Document ID: EPA-HQ-OPP-2008-0652-0004
Agency: epa
Document Type: Supporting & Related Material
Title: 
Posted Date: 2010-03-24T04:00Z

February 2, 2010

MEMORANDUM

SUBJECT:	Decision Document for Petition Number 8E7402; 

	Ammonia salts of higher fatty acids (C8-C18 saturated) 

		

FROM:	Deirdre Sunderland, Industrial Hygienist

		Inert Ingredient Assessment Branch (IIAB)

		Registration Division (7505P)

TO:		PV Shah, Chief

		Inert Ingredient Assessment Branch (IIAB)

		Registration Division (7505P)

EXCUTIVE SUMMARY

A petition requesting an exemption from the requirement of tolerance for
ammonium salts of fatty acids (C8-C18 saturated) under 40 CFR 180.910
was submitted to the Environmental Protection Agency, herein referred to
as the Agency or EPA, by Falcon Lab, LLC. 

Ammonium salts of fatty acids are mineral salts of naturally occurring
fatty acids found in the environment. Fatty acids play a significant
role in the normal diet of humans, animals, and plants and currently
have FDA and EPA approved uses in food products. They are also found in
cosmetics and household cleaners. 

Ammonium salts of fatty acids have shown to be of low toxicity via the
oral and dermal routes of exposure, Toxicity category IV and III,
respectively (40 CFR 156.62). When applied for long periods of time,
they have the potential to be dermal irritants. Ammonium salts of fatty
acids are eye irritants and have the potential to cause permanent eye
injury. Limited data are available regarding the inhalation toxicity of
soap salts; however, they are anticipated to be irritating via the
inhalation route of exposure. 

A subchronic range finding study did not see any significant systemic
toxicity of nonanoic acid (C9 saturated) given to rats at doses up to
1,834 mg/kg/day. Ammonium salts of fatty acids are not believed to be
mutagenic.  When used at high doses, reproductive and mutagenic effects
were observed in laboratory animals given potassium salts of coco fatty
acids; however, studies on one of the ammomium salts, pelargonic acid
(nonanoate acid), did not show developmental or mutagenic effects. Due
to the lack of mutagenicity, the low toxicity, and the anticipated
exposure from the use of these chemicals as inert ingredients in
pesticide products the Agency does not believe ammonium salts of fatty
acids (C8-C18 saturated) will be carcinogenic in humans. 

Oral exposure to soaps is generally self-limiting because the taste of
soap is easily recognized and unpleasant. In addition, ammonium soap
salts have an ammonia odor that is limiting. Because of their strong
soil adsorption and the rapid degradation they are not expected to reach
surface water via runoff nor are they expected to leach into ground
water. 

Ammonium salts of fatty acids have the potential to cause dermal, eye,
and inhalation effects. However, due to the vapor pressure and the
unlikelihood of fatty acid forming aerosol particulates the anticipated
risk from the inhalation route of exposure is not expect to cause
adverse harm to occupational and residentially exposed individuals.
Dermal and ocular exposure is expected to be negated by the use of
personal protective equipment (e.g. chemical resistant gloves, goggles,
face shield, etc). 

Fatty acids are an essential component of the mammalian diet and the
body is able to metabolize these soap salts and use them as an energy
source. Due to the self limiting nature of these chemicals, their
natural occurrence in the environment, their rapid environmental
degradation, and their presence in commonly eaten foods (both naturally
and intentionally added) the anticipated exposure from the use of
ammonium salts of fatty acids as inert ingredients in pesticide products
is expected to be minimal and is not anticipated to significantly
increase the overall exposure to all populations including infants and
children.

Ammonium salts of fatty acids are expected to be only minimally toxic to
nontarget organisms, with the exception of aquatic invertebrates.
“Soap salts of fatty acids are slightly toxic to birds on an acute
basis and are practically non-toxic to birds on a dietary basis,
slightly toxic to fish, and highly toxic to aquatic
invertebrates”.(EPA Memorandum: Jones, 2006) Appropriate precautionary
labeling stipulating the product is hazardous to aquatic invertebrates
and that the product should not be used on or near water bodies, where
surface water is present, or to intertidal areas below the mean high
water mark will further minimize potential exposure and mitigate risk to
humans and aquatic organism. 

It is highly unlikely that concentrations needed to invoke a toxic
response would be reached from the use of ammonium salts of fatty acids
(C8-C18 saturated) as inert ingredients in pesticide products;
therefore, the Agency believes that there is a reasonable certainly of
no harm to human health and the environment. Hence, an exemption from
the requirement of tolerance has been granted under 40 CFR 180.910 for
ammonium salts of fatty acids (C8-C18 saturated). 

BACKGROUND AND USES

On August 12, 2008 Falcon Lab, LLC, 1103 Norbee Drive, Wilmington, DE
19803, submitted a petition to amend 40 CFR 180.910 (Inert ingredients
used pre- and post-harvest) by establishing an exemption from the
requirement of a tolerance for ammonium salts of fatty acids (C8-C18
saturated), (see Table 1 for chemical name and CAS Reg No.) as inert
ingredients in pesticide products on all food commodities.  

