Testing Information

Testing Status of Agents at NTP

CAS Registry Number: 111-15-9 Toxicity Effects

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Selected toxicity information from HSDB, one of the National Library of Medicine's databases. 1

Names (NTP)

  • Ethylene glycol monoethyl ether acetate
  • 2-ETHOXYETHANOL ACETATE

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**
  • There are no records of adverse worker experience attributable to 2-ethoxyethyl acetate, possibly for the reason that its vapors are objectional at concn necessary to cause adverse effects. [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., p. 567]**PEER REVIEWED**
  • ... IS IN THE SAME RANGE OF TOXICITY AS METHYL ETHYL KETONE, PROPYLENE DICHLORIDE, AND TETRACHLOROETHANE, BUT ITS HAZARDS ARE BELIEVED TO BE LESS BECAUSE ITS VAPOR PRESSURE IS SUBSTANTIALLY LOWER. [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., p. 4026]**PEER REVIEWED**
  • SYMPTOMATOLOGY: 1. CENTRAL NERVOUS DEPRESSION ... 2. NO HYPOCALCEMIC TETANY OR METABOLIC ACIDOSIS ... 3. NAUSEA, VOMITING, & SOMETIMES DIARRHEA. 4. PROMINENT HEADACHE. LATER ABDOMINAL & LUMBAR PAIN & COSTOVERTEBRAL ANGLE TENDERNESS. SYMPTOMATOLOGY: 5. TRANSIENT POLYURIA & THEN OLIGURIA, PROGRESSING TO ANURIA. 6. ACUTE RENAL FAILURE ... 7. LESS CRITICAL PATHOLOGICAL LESIONS MAY APPEAR IN BRAIN, LUNG, LIVER, MENINGES & HEART. /ETHYLENE GLYCOL MONO-ETHERS/ [Gosselin, R.E., R.P. Smith, H.C. Hodge. Clinical Toxicology of Commercial Products. 5th ed. Baltimore: Williams and Wilkins, 1984., p. II-123]**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., p. 301]**PEER REVIEWED**
  • May be harmful if inhaled or absorbed through the skin, may cause reproductive effects; avoid breathing vapor ... [Ash, M. and I. Ash. Encyclopedia of Industrial Chemical Additives. Vols 1, II, III. New York, NY: Chemical Publishing Co., Inc., 1984-1985., p. V3 210]**PEER REVIEWED**
  • The exposure of workers to methylene chloride and phenol in an aeronautical workshop was measured during stripping of paint from a Boeing B 747. Methylene chloride exposure was measured during two work days by personal air sampling, while area sampling was used for phenol. During paint stripping operations, methylene chloride air concentrations ranged from 299.2 mg/cu m (83.1 ppm) to 1888.9 mg/cu m (524.7 ppm). The exposures to methylene chloride calculated for an 8-hr work day ranged from 86 mg/cu m (23.9 ppm) to 1239.5 mg/cu m (344.3 ppm). In another aeronautical workshop, exposure to organic solvents, especially ethylene glycol monoethyl-ether acetate, was controlled during the painting of an Airbus A 320. The external exposure to solvents and ethylene glycol monoethyl ether acetate was measured by means of individual air sampling. The estimation of internal exposure to ethylene glycol monoethyl ether acetate was made by measuring its urinary metabolite, ethoxyacetic acid. Both measurements were made during the course of 3 days. The biological samples were taken pre- and post-shift. During painting operations, methyl ethyl ketone, ethyl acetate, n-butyl alcohol, methyl isobutyl ketone, toluene, n-butyl acetate, ethylbenzene, xylenes and ethylene glycol monoethyl ether acetate were detected in working atmospheres. For these solvents, air concentrations ranged from 0.1 ppm to 69.1 ppm. Ethylene glycol monoethyl ether acetate concentrations ranged from 29.2 mg/cu m (5.4 ppm) to 150.1 mg/cu m (27.8 ppm). For biological samples, the average concentrations of ethoxyacetic acid were 108.4 mg/g creatinine in pre-shift and 139.4 mg/g creatinine in post-shift samples. Despite the fact that workers wore protective respiratory equipment during paint spraying operations, monoethyl ether acetate urinary concentrations are high and suggest that percutaneous uptake is the main route of exposure for ethylene-glycol-monoethyl ether-acetate. The introduction of new paint stripping processes in the aeronautical industry could help to reduce future exposure to methylene chloride. [Vincent R et al; International Archives of Occupational and Environmental Health 65 (6): 377-80 (1994)]**PEER REVIEWED**

