Docket Number:  EPA-HQ-OPP-2008-0024

www.regulations.gov

Propionic Acid and Salts Summary Document

Registration Review: Initial Docket

March 2008

Registration Review Document for

Propionic Acid and Salts 

Case No. 4078

Approved By:

								

___________________

								Steven Bradbury, Ph.D.

								Director, Special Review and

		       	      Reregistration Division

TABLE OF CONTENTS

										Page #

Preliminary Work Plan (PWP)					4

Fact Sheet								9

Ecological Risk Assessment Problem Formulation	        13	

Human Health Effects Problem Formulation 	        27	     Document

Glossary of Terms and Abbreviations			        34I. Preliminary Work
Plan – Propionic Acid & Salts

Introduction:

The Food Quality Protection Act of 1996 mandated a new program:
registration review.  All pesticides distributed or sold in the United
States generally must be registered by EPA, based on scientific data
showing that they will not cause unreasonable risks to human health,
workers, or the environment when used as directed on product labeling. 
The new registration review program is intended to make sure that, as
the ability to assess risk evolves and as policies and practices change,
all registered pesticides continue to meet the statutory standard of no
unreasonable adverse effects.  Changes in science, public policy, and
pesticide use practices will occur over time.  Through the new
registration review program, the Agency periodically reevaluates
pesticides to make sure that as change occurs, products in the
marketplace can be used safely.  Information on this program is provided
at: http://www.epa.gov/oppsrrd1/registration_review/. 

The Agency has begun to implement the new Registration Review program,
and will review each registered pesticide every 15 years to determine
whether it continues to meet the FIFRA standard for registration.  The
public phase of registration review begins when the initial docket is
opened for each case.  The docket is the Agency’s opportunity to state
what it knows about the pesticide and what additional risk analyses and
data or information it believes are needed to make a registration review
decision.  After reviewing and responding to comments and data received
in the docket during this initial comment period, the Agency will
develop and commit to a final work plan and schedule for the
registration review of propionic acids and salts.  

The active ingredient propionic acid is a fungicide and bactericide that
is used to control fungi and bacteria in stored hay and grains, inhibit
bacterial growth in drinking water for livestock and poultry, control
mold and fungi in poultry litter and animal feed, and sanitize
pre-cleaned food contact surfaces.  Propionic acid is also used as an
inert ingredient in pesticide formulations.  Propionic acid and its
salts, sodium and calcium propionates, are approved by the Food and Drug
Administration (FDA) in the United States as Generally Recognized As
Safe (GRAS) for use in food.  Propionic acid was first registered in the
early 1970’s.  Calcium propionate and sodium propionate (salts of
propionic acid) are not currently registered for use as pesticide active
ingredients.   

Anticipated Risk Assessment and Data Needs:

The Agency anticipates that no quantitative ecological risk assessment
will be needed unless the assumptions listed below are incorrect.  An
endangered species assessment will be conducted for all uses of
propionic acid.  The Agency anticipates that no additional human health
risk assessments will be needed.

Ecological Risk:

The most recent ecological risk assessment was completed October 19,
2001 to review propionic acid as an active and as an inert ingredient.  

The Agency is seeking additional information regarding the typical
application process to confirm that exposure to non-target organisms
will be extremely limited based on the use pattern and the following
assumptions:  

numerous uses occur indoors;

when used outdoors, the product is applied simultaneously with baling
activities resulting in minimal spray drift off field.

The Agency is also seeking answers to the following questions regarding
assumed application practices to determine if a quantitative assessment
is necessary.  

Is propionic acid ever sprayed over large areas before a crop is
harvested? 

When propionic acid is applied during baling operations, does the method
ensure that excess product (drips) is collected and not left on the
field?

Do outdoor application equipment and techniques usually prevent spray
drift? 

The Agency does not expect to require additional environmental fate data
studies but may require ecological effects studies for plants in the
Final Work Plan.  If a quantitative assessment is needed, seedling
emergence and vegetative vigor data will be required to complete the
assessment.

  

The planned ecological risk assessment will allow the Agency to
determine whether propionic acid’s use has “no effect” or “may
affect” federally listed threatened or endangered species (listed
species) or their designated critical habitat.  If the assessment
indicates that propionic acid “may affect” a listed species or its
designated critical habitat, the assessment will be refined.  The
refined assessment will allow the Agency to determine whether use of
propionic acid is “likely to adversely affect” the species or
critical habitat or “not likely to adversely affect” the species or
critical habitat.  When an assessment concludes that a pesticide’s use
“may affect” a listed species or its designated critical habitat,
the Agency will consult with the U.S. Fish and Wildlife Service and/or
National Marine Fisheries Services (the Services), as appropriate.

Human Health Risk:

The most recent health risk assessment for the tolerance reassessment
eligibility decision was completed in February 2002, which addressed
potential dietary and residential exposures to propionic acid from
pesticide uses. 

The findings of the February 2002 assessment that propionic acid is not
expected to result in any adverse health effects are still valid for the
current uses of propionic acid.  This is based on its low toxicity,
limited use pattern, and affirmation as a GRAS chemical when used as a
food additive.  Propionic acid is not expected to result in any adverse
health effects via the food, drinking water, or residential exposure
pathways.

The Agency does not anticipate requiring any further human health
effects data or the need to perform any further human health risk
assessments.

Timeline:

EPA has created the following estimated timeline for the completion of
the propionic acid and salts registration review.  

Registration Review for Propionic Acid – Projected Registration Review
Timeline

Activities	Time

Phase 1:  Opening the docket

Open Docket and Public Comment  	2008 – March

Close Public Comment	2008 – June

Phase 2:  Case Development

Final Work Plan 	2008 -  July – Sept.

Preliminary Risk Assessments and Public Comment 	2010 -  Jan. – Mar.

Close Public Comment Period	2010 – Apr. – June

Phase 3:  Registration Review Decision

Proposed Registration Review Decision 	2010 – Jul. – Sept.

Public Comment Period 	2010 – Oct. – Dec.

Final Registration Review Decision and Begin Post-Decision Follow-up
2011 – Jan – Mar.

Total (years)	3.0

Note:  The Agency reserves the option to issue a DCI if it is determined
that additional data are needed during the final work plan for
registration review of propionic acid.  If a DCI is issued, additional
time to complete registration review will be necessary.

Guidance for Commenters:

The public is invited to comment on EPA’s preliminary registration
review work plan and rationale.  The Agency will carefully consider all
comments as well as any additional information or data provided prior to
issuing a final work plan for the propionic acid case.

Through the registration review process, the Agency intends to solicit
information on trade irritants and, to the extent feasible, take steps
toward facilitating irritant resulting resolution.  Growers and other
stakeholders are asked to comment on any trade irritant issues resulting
from lack of Maximum Residue Limits (MRLs) or disparities between U.S.
tolerances and MRLs in key export markets, providing as much specificity
as possible regarding the nature of the concern. The Agency would not
expect any trade irritant issues because propionic acid, and its sodium
and calcium salts are exempt from the requirements of a tolerance.

Propionic acid and its salts are not identified as a cause of impairment
for any water bodies listed as impaired under section 303(d) of the
Clean Water Act, based on information provided at
http://oaspub.epa.gov/tmdl/waters_list.impairments?p_impid=3.  The
Agency invites submission of water quality data for this pesticide.  To
the extent possible, data should conform to the quality standards in
Appendix A of the OPP Standard Operating Procedure: Inclusion of
Impaired Water Body and Other Water Quality Data in OPP’s Registration
Review Risk Assessment and Management Process (see:   HYPERLINK
"http://www.epa.gov/oppfead1/cb/ppdc/2006/november06/session1-sop.pdf" 
http://www.epa.gov/oppfead1/cb/ppdc/2006/november06/session1-sop.pdf ),
in order to ensure they can be used quantitatively or qualitatively in
pesticide risk assessments. 