Table 1- Chemical Name and CAS Reg. No. for Ammonium Salts of Fatty
Acids C8-C18 (saturated)

Chain length	CAS Reg. No	Name

Saturated

C8	5972-76-9	Ammonium caprylate or ammonium octanoate

C9	63718-65-0	Ammonium nonanoate

C10	16530-70-4	Ammonium decanoate

C11	32582-95-9	Undecanoic acid, ammonium salt

C12	2437-23-2	Ammonium laurate or Dodecanoic acid, ammonium salt

C13	191799-95-8	Tridecanoic acid, ammonium salt

C14	16530-71-5	Ammonium myristate

C15	93917-76-1	Ammonium pentadecanoate

C16	5297-93-8	Ammonium palmitate

C17	94266-36-1	Ammonium heptadecanoate

C18	1002-89-7	Ammonium stearate

	Ammonium salts of fatty acids are mineral salts of naturally occurring
fatty acids. Fatty acids play a significant role in the normal diet of
humans, animals and plants. They are naturally present in commonly eaten
fats and oils, accounting for approximately 30-40% of the caloric intake
in the U.S. diet (~ 90 grams/day). (EPA RED: Soap Salts, 1992; EPA
Memorandum: Boyle, 2003) Additional exposure to fatty acids may come
from a wide variety of sources, including (but not limited to)
FDA-approved uses as direct food additives (2l CFR 172.860; 21 CFR
172.862; and 21 CFR 172.863), in food packaging products (21 CFR
176.200), or through their use in cosmetics. These fatty acids are also
used as a waterproofing agent for concrete, stucco, paper and textiles.
Currently, they are approved as active and inert ingredients in
pesticide product formulations. 

 

	Ammonium stearate (C18 saturated; CAS Reg. No. 1002-89-7), one of the
soap salts, has been approved as an inert ingredient under 40 CFR
180.910 since 1962 for use in pesticide products applied to growing
crops or to raw agricultural commodities after harvest. A document
published in July of 2002 by the Environmental Protection Agency’s
Inert Ingredient Focus Group (IIFG) illustrated the reassement of the 40
CFR 180.910 classification and determined that a reasonable certainty of
no harm will result to the general population and to infants and
children from the aggregate exposure to residues of ammonium salts of
fatty acids (C8-C18 saturated and C18 unsaturated). (EPA Memorandum:
Boyle and Leifer, 2002)  

According to the EPA’s “IIFG Decision Documents on Reassessment of
Exemptions from Tolerance for Various Salts of Stearic Acid” (2002),
in 1974 the Food and Agriculture Organization/World Health Organization
(FAO/WHO) published the “Toxicological Evaluation of Certain Food
Additives with a Review of General Principles and of Specifications”.
This evaluation addressed numerous chemicals including ammonium,
calcium, and magnesium stearate as anticaking agents in food. As a
result of the evaluation, a “not limited” ADI (acceptable daily
intake) classification was applied to ammonium, calcium and magnesium
stearate as anticaking agents. Furthermore, the report summary states
that “stearic acid and [their] salts are normal products of the
metabolism of fats and their metabolic fate is well established.
Provided the contribution of the cations does not add excessively to the
normal body load, there is no need to consider the use of these
substances in any different light to that of dietary fatty acids.”

In 1982 the EPA approved an exemption from the requirement of tolerance
for ammonium and potassium salts of fatty acid when used as pesticide
active ingredients on food commodities; however, formal notice was not
provided in the Federal Register. That same year, a safety assessment of
ammonium stearate by an expert panel of the Cosmetic Ingredient Review
(CIR) was published in the Journal of the American College of
Toxicology. Acute oral, dermal, skin irritation, teratology and
mutagenicity studies were evaluated. The review concluded that these
materials are “safe as cosmetic ingredients in the present practices
of use and concentration.” The use concentration of ammonium stearate
in cosmetic products varies from 0.1 to nearly 50 percent. (EPA
Memorandum: Boyle and Leifer, 2002).

In 1992 EPA issued a Reregistration Eligibility Document (RED) on soap
salts which evaluated two chemically-similar pesticide active
ingredients: potassium salts of fatty acids (C12-C18 saturated and C18
unsaturated) and ammonium salts of fatty acids (C8-C18 saturated and C18
unsaturated). The Agency RED for soap salts treats ammonium salts of
fatty acids (C8-C18 saturated and C18 unsaturated) as one active
ingredient. This document also made the finding that all compounds, as
defined within these two classes of active ingredients (ammonium soap
salts and potassium soap salts), are similar in regard to chemistry,
toxicology, and environmental fate and effects. It was determined that
all registered pesticide products containing the active ingredient soap
salts are not likely to cause unreasonable adverse effects in people or
the environment and were eligible for reregistration. 

	Ammonium soap salts of fatty acids were approved in 2006 as active
ingredients in non-food use pesticide products for the suppression and
control of a wide variety of undesirable grasses and weeds. Previously,
ammonium salts of fatty acids had been registered for other non-food
uses, including repelling rabbits and deer from forage and grain crops.
(73 FR 39264, July 9, 2008) They also have some insecticidal properties.

	In July 2008, 40 CFR 180.1284 established an exemption from the
requirement of a tolerance for residues of the active ingredient
ammonium salts of higher fatty acids (C8–C18 saturated and C8–C12
unsaturated) in or on all food commodities when applied for the
suppression and control of a wide variety of grasses and weeds.
According to the final rule (73 FR 39264, July 9, 2008), ”All soap
salts with fatty acids having aliphatic carbon chains lengths in the
range between C8 and C18 saturated are virtually identical in regard to
chemistry and toxicology”.

