Document ID: EPA-HQ-OPP-2006-0831-0003
Agency: epa
Document Type: Supporting & Related Material
Title: 
Posted Date: 2007-02-21T05:00Z

UNITED STATES ENVIRONMENTAL PROTECTION AGENCY

						WASHINGTON, D.C.  20460

													   																	OFFICE OF 

PREVENTION, PESTICIDE AND 

         														TOXIC SUBSTANCES   SEQ CHAPTER \h \r 1 

DATE:  	February 5, 2007			

MEMORANDUM

SUBJECT:	PROPYLENE GLYCOL/DIPROPYLENE GLYCOL: AD’s Risk Assessment for
Issuance of the Reregistration Eligibility Decision (RED) Document.
Reregistration Case No.: 3126.  PC Codes: 068603, 068604.  CAS Registry
No.: Propylene Glycol, 57-55-6; Dipropylene Glycol, 25265-71-8.

FROM:	SanYvette Williams-Foy, D.V.M., Science Coordinator

Antimicrobials Division (7504P)	

		

Michelle Centra, Pharmacologist/Risk Assessor

		Najm Shamim, Ph.D., Chemist

		Timothy Leighton, Environmental Scientist

		Regulatory Management Branch II

		Antimicrobials Division (7504P)

 

				And

		Jonathan Chen, Ph.D., Toxicologist

		Kathryn Montague, Biologist

		Risk Analysis and Science Support Branch

		Antimicrobials Division (7504P)

		

THRU:	Timothy F. McMahon, Ph.D.

		Division Senior Scientist

		Antimicrobials Division (7504P)

TO:	Michelle Centra, Chemical Review Manager

Diane Isbell, Acting Team Leader

Mark Hartman, Branch Chief

		Regulatory Management Branch II

		Antimicrobials Division (7504P)

Attached is the Antimicrobials Division’s (AD) risk assessment
supporting issuance of a Reregistration Eligibility Decision (RED) for
the active ingredients propylene glycol and dipropylene glycol, as well
as the tolerance reassessment for the inert uses of propylene glycol and
dipropylene glycol in antimicrobial and agricultural pesticide products.
 This assessment summarizes available information on the use,
physical/chemical properties, toxicological effects, exposure profile,
environmental fate, and ecotoxicity of propylene glycol and dipropylene
glycol.

Based on a low order of toxicity via the oral, dermal and inhalation
routes, AD has determined that a qualitative approach to assessing human
health risks from exposure to propylene glycol and dipropylene glycol is
appropriate.  AD concludes there is a reasonable certainty of no harm to
the general population and to infants and children which may result from
exposures to propylene glycol and dipropylene glycol when used as an
active ingredient (air sanitizers and surface disinfectants) or an inert
ingredient (formulated into antimicrobial and agricultural pesticide
products).  Thus, no changes to the tolerance exemptions are necessary
and they are considered reassessed as safe under section 408(q) of the
Federal Food, Drug, and Cosmetic Act (FFDCA).  In addition, AD has no
risk concerns for propylene glycol and dipropylene glycol with respect
to non-target organisms and expects no effects to listed species or
critical habitat. Therefore, AD makes a "No Effect" determination for
propylene glycol and dipropylene glycol with respect to environmental
risks.  

The supporting science documents incorporated into this risk assessment
are listed below:

1.	Propylene Glycol/Dipropylene Glycol - Report of the Antimicrobials
Division Toxicology Endpoint Selection Committee. (Memorandum: Timothy
F. McMahon, Ph.D., Chair, July 20, 2004). 

2.	Propylene Glycol/Dipropylene Glycol: Revised Toxicology Chapter in
Support of issuance of the Reregistration Eligibility Decision (RED)
Document. PC Code for Propylene Glycol:  068603.  PC Code for
Dipropylene Glycol: 068604.  CAS Registry Number for Propylene Glycol:
57-55-6:  CAS Registry Number for Dipropylene Glycol: 25265-71-8. 
Reregistration Case Number: 3126, DP #: 327061. (Memorandum: Michelle
Centra, Pharmacologist February 5, 2007).

3.   Data Evaluation Records (DER) for the Product Chemistry of
Propylene Glycol (Memorandum: N. Shamim, December 10, 2003).

4.	Data Evaluation Records (DER) for the Product Chemistry of
Dipropylene Glycol (Memorandum: N. Shamim, December 10,2003).

5.   Science Chapter: Revised Environmental Fate Studies and
Environmental Fate                   Assessment of Dipropylene Glycol
(Memorandum: N. Shamim, February 5, 2007).

6.   Science Chapter: Revised Environmental Fate Studies and
Environmental Fate Assessment of Propylene Glycol (Memorandum: N.
Shamim, February 5, 2007).

7.	Propylene/Dipropylene Glycol–Data Evaluation Records (DER) for
Estimated Drinking Water Concentrations in the Environment (Memorandum:
N. Shamim, July 2, 2004).

8.	AD’s Revised Occupational and Residential Exposure Chapter for the
Propylene and Dipropylene Glycol Reregistration Eligibility Decision
(RED) Document.  Case No. 3126.  PC Code 068603, 068604.  (Memorandum:
Timothy Leighton, February 5, 2007).

9.	Propylene/Dipropylene Glycol Revised Ecological Hazard and
Environmental Risk Characterization Chapter for the Reregistration
Eligibility Decision (RED) Document, 

Case 3126.  (Memorandum: Kathryn Montague, M.S., Biologist, February 14,
2006).

TABLE OF CONTENTS

                                                              

 TOC \f 

1.0   EXECUTIVE SUMMARY	6

1.1  Regulatory History	6

1.2  Hazard Profile	7

1.3  Dietary Exposure/Drinking Water Assessment	8

1.4  Occupational/Residential Exposures and Risks	9

1.5  Aggregate Exposure and Risk	9

1.6  Environmental Fate	9

1.7  Ecological Toxicity and Environmental Risk Assessment	10

1.8  Conclusions	10

2.0   USE PROFILE AND REGULATORY HISTORY	11

3.0   PHYSICAL AND CHEMICAL PROPERTIES	14

4.0   HAZARD PROFILE	15

4.1  Hazard-based Special FQPA Safety Factor(s) for Infants and Children
22

4.2  Dose Response Assessment	22

4.3  Endocrine Disruption	22

5.0   EXPOSURE ASSESSMENT	23

5.1    Drinking Water/Dietary Risk Assessment	23

5.2a  Occupational/Residential Exposure and Risk from Active Uses	24

5.2b  Residential Exposure and Risk Inert Uses	26

5.2c  Occupational/Residential Exposure and Risk Assessment	26

6.0   AGGREGATE EXPOSURE	27

7.0   ENVIRONMENTAL FATE/ECOLOGICAL TOXICITY	27

7.1  Environmental Fate	27

7.2  Ecological Toxicity	28

 tc "1.0   EXECUTIVE SUMMARY	6

1.1  Regulatory History	6

1.2  Hazard Profile	7

1.3  Occupational/Residential Exposure and Risk	8

1.4  Dietary Exposure and Risk	9

1.5  Drinking Water Assessment	9

1.6  Aggregate Exposure and Risk	9

	1.7  Environmental Risk	10

1.8  Ecological Toxicity	10

1.9  Conclusions	10

2.0   USE PROFILE AND REGULATORY HISTORY	10

3.0   PHYSICAL/CHEMICAL PROPERTIES	13

                  4.0   HAZARD PROFILE	14

4.1  Hazard-based Special FQPA Safety Factor(s) for Infants and Children
21

4.2  Dose Response Assessment	21

4.3  Endocrine Disruption	22

	

                  5.0   EXPOSURE ASSESSMENT	22

5.1a  Occupational/Residential Exposure and Risk from Active Uses	22

	5.1b  Residential Exposure and Risk Inert Uses	24

5.2    Drinking Water Assessment	24

6.0   AGGREGATE EXPOSURE	26

7.0   ENVIRONMENTAL FATE/ECOLOGICAL TOXICITY	27

	

	7.1  Environmental Fate	27

	7.2  Ecological Toxicity	28

" 7.3  Environmental Risk Assessment	33

7.4  Listed Species Considerations	34

8.0   CUMULATIVE RISKS	35

9.0   INCIDENT DATA (INCIDENT EXPOSURE)	35

10.0  SUMMARY OF RISK ASSESSMENT FINDINGS	36

11.0  REFERENCES	37

12.0  DATABASES AND WEBSITES	44

13.0  SUPPORTING DOCUMENTATION	44

1.0   EXECUTIVE SUMMARY

The Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA) was
amended in 1988 to accelerate the reregistration of products with active
ingredients registered prior to November 1, 1984.  The amended Act calls
for the development and submissions of data to support the
reregistration of an active ingredient, as well as a review of all
submitted data by the U.S. Environmental Protection Agency (referred to
as “EPA” or “the Agency”).  Reregistration involves a thorough
review of the scientific database underlying a pesticide’s
registration.   The purpose of the Agency’s review is to reassess the
potential hazards arising from the currently registered uses of the
pesticide; to determine the need for additional data on health and
environmental effects; and to determine whether the pesticide meets the
“no unreasonable adverse effects” criteria of FIFRA.  

This document presents the Agency’s human health and ecological risk
assessments by addressing the exposures and risks from uses of propylene
glycol (air sanitizer and surface disinfectant) and dipropylene glycol
(air sanitizer) as active ingredients or as inert ingredients
(formulated into antimicrobial and/or agricultural pesticide products). 
Potential residential exposures and risks are also addressed pursuant to
the language and intent of the Food Quality Protection Act (FQPA).  The
insecticidal products containing propylene glycol, as an active
ingredient, in addition to other active ingredients will be reregistered
only when all of the active ingredients are also determined to be
eligible for reregistration.  Therefore, the exposures and risks from
the insecticidal uses of propylene glycol are not addressed at this
time.

1.1   Regulatory History

	Active Ingredient Status

The active ingredients, propylene glycol and dipropylene glycol, were
first registered in 1950 and 1959, respectively, by the FDA as air
sanitizers.  As active ingredients, propylene glycol and dipropylene
glycol are formulated primarily as pressurized liquids and ready-to-use
solutions.  Propylene glycol is used in air sanitization and hard
surface disinfection and dipropylene glycol is used in air sanitization.
 Pest (fleas, mites, red lice, and various bacteria and viruses) control
for pets (cats, dogs, and birds) is also a major active use for
propylene glycol.  Products containing propylene glycol in combination
with other active ingredients will be reregistered only when all of the
active ingredients have been determined to be eligible for
reregistration.  This document does not address the use of propylene
glycol as an insecticide for domestic pets.

	Inert Ingredient Status

As an inert ingredient, propylene glycol is formulated into end-use
agricultural and antimicrobial pesticide products.  Dipropylene glycol
is also formulated into end-use pesticide products as an inert
ingredient for use in agricultural settings.  

	

	Tolerance Exemptions

Propylene glycol and dipropylene glycol are exempted from the
requirement of a tolerance when used as a diluent (solvent, cosolvent). 
The following tolerance exemptions for propylene glycol and dipropylene
glycol are listed in 40 CFR 180.910 [formerly 180.1001(c)] and only for
propylene glycol in 180.930 [formerly 180.1001 (e)]:

180.910.  Propylene glycol and dipropylene glycol are exempted from the
requirement of a tolerance when used as a diluent (solvent, cosolvent)
in accordance with good agricultural practice as inert (or occasionally
active) ingredients in pesticide formulations when applied to growing
crops or to raw agricultural commodities after harvest.  

