When used in average quantities, propylene glycol has no measurable effect on development and/or reproduction on animals and probably does not adversely affect human development or reproduction without active use. The
safety of electronic cigarettes—which use propylene glycol-based preparations of nicotine or THC and other cannabinoids—is the subject of much controversy.
Vitamin E acetate has also been identified in this controversy.
Oral administration The acute oral toxicity of propylene glycol is very low, and large quantities are required to cause perceptible health effects in humans; Propylene glycol is metabolized in the human body into
pyruvic acid (a normal part of the glucose-metabolism process, readily converted to energy),
acetic acid (handled by ethanol-metabolism),
lactic acid (a normal acid generally abundant during digestion), and
propionaldehyde (a potentially hazardous substance). According to the
Dow Chemical Company, the
LD50 (dose that kills 50% of the test population) for rats is 20 g/kg (oral/rat). Toxicity generally occurs at plasma concentrations over 4 g/L, which requires extremely high intake over a relatively short period of time, or when used as a vehicle for drugs or vitamins given intravenously or orally in large
bolus doses. It would be nearly impossible to reach toxic levels by consuming foods or supplements, which contain at most, by mass, one
per mille of PG, except for alcoholic beverages in the US, which are allowed five percent by mass. The potential for long-term oral toxicity is also low. In a
National Toxicology Program continuous breeding study, no effects on fertility were observed in male or female mice that received propylene glycol in drinking water at doses up to 10100 mg/kg bw/day. No effects on fertility were seen in either the first or second generation of treated mice.
Skin and eye contact . Propylene glycol may be non-irritating to the skin, see section
Allergic reaction below for details on allergic reactions. Undiluted propylene glycol is minimally irritating to the eye, producing slight transient
conjunctivitis; the eye recovers after the exposure is removed. Propylene glycol has not caused
sensitization or carcinogenicity in laboratory animal studies, nor has it demonstrated
genotoxic potential.
Inhalation Inhalation of propylene glycol vapors appears to present no significant hazard in ordinary applications. Due to the lack of chronic inhalation data, it is recommended that propylene glycol not be used in inhalation applications such as theatrical productions, or antifreeze solutions for emergency
eye wash stations. Recently, propylene glycol (commonly alongside
glycerol) has been included as a carrier for nicotine and other additives in
e-cigarette liquids, the use of which presents a novel form of exposure. The potential hazards of chronic inhalation of propylene glycol or the latter substance as a whole are as-yet unknown. According to a 2010 study, the concentrations of PGEs (counted as the sum of propylene glycol and
glycol ethers) in indoor air, particularly bedroom air, has been linked to increased risk of developing numerous respiratory and immune disorders in children, including
asthma,
hay fever,
eczema, and allergies, with increased risk ranging from 50% to 180%. This concentration has been linked to use of water-based paints and water-based system cleansers. However, the study authors write that
glycol ethers and not propylene glycol are the likely culprit.
Intravenous administration Studies with intravenously administered propylene glycol have resulted in LD50 values in rats and rabbits of 7 mL/kg BW. Ruddick (1972) also summarized intramuscular LD50 data for rat as 13–20 mL/kg BW, and 6 mL/kg BW for the rabbit. Adverse effects to
intravenous administration of drugs that use propylene glycol as an
excipient have been seen in a number of people, particularly with large bolus dosages. Responses may include CNS depression, "hypotension,
bradycardia,
QRS and
T abnormalities on the ECG,
arrhythmia, cardiac arrhythmias, seizures, agitation, serum
hyperosmolality,
lactic acidosis, and
haemolysis". A high percentage (12–42%) of directly-injected propylene glycol is eliminated or secreted in urine unaltered depending on dosage, with the remainder appearing in its
glucuronide-form. The speed of
renal filtration decreases as dosage increases, which may be due to propylene glycol's mild anesthetic /
CNS-depressant properties as an alcohol. In one case, intravenous administration of propylene glycol-suspended
nitroglycerin to an elderly man may have induced coma and
acidosis. However, no confirmed lethality from propylene glycol was reported.
Animals Propylene glycol is an approved food additive for dog and
sugar glider food under the category of animal feed and is
generally recognized as safe for dogs, with an LD50 of 9 mL/kg. The LD50 is higher for most laboratory animals (20 mL/kg). However, it is prohibited for use in food for cats due to links to
Heinz body formation and a reduced lifespan of red blood cells. Heinz body formation from MPG has not been observed in dogs, cattle, or humans.
Allergic reaction Estimates on the prevalence of propylene glycol allergy range from 0.8% (10% propylene glycol in aqueous solution) to 3.5% (30% propylene glycol in aqueous solution). The North American Contact Dermatitis Group (NACDG) data from 1996 to 2006 showed that the most common site for propylene glycol
contact dermatitis was the face (25.9%), followed by a generalized or scattered pattern (23.7%). Because of its potential for allergic reactions and frequent use across a variety of topical and systemic products, propylene glycol was named the American Contact Dermatitis Society's
Allergen of the Year for 2018. Recent publication from The Mayo Clinic reported 0.85% incidence of positive patch tests to propylene glycol (100/11,738 patients) with an overall irritant rate of 0.35% (41/11,738 patients) during a 20-year period of 1997–2016. 87% of the reactions were classified as weak and 9% as strong. The positive reaction rates were 0%, 0.26%, and 1.86% for 5%, 10%, and 20% propylene glycol respectively, increasing with each concentration increase. The irritant reaction rates were 0.95%, 0.24%, and 0.5% for 5%, 10%, and 20% propylene glycol, respectively. Propylene glycol skin sensitization occurred in patients sensitive to a number of other concomitant positive allergens, most common of which were: Myroxylon pereirae resin, benzalkonium chloride, carba mix, potassium dichromate, neomycin sulfate; for positive propylene glycol reactions, the overall median of 5 and mean of 5.6 concomitant positive allergens was reported. ==Environmental impacts==