EPA seeks to achieve environmental justice, the fair treatment and
meaningful involvement of all people, regardless of race, color,
national origin, or income, in the development, implementation, and
enforcement of environmental laws, regulations, and policies. To help
address potential environmental justice issues, the Agency seeks
information on any groups or segments of the population who, as a result
of their location, cultural practices, or other factors, may have
atypical, unusually high exposure to propionic acid and its salts
compared to the general population.  Please comment if you are aware of
any sub-populations that may have atypical, unusually high exposure
compared to the general population.

Stakeholders are also specifically asked to provide information and data
in the following areas for propionic acid.

1.  Typical application process 

	a.  methods

	b.  techniques 

	c.  equipment used

            d.  information regarding the potential for drift.

2.   Any geographic limitations on use.

3.   Application timing (date of first application and application
intervals) by crop – 

      national, state, county.

4.   State or local use restrictions.

5.   Ecological incidents (non-target plant damage and avian, fish,
reptilian, amphibian 

      and mammalian mortalities) not already reported to the Agency.

6.   Monitoring data.

7.   Is propionic acid sprayed over large areas before a crop is
harvested (i.e., hay)?

8.   When propionic acid is applied during baling operations, does the
method ensure  

      that excess product (drips) is collected and not left on the
field?

9.   Do outdoor application equipment and techniques prevent spray
drift?  

10. Did the problem formulation documents include all uses?  

11. Are there any uses on the labels that are not being used?

Next Steps:

After the 90-day comment period closes, the Agency will review any
comments received, and then issue a Final Work Plan for this pesticide.

II. FACT SHEET

 

Background Information:

Propionic acid registration review case number: 4078.

Propionic acid PC Code: 077702, CAS#: 79-09-4.

Propionic acid, sodium salt: 877703, CAS# 137-40-6; Propionic acid,
calcium salt: 877701, CAS# 4075-81-9. 

Technical registrants: Dow Chemical Co., BASF Corporation, Eastman
Chemical Co.

Three technical products, and 25 end-use products.  

First approved for use in a registered product in 1970’s.

Reregistration Eligibility Decision (RED) completed in September 1991. 

Propionic acid, and its sodium and calcium salts, are exempt from all
tolerance requirements when used on crops and animals.  

Special Review and Reregistration Division Chemical Review Manager
(CRM): Wilhelmena Livingston: livingston.wilhelmena@epa.gov.

Registration Division Product Manager (PM): kish.tony@epa.gov.  

Use & Usage Information:  (For additional details, please refer to the
BEAD Appendix A document in the propionic acid docket.)

Propionic acid is registered as a pesticidal active ingredient to
control fungi and bacteria in stored grains, hay grain storage areas,
poultry litter, and drinking water for livestock and poultry.  

It is also registered in food contact surface sanitizing solutions. 

Propionic acid, calcium propionate, and sodium propionate may be found
as inert  ingredients in various pesticide formulations.

Propionic acid and it salts may also be used as direct food additives
and are classified as Generally-Recognized-As-Safe (GRAS).

Calcium propionate and sodium propionate (salts of propionic acid) are
not currently registered for use as pesticide active ingredients.  

There are no residential or public recreational uses.

Propionic acid products are sprayed using a low pressure hand-wand
system. 

Nearly 9,000 pounds of propionic acid are used annually.

Propionic acid is formulated as soluble concentrate and a ready-to-use
liquid.

Recent Actions:

There are no recent new uses or significant amendments for propionic
acid.

Ecological Risk Assessment Status:

The following are key findings of the propionic acid risk assessment. 
Please refer to Section III, Ecological Risk Assessment Problem
Formulation, for a detailed discussion of the ecological risk
assessment.

   

The most recent ecological risk assessment was completed October 19,
2001 to review propionic acid as an active and as an inert ingredient.  

In the 1991 Reregistration Eligibility Document (RED) for propionic
acid, the Agency waived all of the environmental fate and ecological
effects data requirements because the use profile did not lead the
Agency to foresee the potential for significant environmental risks
associated with the registered uses of the propionic acid.

Propionic acid has limited outdoor use and low toxicity to fish,
invertebrates, birds, and mammals, therefore its hazard to these
nontarget organisms is expected to be minimal.  

The Agency also believes that exposure to all non-target organisms will
be extremely limited, based on the use profile and the assumptions that
numerous uses occur indoors and when used outdoors, the product is
applied simultaneously with baling activities.  

Human Health Risk Assessment Status:

Please refer to Section IV of this document, Human Health Effects
Problem Formulation for Registration Review, for a detailed discussion
of the human health risk assessment.  

Hazard Characterization:

At the time that the propionic acid tolerance reassessment was completed
in 2002, the toxicological database was determined to be adequate for
the purposes of tolerance reassessment, and no further toxicity data on
propionic acid were required by the Agency. A comprehensive open
literature search, conducted from 2002 to the present and including
databases such as PubMed and ToxNet, has not revealed any new studies on
propionic acid that would alter the previous toxicological conclusions. 
The Agency has not received any new toxicity studies that would have a
significant impact on the toxicological findings for propionic acid. 
Therefore, the Agency concludes that the toxicology determinations made
in 2002 are still valid and no additional toxicity data are required.  A
summary of these toxicology findings is presented below.

Propionic acid is of moderate to low acute toxicity via the oral,
dermal, and inhalation routes of exposure, and is not a skin sensitizer.
 However, propionic acid is highly irritating to the eye and skin
(toxicity category I).  Subchronic and chronic oral toxicity studies
(rats and dogs) with propionic acid, or its salts, indicate local
irritation as the primary effects.  At high dose levels, animals can
exhibit lesions/ulcers in the forestomach and an increased incidence of
epithelial hyperplasia in the esophagus.  There do not appear to be any
significant systemic effects.

Dietary (Food and Water):

A dietary risk assessment has not been conducted and is not required. 
No residue chemistry data are required.  The findings of the February
2002 assessment are still valid for the current uses of propionic acid. 
This is based on its low toxicity, limited use pattern, and affirmation
as a GRAS chemical when used as a food additive.  Propionic acid is not
expected to result in any adverse health effects through dietary
exposure.

The residues in water from the pesticidal use of propionic acid are
considered negligible, and there is little likelihood of significant
residues in livestock fed treated feed and water, and the likelihood of
any significant dietary exposure to humans is very low.   

 

Potential exposure and risk from the use of propionic acid as a direct
food additive is also considered to be low.  This is based on the
presence of propionic acid as a normal component of metabolism in the
human body, and because propionic acid is a naturally occurring
component in dairy products such as butter and cheese.

Residential:

 

There are no propionic acid-containing products registered for use in/on
residential or public recreational sites.  Therefore, a residential risk
assessment is not required.  

Aggregate:

An aggregate risk assessment is not required.  There are no residential
uses and a dietary risk assessment is not necessary.  

Occupational:

A quantitative occupational risk assessment has not been performed for
propionic acid and is not required.  There is a possibility of eye and
skin irritation to occupational handlers.  Therefore the current labels
for EUPs containing propionic acid are as specified, “Products
containing greater than 63% a.i. must include the following protective
clothing label requirements: Wear chemical-resistant gloves,
chemical-resistant aprons, chemical-resistant footwear and goggles or
face shield when loading application equipment unless a closed loading
system is used. Avoid working near high concentrations of spray
mist/vapor. Use with adequate ventilation. Wash thoroughly after
handling.”

The potential for post-application exposures is expected to be minimal
provided that the areas are adequately ventilated as required on the
labels.

Incidents:

No cases have been reported in OPP’s Incident Data System (IDS) from
2000 to present.

Data Call-In Status:

There are no current data call-ins for propionic acid.