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Non-Human Toxicity Excerpts

  • ... ONLY WEAKLY ... /CNS DEPRESSANT/ TO ANIMALS AND NOT HIGHLY TOXIC, THOUGH IN HIGH DOSAGE IT CAN CAUSE DEPRESSION OF CNS & INJURY TO LUNG AND KIDNEYS. WITH ORAL DOSAGE ITS ACUTE TOXICITY IS LESS THAN THAT OF THE METHYL ETHER-ESTER, AND WITH REPEATED APPLICATION TO THE SKIN IT IS CONSIDERABLY LESS TOXIC. [Browning, E. Toxicity and Metabolism of Industrial Solvents. New York: American Elsevier, 1965., p. 620]**PEER REVIEWED**
  • IT IS SOMEWHAT IRRITATING TO THE EYES BUT NOT SIGNIFICANTLY SO TO THE SKIN. HIGH DOSAGES BY INHALATION CAUSE DEFINITE INJURY TO THE KIDNEYS OF ANIMALS. [Browning, E. Toxicity and Metabolism of Industrial Solvents. New York: American Elsevier, 1965., p. 620]**PEER REVIEWED**
  • SYMPTOMS OF INTOXICATION: ACUTE; VERY SLIGHT ... /CNS DEPRESSION/, VOMITING, CRAMPS, PARALYSIS, ALBUMINURIA, DEATH FROM CENTRAL NERVOUS SYSTEM PARALYSIS. CHRONIC; WITH REPEATED SUBCUTANEOUS INJECTION OF 1 ML, TEMPORARY EMACIATION, EXHAUSTION AFTER EACH INJECTION. [Browning, E. Toxicity and Metabolism of Industrial Solvents. New York: American Elsevier, 1965., p. 620]**PEER REVIEWED**
  • SYMPTOMS OF INTOXICATION: CHRONIC; WITH INHALATION, INCREASING WEAKNESS AND ALBUMINURIA ... . [Browning, E. Toxicity and Metabolism of Industrial Solvents. New York: American Elsevier, 1965., p. 620]**PEER REVIEWED**
  • CATS EXPOSED ONCE FOR 2-6 HR TO ATMOSPHERE LADEN ... SURVIVED BUT 2 SUCH EXPOSURES CAUSED VOMITING, PARALYSIS, ALBUMIN IN URINE, & DEATH. [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., p. 4026]**PEER REVIEWED**
  • ... A 1 hr exposure to an atm essentially saturated with vapor (< 4000 ppm) was survived by guinea pigs. [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., p. 4026]**PEER REVIEWED**
  • Dogs survived 120 daily 7 hr exposures to a concentration of 600 ppm without apparent injury. ... Unable to detect methemoglobin in the blood, other hematologic changes, any effect upon numerous clinical tests or any histopathologic changes in the tissues. [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., p. 4026]**PEER REVIEWED**
  • CHRONIC EXPOSURE: BY SUBCUTANEOUS INJECTION, FOR GUINEA PIGS, 0.5 OR 1 ML REPEATED 7 TIMES DID NOT CAUSE DEATH ... . [Browning, E. Toxicity and Metabolism of Industrial Solvents. New York: American Elsevier, 1965., p. 620]**PEER REVIEWED**
  • ACUTE TOXICITY IN RATS & RABBITS AFTER INGESTION WAS SEVERE HEMATURIA; SKIN CONTACT MAINLY INDUCED MARKED DECR IN WHITE BLOOD CELLS. INHALATION EXPOSURE PRODUCED IN ANIMALS WHICH DIED KIDNEY INJURY, NECROSIS & GLOMERULAR INJURY. [TRUHAUT R ET AL; TOXICOL APPL PHARMACOL 51 (1): 117 (1979)]**PEER REVIEWED**
  • MICE GIVEN ORAL DOSES OF ETHYLENE GLYCOL MONOALKYL ETHERS DAILY FOR 5 DAYS/WK FOR 5 WK PRODUCED TESTICULAR ATROPHY & LEUKOPENIA. [NAGANO K ET AL; SANGYO IGAKU 21 (1): 29 (1979)]**PEER REVIEWED**
  • The toxicity of ethylene glycol ethers is reviewed. Testicular changes have been studied in mice. Ethylene glycol monomethyl ether appears to be most toxic, followed by ethylene glycol dimethyl ether, ethylene glycol monomethyl ether acetate, ethylene glycol monoethyl ether, and ethylene glycol monoethyl ether acetate. Preliminary studies have been made of the effect of ethylene glycol monomethyl ether on hamsters and guinea-pig testes. Decreased testicular weight had been found in hamsters receiving doses from 62.5 to 500 mg/kg and in guinea pigs receiving 500 or 250 mg/kg. The methyl ethers have the same effect. Both ethylene glycol monomethyl ether and ethyleneglycol dimethyl ether have been seen demonstrated to have embryotoxic effects. Both methyl and ethyl ethers of ethylene glycol cause testicular atrophy. Esterification of these chemicals does not affect poteny of the toxicity. Dimethyl and monomethyl ethers have about the same testicular toxicity. Alkyl ethers of other glycols are without these effects in the testes. Ethylene-glycol alkyl ethers appear to affect dividing cells and inhibit cell proliferation. Changes induced by these agents can be distinguished from those induced by hormonal subtances by their lack of effect on Leydig and Sertoli cells. Some ethylene glycol alkyl ethers have toxic effects on both testes and fetus. Substances known to inhibit cell proliferation are expected to damage the fetus if given to pregnant animals. [Nagano K et al; Environ Health Perspect 57: 75-84 (1984)]**PEER REVIEWED**
