Testing Information

Testing Status of Agents at NTP

CAS Registry Number: 111-46-6 Toxicity Effects

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

Names (NTP)

  • Diethylene glycol
  • 2,2'-OXYBISETHANOL (9CI)

Human Toxicity Excerpts

  • CAUSES CENTRAL NERVOUS DEPRESSION & HYDROPIC DEGENERATIVE LESIONS IN LIVER & KIDNEY (PROBABLY WITHOUT SIGNIFICANT OXALATE FORMATION). ANURIA FROM TUBULAR DEGENERATION MAY PROVE FATAL WITHIN FEW DAYS. [Gosselin, R.E., H.C. Hodge, R.P. Smith, and M.N. Gleason. Clinical Toxicology of Commercial Products. 4th ed. Baltimore: Williams and Wilkins, 1976., p. II-119]**PEER REVIEWED**
  • .../PREPN OF SULFANILAMIDE & DIETHYLENE GLYCOL/ WAS CONSUMED...IN...DIVIDED DOSES FOR 6-13 DAYS.../&/ VICTIMS EXHIBITED NAUSEA, VOMITING, HEADACHE, DIARRHEA, ABDOMINAL PAIN, & ADDITIONAL SIGNS & SYMPTOMS...ASSOCIATED WITH ACUTE RENAL FAILURE. ... PULMONARY EDEMA, PERICARDIAL HEMORRHAGE & DISTENSION OF LEPTOMENINGEAL VEINS ARE ALSO ENCOUNTERED. /ORAL/ [Gosselin, R.E., H.C. Hodge, R.P. Smith, and M.N. Gleason. Clinical Toxicology of Commercial Products. 4th ed. Baltimore: Williams and Wilkins, 1976., p. III-148]**PEER REVIEWED**
  • IN FATAL CASES...POLYURIA, &...OLIGURIA & ANURIA, DROWSINESS, SLIGHT EDEMA... SLIGHT JAUNDICE. PROGRESSIVE COMA... TEMP...SUBNORMAL...PULSE SLOW...MODERATE LEUKOCYTOSIS. URINE CONTAINED ALBUMEN, CASTS...LEUKOCYTES. NON-PROTEIN NITROGEN OF BLOOD ROSE TO 200 MG & CREATININE IN SOME CASES TO 12 MG/100 ML. [Browning, E. Toxicity and Metabolism of Industrial Solvents. New York: American Elsevier, 1965., p. 628]**PEER REVIEWED**
  • IN FATAL CASES...AUTOPSIES SHOWED...ASCITES, HYDROTHORAX, HYDROPERICARDIUM... HEMORRHAGES INTO GI TRACT & LUNGS & BRONCHOPNEUMONIA. ... KIDNEYS...ENLARGED & SHOWED CORTICAL NECROSIS...COLLECTING TUBULES CONTAINED HYALINE CASTS... LIVER ENLARGED... STOMACH & INTESTINES...CONGESTION & HEMORRHAGES. [Browning, E. Toxicity and Metabolism of Industrial Solvents. New York: American Elsevier, 1965., p. 628]**PEER REVIEWED**
  • The major hazard from diethylene glycol occurs following the ingestion of relatively large single doses. ... 105 fatalities among 353 people who ingested a solution of sulfanilamide in an aqueous mixture containing 72% diethylene glycol. The symptoms included nausea, dizziness, and pain in the kidney region. In a few days, oliguria and anuria, with death resulting from uremic poisoning followed. [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**
  • In general, pathology observed in human victims ... consists primarily of degeneration of the kidney with lesser lesions in the liver. Death in practically all these cases was due to renal insufficiency. [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. 3838]**PEER REVIEWED**
