Propylene glycol
| 1. NAME |
| 1.1 Substance |
| 1.2 Group |
| 1.3 Synonyms |
| 1.4 Identification numbers |
| 1.4.1 CAS number |
| 1.4.2 Other numbers |
| 1.5 Main brand names, main trade names |
| 1.6 Main manufacturers, main importers |
| 2. SUMMARY |
| 2.1 Main risks and target organs |
| 2.2 Summary of clinical effects |
| 2.3 Diagnosis |
| 2.4 First-aid measures and management principles |
| 3. PHYSICO-CHEMICAL PROPERTIES |
| 3.1 Origin of the substance |
| 3.2 Chemical structure |
| 3.3 Physical properties |
| 3.3.1 Colour |
| 3.3.2 State/Form |
| 3.3.3 Description |
| 3.4 Hazardous characteristics |
| 4. USES |
| 4.1 Uses |
| 4.1.1 Uses |
| 4.1.2 Description |
| 4.2 High risk circumstance of poisoning |
| 4.3 Occupationally exposed populations |
| 5. ROUTES OF ENTRY |
| 5.1 Oral |
| 5.2 Inhalation |
| 5.3 Dermal |
| 5.4 Eye |
| 5.5 Parenteral |
| 5.6 Other |
| 6. KINETICS |
| 6.1 Absorption by route of exposure |
| 6.2 Distribution by route of exposure |
| 6.3 Biological half-life by route of exposure |
| 6.4 Metabolism |
| 6.5 Elimination by route of exposure |
| 7. TOXICOLOGY |
| 7.1 Mode of Action |
| 7.2 Toxicity |
| 7.2.1 Human data |
| 7.2.1.1 Adults |
| 7.2.1.2 Children |
| 7.2.2 Relevant animal data |
| 7.2.3 Relevant in vitro data |
| 7.2.4 Workplace standards |
| 7.2.5 Acceptable daily intake (ADI) |
| 7.3 Carcinogenicity |
| 7.4 Teratogenicity |
| 7.5 Mutagenicity |
| 7.6 Interactions |
| 8. TOXICOLOGICAL ANALYSES AND BIOMEDICAL INVESTIGATIONS |
| 8.1 Material sampling plan |
| 8.1.1 Sampling and specimen collection |
| 8.1.1.1 Toxicological analyses |
| 8.1.1.2 Biomedical analyses |
| 8.1.1.3 Arterial blood gas analysis |
| 8.1.1.4 Haematological analyses |
| 8.1.1.5 Other (unspecified) analyses |
| 8.1.2 Storage of laboratory samples and specimens |
| 8.1.2.1 Toxicological analyses |
| 8.1.2.2 Biomedical analyses |
| 8.1.2.3 Arterial blood gas analysis |
| 8.1.2.4 Haematological analyses |
| 8.1.2.5 Other (unspecified) analyses |
| 8.1.3 Transport of laboratory samples and specimens |
| 8.1.3.1 Toxicological analyses |
| 8.1.3.2 Biomedical analyses |
| 8.1.3.3 Arterial blood gas analysis |
| 8.1.3.4 Haematological analyses |
| 8.1.3.5 Other (unspecified) analyses |
| 8.2 Toxicological Analyses and Their Interpretation |
| 8.2.1 Tests on toxic ingredient(s) of material |
| 8.2.1.1 Simple Qualitative Test(s) |
| 8.2.1.2 Advanced Qualitative Confirmation Test(s) |
| 8.2.1.3 Simple Quantitative Method(s) |
| 8.2.1.4 Advanced Quantitative Method(s) |
| 8.2.2 Tests for biological specimens |
| 8.2.2.1 Simple Qualitative Test(s) |
| 8.2.2.2 Advanced Qualitative Confirmation Test(s) |
| 8.2.2.3 Simple Quantitative Method(s) |
| 8.2.2.4 Advanced Quantitative Method(s) |
| 8.2.2.5 Other Dedicated Method(s) |
| 8.2.3 Interpretation of toxicological analyses |
| 8.3 Biomedical investigations and their interpretation |
| 8.3.1 Biochemical analysis |
| 8.3.1.1 Blood, plasma or serum |
| 8.3.1.2 Urine |
| 8.3.1.3 Other fluids |
| 8.3.2 Arterial blood gas analyses |
| 8.3.3 Haematological analyses |
| 8.3.4 Interpretation of biomedical investigations |
| 8.4 Other biomedical (diagnostic) investigations and their interpretation |
| 8.5 Overall Interpretation of all toxicological analyses and toxicological investigations |
| 8.6 References |
| 9. CLINICAL EFFECTS |
| 9.1 Acute poisoning |
| 9.1.1 Ingestion |
| 9.1.2 Inhalation |
| 9.1.3 Skin exposure |
| 9.1.4 Eye contact |
| 9.1.5 Parenteral exposure |
| 9.1.6 Other |