A comprehensive risk assessment conducted by the Human and Environmental
Risk Assessment (HERA) on fatty acid salts which included a “Human
Health Risk Assessment” (2002) and an “Environmental Risk
Assessment” (2003) specifically addressed sodium and potassium salt of
fatty acids (even numbered, straight C chains with 10 to 22 C atoms,
with C16-C22 fatty acid chains having saturated or unsaturated with a
C-C double bond) when used as ingredients in European household cleaning
products. Although the HERA assessment only evaluates sodium and
potassium fatty acid salts, the Soap Salts RED (EPA, 1992) considers
potassium and ammonium fatty acid salts to have similar chemistry,
toxicology, and environmental fate and effects and is therefore relevant
to this assessment. (EPA Memorandum: Jones, 2006)

The HERA document estimated that approximately 71,306 tons of fatty acid
soap salts were used annually in household cleaning products (including
fabric washing products, fabric conditioners, laundry additives, and
surface and toilet cleaners) in Europe. This widespread use results in
frequent, regular, and continuous human and non-target organism
exposure. The HERA document concluded: 

Fatty acid salts are of low acute toxicity. Their skin and eye
irritation potential is chain length dependent and decreases with
increasing chain length. They are not skin sensitizers. The available
repeated dose toxicity data demonstrate the low toxicity of the fatty
acids and their salts. Also, they are not considered to be mutagenic,
genotoxic or carcinogenic, and are not reproductive or developmental
toxicants.

PHYSICAL AND CHEMICAL PROPERTIES 

Fatty acids are naturally occurring acids found in fats and oils. A
fatty acid is made up of a long chain of hydrogen and carbon atoms, with
an extra hydrogen atom at one end and a "carboxyl group" (made up of two
oxygen, one hydrogen and one carbon atom) on the other end. Fatty acids
can be "saturated" or "unsaturated". They differ in how they are bound
to hydrogen.  A saturated fatty acid is one where the carbon atoms are
bonded with single bonds; each sharing one set of electrons. As a
result, saturated fatty acids have two hydrogen atoms for each carbon
atom.  Unsaturated fatty acids, on the other hand, have at least one
double bond where one set of carbon atoms is bonded by sharing two sets
of electrons, instead of each being connected to a hydrogen atom. 

When a particular fatty acid reacts with a base such as ammonia, a fatty
acid salt is formed which is also referred to as an ammonium soap salt.
In other words, soap is essentially a fatty acid salt. The type of fatty
acid and length of the carbon chain determines the unique properties of
various soap salts. 

In general ammonium salts of fatty acids are slightly soluble in water
and do not form aerosol particulates. The longer the fatty acid chain
the more insoluble it is. The hydrocarbon chain is non-polar and
hydrophobic. The "salt" end of the soap molecule is ionic and
hydrophilic. Ammonium salts of fatty acids have a vapor pressure near
that of water and do not readily vaporize. Ammonium stearate (C18
saturated), for example, has a water solubility of 0.56 mg/L and a vapor
pressure of 2.5 x 10-8 mmHg at 25° C. It binds strongly to soils (Koc
greater than 10) and the log n-octanol-water partition coefficient is
above 5. (EPA Memorandum: Boyle and Leifer, 2002) 

METABOLISM/PHARMACOKINETICS

The 2002 HERA document makes the claim that: 

The acid and alkali salt forms of the same chemical are expected to have
many similar physicochemical and toxicological properties when they
become bioavailable; therefore, data read across is used for those
instances where data are available for the acid form but not the salt,
and vice versa. This position is based on experimental studies that have
clearly demonstrated a high degree of similarity between the
toxicokinetics and toxicodynamics of acid and salt forms of the same
chemical (BASF, 2001). A general premise in regulatory toxicology is
that testing an acid form of a chemical is representative of the testing
that chemical as an alkali salt.

Exposure to ammonium stearate, for example, would likely result in
dissociation in the body into the free fatty acid (stearic acid) and the
ammonium cation. (EPA Memorandum: Boyle and Leifer, 2002)

Fatty acids are found in commonly eaten fats and oils. Once fats and
oils are consumed, the triglycerides are rapidly hydrolyzed in the human
body into glycerol and free fatty acids. (EPA Memorandum: Boyle and
Leifer, 2002) Fatty acids are normally metabolized by the cells, where
they are oxidized to simple compounds for use as energy sources and as
structural components utilized in all living cells.  Ammonium is also a
normally part of the body’s metabolism and electrolyte balance. 

