PG and VG Toxicology Review


One of the first things I am asked, when people talk to me about my electronic cigarette, is if it is healthy, or at least healthier than a real cigarette.  I also had these concerns, since I have some pretty major health factors to over come myself.  I don’t want to add to the problem, but instead, help make myself recover fully.

As you may know, electronic cigarettes contain an e-liquid, or smoke juice, made up of primarily 3 to 6 items.  These items are, Propylene Glycol, Vegetable Glycerin,  Water, Nicotine (in most, but not all) and flavor extracts.

This study I found that shows toxicology information on PG and VG is pretty good information for those that are looking to see if these e cigs are a safer alternative than tobacco cigarettes.  So far, everything I am finding shows that they are indeed safer.

This below information is taken from a report by HSE Consulting and Sampling, Inc. , Omaha, NE.

To view the report in it’s entirety go here:  http://www.ElectronicCigaretteHelpInfo.com/web-content/Review_of_Glycerol_&_Glycols.pdf

The excerpt begins here:

I. PURPOSE
The purpose of this report is to review all applicable literature concerning the safe inhalation
exposure concentrations for the glycols listed below and glycerol. A proposal outlining additional
research needs to define safe inhalation exposure concentrations for the listed substances
is also presented…

A number of databases were searched to review the available scientific literature for each of the
above substances. The list of databases is located in Appendix A. As a priority, inhalation
toxicity was searched in each database. If no inhalation data was found, then a general toxicology
search was done by CAS number and/or name for each compound. The information obtained
from the databases was reviewed and the relevant scientific literature selected and
incorporated into the summary report for each substance. All references are footnoted and can
be found in the Bibliography. Copies of each database search will be forwarded to the Entertainment
Services & Technology Association.

Toxicology is the study of the adverse effects of chemicals agents on biologic systems. Adverse
or toxic effects in a biologic system are not produced by a chemical agent unless that agent or
its biotransformation products reach the appropriate target within the biologic system at the right
concentration and for a sufficient amount of time. Therefore, whether or not a toxic response
occurs is dependent on the chemical and physical properties of that agent, the exposure situation,
and the susceptibility of the biologic system or subject. Thus, to characterize a potential
hazard or toxicity of a specific chemical agent the following information must be examined:

What is the agent of concern?
What type of effect does the chemical in question produce?
What dose or amount is required to produce the effect?
What are the exposure conditions?
Who are the subjects exposed?

In this report, we will be discussing what type of effects the glycols and glycerol listed produce
on the human or animal system.

Here is the listed information on the products found in most electronic cigarette liquids or e-liquids;

 

A. Propylene Glycol (PG)
1.0 Physical and Chemical Properties 1, 3, 6, 11, 12
Identification: CAS # 57-55-6
Common names: Sirleneâ, PG12
Synonyms: 1,2-Propanediol; 1,2-dihydroxypropane; methyl ethylene glycol; methyl glycol;
propane-1,2-diol
Structure:
OH OH H
H – C – C – C – H
H H H
Molecular Formula: C
3H8O2
Propylene glycol (PG) is a stable, viscous, hygroscopic liquid (hygroscopic pertains to a material
that absorbs moisture readily). It is colorless and has a sight odor and a slight acrid taste. It is
completely miscible with water and alcohols. It will also dissolve in a number of resins, dyes,
essential oils, ether and benzene.3, 6 Under ordinary conditions PG is considered stable, but can
react with oxidizing materials.
Molecular Weight: 76.09 (1 ppm (v/v) = 3.1 mg/m3
Boiling Point: 188 deg C (370 deg F)
Density: 1.038 @ 25 deg C (77 deg F)
Vapor Pressure: 0.05mm Hg @ 20 deg C (68 deg F)
% in Saturated Air: Approximately 0.038 @ 20 deg
Odor Threshold: Practically odorless
Flash point: 107 deg C (225 deg F)
1 ppm is approximately 3.11 mg/m3 @ 25 Deg C, 760 mm Hg