| 9.2 Chronic poisoning |
| 9.2.1 Ingestion |
| 9.2.2 Inhalation |
| 9.2.3 Skin exposure |
| 9.2.4 Eye contact |
| 9.2.5 Parenteral exposure |
| 9.2.6 Other |
| 9.3 Course, prognosis, cause of death |
| 9.4 Systematic description of clinical effects |
| 9.4.1 Cardiovascular |
| 9.4.2 Respiratory |
| 9.4.3 Neurological |
| 9.4.3.1 Central Nervous System (CNS) |
| 9.4.3.2 Peripheral nervous system |
| 9.4.3.3 Autonomic nervous system |
| 9.4.3.4 Skeletal and smooth muscle |
| 9.4.4 Gastrointestinal |
| 9.4.5 Hepatic |
| 9.4.6 Urinary |
| 9.4.6.1 Renal |
| 9.4.6.2 Others |
| 9.4.7 Endocrine and reproductive systems |
| 9.4.8 Dermatological |
| 9.4.9 Eye, ears, nose, throat: local effects |
| 9.4.10 Haematological |
| 9.4.11 Immunological |
| 9.4.12 Metabolic |
| 9.4.12.1 Acid-base disturbances |
| 9.4.12.2 Fluid and electrolyte disturbances |
| 9.4.12.3 Others |
| 9.4.13 Allergic reactions |
| 9.4.14 Other clinical effects |
| 9.4.15 Special risks |
| 9.5 Others |
| 9.6 Summary |
| 10. MANAGEMENT |
| 10.1 General principles |
| 10.2 Life supportive procedures and symptomatic treatment |
| 10.3 Decontamination |
| 10.4 Enhanced elimination |
| 10.5 Antidote treatment |
| 10.5.1 Adults |
| 10.5.2 Children |
| 10.6 Management discussion |
| 11. ILLUSTRATIVE CASES |
| 11.1 Case reports from literature |
| 12. ADDITIONAL INFORMATION |
| 12.1 Specific preventive measures |
| 12.2 Other |
| 13. REFERENCES |
| 14. AUTHOR(S), REVIEWER(S), DATE(S) (INCLUDING UPDATES), COMPLETE ADDRESS(ES) |
PROPYLENE GLYCOL
International Programme on Chemical Safety
Poisons Information Monograph 443
Chemical
1. NAME
1.1 Substance
Propylene glycol
1.2 Group
Alcohol
1.3 Synonyms
1.2-propylene glycol;
Alpha-beta-dioxypropan;
alpha-propylene glycol;
dowfrost;
glicol propilenico;
glikol propylenowy;
methylethylene glycol;
Methylglycol;
monopropylene glycol;
PG 12;
propandiol-1.2;
propane-1.2-diol;
propilenoglicol;
propylene glycol USP;
Propylenglykol;
Sirlene;
solar winter ban;
trimethyl glycol;
1.4 Identification numbers
1.4.1 CAS number
57-55-6
1.4.2 Other numbers
NIOSH TY 2000000
1.5 Main brand names, main trade names
To be completed by each centre.
1.6 Main manufacturers, main importers
To be completed by each centre.
2. SUMMARY
2.1 Main risks and target organs
Relatively non-toxic in acute exposure. It is primarily
a CNS depressant in high doses. On rare occasions stupor and
unconsciousness occurred after parenteral administration).
After chronic exposure, seizures in man and renal and hepatic
damage in animals have been described.
2.2 Summary of clinical effects
Ocular exposure causes mild ocular irritation with
hyperaemia; chronic or prolonged skin and mucous membranes
exposure may also cause irritation; gastrointestinal
disturbances, nausea and vomiting have been observed after
ingestion.
Rapid intravenous injection of preparations of drugs
containing propylene glycol as a solvent (in significant
amounts) may cause unconsciousness, arrhythmias and even
cardiac arrest.
Chronic exposure may cause lactic acidosis, hypoglycaemia,
stupor, and seizures; renal and hepatic damage have been
observed only in animals.
2.3 Diagnosis
Is based on history of exposure (ingestion, inhalation
or parenteral administration) and irritation and/or CNS
effects.
Symptomatology is dose-dependent, ranging from drowsiness to
stupor, deep unconsciousness, and coma. Other signs include
hyperosmolality of serum, lactic acidosis, and hypoglycaemia
(Martin & Finberg, 1970).