 

A 2002 reassessment document on various salts of stearic acid written by
the Agency’s Inert Ingredient Focus Group describes some of the
properties of ammonium stearate:

 

Ammonium stearate salts dissociate to form the positively charged
ammonium ion (NH4+). Nitrogen, a component of the ammonium ion, is an
important element in human metabolism, but humans cannot convert
atmospheric nitrogen to any form that can be used as part of any of the
various metabolic cycles. As a result, nitrogen has to enter the body
through the diet by consumption of nitrogen-containing amino acids in
protein…Generally the body works to maintain a balance of nitrogen
intake and nitrogen excretion. The estimated daily ammonia intake
through food and drinking water is 18 mg. In contrast, 4000 mg of
ammonia per day are produced endogenously in the human intestine.
Ammonia and the ammonium ion are integral components of normal human
metabolic processes...The liver converts ammonia via the urea cycle into
urea. According to FDA, “the normal liver so readily detoxifies
ammonium ion from alimentary sources that blood concentrations of
ammonium salts do not rise to the levels necessary to evoke toxic
response.” Approximately 80% of the body’s excess nitrogen is
eliminated through the kidneys as urea, approximately 25 to 30 grams per
day. 

TOXICOLOGY

The Agency’s Reregistration Eligibility Document (RED) for Soap Salts
(1992) treats ammonium salts of fatty acids  (C8-C18 saturated and C18
unsaturated) as one active ingredient. The document covered both
ammonium salts of fatty acids and potassium salts of fatty acids and
makes the conclusion that all compounds, as defined within these two
classes, are similar in regard to chemistry, toxicology, and
environmental fate and effects.  This document utilizes information on
ammonium and potassium soap salts and their free fatty acids.  

 

Acute Oral and Dermal

According to the 1992 RED, soap salts have low acute oral and dermal
toxicity. Ammonium stearate (C18 saturated), for example, has an acute
oral LD50 of >5 g/kg (rat) and an acute dermal LD50 of >3g/kg (guinea
pig). Pelargonic acid (Nonanoic acid), a C9 saturated fatty acid, showed
an acute oral LD50 of >5g/kg and an acute dermal LD50 of >2g/kg (animal
not identified; test material-60% pelargonic acid emulsifiable
concentrate). Similarly, the oral LD50 of oleic acid (C9 unsaturated) in
rats was 74 g/kg. According to the Agency’s acute toxicity catagories
(40 CFR 156.62) ammonium soap salts are classified as category IV via
the oral route and category III via the dermal route.

Acute Inhalation 

	There were limited data available regarding inhalation of fatty acids,
and none available regarding inhalation of fatty acid salts. Since fatty
acid salts are known eye and skin irritants, it is highly likely that
they will also be strongly irritating via the inhalation route of
exposure. One study exposed male and female albino rats to pelargonic
acid (nonanoic acid) for 4 hours. This study reported an LC50 of 1.244
milligrams/liter (mg/L). (MRID 43843503) 

Dermal Irritation

Several studies were outlined in the 1992 RED document on soap salts, 

On human skin 2.5mg of soap for 24 hours caused moderate irritation; and
10 mg of soap on rabbit skin caused mild irritation. On human skin,
11,800 mg of the potassium salt of palmitic acid was irritating. For the
potassium salt of caprylic acid, 7320 mg was irritating on human skin.
Stearic acid was mildly irritating to human skin when 75 mg was applied
intermittently for 3 days. On rabbit skin, 500 mg of stearic acid
applied for 24 hours was moderately irritating. Oleic acid was
moderately irritation to human skin when 15 mg was applied
intermittently for 3 days; and mildly irritating to rabbit skin when
500mg was applied. 

.  

Skin Sensitization and Eye Irritation

Ammonium soaps of higher fatty acids may cause allergic skin reactions
in some individuals; however, the Agency believes allergic reactions are
uncommon and transient. Soap salts are not classified as skin
sensitizers. Ammonium soap salts are irritating to the eyes and may
cause permanent eye damage. (US EPA RED: Soap Salts, 1992)

Repeat dose

A 14-day range finding study (MRID 43843507, 1995) conducted on male and
female rats given nonanoic acid in their diet at doses up to 1,834
mg/kg/day found no significant effects in regards to survival, clinical
signs, body weight gain, food consumption, hematology (red or white cell
counts, hematocrit, or hemoglobin), clinical chemistry (glucose,
triglycerides, total protein, albumin, blood urea nitrogen, creatinine,
and alanine aminotransferase (ALT)) or gross pathology. Minor changes
were detected in two of the serum chemistry parameters, but neither of
these is considered toxicologically significant nor are they likely to
represent an important risk factor in potential human exposure. 

	In the July 9, 2008 Final Rule (73 FR 39264) establishing an exemption
from the requirement of tolerance for ammonium salts of higher fatty
acids (C8-C18 saturated) the Agency concluded that a 90-day oral
toxicity study was not necessary for a dietary risk assessment. The
decision was based on the lack of effects at extremely high doses in the
range finding study, the natural occurrence of these fatty acids in
nature, the results from the acute mammalian toxicology studies, and the
unlikelihood of prolonged human exposure via the oral route due to the
proposed use patterns. 

Endocrine

    	EPA is required under the FFDCA, as amended by 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 such endocrine effects as the Administrator may designate''.
Ammonium salts of fatty acids (C8-C18 saturated) are not known endocrine
disruptors nor are they or their metabolites related to any class of
known endocrine disruptors.

Mutagenicity/Genotoxicity

 	 According to the 1992 RED, 600 μmol/L of the sodium salt of caprylic
acid, tested on guinea pig kidney cells, showed DNA inhibition.
Unscheduled DNA synthesis occurred in mouse cells treated with 35 mg/kg
of oleic acid (C9 unsaturated). Cytogenetic analysis was positive for
hamster fibroblasts treated with 2500 μg/L of oleic acid and for
Saccharomyces cerevisiae treated with 100 mg/L oleic acid. 