2.0 Background
2.1 Sources and Uses
PG is manufactured in a number of different ways. One way PG is produced commercially is by
hydrolysis of propylene oxide.14 PG is used in many applications including use in various foods,
cosmetics, and pharmaceutical products. The Food and Drug Administration (FDA) has classified
PG as a Generally Recognized as Safe (GRAS) additive. GRAS additives are materials
which are virtually indistinguishable from foods. Such substances are regulated in the Code of
Federal Regulations. These substances may be added in relatively substantial amounts to
food, in some instances at levels representing more than 1 percent of dietary intake.2 The FDA
considers an average daily dietary intake of 23 mg/kg of body weight of PG to be safe for 6
persons 2 to 65 years of age. 11

For an average 70 kg person, this is approximately 1.6 grams
or approximately 1.6 mls. As a solvent and surfactant in food colors and flavors as well as in
food products, the concentrations can range from <0.001% in eggs and soups to 15% in some
seasonings and flavorings. It is also used as a humectant or moistening agent in foods, such as
shredded coconut, tobacco, and pet foods.
In industry, it is used as a lubricant or heat-transfer fluid where leakage might lead to food
contact, in antifreeze and coolant applications and deicing fluids for aircraft. The largest
amounts used are in the textile industry where it used as an intermediate in polyester fiber and
urethane production. 6, 11

2.2 Industrial Exposure
Industrial exposures to PG are from direct contact or from inhalation of vapors and of mists
where the material is heated or violently agitated. Other exposure is by ingestion resulting from
its use in foods and drugs. Although exposures created by operations producing hot vapors, or
fogs have not been studied, it is felt that the inhalation of atmospheres containing PG presents
no hazard to health since the systemic toxicity is so low.12
OELs have been established for PG by a number of organizations. Based on its low toxicity by
all routes of exposure and a NOEL (no observable effect level) of 1000 mg/m3 in rats, the
United Kingdom (UK), Health and Safety Executive (HES) has set an 8-hour time-weighted
average occupational exposure standard (OES) of 150 ppm (470 mg/m3) for total vapor (a vapor
is the gaseous form of substances which are normally found in a solid or liquid state and which
can be changed to these states either by increasing the pressure or decreasing the temperature45)
and particulates, and 10 mg/m3 for particulates only in 1991. The latter level being set to
avoid uncomfortable or visibility impairing conditions if the material were present as a fog. The
AIHA has also set an 8-hour time-weighted WEEL guide of 50 ppm (155 mg/m3) for total vapor
and aerosol (an aerosol is an assemblage of small particles, solid or liquid, suspended in air,
e.g., dust, fog, smoke45), and 10 mg/m3 for aerosol only. The Ontario Ministry of Labour’s Health
and Safety Support Services Branch (HSSSB) had issued a working exposure guideline time
weighted average (WEG-TWA) of 100 ppm for PG in 1984. However, more recently in 1991,
the HSSSB issued a WEG-TWA of 50 ppm for total vapor and aerosol over an 8-hour work day
or a 40-hour work week. The HSSSB further recommends a WEG-TWA of 10 mg/m3 for assessing
the visibility in a work environment where aerosol is present.18

3.0 Toxicology Review
3.1 Summary
PG has been well studied. Its systemic toxicity is very low and it has been used extensively in
food and pharmaceuticals compared to other dihydric glycols. The hazards to health in the
industrial handling and use of PG seem to be negligible. Symptoms of acute PG intoxication are
those of CNS depression or narcosis (unconscious state). No system or organ has been established
as a target for the acute lethal effects of PG. The explanation for the low toxicity of PG
lies in its metabolism. PG is metabolized by alcohol dehydrogenase to lactic acid and ultimately
to pyruvic acid. Both lactic and pyruvic acid are normal constituents of carbohydrate metabolism
and are ultimately broken down to carbon dioxide and water.2

