Absorption, Distribution and Excretion
Orally administered propylene glycol undergoes first-order kinetics in both absorption and excretion via the gastrointestinal tract. It is rapidly cleared from the bloodstream, with a mean half-life of approximately 2 hours. Pyrazole inhibits propylene glycol metabolism, indicating the role of alcohol dehydrogenases in this process. Once absorbed, propylene glycol is rapidly converted to lactate and pyruvate, subsequently entering the systemic metabolic pool. Propylene glycol is readily absorbed from the gastrointestinal tract and distributed throughout the body's water systems. It has been reported that, due to inter-individual variability in clearance rates, significant differences in propylene glycol accumulation have been observed even among individuals receiving repeated oral dosing regimens. This study investigated the absorption of propylene glycol mist in humans using a 10% propylene glycol solution (dissolved in labeled deionized water) nebulized in a nebulization tent. Less than 5% of the mist entered the body, with 90% remaining in the nasopharynx and rapidly entering the stomach. Almost no mist was detected in the lungs.
After intravenous injection of propylene glycol (dose 3-15 g/m²), plasma concentrations ranged from 60 to 425 μg/mL, with a volume of distribution of 0.51 to 0.88 L/kg and a clearance of approximately 300 mL/min/1.73 m². Cerebrospinal fluid concentrations can reach up to 85% of serum concentrations.
For more complete data on the absorption, distribution, and excretion of propylene glycol (20 items in total), please visit the HSDB record page.
Metabolism/Metabolites

Propylene glycol is metabolized and oxidized to pyruvate, acetic acid, lactate, and propionaldehyde.
In mammals, the main metabolic pathway of propylene glycol is as follows: propylene glycol is first oxidized to lactaldehyde by alcohol dehydrogenases, and then oxidized to lactate by aldehyde dehydrogenases. Lactic acid is further metabolized to pyruvate, carbon dioxide, and water. Lactic acid can also participate in glucose production through gluconeogenesis. Lactic acid can be detoxified into glucose via the phosphoenolpyruvate pathway and stored as glycogen… Excessive exposure to propylene glycol leads to excessive lactic acid production, resulting in metabolic anion gap [anion gap = (Na+) - (Cl- + total CO2)] and metabolic acidosis. Serum concentrations >180 mg/L [2.37 mM] can cause poisoning. Propylene glycol synthesis produces D- and L-steromers in a 1:1 ratio. Some information exists in the literature regarding the stereoselectivity of enzymes in the propylene glycol metabolic pathway, but it is incomplete… In the main metabolic pathway, D- and L-form lactaldehyde and lactic acid are produced. In horses and rabbits, ADH oxidizes L-form propylene glycol and lactaldehyde more efficiently than D-form. L-form lactic acidosis has been observed in both humans and animals after exposure to propylene glycol. Lactaldehyde is converted to methylglyoxal by alcohol dehydrogenase (ADH), and then to D-lactic acid by glyoxalase and reduced glutathione, which is considered another metabolic pathway… D-lactic acid is cleared more slowly than L-lactic acid and is therefore considered a poorer gluconeogenic substrate. Methylglyoxal synthase can convert the substrate dihydroxyacetone phosphate to methylglyoxal. However, under conditions of high ketone body levels, such as diabetes or starvation, the activity of methylglyoxal synthase is enhanced, resulting in the production of more methylglyoxal and D-lactic acid. Excessive production of D-lactic acid can lead to its accumulation, especially in the brain where the levels of catabolic enzymes are low. Therefore, in ketosis, propylene glycol may exacerbate the increase in D-lactic acid levels. In a third possible metabolic pathway, propylene glycol can be phosphorylated to acetylacetone phosphate, lactalaldehyde phosphate, lactyl phosphate, and lactate… The metabolism of propylene glycol D-form and L-form in this pathway is species-specific. Rabbits convert phosphorylated propylene glycol L-form to lactate, while rats and mice can convert both forms. /D- and L-isomers/
Studies in humans and rodents have shown that the placenta's ability to metabolize propylene glycol is extremely limited. Class III ADH isolated from full-term human placentas was found to have low activity towards ethanol, and its Km value for octanol was 100 times higher than that of Class I ADH enzymes found in human liver… The activity and Vmax value of ALDH from full-term human placentas were lower than those of ALDH isoenzymes in the liver, while the Km value was higher. In rats, no ADH activity was found in the placenta, and the ALDH activity in the placenta was 4-7% of that in the liver.
For more complete data on the metabolism of propylene glycol (12 metabolites), please visit the HSDB record page.