	Studies on pelarogonic acid; however, showed that it was non-mutgenic
when evaluated using the Ames test (Salmonella/reverse mutation assay).
Negative results were also seen when in vivo cytogenetics testing was
done using micronucleus assay. In a mouse lymphoma forward mutation
study, pelargonic acid appears to induce a weak mutagenic response at
concentrations equal to or greater than 50 milligrams/milliliter
(mg/mL). This was observed in the presence of increasing toxicity, and
may be an indication of gross chromosomal changes or damage and not
actual mutational changes within the thymidine kinese gene locus.”(68
FR 7931, February 19, 2003)

	Ammonium salts of fatty acids are not believed to be mutagenic.  When
used at high doses, reproductive and mutagenic effects were observed in
laboratory animals given potassium salts of coco fatty acids; however,
studies on one of the ammomium salts, pelargonic acid (nonanoate acid),
did not show developmental or mutagenic effects. Due to the low toxicity
of these salts, the lack of mutagenicity, and the anticipated exposure
from the use of these chemicals as inert ingredients in pesticide
products the Agency does believe ammonium salts of fatty acids (C8-C18
saturated) will be carcinogenic in humans.

Reproduction/ Developmental

	The Soap Salts RED (citing, NIOSH 1987 Registry of Toxic Effects of
Chemical Substances) notes that potassium salts of coco fatty acid, when
administered to lab animals at high doses, can cause reproductive
effects. Effects on post-implantation mortality were seen in mice given
6 g/kg on days 2-13 of pregnancy and musculo-skeletal abnormalities were
observed at doses of 600 mg/kg. 

A developmental toxicity study in rats (MRID 43843508) on pelargonic
acid (nonanoate acid) showed no adverse effect of treatment on clinical
signs, body weights, weight gain, or food/water consumption.  Female
rats were gavaged on gestation days 6-15. No fetal toxicity attributed
to the effects of treatment was observed between the treated or the
untreated controls. Evaluated parameters included survival, clinical
signs, body weight data, food and water consumption data, gross
examination of maternal tissues, uterine examination for embryo/fetal
implantation data, fetal weight and crown-rump length data, and fetal
evaluations (external, visceral, and skeletal). The mean number of
viable fetuses, early or late resorptions, implantation sites, corpora
lutea, pre- and post-implantation losses, sex ratios, and fetal body
weights were comparable to those of the control group.  The no observed
effect level (NOEL) for maternal and developmental toxicity was 1,500
mg/kg/day with the lowest observed toxicity level (LOEL) greater than
1,500 mg/kg/day. 

Neurotoxicity

	Although a neurotoxicity study was not performed, no evidence of
neurotoxicity was observed in any of the studies at doses up to 1500
mg/kg. The Agency concluded that ammonium salts of fatty acids are not
neurotoxic.

Special Consideration for Infants and Children (FQPA Safety Factor)

           FFDCA section 408 provides that EPA shall apply an additional
tenfold margin of exposure (safety) for infants and children in the case
of threshold effects to account for prenatal and postnatal toxicity and
the completeness of the data base unless EPA determines that a different
margin of exposure (safety) will be safe for infants and children. There
was no evidence of systemic toxicity or developmental toxicity at doses
up to 1500 mg/kg/day in a developmental toxicity study in rats.  No
systemic toxicity was observed at doses up to and including 1837
mg/kg/day in a 14-day toxicity study in rats.  Since there is no hazard
identified to adults and developing fetuses a quantitative FQPA
assessment was not performed.  In addition, the Agency has previously
concluded that there is a reasonable certainty that no harm to the U.S.
population, including infants and children, will result from aggregate
exposure to residues of ammonium salts of fatty acids (C8-C18 saturated)
due to their use as active ingredients in pesticide formulations. This
includes all anticipated dietary exposures and all other exposures for
which there is reliable information. 

	Although residue data is not required for a tolerance exemption it is
anticipated that the residues on food will be low due to the limiting
nature of the chemical in food use products (e.g. palatability and
herbicidal properties). Moreover, fatty acids are part of the human diet
and the exposure resulting from the use of these soap salts in pesticide
formulation are not expected to exceed the levels of naturally occurring
fatty acids in commonly eaten foods. 

ENVIRONMENTAL FATE AND DRINKING WATER

Ammonium salts of fatty acid are not likely to persist in the
environment and are expected to be indistinguishable from naturally
occurring ammonium ions and fatty acids already present in the
environment as a result of plant metabolism and formation by soil
microbes (EPA Memorandum: Jones, 2006). The expected half-life of these
fatty acids is less than one day. They adsorb strongly to soil and
sediment and are rapidly degraded by microbial organism. Microbial
degradation biotransforms fatty acids by oxidative cleavage of the
carbon chain. Both the rate of metabolism and the solubility of the
fatty acid soap salt increases with decreasing C chain length (HERA,
2003). 