3.2 Inhalation Exposure
Studies have been done in hospital wards using PG in an air-sterilization application. In these
studies, humans were exposed to saturated and super saturated atmospheres for prolonged
periods without adverse effects.12 In 1971, the uptake of PG mist by humans was studied using
a 10% solution in labeled deionized water which was nebulized into a mist tent. Less then 5%
of the mist entered the body, and of this 5%, 90% lodged in the nasopharynx and rapidly disappeared
into the stomach. Very little PG was found in the lungs. 12
Robertson and coworkers (1947) exposed monkeys and rats to atmospheres saturated with PG
vapor and found no adverse effects in animals after periods of 12 to 18 months.30 Rats exposed
to a 90-day inhalation study using PG aerosol at concentrations up to 2,200 mg/m3 (160, 1000
and 2200 mg/m3), for 6 hours/day, 5 days/week did not demonstrate systemic toxicity. However,
it was reported that there was a significant increase in the number of goblet cells (a type of
secretory cell found in the top layer of the intestinal and respiratory tract that secretes mucus)
and/or an increase in the mucin content of the existing goblet cells in the nasal passages of rats
exposed to the high and medium doses. In addition, the PG concentration in this study caused
nasal hemorrhage and ocular discharge in a high proportion of animals, all of these reversible
effects are considered to be the result of dehydration of the nares and eyes.23 The dehydration
would be expected with PG, as it is a hydroscopic material and can cause irritation simply by
removing excess water from the eyes and nasal passages.
Minute changes in cilia cell structures were observed after rabbits had been exposed to 10%
PG for 20 minutes by inhalation. It was reported that the goblet cells were discharging mucous
or were completely exhausted. 3

3.3 Oral Toxicity
A report of a case where PG was used as a vehicle in a vitamin preparation for a 15 month-old
youngster, caused adverse signs characterized by hypoglycemia (low blood sugar) and central
nervous system (CNS) depression. Recovery was prompt upon cessation of treatment. 17 It
should be noted that, PG is given orally (1-1.5g/kg) to humans therapeutically to reduce
intraoccular pressure by raising the osmotic pressure of the blood.6
PG has been investigated by numerous studies under acute conditions. Reports of acute
administration of lethal and sublethal doses of PG to rats, mice, rabbits, guinea pigs and dogs
resulted in CNS depression. PG produced lack of muscular coordination, loss of equilibrium,
analgesia (sleep like state), muscle tremors, and occasionally, convulsions. Additional consequences
included increase and/or decrease in respiration rates, hypotension, irritation of the
digestive tract, hemolysis (destruction of red blood cells) and diuresis (secretion of large
amounts of urine).14
More specifically, acute oral administration to rats, mice, and guinea pigs produced slight hydropic
degeneration of the kidney with debris and casts in a few cortical tubules, slight congestion
of the liver, and hemorrhagic areas in the small intestine.14 When comparing acute oral toxicity,
the LD 50s or the Lethal Dose to kill 50% of the animal test population, in rats, rabbits, and dogs
were approximately 30, 18 and 19 g/kg body weight, respectively.12 As the LD 50 values are
generally used as a method to compare toxicity of various compounds, PG, relatively, is considered
nontoxic.2 8
When chronic and subchronic doses of PG were administered in the drinking water (1-10%) of
rats for up to 234 days or when given by gavage to rabbits for 50 days, no effects where found,
other than at the higher doses, a transient inhibition of growth at the beginning of the experiment
was experienced. No gross or microscopic evidence of pathology was observed.14 In addition,
no effects were found in rats fed up to 50,000 ppm in the diet for 2 years.22 However, other long
term feeding studies showed hemopoietic (blood) changes in dogs.21

3.4 Eye and Skin Irritation
A single drop in the human eye causes immediate stinging, blinking and lacrimation. This
discomfort lasts until the eye tears enough to dilute the material. This is followed by mild transient
conjunctival redness, but no residual discomfort or injury.13
Skin reactions due to PG are generally rare. Irritation of the skin may occur, especially under
occlusive (covered) conditions. Hypersensitivity type reactions (allergic) have been reported.25
Undiluted PG has been applied to human volunteers in various patch test studies. On average
15% of the test subjects demonstrated a reaction, of these
15 %, 60 – 70% had irritant type reactions and 30-40% had allergic type reactions. Most of the
irritation is expected to be due to the dehydration effect of the PG (being a hygroscopic material).
3 Work by Willis et al. suggested that the dehydration effect was due to osmotic hydration
of corneal cells, however, the patterns of cell damage observed in the epidermis (top cell layer
of the skin) was dependent on the amount tested (dose) as well as time left on the skin.22 Because
PG has a very low systemic toxicity, no problem is expected from any possible percutaneous
absorption.12