180.930.  Propylene glycol is exempted from the requirement of a
tolerance when used as a defoaming agent (solvent, cosolvent) in
accordance with good agricultural practice as inert (or occasionally
active) ingredients in pesticide formulations applied to animals.  

In addition to the above, propylene glycol is approved by the Food and
Drug Administration (FDA) as a preservative in food products as listed
in 21 CFR, Part 184-Direct Food Substances Affirmed as Generally
Recognized as Safe (GRAS): 

184.1666(d).  The ingredient is used in foods at levels not to exceed
current good manufacturing practice in accordance with Sec. 184.1(b)(1).
 Current good manufacturing practice results in maximum levels, as
served, of 5 percent for alcoholic beverages, as defined in Sec.
170.3(n)(2) of this chapter; 24 percent for confections and frostings as
defined in Sec. 170.3(n)(9) of this chapter; 2.5 percent for frozen
dairy products as defined in Sec. 170.3(n)(20) of this chapter; 97
percent for seasonings and flavorings as defined in Sec. 170.3(n)(26) of
this chapter; 5 percent for nuts and nut products as defined in Sec.
170.3(n)(32) of this chapter; and 2.0 percent for all other food
categories.  

1.2 Hazard Profile

		Propylene Glycol

Published literature studies show low toxicity (Toxicity Category IV)
following acute exposures to propylene glycol by the oral, dermal, and
inhalation routes.  Propylene glycol exhibited relatively high LD50
values that ranged from 8000 to 46000 mg/kg/day.  There was some
evidence of clinical signs of toxicity (central nervous system
depression, loss of balance and analgesia) in guinea pigs, mice, and
rabbits at doses greater than 13000 mg/kg/day.  However, these effects
occurred at dose levels that far exceed the testing limit doses
established for acute oral toxicity testing in mammalian studies. 
Propylene glycol has been found to penetrate the outermost layer of the
epidermis, however it is non-irritating to the skin.  In addition, this
chemical is non-irritating to the eyes and is not a skin sensitizer.  

Repeat dose toxicity studies conducted via oral, dermal, and inhalation
routes at concentrations near or above the established limit dose (1000
mg/kg/day for oral and dermal studies, 1 mg/L or 1000 mg/m3 for
inhalation studies) do not show systemic/non-systemic toxicities. 
Propylene glycol administered orally to experimental animals in studies
designed to measure developmental and reproductive toxicity failed to
elicit any significant effect at doses up to and including the limit
dose.  Studies of chronic propylene glycol exposure to experimental
animals at doses equivalent to or in excess of the limit dose have shown
little evidence of adverse toxic effects.  Propylene glycol has been
shown to be negative in a battery of mutagenic assays and exhibited no
evidence of carcinogenicity in experimental studies. 

		Dipropylene Glycol

Submitted studies as well as published literature show low acute
toxicity (Toxicity Category IV) for dipropylene glycol when administered
to rodents and non-rodents, regardless of route.  In repeat-exposure
studies, experimental animals showed no adverse toxic effects up to the
established testing limit dose (1000 mg/kg/day for oral and dermal
studies, 1 mg/L or 1000 mg/m3 for inhalation studies).  Dermal
applications of dipropylene glycol did not result in any adverse effects
in experimental animals.  Dipropylene glycol administered orally to
experimental animals in studies designed to measure developmental and
reproductive toxicity did not induce treatment-related effects at the
maternal, reproductive, or developmental stages of the animals at doses
up to and including the limit dose.  Experimental animals demonstrated
low toxicity to chronic dipropylene glycol exposures at doses equivalent
to or in excess of the limit dose.  Dipropylene glycol has been shown to
be negative for mutagenicity and carcinogenicity in a battery of assays
and experimental studies.      

Based on a review of the available toxicology data, the Agency concluded
that propylene glycol and dipropylene glycol exhibit minimal toxic
effects by the oral, dermal, and inhalation routes of exposure.  While
the developmental and reproductive studies are from published sources
and do not report all the data that are normally reported under the
series 870 guidelines, it is apparent that toxic effects are manifested
only at doses that exceed the established limit dose for these types of
studies.  Therefore, the toxicology database is adequate to characterize
the hazards of propylene glycol and dipropylene glycol, and no
additional data are required.  The special 10x hazard-based safety
factor under FQPA is reduced to 1x.

1.3	Dietary Exposure/Drinking Water Assessment

Dietary exposure through the drinking water could potentially occur from
use of propylene glycol or dipropylene glycol as inert ingredients in
agricultural pesticide products. Due to the similarities in
chemical/physical properties as well as similarity in the toxicity
profile of propylene glycol and dipropylene glycol, the drinking water
exposure assessments for propylene glycol were determined to be adequate
for dipropylene glycol.  Based on the FIRST and SCI-GROW model results,
the estimated environmental concentrations (EECs) for these chemicals
are not likely to exceed a 24-hour time-averaged concentration of 887.5
ppb or an annual average concentration of 11 ppb in surface water and
107 ppb in ground water.  Each of these exposures is orders of magnitude
below levels at which health effects are observed from exposure to
propylene glycol or dipropylene glycol.  Thus, the estimated
concentrations of propylene glycol or dipropylene glycol in drinking
water do not present any risk of concern from agricultural uses of these
chemicals when formulated in pesticide products as inert ingredients.

1.4  Occupational/Residential Exposures and Risks

Potential for dermal and/or inhalation exposure may occur during
application as well as post-application following use of propylene
glycol as an active ingredient for air sanitization, hard surface
disinfection and direct use on pets.  These exposures to propylene
glycol may occur in both occupational and non-occupational settings that
include commercial/institutional premises, residential/public access
premises, and various applications for medical premises and equipment. 
Based on the most predominant labeled uses of propylene glycol as an
active ingredient, the maximum application rate for air sanitization is
0.022 lb ai/6000 ft3.  Similar types of exposures are possible for
dipropylene glycol with a maximum application rate of 0.015 lb ai/6000
ft3 when formulated in aerosol spray products for use as an air
sanitizer.  In addition, both propylene glycol and dipropylene glycol
are also formulated as inert ingredients in agricultural pesticide
products as well as in various household/consumer products.  However,
there is no evidence of adverse effects at doses of propylene glycol or
dipropylene glycol up to the established limit dose in repeat-exposure
dermal (1000 mg/kg/day) and inhalation (1 mg/L or 1000 mg/m3)  toxicity
studies.  Thus, no toxicological endpoints of concern have been
established for either of these chemicals based on review of the
available mammalian toxicity data.  Due to the low order of toxicity and
low application rates from the current uses of these chemicals, no risks
associated with potential exposures have been quantified for use of
propylene glycol or dipropylene glycol as active and/or inert
ingredients in pesticide products. 

1.5  Aggregate Exposure and Risk

AD has no human health concerns regarding both the active or inert
ingredient uses of propylene glycol or dipropylene glycol in pesticide
products.  Considering the worst-case exposure scenarios which could
occur from the active and inert uses of propylene glycol or dipropylene
glycol, the total anticipated human exposure is orders of magnitude
below any dose of these chemicals that has been shown to cause adverse
effects.  Therefore, there is no risk of concern from potential
exposures to propylene glycol or dipropylene glycol in agricultural and
antimicrobial pesticide products.

1.6  Environmental Fate

		Propylene Glycol

Propylene glycol is not bioaccumulative (log KOW -0.92), does not
hydrolyze and is highly mobile in soils.  Biodegradation in aerobic
soils occurs in 4 days.  The air half-life of propylene glycol is
relatively short, estimated to be about 32 hours, due to the induced
photochemical reaction with hydroxy-radical in the atmosphere; hence,
its presence in the atmosphere is not likely a concern.  Due to the use
of propylene glycol as a deicing fluid there is a possibility for ground
and surface water contamination.  However, relatively rapid aerobic and
anaerobic degradation with maximum half-lives of 4 and 9 days,
respectively, coupled with a high water solubility indicates a low
potential to migrate to ground water.

		Dipropylene Glycol

Dipropylene glycol has a log KOW of -1.07 and is not bioaccumulative. 
Highly miscible in water, dipropylene glycol does not hydrolyze, has a
low binding constant with soils, and is very mobile in soils.  Due to
high mobility in soil and slow biodegradation, possibility exists for
dipropylene glycol to contaminate ground and surface water systems if
outdoor use occurs.  However, considering the registered pesticide uses
this is not likely.  Soil grab samples and river die-away test data
pertaining to the biodegradation of dipropylene glycol in soil and
natural waters were not available in open-literature.  A few aerobic
biological screening studies that utilized settled waste water, sewage
or activated sludge for inocula, indicate that dipropylene glycol should
biodegrade slowly in the environment. The air half-life is estimated to
be 13 hours due to the induced photochemical reaction with
hydroxy-radical in the atmosphere; hence, its presence in the atmosphere
is not likely to pose any problem.

1.7  Ecological Toxicity and Environmental Risk Assessment

Based on the labeled use patterns, propylene glycol and dipropylene
glycol are not expected to result in significant environmental
exposures, and both chemicals show very low toxicity to birds (LD50
values greater than 2000 mg/kg), mammals (LD50 values greater than 5000
mg/kg and NOAEL values greater than 2500 mg/kg/day), fish and aquatic
invertebrates (LC50 values ranging from 710 to 62000 ppm for fish and
aquatic invertebrates).  Risk quotients calculated for the inert use of
propylene glycol for aquatic organisms, including Endangered Species
(0.001 for fish and 0.0000143 for invertebrates) are well below the
Agency’s LOC.  Adverse effects on endangered/threatened terrestrial
and aquatic animal species are not anticipated from exposure to these
chemicals; therefore, the Agency makes a “no effect” determination
for propylene glycol and dipropylene glycol on the listed terrestrial
and aquatic animal species.  Toxicity and risk to endangered/threatened
plants cannot be addressed at this time due to the lack of phytotoxicity
information.

1.8 Conclusions

From the available animal studies and other data, EPA has concluded that
propylene glycol and dipropylene glycol exhibit low toxicity and that
there is a reasonable certainty of no harm to the general population, as
well as infants and children, from exposures to both propylene and
dipropylene glycol as active and/or inert ingredients, including all
anticipated exposures (i.e., environmental), and all other types of
exposures for which there is reliable information.  Thus, no changes to
the tolerance exemptions are necessary and they are considered
reassessed as safe under section 408(q) of the Federal Food, Drug, and
Cosmetic Act (FFDCA).  In addition, AD has no risk concerns for
propylene glycol and dipropylene glycol with respect to non-target
organisms and expects no effects to listed species or critical habitat.
Therefore, AD makes a "No Effect" determination for propylene glycol and
dipropylene glycol with respect to environmental risks. 

 

2.0   USE PROFILE AND REGULATORY HISTORY

		Propylene Glycol

The major applications for propylene glycol are air sanitization,
surface disinfection, and pesticide treatment for domestic animals. 
Additional uses include unsaturated polyester resins, plasticizers,
food, drugs, cosmetics, pet foods, paints and coatings, antifreeze,
de-icing fluids, liquid detergents, and tobacco.  

As an air sanitizer, this active ingredient has numerous listed active
use sites including industrial/institutional use in washrooms,
auditoriums, public rooms, hotel lobbies, theaters, hospitals,
classrooms, railroads, airplanes, buses, taxicabs, sitting rooms, locker
rooms, factories, mills, and department stores.  Disinfectant properties
are utilized in the household for hard, nonporous surfaces including
windows, shower stalls, countertops, refrigerators, microwave ovens, and
tubs (i.e., non-food contact surfaces).