The serum concentration may be measured by gas liquid
chromatography but it is not helpful clinically. There is a
direct relationship between the serum level of propylene
glycol and the osmolar gap (mg/dl = 84.6 + 78 × osmolar gap
in mOsm/kg).
Some procedures of ethylene glycol measurement in the
biological fluids also measure propylene glycol. This may
lead to misdiagnosis of the severe condition of ethylene
glycol poisoning in a patient who has been given drugs
containing, as a solvent, the relatively innocuous propylene
glycol.
Acid-based parameters, glycaemia, serum electrolytes, serum
lactates and osmolality should be monitored.
2.4 First-aid measures and management principles
Considerable toxicity is unlikely after an acute
exposure, with the exception of rare but dramatic arrhythmias
including cardiac arrest after rapid i.v. injection of drugs
containing large amounts of propylene glycol solvent. In
such cases, regular acute cardiological monitoring should be
undertaken. Other treatment should be supportive.
Ethanol or 4-methylpyrazole administration are absolutely not
needed.
Metabolic acidosis should be monitored, especially after
prolonged exposure.
3. PHYSICO-CHEMICAL PROPERTIES
3.1 Origin of the substance
Synthetic, manufactured by various ways, but recently by
hydration of propylene oxide (Faith, Keyes & Clark's
Industrial Chemicals, 1975).
3.2 Chemical structure
1,2 propanediol: CH3CHOHCH2OH
Gross formula:C3H8O2
3.3 Physical properties
3.3.1 Colour
Colourless
3.3.2 State/Form
Liquid
3.3.3 Description
Liquid at room temperature, thick and sweetish
like glycerol, colourless and odourless,
Boiling point: 188.2°C
Freezing point: -39°C
Flash point: 210 F (= 99°C)
Autoignition temperature: 700°C
Relative vapour density: 2.62
Vapour pressure: 0.08mm at 20°C
Miscible with water and ethanol in all proportions,
soluble in 12 parts of ether, miscible with acetone,
chloroform and some essential oils.
Explosive limits: not available
pH: not available
viscosity: not available
3.4 Hazardous characteristics
Combustible and in the form of vapour explosive when
exposed to heat or flame. Combustion products are carbon
dioxide and water but when heated to decomposition it
produces acrid smoke and irritating fumes (Sax, 1989).
No significantly dangerous substances are produced after
contact with light, humidity or commonly available chemicals.
Propylene glycol may react with hydrofluoric acid + nitric
acid + silver nitrate to form the explosive silver fulminate
(Sax, 1989).
4. USES
4.1 Uses
4.1.1 Uses
4.1.2 Description
Non-toxic antifreeze in breweries and dairies;
brake fluid; substitute for ethylene glycol and
glycerol; manufacture of synthetic resins. Added to
foods as a humefactant or solvent for artificial
colouring or flavouring agents. Is a component of
cosmetic preparations.
Solvent in many pharmaceuticals, including oral,
injectable or topical formulations (Smolinske et al,
1987).
Many oral and parenteral drug preparations contain
propylene glycol in significant amounts as a
solvent:
Trade Name Amount of Propylene Glycol,
W/v-mg/ml
Amidate 362.6mg
Apresoline 103.6mg
Bactrim 414.4mg
Berocca PN 259mg
Brevibloc 25% v/v
Dilantin 414.4mg
Dramamine 518mg
Dramocen 518mg
Embolex 460mg
Hydrocortisone 800-900mg
Konakion 207mg
Lanoxin & Lanoxin Ped. 414.4mg
Librium 207mg
Loxitane 725.2mg
Luminal Sodium 702.4mg
MVC9 Plus 3108mg
MVI-123 108mg
Nitro-BID 45mg
Nembutal 414.4mg
Nitrostat 3108mg
Nitroglycerin 518mg
Pentobarbital Sodium 414.4mg
Phenobarbital Sodium 702.4mg
Phenytoin Sodium 3108mg or 414.4mg
Septra 414.4mg
Tridil 3108mg
Valium 414.4mg
There is no evidence that propylene glycol has been a
substance of abuse. Its actions are similar to those
of ethanol (thrice weaker) although it is only
one-0third as potent; propylene glycol could be used
as an ethanol substitute if it becomes more readily
available or cheaper.
4.2 High risk circumstance of poisoning
Intoxication similar to that caused by ethanol might be
expected if large amounts of propylene glycol were ingested.
In reported cases toxic signs appeared only after repeated
doses of propylene glycol, used as a solvent in medicines,
were ingested in small amounts or repeatedly applied to the
skin (Glasgow et al, 1983; Martin & Finberg, 1970).
