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DIPROPYLENE GLYCOL

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Classification   |    Detailed evidence-based information

Substances Included Synonyms

Therapeutic Toxic Class

    A) Dipropylene glycol is prepared commercially as a by-product of propylene glycol.

Specific Substances

    1) 2,2-Dihydroxyisopropyl ether
    2) 4-Oxaheptane-2,6-diol
    3) 1,1'-Oxybis (propan-2-ol)
    4) DPG
    5) Molecular Formula: C6-H14-O3
    6) CAS 25265-71-8

Available Forms Sources

    A) USES
    1) Dipropylene glycol is used as a solvent for lacquers, paint, printing ink, shellac varnish, and inhalant medicaments. It is also used as a vehicle for topical piperonyl butoxide insecticides in veterinary medicine.

Overview

Life Support

    A) This overview assumes that basic life support measures have been instituted.

Clinical Effects

    0.2.1) SUMMARY OF EXPOSURE
    A) Inhalation, dermal contact and ingestion are the most probable route of human exposure to dipropylene glycol. Dipropylene glycol has a low order of toxicity following acute ingestion, but little data are available. A man developed acute renal failure, polyneuropathy, and myopathy after ingesting more than 500 mL of dipropylene glycol solution, Nyquil, and naproxen sodium.
    B) ANIMAL STUDIES - Based on animal data, it is estimated that the acute lethal dose in adults is greater than 1 pint. Liver and kidney damage were observed in animals.
    0.2.4) HEENT
    A) Minor corneal irritation was reported in animals.
    0.2.6) RESPIRATORY
    A) Dipropylene glycol has little vapor hazard at ordinary temperatures.
    0.2.7) NEUROLOGIC
    A) WITH POISONING/EXPOSURE
    1) Polyneuropathy has been reported following the ingestion of dipropylene glycol solution.
    2) ANIMAL STUDIES - CNS depression was reported in dogs given 6 mL/kg IV. No toxicity was noted when 5 mL/kg was given orally.
    0.2.9) HEPATIC
    A) Extremely large amounts may produce liver injury.
    0.2.10) GENITOURINARY
    A) WITH POISONING/EXPOSURE
    1) Acute renal failure has been reported following the ingestion of dipropylene glycol solution.
    0.2.15) MUSCULOSKELETAL
    A) WITH POISONING/EXPOSURE
    1) Myopathy has been reported following the ingestion of dipropylene glycol solution.

Laboratory Monitoring

    A) Monitor hepatic and renal function.

Treatment Overview

    0.4.2) ORAL/PARENTERAL EXPOSURE
    A) Treatment is symptomatic and supportive.
    B) ACTIVATED CHARCOAL: Administer charcoal as a slurry (240 mL water/30 g charcoal). Usual dose: 25 to 100 g in adults/adolescents, 25 to 50 g in children (1 to 12 years), and 1 g/kg in infants less than 1 year old.

Range Of Toxicity

    A) A man developed acute renal failure, polyneuropathy, and myopathy after ingesting more than 500 mL of dipropylene glycol solution, Nyquil, and naproxen sodium.
    B) It is estimated that the acute lethal dose for a 100 pound human is greater than 1 pint.
    C) LD50 (RAT) - 14.85 g/kg PO; more than 20 mL/kg dermally

Clinical Effects

Summary Of Exposure

    A) Inhalation, dermal contact and ingestion are the most probable route of human exposure to dipropylene glycol. Dipropylene glycol has a low order of toxicity following acute ingestion, but little data are available. A man developed acute renal failure, polyneuropathy, and myopathy after ingesting more than 500 mL of dipropylene glycol solution, Nyquil, and naproxen sodium.
    B) ANIMAL STUDIES - Based on animal data, it is estimated that the acute lethal dose in adults is greater than 1 pint. Liver and kidney damage were observed in animals.

Heent

    3.4.1) SUMMARY
    A) Minor corneal irritation was reported in animals.
    3.4.3) EYES
    A) CORNEAL IRRITATION - Minor corneal irritation has been observed following ocular exposure in animals (Carpenter & Smyth, 1946).

Respiratory

    3.6.1) SUMMARY
    A) Dipropylene glycol has little vapor hazard at ordinary temperatures.
    3.6.2) CLINICAL EFFECTS
    A) RESPIRATORY FINDING
    1) LACK OF EFFECT
    a) VOLATILITY - Due to low volatility, dipropylene glycol has little vapor hazard at ordinary temperatures.