 

F. Glycerol  —-  (VG) Vegetable Glycerine
1.0 Chemical and Physical Properties1, 10, 15, 37
Identification: CAS# 56-81-5
Common Names: Glycerin
Synonyms: Glycerin, Glycerine, 1,2,3-Propanetriol, Trihydroxypropane
Structure:
OH OH OH
H – C – C – C – H
H H H
Molecular Formula: C
3H 14O4
Chemically, glycerol is a trihydric (polyhydric) alcohol, meaning it has three hydroxyl groups (-
OH) in it’s structure. Physically glycerol is a clear, syrupy liquid with a warm, sweet taste.
Glycerol is very hygroscopic, can be volatilized in steam, and can absorb half its weight in water.
It is miscible in water and alcohol; insoluble in ether, benzene, and chloroform and in fixed and
volatile oils. Under normal circumstances glycerol is considered stable, however, it can produce
violent or explosive reactions when it comes in contact with many solid oxidants. This is due to
its unique properties of having three centers of reactivity (OH groups).10
Molecular Weight: 92.09
Boiling Point: 290 Deg C
Density: 1.260 @ 20 Deg C
Vapor Pressure: 0.000158 mm Hg @ 25 Deg C
Odor Threshold: Odorless
Flash Point: 176 Deg C (Open Cup)
1 ppm is approximately 3.76 mg/m3 @ 25 Deg C, 760 mm Hg

2.0 Backgound10, 15
2.1 Sources and Uses
Documentation on glycerol goes back as early as the 1870’s. Over the years glycerol has been
used in many different applications. Glycerol can be manufactured synthetically, by fermentation
of sugars, or by hydrolysis of fats and oils or as a by-product of soap manufacture. They
are used in the manufacture of alkyd resins, dynamite, ester gums, pharmaceuticals, perfume,
plasticizers for regenerated cellulose, cosmetics, foodstuffs including confectioneries, conditioning
tobacco, liquors, solvent, printer’s ink rolls, polyurethane polyols, emulsifying agents, rubber
stamp and copying inks, binders for cements and mixes, special soaps, lubricants and softeners,
bacteriostats, penetrants, hydraulic fluids, humectants, fermentation nutrients, and antifreeze
mixtures to name a few. 10 23
The chief end markets for glycerol are drugs, toothpaste, cosmetics and personal care products
and food. Glycerol is used as a multiple purpose GRAS (Generally Recognized as Safe) food
additive in food for human consumption, animal feeds, and drug applications, and related
products when used in accordance with good manufacturing pratice. 10, 43
Glycerol is used in many applications in the pharmaceutical industry. It is probably used more
frequently in prescriptions than any other substance besides water.37 Therapeutically glycerin is
added to humidifying inhalants. It is added as a hygroscopic agent, used to draw more water
into bronchial secretions and reduce viscosity. Glycerol is used in suppositories, and works by
forcing water into the intestinal lumen through osmotic forces. Given orally, glycerol reduces
intraocular pressure and cerebral edema, especially in patients with acute angle-closure glaucoma
and after ophthalmic surgery.10
As of 1992 there were not appropriate studies on the relationship of age to the effects of oral
glycerol performed in the pediatric population.

2.2 Industrial Exposure
Glycerol mist is considered a “nuisance” particulate. It seems to have little adverse effect on the
lung and does not produce significant organic disease or toxic effects when exposures are kept
under reasonable control. The OSHA PEL for glycerol mist is 15 mg/m3 as total dust and 5 mg/
m3 as a respirable fraction. Total dust generally refers to all airborne particulate independent of
size, whereas the respirable fraction represents particles of 10 microns or less in size. OSHA
feels that this limit will provide protection against the risk of kidney damage, and testicular
effects which have been recently examined in the scientific literature.43
NIOSH states that at high concentrations, exposure may cause hemolysis, hemoglobinuria, and
renal failure.43 However, NIOSH has not recommended an occupational exposure limit to date.
ACGIH has established a TLV of 10 mg/m3 , as a total particulate, until additional toxicology data
and industrial hygiene experience becomes available.15 ACGIH has reported that glycerin mist
is easily metabolized and excreted. In the adult human of average weight, 2 grams of glycerol
can be metabolized and excreted in an 8 hour work day. At this metabolic and elimination rate,
the ACGIH believes that no ill effects are likely to occur as a result of exposure at or below 10
mg/m3 as an 8 hour TWA. 15 Additional international standards include, 10 mg/m3 for Australia
and the United Kingdom.15