  • Previous NIOSH studies demonstrated the embryo- and fetotoxicity and teratogenicity of ethylene glycol monoethyl ether applied to the shaved skin of pregnant rats. In the present study ethylene glycol monoethyl ether acetate, ethylene glycol monobutyl ether, and diethylene glycol monoethyl ether were tested in the same experimental model, using distilled water as the negative control and ethylene glycol monoethyl ether as a positive control. Water or undiluted glycols were applied four times daily on days 7 to 16 gestation to the shaved interscapular skin with automatic pipetter. Volumes of ethylene glycol monoethyl ether (0.25 ml), ethylene glycol monoethyl ether acetate (0.35 ml), and diethylene glycol monoethyl ether (0.35 ml) were approximately equimolar (2.6 mmole per treatment). Ethylene glycol monobutyl ether at 0.35 ml four times daily (approximately 2.7 mmole per treatment) killed 10 of 11 treated rats, and was subsequently tested at 0.12 ml (0.9 mmole) per treatment. Ethylene glycol monoethyl ether and ethylene glycol monoethyl ether acetate treated rats showed a reduction in body weight relative to water controls that was associated with completely resorbed litters and significantly fewer live fetuses per litter. Visceral malformations and skeletal variations were significantly increased in ethylene glycol monoethyl ether and ethylene glycol monoethyl ether acetate groups over the negative control group. No embryotoxic, fetotoxic, or teratogenic effects were detected in the ethylene glycol monobutyl ether or diethylene glycol monoethyl ether treated litters. [Hardin BD et al; Environ Health Perspect 57: 69-74 (1984)]**PEER REVIEWED**
  • Investigated the teratogenicity of five compounds. Each chemical was vaporized and administered to pregnant rats in one to three concentrations for 7 hr/day on gestation days 7 to 15, and dams were sacrificed on day 20. At concentrations which were apparently not maternally toxic, 2-methoxyethanol was highly embryotoxic, producing complete resorptions at 200 ppm; increased resorptions, reduced fetal weights and skeletal and cardiovascular defects occured at both 100 and 50 ppm. 2-Ethoxyethyl acetate at 600 ppm induced complete resorption of litters; 390 ppm reduced fetal weights and induced skeletal and cardiovascular defects, but only a single defect was observed at 130 ppm. 2-Butoxyethanol evidenced slight maternal toxicity at 200 ppm but produced no increase in congenital defects at that concentration. Neither 2-(2-ethoxyethoxy)ethanol (100 ppm) nor 2-methylaminoethanol (150 ppm) was maternally toxic or embryotoxic. Shorter alkyl chained glycol ethers produced greater embryotoxicity than those having longer chains, and the ester produced effects equivalent to the ether. [Nelson BK et al; Environ Health Perspect 57: 261-71 (1984)]**PEER REVIEWED**
  • Mice, guinea pigs, and a rabbit appeared unaffected after 12, eight-hour exposures to 2-ethoxyethyl acetate at a concentration of 450 ppm, but another rabbit and two cats died before the termination of the experiment. Albumin was found in the urine, and the kidneys were damaged in those that died. [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., p. 567]**PEER REVIEWED**
  • Dogs, after 120 seven-hour exposures at 600 ppm, exhibited only a small increase in sulfobromophthalein retention, with ocular and nasal irritation. [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., p. 567]**PEER REVIEWED**

