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Description of key information

An oral lethal dose for humans was determined to be 0.014 mg/kg bw.

The dermal LD50 for rabbits was determined to be 13330 mg/kg bw.

The inhalation LC50 for rats was determined to be 4.6 mg/L.

Key value for chemical safety assessment

Acute toxicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
discriminating conc.
4.6 µg/m³ air

Acute toxicity: via dermal route

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
13 330 mg/kg bw

Additional information

Acute oral toxicity

Lenk et al. (1989) found an oral LD50 value of 19600 mg/kg bw for male rats. Narcotic phase, diuretic phase and thirst, drop of the pH of the urine and blood, either recovery or hydrotropic degeneration of the renal tubules and anuria, accumulation of urea and uric acid in the blood and finally death after 2 - 7 days from non-compensated metabolic acidosis and uremia were found in this study.

Laug et al. (1939) found an oral LD50 value of 16500 mg/kg bw for male/female rats. Thirst, diuresis, ruffled coat and refusal of food were reported. After the first 2 to 3 days there was cessation of urine excretion with heavy proteinuria. Prostration, dyspnea, bloated appearance, coma, and pronounced lowering of body temperature were reported for about 24 hours before death. The following histopathologic effects were observed. There was extensive degeneration of the renal cortex with vacuolar (hydropic) degeneration of the convoluted tubules. In the liver there was widespread diffuse hydropic degeneration of the central of lobules. The lung of some animals showed congestion, edema and focal interstitial  pneumonia and hemorrhage in some cases. The spleen in many cases showed  excessive phagocytosis of blood pigment.

In the same article information about a mass poisoning of patients was reported. After a mass poisoning through DEG (application of 10% Sulfanilamid in 72% DEG) 30% of patients died after a dose of about  1120 mg/kg bw (retrospectiv calculation).

In a review article from Schep et al. (2009) all main aspects of DEG poisoning including epidemiology, toxicokinetics, mechanisms of toxicity, clinical features, toxicity of DEG, diagnosis, and management were summarized. Most of the documented cases of DEG poisoning have been where DEG was substituted in pharmaceutical preparations. More often, these epidemics have occurred in developing and impoverished nations where there is limited access to intensive medical care and quality control procedures are substandard. The clinical effects of DEG poisoning can be divided into three stages: The first phase consists of gastrointestinal symptoms with evidence of inebriation and developing metabolic acidosis. lf poisoning is pronounced, patients can progress to a second phase with more severe metabolic acidosis and evidence of emerging renal injury which, in the absence of appropriate supportive care, can lead to death. If patients are stabilized, they may then enter the final phase with various delayed neuropathies and other neurological effects, sometimes fatal. Initial treatment consists of appropriate airway management and attention to acid- base abnormalities. Prompt use of fomepizole or ethanol is important in preventing the formation of the toxic metabolite 2- hydroxyethoxyacetic acid (HEAA) ; hemodialysis can also be critical, and assisted ventilation may be required.

To investigate an outbreak of deaths among children from acute renal failure in Haiti to determine the etiology and institute control measures a case-control study (cohort study) and laboratory toxicologic evaluations were conducted (O'Brien, 1998). It was shown, that an epidemic of severe systemic toxicity and deaths from DEG-contaminated acetaminophen syrup occurred in Haiti. In the study 109 cases of acute renal failure among children were identified. The clinical syndrome included renal failure, hepatitis, pancreatitis, central nervous system impairment, coma, and death. Of 87 patients with follow-up information who remained in Haiti for treatment, 85 (98%) died; 3 (27%) of 11 patients transported to the United States for intensive care unit management died before hospital discharge. A locally manufactured acetaminophen syrup was highly associated with the disease (odds ratio, 52.7; 95% confidence interval, 15.2-197.2). Diethylene glycol (DEG) was found in patients' bottles in a median concentration of 14.4%. The median estimated toxic dose of DEG was 1.34 mL/kg (range, 0.22-4.42 mL/kg). Glycerin, a raw material imported to Haiti and used in the acetaminophen formulation, was contaminated with 24% DEG.

For more information on human intoxication cases please see chapter 7.10 - Exposure related observations.

Acute inhalation toxicity

Cascieri et al. (1991) reported an inhalative LC50 value of > 4.6 mg/L for 4 hours. Rats were given diethylene glycol as an aerosol with maximum attainable concentrations of 4.4 - 4.6 mg/L. There were no deaths during the 14-day observation period. Rapid recovery on removal, a transient body weight loss with recovery within 3 - 5 days and nasal discharge or lacrimation suggestive of minor irritation which persisted for several days were seen in this study. Post-mortem examinations were unremarkable.

Acute dermal toxicity

Union Carbide (1978) reported a dermal LD50 value of 13330 mg/kg for rabbits. This test was done under occlusive conditions. No further information about this study is available.

There are reports that also dermal exposure in certain scenarios (whole-body exposure from creams) can be toxic in man.

Justification for classification or non-classification

The available experimental animal data are reliable and suitable for classification purposes under Regulation (EC) No 1272/2008. As a result the substance is not considered to be classified for acute toxicity under Regulation (EC) No 1272/2008.

However, as the substance is classified as Acute Tox 4, H302 according to Annex VI under Regulation (EC) No 1272/2008 this classification is followed.