Neurologic

    3.7.1) SUMMARY
    A) WITH POISONING/EXPOSURE
    1) Polyneuropathy has been reported following the ingestion of dipropylene glycol solution.
    2) ANIMAL STUDIES - CNS depression was reported in dogs given 6 mL/kg IV. No toxicity was noted when 5 mL/kg was given orally.
    3.7.2) CLINICAL EFFECTS
    A) POLYNEUROPATHY
    1) WITH POISONING/EXPOSURE
    a) CASE REPORT - A 32-year-old man developed acute renal failure, polyneuropathy, and myopathy after ingesting more than 500 mL of dipropylene glycol solution (Fantasia fog), 120 mL of Nyquil, and approximately 10 tablets of 220 mg of naproxen sodium. His physical exam showed a left facial palsy and proximal muscle weakness. A muscle biopsy revealed inflammatory myositis and an electromyograph was consistent with peripheral axonopathy. An MRI showed abnormal enhancement of cranial nerves, V, VII, IX, and X. Following tracheostomy and feeding tube placement, he was discharged to a long-term facility. He had persistent neurologic deficits and still required hemodialysis at 6-month follow-up (LoVecchio et al, 2008).
    3.7.3) ANIMAL EFFECTS
    A) ANIMAL STUDIES
    1) CNS DEPRESSION
    a) DOGS - CNS depression was observed in dogs following intravenous doses of 6 mL/kg. Oral doses of 5 mL/kg produced no evidence of toxicity (Hanzlik et al, 1939).

Hepatic

    3.9.1) SUMMARY
    A) Extremely large amounts may produce liver injury.
    3.9.3) ANIMAL EFFECTS
    A) ANIMAL STUDIES
    1) HEPATOCELLULAR DAMAGE
    a) Hepatic injury may occur following ingestion of extremely large amounts. Dipropylene glycol was less toxic to the liver than ethylene or diethylene glycol in animals. Administration of 10% in drinking water resulted in liver parenchymal degeneration in rats (Kesten et al, 1939).

Genitourinary

    3.10.1) SUMMARY
    A) WITH POISONING/EXPOSURE
    1) Acute renal failure has been reported following the ingestion of dipropylene glycol solution.
    3.10.2) CLINICAL EFFECTS
    A) ACUTE RENAL FAILURE SYNDROME
    1) WITH POISONING/EXPOSURE
    a) CASE REPORT - A 32-year-old man developed acute renal failure, neuropathy, and myopathy 3 days after ingesting more than 500 mL of dipropylene glycol solution (Fantasia fog), 120 mL of Nyquil, and approximately 2200 mg of naproxen sodium. On admission, his serum urea nitrogen and creatinine levels were 53 mg/dL (reference range, 8 to 25 mg/dL) and 6.4 mg/dL (reference range, 0.6 to 1.5 mg/dL), respectively. All other tests including serum acetaminophen, salicylate, methanol, ethanol, and plasma ethylene glycol were negative. He later became oliguric and underwent hemodialysis. His serum urea nitrogen and creatinine levels on day 6 were 171 and 17.7 mg/dL, respectively. On day 10, a renal biopsy revealed cortical necrosis. Despite supportive treatment, he required tracheostomy and feeding tube placement. He later was discharged to a long-term facility. He had persistent neurologic deficits and still required hemodialysis at 6-month follow-up (LoVecchio et al, 2008).
    3.10.3) ANIMAL EFFECTS
    A) ANIMAL STUDIES
    1) RENAL FUNCTION ABNORMAL
    a) Renal injury may occur following ingestion of extremely large amounts. Acute administration of 4 mL/kg resulted in renal tubular degeneration in rats (Karel et al, 1947). Chronic administration of 10% in drinking water produced kidney tubular epithelium degeneration in rats (Kesten et al, 1939).

Acid-Base

    3.11.2) CLINICAL EFFECTS
    A) LACTIC ACIDOSIS
    1) LACK OF EFFECT
    a) Lactic acid was not increased, in contrast to other glycols (Newman et al, 1940).