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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., p. 704]**PEER REVIEWED**

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Non-Human Toxicity Values

  • LD50 RAT MALE ORAL 3900 MG/KG [TRUHAUT R ET AL; TOXICOL APPL PHARMACOL 51 (1): 117 (1979)]**PEER REVIEWED**
  • LD50 RAT FEMALE ORAL 2900 MG/KG [TRUHAUT R ET AL; TOXICOL APPL PHARMACOL 51 (1): 117 (1979)]**PEER REVIEWED**
  • LD50 Rat oral 5.1 g/kg [Budavari, S. (ed.). The Merck Index - Encyclopedia of Chemicals, Drugs and Biologicals. Rahway, NJ: Merck and Co., Inc., 1989., p. 593]**PEER REVIEWED**
  • LD50 Rabbit /dermal/ 10,300 mg/kg [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., p. 567]**PEER REVIEWED**
  • LD50 Guiena pig oral 1.91 g/kg [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., p. 4025]**PEER REVIEWED**
  • LD50 Rabbit oral 1.95 g/kg [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., p. 4025]**PEER REVIEWED**

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Absorption, Distribution and Excretion

  • ... NOT READILY ABSORBED BY SKIN, BUT WITH INTENSIVE PROLONGED APPLICATION TOXIC AMT CAN BE ABSORBED. [Browning, E. Toxicity and Metabolism of Industrial Solvents. New York: American Elsevier, 1965., p. 619]**PEER REVIEWED**
  • ... ONCE ABSORBED INTO BODY, ESTERS ARE SAPONIFIED & SYSTEMIC EFFECT IS QUITE TYPICAL OF PARENT GLYCOL OR GLYCOL ETHER. /ETHER-ESTERS OF GLYCOLS/ [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., p. 4010]**PEER REVIEWED**
  • Pulmonary absorption and elimination of ethylene glycol monoethyl ether acetate were studied in humans. Male volunteers were exposed at rest or while exercising. Exposure periods were 4 hr with a 10 min break between each hour of exposure. ... Retention, atmospheric clearance, and rate of uptake of ethylene glycol monoethyl ether acetate decreased as exposure proceeded. Steady state values of these parameters were attained after 3 to 4 hr. The relative amounts of ethylene glycol monoethyl ether acetate in the expired air decreased as uptake increased. Individual uptake of ethylene glycol monoethyl ether acetate was mainly governed by pulmonary ventilation rate, cardiac output and anthropometric factors such as percent body fat. Retention increased with increasing ethylene glycol monoethyl ether acetate exposure concentration and increasing workload during exercise. The rate of uptake also increased with workload during exercise. This was attributed primarily to an increased pulmonary ventilation rate. Ethylene glycol monoethyl ether as well as ethylene glycol monoethyl ether acetate was detected in the expired air. Respiratory elimination of ethylene glycol monoethyl ether after exposure ended was biphasic. Respiratory elimination of ethylene glycol monoethyl ether acetate, however, was a minor route of excretion, only around 0.5% uptake being recovered in the expired air. Respiratory elimination of ethylene glycol monoethyl ether acetate was significantly correlated only with total body uptake, body fat content, and pulmonary ventilation rate. [Groeseneken D et al; Br J of Ind Med 44 (5): 309-16 (1987)]**PEER REVIEWED**
  • The absorption and elimination rates of 2-propoxyethyl acetate and 2-ethoxyethyl acetate were compared following inhalation, dermal application, and intravenous administration in male beagle-dogs. Exposure to 50 ppm 2-propoxyethyl acetate and 2-ethoxyethyl acetate resulted in rapid absorption through the lungs. Breath concentrations of 2-propoxyethyl acetate and 2-ethoxyethyl acetate showed a rapid increase with the duration of the exposure and reached a plateau after 3 hours. After iv administration of 1 mg/kg radiolabeled 2-propoxyethyl acetate, dogs eliminated about 88% of the radioactivity in the urine within 24 hours; about 61% of an equivalent dose of 2-ethoxyethyl acetate was excreted in the urine within 24 hours. Blood radioactivity after 2-propoxyethyl acetate administration was cleared more rapidly than after 2-ethoxyethyl acetate. For each compound, the amounts absorbed were similar after 30 and 60 minute exposures. The in vitro percutaneous absorption lag times were 1.2 and 1.6 hours for 2-propoxyethyl acetate and 2-ethoxyethyl acetate, respectively. Neither 2-ethoxyethyl acetate nor 2-propoxyethyl acetate altered the diffusion properties of the skin preparations. Although the excretion rates for 2-propoxyethyl acetate and 2-ethoxyethyl acetate are markedly different, the total amount of each compound absorbed through the skin and lungs is similar. [Guest D et al; Environ Health Perspectives 57: 177-83 (1984)]**PEER REVIEWED**
  • A study was conducted on 19 employees of four silk screen printing installations, to investigate the usefulness of alkoxyacetic acids in urine as biological indicators of occupational exposure to ethylene glycol ethers. Individual exposures to ethylene glycol ethers were measured by personal air sampling during 1 workday and biological monitoring of urine from these employees. All ethylene glycol ethers air levels were well below the Swedish and American Conference of Governmental Industrial Hygienists threshold limit values. Ethylene glycol monoethyl ether acetate at an average concentration of 5.0 mg/cu m and ethylene glycol monobutyl ether acetate at an average concentration of 2.9 mg/cu m were found in air samples from eight and five subjects, respectively; no ethylene glycol monomethyl ether acetate was found in any air samples. Average urinary levels of methoxyacetic acid, ethoxyacetic acid, and butoxyacetic acid were 6, 80, and 8 uM, respectively. [Johanson G et al; Archives of Toxicol Suppl 13: 108-11 (1989)]**PEER REVIEWED**

