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SECTION 1. CHEMICAL IDENTIFICATION

CHEMINFO Record Number: 175
CCOHS Chemical Name: Propylene glycol monomethyl ether acetate

Synonyms:
Acetic acid, 2-methoxy-1-methyl ethyl ester
1-Methoxy-2-acetoxypropane
1-Methoxy-2-propanol acetate
1-Methoxy-2-propyl acetate
Propylene glycol methyl ether acetate
1,2-Propanediol monomethyl ether acetate
Methoxyisopropyl acetate
2-Propanol, 1-methoxy, acetate

Chemical Name French: Acétate de l'éther monométhylique du propylène glycol
Chemical Name Spanish: Acetato de 1-metil-2-metoxietilo

Trade Name(s):
Arcosolv PMA
DOWANOL PMA
Eastman PM Acetate
METHYL-PROXITOL Acetate

CAS Registry Number: 108-65-6
Other CAS Registry Number(s): 84540-57-8
RTECS Number(s): AI8925000
EU EINECS/ELINCS Number: 203-603-9
Chemical Family: Ether ester / glycol ether ester / glycol ether acetate / aliphatic ether alcohol ester / alkoxy alkanoate / aliphatic glycol ether ester / propylene glycol ether ester / alkoxy propanol ester / propylene oxide glycol ether ester / propylene glycol alkyl ether ester / alkoxy propanol acetate / propylene oxide glycol ether acetate / propylene glycol alkyl ether acetate
Molecular Formula: C6-H12-O3
Structural Formula: CH3-CH(-O-C(=O)-CH3)-CH2-O-CH3

SECTION 2. DESCRIPTION

Appearance and Odour:
Clear, colourless liquid with a mild, fruity or characteristic ester odour. Hygroscopic, absorbs moisture.(5,7,24)

Odour Threshold:
Information not available.

Warning Properties:
Insufficient information for evaluation.

Composition/Purity:
Propylene glycol monomethyl ether acetate (alpha-PGMMEA; CAS no. 108-65-6) is generally available with a minimum purity of 99%.(5,7,23) The main impurities are the isomeric compound 2-methoxy-1-propanol acetate (beta-PGMMEA; CAS no. 70657-70-4), which is present up to 0.5%, 2-methoxy-1-propanol (CAS no. 1589-42-5), which is present up to 0.3%, and 1-methoxy-2-propanol (CAS no. 107-98-2), which is present up to 0.3%. Some commercial mixtures may contain beta-PGMMEA in higher concentrations and may report the identity of the alpha and beta acetates either with the individual CAS numbers or with the CAS number 84540-57-8, which has been assigned to the mixture. Depending on the preparation method, some of the impurities that may be present in trace quantities are acetic acid, acetic anhydride, propylene glycol, dipropylene glycol, tripropylene glycol, 1,2-acetoxypropane, dipropylene glycol ethers and acetates, tripropylene glycol ethers and acetates, methoxy acetone, and methyl formate. In addition, 2,6-di-tert-butyl-p-cresol (BHT; CAS no. 128-37-0) may be added as a stabilizer to control the level of peroxides formed when the product is exposed to air.(5,7,23)

Uses and Occurrences:
Propylene glycol monomethyl ether acetate was formulated as a replacement for the more toxic ethylene glycol methyl or ethyl ether acetate and chlorinated solvents like methylene chloride. It is used as a solvent in the manufacture of coating polymers such as cellulose acetate butyrate, nitrocellulose, epoxy resins, acrylic copolymers, and phenoxy resins; cosmetic formulations, agricultural products, ink formulations, textile and adhesive products. It is also used as retarder solvent in lacquers, thinners, and baking elements; in photoresist formulations in the semiconductor processing, in cleaning solvent formulations to degrease circuit boards, and in food contact applications.(5,7,23)


SECTION 3. HAZARDS IDENTIFICATION

EMERGENCY OVERVIEW:
Clear, colourless liquid with a mild, fruity or characteristic, ester odour. COMBUSTIBLE LIQUID AND VAPOUR. Vapour is heavier than air, may spread long distances and will accumulate at low points (e.g. open or closed drain) and may result in an explosion hazard. Material has low autoignition temperature and can ignite easily on hot surfaces. May form explosive peroxides. Decomposes at high temperatures forming toxic gases, such as carbon monoxide and formaldehyde. Vapour and mist may be irritating to respiratory tract at high concentrations. May be a moderate eye irritant.