  • Signs and symptoms: Colicky pain, convulsions, kidney toxicity (oxalate crystal formation), liver toxicity. /From table/ [Kimbrough, R.D., P. Grandjean, D.D. Rutstein. Clinical Effects of Environmental Chemicals. New York, NY: Hemisphere Publishing Corp., 1989., p. 19]**PEER REVIEWED**
  • Diethylene glycol was the cause of more than 100 deaths in 1937 when it was inadvertently used as a solvent for sulfanilamide ion a pharmaceutical preparation. After 2 to 5 days of consuming this "elixir," which contained 72% diethylene glycol, patients complained of nausea with vomiting, intense gastrointestinal cramping and diarrhea, and back pain referred to the kidney area. These symptoms soon led to progressive liver necrosis, renal tubular degeneration, and death. [Gossel, T.A., J.D. Bricker. Principles of Clinical Toxicology. 3rd ed. New York, NY: Raven Press, Ltd., 1994., p. 85]**PEER REVIEWED**
  • Objective: To determine the cause of a large increase in the number of children with unexplained renal failure. Design: Case-control study. Setting: Children's hospital in Dhaka, Bangladesh. Subjects: Cases were all 339 children with initially unexplained renal failure; controls were 90 children with cause of renal failure identified; all were admitted to hospital during 35 months after January 1990. Main Outcome Measures--Differences between the case and control patients in clinical and histological features and outcome; toxicological examination of 69 bottles of paracetamol from patients and pharmacies. Results--Compared with children with an identified cause for their renal failure, children with initially unexplained renal failure were significantly (p< 0.05) more likely to have hepatomegaly (58% vs 33%), oedema (37% vs 20%), and hypertension (58% vs 23%); to have a higher serum creatinine concentration (mean 519 umol/l vs 12.4 mm/l) and lower serum bicarbonate concentration (10.1 mmol/l vs 12.4 mmol/l); to have been given a drug for fever (91% vs 31%); to have ingested a brand of paracetamol shown to contain diethylene glycol (20% vs 0%); and to have died in hospital (70% vs 33%). Diethylene glycol was identified in 19 bottles of paracetamol, from 7 too 28 brands tested. In the 12 months after a government ban on the sale of paracetamol elixir, new cases of renal failure decreased by 54%, and cases of unexplained renal failure decreased by 84%. Conclusion--Paracetamol elixirs with diethylene glycol as a diluent were responsible for a large outbreak of fatal renal failure in Bangladesh. [Hanif M et al; Br Med J 311 (6997): 88-91 (1995)]**PEER REVIEWED**