Because of their strong soil adsorption and the rapid degradation of
ammonium salts of fatty acids they are not expected to reach surface
water via runoff nor are they are expected to leach into ground water.
Based on the physical/chemical properties, volatilization from soils and
water is not expected. There is no expected translocation into plants.
(Health Canada, 2008)  

According to the Agency’s 2002 document entitled ‘Reassessment of
Exemptions from the Requirement of a Tolerance for Various Salts of
Stearic Acid” (including ammonium stearate):

Although the potential to bioaccumulate is high, bioavailability is
offset by the tendency to adsorb strongly to soil and sediment
particulates. However, concentration at the water-air interface is
likely to be higher than in the water column, which results in lowering
the surface tension of the aqueous system. The lowering of the surface
tension and the hydrophobic layer at the water-air interface has the
potential to alter the physical and chemical characteristics of the
aquatic environment.

EXPOSURE ASSESSMENT

Exposure Profile

The primary route of residential exposure to ammonium salts of fatty
acids when used as inert ingredients in pesticide formulations is
through oral exposure to food.  However, the levels of ammonium salts of
fatty acids is not expected to exceed the concentration of naturally
occurring or intentional added fatty acids in commonly consumed foods.
Based on the natural presence of these compounds in the environment, the
body’s ability to metabolize them, and their low toxicity, a
qualitative approach has been used to assess exposure. 

According to the RED, oral exposure to soaps is generally self-limiting
because the taste of the soap is easily recognizable. In addition,
ammonium soap salts have a notable ammonia odor that is also limiting.
Dietary exposure would be further minimized via plant metabolism of the
chemical through oxidative pathways. (73 FR 39264, July 9, 2008)
Ammonium salts are not expected to enter drinking water because of the
high binding capability of these salts to soil and the lack of
persistence due to the rapid microbial degradation of the chemical. 

	Although dermal exposure would be possible, the low toxicity of the
chemical and the use of personal protective equipment, as would be
expected with the registration of a pesticide formulation containing
this inert ingredient, the Agency concluded that the effect from dermal
exposure will be low. Ammonium salts of fatty acids are irritating to
eye and therefore, protective eye wear would be necessary to negate the
potential for permanent eye damage. Non-occupational inhalation exposure
is not expected because ammonium salts of fatty acids do not form
aerosol particulates, have a vapor pressure near that of water, and do
not readily vaporize. (73 FR 39264, July 9, 2008)

	Occupation exposure is possible; however, due to the low toxicity of
the chemical and the use of personal protective equipment, the Agency
concluded that the risk to workers will be minimal. 

Aggregate Exposure

Section 408 of the Federal Food, Drug, and Cosmetic Act (FFDCA) directs
the Agency to evaluate aggregate exposure from “pesticide chemical
residue and to other related substances, including dietary exposure
under the tolerance and all other tolerances in effect for the pesticide
chemical residue, and exposure from other non-occupational sources”.
The expected exposure pathway for ammonium salts of fatty acid is
through the oral and the dermal routes of exposure. 

Ammonium salts of fatty acids have been granted an exemption from
tolerance as an active ingredient under 40 CFR 180.1284 in food use
products. They have also been registered for non-food use as a repellant
for rabbits and deer from forage and grain crops. (73 FR 39264, July 9,
2008) 

	In addition to exposure from naturally occurring fatty acids, exposure
to fatty acids may come from a wide variety of sources, including (but
not limited to) FDA-approved uses as food additives (2l CFR 172.860; 21
CFR 172.862; and 21 CFR 172.863), in food packaging products, or through
their use in cosmetic products. (EPA Memorandum: Boyle, 2003) 

	Because of the low oral and dermal toxicity, the rapid degradation of
the chemical, and the natural presence of fatty acids in the
environment, the Agency concluded that aggregate exposure will result in
minimal risk to all subpopulation including infants and children. Since
the inhalation route is not a likely exposure pathway the anticipated
risk from inhalation exposure is also considered minimal. (July 9, 2008,
73 FR 39264)

Cumulative Exposure

Section 408(b)(2)(D)(v) requires that, when considering whether to
establish, modify, or revoke a tolerance, 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 fatty acid salts are structurally related; however,
all are low toxicity chemicals. Therefore, the resultant risks
separately and/or combined should also be low. In addition, the rapid
environmental degradation and the body’s ability to utilize these
fatty acids as a natural part of the diet further supports the
Agency’s findings that, based on available information, there is no
concern from cumulative effects of ammonium salts of fatty acids (C8-C18
saturated)  and other substances with a common mechanism of toxicity.  

RISK CHARACTERIZATION

In addition to naturally occurring fatty acids found in the environment
and commonly consumed foods, ammonium salts of fatty acids are used as
food additives and in food packing products, cosmetics, and have been
previously approved by the EPA for use in pesticide formulations both as
active and inert ingredients. They have proven to be of low toxicity via
the oral and dermal routes of exposure. When applied for long periods of
time, they have the potential to be dermal irritants. Allergic skin
reactions may occur in some individuals; however, the Agency concluded
that allergic reactions are uncommon and transient. Soap salts are not
classified as skin sensitizers.

Studies have shown ammonium salts of fatty acids are eye irritants and
have the potential to cause permanent eye injury. Although there is
limited data available regarding the inhalation of soap salts they are
anticipated to be strongly irritating via the inhalation route of
exposure because of their known eye and skin irritation potential;
therefore, it is highly likely that they also will be strongly
irritating via the inhalation route of exposure. 