POTENTIAL HEALTH EFFECTS

Effects of Short-Term (Acute) Exposure

Inhalation:
Propylene glycol monomethyl ether acetate (PGMMEA) does form a vapour at normal temperatures. High vapour or mist concentrations may irritate the eyes and nose, based on animal information and comparison to propylene glycol monomethyl ether. Very high concentrations may cause central nervous system depression, with symptoms such as headache, nausea and dizziness.
One case report an employee described dizziness, headache, and "general illness" after filling a tank with a resin containing PGMMEA. Exposures to PGMMEA ranged from 0.9-15.9 ppm. Propylene glycol monomethyl ether concentrations were less than 0.2 ppm.(8, unconfirmed) There are insufficient details available to evaluate this report.

Skin Contact:
PGMMEA is not a skin irritant, based on animal information. No human information was located.
PGMMEA can be absorbed through the skin, but harmful effects are not expected by this route of exposure.

Eye Contact:
PGMMEA may be a slight to moderate eye irritant, based on animal information. No human information was located.

Ingestion:
PGMMEA has very low oral toxicity based on animal information. No human information was located. Ingestion is not a typical route of exposure.

Effects of Long-Term (Chronic) Exposure

Based on its similarity and metabolism to the chemically related propylene glycol methyl ether, PGMMEA is not expected to produce harmful effects following long-term exposure.

Skin:
Repeated or prolonged contact may cause skin irritation, based on animal information.

Skin Sensitization:
PGMMEA is not a skin sensitizer, based on unconfirmed animal information. No human information was located.

Carcinogenicity:

No human or animal information was located.

The International Agency for Research on Cancer (IARC) has not evaluated the carcinogenicity of this chemical.

The American Conference of Governmental Industrial Hygienists (ACGIH) has no listing for this chemical.

The US National Toxicology Program (NTP) has not listed this chemical in its report on carcinogens.

Teratogenicity and Embryotoxicity:
Commercial PGMMEA is largely the alpha isomer, with small amounts of the beta isomer. The commercial product has not cause developmental toxicity in animal studies, even in the presence of maternal toxicity, and, therefore, is not considered a developmental toxin. The beta isomer is metabolized differently in the body than the alpha isomer. beta-PGMMEA is considered teratogenic and embryotoxic based on animal information and comparison to ethylene glycol monomethyl ether acetate, which is metabolized in the same way as the beta isomer. Based on research on propylene glycol monomethyl ether, the potential for developmental effects occurring following exposure to commercial PGMMEA is considered low.(18) Although, it is important to know how much of the teratogenic beta isomer is in the product that you are using.
Four human studies have assessed the relationship between occupational exposure to glycol ethers (including the more toxic ethylene glycol ethers) and birth defects. Two studies found a positive association between glycol ether exposure and malformations in a number of different organs and one found no association between glycol ether exposure and neural tube defects. Detailed analysis of these 3 studies showed that the results could have been due to problems with the methods used by the researchers. The fourth study was determined to be uninformative due to the small number of people evaluated.(17)
Two human population studies examined the miscarriage rate in female employees exposed to a number of chemicals, one of which was PGMMEA, in the semiconductor industry. In both studies, detailed analysis of the data did not show a statistically significant increased risk of miscarriages in workers exposed to ethylene glycol ethers (including PGMMEA).(14)

Reproductive Toxicity:
The available information does not suggest that PGMMEA causes reproductive toxicity. No human or animal information was located for PGMMEA. In animal studies using commercial propylene glycol monomethyl ether, a closely related chemical, reproductive toxicity was not observed in the absence of significant other toxicity in the test animals. Ethylene glycol monomethyl ether acetate, which is metabolized in the same way as beta-PGMMEA, is considered a male reproductive toxin. There are no studies available for beta-PGMMEA.