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Non-Human Toxicity Excerpts

  • ...PREGNANCY DID NOT OCCUR /IN RATS/ WHEN MALES & FEMALES...RECEIVING 0.5% OF PURE.../CMPD/ WERE.../MATED/. ... /ANOTHER INVESTIGATOR/...CONCLUDED THAT 1 ML/100 G OF 20% AQ SOLN DAILY FOR 12 WK HAD NO INFLUENCE ON REPRODUCTIVE ABILITY... [Browning, E. Toxicity and Metabolism of Industrial Solvents. New York: American Elsevier, 1965., p. 627]**PEER REVIEWED**
  • IN ANIMALS SLIGHTLY LESS TOXIC THAN ETHYLENE GLYCOL, CELLOSOLVE, OR CARBITOL (TOXICITY RATING IN ANIMALS 1 OR 2)... [Gosselin, R.E., H.C. Hodge, R.P. Smith, and M.N. Gleason. Clinical Toxicology of Commercial Products. 4th ed. Baltimore: Williams and Wilkins, 1976., p. II-119]**PEER REVIEWED**
  • .../RESULTS FROM STUDIES/ SUGGEST THAT DIETHYLENE GLYCOL IS NOT A PRIMARY CARCINOGEN BUT, WHEN FED IN VERY HIGH CONCN, DOES RESULT IN FORMATION OF CALCIUM OXALATE BLADDER STONES AND SUBSEQUENT RARE BLADDER TUMORS. [Amdur, M.O., J. Doull, C.D. Klaasen (eds). Casarett and Doull's Toxicology. 4th ed. New York, NY: Pergamon Press, 1991., p. 705]**PEER REVIEWED**
  • INTRAVENOUSLY MINIMUM FATAL DOSES ARE 5 ML/KG FOR RATS AND 2 ML/KG FOR RABBITS; INTRAMUSCULARLY THEY ARE 7 ML/KG FOR RATS AND 4 ML/KG FOR RABBITS... [Lefaux, R. Practical Toxicology of Plastics. Cleveland: CRC Press Inc., 1968., p. 373]**PEER REVIEWED**
  • Diethylene glycol: ... administered ... to rats in concn of 1, 2, 5, 10, and 20 percent in their drinking water ... /was found/ ... to have a /CNS depressant/ effect and to cause central paralysis of the respiratory and cardiac centers. [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. 3835]**PEER REVIEWED**
  • ...DEPRESSANT EFFECT ON CNS...&...CHANGES IN KIDNEY & CALCULI IN URINARY TRACT. [Browning, E. Toxicity and Metabolism of Industrial Solvents. New York: American Elsevier, 1965., p. 625]**PEER REVIEWED**
  • ACUTE. WITH LETHAL SINGLE DOSES DEATH MAY OCCUR... IN SOME CASES...ACUTE RENAL INSUFFICIENCY...ANURIA & UREMIC COMA. CHRONIC. ...FUR BECOMES RUFFLED...INCR THIRST...REFUSAL OF FOOD...DIURESIS...SCANTY URINARY EXCRETION...ANURIA. ...LIVER DAMAGE... [Browning, E. Toxicity and Metabolism of Industrial Solvents. New York: American Elsevier, 1965., p. 626]**PEER REVIEWED**
  • ACUTE. ...NO ABNORMALITY OF...INTERNAL ORGANS OF RATS DYING OF ACUTE ORAL POISONING...THOUGH...IRRITATION OF STOMACH & INTESTINES. ...RATS GIVEN SINGLE IV INJECTION...KIDNEY LESIONS IN FORM OF CALCIFICATION & DEGENERATION OF CONVOLUTED TUBULES. [Browning, E. Toxicity and Metabolism of Industrial Solvents. New York: American Elsevier, 1965., p. 626]**PEER REVIEWED**
  • CHRONIC. LIVER...ENLARGED...PALE, WITH VACUOLATION OF CYTOPLASM...NO NECROSIS. ADRENALS...VACUOLIZATION OF EPITHELIAL CELLS OF CORTEX. [Browning, E. Toxicity and Metabolism of Industrial Solvents. New York: American Elsevier, 1965., p. 627]**PEER REVIEWED**
  • NO IRRITATION OF EYES OF RABBITS...BY INSTILLATION OF DIETHYLENE GLYCOL. [Browning, E. Toxicity and Metabolism of Industrial Solvents. New York: American Elsevier, 1965., p. 627]**PEER REVIEWED**
  • RATS AND MICE EXPOSED TO DIETHYLENE GLYCOL AT 5 MG/M3 FOR 3-7 MONTHS SHOWED STRUCTURAL CHANGES IN CENTRAL NERVOUS SYSTEM AND ENDOCRINE AND INTERNAL ORGANS ALONG WITH OTHER PATHOLOGICAL EFFECTS. [MARCHENKO SA; FARMAKOL TOKSIKOL (KIEV) 8: 175 (1973)]**PEER REVIEWED**
  • DIETHYLENE GLYCOL WAS INEFFECTIVE IN THE HISTIDINE-DEPENDENT SALMONELLA TYPHIMURIUM STRAINS TA1535, TA100, TA1537, & TA98. [PFEIFFER EH, DUNKELBERG H; FOOD COSMET TOXICOL 18 (2): 115 (1980)]**PEER REVIEWED**
  • THE HIGH TOXICITY TO CHICK EMBRYOS OF GLYCOLS INJECTED INTO AIR CHAMBER ON 4TH DAY MAY BE ATTRIBUTED TO THEIR CAPACITY OF DESTROYING THE VASCULAR SYSTEM OF THE YOLK SAC. [GEBHARDT DOE; TERATOLOGY 1: 153 (1968)]**PEER REVIEWED**