As an inert ingredient, propylene glycol can be incorporated into
food-use pesticide products applied to agricultural crops and into
end-use antimicrobial formulations.

The active ingredient propylene glycol was first registered by the USDA
for use as an air sanitizer in 1950 (Hysan/AMP’s Air-Gly, EPA Reg. No.
334-100; James Varley & Sons, LLC’s Glyco-Mist, EPA Reg. No. 421-158;
Chemical Service’s Sprayfect, EPA Reg. No. 900-24) in 1959
(dipropylene glycol: Dewitt Chemical Company’s Witodorant Space
Deodorant, EPA Reg. No. 1269-24; Zep Manufacturing Company’s
Zep-O-Zone Space Deodorant, EPA Reg. No. 1270-45).  The majority of
manufactures of propylene glycol formulated pesticidal products are
represented by the CSPA (Consumer Specialty Products Association)
Glycols Joint Venture (a consortium formerly known as the CMSA Glycols
Joint Venture).  Currently, the CSPA Glycols Joint Venture members
include the following companies: Amrep, Inc., Beaumont Products, Inc.,
Chase Products, MEDO-SOPUS, Industries, Reckitt Benkiser, Inc., S.C.
Johnson & Son, Inc. and Wellmark International.

Propylene glycol is formulated primarily as a pressurized liquid and
used as an active ingredient in three types of applications: air
sanitizers, surface disinfectants and pest (mites and red lice) control
on cats, dogs and caged birds.  The latter use of propylene glycol as a
domestic pet insecticide for the control of mites and lice will be
addressed in a separate risk assessment.  Products containing propylene
glycol in combination with other active ingredients will be reregistered
only when all of the active ingredients have been determined to be
eligible for reregistration.  This document does not address the use of
propylene glycol as an insecticide for domestic pets.  

For each use category, Table 1 lists the registrants and their
respective EPA registration numbers for products containing propylene
glycol. 



Table 1.  EPA Registration Numbers for Propylene Glycol Products

Use Category	Formulation	Registrant	EPA Registration Numbers

Air Sanitizer/ Disinfectant	Pressurized Liquid	S. C. Johnson & Son,
Inc.*	4822-491

Air Sanitizer	Pressurized Liquid	Amrep, Inc.*	10807-24, 10807-37,
10807-43

Air Sanitizer	Pressurized Liquid	Medo-Sopus Industries, Inc.*	51838-1,
51838-2

Mite, flea, and Lice Control	Pressurized Liquid	Wellmark International
*,**	2724-514, 2724-618, 

2724-763, 2724-764

*Member companies of the GSPA Glycols Joint Venture.

**The insecticidal products containing propylene glycol in addition to
other active ingredients will be reregistered only when all of the
active ingredients have been determined to be eligible for
reregistration. 

		Dipropylene Glycol

The major applications for dipropylene glycol are air sanitization and
hard surface disinfection.  Additional uses include unsaturated
polyester resins, plasticizers, polyurethanes, textile lubricants,
automotive fluids, cutting oils, defoamers, de-icing fluids, solvent
(for printing dyes, cellulose acetate, nitrocellulose and shellac),
cosmetics, fragrances and extractant (for aromatics in the petrochemical
industry). 

As an air sanitizer, this active ingredient has numerous listed active
use sites including industrial/institutional use in washrooms, lobbies,
theaters, hospitals, locker rooms, reception rooms, and shops.  

As an inert ingredient, dipropylene glycol can be incorporated into
food-use pesticide products applied to agricultural crops.  Currently,
no known products are registered with the Agency that includes
dipropylene glycol as an inert ingredient.

The active ingredient dipropylene glyco, was first registered by the
USDA as an air sanitizer in 1959 (Dewitt Chemical Company’s Witodorant
Space Deoderant, EPA Reg. No. 1269-24; Zep Manufacturing Company’s
Zep-O-Zone Space Deodorant, EPA Reg. No. 1270-45).  Currently, the three
formulated products containing dipropylene glycol as an active
ingredient are manufactured by Waterbury Companies, Inc. and Beaumont
Products, Inc., member companies represented by the CSPA Glycols Joint
Venture.  

Dipropylene glycol is formulated primarily as a pressurized liquid and
used in as an air sanitizer.  Table 2 lists the registrants and the
respective EPA registration numbers for products containing the active
ingredient, dipropylene glycol.

Table 2.  EPA Registration Numbers for Dipropylene Glycol Products

Use Category	Formulation	Registrant	EPA Registration Numbers

Air Sanitizer	Pressurized Liquid	Waterbury Companies, Inc.*	9444-19,
9444-136

*Member Company of the CSPA Glycols Joint Venture.

	Tolerance Exemptions

The following tolerance exemptions for propylene glycol and dipropylene
glycol are listed in 40 CFR 180.910 [formerly 180.1001(c)] and for
propylene glycol alone in 180.930 [formerly    180.1001 (e)]:

180.910.  Propylene glycol and dipropylene glycol are exempted from the
requirement of a tolerance when used as a diluent (solvent, cosolvent)
in accordance with good agricultural practice as inert (or occasionally
active) ingredients in pesticide formulations applied to growing crops
or to raw agricultural commodities after harvest.  

180.930.  Propylene glycol is exempted from the requirement of a
tolerance when used as a defoaming agent (solvent, cosolvent) in
accordance with good agricultural practice as inert (or occasionally
active) ingredients in pesticide formulations applied to animals.  

Propylene glycol is approved by the FDA as a preservative in food
products as listed in 21 CFR, Part 184-Direct Food Substances Affirmed
as GRAS: 

184.1666(d). The ingredient is used in foods at levels not to exceed
current good manufacturing practice in accordance with Sec. 184.1(b)(1).
Current good manufacturing practice results in maximum levels, as
served, of 5 percent for alcoholic beverages, as defined in Sec.
170.3(n)(2) of this chapter; 24 percent for confections and frostings as
defined in Sec. 170.3(n)(9) of this chapter; 2.5 percent for frozen
dairy products as defined in Sec. 170.3(n)(20) of this chapter; 97
percent for seasonings and flavorings as defined in Sec. 170.3(n)(26) of
this chapter; 5 percent for nuts and nut products as defined in Sec.
170.3(n)(32) of this chapter; and 2.0 percent for all other food
categories.

3.0   PHYSICAL AND CHEMICAL PROPERTIES

	Propylene Glycol

Propylene glycol (chemical name: 1,2-Propanediol or 1,2-hydroxypropane)
is an aliphatic alcohol manufactured by a continuous 30 minute process
involving the non-catalytic liquid phase reaction of propylene oxide and
water with a molecular formula of C3H8O2.  The structure of propylene
glycol is:

			OH-CH2-CH(OH)-CH3

Propylene glycol (CAS Registry Number: 57-55-6) is a colorless, slightly
acrid to odorless, viscous, hygroscopic liquid with the following
chemical properties:  molecular weight of 76.0 amu, boiling point of 188
oC at 760 mm Hg, specific gravity of 1.038 at 20 oC, vapor pressure of
0.03 mm Hg at 20 oC, Log KOW (octanol/water partition coefficient) of
-0.92, viscosity of 48.6 cPS at 25 oC and 8.42 cPS at 60 oC, and
Henry’s Law Constant (air/water partition coefficient) of 1.31 x 10-10
atm m3/mole.  Propylene glycol does not undergo direct air photolysis
but has an estimated half-life of 32 hours due to induced photochemical
reaction of atmospheric hydroxyl radical.  It is highly miscible in
water, stable at normal temperatures, highly hygroscopic, and should be
kept at ambient temperature in special containers (tanks).  Propylene
glycol has a low absorptivity and consequently, is highly mobile in
soil.

				Dipropylene Glycol

Dipropylene glycol (chemical name: Oxybispropanol) is an aliphatic
alcohol that is produced as a byproduct of the manufacture of propylene
glycol with a molecular formula of C6H14O3. The structure of dipropylene
glycol is:

						CH3-CH(OH)-CH2-O-CH2-CH(OH)-CH3

Dipropylene glycol (CAS Registry Number: 25265-71-8) is a colorless,
essentially odorless, viscous, hygroscopic liquid with the following
chemical properties:  molecular weight of 134.0 amu, boiling point of
216-236 oC at 760 mm Hg, melting point (not applicable), specific
gravity of 1.036 at 20 oC, vapor pressure of 0.03 mm Hg at 20 oC, Log
KOW of -0.67 at 25 oC and -1.07, viscosity of 75.0 cPS at 25 oC and 10.9
cPS at 60 oC, Henry’s Law Constant (air/water partition coefficient)
of 3.58 x 10-9 atm m3/mole, and KOC (organic carbon ratio in soil) of 6.
 Dipropylene glycol does not undergo direct air photolysis but has an
estimated half-life of 13 hours due to induced photochemical reaction of
atmospheric hydroxyl radical.  It is highly miscible in water, stable at
normal temperatures, highly hygroscopic, and should be kept at ambient
temperature in special containers (tanks).  Dipropylene glycol has a low
absorptivity; therefore, it is highly mobile in soil.

HAZARD PROFILE

		Adequacy of the Database

The propylene/dipropylene glycol mammalian toxicity database consists of
published literature studies and submitted studies from the CSPA Glycols
Joint Venture.  These available data were determined to be adequate in
the identification and characterization of hazard for the registered
uses of technical grade propylene and dipropylene glycol as an air
sanitizer and a hard surface disinfectant.

		Acute Toxicity

			Propylene glycol 

The toxicological database for propylene glycol is supported by
published literature studies (Table 3).  Acute oral toxicity studies
yielded similar, low acute toxicities with relatively high LD50 values
(all considered to be Toxicity Category IV) ranging from 8000-46000
mg/kg propylene glycol for rodents and 18000-20000 mg/kg for both
rabbits and guinea pigs.  Clinical signs (loss of balance, marked
depression, and analgesia) were reported in the rabbit and guinea pig
only at extremely high doses that exceeded the established limit dose
(5000 mg/kg) for an acute oral toxicity study.  Similar effects were
also evident in one study with mice only at doses that resulted in
lethality (LD50 values of 23000-24900 mg/kg). 

Propylene glycol induced degeneration of goblet cells (+69%) in tracheal
lining of rabbits following a 20 and 120 minute exposure to 10% aerosol
in an acute inhalation toxicity study; no other toxicological effects
were observed.  In primary eye irritation studies, propylene glycol was
instilled in the eyes of rabbits (0.1-0.5 mL).  There were no
treatment-related effects on the corneas of the animals and propylene
glycol was classified as a non-irritant.  No acute LD50 value has been
reported for dermal toxicity.  In a series of skin sensitization tests,
no reactions were observed in guinea pigs exposed to solutions up to 70%
propylene glycol.

Additionally, several studies established intraperitoneal and
intravenous LD50 values for mice, rats, and rabbits.  The acute LD50
values for intraperitoneal injection of propylene glycol ranged from
11200-13000 mg/kg/day for rodents.  Similar, but lower, values were
observed in intravenous injections experiments; with LD50 ranges of
6200-8000 mg/kg/day for rodents and 6500 mg/kg/day for rabbits.

			Dipropylene Glycol 

The dipropylene glycol toxicological database was comprised of studies
submitted by the CSPAGlycols Joint Venture and published literature
studies (Table 3). Low acute toxicities for dipropylene glycol were
established in rodents, rabbits, and guinea pigs.  Acute LD50 values
appear to be relatively high concentrations and fall within the toxicity
classification of category IV for all of the acute experiments.  