Mutagenicity:
No human or animal studies were located. Negative results were obtained in tests using cultured mammalian cells and bacteria, suggesting that PGMMEA is not mutagenic.

Toxicologically Synergistic Materials:
No information was located.

Potential for Accumulation:
Does not accumulate. In rats exposed by inhalation or ingestion, PGMMEA (alpha isomer; less than 2.5% beta isomer) was rapidly metabolized to propylene glycol monomethyl ether (PGMME), propylene glycol, sulfate and glucuronide conjugates of PGMME and acetic acid (a normal body substance). The metabolites of PGMMEA are largely eliminated in the urine and expired air (as carbon dioxide).(2,3,20) The main metabolite of the beta isomer is 2-methoxypropionic acid, which is excreted in the urine (approximately 77%), followed by expiration of carbon dioxide (approximately 10%).(15,20)

Health Comments:
PGMMEA rapidly hydrolyzes to propylene glycol methyl ether once absorbed into the body. Thus, PGMMEA is expected to produce similar effects to propylene glycol methyl ether, except it is more irritating at the site of contact.(16,20) Refer to the CHEMINFO review of propylene glycol methyl ether for additional information.


SECTION 4. FIRST AID MEASURES

Inhalation:
If symptoms are experienced, remove source of contamination or move victim to fresh air. If symptoms persist, obtain medical advice.

Skin Contact:
Remove contaminated clothing, shoes and leather goods (e.g. watchbands, belts). Flush with lukewarm, gently flowing water for 5 minutes. If irritation persists, repeat flushing. Obtain medical advice. Completely decontaminate clothing, shoes and leather goods before re-use or discard.

Eye Contact:
Immediately flush the contaminated eye(s) with lukewarm, gently flowing water for 5 minutes, while holding the eyelid(s) open. If irritation persists, obtain medical advice.

Ingestion:
If irritation or discomfort occur, obtain medical advice.

First Aid Comments:
Consult a doctor and/or the nearest Poison Control Centre for all exposures except minor instances of inhalation or skin contact.
All first aid procedures should be periodically reviewed by a doctor familiar with the material and its conditions of use in the workplace.



SECTION 5. FIRE FIGHTING MEASURES

Flash Point:
42 deg C (108 deg F) (closed cup) (6,23)

Lower Flammable (Explosive) Limit (LFL/LEL):
Not available at room temperature; 1.3% at 78 deg C (24,28)

Upper Flammable (Explosive) Limit (UFL/UEL):
Not available at room temperature; 13.1% at 139 deg C (24,28)

Autoignition (Ignition) Temperature:
272 deg C (522 deg F) (5)

Electrical Conductivity:
2 x 10(5) pS/m (7)

Combustion and Thermal Decomposition Products:
Thermal decomposition of propylene glycol monomethyl ether acetate releases gaseous hydrocarbons, 1-methoxy-2-methylethylene (vinyl ether), acetic acid, hydrogen gas and carbon monoxide. Combustion of propylene glycol monomethyl ether acetate releases carbon monoxide, carbon dioxide, and carbonyl compounds such as formaldehyde, acetaldehyde, methylglyoxal, and other irritating and toxic fumes.(29,30)

Flammable Properties:

Specific Hazards Arising from the Chemical:
During a fire, very toxic gases such as carbon monoxide and formaldehyde are formed. Heat from a fire can cause a rapid build-up of pressure inside containers, which may cause explosive rupture.

Extinguishing Media:
Small fires: Carbon dioxide or dry chemical powder. Large fires: Water spray or alcohol resistant foam.

