEVERAL HR WOULD BE EXPECTED TO CAUSE RESP & EYE IRRITATION ... /CNS DEPRESSION/, & DAMAGE TO KIDNEY & LIVER.
[Clayton, G. D. and F. E. Clayton (eds.). Patty's Industrial Hygiene and Toxicology: Volume 2A, 2B, 2C: Toxicology. 3rd ed. New York: John Wiley Sons, 1981-1982. 3933]**PEER REVIEWED**

FIRST SIGN OF ORGANIC ABNORMALITY ... RESULTING FROM EXCESSIVE EXPOSURE BY ANY ROUTE LIKELY WOULD BE ABNORMAL BLOOD PICTURE CHARACTERIZED BY ERYTHROPENIA, RETICULOCYTOSIS, GRANULOCYTOSIS, & LEUCOCYTOSIS. SOMEWHAT MORE INTENSE EXPOSURE WOULD BE LIKELY TO CAUSE FRAGILITY OF ERYTHROCYTES & HEMATURIA.
[Clayton, G. D. and F. E. Clayton (eds.). Patty's Industrial Hygiene and Toxicology: Volume 2A, 2B, 2C: Toxicology. 3rd ed. New York: John Wiley Sons, 1981-1982. 3933]**PEER REVIEWED**

BONE MARROW DAMAGE. /FROM TABLE/
[Dreisbach, R.H. Handbook of Poisoning. 12th ed. Norwalk, CT: Appleton and Lange, 1987. 176]**PEER REVIEWED**

2-Butoxyethanol penetrates the skin readily, and toxic action from excessive skin exposure may be more likely than from vapor inhalation.
[American Conference of Governmental Industrial Hygienists, Inc. Documentation of the Threshold Limit Values and Biological Exposure Indices. 6th ed. Volumes I, II, III. Cincinnati, OH: ACGIH, 1991.163]**PEER REVIEWED**

IT APPEARS THAT THIS CHEMICAL IS ONE OF THE FEW MATERIALS TO WHICH HUMAN IS MORE RESISTANT THAN THE USUAL EXPERIMENTAL ANIMALS. THIS APPEARS TO BE DUE, IN PART AT LEAST, TO THE FACT THAT HUMANS ARE MORE RESISTANT THAN ARE MOST LAB ANIMALS TO THE HEMOLYTIC EFFECTS CAUSED BY THE MATERIAL ITSELF OR ITS METABOLITE.
[Clayton, G. D. and F. E. Clayton (eds.). Patty's Industrial Hygiene and Toxicology: Volume 2A, 2B, 2C: Toxicology. 3rd ed. New York: John Wiley Sons, 1981-1982. 3937]**PEER REVIEWED**

... REGARDED AS MOST TOXIC GLYCOL MONOALKYL ETHER USED AS SOLVENT ... .
[Browning, E. Toxicity and Metabolism of Industrial Solvents. New York: American Elsevier, 1965. 610]**PEER REVIEWED**

THE EFFECTS /OF ALKYL DERIV OF ETHYLENE GLYCOL/ ... UPON THE CNS INCLUDE HEADACHE, DROWSINESS, WEAKNESS, SLURRED SPEECH, RECRUDESCENT STUTTERING, STAGGERING GAIT, TREMOR, AND BLURRED VISION. CHANGES OF PERSONALITY ARE OFTEN NOTED ... THESE CHANGES ARE SUCH THAT THE PATIENT, IN THE ABSENCE OF AN ACCURATE OCCUPATIONAL HISTORY, MAY BE TREATED FOR SCHIZOPHRENIA OR NARCOLEPSY. IN ACUTE POISONING WITH THE ETHYLENE GLYCOL MONOALKYL ETHERS, THERE IS ... RENAL INJURY: ALBUMINURIA & HEMATURIA. /ETHYLENE GLYCOL MONOALKYL ETHERS/
[Hamilton, A., and H. L. Hardy. Industrial Toxicology. 3rd ed. Acton, Mass.: Publishing Sciences Group, Inc., 1974. 301]**PEER REVIEWED**

A case of severe poisoning with ethylene glycol butyl ether after massive ingestion is described. Deep coma, metabolic acidosis, hypokalemia hemoglobinuria, oxaluria and a transitory rise in the serum creatinine level were observed. The elimination of the various metabolites butoxyacetic acid and oxalate was assessed in urine and a metabolic pattern for ethylene glycol butyl ether is suggested.
[Rambourg-Schepens MO et al; Hum Toxicol 7 (2): 187-9 (1988)]**PEER REVIEWED**

The effects of 2-butoxyethanol and its metabolites, 2-butoxyacetaldehyde and butoxyacetic acid, on erythrocytes from humans were investigated in vitro. ... Incubation of human blood with butoxyacetic acid showed minimal swelling or hemolysis of erythrocytes with minimal decline in blood ATP levels at butoxyacetic acid concentrations several-fold higher than required to cause complete hemolysis of rat erythrocytes. ... Human erythrocytes are comparatively insensitive to the hemolytic effects of butoxyacetic acid in vitro.
[Ghanayem BI; Biochem Pharmacol 38 (10): 1679-84 (1989)]**PEER REVIEWED**