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Biological Half-Life
Systemic: 1.4–30.5 hours (longer in infants, shorter in adults); [TDR, page 10] 1056]
After intravenous injection of propylene glycol (dose 3–15 g/m²), plasma concentrations ranged from 60 to 425 μg/mL, with half-lives of 1.8 to 3.3 hours…
/Preterm Infants/Oral: The mean half-life in preterm infants was 19.3 hours (range 108–30.5 hours).
/Infants/Dermal: The half-life in 8-month-old infants was 16.9 hours.
Parenteral Administration: 2.4–5.2 hours, 1.4–3.3 hours (mean 2.3 ± 0.7 hours).
For more complete biological half-life data for propylene glycol (7 types), please visit the HSDB record page.

Toxicity Summary
Exposure. In 1998, the U.S. production capacity of propylene glycol (PG) was 1.312 billion pounds (59.6 thousand tons). Domestic demand was 1.05 billion pounds (47.7 thousand tons). PG is used as a cosmetic ingredient at concentrations ranging from <0.1% to >50%. In 1994, approximately 4,000 cosmetic products contained PG. The uses of PG and their percentage demand are as follows: unsaturated polyester resins, 26%; antifreeze and de-icing fluids, 22%; food, pharmaceutical, and cosmetic uses, 18%; liquid detergents, 11%; functional liquids (inks, specialty antifreezes, de-icing lubricants), 4%; pet food, 3%; paints and coatings, 5%; tobacco, 3%; other uses, including plasticizer uses, 8%. Health. Propylene glycol (PG) is not acutely toxic. Its lowest oral LD50 values range from 18 to 23.9 mg/kg (5 different species), and the reported dermal LD50 is 20.8 mg/kg. PG is essentially non-irritating to the skin and slightly irritating to the eyes. Numerous studies have shown that PG does not cause skin sensitization. In rats repeatedly exposed to propylene glycol in drinking water or feed for up to 2 years, at concentrations up to 10% in drinking water (estimated at approximately 10 g/kg body weight/day) or up to 5% in feed (reported dose 2.5 g/kg body weight/day), no adverse reactions were observed. In cats, two studies lasting at least 90 days demonstrated that propylene glycol has species-specific effects, manifested as an increase in Heinz body count (No Observed Adverse Effect Level [NOAEL] = 80 mg/kg body weight/day; Lowest Observed Adverse Effect Level [LOAEL] = 443 mg/kg body weight/day). Other hematological effects (reduced red blood cell count and decreased red blood cell viability) were also observed at higher doses (6–12% in feed, or 3.7–10.1 g/animal/day). Propylene glycol showed no fetal or developmental toxicity in rats, mice, rabbits, and hamsters (NOAEL range of 1.2–1.6 g/kg body weight/day in all four animals). No reproductive toxicity was observed when propylene glycol was added to drinking water in mice at concentrations up to 5% (reported dose 10.1 g/kg body weight/day). A series of in vivo (micronucleus, dominant lethality, chromosomal aberration) and in vitro (bacterial and mammalian cell and culture) studies demonstrated that propylene glycol is not genotoxic. No tumor growth was observed in any tissues examined when rats were fed propylene glycol (2.5 g/kg body weight/day for 2 years) or when it was applied to the skin of female rats (100% propylene glycol; total dose not reported; for 14 months) or mice (mice dose estimated at approximately 2 g/kg body weight/week; lifetime). These data support that propylene glycol is not carcinogenic. Regarding environmental factors… Freshwater aquatic toxicity measurements in fish, daphnia, and algae showed that the LC/EC50 values of propylene glycol were all greater than 18,000 mg/L. Therefore, except at very high concentrations, propylene glycol has no acute toxicity to aquatic organisms. Using an evaluation factor of 100 and daphnia (48-hour EC50 = 18,340 mg/L) data, the predicted no-effect concentration was 183 mg/L.