Studies submitted by the Joint Venture included acute oral LD50 values
greater than 5010 mg/kg/day when dipropylene glycol was administered to
Sprague-Dawley male and female rats.  Instillation of 0.1 mL dipropylene
glycol in eyes of New Zealand White (NZW) rabbits showed no evidence of
corneal damage and was classified as a slight irritant based on observed
conjunctival irritation that subsided within 24 hours. 

When dipropylene glycol was administered topically to NZW rabbits the
dermal LD50 was greater than 5010 mg/kg/day (highest dose tested).  No
toxicological effects were observed at the doses used in these acute
dermal toxicity studies.  Dipropylene glycol (0.5 mL of 100% TGAI) was
administered to NZW rabbits in a primary dermal irritation study.  There
was evidence of erythema in a single site that subsided in 24 hours
while there were no traces of edema observed in treated animals;
dipropylene glycol was classified as a non irritant.  A Glycols Joint
Venture submitted study for dermal sensitization assessed a single
challenge application of 0.5 mL dipropylene glycol (100% purity) to
guinea pigs that had previously been treated with dipropylene glycol. 
The topical administration did not produce any evidence of dermal
sensitization in animals. 

In a 4-hour inhalation whole-body exposure study conducted in
Sprague-Dawley rats using dipropylene glycol, the LC50 was found to be
greater than 2.34 mg/L.  There were no treatment-related effects
observed in rats exposed to dipropylene glycol and all of the animals
survived the exposure and observation period with no indication of
toxicity. 

In multiple open literature reports, when rats were exposed to
dipropylene glycol, the acute oral toxicity LD50 values were similar to
dipropylene glycol values and ranged from greater than 5000 to 15000
mg/kg/day for treated animals.  An acute dermal administration of 7.2%
dipropylene glycol to rabbits yielded an LD50 value greater than 2000
mg/kg/day.   Dipropylene glycol was found to be an irritant to rabbits
when administered in an undiluted dose of 510 mg in a primary eye
irritation study.  Intraperitoneal and intravenous injections to rodents
resulted in toxicity values similar to other acute studies, with LD50
values ranging from 4600-10000 and 5800-11500 mg/kg/day, respectively.

Table 3.  Acute Toxicity Profile of Propylene/Dipropylene Glycol

Guideline	

Study Type	

Results	

Toxicity Category

Propylene Glycol

870.1100	

Acute Oral - Rat	

LD50 range = 8000 - 46000 mg/kg	

IV

870.1100	

Acute Oral - Mouse	

LD50 = 24800 mg/kg	

IV

870.1100	

Acute Oral - Rabbit, Guinea pig	

LD50 range = 18350 - 19600 mg/kg	

IV

870.2400	

Acute Eye Irritation - Rabbit	

non irritant	

IV

870.2500	

Acute Skin Irritation - Rabbit	

non irritant	

IV

870.2600	

Skin Sensitization	

non sensitizer	

N/A

Dipropylene Glycol

870.1100	

Acute Oral - Rat	

LD50 > 5010 mg/kg	

IV

870.1100	

Acute Oral - Rat	

LD50 range > 5000 to >15000 mg/kg	

IV

870.1200	

Acute Dermal - Rabbit	

LD50 > 5010 mg/kg	

IV

870.1200	

Acute Dermal - Rabbit	

LD50 > 2000  mg/kg	

IV

870.1300	

Acute Inhalation - Rat	

LC50 > 2.34 mg/L	

IV

870.2400	

Acute Eye Irritation - Rabbit	

slight irritant	

IV

870.2400	

Acute Eye Irritation - Rabbit	

slight irritant	

IV

870.2500	

Acute Skin Irritation - Rabbit	

non irritant	

IV

870.2600	

Skin Sensitization - Guinea Pig	

non sensitizer	

 N/A

N/A = Not applicable

		Subchronic Toxicity

			Propylene Glycol 

Subchronic toxicity studies from the published literature show low
toxicity in animals repeatedly exposed to propylene glycol for an
intermediate length of time.  In a 15-week oral toxicity study, there
were no significant differences in serum, urine and hematological
parameter measurements and organ weights between control rats and those
fed a diet containing propylene glycol up to a dose of 2500 mg/kg/day. 
No abnormalities were observed at necropsy in any animal tested.  In a
second subchronic toxicity study, propylene glycol was administered to
rats via the drinking water for 140 days.  Although there were clinical
signs (CNS depression and minor liver abnormalities) exhibited in
animals at a dose of 13200 mg/kg/day, these effects occurred at a dose
level well above the limit dose of 1000 mg/kg/day established for an
oral subchronic toxicity study in rodents. 

In a 90-day inhalation study, female rats were exposed to propylene
glycol vapors (1.0 or 2.2 mg/L) for 6 hours/day, 5 days/week over a
period of 90 days.  Animals experienced decreases in body weight and
food consumption, although there were no changes in respiratory rates,
minute volumes, or tidal volumes during exposure.  With the exception of
a significant increase in the number of goblet cells in the nasal
passages of the mid- and high-dose animals (males and females), animals
were otherwise unaffected by propylene glycol treatment (0.16, 1.0, or
2.2 mg/L) in this subchronic inhalation study. 

			Dipropylene glycol

In a subchronic oral toxicity study, dipropylene glycol was administered
via the drinking water to mice at concentrations of 715, 1350, 2620,
4790, or 11000 mg/kg/day for males and 1230, 2140, 4020, 7430, or 14700
mg/kg/day for females over a period of 90 days. There were
treatment-related increases in mortality at the high-dose of 11000
mg/kg/day for both males and females and increased body weight in
females treated with 2140 mg/kg/day dipropylene glycol.  Minimal
toxicity was observed at these relatively high doses of dipropylene
glycol; 11000 and 14700 mg/kg/day for males and females, respectively. 

In a second study, male and female rats exhibited reductions in body
weight at 425 and 1690 mg/kg/day, respectively, when exposed to
dipropylene glycol in drinking water for 90 days (425, 890, 1840, 3890,
or 12800 mg/kg/day for males and 460, 920, 1690, 3340, or 8950 mg/kg/day
for females).  Water consumption increased at the high-dose for all
animals by the second week and continued throughout the remainder of the
study.  There were increases in weight and appearance of lesions in
liver and kidneys of treated animals at concentrations (890 mg/kg/day
for males; 3340 mg/kg/day for females) exceeding those that induced body
weight reductions.  High-dose (12800 mg/kg/day) males experienced
testicular effects, hypoactivity and poor hair coats.  

		Chronic Toxicity and Carcinogenicity

Published literature studies examining the chronic toxicity and
carcinogenic potential of propylene glycol and dipropylene glycol have
shown the chemicals to be non-carcinogenic in rodent and non-rodent
species under the conditions of each study protocol.  In addition,
systemic adverse effects were noted only at doses of propylene glycol
and dipropylene glycol that exceed the limit doses or concentrations
established for mammalian chronic toxicity studies (1000 mg/kg/day for
oral studies, 1 mg/L or 1000 mg/m3 for inhalation studies) established
for mammalian chronic toxicity studies.

  

			Propylene glycol

Several studies in the rat involving dietary, drinking water, and
inhalation exposure to propylene glycol comprise the chronic toxicity
database.  There was little evidence of chronic toxicity from exposure
to propylene glycol (at the relatively high doses or concentrations that
exceeded the established testing limits) used in these studies.  

With the exception of slight abnormalities in the liver of treated
animals, there were no signs of toxic effects when propylene glycol was
administered at dose levels of 1230 or 2450 mg/kg/day in the diet for
two years.  Similarly, slight liver abnormalities were noted in a
two-year drinking water study that administered 1834 mg/kg/day propylene
glycol to rats.  However, no other effects were observed in this
drinking water study at 1834 mg/kg/day propylene glycol. 

In a continuous-exposure inhalation study, rats were exposed to
0.17-0.35 mg/L propylene glycol for 18 months.  A 50% increase in body
weight was observed at an exposure concentration of 0.35 mg/L.  No other
effects were observed in treated animals in this inhalation toxicity
study.

A carcinogenicity study conducted in rats administered propylene glycol
in the feed for two years at concentrations of 200, 400, 900, or 1700
mg/kg/day for males and 300, 500, 1000, or 2100 mg/kg/day for females
showed no significant evidence of chronic toxicity or significant
treatment-related neoplasm.  In another study, the carcinogenicity
potential of propylene glycol was examined in mice when concentrations
of 0.02 mL of 10, 50 or 100% propylene glycol were applied to the skin
of these animals twice a week for 110 weeks.  There was no effect on
survival rate or the incidence of tumors between the control animals and
the propylene glycol-treated groups. 

			Dipropylene glycol  

There were decreases in body weight and survival of male and female rats
treated with the high doses of 2330 mg/kg/day and 3040 mg/kg/day
dipropylene glycol, respectively, in drinking water for two years. 
Clinical signs of toxicity were also noted in males with an increase in
focal histiocytic and focal granulomatous inflammation in the liver. 
However, there was no evidence of carcinogenic activity in rats treated
with dipropylene glycol over the course of 24 months.  In a similar
study conducted in mice, animals experienced decreased survival and body
weight at the high-dose (2390 mg/kg/day for males and 1950 mg/kg/day for
females) of dipropylene glycol tested in the study.  Males in the 2390
mg/kg/day dose group also exhibited reduced water consumption. 
Following two years of dipropylene glycol administration in the drinking
water, mice failed to show any evidence of carcinogenic activity.

		Mutagenicity

Published literature studies comprise the mutagenicity database for
propylene glycol and dipropylene glycol.  In this battery of studies,
propylene glycol and dipropylene glycol did not exhibit any mutagenic or
genotoxic activity.  

			Propylene glycol

There were no signs of mutagenicity in several bacterial reverse
mutation tests in tester strains TA 1535, TA 1537, TA 100, TA 98, and TA
1538 that were performed with concentrations of propylene glycol ranging
from 1-10000 μg/plate.  Propylene glycol did not induce mutant colonies
and was negative in all cases.  Similarly, negative results were
observed in additional mutagenicity studies, including an in vitro
mammalian cell gene mutation test, in vitro mammalian chromosome
aberration test, mammalian erythrocyte micronucleus test, and a dominant
lethal assay. 

			

Dipropylene glycol  

μg/plate) to the bacterial tester strains TA 98, TA 100, TA 1535, and
TA 1537.  In an in vitro mammalian cell gene mutation test, mice were
given 0.005, 0.01, 0.05, 0.1, 0.5, 1.0, 5.0, 10, or 50 μL/mL
dipropylene glycol and failed to produce a positive response in either
the presence or absence of metabolic activation. 

		Dermal Absorption

			Propylene glycol  

Propylene glycol has been found to penetrate the outermost layer of the
epidermis.  Although absorption through the skin is possible, it is
doubtful any appreciable systemic/dermal injury would occur based on the
lack of irritation in acute dermal studies and the lack of systemic
toxicity or carcinogenicity in a two-year dermal toxicity study. 

			Dipropylene glycol  

Similar to propylene glycol, exposure to dipropylene glycol is unlikely
to cause adverse effects considering that absence of: (1) dermal
irritation/toxicity in acute studies, (2) dermal and systemic toxicities
in repeat-dose studies and (3) skin sensitization.