Acute toxicity following i.v. injection of drugs dissolved in
significant amounts of propylene glycol has been reported
(Hegarty & Dundee, 1977; Demey et al, 1988).
4.3 Occupationally exposed populations
Workers of chemical plants producing propylene glycol;
using it as a raw material in chemical processes; or as a
solvent in the manufacture of drugs, cosmetics, and household
chemicals.
Estimated acceptable daily intake: up to 25 mg propylene
glycol per kg body weight (Seventeeth Report of the FAO/WHO
Expert Committee, 1974).
5. ROUTES OF ENTRY
5.1 Oral
Several oral drug formulations contain propylene glycol
as a solvent but may cause poisoning only after repeated
ingestion (Arulanantham & Genel, 1978; Martin & Finberg,
1970).
5.2 Inhalation
Not relevant.
5.3 Dermal
When applied as a topical formulation it may
occasionally irritate the skin and cause hypersensitivity
reactions (Fisher,1978; Adams & Maibach, 1985).
Mild lactic acidosis has been reported in an infant treated
topically with a cream for burns containing propylene glycol
(Yu et al, 1985). Serum hyperosmolality occurred in patients
with burns when large areas of damaged skin were covered with
sulfadiazine cream containing propylene glycol (Kulich et al,
1980; Fligner et al, 1985).
5.4 Eye
Eye irritation without further sequelae has been
reported (Reinhardt et al, 1978).
5.5 Parenteral
Generalized symptoms and signs of propylene glycol
poisoning were reported after intramuscular or intravenous
injections of drugs containing significant amounts of
propylene glycol as a solvent. The drugs involved were
solutions of benzodiazepines (Hegarty & Dundee, 1977),
nitroglycerin (Demey et al, 1984; Demey et al, 1988), and
phenytoin (Karliner, 1967; Voigt, 1968).
5.6 Other
Ear: There is a risk that instillation of propylene
glycol into the middle ear in patients with defects of the
tympanic membrane may cause cochlear toxicity, according to
animal data (Morizono et al, 1980).
6. KINETICS
6.1 Absorption by route of exposure
Oral: As with ethanol, absorption occurs rapidly. The
peak plasma level occurs within one hour after oral
administration (Yu et al, 1985).
Inhalation: Not relevant.
Dermal: Absorption may be rapid: in an infant with burns who
received cream containing propylene glycol for ten
consecutive days, cardiopulmonary arrest occurred one hour
after the cream had been re-administered after a two-day
drug-free interval (Fligner et al, 1985).
Eye: Immediate local irritation immediate; systemic
absorption not reported.
Parenteral: Absorption is immediate.
6.2 Distribution by route of exposure
After oral administration, the mean volume of
distribution is 0.58 (range 0.41-0.77) L/kg (Yu et al,
1985).
Inhalation: Not relevant
Dermal: Not available
Eye: Not relevant
After intravenous infusion, the volume of distribution is
36-62L (Speth et al, 1987).
6.3 Biological half-life by route of exposure
Oral: Mean half-life in premature infants was 19.3
hours (range 108-30.5) (Glasgow et al, 1983), no data
available in adults.
Dermal: 16.9 hours in an8-month-old infant (Fligner et al,
1985).
Parenteral: 2.4-5.2 hours [17, 22] 1.4-3.3 hours (mean
2.3+/-07h) (Speth et al, 1987).
6.4 Metabolism
Propylene glycol undergoes metabolic oxidation to
pyruvic acid,acetic acid, lactic acid, and propionaldehyde
(Miller & Bazzano, 1965; Ruddick, 1972).
6.5 Elimination by route of exposure
The route of elimination depends on the dose
administered, not on the route of exposure. It is mainly
excreted in the urine as the glucuronide conjugate but 12-45%
is excreted unchanged (Ruddick, 1972). Renal clearance
decreases with dose (390 mL/min/1.73 m2 at a dose of 5 g/day,
but only 144 mL/min/1.73 m2 at a dose of 21 g/day) (Speth et
al, 1987).
7. TOXICOLOGY
7.1 Mode of Action
The toxicity of propylene glycol is mainly due to the
parent compound and not to its metabolites. Propylene glycol
has an irritatant effect on direct contact with eyes, mucous
membranes and possibly after prolonged contact with skin.
Propylene glycol causes CNS depression similar to that caused
by ethanol but it is only one-third as potent. Cardiotoxic
effects include arrhythmias and cardiac arrest. Renal and
hepatic damage has been reported in animals (Seidenfeld &
Hanzlik, 1932), but there are no clinical data confirming
this effect.
The metabolites are relatively non-toxic: lactic acidosis
and serum hyperosmolality may occur.