Tolerances and International Harmonization: 

Propionic acid, and its sodium and calcium salts, are exempt from the
requirement of a tolerance.

Labels:

 

A list of registration numbers may be found in the propionic acid docket
and the labels can then be obtained from the Pesticide Product Label
System (PPLS) website:   HYPERLINK
"http://oaspub.epa.gov/pestlabl/ppls.home" 
http://oaspub.epa.gov/pestlabl/ppls.home . 

III.   ECOLOGICAL RISK ASSESSMENT PROBLEM FORMULATION

UNITED STATES ENVIRONMENTAL PROTECTION AGENCY

WASHINGTON D.C., 20460

PC Code: 077702

DP Barcode: 344574 

MEMORANDUM

Subject:	Registration Review – Preliminary problem formulation for the
Ecological Risk Assessment of Propionic Acid

To:	Wilhelmena Livingston

	Reregistration Branch 7508P

	Special Review and Reregistration Division

From:	William Shaughnessy, Ph.D., Environmental Scientist

	Carolyn Hammer, Environmental Scientist

Through:	Dana Spatz, Acting Chief

	Environmental Risk Branch 2

	Environmental Fate and Effects Division

	Office of Pesticide Programs

Attached is the preliminary problem formulation for the ecological risk
assessment to be conducted as part of the Registration Review of the
fungicide and bactericide propionic acid.

Registration Review

Ecological Risk Assessment

Problem Formulation For

Propionic Acid and Salts

Synonyms: Methylacetic acid; ethylformic acid; propanoic acid;
carboxyethane PC Code: 077702

Chemical Formula: CH3CH2COOH

 

Prepared By:

Carolyn Hammer, Environmental Scientist

Wm. J. Shaughnessy, Ph.D., Environmental Scientist

Environmental Risk Branch 2

Environmental Fate and Effects Division

Office of Pesticide Programs

Approved By:

Dana Spatz, Chief

Environmental Risk Branch 2

Environmental Fate and Effects Division

Office of Pesticide Programs

Stressor Source and Distribution

Propionic acid is a fungicide and bactericide that is registered to
control fungi and bacteria in stored hay and grains.  It is formulated
as a liquid and sprayed onto hay and grain at the time of baling. 
Currently, two manufacturing-use pesticide products are registered, as
are 12 end-use products, each containing propionic acid as its sole
active ingredient.

The pesticide is a colorless, oily, pungent liquid that is soluble in
water and occurs naturally in animals and dairy products. It also is a
normal component of metabolism in the human body.  Humans consume
naturally-occurring propionic acid in common foods such as butter and
cheese (Swiss cheese may contain as much as one percent propionic acid),
and as an added ingredient in other foods.  In its more concentrated
form it is corrosive and flammable, thus requiring special handling. 

The active ingredient propionic acid is a fungicide/bactericide used to:
(1) preserve stored grains for animal and human consumption, (2) inhibit
bacterial growth in drinking water for livestock and poultry, (3)
control mold and fungi in poultry litter and animal feed, and (4)
sanitize pre-cleaned food contact surfaces.  Propionic acid is
formulated as soluble concentrate (10%, 70.5- 70.6% a.i.), solution
(70.5% a.i.), and granular (15% a.i.).  Application rates to grains are
dependent on the moisture content of the grain at the time it is placed
in storage, up to 31 pounds per ton.  Propionic acid is also used as an
inert ingredient in pesticide formulations.  EFED was not provided with
the name(s) of chemicals that are formulated with this inert ingredient.

Propionic acid and its salts, sodium and calcium propionates, are
approved in the United States as Generally Recognized As Safe (GRAS) (21
CFR 184.1081) for use in food.  Their antimicrobial action is directed
to molds and rope bacteria, with almost no effect on yeast, thus making
them an ideal choice for products that use commercial yeast as an
ingredient.

Propionic acid is applied undiluted to grain and hay with a calibrated
liquid metering applicator that provides the desired coverage to grain
as it is moved into storage, or to hay just prior to bailing and
stacking.  In general, the rate of application is a function of the
moisture content of the grain or hay and occurs within the bailing
equipment.  It has also been approved for outdoor use as an additive to
poultry and live stock drinking water.  The application rate of active
ingredient ranges significantly per ton of hay and grain, depending on
the moisture content (see Table 1).  The following parameters are not
specified on the label and therefore not included in the table below: 
the maximum number of applications per crop cycle or year, maximum
application rate, and minimum application interval (days).

Table 1.  Listing of the label uses, application rates, form and
equipment for propionic acid as an active ingredient.

  SEQ CHAPTER \h \r 1 Use Site	Max. Rate

per App	 Max. Rate

 Unit/Area

*UG 	Form	 Application Equipment

 //Type

(Reg # Code)

NON-FOOD/NON-FEED USES





silos 	.2981 	lb 1K sq.ft

*M1         	SC/L 	Not on label                  

//Indoor general surface treatment (a)

FOOD/FEED USES





alfalfa 	15 	lb ton (L)

*B1         	RTU 	Sprayer                       

//Spray/ Stored commodity non-fumigation (a)

animal drinking water 	8824 	W ppm

*L1         	SC/L 	Not on label                  

//Water treatment (a)

barley 	1.528 	lb cwt

*L1         	RTU 	Sprayer                       

//Spray (a)

 Barley	31 	lb ton (L)

*B1         	RTU 	Sprayer                       

//Stored commodity non-fumigation (b)

cereal grains 	29 	lb ton (L)

*A2         	RTU 	Low pressure                  

//Grain treatment (a)

corn (silage) 	3 	lb ton (L)

*B1         	RTU

SC/L 	Low pressure/ Low pressure ground sprayer/ Sprayer       

//Spray (a)

corn (unspecified) 	.8458 	lb cwt

*A2         	RTU 	Sprayer                       

//Spray (a)

 corn (unspecified)	6 	lb A (L)

*A2         	SC/L 	Low pressure                  

//Spray (b)

 corn (unspecified)	23 	lb ton (L)

*B1         	RTU 	Sprayer                       

//Stored commodity non-fumigation (c)

corn, field 	1.156 	lb cwt

*A2         	RTU 	Sprayer                       

//Spray (a)

cowpeas 	31 	lb ton (L)

*B1         	RTU 	Low pressure ground sprayer   

//Stored commodity non-fumigation (a)

dairies/cheese processing plant equipment (food contact) 	158 	W ppm

*L1         	SC/L 	Not on label                  

//Circulation treatment (a)

feed/food commodities (bagged/temporary storage) 	4 	lb ton (L)

*L1         	RTU

SC/L 	Sprayer                       

//Spray (a)

food processing plant equipment (food contact) 	158 	W ppm

*L1         	SC/L 	Not on label                  

//Circulation treatment (a)

grain/cereal/flour (bagged/temporary storage) 	1 	lb ton (L)

*L1         	RTU 	Low pressure                  

//Spray (a)

grain/cereal/flour storage areas-empty 

	.2981 	lb 1K sq.ft

*L1         	SC/L 	Not on label                  

//Indoor general surface treatment (a)



grass forage/fodder/hay 	

20 	

lb ton (L)

*B1         	

RTU

SC/L 	

Low pressure/ Low pressure ground sprayer/ Metering pump 

//Spray (a)

Hay (silage) 	4 	lb ton (L)

*B1         	RTU

SC/L 	Low pressure/ Sprayer         

//Spray (a)

livestock feed (processed) 	1.428 	lb ton

*L1         	SC/L 	Not on label                  

//Stored commodity non-fumigation (a)

nongrass forage/fodder/straw/hay 	31 	lb ton (L)

*B1         	RTU 	Low pressure                  

//Grain treatment (a)

Oats 	1.528 	lb cwt

*L1         	RTU 	Sprayer                       

//Spray (a)