		Metabolism and Excretion

			Propylene glycol  

In an elimination and metabolism study a maximum concentration of
29.21-2.92 mmol/L Propylene glycol was found in the blood of rats at 2
hours with the high-dose administration of propylene glycol (treatment
with 4.83, 9.66, 19.32, 38.64, and 77.28 mmol/kg propylene glycol). 
Propylene glycol was readily absorbed in the gastrointestinal tract of
several animals in other studies.  The absorption was rapid and complete
and propylene glycol was broken down into glycogen.  Propylene glycol
was administered orally to humans (70 g) and dogs (150 g) in a NTIS
study in which this chemical was metabolized and an appreciable fraction
of the administered dose was excreted in the urine.  Within 10 hours,
20-25% of the 70 g dose given to the human subjects was excreted
whereas, dogs excreted 20% of the 150 g dose within 24 hours.   

			Dipropylene glycol

No studies are available in the toxicity database which examines the
metabolism of dipropylene glycol.

		

Developmental and Reproductive Toxicity tc \l2 "Dermal
AbsorptionPropylene glycol:  There have been no studies reported dealing
with PG and skin absorption.  PG has been found to penetrate the
outermost layer of the epidermis; however, because of this PG is
commonly used as a cosmetic ingredient in many products.  Although
absorption through the skin is possible, it is doubtful any appreciable
systemic/dermal injury would occur based on the lack of irritation in
acute dermal studies, no evidence of chronic toxicity or tumor response
following a 2-year dermal application study, and the widespread use in
cosmetics that is considered safe.5, 37  Dipropylene glycol:  No dermal
penetration/skin absorption studies were recovered for dipropylene
glycol.  Similar to PG, DiPG is also used in many cosmetic formulations
and has been generally recognized as safe by the FDA.  Dermal and
systemic injury from skin exposure to DiPG is unlikely considering its
widespread use in cosmetics, no evidence of dermal toxicity in acute
studies, and no evidence of skin sensitization in repeated exposure
studies.24-26, 28Metabolism and ExcretionPropylene glycol:  In an
elimination and metabolism study a maximum concentration of 29.212.92
mmol/L PG was found in the blood of rats 2 hours with the high-dose
administration of PG (treatment with 4.83, 9.66, 19.32, 38.64, and 77.28
mmol/kg PG).47  PG was readily absorbed in the gastrointestinal tract of
several animals in other studies.  The absorption was rapid and complete
and PG was broken down into glycogen.48-51  PG was administered orally
to humans (70 g) and dogs (150 g) in a NTIS study in which a portion of
PG was metabolized and an appreciable fraction was excreted in the
urine.  Within 10 hours, 20-25% of the 70 g dose given to the human
subjects was excreted.  The dogs excreted 20% of the 150 g dose within
24 hours.48   Dipropylene glycol:  No studies have been found that
examined the metabolism of DiPG.Developmental and Reproductive Toxicity 

Open literature studies examining the developmental and reproductive
toxicity of propylene glycol and dipropylene glycol showed minimal
evidence of toxicity at relatively high concentrations (10000 mg/kg/day)
that exceed the established limit dose of 1000 mg/kg/day.  

			Propylene glycol

Propylene glycol, administered to mice at a concentration of 10000
mg/kg/day in drinking water, did not produce any overt adverse effects
in fetal development.  A second study testing at a similar dose (10400
mg/kg/day) administered subcutaneous injections of propylene glycol on
gestation day (GD) 9, 10, and 11 to mice which did not result in
significant increases in fetal malformations compared to the untreated
control animals.  Two additional studies involving mice administered
propylene glycol via the oral route at doses up to 10400 mg/kg/day did
not induce any maternal, reproductive, or developmental toxicities in
theses animals. 

Several other developmental studies were performed on rats, mice,
rabbits, and hamsters in which oral doses of propylene glycol ranging
from 12.3-1600 mg/kg/day were administered orally during the gestation
period.  In all four studies, there were no incidents of
treatment-related toxicity observed in the maternal, reproductive, or
developmental parameters measured in these animals.  



Propylene glycol was also administered to rats (1600-6200 mg/kg/day),
mice (1550-10000 mg/kg/day), and rabbits (1230 mg/kg/day) during
gestation via a stomach tube.  There were no adverse reproductive
effects observed in any of these experiments.  However, a slight
maternal toxicity was noted in mice treated with 10000 mg/kg/day PG
(highest dose administered) on GD 8-12. 

Rats, in three successive generations, were exposed to 2.5, 5, 7.5, 10,
20, or 30% propylene glycol.  No adverse effects were observed until a
dose of 20% propylene glycol (approximate dietary level of 11900
mg/kg/day) was administered and 50% (approximate dietary level of 29750
mg/kg/day) of the animals failed to produce offspring.  No offspring
were produced by any of the rats in the high-dose group (30% propylene
glycol).  

In a reproductive study conducted in mice, propylene glycol was
administered in the drinking water at doses of 1820, 4800, or 10100
mg/kg/day for 18 weeks.  There were no treatment-related maternal,
reproductive, or developmental toxicity effects observed at any of the
propylene glycol doses tested in this study.  

			Dipropylene glycol 

Dipropylene glycol was administered to New Zealand White rabbits at
concentrations up to 1200 mg/kg/day on GD 6-19 and no treatment-related
effects were observed at the maternal, reproductive, or developmental
stages of the animals.  There were decreases in maternal food
consumption and body weight in rats treated with 2000 and 5000 mg/kg/day
dipropylene glycol.  Increases in liver weight were also observed in
these dose groups.  No reproductive or developmental toxicity effects
were established at any of the dose levels (ranging from 800-5000
mg/kg/day dipropylene glycol).

		Neurotoxicity

From the available toxicity studies, clinical signs of toxicity (loss of
balance, marked depression, and analgesia) were observed in mice,
rabbits, and guinea pigs following single oral dose exposures of
propylene glycol that range from 18400-24900 mg/kg/day).  Toxic effects
observed at the excessively high doses tested in these studies usually
preceded animal mortality.  Central nervous system depression was also
noted in rats administered propylene glycol at greater than 13200
mg/kg/day in the drinking water for 140 days.   However, all of the
noted central nervous system effects in acute and repeat-exposure
studies were observed only at dose levels that far exceed the testing
limit doses established for mammalian toxicity testing.  Based on a
weight-of-evidence evaluation of the available data, the Agency does not
require neurotoxicity testing, including a developmental neurotoxicity
study for either propylene glycol or dipropylene glycol.

4.1  Hazard-based Special FQPA Safety Factor(s) for Infants and Children

As required by the Food Quality Protection Act (FQPA) of 1996, the
Agency evaluated the potential for increased susceptibility of infants
and children from exposure to propylene glycol and dipropylene glycol. 
Based on the available data, there is no evidence for pre- or post-natal
increased susceptibility following exposure to these active ingredients.
 The Agency’s Antimicrobials Division Toxicology Endpoint Selection
Committee (ADTC) determined that the special 10x hazard-based safety
factor under the FQPA is not applicable at this time.  Therefore, the
FQPA safety factor was reduced to 1x. 

4.2  Dose Response Assessment

On February 26, 2004, the ADTC reviewed the available toxicology data
for propylene glycol and dipropylene glycol and discussed endpoint
selection for appropriate use in occupational/residential exposure risk
assessments.  In addition to the submitted mammalian toxicity data,
study reports were obtained and reviewed from other sources: published
studies from the scientific literature and study reports from the
National Cancer Institute (NCI) and National Toxicology Program (NTP). 
The ADTC concluded that there were no endpoints of concern for oral,
dermal, or inhalation exposure to propylene glycol and dipropylene
glycol based on the low toxicity profile from the available toxicology
studies. 

Endocrine Disruption

EPA is required under the Federal Food, Drug and Cosmetic Act (FFDCA),
as amended by the Food Quality Protection Act (FQPA), to develop a
screening program to determine whether certain substances (including all
pesticide active and other ingredients) “may have an effect in humans
that is similar to an effect produced by a naturally occurring estrogen,
or other endocrine effects as the Administrator may designate.” 
Following recommendations of its Endocrine Disruptor Screening and
Testing Advisory Committee (EDSTAC), EPA determined that there was a
scientific basis for including, as part of the program, the androgen and
thyroid hormone systems, in addition to the estrogen hormone system. 
EPA also adopted EDSTAC’s recommendation that EPA include evaluations
of potential effects in wildlife.  For pesticides, EPA will use FIFRA
and, to the extent that effects in wildlife may help determine whether a
substance may have an effect in humans, FFDCA authority to require the
wildlife evaluations.  As the science develops and resources allow,
screening of additional hormone systems may be added to the Endocrine
Disruptor Screening Program (EDSP).

When the appropriate screening and/or testing protocols being considered
under the Agency’s EDSP have been developed, propylene glycol and
dipropylene glycol may be subject to additional screening and/or testing
to better characterize effects related to endocrine disruption.

EXPOSURE ASSESSMENT

5.1  Drinking Water/Dietary Risk Assessment

	Propylene Glycol

The EECs of propylene glycol from inert agricultural uses were
calculated in surface water and ground water.  For the outdoor
application of propylene glycol, application rates of 1 lb/acre (a
minimum low-end exposure scenario) and 10 lbs/acre (a maximum high-end
exposure scenario) were used to assess the potential concentrations of
this chemical in surface water and ground water.  

Key assumptions for the application of FIRST (FQPA Index Reservoir
Screening Tool) to estimate the concentrations of propylene glycol at
the intake of a community water system and SCI-GRO to estimate the
concentrations in ground water and drinking water resources (shallow
ground water and surface water) are as follows: 1) a high-end
application rate of 10 lbs/acre is used; 2) in the absence of soil data
on propylene glycol, data on inoculum on sludge was applied with an
uncertainty factor of 3x; 3) mineralization of propylene glycol is
attained in 28 days; hence soil metabolism will be 28 x 3 (uncertainty
factor) = 84 days; 4) no more than 10% of the propylene glycol is
removed from the wastewater treatment plants and enters into the
household drinking water; 5) no value is assigned in literature for KOC
for propylene glycol, assume KOC=8 and for dipropylene glycol KOC=6.

Because of the high miscibility of propylene glycol in water and its
hydrolytic stability (abiotic conditions) and high mobility in water,
the Agency estimated the concentration of propylene glycol in surface
and ground water using FIRST and SCI GRO to estimate the EECs.  Table 4
outlines the Input Parameters for propylene glycol.

Table 4.  Input Parameters for Propylene Glycol for FIRST Program 

Parameter	Scenario #1

Application Rate	10 lbs/acre

Soil KOC	8

Water solubility	100,000

Hydrolysis	Stable

Aq. Photolysis	Stable

Soil Metabolism T1/2 (days)	84 

Aquatic Aerobic  metabolism T1/2 (days)	4

Anaerobic Aq. Metabolism T1/2 (days)	9

No of applications	1

% Crop Area Covered 	87

OutPuts: 1) Untreated water concentration of propylene glycol at the
peak day was 887.538 ppb (acute) and 2) Untreated water concentration at
the annualized average was 11.068 ppb (chronic).  For ground water
screening using SCI-GRO, the concentration of propylene glycol in the
ground water was 107 ppb.

	Dipropylene Glycol

Due to the similarities in chemical/physical properties and toxicities
of propylene glycol and dipropylene glycol, the exposure assessments for
propylene glycol are adequate for dipropylene glycol.  Based on the
FIRST and SCI-GROW model results, the calculated EECs are not likely to
exceed a 24-hour time-averaged concentration of 887.5 ppb or an annual
average concentration of 11 ppb in surface water and 107 ppb in ground
water.  Considering that each of these exposures are orders of magnitude
below the level at which health effects are observed from exposure to
propylene glycol or dipropylene glycol, the estimated concentrations in
drinking water do not present any risk of concern from agricultural uses
of these chemicals when formulated in pesticide products as inert
ingredients.