7.2 Toxicity
7.2.1 Human data
7.2.1.1 Adults
The estimated acceptable daily
intake is 25 mg/kg (17th Report of the Joint
FAO/WHO Expert Committee on Food Additives,
1974). Single oral doses of 1.5 g/kg (used
in the treatment of glaucoma) caused
dizziness (Goldsmith, 1978). Lactic acidosis
and coma with hyperosmolality were seen in an
elderly patient with a propylene glycol serum
concentration of 910 mg/dl after IV
administration of nitroglycerin dissolved in
propylene glycol (Demey et al,
1984).
7.2.1.2 Children
Doses of 60 ml of propylene glycol
caused stupor in infants (Martin & Finberg,
1970). Administration of 3 g/day in a
premature infant weighing 800 g resulted in
hyperosmolality; the serum concentration of
propylene glycol was 930 mg/dl (Glasgow et
al, 1983).
7.2.2 Relevant animal data
LD50 oral, rat = 20g/kg
iv, rat = 68g/kg
oral, dog = 22g/kg (Sax, 1989)
7.2.3 Relevant in vitro data
7.2.4 Workplace standards
No ACG/IH TLV-TWA, OSHA PEL, or IDLH values
have been established for this agent (ACGIH, 1989;
NIOSH, 1985).
7.2.5 Acceptable daily intake (ADI)
25 mg/kg as food additive (17th Report of the
Joint FAO/WHO Expert Committee on Food Additives,
1974).
7.3 Carcinogenicity
No data available.
7.4 Teratogenicity
No teratogenic effects were seen in the rabbit
(Schumacher et al, 1968).
7.5 Mutagenicity
No data available.
7.6 Interactions
No data available.
8. TOXICOLOGICAL ANALYSES AND BIOMEDICAL INVESTIGATIONS
8.1 Material sampling plan
8.1.1 Sampling and specimen collection
8.1.1.1 Toxicological analyses
8.1.1.2 Biomedical analyses
8.1.1.3 Arterial blood gas analysis
8.1.1.4 Haematological analyses
8.1.1.5 Other (unspecified) analyses
8.1.2 Storage of laboratory samples and specimens
8.1.2.1 Toxicological analyses
8.1.2.2 Biomedical analyses
8.1.2.3 Arterial blood gas analysis
8.1.2.4 Haematological analyses
8.1.2.5 Other (unspecified) analyses
8.1.3 Transport of laboratory samples and specimens
8.1.3.1 Toxicological analyses
8.1.3.2 Biomedical analyses
8.1.3.3 Arterial blood gas analysis
8.1.3.4 Haematological analyses
8.1.3.5 Other (unspecified) analyses
8.2 Toxicological Analyses and Their Interpretation
8.2.1 Tests on toxic ingredient(s) of material
8.2.1.1 Simple Qualitative Test(s)
8.2.1.2 Advanced Qualitative Confirmation Test(s)
8.2.1.3 Simple Quantitative Method(s)
8.2.1.4 Advanced Quantitative Method(s)
8.2.2 Tests for biological specimens
8.2.2.1 Simple Qualitative Test(s)
8.2.2.2 Advanced Qualitative Confirmation Test(s)
8.2.2.3 Simple Quantitative Method(s)
8.2.2.4 Advanced Quantitative Method(s)
8.2.2.5 Other Dedicated Method(s)
8.2.3 Interpretation of toxicological analyses
8.3 Biomedical investigations and their interpretation
8.3.1 Biochemical analysis
8.3.1.1 Blood, plasma or serum
8.3.1.2 Urine
8.3.1.3 Other fluids
8.3.2 Arterial blood gas analyses
8.3.3 Haematological analyses
8.3.4 Interpretation of biomedical investigations
8.4 Other biomedical (diagnostic) investigations and their
interpretation
8.5 Overall Interpretation of all toxicological analyses and
toxicological investigations
Sample collection
To be filled by the Analytical Group.
Biomedical analysis
Gasometric blood measurements (pH and bicarbonates) are
necessary, serum osmolality, glucose, BUN, serum lactate and
electrolytes may be helpful. If the patient is vomiting,
serum electrolytes should be monitored.
Toxicological analysis
To be filled by the Analytical Group. Its attention is
called to the false positive results of colorimetric tests
for Ethylene glycol if Propylene glycol (e.g. administered as
drug solvent) is present in the blood (Robinson et al,
1983).
Other investigations
No data available
8.6 References
9. CLINICAL EFFECTS
9.1 Acute poisoning
9.1.1 Ingestion
Symptomatology is dose-dependent, ranging from
drowsiness to stupor, deep unconsciousness, and
coma.