  • EFFECT ON CHICK EMBRYOS OF 0.05 ML INJECTED INTO AIR CHAMBER PRIOR TO INCUBATION OR ON 4TH DAY OF INCUBATION: DAY OF INJECTION 0; NUMBER OF EGGS 18; MORTALITY 6%; NO MALFORMATION. DAY OF INJECTION 4TH; NUMBER OF EGGS 19; MORTALITY 79%; NO MALFORMED SURVIVORS. [GEBHARDT DOE; TERATOLOGY 1: 153 (1968)]**PEER REVIEWED**
  • EFFECT ON CHICK EMBRYO OF 0.05 ML INJECTED INTO YOLK SAC ON 4TH DAY OF INCUBATION: NUMBER OF EGGS 18; MORTALITY 0%. THE EMBRYOS WERE NOT MALFORMED. [GEBHARDT DOE; TERATOLOGY 1: 153 (1968)]**PEER REVIEWED**
  • DIETHYLENE GLYCOL INDUCED HISTOLOGIC CHANGES WITHIN THE KIDNEYS WITHOUT OXALATE DEPOSITION. OXALATE LEVELS IN THE KIDNEYS DID NOT PEAK UNTIL 4 HR AFTER MAX BLOOD OXALATE LEVELS. ETHYLENE & DIETHYLENE GLYCOLS INDUCED DIFFERENT MODES OF DEATH IN RATS. [WINEK ET AL; CLIN TOXICOL 13 (2): 297 (1978)]**PEER REVIEWED**
  • Diethylene glycol (DEG) was evaluated for mutagenicity in the Salmonella/microsome preincubation assay using a standard protocol approved by the National Toxicology Program. DEG was tested at doses of 0, 100, 333, 1000, 3333, and 10,000 ug/plate in four Salmonella typhimurium strains (TA98, TA100, TA1535, and TA1537) in the presence and absence of Aroclor-induced rat or hamster liver S9. DEG was negative in these tests and the highest ineffective dose level tested in any Salmonella tester strain was 10,000 ug/plate. [Zeiger E et al; Environ Mutagen 9:1-110 (1987)]**PEER REVIEWED**
  • An essentially saturated atmosphere generated at approximately 170 deg C and a fog generated at about 70 deg C caused no deaths of rats exposed for 8 hours. [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. 3836]**PEER REVIEWED**
  • Diethylene glycol tested by application of a drop to rabbit corneas is found not injurious, and tests on excised beef corneas have shown that it does not alter the adhesion of epithelium to stroma. [Grant, W.M. Toxicology of the Eye. 3rd ed. Springfield, IL: Charles C. Thomas Publisher, 1986., p. 335]**PEER REVIEWED**
  • A long term rat feeding study ... showed that 1% diethylene glycol in the diet over a two year period resulted in slight growth depression, a few calcium oxalate bladder stones, minimal kidney damage, and occasional liver damage. At 4% dietary level, thre was increased mortality, a marked depression of growth rate, bladder stones, severe kidney damage, and moderate liver damage. In addition, bladder tumors appeared rather frequently. [Amdur, M.O., J. Doull, C.D. Klaasen (eds). Casarett and Doull's Toxicology. 4th ed. New York, NY: Pergamon Press, 1991., p. 704-5]**PEER REVIEWED**
  • ... Diethylene glycol containing only 0.031 percent of ethylene glycol /was fed/ to weanlings, 2 month old, and year old rats for up to 2 years at levels of 4.0 and 2.0% in a laboratory chow. Because of the difference in chemical intake, the year old rats were given a diet containing 67% diethylene glycol after 1 month on the 4 percent diet. Although the weanling rats developed more bladder stones than the other groups, the difference was insignificant. The yearling rats developed their bladder stones somewhat earlier. The highest stone formation was 8 in 20 rats at the 4% dosage level. None was found in the rats fed the 2% level /which is contrary to the conclusions of the previous study/. ... /The results indicate/ ... that diethylene glycol substantially free of ethylene glycol does not cause bladder stones, suggesting that it is not metabolized to any great degree to ethylene glycol. [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. 3835]**PEER REVIEWED**
  • ... Diethylene glycol /was injected/ intraperitoneally for 3 months to rats at a daily dose of 300 mg/kg and found that it caused brain edema, plethora of brain tissue, petechial hemorrhages, and irregular distribution of cytoplasmic RNA. Histologically, some degenerative changes and vacuolization were seen. [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. 3836]**PEER REVIEWED**