Fire Fighting Instructions:
Evacuate area. Fight fire from a safe distance or protected location. Approach fire from upwind to avoid hazardous vapours and toxic decomposition products. Wear full protective gear if exposure is possible. See advice in Protection of Firefighters.
Stop leak before attempting to stop the fire. If the leak cannot be stopped, and if there is no risk to the surrounding area, let the fire burn itself out. If the flames are extinguished without stopping the leak, the vapours may form explosive mixtures with air and re-ignite.
Water can be applied as a fine spray to absorb the heat of the fire and to cool exposed containers and materials, and can be used to extinguish the fire when hose streams are applied by experienced firefighters trained in fighting all types of combustible or flammable liquid fires.
If a leak or spill has not ignited, use water spray in large quantities to disperse the vapours, and to protect personnel attempting to stop a leak. Water spray can be used to dilute spills to raise the flash point and to flush spills away from ignition sources. Solid streams of water may be ineffective and spread material.
Closed containers may explode in the heat of the fire. Always stay away from ends of tanks, but be aware that flying material (shrapnel) from ruptured tanks may travel in any direction. Withdraw immediately in case of rising sound from venting safety device or any discolouration of tank due to fire. If possible isolate materials not yet involved in the fire and move containers from fire area if this can be done without risk. Protect personnel. Otherwise, cool fire-exposed containers, tanks or equipment by applying hose streams. Cooling should begin as soon as possible (within several minutes) and should concentrate on vapour space and any unwetted portions of the container. Apply water from the side and a safe distance. Cooling should continue until well after the fire is out. If this is not possible, use unmanned monitor nozzles and immediately evacuate area.
For an advanced or a massive fire in a large area, use unmanned hose holder or monitor nozzles; if this is not possible withdraw from fire area and allow fire to burn.
After the fire has been extinguished, the resulting water solutions of propyl glycol monomethyl ether acetate may be combustible. Explosive atmospheres may be present. Before entering such an area especially confined areas, check the atmosphere with an appropriate monitoring device while wearing full protective gear.
Containers or tanks should not be approached directly after they have been involved in a fire, until they have been completely cooled down.

Protection of Fire Fighters:
This material is essentially non-hazardous to health. However, the decomposition products such as carbon monoxide and formaldehyde are very hazardous to health. Firefighters may enter the area if positive pressure self-contained breathing apparatus (NIOSH approved or equivalent) and full Bunker Gear is worn.



NATIONAL FIRE PROTECTION ASSOCIATION (NFPA) HAZARD IDENTIFICATION

NFPA - Health: 1 - Exposure would cause significant irritation, but only minor residual injury.
NFPA - Flammability: 2 - Must be moderately heated or exposed to relatively high ambient temperatures before ignition can occur.
NFPA - Instability: 0 - Normally stable, even under fire conditions, and not reactive with water.

SECTION 9. PHYSICAL AND CHEMICAL PROPERTIES

Molecular Weight: 132.2

Conversion Factor:
1 ppm = 5.41 mg/m3; 1 mg/m3 = 0.185 ppm at 25 deg C (calculated)

Physical State: Liquid
Melting Point: Less than -66 deg C (less than -87 deg F) (2,23)
Boiling Point: 145-146 deg C (293-295 deg F) (25)
Relative Density (Specific Gravity): 0.967 at 20 deg C (26); 0.966 at 25 deg C (5,23) (water = 1)
Solubility in Water: Soluble (19.8 g/100 mL at 25 deg C (25); 21.4 g/100 g at 20 deg C (27)
Solubility in Other Liquids: Expected to be very soluble in methanol, ethanol, acetone, diethyl ether and most moderately polar and non-polar organic solvents.
Coefficient of Oil/Water Distribution (Partition Coefficient): Log P(oct) = 0.56 (25)
pH Value: Not applicable
Viscosity-Dynamic: 1.31 mPa.s (1.31 centipoises) (7), 1.23 mPa.s (1.23 centipoises) (26) at 20 deg C; 0.8 mPa.s (0.8 centipoises) at 25 deg C (23)
Viscosity-Kinematic: 1.34 mm2/s (1.34 centistokes) at 20 deg C; 0.83 mm2/s (0.83 centistokes) at 25 deg C (calculated)
Saybolt Universal Viscosity: 28.3 Saybolt Universal Seconds at 37.8 deg C (100 deg F) (calculated)
Surface Tension: 27.6 mN/m (27.6 dynes/cm) at 20 deg C (7); 26.9 mN/m (26.9 dynes/cm) at 25 deg C (23)
Vapour Density: 4.6 (air = 1) (calculated)
Vapour Pressure: 0.523 kPa (3.92 mm Hg) at 25 deg C (25)
Saturation Vapour Concentration: 5200 ppm (0.52%) at 25 deg C (calculated)
Evaporation Rate: 0.33 (n-butyl acetate = 1) (7,23)
Henry's Law Constant: 0.35 Pa.m3/mol (cited as 3.44 x 10(-6) atm.m3/mol) at 25 deg C (estimated) (25); log H = -3.85 (dimensionless constant; calculated)