Due to the low toxicity of these soap salts and the natural occurrence
of fatty acids in the environment and food products, a chronic study was
not required. A 14-day range finding study did not produce any
significant effects of nonanoic acid (C9 saturated) given to rats at
doses up to 1,834 mg/kg/day. Ammonium salts of fatty acids are not
believed to be mutagenic.  When used at high doses, reproductive and
mutagenic effects were observed in laboratory animals given potassium
salts of coco fatty acids; however, studies on one of the ammomium
salts, pelargonic acid (nonanoate acid), did not show developmental or
mutagenic effects. Due to the low toxicity of these salts, the lack of
mutagenicity, and the anticipated exposure from the use of these
chemicals as inert ingredients in pesticide products the Agency does not
believe ammonium salts of fatty acids (C8-C18 saturated) will be
carcinogenic in humans. 

Ammonium salts of fatty acids have the potential to cause dermal, eye,
and inhalation effects. Due to the vapor pressure and the unlikelihood
of fatty acid forming aerosol particulates, the anticipated risk from
the inhalation route of exposure is not expect to cause adverse harm to
occupational and residentially exposed individuals. Dermal and ocular
exposure is expected to be negated by the use of personal protective
equipment (e.g. chemical resistant gloves, goggles, face shield, etc). 

According to the 1992 EPA RED on soap salts, oral exposure to soaps is
generally self-limiting, because the taste of soap is easily recognized
and unpleasant. In addition, ammonium soap salts have an ammonia odor
that is limiting. Because of their strong soil adsorption and the rapid
degradation of ammonium salts of fatty acids they are not expected to
reach surface water via runoff nor are they expected to leach into
ground water. Due to the self limiting nature of these chemical and
their natural occurrence in the environment it is highly unlikely that
concentrations needed to invoke a toxic response would be reached;
therefore, the Agency believes that there would not be any reproductive
or mutagenic effects for this inert ingredient. 

Fatty acids are an essential component of the mammalian diet and the
body is able to metabolize these soap salts and use them as an energy
source. Because of their natural occurrence in the environment, their
rapid environmental degradation, and their presence in commonly eaten
foods (both naturally and intentionally added) the anticipated exposure
from the use of ammonium salts of fatty acids as inert ingredients is
expected to be minimal and is not anticipated to significantly increase
the overall exposure to all populations including infants and children. 

Ammonium salts of fatty acids are expected to be only minimally toxic to
nontarget organisms, with the exception of aquatic invertebrates.
“Soap salts of fatty acids are slightly toxic to birds on an acute
basis and are practically non-toxic to birds on a dietary basis,
slightly toxic to fish, and highly toxic to aquatic invertebrates”.
(EPA Memorandum: Jones, 2006) Appropriate precautionary labeling of end
use products containing ammonium soap salts will further minimize
potential exposure and mitigate risk to humans and nontarget organisms. 

VIII.      ECOTOXICITY AND ECOLOGICAL RISH CHARACTERIZATION

Evaluation of the ecotoxicity of ammonium salts of fatty acids was
previously performed by the Agency and has been outlined in the 1992 RED
on Soap Salts and the 2006 Biopesticide Registration Action Document
(BRAD) on ammonium nonanoate.  It was determined that ammonium soap
salts are slightly toxic to birds on an acute basis and are practically
non-toxic to birds on a dietary basis (see Table 2). Although the study
used a test substance that was only 14.65% pure, the Agency feels that
the exposure to bird species will not be significantly greater than the
natural occurrence of fatty acids in the environment.  In addition, the
avian diet calls for fatty acids; therefore, mechanisms are in place to
metabolize these chemical in the body. Based on this information the
Agency does not feel there is increased risk to birds or other
terrestrial animals. 

Ammonium salts of fatty acids are slightly toxic to fish and highly
toxic to aquatic invertebrates (see Table 2). Ammonium salts of fatty
acids are readily biodegradable and are rapidly metabolized by soil
microorganisms (half-life < 1 day) and; therefore, are not expected to
persist in the environment. Because the product is not intended for
direct application to aquatic sites, exposure to aquatic organisms (fish
and invertebrates) is further mitigated.

As would be expected for a herbicide, ammonium soap salts of fatty acids
are toxic to freshwater algae and aquatic plants. However, based on the
intended use pattern (will not be applied directly to water, areas where
surface water is present, or to intertidal areas below the mean high
water mark) and the high soil binding properties of these salts, it is
not expected that ammonium soap of fatty acids will enter aquatic
systems; therefore, risk to aquatic plants and algae is expected to be
negligible. (Health Canada, 2008)

In addition to their herbicidal properties, soap salts also have
insecticidal properties. There are relatively selective in toxicity
based on the insect species and stage of development. Soft-bodied
insects such as aphids, whiteflies, and mealybugs are more susceptible
to desiccation. Insects with more durable exteriors such as ladybird
beetles are least effect whereas insects in the immature, flightless
stage of development are more vulnerable to the effects of this the
chemical ingredient. (NPTC, 2001) The exposure to insects from the use
of ammonium salts of fatty acids as inert ingredients in pesticide
formulations is expected to be low. 

