National Toxicology Program

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

Human Toxicity Excerpts

• 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**
  
• 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**
  

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Non-Human Toxicity Excerpts

• INGESTION BY RATS WAS FOLLOWED BY SEVERE HEMATURIA, WHICH DECR PROGRESSIVELY BUT PERSISTED OVER 1 WK. AFTER SKIN CONTACT IN RABBITS HEMATURIA &/OR HEMOLYSIS & FALL OF RED BLOOD CELLS & HEMOGLOBIN. [TRUHAUT R ET AL; TOXICOL APPL PHARMACOL 51 (1): 117 (1971)]**PEER REVIEWED**
  
• RATS & RABBITS SURVIVED SINGLE INHALATION EXPOSURE OF 4 HR TO APPROX 400 PPM. 1 MONTH PULMONARY INTOXICATION INDUCED HEMOGLOBINURIA &/OR HEMATURIA, MAINLY IN RABBITS. [TRUHAUT R ET AL; TOXICOL APPL PHARMACOL 51 (1): 117 (1979)]**PEER REVIEWED**
  
• RATS & RABBITS EXPOSED FOR 10 MO BY INHALATION, ANIMALS WHICH DIED EXHIBITED KIDNEY INJURY CONSISTING OF NECROTIZING HEMORRHAGE INTERSTITIAL TUBULAR NEPHROSIS, NONLITHIASIC, WITH OCCASIONAL GLOMERULAR LESIONS. [TRUHAUT R ET AL; TOXICOL APPL PHARMACOL 51 (1): 117 (1979)]**PEER REVIEWED**
  
• Human dermal exposure to diethylene glycol butyl ether and its acetate derivative may occur through contact with a variety of commercial products. Absorption and elimination of dermally applied doses of (14)C-diethylene glycol butyl ether and (14)C-diethylene glycol butyl ether acetate derivative were determined in Sprague-Dawley rats. The materials were applied under occlusion for 24 hr at dose levels of 0.2 and 2.0 g/kg (undiluted) and as a 10% aqueous solution (0.2 g/kg diethylene glycol butyl ether). Preliminary washing efficiency studies with soap and water indicated that greater than 89% of each chemical could be removed from rat skin following 5 min exposures. Female rats excreted a larger proportion of the applied dose of diethylene glycol butyl ether than did male rats. Similar results were obtained with the low dose of diethylene glycol butyl ether applied neat or as a 10% aqueous solution, suggesting that the low dose represents a saturating dose. The total recovered (14)C for all studies with (14)C-diethylene glycol butyl ether ranged from 83% to 89%, with (14)C-diethylene glycol butyl acetate derivative, from 80% to 88%. Urinary excretion accounted for the majority of recovered 14C in all studies. The acid, 2-(2-butoxyethoxy)acetate acid was the major urinary metabolite identified. The glucuronide of diethylene glycol butyl ether was present at levels of from 5.2 to 8.2% of the urinary (14)C. The dermal absorption rates were estimated to be 1.58 (diethylene glycol butyl acetate derivative, male), 1.28 (diethylene glycol butyl acetate derivative, female), 0.73 (diethylene glycol butyl ether, male), and 1.46 (diethyl glycol butyl ether, female), expressed as mg/cu cm/hr. [Boatman RJ et al; J Am Coll Toxicol 12 (2): 145-54 (1993)]**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/ [Doull, J., C.D.Klassen, and M.D. Amdur (eds.). Casarett and Doull's Toxicology. 3rd ed., New York: Macmillan Co., Inc., 1986., p. 654]**PEER REVIEWED**
  

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Non-Human Toxicity Values

• LD50 RAT FEMALE ORAL 2400 MG/KG [TRUHAUT R ET AL; TOXICOL APPL PHARMACOL 51 (1): 117 (1979)]**PEER REVIEWED**
  
• LD50 RAT MALE ORAL 3000 MG/KG [TRUHAUT R ET AL; TOXICOL APPL PHARMACOL 51 (1): 117 (1979)]**PEER REVIEWED**
  

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Absorption, Distribution and Excretion

• ... 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**
  

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Metabolism/Metabolites

• 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**
  
• The metabolism of diethylene glycol monobutyl ether acetate was studied in-vitro and in-vivo. Blood samples from male Sprague-Dawley rats or saline were incubated with 0 or 5 millimolar diethylene glycol butyl acetate derivative for 0 to 14 minutes. Aliquots were taken at various times. The extent of conversion of diethylene glycol butyl acetate derivative to diethylene-glycol-monobutyl-ether was determined. In-vivo, male Sprague-Dawley rats were gavaged with 0, 200, or 2000 mg/kg (14)C labeled diethylene glycol butyl acetate derivative. Urine, feces, and expired air were collected for up to 72 hours and assayed for (14)C activity. The urine samples were analyzed for diethylene glycol butyl acetate derivative metabolites. The rats were killed 72 hours post dosing to determine the tissue distribution of (14)C activity. In-vitro, diethylene glycol monobutyl ether acetate was rapidly hydrolyzed by rat blood to diethylene glycol monobutyl ether; the biological half-life was less than 3 minutes. Only 3.8% of the diethylene glycol monobutyl ether acetate was hydrolyzed by saline after 14 minutes. The urine was the major pathway for eliminating diethylene glycol monobutyl ether acetate derived (14)C activity, 82.3 and 81.3% of the 200 and 2000 mg/kg doses, respectively, being eliminated after 24 hours. Only 2 to 3% of each dose was eliminated in the feces. About 5% of each dose was eliminated in the expired air, mostly as radioactive carbon dioxide. Only about 1.1 and 3.0% of the 200 and 2000 mg/kg doses were found in the tissues and carcass. Most of that radioactivity was found in the carcass. 2-(2-Butoxyethoxy)acetic acid was the major metabolite identified. No unchanged diethylene glycol monobutyl ether acetate or diethylene glycol monobutyl ether or 2-butoxyacetic acid, a putative hematotoxic diethylene glycol monobutyl ether acetate metabolite, was found. /Results indicate/ that diethylene glycol monobutyl ether acetate is rapidly hydrolyzed to diethylene glycol monobutyl ether acetate by rat blood. This suggests that the biological effects of diethylene glycol monobutyl ether acetate and diethylene glycol monobutyl ether would be indistinguishable. No butoxyacetic acid is produced. The data are consistent with the low subchronic toxicity of diethylene glycol monobutyl ether acetate. [Deisinger PJ, Guest D; Xenobiotica 19 (9): 981-89 (1989)]**PEER REVIEWED**
  

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TSCA Test Submissions

• None found

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Footnotes

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