Other signs include hyperosmolality of serum, lactic
acidosis, and hypoglycaemia (Martin & Finberg,
1970).
9.1.2 Inhalation
Not relevant.
9.1.3 Skin exposure
Absorption through intact skin is minimal, but
may become important in infants with skin lesions
(Fligner et al., 1985).
Local irritation and hypersensitivity reactions may
occur (Fisher, 1978; Adams & Maibach, 1985). Systemic
effects are less marked than after oral ingestion and
are more likely after repeated administration.
However, there is evidence that systemic effects may
immediately follow local application (Fligner et al.,
1985).
9.1.4 Eye contact
Eye irritation has been reported (Reinhardt et
al, 1978).
9.1.5 Parenteral exposure
Toxic effects have been reported after IV
injection or instillation of drugs dissolved in
propylene glycol. Propylene glycol may cause
hypotension; bradycardia, and QRS and T abnormalities
on the ECG; arrhythmia and cardiac arrest; and serum
hyperosmolality and lactic acidosis (Karliner, 1967;
Demey et al, 1988). Haemolysis may occur after i.v.
administration (Demey et al, 1988).
9.1.6 Other
Not relevant
9.2 Chronic poisoning
9.2.1 Ingestion
Most of the reported cases are of sub-acute
poisoning, since toxicity was observed usually after
several days of of administration of propylene glycol
as a solvent in oral, parenteral or topical
formulations of drugs.
Grand mal seizures occurred in an 11-year old boy
after taking a medication containing propylene glycol
over one year (Arulanantham & Genel, 1978). CNS
depression has been reported in patients taking
phenytoin dissolved in propylene glycol; this did not
recur when the solvent had been changed (Yu et al,
1985).
Sinus arrhythmia, tachypnea, tachycardia, stupor and
hypoglycaemia occurred in a 15-month-old boy who
received 7.5 ml of propylene glycol as a solvent in
vitamin C syrup (Martin & Finberg, 1970).
9.2.2 Inhalation
Not relevant
9.2.3 Skin exposure
Most of the reported cases are of sub-acute
poisoning, since toxicity was observed usually after
several days of of administration of propylene glycol
as a solvent in oral, parenteral or topical
formulations of drugs.
Local irritation and hypersensitivity reactions may
occur (Trancik & Maibach, 1982). Serum hyperosmolality
may also occur after percutaneous absorption (Kulich
et al, 1980; Bekeris et al, 1979).
9.2.4 Eye contact
Eye irritation is an acute, not a chronic
effect (Reinhardt et al, 1978).
9.2.5 Parenteral exposure
Most of the reported cases are of sub-acute
poisoning, since toxicity was observed usually after
several days of of administration of propylene glycol
as a solvent in oral, parenteral or topical
formulations of drugs. Seizures believed to be due to
propylene glycol solvent were seen in infants
receiving parenteral multivitamins (MacDonald et al,
1987). Lactic acidosis and hyperosmolality have been
reported (Glasgow et al, 1983; Demey et al, 1984;
Demey et al, 1988).
9.2.6 Other
Not relevant.
9.3 Course, prognosis, cause of death
The course of poisoning is usually benign but ingestion
of large amounts may be as dangerous as severe ethanol
intoxication. Large doses ingested or injected may cause
severe arrhythmia, including cardiac arrest, resulting in
sudden death (Karliner, 1967; Russell & Bousvaros, 1968;
Voigt,1968).
9.4 Systematic description of clinical effects
9.4.1 Cardiovascular
Acute: Rapid intravenous injection may cause
arrhythmia, even cardiac arrest. Bradycardia, QRS and
T abnormalities may occur (Gellerman & Martinez, 1967;
Demey et al, 1988).
Chronic: No data available.
9.4.2 Respiratory
Acute: No adverse respiratory effects have
been reported but in extremely severe intoxication
respiratory disturbances may occur due to CNS
depression.
Chronic: No data available.
9.4.3 Neurological
9.4.3.1 Central Nervous System (CNS)
Acute: Depression of the CNS may
appear as drowsiness, stupor, and rarely as
coma (Martin & Finberg, 1970; Demey et al,
1984; Demey et al, 1988; Yu et al, 1985;
Goldsmith, 1978).
Chronic: Seizures have been reported
(Arulanantham & Genel, 1978; Mac Donald et
al, 1987).
9.4.3.2 Peripheral nervous system
No data available.
9.4.3.3 Autonomic nervous system
No data available.
9.4.3.4 Skeletal and smooth muscle
Hypotonia has been reported.
9.4.4 Gastrointestinal
No data available.