5.2a  Occupational/Residential Exposure and Risk from Active Uses

The Occupational and Residential Exposure (ORE) assessment addresses
potential exposures and risks to humans who may be exposed in
“occupational settings” and the general population in “residential
settings”.  An occupational and/or residential exposure risk
assessment is required for an active ingredient if (1) certain
toxicological criteria are triggered and (2) there is potential exposure
to handlers (mixers, loaders, applicators, etc.) during use or to
persons entering treated sites after application is complete.  For
propylene glycol and dipropylene glycol, there are potential exposures;
however, there are no toxicological endpoints of concern, according to a
review of the available toxicity data.  Both propylene glycol and
dipropylene glycol are listed as toxicity category IV for all routes of
acute exposures.

Propylene glycol and dipropylene glycol products can be used where
exposure may occur in both occupational and non-occupational settings. 
Propylene glycol is currently used as an air sanitizer, hard surface
disinfectant, and insecticide.  Usage sites include, but are not limited
to, household pets, eating establishments, air sanitization, laundry
equipment, and hospital and medical premises.  Although the air
sanitizer use is intended only for applications in
industrial/institutional settings, the potential for exposure to the
general population exists as a result of these applications in areas
such as theaters, hotels, schools, airplanes, etc.  

Propylene glycol is formulated as a pressurized liquid from 0.25 to 5.13
percent for air sanitizers, at 0.25 percent for the disinfectant, and up
to 10 percent for pet uses.  Application rates vary.  The high end air
sanitizer rate is 7 ounces of product per 6000 ft3 or 0.022 lb ai/6000
ft3 (EPA Reg. No. 10807-38).  Dipropylene glycol, on the other hand, is
only used as an air sanitizer.  The products containing dipropylene
glycol are formulated at approximately 4 percent.  The products are used
as aerosol sprays (metered delivery devices).  Application rates are 6.2
ounces (weight basis) of a 4 percent product per 6,000 ft3 and 7 ounces
(weight basis) of a 3.43 percent product per 6000 ft3.  These rates are
equivalent to 0.015 lb ai/6000 ft3. 

	

The potential handler scenarios identified are illustrated in Table 5. 
These scenarios were selected based on the product labels.   Air
disinfectants can be applied in a wide variety of rooms, therefore, the
list of possible application scenarios is exhaustive.

Table 5.  Propylene and Dipropylene Glycol Handler Scenarios

Antimicrobial Use Site Category	Scenario

Commercial, institutional and industrial premises and equipment	• 
Spraying disinfectant in rooms of institutions, offices, schools,
motels, hotels, etc.

Residential and public access premises	•  Spraying disinfectant in
rooms such as lobbies, theaters, reception rooms, sleeping rooms,
bathrooms, etc.

•  Spraying pest control spray on caged birds and to small animals
(e.g., dogs/cats).  

Medical premises and equipment	•  Spraying disinfectant on surfaces in
hospitals and nursing homes.

•  Spraying disinfectant in hospital rooms.

No chemical-specific handler data were submitted to estimate the
potential exposures associated with these uses of propylene glycol and
dipropylene glycol (nor are they required at this time).  Specifically,
exposure data associated with spraying an aerosol can indoors, away from
any surfaces (i.e., air sanitizer), or with spraying pets, are
unavailable.  However, similar exposures associated with spraying
surfaces (i.e., aerosol cans), such as crack and crevice treatments, are
available from data provided by the Chemical Manufacturers Association
(CMA) Antimicrobial Assessment Study and the Pesticide Handlers Exposure
Database (PHED).  The PHED exposure data for aerosol can spraying is
deemed more appropriate than the CMA data (e.g., more replicates, better
analytical recovery values, etc).  However, because no toxicological
endpoints of concern were identified, the exposures have not been
quantified.

In addition to potential dermal and inhalation handler exposure, there
is the potential for post application exposure to individuals reentering
treated rooms and/or contacting sprayed surfaces.  OPPT/EETD has
developed a model, EFAST (Exposure and Fate Assessment Screening Tool),
to estimate air concentrations.  More information and access to the
EFAST model is available at   HYPERLINK
"http://www.epa.gov/opptintr/exposure/" 
http://www.epa.gov/opptintr/exposure/ .  In summary, EFAST Version 1.0
bases its air concentration estimates on physical/chemical properties. 
Potential air concentration estimates for the glycols could be developed
based on the model’s standard input parameters.  Post application
inhalation exposure would be expected from both the aerosol (e.g., air
sanitizer is metered spray every 15 minutes) and the vapor phase.  The
following information is presented in the EFAST model:

	“For a “Product Sprayed on Surface,” such as a fabric protector
or an aerosol paint, a portion (default of  1%) is assumed to be
aerosolized and is therefore immediately available for uptake by
inhalation.  The remainder is assumed to contact the target surface, and
to subsequently volatilize at a rate that depends upon the chemical’s
molecular weight and vapor pressure.”

No estimates are available to determine the spray deposition, if any, on
surfaces to estimate potential dermal contact.  

A review of the available toxicity data shows no evidence of either
dermal or inhalation adverse effects from repeat-dose toxicity studies
conducted with propylene glycol or dipropylene glycol up to an
established testing limit dose of 1000 mg/kg/day for dermal toxicity and
1mg/L (1000 mg/m3) for inhalation toxicity.  No toxicological endpoints
were identified for propylene glycol or dipropylene glycol and
therefore, no risks associated with potential exposures have been
quantified for the use of these chemicals as active or inert ingredients
in pesticide products.

5.2b Residential Exposure and Risk from Inert Uses

Propylene and dipropylene glycol can be used as inerts in a variety of
consumer and household products.  The Consumer Exposure Model (CEM)
component of the Exposure, Fate Assessment Screening Tool (EFAST) is
available to estimate dermal and inhalation exposure from the use of
propylene and dipropylene glycol as inert ingredients in representative
products.  Background information and the downloadable executable files
for CEM and EFAST can be found at     HYPERLINK
"http://www.epa.gov/opptintr/exposure/docs/efast.htm." 
http://www.epa.gov/opptintr/exposure/docs/efast.htm.  and the National
Institute of Health’s Household Products Database can be found at    
HYPERLINK "http://householdproducts.nlm.nih.gov/." 
http://householdproducts.nlm.nih.gov/.   In the absence of dermal or
inhalation toxicological endpoints of concern, no risks have been
quantified for the use of propylene glycol or dipropylene glycol as
inert ingredients in pesticide products. 

5.2c  Occupational and Residential Exposure Risk Assessment

Based on the lack of toxicological concerns for both the active and
inert uses of propylene glycol and dipropylene glycol, a quantitative
risk assessment is not required at this time.  If the labeled uses for
either propylene glycol or dipropylene glycol change and inhalation
toxicological endpoints are identified, a screening-level occupational
and/or residential inhalation exposure estimate is available using EFAST
and PHED.  In contrast, if dermal toxicological endpoints are identified
in the future, potential dermal exposure estimates from treated surfaces
may need to be developed.  

6.0  AGGREGATE EXPOSURE

In examining aggregate exposure, FFDCA section 408 (b)(2)(d)(vi)
stipulates that “when establishing, modifying, leaving in effect, or
revoking a tolerance or exemption for a pesticide chemical residue, that
EPA considers available information concerning the aggregate exposure
levels of consumers (and major identifiable subgroups of consumers) to
the pesticide chemical residue”  in food and all other
non-occupational exposures, including drinking water from ground water
or surface water and exposure through pesticide use in gardens, lawns,
or buildings (residential and other indoor uses).  

The Agency has determined that there are no human health concerns
regarding the pesticide chemicals propylene glycol and dipropylene
glycol, because no toxicological effects were noted up to the
established limit doses for mammalian toxicity testing.  Additionally,
the anticipated human exposure from worst-case scenarios for both active
and inert uses of these chemicals is orders of magnitude below any dose
that has been shown to cause adverse effects. Therefore, a quantitative
aggregate risk assessment was not conducted and a qualitative risk
assessment is considered more appropriate to assess human health risks
from potential exposures to propylene glycol or dipropylene glycol.

	Determination of Safety

	

Based on its review and evaluation of the available information, the
Agency concludes there is a reasonable certainty that no harm to the
general population, including infants and children, will result from
exposure (anticipated aggregate exposures and all other types of
exposures for which there is reliable information) to residues of
propylene glycol or dipropylene glycol when used as an active and/or
inert ingredient in pesticide products. 

7.0  ENVIRONMENTAL FATE/ECOLOGICAL TOXICITY

7.1  Environmental Fate

	Propylene Glycol

For the assessment of environmental health risks, the Agency has relied
on data and fate properties of propylene glycol obtained from published
literature.  Propylene glycol has a high vapor pressure (0.129 mm Hg at
25 oC) in the atmosphere, however, this poses no concern because it
degrades rapidly (estimated half-life of 32 hours) as a result of an
induced photochemical reaction with hydroxyl radicals.  This chemical
has a low absorptivity to sediment and is consequently very mobile in
soil.  Propylene glycol rapidly degrades to CO2 in soil within 4 days
under aerobic conditions and within 4-9 days under anaerobic conditions.
 Degradation does not appear to be dependent on high glycol
concentrations.  It is highly miscible in water and does not hydrolyze
due to the lack of a hydrolysable hydrogen within its structure, an
aliphatic trihydroxy chemical.  For these reasons, the Agency has
granted a data waiver from the requirement of an aquatic hydrolysis
study for propylene glycol.  The low octanol/water partition coefficient
(log KOW of -0.92) indicates that propylene glycol is not likely to
bioaccumulate in aquatic organisms such as fish and its low Henry’s
Law Constant (air/water partition coefficient (1.31 x 10-10 atm-cu
m/mole at 25 oC) limits the potential to partition from surface water to
air.  These data suggest that aquatic hydrolysis, oxidation,
volatilization, bioconcentration, and absorptivity to soil are not
expected to be significant fate processes for propylene glycol and
therefore, the presence of this chemical in the environment does not
pose a risk of concern. 	

	Dipropylene Glycol

Similar to propylene glycol, the Agency has relied on data and fate
properties of dipropylene glycol obtained from published literature to
assess environmental health risks.  The available data for dipropylene
glycol suggest that aquatic hydrolysis, oxidation, volatilization,
bioconcentration, and absorption to sediment are not expected to be
significant fate processes for this chemical because of its high
miscibility in water and lack of hydrolysable hydrogen.  As a result of
its low Henry’s Law Constant, there is little potential for
dipropylene glycol to partition from surface water to air.  Dipropylene
glycol has low absorptivity (low soil-binding constant) and therefore is
very mobile in soil.  Biodegradability of dipropylene glycol may be slow
according to aerobic biological screening tests, however, this process
may be an important removal mechanism from aerobic soil.  Consequently,
there is potential for dipropylene glycol to be present in ground water
and surface water.  The low KOW of -1.07 indicates that it is not likely
to bioaccumulate in aquatic organisms like fish.  With a vapor pressure
of 0.129 mm Hg at 25 oC, dipropylene glycol exists almost entirely in
the vapor phase in the atmosphere and degrades rapidly (approximate
half-life in air, 13 hours) by reaction with photochemically produced
hydroxyl radicals.  Therefore, the presence of dipropylene glycol in the
atmosphere is not likely to be of concern.