 Oats	31 	lb ton (L)

*B1         	RTU 	Sprayer                       

//Stored commodity non-fumigation (b)

peanuts 	31 	lb ton (L)

*B1         	RTU 	Low pressure ground sprayer   

//Stored commodity non-fumigation (a)

peas (including vines) 	31 

	lb ton (L)*B1         	RTU 

	Low pressure ground sprayer   

//Stored commodity non-fumigation (a)

poultry drinking water 	8824 	W ppm

*L1         	SC/L 	Not on label                  

//Water treatment (a)

poultry feed (processed) 	1.428 	lb ton

*L1         	SC/L 	Not on label                  

//Stored commodity 

non-fumigation (a)

poultry litter 	.2981 	lb 1K sq.ft

*L1         	SC/L 	Not on label                  

//Animal bedding/litter treatment (a)

small grains 	4 	lb ton (L)

*B1         	RTU

SC/L 	Low pressure/ Sprayer         

//Spray (a)

sorghum 	1.528 	lb cwt

*L1         	RTU 	Sprayer                       

//Spray (a)

 Sorghum	31 	lb ton (L)

*B1         	RTU 	Sprayer                       

//Stored commodity non-fumigation (b)

sorghum (unspecified) 	.8458 	lb cwt

*A2         	RTU 	Sprayer                       

//Spray (a)

soybeans 	31 	lb ton (L)

*B1         	RTU 	Low pressure ground sprayer   

//Stored commodity non-fumigation (a)

wheat 	1.528 	lb cwt

*L1         	RTU 	Sprayer                       

//Spray (a)

 Wheat	31 	lb ton (L)

*B1       	RTU 	Sprayer                       

//Stored commodity non-fumigation (b)



LEGEND 

HEADER 

ABBREVIATIONS 

Use Site:   		 The use site refers to the entity (crop, building,
surface or article) where a 

	                       	 pesticide is applied and/or which is being
protected. 

Max.Rate per App:      	 Maximum dose for a single application to a
single site. System calculated. 

Max.Rate Unit/Area:      	 Units and Area associated with the maximum
dose. 

*UG:               		Use Group codes. 

Form:		               The physical form of the end use product found in
the container. 

Max. # Apps cc & yr:	The maximum number of applications. 

Max. App Rate/cc & yr:     The maximum amount of pesticide product that
can be applied to a site in one 

                          		 growing season (/cc) or during the span of
one year (/yr). 

Min. App Interval (days):   The minimum retreatment interval between
applications in days (aggregated). 

Application Equipment      The equipment used to apply pesticide
(aggregated). 

Application Type:        	 The type of pesticide application
(aggregated). 

Current as of:		 The label data for the listed products in this report
is current as of this date. 

ABBREVIATIONS 

AN  - 			As Needed. 

NA  - 			Not Applicable. 

NS  - 			Not Specified (on label). 

(L) - 			The dosage information provided is from the label in terms of
product (e.g., ounces, 				gallons, or 

         			pounds of the product) because there was insufficient
information (e.g., missing density, 				area, or  active ingredient
percentages) to provide converted dosage information. 

~  -   			The tilde in "Max. Rate per App" indicates a dosage that
includes information from a 				SLN label. 

UC - 			Unconverted due to lack of data (on label). 

APPLICATION RATE 

W:		 	PPM calculated by weight 

V:		 	PPM calculated by volume 

U:		 	Unknown whether PPM is given by weight or by volume 

cwt:                       	Hundred Weight. 

nnE-xx:                 	nn times (10 power -xx), for instance,
"1.234E-4" is equivalent to ".0001234".  

--:                          	No description available in LUIS unit
conversion vocabulary. 

~:                          	The dosage information includes a
contribution from one or more (TQ, CL, BR, I) 

                             	active ingredients. 

FORMULATION CODES 

RTU:			Liquid-ready To Use 

SC/L:			Soluble Concentrate/liquid 

USE GROUP CODES 

A2:			TERRESTRIAL FOOD+FEED CROP 

B1:			TERRESTRIAL FEED CROP 

L1:	 		INDOOR FOOD 

M1:	 		INDOOR NON-FOOD 

	

Integration of Available Information

Propionic acid was first registered as a pesticide in the early 1970's. 
In 1975, EPA first exempted propionic acid from tolerances for residues
following post-harvest application in grains or hays (40 CFR 180.1023). 
In September 1991, EPA completed a Reregistration Eligibility Document
(RED) for propionic acid and salts.  In this document the EPA noted that
data available at that time was sufficient to support the conclusion
that the registered uses of propionic acid would not result in
unreasonable adverse effects to human health and the environment.  The
RED also noted that propionic acid is exempt from the requirement of a
tolerance when applied (as an inert ingredient) to growing crops or to
raw agricultural commodities after harvest as described in 40 CFR
180.1001c.  The current assessment considers the risks from propionic
acid as an active ingredient applied post-harvest.  When the RED was
published in 1991, EPA waived all environmental fate and ecological
effects data requirements because the use profile did not lead the
Agency to foresee the potential for significant environmental risks
associated with the registered uses of propionic acid.

Ecological Effects

Propionic acid has limited outdoor use and low toxicity, therefore its
hazard to non-target organisms is expected to be minimal.  Previous
assessments have determined that all ecological effects data
requirements were waived but this conclusion will be reconsidered in the
current reregistration assessment.  

The existing toxicity dataset includes acute studies on freshwater fish
and invertebrates, birds, and mammals.  Propionic acid is classified as
slightly toxic to aquatic organisms on an acute basis.  Toxicity data
are not available to assess the effects of chronic exposure to
freshwater organisms or acute and chronic effects to estuarine/marine
organisms.  Propionic acid is classified as practically non-toxic to
birds and mammals on an acute basis.  There are no available data on
reproductive effects to birds and mammals.  

Aquatic Effects

An acute toxicity study with freshwater fish, Rainbow trout, resulted in
a 96-hr LC50= 51 ppm.  For the freshwater invertebrate Daphnia magna,
acute toxicity testing resulted in a 48-hour EC50=22.7 ppm (MRID #
00068178).  Each study was a static test where propionic acid was
assumed to be 100% a.i.  It was not measured for verification.

 

Terrestrial Effects

Mammalian acute toxicity tests resulted in a rat LD50=2,600 mg/kg
(Accession no.091042).  Although death was not an obvious endpoint
resulting from exposure to propionic acid, ocular and dermal irritation
was reported (MRID # 41456306, 46125010).  

An avian acute oral toxicity test with mallard duck resulted in an LD50
1467 mg/kg (MRID #: 00079594).  Sub-acute, 8-day dietary exposure of
mallard duck and bobwhite quail to the salts of propionic acid resulted
in LC50 values greater than 10,000 (MRID #: 00085932, 00079595).  These
studies need to be reevaluated to verify the rates/units of exposure as
well as the exposure media.  The use of propionic salts data may not be
relevant and therefore would not qualify as a measurement endpoint with
which to assess effects to birds, amphibians, and reptiles. Dermal
effects tests were not conducted with birds.  However, based on
mammalian testing described above and label warnings of danger to
wildlife, it can be assumed that exposure to propionic acid will have a
severely irritating and corrosive effect on birds, amphibians and
reptiles.  The impacts of such an effect may vary by species. 
Amphibians, which respire through their skin, may experience severe
effects from this type of exposure.  

Although plant toxicity data are not available, the product label warns
“Treatment inhibits germination; do not use on grain intended for seed
or malting, or for use in human foods.”  This indicates a potential
for effects to non-target plants if they are exposed to propionic acid. 
Therefore, it can be assumed that if non-target plants are exposed, seed
germination will be inhibited and plants may exhibit reproductive
effects.  