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Human Toxicity Values

  • Single oral /lethal/ dose for humans is approximately 1 ml/kg. [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 oral 15.6 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. 3834]**PEER REVIEWED**
  • LD50 Mouse oral 13.3 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. 3834]**PEER REVIEWED**
  • LD50 Rabbit oral 26.9 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. 3834]**PEER REVIEWED**
  • LD50 Guinea pig oral 14.0 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. 3834]**PEER REVIEWED**
  • LD50 Mouse ip 9.6 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. 3835]**PEER REVIEWED**
  • LD50 Rat ip 6.86 ml/kg (7.7 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. 3836]**PEER REVIEWED**
  • LD50 Rat iv 8.0 ml/kg (8.9 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. 3836]**PEER REVIEWED**
  • LD50 Rat sc 16.8 ml/kg (18.8 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. 3836]**PEER REVIEWED**

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Absorption, Distribution and Excretion

  • In metabolism studies with the dog ... a large portion of the diethylene glycol administered was excreted in the urine unchanged. [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. 3838]**PEER REVIEWED**
  • ... Diethylene glycol may be absorbed through the skin especially upon essentially continuous contact ... . [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. 3836]**PEER REVIEWED**

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Metabolism/Metabolites

  • Repeated administration to dogs for a week did not lead to consistent increase in urinary oxalate. However, the urinary oxalate was increased in rats maintained on water containing diethylene glycol. [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. 3837]**PEER REVIEWED**
  • Although diethylene glycol is more nephrotoxic than the parent compound, ethylene glycol, metabolic acidosis occurs rarely because diethylene glycol is not metabolized in significant amounts to oxalate or formate. [Ellenhorn, M.J. and D.G. Barceloux. Medical Toxicology - Diagnosis and Treatment of Human Poisoning. New York, NY: Elsevier Science Publishing Co., Inc. 1988., p. 810]**PEER REVIEWED**

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TSCA Test Submissions

  • Teratogenicity was evaluated in pregnant Dutch rabbits (8/group) exposed by inhalation to diethylene glycol at nominal concentrations of 0, 100, 250 or 450 ppm on gestation days (GD) 6-18. All surviving rabbits were sacrificed on GD 21. There were significant differences observed between treated and control animals in the following: decreased body weight and food consumption (high-dose group), increased mean percentage pre-implantation losses and litters with any pre-implantation loss (100 and 450 ppm), mean number of intra-uterine deaths (450 ppm), and decreased mean fetal and gravid uterine weights (all treated groups). There were no significant differences observed between treated and control animals in the following: maternal mortality, hematology values, organ weights, and macroscopic observations, post-implantation loss, and mean number of live fetuses. One high-dose group rabbit was found to have marked ataxia, loss of withdrawal reflex, and slight head tremors; this rabbit was sacrificed and found to have undergone 100% post-implantation losses.[Imperial Chemical Industries PLC; Ethylene Glycol Monoethyl Ether Acetate (EEAc): Probe Inhalation Teratogenicity Study in Rabbits. (1983), EPA Document No. FYI-AX-0683-0178, Fiche No. 0000178-1 ]**UNREVIEWED**
  • Reproductive toxicity was evaluated in groups of 10 pregnant Charles River CD female mice receiving an oral gavage dose of diethylene glycol at 10 ml/kg body weight on gestation days 7 through 14. Maternal mortality, clinical observations or gross necropsy were not reported. There was a significant reduction (p<0.05) in the number of live pups per litter, reduced survival, and reduced birth weight among the offspring of treated dams.[Department of Health & Human Services; Results of Testing Fifteen Glycol Ethers in a Short-Term In Vivo Reproductive Toxicity Assay With Attachments, EPA Doc. 40-8385037, Fiche No. OTS0521552]**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