9.4.5 Hepatic
Acute: Hepatotoxicity has been observed in
animals (Seidenfeld & Hanzlik, 1932).
Chronic: No data available.
9.4.6 Urinary
9.4.6.1 Renal
Acute: Pre-existing renal failure
aggravates propylene glycol poisoning and
worsens lactic acidosis (Cate & Hendrick,
1980). Renal toxicity has been reported in
animals (Seidenfeld & Hanzlik, 1932) but have
not been reported clinically.
Chronic: No data available.
9.4.6.2 Others
No data available.
9.4.7 Endocrine and reproductive systems
No data available.
9.4.8 Dermatological
Acute: No data available.
Chronic: Irritation of skin and mucous membranes is
usually negligible but may become marked especially if
propylene glycol is incorporated into impermeable pads
(Trancik & Maibach, 1982). Hypersensitivity reactions
have been reported (Hannuksela & Forstrom, 1978; Unger
& Sklaroff, 1967).
9.4.9 Eye, ears, nose, throat: local effects
Acute: Local irritation of the eye may occur
without any serious sequelae (Reinhardt et al,
1978).
Administration of drugs with propylene glycol as a
solvent into the ear should be avoided in patients
with defects in the ear drum since it may cause
cochlear toxicity (Morizono et al, 1980).
Chronic: No data available.
9.4.10 Haematological
Acute: Rapid intravenous injection of drugs
dissolved in propylene glycol may cause haemolysis
(Demey et al, 1984).
Chronic: No data available.
9.4.11 Immunological
In vitro, 1% propylene glycol is cytotoxic to
natural killer cells (Denning & Webster,
1987).
9.4.12 Metabolic
9.4.12.1 Acid-base disturbances
Acute: Lactic acidosis, with an
increase of serum lactate up to 15.5 mEq/L
[43] occurs when large doses are absorbed
regardless of the route of exposure (Demey et
al, 1984; Demey et al, 1988; Fligner et al,
1985; Cate & Hendrick, 1980; Kelner &
Bailey, 1985).
Chronic: No data available.
9.4.12.2 Fluid and electrolyte disturbances
No data available.
9.4.12.3 Others
Hyperosmolality occurs after marked
absorption of propylene glycol regardless of
the route of exposure (Glasgow et al, 1983;
Demey et al, 1988; Kulich et al, 1980;
Bekeris et al, 1979; Fligner et al,
1985).
There is a good correlation between the
osmolar gap and the serum propylene glycol
concentration. An estimation of the serum
propylene glycol concentration may be
calculated from the osmolar gap. 1 g of
propylene glycol has an osmotic effect of
13.1 mOsm/L. In a case reported by Fligner et
al (1985) the following correlation between
osmolality and propylene glycol concentration
was found:
propylene glycol level =84.6 + (78 × osmolar
gap in mOsm/kg H20).
Hypoglycaemia has been described in a little
boy after treatment with an oral vitamin C
preparation dissolved in propylene glycol
(Martin & Finberg, 1970). No effects on the
reproductive system have been
reported.
9.4.13 Allergic reactions
Acute: Hypersensitivity reactions affecting
the skin may occur (Hannuksela & Forstrom, 1978;
Adams & Maibach, 1985).
Chronic: No data available.
9.4.14 Other clinical effects
No data available
9.4.15 Special risks
No data available
9.5 Others
No data available
9.6 Summary
10. MANAGEMENT
10.1 General principles
Acute or chronic poisoning rarely need action other
than to withdraw the patient from the source of exposure and
observe until the symptoms disappear.
After exposure to large doses, coma, seizures and/or cardiac
arrhythmias necessitate monitoring of vital functions and
intensive care measures. Since the metabolites of propylene
glycol are less toxic than the parent substance, inhibition
of the metabolism of propylene glycol by ethanol or 4-methyl
pyrazole is unnecessary. Lactic acidosis does not usually
justify alkalinisation.
10.2 Life supportive procedures and symptomatic treatment
Acute or chronic poisoning rarely need action other
than to withdraw the patient from the source of exposure and
observe until the symptoms disappear. After large doses,
coma, seizures and/or cardiac arrhythmias necessitate
monitoring of vital functions and intensive care
measures.
10.3 Decontamination
In case of eye exposure wash with copious amounts of
water. Remove gastric contents by inducing vomiting or
lavage only after ingestion of large doses (>100 ml) and
very recent ingestion.
10.4 Enhanced elimination
No enhanced elimination procedures are needed.
10.5 Antidote treatment
10.5.1 Adults
Antidotes are not needed. Ethanol and
4-methylpyrazole have no place in the treatment of
propylene glycol poisoning.