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Metabolism/Metabolites

  • ... ITS METABOLIC PRODUCT IS ETHYLENE GLYCOL MONOETHYL ETHER TO WHICH ITS SYSTEMIC EFFECTS MAY BE RELATED. [Browning, E. Toxicity and Metabolism of Industrial Solvents. New York: American Elsevier, 1965., p. 619]**PEER REVIEWED**
  • The urinary excretion of ethoxyacetic acid was studied in male volunteers exposed to ethylene glycol monoethyl ether acetate, of which ethoxyacetic-acid is a metabolite. Five of the volunteers, aged 21 to 30 years, were exposed to 14, 28, and 50 mg/cu m at rest, and five were exposed to 28 mg/cu m at rest and during exercise at 30 and 60 watts. Individuals were exposed to each concentration for periods of 4 hours. Unexposed periods between the experiments lasted 2 to 3 weeks. Maximal ethoxyacetic acid excretion took place 3 to 4 hours after exposure was discontinued; the half life for elimination was 23.6 hours. It was found that after physical exercise, a second maximum of excretion was observed approximately 3 hours after the first one. Approximately 22% of the absorbed ethylene glycol monoethyl ether acetate dose was recovered in the urine as ethoxyacetic acid after 42 hours. [Groeseneken D et al; Br J of Ind Med 44 (7): 488-93 (1987)]**PEER REVIEWED**
  • The urinary excretion of ethoxyacetic acid was studied in a group of five women daily exposed to the ethyl ether of ethylene glycol and the ethyl ether of ethylene glycol acetate during 5 days of normal production and 7 days after a 12 days production stop. The mean combined exposure concentration of ethyl ether of ethylene glycol and ethylene glycol ethyl ether acetate (expressed in equivalent weight of ethyl ether of ethylene glycol was 14.0 mg/cu m with occasional slight excursions above the current Belgian occupational exposure limit. The daily combined exposures profiles for ethylene glycol ethyl ether and ethylene glycol ethyl ether acetate were rather constant during the first observation period, but they tended to decrease during the last week. The urinary ethoxyacetic acid excretion clearly increased during the work week. Over the weekends the elimination was far from complete, and even after a prolonged nonexposure period of 12 days of traces of the metabolic were still detectable. Based on the observations from the first period, a good linear correlation was found between the average exposure over 5 days (914.4 mg/cu m) and the ethoxyacetic acid excretion of the end of the week (105.7 mg/g creatinine). An ethoxyacetic acid estimate of 150 + or - 35 mg/g was found to correspond with repeated 5 days full-shift exposures to the respective occupational exposure limit of ethylene glyol ethyl ether (19 mg/cu m) or ethylene glycol ethyl ether acetate (27 mg/cu m). [Veulemans H et al; Scand J Work Environ Health 13 (3): 239-42 (1987)]**PEER REVIEWED**
  • Seventeen persons who were exposed to glycolethers in a varnish production plant, were examined according to their external and internal solvent exposure. The workers in the production plant (n= 12) were exposed to average concentrations of ethoxyethanol, ethoxyethyl acetate, butoxyethanol, 1-methoxypropanol-2, 2-methoxypropyl-1-acetate and xylene of 2.8; 2.7; 1.1; 7.0; 2.8 and 1.7 ppm. Internal exposure was estimated by measuring butoxyethanol in blood as well as ethoxyacetic acid and butoxyacetic acid in urine samples. As expected, the highest values were found in the varnish production. The average post shift concentrations of butoxyethanol, ethoxyacetic acid and butoxyacetic acid were 121.3 ug/l; 167.8 and 10.5 mg/l. The relatively high concentrations of ethoxyacetic acid and butoxyacetic acid in pre-shift samples can be explained by the long half-lives of these metabolites. Most of the glycolethers were taken up through the skin. The authors think that a future tolerable limit value for the concentration of ethoxyacetic acid in urine should be in the order of 100 to 200 mg/l. [Angerer J et al; Int Arch Occup Environ Health 62 (2): 123-6 (1990)]**PEER REVIEWED**