Exposure Characteristics

Environmental Fate/Exposure:

Propionic acid's production and use as a grain preservative and as an
additive in livestock drinking water, may result in its release to the
environment through various waste streams.  Propionic acid is formed
from various enzymatic and fermentation processes and is produced during
anaerobic carbohydrate fermentation in the stomachs of ruminants.  It
occurs in dairy products in small amounts and its esters are found in
some essential oils.

TERRESTRIAL FATE: With an estimated Koc value of 36 derived from a log
Kow of 0.33 propionic acid is expected to have very high mobility in
soil, therefore, leaching into groundwater may occur. The pKa of
propionic acid is 4.87, indicating that this compound will exist
primarily in the anion form in the environment and anions generally do
not adsorb more strongly to soils containing organic carbon and clay
than their neutral counterparts.  Propionic acid in its anionic form
would not volatilize from water or moist soil surfaces.  The Henry’s
Law Constant for Propionic acid is 4.45E-7  atm-cu m/mole.  Propionic
acid is expected to volatilize from dry soil surfaces based upon a vapor
pressure of 3.53 mm Hg.  Propionic acid is expected to be readily
biodegradable under most environmental conditions based on the results
of a sewage inoculum screening test that measured theoretical BODs
ranging from 23-55%. 

AQUATIC FATE: The estimated Koc value of 36 suggests that propionic acid
is not expected to adsorb to suspended solids and sediment.  A pKa of
4.87 indicates propionic acid will exist almost entirely in the anion
form at pH values of 5 to 9 and therefore volatilization from water
surfaces is not expected to be an important fate process.  Leaching into
groundwater may occur.  Hydrolysis is not expected to be an important
environmental fate process since this compound lacks functional groups
that hydrolyze under environmental conditions.  According to a
classification scheme, an estimated BCF of 3.2, from its log Kow and a
regression-derived equation, suggests the potential for bioconcentration
in aquatic organisms is low.  Propionic acid is expected to be readily
biodegradable in most environmental conditions based on the results of a
sewage screening test that measured theoretical BODs of 23-55%.

ATMOSPHERIC FATE: According to a model of gas/particle partitioning of
semi-volatile organic compounds in the atmosphere, propionic acid, which
has a estimated vapor pressure of 3.53 mm Hg at 25 deg C, is expected to
exist solely as a vapor in the ambient atmosphere. Vapor-phase propionic
acid is degraded in the atmosphere by reaction with
photochemically-produced hydroxyl radicals; the half-life for this
reaction in air is estimated to be 13 days, calculated from its rate
constant of 1.22X10-12 cu cm/molecule-sec at 25 deg C.  Propionic acid
is not expected to directly photolyze due to the lack of absorbance in
the environmental UV spectrum.  Evaporation from dry surfaces is
expected, especially when present in high concentrations such as in
spill situations.

Table 2 contains a summary of the physical-chemical properties of
propionic acid.

Table 2. Chemical-Physical Properties

Property	Value	Reference

CAS	79-09-4	Hazardous Substance Data Base (HSDB)

Formula	C3H6O2	HSDB

Molecular weight	74.08	HSDB

Dissociation constant; pKa	4.88	Serjeant EP, Dempsey B; Ionization
Constants of Organic Acids in Aqueous Solution. IUPAC Chem Data Ser No.
23. NY, NY: Pergamon Press, Inc. 1979

Koc	36	Swann RL et al; Res Rev 85: 17-28. 1983.

Log Kow	0.33	Hansch C et al; Exploring QSAR. Hydrophobic, electronic,
and Steric Constants. ACS Prof Ref Book. Heller SR, Consult. Ed., Wash.,
DC

Solubility (mg/L at 25°C)	1E+6	HSDB

Vapor pressure (mm Hg at 25°C)	3.53	Lyman WJ; p. 31 in Environmental
Exposure From Chemicals Vol I, Neely WB, Blau GE, eds, Boca Raton, FL:
CRC Press. 1985

Henry’s law constant (atm-cu m/mole)	4.45E-7	HSDB



Characteristics of Ecosystems Potentially at Risk

For propionic acid and pesticides in general, the ecosystems at risk are
those in close proximity to the use areas.  These would include
agricultural fields, surrounding terrestrial habitats, and water bodies
directly adjacent to treated fields that may receive chemical residues
via drift, volatilization, or runoff.  Within water bodies, the water
column, sediment, and pore water are all compartments of concern.  In
the case of propionic acid, which is applied during or after harvest,
exposure to the environment decreases.  The elements of the ecosystem
that may be impacted include birds, amphibians, reptiles and small
mammals that utilize the harvested field for all or part of their
life-cycle.  Non-target plants near the edge-of-field may be exposed by
spray drift or over spray.  

The assessment endpoints are intended to reflect population
sustainability and community structure within ecosystems and hence
relate back to ecosystems at risk.  If risks are expected for given
species/taxa based on the screening-level assessment, then risks might
be expected to translate to higher levels of biological organization.

Organisms of concern include birds, mammals, reptiles, fish, and
terrestrial and aquatic invertebrates, plants, and amphibians.  Based on
the known effects to plants, as listed on the label, terrestrial plants
may be the primary concern.

Assessment Endpoints

Assessment endpoints are defined as “explicit expressions of the
actual environmental value that is to be protected.”  Defining an
assessment endpoint involves two steps: 1) identifying the valued
attributes of the environment that are considered to be at risk; and 2)
operationally defining the assessment endpoint in terms of an ecological
entity (i.e., a community of fish and aquatic invertebrates) and its
attributes (i.e., survival and reproduction).  Therefore, selection of
the assessment endpoints is based on valued entities (i.e., ecological
receptors), the ecosystems potentially at risk, the migration pathways
of pesticides, and the routes by which ecological receptors are exposed
to pesticide-related contamination.  The selection of clearly defined
assessment endpoints is important because they provide direction and
boundaries in the risk assessment for addressing risk management issues
of concern.  Changes to assessment endpoints are typically estimated
from the available toxicity studies, which are used as the measures of
effects to characterize potential ecological risks associated with
exposure to a pesticide, such as propionic acid.

To estimate exposure concentrations, the ecological risk assessment
considers a single application at the maximum application rate to fields
that have vulnerable soils.  However, in this case, the pesticide is not
applied to the field.   The most sensitive toxicity endpoints are used
from surrogate test species to estimate treatment-related direct effects
on acute mortality and chronic reproductive, growth and survival
assessment endpoints.  Toxicity tests are intended to determine effects
of pesticide exposure on birds, mammals, fish, terrestrial and aquatic
invertebrates, and plants.  These tests include short-term acute,
sub-acute, and reproduction studies and are typically arranged in a
hierarchical or tiered system that progresses from basic laboratory
tests to applied field studies.  The toxicity studies are used to
evaluate the potential of a pesticide to cause adverse effects, to
determine whether further testing is required, and to determine the need
for precautionary label statements to minimize the potential adverse
effects to non-target animals and plants.  In past assessments of
propionic acid, many of the effects testing requirements have been
waived.

Conceptual Model

The conceptual model (see Figure TBD) depicts the potential pathways for
ecological risk associated with propionic acid use.  The conceptual
model provides an overview of the expected exposure routes for organisms
within the propionic acid action area.  For terrestrial organisms, the
major route of exposure considered is spray drift or overspray.  Aquatic
animal species are unlikely to be exposed to propionic acid due to label
restrictions.  For terrestrial and wetland plants, the major route is
spray drift and overspray.  

Figure 1.  Conceptual Diagram of Ecological Exposure to Propionic Acid.