A case of acute poisoning with ethylene glycol butyl ether is reported in a chronic alcoholic abuser. On admission the 53 yr old patient was comatose with metabolic acidosis, shock and noncardiogenic pulmonary edema confirmed by hemodynamic study. Following supportive treatment and hemodialysis the outcome was favorable. ...
[Bauer P et al; Intensive Care Med 18 (4): 250-1 (1992)]**PEER REVIEWED**

In several, single, 8 hour exposures of humans at concentrations of 200 or 100 ppm, no objective effects were seen except for urinary excretion of butoxyacetic acid. No increased osmotic fragility was observed in these short term exposures. Subjectively, these concentrations were found to be uncomfortable, and mild eye, nose, and throat irritation followed exposure.
[American Conference of Governmental Industrial Hygienists, Inc. Documentation of the Threshold Limit Values and Biological Exposure Indices. 6th ed. Volumes I, II, III. Cincinnati, OH: ACGIH, 1991.163]**PEER REVIEWED**

No clinical signs of adverse effects nor subjective complaints occurred among seven male volunteers exposed at 20 ppm for 2 hours during light physical exercise.
[American Conference of Governmental Industrial Hygienists, Inc. Documentation of the Threshold Limit Values and Biological Exposure Indices. 6th ed. Volumes I, II, III. Cincinnati, OH: ACGIH, 1991.163]**PEER REVIEWED**

Human Toxicity Values:

The lethal oral dose /of ethylene glycols/ in humans is approximately 1.4 ml/kg, which would be equivalent to approximately 100 ml for a 70-kg person. /Ethylene glycols/
[Amdur, M.O., J. Doull, C.D. Klaasen (eds). Casarett and Doull's Toxicology. 4th ed. New York, NY: Pergamon Press, 1991. 703]**PEER REVIEWED**

Skin, Eye and Respiratory Irritations:

Irritation of eyes, nose and throat ...
[Sittig, M. Handbook of Toxic and Hazardous Chemicals and Carcinogens, 1985. 2nd ed. Park Ridge, NJ: Noyes Data Corporation, 1985. 155]**PEER REVIEWED**

Medical Surveillance:

Consider the points of attack (liver, kidneys, lymphoid system, skin, blood, eyes, respiratory system) in placement and periodic physical examinations.
[Sittig, M. Handbook of Toxic and Hazardous Chemicals and Carcinogens, 1985. 2nd ed. Park Ridge, NJ: Noyes Data Corporation, 1985. 155]**PEER REVIEWED**

Probable Routes of Human Exposure:

The most probable route of human exposure to ethylene glycol mono-n-butyl ether is by inhalation, dermal contact and ingestion. Workplace exposures have been documented(2-6). Drinking water supplies have been shown to contain ethylene glycol mono-n-butyl ether(1).
[(1) Lucas SV; GC/MS Anal of Org in Drinking Water Concentrates and Advanced Treatment Concentrates Vol 1 USEPA-600/1-84-020A (NTIS PB85-128239) p 397 (1984) (2) Lehmann E et al; pp. 31-41 in Safety and Health Aspects of Organic Solvents. Riihimaki V, Ulfvarson U eds Alan R Liss Inc. (1986) (3) Hahn WJ, Werschulz PO; Evaluation of Alternatives to Toxic Organic Paint Strippers. NTIS PB86 219-177/AS USEPA 600/S2-86/063 (1986) (4) Clapp DE et al; Environ Health Perspective 57: 91-5 (1984) (5) Shah JJ, Heyerdahl EK; National Ambient VOC Database Update USEPA 600/3-88/010 (1988) (6) Yasuhara, A et al; Agric Bio Chem 50: 1765-70 (1986)]**PEER REVIEWED**

THERE IS ... HAZARD OTHER THAN VAPOR THAT MUST NOT BE OVERLOOKED WHEN HANDLING THIS MATERIAL--THAT OF POSSIBLE ABSORPTION OF TOXIC QUANTITIES THROUGH SKIN, BECAUSE OF LOW VAPOR PRESSURE ... @ ROOM TEMP, HAZARD FROM SKIN ABSORPTION COULD WELL BE GREATER, OR CONTRIBUTE SUBSTANTIALLY TO OVER-ALL HAZARD.
[Clayton, G. D. and F. E. Clayton (eds.). Patty's Industrial Hygiene and Toxicology: Volume 2A, 2B, 2C: Toxicology. 3rd ed. New York: John Wiley Sons, 1981-1982. 3938]**PEER REVIEWED**