Musculoskeletal

    3.15.1) SUMMARY
    A) WITH POISONING/EXPOSURE
    1) Myopathy has been reported following the ingestion of dipropylene glycol solution.
    3.15.2) CLINICAL EFFECTS
    A) DISORDER OF MUSCLE
    1) WITH POISONING/EXPOSURE
    a) CASE REPORT - A 32-year-old man developed acute renal failure, polyneuropathy, and myopathy after ingesting more than 500 mL of dipropylene glycol solution (Fantasia fog), 120 mL of Nyquil, and approximately 2200 mg of naproxen sodium. His physical exam showed a left facial palsy and proximal muscle weakness. A muscle biopsy revealed inflammatory myositis and an electromyograph was consistent with peripheral axonopathy. An MRI showed abnormal enhancement of cranial nerves, V, VII, IX, and X. Following tracheostomy and feeding tube placement, he was discharged to a long-term facility. He had persistent neurologic deficits and still required hemodialysis at 6-month follow-up (LoVecchio et al, 2008).

Carcinogenicity

    3.21.1) IARC CATEGORY
    A) IARC Carcinogenicity Ratings for CAS25265-71-8 (International Agency for Research on Cancer (IARC), 2016; International Agency for Research on Cancer, 2015; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2010; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2010a; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2008; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2007; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2006; IARC, 2004):
    1) Not Listed

Laboratory Monitoring

Monitoring Parameters Levels

    4.1.1) SUMMARY
    A) Monitor hepatic and renal function.

Treatment

Life Support

    A) Support respiratory and cardiovascular function.

Monitoring

    A) Monitor hepatic and renal function.

Oral Exposure

    6.5.1) PREVENTION OF ABSORPTION/PREHOSPITAL
    A) ACTIVATED CHARCOAL
    1) PREHOSPITAL ACTIVATED CHARCOAL ADMINISTRATION
    a) Consider prehospital administration of activated charcoal as an aqueous slurry in patients with a potentially toxic ingestion who are awake and able to protect their airway. Activated charcoal is most effective when administered within one hour of ingestion. Administration in the prehospital setting has the potential to significantly decrease the time from toxin ingestion to activated charcoal administration, although it has not been shown to affect outcome (Alaspaa et al, 2005; Thakore & Murphy, 2002; Spiller & Rogers, 2002).
    1) In patients who are at risk for the abrupt onset of seizures or mental status depression, activated charcoal should not be administered in the prehospital setting, due to the risk of aspiration in the event of spontaneous emesis.
    2) The addition of flavoring agents (cola drinks, chocolate milk, cherry syrup) to activated charcoal improves the palatability for children and may facilitate successful administration (Guenther Skokan et al, 2001; Dagnone et al, 2002).
    2) CHARCOAL DOSE
    a) Use a minimum of 240 milliliters of water per 30 grams charcoal (FDA, 1985). Optimum dose not established; usual dose is 25 to 100 grams in adults and adolescents; 25 to 50 grams in children aged 1 to 12 years (or 0.5 to 1 gram/kilogram body weight) ; and 0.5 to 1 gram/kilogram in infants up to 1 year old (Chyka et al, 2005).
    1) Routine use of a cathartic with activated charcoal is NOT recommended as there is no evidence that cathartics reduce drug absorption and cathartics are known to cause adverse effects such as nausea, vomiting, abdominal cramps, electrolyte imbalances and occasionally hypotension (None Listed, 2004).
    b) ADVERSE EFFECTS/CONTRAINDICATIONS
    1) Complications: emesis, aspiration (Chyka et al, 2005). Aspiration may be complicated by acute respiratory failure, ARDS, bronchiolitis obliterans or chronic lung disease (Golej et al, 2001; Graff et al, 2002; Pollack et al, 1981; Harris & Filandrinos, 1993; Elliot et al, 1989; Rau et al, 1988; Golej et al, 2001; Graff et al, 2002). Refer to the ACTIVATED CHARCOAL/TREATMENT management for further information.
    2) Contraindications: unprotected airway (increases risk/severity of aspiration) , nonfunctioning gastrointestinal tract, uncontrolled vomiting, and ingestion of most hydrocarbons (Chyka et al, 2005).
    6.5.2) PREVENTION OF ABSORPTION
    A) ACTIVATED CHARCOAL
    1) CHARCOAL ADMINISTRATION
    a) Consider administration of activated charcoal after a potentially toxic ingestion (Chyka et al, 2005). Administer charcoal as an aqueous slurry; most effective when administered within one hour of ingestion.
    2) CHARCOAL DOSE
    a) Use a minimum of 240 milliliters of water per 30 grams charcoal (FDA, 1985). Optimum dose not established; usual dose is 25 to 100 grams in adults and adolescents; 25 to 50 grams in children aged 1 to 12 years (or 0.5 to 1 gram/kilogram body weight) ; and 0.5 to 1 gram/kilogram in infants up to 1 year old (Chyka et al, 2005).
    1) Routine use of a cathartic with activated charcoal is NOT recommended as there is no evidence that cathartics reduce drug absorption and cathartics are known to cause adverse effects such as nausea, vomiting, abdominal cramps, electrolyte imbalances and occasionally hypotension (None Listed, 2004).
    b) ADVERSE EFFECTS/CONTRAINDICATIONS
    1) Complications: emesis, aspiration (Chyka et al, 2005). Aspiration may be complicated by acute respiratory failure, ARDS, bronchiolitis obliterans or chronic lung disease (Golej et al, 2001; Graff et al, 2002; Pollack et al, 1981; Harris & Filandrinos, 1993; Elliot et al, 1989; Rau et al, 1988; Golej et al, 2001; Graff et al, 2002). Refer to the ACTIVATED CHARCOAL/TREATMENT management for further information.
    2) Contraindications: unprotected airway (increases risk/severity of aspiration) , nonfunctioning gastrointestinal tract, uncontrolled vomiting, and ingestion of most hydrocarbons (Chyka et al, 2005).
    6.5.3) TREATMENT
    A) SUPPORT
    1) No specific treatment recommendations. Treatment with ethanol as for ethylene glycol is not likely to be useful.
    B) MONITORING OF PATIENT
    1) Monitor hepatic and renal function in substantial overdoses.