10.5.2 Children
Antidotes are not needed. Ethanol and
4-methylpyrazole have no place in the treatment of
propylene glycol poisoning.
10.6 Management discussion
Not relevant.
11. ILLUSTRATIVE CASES
11.1 Case reports from literature
Case 1
A 6 month-old infant sustained a deep second to third degree
burn of the anterior part of the chest (8% of the total body
area). Initial therapy included topical silver sufadiazine
for six days. On the tenth day after the burn, erythema and
desquamation occurred over more than 70% on his total body
surface area. The desquamation was diagnosed as toxic
epidermal necrolysis and was considered equivalent to a
superficial and deep second-degree burn. Treatment with
topical silver sulfadiazine and dicloxacillin was begun, 78%
of the total body surface area was covered with the
preparation. The infant was alert, with a temperature of
38.4°C, pulse rate 132/min, respirations, 28/min, and weight
9.3kg. Continued topical therapy consisted of application
twice daily of gauze impregnated with 600 to800g of silver
sufadiazine.
On day 12, cardiorespiratory arrest occurred approximately
one hour after a debridement bath and a dressing change; no
medication had been given other than 15mg of oral
diphenhydramine given four hours before the arrest. An acute
respiratory acidosis was reflected by a pH of 7.28 and a
PC02 of 50 mmHg. After resuscitation, the results of
neurological examination reflected substantial hypoxic
damage.
The next day, the measured serum osmolality was 388 mOsm/kg
H20 with a simultaneously calculated serum osmolality of 314
mOsm/kg H20, so the osmolal gap was 74 mOsm/kg H20. During
the course of the day, the serum osmolality increased to 420
(osmolal gap to 130) mOsm/kg H20. The following day the
serum propylene glycol was 771 mg/dL. No source of serum
propylene glycol other than silver sufadiazine was detected
and this medication contained 76.7 mg/g of propylene glycol.
During the preceding 79 hours of hospitalization, 3,400 g of
the preparation had been applied resulting in a total
propylene glycol dose 9 g/kg/24 hr. Silver sulfadiazine
therapy was discontinued and the serum osmolality gradually
decreased to 298 mOsm/kg H20; blood lactate was 58 mmol/L,
alkalinising therapy was never required.
Mechanical ventilation continued for three weeks. The
patient's later course was marked by severe, persistent
hypoxic encephalopathy (Fligner et al, 1985).
Case 2
A 15-year-old was admitted for removal of the Wilm's tumour.
Surgery was followed by administration of actinomycin D and
radiotherapy. The postoperative course was complicated by
spiking fever and gastrointestinal bleeding, but by 40 days
after admission he was afebrile, eating well, and gaining
weight. He received ascorbic acid in large doses as a
preparation suspended in propylene glycol, 250 mg thrice a
day (7.5 ml), beginning on the 48th hospital day. Eight days
after starting vitamin C therapy he was noted to have a
sinus arrhythmia and two days later he was found unresponsive
with tachypnoea, tachycardia, and diaphoresis. He awoke soon
without further treatment. The cerebrospinal fluid was
normal, blood glucose was 70 mg/dL. Several similar episodes
occurred during the following 3 days, and serum glucose was
41 and 42 mg/dl, respectively, during the periods of
unresponsiveness. On one of those occasions he regained
consciousness after having received an i.v. infusion of a
solution containing 10 g of glucose. The fasting blood
glucose on the following day was 48, and the 2 hour
postprandial level was 42 mg/dL.
At that time, vitamin C therapy was stopped and no further
episodes occurred. A fasting blood glucose was84 mg/dl and a
glucose tolerance test normal 2 days after the therapy had
been discontinued (Martin & Finberg, 1970).
12. ADDITIONAL INFORMATION
12.1 Specific preventive measures
Avoiding production of pharmaceuticals containing
amounts of propylene glycol which may cause acute or chronic
poisoning when the drug is administered in therapeutic doses
parenterally, orally, or on the skin.
In the occupational setting the recommendations are: keep
away from flame (it is combustible), no smoking, ventilate
areas, use goggles.
12.2 Other
No data available.
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14. AUTHOR(S), REVIEWER(S), DATE(S) (INCLUDING UPDATES), COMPLETE
ADDRESS(ES)
Author: Janusz Szajewski, MD
Warsaw Poison Control Centre
Szpital Praski
03-701 Warszawa
Poland
Tel: 48-22-190897/196654
Fax: 48-22-196943
Tlx: 813601 sbtpl
Date: August 1991
Peer Review: Newcastle-upon-Tyne
United Kingdom
Date: February 1992
Review: IPCS
Date: May 1994