FROM INDUST POINT OF VIEW, ONLY ONE CASE OF POSSIBLE SYSTEMIC INJURY WAS THAT OF MAN WHO WAS REPORTED ... AS HAVING HAD TWO ISOLATED ATTACKS OF HEMATURIA, WITH 5 MO INTERVAL. ... HIS EXPOSURE ... INCL BUTYL CARBITOL AS WELL AS BUTYL CELLOSOLVE.
[Browning, E. Toxicity and Metabolism of Industrial Solvents. New York: American Elsevier, 1965. 612]**PEER REVIEWED**

OCCUPATIONAL EXPOSURES TO BUTYL CELLOSOLVE, ETHANOL, & XYLENE IN FILAMENT-DRAW DEPARTMENT OF ELECTRICAL RESISTOR MFR FACILITY DID NOT POSE A HEALTH HAZARD.
[GILLES ET AL; US NTIS PB REP; ISS PB-273739 (1976) 16 PP]**PEER REVIEWED**

NIOSH (NOES Survey as of 3/28/89) has estimated that 1,680,764 workers are potentially exposed to ethylene glycol mono-n-butyl ether in the USA(1). According to the National Ambient Volatile Organic Compounds (VOCs) Database, the median workplace atmospheric concn of ethylene glycol mono-n-butyl ether is 0.075 ppbV for 14 samples(3). Workers at paint stripping operations that used stripping agents containing ethylene glycol mono-n-butyl ether were exposed to it(2).
[(1) NIOSH; National Occupational Exposure Survey (NOES) (1989) (2) Hahn WJ, Werschulz PO; Evaluation of Alternatives to Toxic Organic Paint Strippers. NTIS PB86 219-177/AS USEPA 600/S2-86/063 (1986) (3) Shah JJ, Heyerdahl EK; National Ambient VOC Database Update USEPA-600/3-88/010 (1988)]**PEER REVIEWED**

Personal exposures to atmospheric ethylene glycol mono-n-butyl ether at a specialty chemical production facility in June of 1981 ranged from undetected levels to 0.1 ppm; indoor air concn within the facility were as high as 1.7 ppm(2). A national survey of workplaces in the Federal Republic of Germany showed that workers were exposed to solvents containing ethylene glycol mono-n-butyl ether with a 0.4% frequency of occurrence(1).
[(1) Lehmann E et al; pp 31-41 in Safety and Health Aspects of Organic Solvents. Riihimaki V, Ulfvarson U eds Alan R Liss Inc. (1986) (2) Clapp DE et al; Environ Health Perspective 57: 91-5 (1984)]**PEER REVIEWED**

A study initiated in 1983, which surveyed the workplace atmospheres of 336 businesses in Belgium, showed that ethylene glycol mono-n-butyl ether was present in 25 of 94 air samples taken from sites that utilize printing pastes; 10 of 81 samples from where painting took place; 1 of 20 samples from automobile repair shops; and 17 of 67 samples from sites where various materials such as varnishes, sterilization agents and cleaners are employed(1). The geometric mean concn of ethylene glycol mono-n-butyl ether in the air of printing shops was 4.1 mg/cu m with a range of 1.5 to 17.7 mg/cu m; 18.8 mg/cu m with a range of 3.4 to 93.6 mg/cu m for painting areas; 5.9 mg/cu m for car repair shops; and 8.5 mg/cu m with a range of 0.2 to 1775 mg/cu m for various industries(1).
[(1) Veulemans H et al; Am Indust Hyg Assoc J 48: 671-7 (1987)]**PEER REVIEWED**

Ethylene glycol mono-n-butyl ether was identified as a volatile emission from used machine cutting oils in an automobile manufacturing facility in Japan(1). Non-occupational exposures may occur among populations with contaminated drinking water supplies(2). Because ethylene glycol mono-n-butyl ether is a component of solvent based building materials such as silicone caulk(3), human exposures may occur at construction sites and areas that have undergone remodelling(SRC).
[(1) Yasuhara A et al; Agric Bio Chem 50: 1765-70 (1986) (2) Lucas SV; GC/MS Anal of Org in Drinking Water Concentrates and Advanced Treatment Concentrates Vol 1 USEPA-600/1-84-020A (NTIS PB85-128239) p 397 (1984) (3) Tichenor BA, Mason MA; JAPCA 38: 264-8 (1988)]**PEER REVIEWED**

Exposure of cleaning women and cleaners of cars to ethylene glycol mono-n-butyl ether resulted in urine levels of <0.1-7.33 ppm (time-weighted averages)(1). It was established that the predominant route of exposure to ethylene glycol mono-n-butyl ether was through skin penetration(1). Ethylene glycol mono-n-butyl ether was identified in air from automotive repair shops in Sydney, Australia in 8 out of 70 samples at an average concentration of 2.0 mg/cu m(2).
[(1) Vincent R et al; Appl Occup Environ Hyg 8: 580-6 (1993) (2) Winder C, Turner PJ; Am Occup Hyg 36: 385-94 (1992)]**PEER REVIEWED**

Middaugh said federal investigators took exhaustive air and water samples to make sure workers weren't being endangered. "It was concluded there was no risk," he said, "as long as there was meticulous adherence to standards developed by the company and NIOSH and OSHA."