7.2  Ecological Toxicity

All registered pesticide uses of propylene glycol and dipropylene glycol
as active ingredients occur indoor.  Propylene glycol and dipropylene
glycol are used as an inert ingredient in certain pesticide
(antimicrobial and agricultural) formulations. There are also
non-pesticide uses of both propylene and dipropylene glycol, e.g.,
solvents and de-icing fluids, among others.

Propylene glycol and dipropylene glycol show very low acute toxicity to
terrestrial and aquatic animals.  The toxicity endpoints presented below
are based on the results of toxicity studies submitted by registrants to
meet the Agency’s ecological effects data requirements for the uses of
propylene glycol and dipropylene glycol.  Additional information was
located in EPA/ORD’s ECOTOX database, which provides summary endpoints
from the open scientific literature as well as studies submitted to the
Agency.  No data were available to address the chronic toxicity of
either chemical to animals and the acute or chronic toxicity to plants.

	1.	Toxicity to Terrestrial Animals

			(a)  Birds, Acute and Subacute

To establish the toxicity of propylene glycol and dipropylene glycol to
birds, the Agency required an acute oral toxicity study using the
technical grade of the active ingredient (TGAI).  The preferred test
species is either mallard duck (a waterfowl) or bobwhite quail (an
upland game bird).  The results of submitted studies are provided in the
following table (Table 6).

Table 6.  Acute Oral Toxicity of Propylene/Dipropylene Glycol to Birds

Species

			% Active Ingredient (ai)	Endpoint

(mg/kg)	Toxicity Category (TGAI)	Satisfies Guidelines/

Comments	Reference

Propylene Glycol

Northern bobwhite

(Colinus virginianus)	100	LD50 > 2000

NOEL = 2000	Practically non- toxic	Yes	Campbell and Beavers, 1995

MRID 43762301

Northern bobwhite

(Colinus virginianus)	99.88	LD50 > 2150

NOEL = 2150	Practically non-toxic	Yes	Pedersen, 1995

MRID 43888002

Dipropylene Glycol

Northern bobwhite

(Colinus virginianus)	100	LD50 > 2000

NOEL = 2000	Practically non- toxic	Yes

•  core study

•  14-day test duration	Campbell and Beavers, 1995

MRID 43760807

The results indicate that both propylene and dipropylene glycol are
practically non-toxic to birds on an acute oral basis. The studies are
acceptable and fulfill guideline requirements (71-1/OPPTS 850.2100). 

A subacute dietary study using the TGAI may be required on a
case-by-case basis depending on the results of lower tier ecological
studies and pertinent environmental characteristics to establish the
toxicity of a chemical to avian species.  This testing was not required
for propylene glycol or dipropylene glycol. 



			(b) Mammals

Table 7. Toxicity of Propylene/Dipropylene Glycol to Mammals (excerpted
from Toxicology chapter)

Species	Test Type	Results

Propylene Glycol

Rat	Acute oral	LD50  8000 - 46000 mg/kg (Toxicity Category IV)

Rat	15-week Subchronic

(feeding)	NOAEL = 2500 mg/kg/day

Mouse	Developmental	maternal, reproductive, developmental NOAEL = 10400
mg/kg/day (oral)

Dipropylene Glycol

Rat	Acute oral	LD50 >5010 mg/kg (Toxicity category IV)

Mouse	90-day Subchronic (drinking water)	NOAEL = 4790mg/kg/day  male,
7430 mg/kg/day female

Rat	Developmental	reproductive, developmental NOAEL = 5000 mg/kg/day 

Both propylene and dipropylene glycol show low acute toxicity to mammals
in laboratory studies, and do not produce developmental or reproductive
effects at fairly high doses (Table 7).

		2.  Toxicity to Aquatic Animals

			(a)  Freshwater Fish, Acute

In order to establish the acute toxicity of an indoor use antimicrobial
pesticide to freshwater fish, the Agency requires a freshwater fish
toxicity study using the TGAI.  Data are generally required on only one
species for indoor-use antimicrobial pesticides.  The preferred test
species are rainbow trout (a coldwater fish) or bluegill sunfish (a
warmwater fish). Fish acute testing was required for propylene glycol,
and was reserved for dipropylene glycol, depending upon the results of
the propylene glycol fish test.  No fish acute toxicity testing has been
submitted to the Agency. A survey of the EPA/ORD database ECOTOX
provided multiple freshwater fish acute toxicity endpoints for propylene
glycol, which are summarized in the Table 8.



Table 8.  Acute Toxicity of Propylene/Dipropylene Glycol to Freshwater
Fish

Species	Endpoints	Toxicity Category 	Reference

Propylene Glycol

Goldfish (Carassius auratus)	Static 24 hr. LC50 >5000 ppm ai	Practically

non-toxic 	Bridie et al., 1979 (ECOTOX reference #623)

Rainbow trout (Oncorhynchus mykiss)	Static 24-hr LC50 = 50,000 ppm
Practically non-toxic

	Majewski et al., 1978 (ECOTOX reference # 991)

Fathead minnow (Pimephales promelas)	48 hr LC50 = 790 ppm	Practically
non-toxic

	Pillard, 1995

(ECOTOX reference #13727)

Fathead minnow (Pimephales promelas)	96 hr LC50 = 710 ppm	Practically
non-toxic

	Pillard, 1995

(ECOTOX reference #13727)

Fathead minnow (Pimephales promelas)	96 hr LC50 = 62,000 ppm ai
Practically non-toxic

	Pillard, 1995

(ECOTOX reference #13727)

Dipropylene Glycol

Goldfish (Carassius auratus)	24 hr. LC50 >5000 ppm ai	Practically
non-toxic

	Bridie et al., 1979 (ECOTOX reference #623)

The results indicate that propylene glycol and dipropylene glycol are
practically non-toxic to freshwater fish on an acute basis.  Since these
data are supplemental information, Guideline 72-1/850.1075 is not
fulfilled; however, because multiple published studies demonstrate very
low toxicity to freshwater fish, no further testing is required for
propylene glycol or dipropylene glycol.

			(b)  Freshwater Invertebrates, Acute

The Agency requires a freshwater aquatic invertebrate toxicity study
using the TGAI to establish the acute toxicity of an antimicrobial
pesticide to freshwater invertebrates.  The preferred test species is
Daphnia magna.  Results of submitted studies for propylene glycol and
dipropylene glycol are provided in the following tables (9-11):



Table 9.  Acute Toxicity of Propylene/Dipropylene glycol to Freshwater
Invertebrates

Species

			% Active Ingredient (ai)	Endpoints

(ppm)	Toxicity Category (TGAI)	Satisfies Guidelines/

Comments	Reference

Propylene Glycol

Waterflea  (Daphnia magna)	100

	48-hr. EC50>110 ppm ai

NOEC = 110 ppm ai	Practically non-toxic	Yes	Graves and Swigert, 1995. 
MRID 43762302

Waterflea

(Daphnia magna)	99.76	48-hr. EC50>1000 ppm ai

NOEC = 1000 ppm ai	Practically non-toxic	Yes	Collins, 1995

MRID 43888003

Dipropylene Glycol

Waterflea

(Daphnia magna)	100

	48-hr. EC50> 109 ppm ai

NOEC = 109 ppm ai	Practically non-toxic	Yes	Graves and Swigert, 1995. 
MRID 43760808

The results of these studies indicate that propylene and dipropylene
glycol are practically non-toxic to freshwater invertebrates.  The
testing guideline requirement has been fulfilled (850.1010/72-2).
Additional data on the acute toxicity of propylene glycol to freshwater
invertebrates were retrieved from the ECOTOX database.  This information
is provided below:

Table 10.  Additional Data on the Acute Toxicity of Propylene Glycol to
Freshwater Invertebrates

Species	Endpoints	Toxicity Category 	Reference

Waterflea (Ceriodaphnia dubia)	48 hr. LC50 = 1020  ppm ; NOEC = 660 ppm	
Practically 

non-toxic	Pillard, 1995

(ECOTOX reference #13727)

Waterflea (Ceriodaphnia dubia)	48 hr LC50= 18340 ppm ai; NOEC = 13020
ppm ai	Practically 

non-toxic	Pillard, 1995

(ECOTOX reference #13727)

Waterflea (Ceriodaphnia dubia)	48 hr LC50 = 4919 ppm ai	Practically 

non-toxic	Cornell et al., 2000

(ECOTOX reference #48385)

Waterflea (Daphnia magna)	48 hr EC50 > 10000 ppm	Practically 

non-toxic	Kuhn et al., 1989

(ECOTOX reference #846)

These results further indicate that propylene glycol demonstrates very
low toxicity to freshwater invertebrates.



			(c)  Estuarine and Marine Organisms, Acute

Acute toxicity testing with estuarine and marine organisms using the
TGAI is required when the end-use product is intended for direct
application to the marine/estuarine environment or effluent containing
the active ingredient is expected to reach this environment.  Neither
propylene glycol nor dipropylene glycol has such uses on their labels;
therefore, testing with marine/estuarine organisms is not required. 
Some information on the acute toxicity of propylene glycol to
marine/estuarine invertebrates was found in ECOTOX, and the results are
provided below:

Table 11. Acute Toxicity of Propylene Glycol to Marine/Estuarine
Organisms

Species	Endpoints	Toxicity Category 	Reference

Brine Shrimp (Artemia salina)	Static 24 hr. LC50 > 10000 ppm	Practically
non-toxic

	Price et al., 1974

(ECOTOX reference #2408)

The results of this study indicate that propylene glycol is practically
non-toxic to brine shrimp on an acute basis.

			(d)  Aquatic Organisms, Chronic

Chronic toxicity testing (Fish early life stage, 850.1300/72-4a and
aquatic invertebrate life cycle, 850.1400/72-4b) is not required for the
currently registered uses of propylene glycol or dipropylene glycol.  No
comparable endpoints were found in the ECOTOX database.

		3.  Toxicity to Plants

No data, such as phytotoxicity, were available to address the risk to
plants.  However, exposure to plants is not expected from the current
registered uses of propylene glycol and dipropylene glycol. Therefore,
plant toxicity testing is not required at this time.  

7.3  Environmental Risk Assessment

The registered, active uses for propylene glycol or dipropylene glycol
are all indoors and are not expected to result in any appreciable
environmental exposure, particularly to terrestrial or aquatic
organisms. The lack of exposure coupled with the very low acute toxicity
of these compounds to birds, mammals, and aquatic organisms, indicate
very low ecological risk from their use.  Therefore, environmental
exposure modeling was not conducted for use of propylene glycol or
dipropylene glycol as active ingredients.  However, due to the
agricultural use of propylene glycol, environmental modeling was
performed for the outdoor use of propylene glycol as an inert ingredient
in pesticide products.  Using the estimated environmental concentration
(EEC) of 887.5 ppb or an annual average concentration of 11 ppb for
drinking water together with the available ecotoxicity endpoints, the
calculated risk quotients (RQs) for propylene glycol are well below the
LOCs established by the Agency for aquatic organisms, including
Endangered Species (0.001 for fish and 0.0000143 for invertebrates).
Chronic risk and risk to plants could not be assessed at this time due
to a lack of chronic toxicity and phytotoxicity information for
propylene glycol or dipropylene glycol.  However, exposure to plants is
not anticipated from the currently registered, indoor uses of propylene
glycol or dipropylene glycol.  