Range Of Toxicity

Summary

    A) A man developed acute renal failure, polyneuropathy, and myopathy after ingesting more than 500 mL of dipropylene glycol solution, Nyquil, and naproxen sodium.
    B) It is estimated that the acute lethal dose for a 100 pound human is greater than 1 pint.
    C) LD50 (RAT) - 14.85 g/kg PO; more than 20 mL/kg dermally

Minimum Lethal Exposure

    A) ACUTE
    1) Based on animal data, it is estimated that the acute lethal dose for a 100 pound human is greater than 1 pint.

Maximum Tolerated Exposure

    A) CASE REPORT - A 32-year-old man acute renal failure, polyneuropathy, and myopathy after ingesting more than 500 mL of dipropylene glycol solution (Fantasia fog), 120 mL of Nyquil, and approximately 10 tablets of 220 mg of naproxen sodium. Despite supportive treatment, he required tracheostomy and feeding tube placement. He later was discharged to a long-term facility. He had persistent neurologic deficits and still required hemodialysis at 6-month follow-up (LoVecchio et al, 2008).

Workplace Standards

    A) ACGIH TLV Values for CAS25265-71-8 (American Conference of Governmental Industrial Hygienists, 2010):
    1) Not Listed

    B) NIOSH REL and IDLH Values for CAS25265-71-8 (National Institute for Occupational Safety and Health, 2007):
    1) Not Listed

    C) Carcinogenicity Ratings for CAS25265-71-8 :
    1) ACGIH (American Conference of Governmental Industrial Hygienists, 2010): Not Listed
    2) EPA (U.S. Environmental Protection Agency, 2011): Not Listed
    3) IARC (International Agency for Research on Cancer (IARC), 2016; International Agency for Research on Cancer, 2015; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2010; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2010a; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2008; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2007; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2006; IARC, 2004): Not Listed
    4) NIOSH (National Institute for Occupational Safety and Health, 2007): Not Listed
    5) MAK (DFG, 2002): Not Listed
    6) NTP (U.S. Department of Health and Human Services, Public Health Service, National Toxicology Project ): Not Listed

    D) OSHA PEL Values for CAS25265-71-8 (U.S. Occupational Safety, and Health Administration (OSHA), 2010):
    1) Not Listed

Toxicity Information

    7.7.1) TOXICITY VALUES
    A) ANIMAL DATA
    1) LD50- (INTRAPERITONEAL)MOUSE:
    a) 4494 mg/kg (RTECS , 2001a)
    2) LD50- (INTRAPERITONEAL)RAT:
    a) 10 gm/kg (RTECS , 2001a)
    3) LD50- (ORAL)RAT:
    a) 14850 mg/kg (RTECS , 2001a)

Physicochemical

Physical Characteristics

    A) Dipropylene glycol is colorless and odorless (HSDB , 2001).

Molecular Weight

    A) 134.20 (RTECS , 2001)

References

General Bibliography

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