Risk Hypothesis

If propionic acid travels off field via spray drift, it is possible that
non-target organisms may be affected, especially plants.  Although no
phytotoxicity tests have been submitted, the label warns that applying
propionic acid to seed will inhibit germination.  Therefore, it can be
assumed that if non-target plants are exposed, seed germination will be
inhibited and they may exhibit reproductive effects.  In the absence of
seedling emergence and vegetative vigor studies and information
regarding the likelihood and quantity of spray drift, risk to non-target
plants from propionic acid use will be assumed.

Propionic acid is classified as slightly toxic, to non-toxic on an acute
basis.  Most organisms will metabolize this basic carboxylic acid and
therefore exposure by ingestion is not the route of concern.  Contact
exposure may result in adverse effects to both plants and animals.  

Based on a qualitative review of the available information and the
associated assumptions outlined in the sections below, it is EFED’s
preliminary conclusion that the current labeled uses for propionic acid
will not pose a significant risk to non-target organisms other than
terrestrial plants.  

Analysis Plan Options

Propionic acid is applied to crops post-harvest.  There are no ground or
aerial applications.  Based on the propionic acid use profile and the
assumptions listed below EFED continues to believe that exposure to
non-target organisms will be extremely limited. 

Assumptions:

	

Numerous uses occur indoors.  

When used outdoors, the product is applied simultaneously with baling
activities.  It is assumed that application during these activities will
result in minimal spray drift off field because it is a contained
operation.  Small amounts of propionic acid may land in the field due to
over spraying or windy conditions.  

If these assumptions are confirmed, a quantitative assessment will not
be conducted.  If it is found that the listed assumptions are not
accurate, a quantitative assessment may be required.  

Anticipated Data Needs

The Agency does not expect to require additional environmental fate
studies but may require ecological effects studies for plants, as listed
in 40 CFR Part 158 prior to completing the Registration Review   If a
quantitative assessment is deemed necessary, seedling emergence and
vegetative vigor data will be required to complete the assessment. 

 The Agency will conduct a search of the open literature to ensure that
all best available science is utilized.  The Agency uses the ECOTOX
database as its mechanism for searching the open literature for
ecological effects information.  ECOTOX integrates three previously
independent databases - AQUIRE, PHYTOTOX, and TERRETOX - into a system
which includes toxicity data derived predominately from the
peer-reviewed literature, for aquatic life, terrestrial plants, and
terrestrial wildlife, respectively.

Especially needed, in order to determine if a quantitative assessment is
necessary, is information regarding the typical application process
including methods, techniques and equipment.  Several of the assumptions
that preclude the necessity of a quantitative risk assessment are not
included in the label but are based on assumed application practices. 
EFED is seeking answers to the following questions:

Is propionic acid sprayed over large areas before a crop is harvested
(ie-corn)?

When propionic acid is applied during baling operations, does the method
ensure that excess product (drips) is collected and not left on the
field?  

Do outdoor application equipment and techniques usually prevent spray
drift?  

The analysis plan will be revisited and may be revised depending upon
the data available in the open literature and the information submitted
by the public in response to the opening of the Registration Review
docket.

IV.   HUMAN HEALTH EFFECTS PROBLEM FORMULATION     

         DOCUMENT 

 

UNITED STATES ENVIRONMENTAL PROTECTION AGENCY

WASHINGTON, D.C.  20460

OFFICE OF

PREVENTION, PESTICIDES AND

TOXIC SUBSTANCES

MEMORANDUM

November 20, 2007

SUBJECT:	Propionic Acid (PC 077702 ) Health Effects Division (HED)
Problem Formulation for Registration Review. DP# 344575.

FROM:	Danette Drew, Senior Scientist

		Reregistration Branch 3

		Health Effects Division (7509P)

		Office of Pesticide Programs

	

THROUGH: Catherine Eiden, Branch Chief

		 Reregistration Branch 3

		 Health Effects Division (7509P)

		 Office of Pesticide Programs 

TO:	Wilhelmena Livingston, CRM

		Special Review Branch 

		Special Review and Reregistration Division (7508P)

		Office of Pesticide Programs

Executive Summary.  Propionic acid is registered as a pesticidal active
ingredient to control fungi and bacteria in stored grains, hay, grain
storage areas, poultry litter, and drinking water for livestock and
poultry. It is also registered in food contact surface sanitizing
solutions. Calcium propionate and sodium propionate (salts of propionic
acid) are not currently registered for use as pesticide active
ingredients. Propionic acid, calcium propionate, and sodium propionate
may be found as inert (non-pesticidal, i.e. does not target pests)
ingredients in various pesticide formulations.  Propionic acid and its
salts may also be used as direct food additives and are classified as
Generally-Recognized-As-Safe (GRAS). Propionic acid, calcium propionate,
and sodium propionate are exempt from all tolerance requirements when
used on crops and animals. There are no residential uses.

The most recent health risk assessment was completed by EPA’s Health
Effects Division (HED) in February 2002 and addressed potential dietary
and residential exposures to propionic acid from pesticide uses. The
toxicity and exposure databases are adequate to support the 2002 human
health risk assessments and make safety findings under FQPA. 

Propionic acid is of moderate to low acute toxicity via the oral,
dermal, and inhalation routes of exposure, and is not a skin sensitizer.
 However, propionic acid is highly irritating to the eye and skin
(toxicity category 1).  Subchronic and chronic oral toxicity studies
(rats and dogs) with propionic acid, or its salts, indicate local
irritation as the primary effect. At high dose levels, animals can
exhibit lesions/ulcers in the forestomach and an increased incidence of
epithelial hyperplasia in the esophagus. There do not appear to be any
significant systemic effects.

No new data are required. The findings of the February 2002 assessment
are still valid for the current uses of propionic acid, namely that,
based on its low toxicity, limited use pattern, and affirmation as a
GRAS chemical when used as a food additive, propionic acid is not
expected to result in any adverse health effects via the food, drinking
water, or residential exposure pathways. 

 A quantitative occupational exposure assessment has not been conducted.
There is a possibility of eye and skin irritation to occupational
handlers; this was mitigated through the reregistration process (1991
RED), on a product-by-product basis, by the requirement for personal
protective equipment on existing propionic acid labels. During the
registration review process, it will be determined if the 1991
conclusions and recommendations for occupational handlers are
appropriate for all the currently registered pesticidal uses of
propionic acid.

HED has not performed a review of the available databases for poisoning
incidents related to propionic acid. A review of the databases will be
conducted and, if necessary, an incident report will be prepared during
the registration review process.

 

Regulatory Background. Propionic acid (PC 077702) was first registered
for pesticidal use in the early 1970's.  As an active ingredient, it is
formulated into products that control fungi and bacteria in stored
grains, hay, storage areas for silage and grains, poultry litter, and
poultry and livestock drinking water. It is also use in food processing
plants as a food contact surface sanitizer. Calcium propionate (PC
077701) and sodium propionate (PC 077703) (salts of propionic acid) are
not currently registered for use as pesticide active ingredients. 

Propionic acid, calcium propionate, and sodium propionate may be found
as inert (non-pesticidal, i.e does not target pests) ingredients in
various pesticide formulations.  Propionic acid and its salts may also
be used as direct food additives.

In May 1984, propionic acid, calcium propionate, and sodium propionate
were affirmed as Generally-Recognized-As-Safe (GRAS) by the Food and
Drug Administration (FDA) for use as direct food additives (i.e., as
chemical preservatives and antimicrobial agents in food). The
specifications for the affirmation of propionic acid, calcium
propionate, and sodium propionate as GRAS chemicals are listed in 21 CFR
184.1081, 184.1221, and 184.1784, respectively, and can be summarized as
follows: The ingredient is used in food with no limitation other than
current good manufacturing practice.  

The Reregistration Eligibility Decision (RED) Document for propionic
acid was completed in September 1991 and concluded that all products
containing propionic acid as the pesticide active ingredient were
eligible for reregistration.