Other Physical Properties:
DIELECTRIC CONSTANT: 8.3 at 20 deg C (dimensionless) (7)
NOTE: Forms an azeotrope with water at 51.5% (m/m). Boiling point of azeotrope is 98 deg C (208 deg F).(7)
Solubility of water in propylene glycol monomethyl ether acetate: Moderately soluble (5 g /100 g) at 20 deg C (27)


SECTION 10. STABILITY AND REACTIVITY

Stability:
Normally stable. Oxidizes on prolonged contact with air to form peroxides. The rate of oxidation is not known. Stabilizers such as 2,6-di-tert-butyl-p-cresol (BHT) may be added to prevent the air oxidation of this substance. (43)

Hazardous Polymerization:
Will not occur.

Incompatibility - Materials to Avoid:

NOTE: Chemical reactions that could result in a hazardous situation (e.g. generation of flammable or toxic chemicals, fire or detonation) are listed here. Many of these reactions can be done safely if specific control measures (e.g. cooling of the reaction) are in place. Although not intended to be complete, an overview of important reactions involving common chemicals is provided to assist in the development of safe work practices.


The risk of a hazardous incident occurring due to accidental mixing of propylene glycol monomethyl ether acetate with other substances is low to moderate because propylene glycol monomethyl ether acetate reacts with a small number of chemical classes that are commonly used in the workplace. If an accidental mixing does occur, some of these reactions may be severe.

STRONG OXIDIZING AGENTS (e.g. hydrogen peroxide, nitric acid, perchlorates, hypochlorites) - React violently with risk of fire or explosion. Carbon dioxide gas may be released which will cause pressurization in the container. Reaction with hypochlorites may form alkyl hypochlorites, which are explosive, and chloroform, which is very toxic and carcinogenic.(35,36)
ALKALI METALS (e.g. sodium, potassium), ALKALINE EARTH METALS (e.g. calcium, magnesium); METAL HYDRIDES (e.g. lithium aluminum hydride or sodium hydride) - Reaction is exothermic. Forms flammable ethanol and may release flammable hydrogen gas.(30,35)
HALOGENS (e.g. chlorine gas) - Reaction may evolve heat. Explosions have occurred when mixtures of halogen and ethers were exposed to air and light.(35) Toxic chlorohydrocarbons (e.g. methyl chloride) may be formed.(35,38)
BASES (e.g. potassium tert-butoxide, ammonia) - Reaction may evolve heat.(35)
STRONG ACIDS (e.g. hydrogen halides, sulfuric acid) - Reaction with concentrated acids may form flammable alcohols and alkenes.(31,37)
COPPER and COPPER ALLOYS, ALUMINUM and ALUMINUM ALLOYS, ZINC and GALVANIZED METALS - Accelerate the decomposition of this material. Flammable hydrogen gas may be produced.(23)

Hazardous Decomposition Products:
Propylene glycol monomethyl ether acetate can form peroxides on prolonged exposure to air. Light and or heat increase the rate of peroxide formation. Peroxides accumulate at hazardous levels during distillation, evaporation, or any other method that will cause concentration of the peroxide impurities.(32,33,34)

Conditions to Avoid:
Static discharge, sparks, temperatures of 42 deg C or above, open flames, hot surfaces, and other sources of ignition; prolonged exposure to air.