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TSCA Test Submissions

  • Teratogenicity was evaluated in pregnant Fischer 344 rats (24/group) exposed by inhalation to ethylene glycol monoethyl ether acetate (EGMA, trade name CELLOSOLVE acetate) at nominal concentrations of 0, 50, 100, 200 or 300 ppm on gestation days (GD) 6-15. The rats were sacrificed on GD 21. There were significant differences observed between treated and control animals in the following: decreased food consumption (200 and 300 ppm groups), increased absolute liver weights (all treated groups), increased relative liver weights (all but low-dose group), increased white blood cell count (200 and 300 ppm), decreased red blood cell count, hemoglobin, hematocrit, and red blood cell size (all but low-dose and control groups), decreased platelet count (200 and 300 ppm), increased number of non-viable implantations/litter (high-dose), decreased fetal body weight/litter (200 and 300 ppm), increased incidence of numerous visceral and skeletal malformations (all at 300 ppm and most at 200 ppm also) including dysphagia lusoria, ventricle centra defect, ringed aorta, missing innominate artery, right aortic arch, pulmonary semilunar valve flaps thickened, retarded and non-ossifications of numerous bones including non-ossification of vertical centra (200 and 300 ppm), and other skeletal malformations. There were no significant differences observed between treated and control animals in the following: pregnancy rates, maternal mortality, number of dams having at least one live fetus, water consumption, clinical observations, maternal body and gravid uterine weights, kidney, thymus and spleen weights, number of corpora lutea, number of total or viable implantations/litter, percent preimplantation loss, and fetal external malformations.[Bushy Run Research Center, Union Carbide Corp.; Teratologic Evaluation of CELLOSOLVE Acetate in Fischer 344 Rats and New Zealand White Rabbits Following Inhalation Exposure. (1984), EPA Document No. FYI-AX-1184-0360, Fiche No. 0000360-0 ]**UNREVIEWED**
  • Teratogenicity was evaluated in mated New Zealand white rabbits (24/group) exposed by inhalation to ethylene glycol monoethyl ether acetate (EGMA, tradename CELLOSOLVE acetate) at nominal concentrations of 0, 50, 100, 200 or 300 ppm on gestation days (GD) 6-15. The rats were sacrificed on GD 21. There were significant differences observed between treated and control animals in the following (some differences at 300 ppm not significant due mainly to high number of totally resorbed litters): decreased maternal weight gain (200 and 300 ppm, exposure period), increased weight gain (300 ppm, GD 6-29), increased occult blood (300 ppm), decreased gravid uterine weight (300 and 200 ppm), increased absolute liver weight (300 ppm), increased number of dams with only nonviable implantations (200 and 300 ppm), increased mean corpuscular volume (300 ppm), decreased platelets (highest three dose groups), decreased corpora lutea/dam and increased early resorptions/litter (300 ppm), decreased viable implants and increased non-viable implants/litter (200 and 300 ppm), increased incidence of dark brown material in brain (blood), split sternebrae (100 ppm), increased individual and total fetal malformations, increased individual visceral and total malformations, litters with external variations, partial atectasis, bilobed cervical centra, and frontal bone with hole (200 ppm), one or both kidneys missing, dilatation of lateral brain ventricles, reduced right ventricle of the heart, globular heart, liver and kidneys, small spleen, poorly ossified pubis, skull and knee (300 ppm), increased malformed tails, individual visceral malformations, ventricular septal defect, incomplete septation of lung lobes, poorly ossified sternebra (200 and 300 ppm), poorly ossified sternebra 6, unossified pubis and extra ribs (100 and 200 ppm). There were no significant differences observed between treated and control animals in the following: maternal mortality, pregnancy rates, kidney, thymus and spleen weights, fetal body weights and sex ratios.[Bushy Run Research Center, Union Carbide Corp.; Teratologic Evaluation of CELLOSOLVE Acetate in Fischer 344 Rats and New Zealand White Rabbits Following Inhalation Exposure. (1984), EPA Document No. FYI-AX-1184-0360, Fiche No. 0000360-0 ]**UNREVIEWED**
  • The hydrolysis of ethylene glycol monoethyl ether (EGEEAc) by carboxylesterase from nasal mucosal tissue of B6C3F1/Cr1BR mice was evaluated in vitro. For determination of enzyme kinetics, tissue (0.2 ml containing 0.4-0.7 mg protein) from the nasal cavity of mice (numbers and sex ratio not reported) was incubated with 2-115 mM EGEEAc. For determination of enzyme inhibition, groups of 3-5 mice were injected intraperitoneally with 0 or 1 g triorthocresyl phosphate/kg bw, 15-18 hours prior to sacrifice, then nasal tissue was incubated with 76 mM EGEEAc; extent of hydrolysis of EGEEAc was determined by measuring ethylene glycol monoethyl ether levels in the supernatant by gas chromatography. The Vmax, Km, and Vmax/Km were 0.730, 9.52, and 0.77, respectively, indicating that mouse nasal carboxylesterase has significant affinity for EGEEAc. Pretreatment of mice with TOCP decreased nasal carboxylesterase activity to less than 26% of control values. The authors concluded that significant hydrolysis of inhaled EGEEAc by carboxylesterase may occur in nasal passages of mice.[Dow Chemical Company; Hydrolysis of Several Glycol Ether Acetates and Acrylate Esters by Nasal Mucosal Carboxylesterase In Vitro, (1983), EPA Document No. 86-890001242S, Fiche No. OTS0520750]**UNREVIEWED**