 In February 2002, EPA’s Health Effects Division performed a tolerance
reassessment which addressed possible exposures to residues of propionic
acid in food, drinking water, and from residential sources as pursuant
to FQPA. HED concluded the following:

“Based on its low toxicity, limited use pattern, and affirmation as a
GRAS chemical when used as a food additive, propionic acid is not
expected to result in any adverse health effects via the food, drinking
water, or residential exposure pathways.  There is a possibility of eye
and skin irritation to occupational handlers; this was mitigated through
the reregistration process, on a product-by-product basis, by the
requirement for personal protective equipment on existing propionic acid
labels.  A review of the toxicology database, with an emphasis on
sensitivity of infants and children, shows no significant findings since
the date of the original propionic acid RED from 1991.  HED concludes
that a FQPA safety factor analysis is not required for propionic acid. 
Propionic acid, calcium propionate, and sodium propionate will be exempt
from all tolerance requirements.”

In April 2002, EPA’s Inert Ingredient Focus Group provided a decision
document for the tolerance reassessment of propionic acid and its
calcium and sodium salts as active and inert (pesticidal and
non-pesticidal) ingredients. The Group reiterated HED’s conclusions
that propionic acid is not expected to result in any adverse heath
effects via food, drinking water or residential exposure, that the
occupational handler risk of eye and skin irritation should be addressed
on a product-specific basis, and that the tolerance exemptions should be
in effect for propionic acid and its sodium and calcium salts. 

The following tolerance exemptions for propionic acid and its salts are
currently listed in 40 CFR 180.1023:

 (a) Postharvest application of propanoic acid or a mixture of methylene
bispropionate and oxy(bismethylene) bisproprionate when used as a
fungicide is exempted from the requirement of a tolerance for residues
in or on the following raw agricultural commodities: Alfalfa, barley
grain, Bermuda grass, bluegrass, brome grass, clover, corn grain, cowpea
hay, fescue, lespedeza, lupines, oat grain, orchard grass, peanut hay,
peavine hay, rye grass, sorghum grain, soybean hay, sudan grass,
timothy, vetch, and wheat grain.

(b) Propanoic acid is exempt from the requirement of a tolerance for
residues in or on meat and meat byproducts of cattle, sheep, hogs,
goats, horses, and poultry, milk, and eggs when applied as a
bactericide/fungicide to livestock drinking water, poultry litter, and
storage areas for silage and grain.

(c) Preharvest and postharvest application of propanoic acid (CAS Reg.
No. 79–09–4), propanioc acid, calcium salt (CAS Reg. No.
4075–81–4), and propanioc sodium salt (CAS Reg. No. 137–40–6)
are exempted from the requirement of a tolerance on all crops when used
as either an active or inert ingredient in accordance with good
agricultural practice in pesticide formulations applied to growing
crops, to raw agricultural commodities before and after harvest and to
animals.

[69 FR 47025, Aug. 4, 2004]

Use Pattern and Exposure Potential. Propionic acid is used on stored
grains, hay, grain storage areas, poultry litter, and drinking water for
livestock and poultry. It is also used to sanitize food contact areas in
processing facilities. There are no residential uses. According to a
November 2007 OPPIN search there are currently 25 end-use products
(EUPs) and 5 manufacturing use products (MUPs. EUPs are formulated as
soluble concentrates and ready-to-use liquids at 10% to 99.5% a.i..
Products are sprayed using a low pressure hand-wand system. Application
rates range from 8.27- 10.14 lbs per gallon. Based on its registered use
patterns, there is some potential for dietary and occupational exposures
to propionic acid.  Homeowner exposures via residential uses are not
expected.

Hazard Characterization. At the time that the propionic acid tolerance
reassessment was completed in 2002, the toxicological database was
determined to be adequate for the purposes of tolerance reassessment,
and no further toxicity data on propionic acid were required by the
Agency. A comprehensive open literature search, conducted from 2002 to
the present and including databases such as PubMed and ToxNet, has not
revealed any new studies on propionic acid that would alter the previous
toxicological conclusions.  A search of the OPPIN conducted in November
2007 has also not revealed any new toxicity studies that would have a
significant impact on the toxicological findings for propionic acid. 
Therefore, the Agency concludes that the toxicology determinations made
in 2002 are still valid and no additional toxicity data are required.  A
summary of these toxicology findings is presented below.

 Acute Toxicity

Technical propionic acid is of moderate to low acute toxicity via the
oral, dermal, and inhalation routes of exposure (toxicity category 
III), and is not a skin sensitizer.  However, propionic acid is highly
irritating to eyes and skin (toxicity category 1).  

Subchronic Toxicity

Subchronic toxicity data are available on propionic acid and its salts.
Data on calcium and sodium propionate can be used to assess subchronic
toxicity of propionic acid.  Rats fed calcium or sodium propionate at
one percent of the diet (equivalent to 750 mg/kg/day of propionic acid)
for four weeks followed by three percent (equivalent to 1200 mg/kg/day
of propionic acid) for three weeks showed no changes in weight gain
compared to the controls.  Rats fed five percent propionic acid in the
diet (approximately 5000 mg/kg body weight) for 110 days developed
lesions of the forestomach.

Propionic acid was given in the feed to dogs at 220, 735, or 2066
mg/kg/day for 90 days.  The high dose dogs showed reduced food
consumption, increased incidence of epithelial hyperplasia in the
esophagus, and increased nitrite in the urine.  These effects were no
longer present in dogs held for a six week recovery period.  A limited
study with calcium propionate in dogs for 90 days showed vomiting and
diarrhea in animals fed 2523 mg/kg/day.

Chronic Toxicity, Reproduction, and Teratology

Twenty male rats per group were fed four percent propionic acid in the
diet for two years. The highest dose animals had hyperplasia and
hyperplastic ulcers in the forestomach.  Available data on calcium and
sodium propionate indicate the following:

Rats fed bread containing sodium propionate (4000 mg/kg/day) for a year
showed no adverse effects, nor did rats fed a similar diet for 32 weeks,
other than an initial depression of growth.

No maternal or fetal effects were seen upon feeding calcium propionate
to pregnant animals at rates up to 300 mg/kg/day for rats and mice, or
up to 400 mg/kg/day for hamsters and rabbits.

No teratogenicity was found in developing chick embryos when up to 100
mg/kg calcium

 propionate was injected into the yolk or air cell, although there was
increased mortality 

at 5 and 10 mg/kg.

Mutagenicity

Propionic acid tested negative for mutagenicity.

Metabolism

Propionic acid is rapidly absorbed from the mammalian gastrointestinal
tract.  Propionic acid is a normal intermediary metabolite in the body. 
It is utilized by most organs and tissues, and can be metabolized to
glucose, carbohydrates, amino acids, and lipids.  It is produced in
large quantities in ruminants, and is one of the metabolic products from
the breakdown of several amino acids in nonruminants.  Propionic acid is
formed in the oxidation of fatty acids and from the side chain of
cholesterol.

Dietary (food and water) Exposure and Risk Estimates.  A dietary risk
assessment has not been conducted and is not required. No residue
chemistry data are required.

EFED has conducted a review of propionic acid (both as an active
ingredient and as an inert ingredient) to determine potential
concentrations in drinking water.  Based on its review, EFED has
concluded that propionic acid drinking water concentrations as a result
of its use as an active ingredient are expected to be negligible. A
review of registered uses of propionic acid indicates that all uses are
either indoor treatments or limited outdoor uses for animal watering.

Since residues in water from the pesticidal use of propionic acid are
considered negligible, and there is little likelihood of significant
residues in livestock fed treated feed and water, the likelihood of any
significant dietary exposure to humans is very low.  Potential exposure
and risk from the use of propionic acid as a direct food additive is
also considered to be very low.  This conclusion is strengthened by the
presence of propionic acid as a normal component of metabolism in the
human body, and because propionic acid is a naturally occurring
component in dairy products such as butter and cheese.  When considered
together, these facts all support HED’s conclusion that dietary
exposure and dietary risk to propionic acid is extremely low and a
dietary risk assessment is not necessary.