Corrosivity to Metals:
There is no specific information available. Propylene glycol monomethyl ether acetate is expected to be slightly to moderately corrosive to aluminum and aluminum alloys, copper and copper alloys, zinc and zinc alloys, and 301, 302, and 400 series stainless steel.(39,40) It is expected to be slightly corrosive to carbon steel 1010 and 1020, and not corrosive to most other 300 series stainless steel alloys. These conclusions are based upon physical and chemical properties of propylene glycol monomethyl ether acetate as well as corrosion data for cellosolve acetate.(40)

Corrosivity to Non-Metals:
There is no specific information available. Propylene glycol monomethyl ether acetate is expected to attack chlorinated polyvinyl chloride, polyvinyl chloride, polypropylene (PP), aromatic polyamides (Kevlar), chlorinated polyether at high temperatures, polyurethane, high density polyethylene at elevated temperatures (140 deg F), polyphenylene oxide, polymethacrylate acrylic, polycarbonate, and polystyrene. May slightly attack polyvinylidene chloride, thermoset polyesters and thermoset epoxy plastics. It is not expected to attack fluorinated plastics such as Teflon; polyamide, and polyamide-imide plastics. These conclusions are based upon physical and chemical properties of propylene glycol monomethyl ether acetate as well as corrosion data for cellosolve acetate.(41)


SECTION 11. TOXICOLOGICAL INFORMATION

Note: Unless specified, the studies reviewed here were conducted with commercial propylene glycol monomethyl ether acetate (PGMMEA) of an unspecified isomeric composition, but generally composed of greater than 97% alpha-PGMMEA (1-methoxy-2-propyl acetate) and smaller amounts of beta-PGMMEA (2-methoxy-1-propyl acetate). beta-PGMMEA is present in commercial PGMMEA, but is not commercially available by itself.

LC50 (rat): greater than 5320 ppm (4-hour exposure); cited as greater than 4345 ppm (6-hour exposure) (2,9-unconfirmed)
LC50 (rabbits and dogs): greater than 490 ppm (4-hour exposure); cited as greater than 400 ppm (6-hour exposure) (beta isomer) (2, unconfirmed)

LD50 (oral, female rat): 8532 mg/kg (22)
LD50 (oral, male rat): greater than 10000 mg/kg (22)
LD50 (oral, rat): 2900-9600 mg/kg (cited as 3-10 mL/kg; all animals survived dosing with 3 mL/kg; 3/5 animals died following dosing with 10 mL/kg) (1, unconfirmed)
LD50 (oral, rat): 13535 mg/kg (cited as 14.1 mL/kg) (19)
LD50 (oral, rat): greater than 5000 mg/kg (beta isomer) (2, unconfirmed)

LD50 (dermal, rabbit): greater than 5000 mg/kg (2,9-unconfirmed)
LD50 (dermal, rabbit): greater than 2000 mg/kg (15, unconfirmed)
LD50 (dermal, rabbit): greater than 2000 mg/kg (beta isomer) (2,15-unconfirmed)
LD50 (dermal, rabbit): greater than 19200 mg/kg (cited as greater than 20 mL/kg; 0/4 died) (19)

Eye Irritation:

PGMMEA may be a slight to moderate eye irritant.

Application of 0.5 mL undiluted PGMMEA caused very mild injury in rabbits (scored 1-5 where 5 is severe injury; graded 2/10).(19) Undiluted PGMMEA caused slight conjunctival redness and swelling, slight iritis and corneal opacity in rabbits. These effects were reversed within 7 days.(2, unconfirmed) Scoring information was not provided. Undiluted PGMMEA produced moderate discomfort, slight conjunctival redness, and slight corneal injury in rabbits. Recovery was complete within 48 hours after exposure.(8, unconfirmed) Scoring information was not provided.

Skin Irritation:

PGMMEA is not irritating to the skin.

Application of 0.5 mL PGMMEA was not irritating to rabbit skin after a 4-hour contact, under cover. Application of 0.5 mL PGMMEA produced slight irritation in a Draize test, with a 24-hour contact (primary irritation index 2.0/8).(10) Application of 0.01 mL undiluted PGMMEA caused no irritation in rabbits (graded 1/10).(19) Undiluted PGMMEA (beta isomer) was not irritating to rabbits.(2, unconfirmed)

Effects of Short-Term (Acute) Exposure:

PGMMEA has low short-term toxicity following inhalation, skin contact or ingestion.