  • In an absorption study, the permeability of human abdominal skin to 2-ethoxyethyl acetate was measured in vitro using Franz-type glass diffusion cells. Epidermal layers from human skin were exposed for 8 hours to a solution containing radiolabeled test compound in the donor chamber and the appearance of radioactivity was measured in the receptor chamber. Damage to skin was calculated by comparing the water absorption rates of skin before and after exposure to the test compound. The rate of absorption of the test compound across human skin was 0.80 mg/cm2/hr. Exposure to the test chemical did not alter the permeability of skin to water.[Central Toxicology Lab; 2-butylethanol, 2-ethoxyethanol, 2-ethoxyethyl acetate, 2-methoxyethanol, and 1-methoxypropan-2-ol: Absorption Through Human Skin In Vitro, (1982), EPA Document No. 86-890000943; Fiche No. OTS0520381]**UNREVIEWED**
  • In an absorption study, the permeability of human abdominal skin to 2-ethoxyethyl acetate was measured in vitro using Franz-type glass diffusion cells. Epidermal layers from human skin were exposed for 8 hours to a solution containing radiolabeled test compound in the donor chamber and the appearance of radioactivity was measured in the receptor chamber. Damage to skin was calculated by comparing the water absorption rates of skin before and after exposure to the test compound. The rate of absorption of the test compound across human skin was 0.80 mg/cm2/hr. Exposure to the test chemical did not alter the permeability of skin to water.[Central Toxicology Lab; Glycol ethers (2-methoxyethanol, 2-ethoxyethanol, 2-butoxyethanol, 2-ethoxyethyl acetate, and 1-methoxypropan-2-ol: Relationships Between Human Skin Absorption and Inhaled Doses, (1982), EPA Document No. 86-890000944; Fiche No. OTS0520382]**UNREVIEWED**
  • Teratogenicity was evaluated in pregnant Fischer 344 rats (24/group) exposed by inhalation to ethylene glycol monoethyl ether acetate (EGMA, trade name CELLOSOLVE acetate) at nominal concentrations of 0, 50, 100, 200 or 300 ppm on gestation days (GD) 6-15. The rats were sacrificed on GD 21. There were significant differences observed between treated and control animals in the following: decreased food consumption (200 and 300 ppm groups), increased absolute liver weights (all treated groups), increased relative liver weights (all but low-dose group), increased white blood cell count (200 and 300 ppm), decreased red blood cell count, hemoglobin, hematocrit, and red blood cell size (all but low-dose and control groups), decreased platelet count (200 and 300 ppm), increased number of non-viable implantations/litter (high-dose), decreased fetal body weight/litter (200 and 300 ppm), increased incidence of numerous visceral and skeletal malformations (all at 300 ppm and most at 200 ppm also) including dysphagia lusoria, ventricle centra defect, ringed aorta, missing innominate artery, right aortic arch, pulmonary semilunar valve flaps thickened, retarded and non-ossifications of numerous bones including non-ossification of vertical centra (200 and 300 ppm), and other skeletal malformations. There were no significant differences observed between treated and control animals in the following: pregnancy rates, maternal mortality, number of dams having at least one live fetus, water consumption, clinical observations, maternal body and gravid uterine weights, kidney, thymus and spleen weights, number of corpora lutea, number of total or viable implantations/litter, percent preimplantation loss, and fetal external malformations.[Bushy Run Research Center, Union Carbide Corp.; Teratologic Evaluation of CELLOSOLVE Acetate in Fischer 344 Rats and New Zealand White Rabbits Following Inhalation Exposure. (1984), EPA Document No. FYI-AX-1184-0360, Fiche No. 0000360-0]**UNREVIEWED**
  • Teratogenicity was evaluated in mated New Zealand white rabbits (24/group) exposed by inhalation to ethylene glycol monoethyl ether acetate (EGMA, tradename CELLOSOLVE acetate) at nominal concentrations of 0, 50, 100, 200 or 300 ppm on gestation days (GD) 6-15. The rabbits were sacrificed on GD 21. There were significant differences observed between treated and control animals in the following (some differences at 300 ppm not significant due mainly to high number of totally resorbed litters): decreased maternal weight gain (200 and 300 ppm, exposure period), increased weight gain (300 ppm, GD 6-29), increased occult blood (300 ppm), decreased gravid uterine weight (300 and 200 ppm), increased absolute liver weight (300 ppm), increased number of dams with only nonviable implantations (200 and 300 ppm), increased mean corpuscular volume (300 ppm), decreased platelets (highest three dose groups), decreased corpora lutea/dam and increased early resorptions/litter (300 ppm), decreased viable implants and increased non-viable implants/litter (200 and 300 ppm), increased incidence of dark brown material in brain (blood), split sternebrae (100 ppm), increased individual and total fetal malformations, increased individual visceral and total malformations, litters with external variations, partial atectasis, bilobed cervical centra, and frontal bone with hole (200 ppm), one or both kidneys missing, dilatation of lateral brain ventricles, reduced right ventricle of the heart, globular heart, liver and kidneys, small spleen, poorly ossified pubis, skull and knee (300 ppm), increased malformed tails, individual visceral malformations, ventricular septal defect, incomplete septation of lung lobes, poorly ossified sternebra (200 and 300 ppm), poorly ossified sternebra 6, unossified pubis and extra ribs (100 and 200 ppm). There were no significant differences observed between treated and control animals in the following: maternal mortality, pregnancy rates, kidney, thymus and spleen weights, fetal body weights and sex ratios.