3.0 Toxicology

3.1 Summary
Glycerol has been safely used in many industrial and pharmaceutical applications for over 100
years and is generally recognized for its low risk health effects. The majority of the toxicologic
information on this material is from human data. Toxic doses of glycerol, as with all chemicals,
can be obtained when administered in sufficient
quantities. However, healthy individuals can easily tolerate doses of up to 1.5 g/kg or
less with only slight diuresis (passage of large amounts of urine) occurring. 10 Glycerol is absorbed
from the intestinal tract and is metabolized to carbon dioxide and glycogen in the liver.
Glycerol is considered a nuisance particulate which seems to have little effects on the lung and
does not produce significant disease or toxic effects when exposures are kept under reasonable
24 control.15 Appropriate studies on the relationship of age to the effects of oral glycerol have not
been performed in children or geriatric populations. 10, 41
3.2 Inhalation Toxicity
There is very little data regarding the inhalation toxicity of glycerol in both animal species or
humans. However, glycerol is used therapeutically to increase the efficiency of inhalants. Due
to its hydroscopic properties it is added in an attempt to draw more water into bronchial secretions
and thus reduce their viscosity.10

3.3 Oral Toxicity
Adverse effects in humans following oral administration of glycerol include mild headache,
dizziness, nausea, vomiting, thirst, and diarrhea. The quantity necessary to cause death varies
with the mode of administration. In both human and animal studies, oral administration requires
the highest dose of all routes to produce lethality. Lethal oral doses produce death ultimately
due to the combine effect of failing circulation and respiration. Oral administered glycerol also
produces increases in the degree of irritability of muscle, causes relaxation of the sphincter of
the gall bladder, and appears to increase the force and amplitude of intestinal contractions. No
significant blood changes have been reported after oral administration.37
One fatal and one non-fatal oral poisoning case has been reported in children. One case, of
unknown amounts, caused death. The second child, a 2 1/2 year old took 300 grams orally,
loss consciousness and recovered after its stomach was pumped. 37, 39 Another report of an adult
patient who took repeated oral and rectal doses of glycerol over a 2 week period, suffered from
debility, vomiting, diarrhea, and muscular cramps which disappeared promptly after discontinuation.
This paper stated that this reaction is possible due to the irritant effects of glycerol, however,
it is more likely that the patient was using contaminated product.39 Ingestion of 30 ml of
glycerol 3X daily for a period of 50 days by normal human subjects was found to be harmless.37
3.4 Eye and Skin Irritation
Glycerol is regularly used as an ophthalmic solution to reduce superficial corneal edema resulting
from disease or trauma. Adverse effects reported when used as a pharmaceutical application
suggest pain and or irritation may occur following topical application to the eye.41 Specular
microscopy has shown that repeated application of
100% glycerol to the surface of the human eye causes extensive changes in the appearance of
the endothelium, but most of these changes disappear within 90 minutes after exposure is
ended.10 When applied to unbroken skin, pure glycerol apparently is not appreciably absorbed
and systemic effects do not occur.10

“The glycols and glycerol reported herein are used as components in theatrical fog fluids. These
fluids are commonly composed of multiple glycols and water. The application of these mixtures
is used to create a visible fog. This is commonly accomplished by heating the fluid to a vapor,
where it then cools to form an aerosol fog.”

There is a lot of good information on the health and safety of the main ingredients of e liquids.  I found the report very helpful in my search for heath information on both PG and VG.  To see this full report uncut, to read everything in context, you can view the pdf file here:  To view the report in it’s entirety go here:  http://www.ElectronicCigaretteHelpInfo.com/web-content/Review_of_Glycerol_&_Glycols.pdf