Inhalation:
No adverse effects were noted in rats following a single 6-hour exposure to a saturated vapour concentration of PGMMEA (greater than 4345 ppm).(2,8-unconfirmed) Single acute exposures to the saturated vapours of PGMMEA for 7 hours caused only eye and nose irritation.(1, unconfirmed) Rats and mice were exposed to 0, 300, 1000 or 3000 ppm PGMMEA for 9/11 days (6 hrs/d). There were no changes in growth, or blood and clinical chemistry results. Rats exposed to 3000 ppm had slight changes in kidney function and appearance. The livers were heavier in female rats, but there were no structural or functional changes noted. Rats exposed to 3000 ppm and mice in all exposure groups showed signs of damage to the lining of the nose.(3) Rats were exposed to 0, 110, 560 or 2800 ppm of PGMMEA (beta isomer) for 28 days (6 hrs/d; 5 d/wk). There were no effects at 110 ppm and slight irritation (irregular breathing and rugged fur) was observed at 560 ppm. At 2800 ppm, observations included marked irritation (irregular and laboured breathing, secretions from the eyes and nose, slight apathy, salivation and rugged fur) and atrophy of the thymus in both sexes, as well as reduced weight gain and decreased liver weight in males. No testicular or bone marrow effects were noted. High dose animals showed some changes in their blood chemistry.(21)

Skin Contact:
Repeated application of an unspecified dose of PGMMEA for 2 weeks caused slight redness and exfoliation in rabbits.(8, unconfirmed) The PGMMEA (beta isomer; greater than 95% pure) caused mild skin irritation and no signs of toxicity when 1000 or 2000 mg/kg was applied to the skin of pregnant rabbits for 13 days (6 hr/d).(11) In vitro testing, application of 0.2 mL PGMMEA to human skin cells resulted in quick penetration (within about half an hour).(12)

Ingestion:
Rats receiving 5000 mg/kg PGMMEA (beta isomer) showed signs of central nervous system depression.(2, unconfirmed) Rats receiving 10 oral doses of 2600 mg/kg PGMMEA (beta isomer) over a 2-week period had no changes in clinical chemistry or effects seen upon detailed autopsy.(2, unconfirmed)

Effects of Long-Term (Chronic) Exposure:

Ingestion:
Rats were orally exposed to 100, 300 or 1000 mg/kg/day for 44 days. At 1000 mg/kg/day, body weight was depressed and food consumption reduced, with decreases in blood glucose and inorganic phosphorus and a slight increase in relative adrenal weight. No effects were noted at the lower doses.(2, unconfirmed)

Skin Sensitization:
Negative results were obtained when PGMMEA was tested in guinea pigs.(2,15-unconfirmed)