Residential Exposure and Risk Estimates.  Propionic acid-containing
products are not registered for use in/on residential or public
recreational sites; there are no registered lawn or garden uses. A
residential risk assessment is not required.

Aggregate Risk Estimates. An aggregate risk assessment is not required.
There are no residential uses and a dietary risk assessment is not
necessary.

Occupational Exposure and Risk Estimates. A quantitative occupational
risk assessment has not been performed for propionic acid. There are
potential exposures to product handlers. The potential for
post-application exposures is expected to be minimal (provided areas are
adequately ventilated as stipulated on labels).  The 1991 RED stated
that “Other than eye and skin exposure, the human risks from
occupational exposures are considered to be very low, because of the
general knowledge of the chemical as well as its ongoing history of use
by humans, including some pharmaceutical applications. However, eye and
skin exposures do pose risks, i.e. the chemical is corrosive to the
surface of the human eye and skin. Thus, adequate precautions must be
taken to shield the eyes and prevent skin contact when the chemical is
being handled.” The RED labeling requirements for EUPs containing
propionic acid are specified as “Products containing greater than 63%
a.i. must include the following protective clothing label requirements:
Wear chemical-resistant gloves, chemical-resistant aprons,
chemical-resistant footwear and goggles or face shield when loading
application equipment unless a closed loading system is used. Avoid
working near high concentrations of spray mist/vapor. Use with adequate
ventilation. Wash thoroughly after handling.”

During the registration review process, it will be determined if the
1991 conclusions and recommendations for occupational handlers are
appropriate for the currently registered uses of propionic acid.

Public Health and Incident Reports.

A summary report listing reported incidents for propionic acid will be
provided for the docket. The reported incidents will be screened in more
detail during the development of the Preliminary Work Plan (PWP) for
propionic acid.

Data Requirements.  No new data are required.

Tolerances and International Harmonization. Propionic acid, and its
sodium and calcium salts, are exempt from the requirements of a
tolerance.

Considerations

In preparation of this problem formulation document for propionic acid
in support of registration review the following has been considered:

Search for and review of the most current human health risk assessments,
including occupational/residential and dietary assessments conducted for
new uses, Section 18 Emergency Exemptions, and Special Local Needs
(24Cs) using internal Lotus Notes databases

Review of the most recent decisions regarding hazard characterization,
the adequacy and completeness of the toxicity database, the FQPA Safety
Factor neurotoxicity, thyroid and immune system effects, and cancer
issues to ensure their reflection in the most recent risk assessments

Search of the OPPIN database to identify data submitted that have not
been reviewed or included in the most current risk assessments

Review E Jackets to clarify the status of a use

Review of the most current labels to ensure all current registrations
have been included in the most recent risk assessments

Conduct a search of the general literature for information on propionic
acid not captured in current risk assessments

Review of labeled uses and use information from BEAD

Review of tolerances and exemptions from tolerances listed in Part 180
of the Code of Federal Regulations (CFR) 

V.   GLOSSARY AND TERMS AND ABBREVIATIONS

Glossary of Terms and Abbreviations   

AGDCI		Agricultural Data Call-In

ai			Active Ingredient

aPAD			Acute Population Adjusted Dose

BCF			Bioconcentration Factor 

CFR			Code of Federal Regulations

cPAD			Chronic Population Adjusted Dose

CSF			Confidential Statement of Formula

CSFII			USDA Continuing Surveys for Food Intake by Individuals

DCI			Data Call-In

DEEM		Dietary Exposure Evaluation Model

DFR			Dislodgeable Foliar Residue

DNT			Developmental Neurotoxicity

EC			Emulsifiable Concentrate Formulation

EDWC		Estimated Drinking Water Concentration

EEC			Estimated Environmental Concentration

EPA			Environmental Protection Agency

EUP			End-Use Product

FDA			Food and Drug Administration

FIFRA		Federal Insecticide, Fungicide, and Rodenticide Act

FFDCA		Federal Food, Drug, and Cosmetic Act

FQPA			Food Quality Protection Act

GLN			Guideline Number

IR			Index Reservoir

LC50			Median Lethal Concentration.  A statistically derived
concentration of a substance that can be 	expected to cause death in 50%
of test animals.  It is usually expressed as the weight of substance 
per weight or volume of water, air or feed, e.g., mg/l, mg/kg or ppm.

LD50			Median Lethal Dose.  A statistically derived single dose that can
be expected to cause death in 	50% of  the test animals when
administered by the route indicated (oral, dermal, 	inhalation).  It is 
expressed as a weight of substance per unit weight of animal, e.g.,
mg/kg.

LOC			Level of Concern

LOAEL		Lowest Observed Adverse Effect Level

MATC		Maximum Acceptable Toxicant Concentration

µg/g			Micrograms Per Gram

µg/L			Micrograms Per Liter

mg/kg/day		Milligram Per Kilogram Per Day

mg/L			Milligrams Per Liter

MOE			Margin of Exposure 

MRID			Master Record Identification (number).  EPA's system of recording
and tracking studies 	submitted.

MUP			Manufacturing-Use Product

NOAEL		No Observed Adverse Effect Level

OPP			EPA Office of Pesticide Programs

OPPTS		EPA Office of Prevention, Pesticides and Toxic Substances

PAD			Population Adjusted Dose

PCA			Percent Crop Area

PDP			USDA Pesticide Data Program

PHED			Pesticide Handler's Exposure Data 

PHI			Preharvest Interval

ppb			Parts Per Billion

PPE			Personal Protective Equipment

ppm			Parts Per Million

PRZM/EXAMS	Tier II Surface Water Computer Model  

Q1*			The Carcinogenic Potential of a Compound, Quantified by the EPA's
Cancer Risk Model

RAC			Raw Agriculture Commodity

RED			Reregistration Eligibility Decision

REI			Restricted Entry Interval

RfD			Reference Dose

RQ			Risk Quotient

SCI-GROW		Tier I Ground Water Computer Model

SAP			Science Advisory Panel

SF			Safety Factor

SLC			Single Layer Clothing

TGAI			Technical Grade Active Ingredient

USDA		United States Department of Agriculture

USGS			United States Geological Survey

UF			Uncertainty Factor

UV			Ultraviolet 

WPS			Worker Protection Standard

 USEPA 1991.  Reregistration Eligibility Document – Propionic Acid,
and Salts. Office of Pesticide Programs, Special Review and
Reregistration Division. September 1991.

 Acute Toxicity to Freshwater Fish. Animal Biol. Lab., EPA-TSD, Test No.
604, June 1973; Test No. 609, September 1973. 

 Doucette WJ; pp. 141-188 in Handbook of Property Estimation Methods for
Chemicals. Boethling RS, Mackay D, eds. Boca Raton, FL: Lewis Publ
(2000)

 Heukelekian H, Rand MC; J Water Pollut Control Assoc 29: 1040-53 (1955)

 Doucette WJ; pp. 141-188 in Handbook of Property Estimation Methods for
Chemicals. Boethling RS, Mackay D, eds, Boca Raton, FL: Lewis Publ
(2000)

 Franke C et al; Chemosphere 29: 1501-14 (1994)

 Meylan WM et al; Environ Toxicol Chem 18: 664-72 (1999)

 Heukelekian H, Rand MC; J Water Pollut Control Assoc 29: 1040-53 (1955)

 Bidleman TF; Environ Sci Technol 22: 361-367 (1988)

 Atkinson R; J Phys Chem Ref Data Monograph No. 1 (1989)

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