7.4  Listed Species Considerations

  XE "IV. Risk Management, Reregistration, and Tolerance Reassessment
Decision:D. Regulatory Rationale: 4. Threatened and Endnagered Species
Considerations: a. The Endangered Species Program"  

Section 7 of the Endangered Species Act, 16 U.S.C. Section 1536(a)(2),
requires all federal agencies to consult with the National Marine
Fisheries Service (NMFS) for marine and anadromous listed species, or
the United States Fish and Wildlife Services (FWS) for listed wildlife
and freshwater organisms, if they are proposing an "action" that may
affect listed species or their designated habitat.  Each federal agency
is required under the Act to ensure that any action they authorize,
fund, or carry out is not likely to jeopardize the continued existence
of a listed species or result in the destruction or adverse modification
of designated critical habitat.  To jeopardize the continued existence
of a listed species means "to engage in an action that reasonably would
be expected, directly or indirectly, to reduce appreciably the
likelihood of both the survival and recovery of a listed species in the
wild by reducing the reproduction, numbers, or distribution of the
species." 50 C.F.R. § 402.02.

To facilitate compliance with the requirements of the Endangered Species
Act subsection (a)(2) the Environmental Protection Agency, Office of
Pesticide Programs has established procedures to evaluate whether a
proposed registration action may directly or indirectly reduce
appreciably the likelihood of both the survival and recovery of a listed
species in the wild by reducing the reproduction, numbers, or
distribution of any listed species (U.S. EPA 2004).  After the
Agency’s screening-level risk assessment is performed, if any of the
Agency’s Listed Species LOC Criteria are exceeded for either direct or
indirect effects, a determination is made to identify if any listed or
candidate species may co-occur in the area of the proposed pesticide
use.  If determined that listed or candidate species may be present in
the proposed use areas, further biological assessment is undertaken. 
The extent to which listed species may be at risk then determines the
need for the development of a more comprehensive consultation package as
required by the Endangered Species Act.

For certain use categories, the Agency assumes there will be minimal
environmental exposure, and only a minimal toxicity data set is required
(Overview of the Ecological Risk Assessment Process in the Office of
Pesticide Programs U.S. Environmental Protection Agency - Endangered and
Threatened Species Effects Determinations, 1/23/04, Appendix A, Section
IIB, pg.81).  Chemicals in these categories therefore do not undergo a
full screening-level risk assessment, and are considered to fall under a
“no effect” determination.  The active ingredient uses of propylene
glycol and dipropylene glycol fall into this category.

Exposure to non-target organisms from the inert use of propylene glycol
in pesticide formulations was assessed.  Resulting RQs were well below
acute LOCs for endangered birds, mammals, fish and aquatic
invertebrates.  Therefore, the inert uses of propylene glycol are also
considered to have no effect (NE) on listed species in those taxa.  Risk
to plants cannot be addressed at this time due to a lack of
phytotoxicity data.

Based on the labeled use patterns, propylene glycol and dipropylene
glycol are not expected to result in significant environmental exposure,
and both chemicals show very low toxicity to birds, mammals, fish and
aquatic invertebrates.  Risk quotients for aquatic organisms for the
inert use of propylene glycol were well below the Agency LOCs for
Endangered Species.  In summary, adverse effects on
endangered/threatened terrestrial and aquatic animal species are not
anticipated from exposure to propylene glycol or dipropylene glycol 
Therefore, the Agency makes a “no effect” determination for
propylene glycol or dipropylene glycol on the listed terrestrial and
aquatic animal species.  However, toxicity and risk to
endangered/threatened plants cannot be addressed at this time due to the
lack of phytotoxicity information.  

8.0 CUMULATIVE RISKS

Risks summarized in this document are those that result only from the
use of propylene glycol or dipropylene.  The Food Quality Protection Act
(FQPA) requires that the Agency consider “available information”
concerning the cumulative effects of a particular pesticide’s residues
and “other substances that have a common mechanism of toxicity.” 
The reason for consideration of other substances is due to the
possibility that low-level exposures to multiple chemical substances
that cause a common toxic effect by a common toxic mechanism could lead
to the same adverse health effect as would a higher level of exposure to
any of the substances individually.  Unlike other pesticides for which
EPA has followed a cumulative risk approach based on a common mechanism
of toxicity, EPA has not made a common mechanism of toxicity finding for
propylene glycol or dipropylene glycol.  For information regarding
EPA’s efforts to determine which chemicals have a common mechanism of
toxicity and to evaluate the cumulative effects of such chemicals, see
the policy statements released by EPA’s Office of Pesticide Programs
concerning common mechanism determinations and procedures for cumulating
effects from substances found to have a common mechanism on EPA’s
website at     HYPERLINK "http://www.epa.gov/pesticides/cumulative/" 
http://www.epa.gov/pesticides/cumulative/ .

 

9.0 INCIDENT DATA (HUMAN EXPOSURE)

In the data sources available to the Agency, no reports of serious
illness have been associated with human exposure to propylene glycol or
dipropylene glycol.  The agency has reviewed the databases of the OPP
Incidence Data System (IDS), the Poison Control Center, California
Department of Pesticide Regulation, and the National Pesticide
Telecommunications Network (NPTN) for reported incident information of
propylene glycol and dipropylene glycol.  The primary route of exposure
is inhalation, and nasal irritation and sensitization are the most
commonly reported effects associated with exposure to propylene glycol
and dipropylene glycol.  There are incidences of death and severe
illness in animals reported when the chemicals are used with pets. 
However, all the reported incidences are related to end-use products
(residential use) and no one incident reported is connected solely to
propylene glycol or dipropylene glycol exposure.  Other ingredients in
the formulated products may have contributed to the symptoms that have
been reported for exposure to pesticide products that also contain
propylene glycol and/or dipropylene glycol.  

10.0  SUMMARY OF RISK ASSESSMENT FINDINGS

Based on a low order of toxicity via the oral, dermal and inhalation
routes, AD has determined that a qualitative approach to assessing human
health risks from exposure to propylene glycol and dipropylene glycol is
appropriate.  AD concludes there is a reasonable certainty of no harm to
the general population and to infants and children which may result from
exposures to propylene glycol and dipropylene glycol when used as an
active ingredient (air sanitizers and surface disinfectants) or an inert
ingredient (formulated into antimicrobial and agricultural pesticide
products).  Thus, no changes to the tolerance exemptions are necessary
and they are considered reassessed as safe under section 408(q) of the
Federal Food, Drug, and Cosmetic Act (FFDCA).  In addition, AD has no
risk concerns for propylene glycol and dipropylene glycol with respect
to non-target organisms and expects no effects to listed species or
critical habitat. Therefore, AD makes a "No Effect" determination for
propylene glycol and dipropylene glycol with respect to environmental
risks.

AD also notes that propylene glycol and dipropylene glycol are included
on the Agency’s list of chemicals for the High Production Volume (HPV)
Challenge Program.  HPV chemicals are those that are manufactured or
imported into the United States in volumes greater than one million
pounds per year.  There are approximately 3000 HPV chemicals that are
produced or imported into the United States.  The HPV Challenge Program
is a voluntary partnership between industry, environmental groups, and
the EPA, which invites chemical manufacturers and importers to provide
basic hazard data on the HPV chemicals they produce/import.  The goal of
this program is to facilitate the public’s right-to-know about the
potential hazards of chemicals found in their environment, homes,
workplace, and in consumer products.  

Propylene glycol and dipropylene glycol are both being otherwise handled
under the Organization for Economic Cooperation and Development HPV
(OECD) Screening Information Dose Set (SIDS) Program and have been
confirmed by the International Council of Chemical Associations (ICCA)
for incorporation in the HPV Initiative of the ICCA.  However, propylene
glycol and dipropylene glycol are currently not sponsored by any company
or consortium. 

Based on toxicity data already submitted on propylene glycol and
dipropylene glycol and the completeness of the toxicity database
(including subchronic, chronic, reproduction, teratology, and
mutagenicity studies), the Agency feels confident in proceeding with
this reregistration eligibility decision/tolerance reassessment
decision.  Any submission of data by current or future sponsors of
propylene glycol and dipropylene glycol as part of the HPV Challenge
Program may, in the future, be used by the Office of Pesticide Programs
to revise or update their tolerance reassessment decision for propylene
glycol and dipropylene glycol as deemed necessary and appropriate.  

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Campbell and Beavers, 1995.  Acute oral toxicity of propylene glycol to
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Pedersen, 1995.  Acute oral toxicity of propylene glycol to Northern
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	Unpublished data.  MRID  43888002.  

Collins, 1995. Acute toxicity of propylene glycol to the waterflea
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	Unpublished data.  MRID  43888003.				

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#48385).

Kuhn, R., M. Pattard, K. Pernak, and A. Winter. 1989.  Results of the
Harmful Effects of Selected Water Pollutants (Anilines, Phenols,
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Majewski, H.S., J.F. Klaverkamp, and D. P. Scott. 1978.  Acute Lethality
and Sub-Lethal Effects of Acetone, Ethanol, and Propylene Glycol on the
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Pillard, D.A. 1995.  Comparative Toxicity of Formulated Glycol Deicers
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Ethylene and Propylene Glycol to Ceriodaphnia dubia and Pimephales
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Price, K.S., G.T. Waggy, and R. A. Conway. 1974.  Brine Shrimp Bioassay
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	13:627-630.

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	Environmental Fate References

Hansch C. et al; 1995. Exploring QWAR. Hysdrohobic, Electronic, and
Steric Constants.  ACS Prof Ref Book.  Heller SR, consult. Ed.,
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  DATABASES AND WEBSITES

Exposure and Fate Assessment Screening Tool (EFAST Version 1.0): 

	  HYPERLINK "http://www.epa.gov/opptintr/exposure/." 
http://www.epa.gov/opptintr/exposure/. 

Consumer Exposure Model (CEM) Component of the Exposure and Fate
Assessment 

	Screening Tool:   HYPERLINK
"http://www.epa.gov/opptintr/exposure/docs/efast.html." 
http://www.epa.gov/opptintr/exposure/docs/efast.html.  

National Institute of Health’s Household Products Database: 

	    HYPERLINK "http://householdproducts.nlm.nih.gov/." 
http://householdproducts.nlm.nih.gov/. 

Environmental Fate Database: A Database of the Syracuse Research
Corporation (SRC). 

	  HYPERLINK "http://www.syrres.com/esc/databases.htm" 
http://www.syrres.com/esc/databases.htm 

National Institute For Occupational Safety and Health (NIOSH).  (1981).
Toxic 

	Substances List. Washington, DC: U.S. Government Printing Office. 

	  HYPERLINK "http://www.cdc.gov/niosh/homepage.html" 
http://www.cdc.gov/niosh/homepage.html 

Hazard Substances Databank (HSDB), A Database of the National Library of
Medicine’s TOXNET System.

	   HYPERLINK "http://toxnet.nlm.nih.gov/"  http://toxnet.nlm.nih.gov/ 

	

 SUPPORTING DOCUMENTATION

USEPA.  1998.  PHED Surrogate Exposure Guide.  Estimates of Worker
Exposure from 

Pesticide Handler Exposure Database Version 1.1.  Washington, DC:  U.S.
Environmental Protection Agency.

USEPA.  2004.  Overview of the Ecological Risk Assessment Process in the
Office of 

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Pesticide Programs U.S. Environmental Protection Agency - Endangered and
Threatened Species Effects Determinations, 1/23/04.

USEPA.  1999.  Evaluation of Chemical Manufactures Association
Antimicrobial 

Exposure Assessment Study (Amended on 8 December 1992).  Memorandum from
Siroos Mostaghimi, Ph.D., to Julie Fairfax.  Dated November, 4, 1999. 
DP Barcode: D247642.

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