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Interaction
This study investigated the effects of propylene glycol (PG) alone and its interaction with calcium channel blockers on inward calcium currents at mouse motor nerve endings. Phrenic nerve/diaphragm specimens from male ICR mice were used. The effect of 5% PG on nerve ending potassium currents was examined, revealing two positive spikes at the nerve endings after d-tubocurarine (d-Tc) treatment. The second positive spike was attributed to outward potassium currents. PG had no effect on this spike, indicating that the compound has no effect on potassium channels. Pretreatment with d-Tc, tetraethylammonium (TEA), and 3,4-diaminopyridine (DAP) induced a prolonged negative component of the nerve ending action potential. PG enhanced this component, attributed to inward calcium currents. The role of calcium channel blockers was investigated to determine whether they antagonized PG. Cumulative addition of cadmium chloride, manganese chloride, or cobalt chloride inhibited the sustained negative component enhanced after propylene glycol treatment.

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Non-human toxicity values
Oral LD50 in rats: 21,000 - 33,700 mg/kg
Oral LD50 in rats: 22,000 mg/kg
Intraperitoneal LD50 in rats: 6,660 mg/kg
Intravenous LD50 in rats: 6,423 mg/kg
For more complete non-human toxicity data for propylene glycol (out of 20), please visit the HSDB record page.

[1]. Low but inducible contribution of renal elimination to clearance of propylene glycol in preterm and term neonates. Ther Drug Monit. 2014 Jun;36(3):278-87.

[2]. Neurobehavioral effects of 1,2-propanediol in zebrafish (Danio rerio). Neurotoxicology. 2018 Mar;65:111-124.

Therapeutic Uses
Propylene glycol can be used as an excipient for intravenous medications such as lorazepam, etomidate, phenytoin sodium, diazepam, digoxin, hydralazine, esmolol, chlordiazepoxide, multivitamins, nitroglycerin, sodium pentobarbital, sodium phenobarbital, and trimethoprim-sulfamethoxazole. As an antiseptic, it is similar to ethanol; its antifungal activity is similar to glycerin, only slightly less than ethanol. Hygroscopic agents (e.g., propylene glycol…) are added to respiratory inhalers to reduce the viscosity of bronchial secretions. Ointments containing approximately 70% propylene glycol have been used as penetrants with good results in treating corneal edema. For more complete data on the therapeutic uses of propylene glycol, please refer to the HSDB record page (out of 9).

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Drug Warning
Propylene glycol (PG) can induce hyperosmolarity in a variety of clinical situations…especially when nitroglycerin solutions containing propylene glycol are used in intensive care unit patients…
Preparations containing 35% propylene glycol can cause hemolysis in humans.
Hemolysis, central nervous system depression, hyperosmolarity, and lactic acidosis have been reported after intravenous administration of propylene glycol.
Propylene glycol is a commonly used solvent in oral, intravenous, and topical pharmaceutical preparations. While it is considered safe, high-dose intravenous administration over a short period can be toxic. Potential renal insufficiency and hepatic impairment increase the risk of toxicity. Toxic effects include hyperosmolarity, metabolic acidosis with increased anion gap (due to lactic acidosis), acute kidney injury, and sepsis-like syndrome. Treatment for propylene glycol poisoning includes hemodialysis to effectively remove propylene glycol. The best method of prevention is to limit the infused dose of propylene glycol. For more complete data on drug warnings (41 in total) related to propylene glycol, please visit the HSDB records page.

C3H8O2

76.0944

76.052

57-55-6

58858-91-6 (hydrochloride salt)

1030

Colorless viscous liquid

1.0±0.1 g/cm3

184.8±8.0 °C at 760 mmHg

-60ºC

107.2±0.0 °C

0.2±0.8 mmHg at 25°C

1.430

-1.34

2

2

1

5

20.9

0

O([H])C([H])(C([H])([H])[H])C([H])([H])O[H]

DNIAPMSPPWPWGF-UHFFFAOYSA-N

InChI=1S/C3H8O2/c1-3(5)2-4/h3-5H,2H2,1H3

propane-1,2-diol

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

DMSO : ~100 mg/mL (~1314.23 mM)
H2O : ~100 mg/mL (~1314.23 mM)

Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.

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Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)
*Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution.
Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)
Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil)
Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals).

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Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)]
*Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.
Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline)
Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline)
Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline)
Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline
Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil)
Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)

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Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium)
Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose
Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals).

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Oral Formulation 3: Dissolved in PEG400
Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose
Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose
Oral Formulation 6: Mixing with food powders

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Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.

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 (Please use freshly prepared in vivo formulations for optimal results.)