Teratogenicity, Embryotoxicity and/or Fetotoxicity:
The beta isomer is considered teratogenic and embryotoxic, the alpha isomer is not. Inhalation of PGMMEA (alpha isomer) did not cause developmental effects in rats, even in the presence of maternal toxicity. Inhalation of PGMMEA (beta isomer) did caused developmental effects in rats, in the presence of maternal toxicity. In rabbits exposed by inhalation, significant developmental effects were observed in the presence of minimal maternal toxicity. This study is limited by the small number of animals/group (11-15).
Rats (20-23/group) were exposed to 0, 500, 1980 or 4160 ppm of PGMMEA (at least 95% alpha isomer; at most 3% beta isomer) on days 6-15 of pregnancy (6 hrs/d). Mothers exposed to 4000 ppm experienced shortness of breath, red to reddish brown nasal discharge, and reduced muscle tone. At 2000 and 4000 ppm, mothers had reduced body weights, food consumption and weight gain. No significant developmental effects were observed.(13) Rats were orally exposed to 0, 100, 300 or 1000 mg/kg/day PGMMEA (alpha isomer) for 44 days (males) or from 14 days before mating to day 3 of lactation (females). Slight toxicity was observed in both sexes at 1000 mg/kg/day. No teratogenic or developmental effects were observed.(2-unconfirmed) Rats (21-24/group) were exposed by inhalation to 0, 110, 550 or 2700 ppm of PGMMEA (beta isomer; greater than 95% pure) on days 6-15 of pregnancy (6 hrs/d). Maternal toxicity was observed with significantly reduced body weights at 550 and 2700 ppm; sedation and pulsative respiration at 550 ppm; and sedation, respiratory and eye irritation at 2700 ppm. At 2700 ppm, embryotoxicity (increased resorptions), fetotoxicity (reduced fetal weight) and teratogenicity (a slight increase in the incidence of malformations, mostly dumbbell-shaped notches).(11) The embryotoxicity and fetotoxicity were statistically significant observations. It is not clear that statistical analysis was conducted on the teratogenic effects. Rabbits (11-15/group) were exposed by inhalation to 0, 36, 145 or 550 ppm of PGMMEA (beta isomer; greater than 95% purity) on days 6-18 of pregnancy (6 hrs/d). At 550 ppm, minimal maternal toxicity was observed with statistically significantly reduced body weights on days 15, 18 and 21. A non-dose related, slight increase in embryotoxicity (resorptions) was observed in all exposure groups, with statistical significance at 550 ppm. Fetotoxicity (decreased pup weight) was observed for females at 145 and 550 and males at 550 ppm. Teratogenicity was not observed in the control group or the 36 or 145 ppm exposure groups. At 550 ppm, all fetuses had severe anomalies (heart defects, anomalies of the paws and sternum).(11) This study is limited by the relatively small number of animals/group. Rabbits (13-15/group) were dermally exposed to 0, 1000 mg/kg or 2000 mg/kg undiluted PGMMEA (beta isomer; greater than 95% purity) on days 6-18 of pregnancy (6 hrs/d). At 1000 mg/kg, one mother died at day 13 (no details provided). No exposure related effects were observed except mild skin irritation. There were no adverse effects observed in the offspring.(11)

Mutagenicity:
No studies using live animals were located. Negative results have been obtained in tests using cultured mammalian cells and bacteria.
Negative results (unscheduled DNA synthesis, chromosomal aberrations) were obtained when PGMMEA was tested in cultured mammalian cells.(1,2,8,15-unconfirmed) Negative results (gene mutation) were obtained for PGMMEA in bacteria, with and without metabolic activation.(1,2,8,15-unconfirmed) Negative results (mitotic gene conversion) were obtained in yeast.(15, unconfirmed)


SECTION 16. OTHER INFORMATION

Selected Bibliography:
(1) Cragg, S.T., et al. Glycol ethers: ethers of propylene, butylene glycols and other glycol derivatives. In: Patty's Toxicology. 5th ed. Vol. 7, Chpt. 87. John Wiley and Sons, 2001
(2) European Centre for Ecotoxicology and Toxicology of Chemicals) (ECETOC). The toxicology of glycol ethers and its relevance to man. 4th ed. Technical report no. 95. ECETOC, Feb. 2005
(3) Miller, R.R., et al. Propylene glycol monomethyl ether acetate (PGMEA) metabolism, disposition and short-term vapor inhalation toxicity studies. Toxicology and Applied Pharmacology. Vol. 75 (1984). p. 521-530
(4) Johansson, G. NEG and NIOSH basis for an occupational health standard: propylene glycol ethers and their acetates. Arbete och Halsa. Vol. 32 (1990)
(5) Propylene glycol monomethyl ether acetate (ARCOSOLV PMA or ARCOSOLV PM Acetate). Lyondell Website. Lyondell Chemical Company. Technical datasheet, equipment specifications,. sales specifications, material safety data sheet storage and handling publication, and solvent properties chart. Available at: <www.lyondell.com/html/products/product_selector.shtml>
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Information on chemicals reviewed in the CHEMINFO database is drawn from a number of publicly available sources. A list of general references used to compile CHEMINFO records is available in the database Help.


Review/Preparation Date: 2006-04-05



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