[Bushy Run Research Center, Union Carbide Corp.; Teratologic Evaluation of CELLOSOLVE Acetate in Fischer 344 Rats and New Zealand White Rabbits Following Inhalation Exposure. (1984), EPA Document No. FYI-AX-1184-0360, Fiche No. 0000360-0]**UNREVIEWED**
  • Ethylene glycol monoethyl ether acetate (CAS No. 111-15-9) was tested for developmental effects. The test substance was administered by inhalation to female rabbits (number not reported) at concentrations of 25, 100, or 400 ppm. Reduced weight gain and food consumption, increased resorption, and major malformations of the vertebral columns of pups were observed at 400 ppm. Reduced fetal weight and retarded ossification were noted in the 100 and 400 ppm groups. No further information was provided in this summary.[CHEM MANUF ASSOC; Glycol Ethers Program Panel Research Status Report with Cover Sheet Dated 080189 (Sanitized); 09/01/83; Document No. 86-8900001473S; Fiche No. OTS0521087]**UNREVIEWED**
  • CELLOSOLVE acetate (2-ethoxyethyl acetate; 115-15-9) was evaluated for developmental effects in groups of 30 female Fischer rats administered the test substance by inhalation for 6 hours/day on days 6 through 15 of gestation at concentrations of 0, 50, 100, 200, or 300 ppm. Animals were sacrificed on day 21 of gestation. Rats at 200 and 300 ppm showed significantly reduced maternal weight, maternal weight gain, and food consumption. Maternal absolute liver weight was elevated in all exposed groups. Rats at 100, 200 and 300 ppm showed significantly elevated relative liver weights. Significantly increased white blood cell counts and reduced platelet counts were observed in rats at 200 and 300 ppm. Rats at 100, 200, and 300 ppm showed significantly reduced red blood cell count, hemoglobin, hematocrit, and red blood cell size. The number of non-viable implantations and early resorptions per litter was significantly increased at 300 ppm. Fetal body weights were significantly reduced at both 200 and 300 ppm. There was an increased incidence of external, visceral, and skeletal malformations at 200 and 300 ppm. An increased incidence of external variation was seen at 300 ppm while the incidence of visceral and skeletal variations was elevated at 100, 200, and 300 ppm. The level of significance for all cases was p<0.05.[Bushy Run Research Center; Initial Submission: A Teratologic Evaluation of Cellusolve Acetate in Fischer 344 Rats and New Zealand White Rabbits Following Inhalation Exposure (Final Report) with Letter 110791, (1984), EPA Doc. 88-920000149, Fiche No. OTS0534598]**UNREVIEWED**
  • CELLOSOLVE acetate (2-ethoxyethyl acetate; 115-15-9) was evaluated for developmental effects in groups of 24 female New Zealand white rabbits administered the test substance by inhalation for 6 hours/day on days 6 through 15 of gestation at concentrations of 0, 50, 100, 200, or 300 ppm. Animals were sacrificed on day 29 of gestation. Rabbits at 200 and 300 ppm showed reduced maternal weight gain and gravid uterine weight. Maternal absolute liver weight was elevated at 300 ppm. The number of non-viable implantations and early resorptions per litter was significantly increased at 300 ppm, while at 200 ppm the number of live fetuses per litter was decreased and the number of non-viable implantations per litter was increased. The incidence of external, visceral, skeletal and total fetal malformations was increased at 200 and 300 ppm. Reduced ossification was seen in fetuses at 100, 200 and 300 ppm.[Bushy Run Research Center; Initial Submission: A Teratologic Evaluation of Cellusolve Acetate in Fischer 344 Rats and New Zealand White Rabbits Following Inhalation Exposure (Final Report) with Letter 11/07/91, (1984), EPA Doc. 88-920000149, Fiche No. OTS0534598]**UNREVIEWED**
  • Ethylene glycol monoethyl ether acetate (111-15-9) was evaluated for developmental effects in groups of 8 female Dutch rabbits administered the test substance by inhalation for 6 hours/day on days 6 through 18 of gestation at concentrations of 0, 100, 250, or 450 ppm. Animals were sacrificed on day 21 of gestation. Reduced bodyweight gain and food consumption was seen in the 100, 250, and 450 ppm groups during the first few days of exposure. Fetal weights were reduced at 100, 250, and 450 ppm. The number of live fetuses per litter was reduced at 450 ppm (not statistically significant)[Imperial Chemical Industries Ltd.; Initial Submission: Ethylene Glycol Monoethyl Ether Acetate: Probe Inhalation Teratogenicity Study in Rabbits with Cover Letter Dated 072492, EPA Doc. No. 88- 920005030, Fiche No. OTS0544004]**UNREVIEWED**

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Footnotes

1 Source: the National Library of Medicine's Hazardous Substance Database, 10/28/2007.

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Web page last updated on May 14, 2008