Table 2: Non-target Organism Data from the Soap Salts RED (EPA, 1992) 

Data Requirement 	LD50\LC50\EC50 	Test Material	Toxicity Category 
Citation 

Avian Acute Oral Toxicity 

OPPTS 850.2100 	>2150 mg/kg (bobwhite quail) 	14.65% pure	Slightly toxic
	MRID 41767112 

Avian Dietary Toxicity 

OPPTS 850.2200 	>5000 mg/kg (bobwhite quail & mallard duck) 	14.65% pure
Practically non-toxic 	MRID 41767113, -14 

Acute Fish Toxicity 

OPPTS 850.1075 	96-hr: 18.06 mg/L (rainbow trout) 

96 hr: 35.35 mg/L1 (bluegill sunfish) 	Potassium salt technical grade
Slightly toxic 	EPA. (1992) 

Aquatic Invertebrates 

OPPTS 850.1010 	48 hr: 0.57 mg/L (D. magna) 	Potassium salt technical
grade	Highly toxic 	MRID 400662-00 

Non-Target Plants 

OPPTS 870.2500 	No data available for any soap salt but product is also
use as a terrestrial herbicide 	-	- 	- 

1 potassium soap salt used; considered by the Agency to be equivalent to
ammonium soap salt for ecorisk assessment purposes (EPA, 1992).

2 sodium decanoate (C10 fatty acid salt) was test substance.

Bibliography 

Health Canada Pest Management Regulatory Agency, (2008) Proposed
Registration Decision: Ammonium Soap of Fatty Acid (PRD2008-12),
received via email from Health Canada, Government of Canadian on May 5,
2009

HERA, (2002) Human & Environmental Risk Assessment on ingredients of
European household cleaning products: Fatty Acid Salts (Soap) Human
Health Risk Assessment. Retrieved on 5/23/09 from   HYPERLINK
"http://www.heraproject.com/files/5-HH-04-HERA%20Fatty%20acid%20salts%20
HH%20web%20wd.pdf" 
http://www.heraproject.com/files/5-HH-04-HERA%20Fatty%20acid%20salts%20H
H%20web%20wd.pdf 

HERA, (2003) Human & Environmental Risk Assessment on ingredients of
European household cleaning products: Fatty Acid Salts (Soap)
Environmental Risk Assessment. Retrieved on 5/24/09 from
http://www.heraproject.com/files/5-E-04-%20HERA%20Fatty%20acid%20salts%2
0Env%20web%20wd.pdf

MRID 43843503, (1993) Holbert, M., Acute Inhalation Toxicity Study in
Rats on Pelargonic Acid. Stillmeadow Inc, Study Number: 0251-93.
Completion Date- August 11, 1993

MRID 43843507, (1995) Kuhn, J., Range Finding for a 90-Day Rat Oral
Toxicity (diet) on Pelargonic Acid. Stillmeadow, Inc., Study Number:
1941-95. Completion Date- August 29, 1995

MRID 43843508, (1994) Wakefield, A.E., Teratology Screen in Rats on
Pelargonic Acid. Hazelton Washington, Inc. Laboratory Project
Identification: HWA 2689-101. Completion Date- April 22, 1994

National Pesticide Telecommunication Center (NPTC), (2001) Potassium
Salts of Fatty Acids (Technical Fact Sheet). Retrieved on 5/23/09 from  
HYPERLINK "http://npic.orst.edu/factsheets/psfatech.pdf" 
http://npic.orst.edu/factsheets/psfatech.pdf  

US Environmental Protection Agency, (2003, September 27) Memorandum from
Kathryn Boyle, Lower Toxicity Pesticide Chemical Focus Group to Susan
Lewis, Minor Use, Inerts, and Emergency Response Branch,
“Recommendations for Tolerance Reassessment”. Office of Pesticide
Programs, Registration Division

US Environmental Protection Agency, (2002, July 31) Memorandum from
Kathryn Boyle and Kerry Leifer, Inert Ingredient Focus Group (IIFG) to
Robert Forrest, Minor Use, Inerts, and Emergency Response Branch,
“IIFG Decision Documents on Reassessment of Exemptions from the
Requirement of Tolerance for Various Salts of Stearic Acid”. Office of
Pesticide Programs, Registration Division

US Environmental Protection Agency, (2006, May 17) Memorandum from
Russell Jones, Biochemical Pesticides Branch (BPB) to Raderrio Wilkins
(BPB). Office of Pesticide Programs, Biopesticide & Pollution Prevention
Division 

US Environmental Protection Agency, (2008) Biopesticides Registration
Action Document (BRAD), Ammonium Nonanoate (PC code 031802) Office of
Pesticide Programs, Biopesticide & Pollution Prevention Division 

US Environmental Protection Agency, (1992) Reregistration Eligibility
Document (RED): Soap Salts. Office of Prevention, Pesticides, and Toxic
Substances

US Environmental Protection Agency, (2008) Final Rule for Ammonium Soap
Salts of Higher Fatty Acids (C8–C18 saturated; C8–C12 unsaturated);
Exemption from the Requirement of a Tolerance. Federal Register Vol. 73,
No. 132, July 9, 2008, FR 39264

US Environmental Protection Agency, (2003) Final Rule for Pelargonic
Acid (Nonanoic Acid); Exemption from the Requirement of a Pesticide
Tolerance. Federal Register Vol. 68, No. 33, February 19, 2003, FR 7931

	

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UNITED STATES ENVIRONMENTAL PROTECTION AGENCY

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