United States
Environmental Protection
Agency
Prevention, Pesticides
And Toxic Substances
(7508W)
EPA-738-F-94-030
September 1994
R.E.D. FACTS
Limonene
Pesticide
Reregistration
Use Profile
All pesticides sold or distributed in the United States must be
registered by EPA, based on scientific studies showing that they can be used
without posing unreasonable risks to people or the environment. Because of
advances in scientific knowledge, the law requires that pesticides which
were first registered years ago be reregistered to ensure that they meet
today's more stringent standards.
In evaluating pesticides for reregistration, EPA obtains and reviews a
complete set of studies from pesticide producers, describing the human
health and environmental effects of each pesticide. The Agency imposes
any regulatory controls that are needed to effectively manage each
pesticide's risks. EPA then reregisters pesticides that can be used without
posing unreasonable risks to human health or the environment.
When a pesticide is eligible for reregistration, EPA announces this and
explains why in a Reregistration Eligibility Decision (RED) document. This
fact sheet summarizes the information in the RED document for
reregistration case 3083, limonene.
Limonene is a naturally occurring chemical which is used in many
food products, soaps and perfumes for its lemon-like flavor and odor.
Limonene also is a registered active ingredient in 15 pesticide products used
as insecticides, insect repellents, and dog and cat repellents.
Pesticide products containing limonene are used for flea and tick
control on pets, as an insecticide spray, an outdoor dog and cat repellent, a
fly repellent tablecloth, a mosquito larvicide, and an insect repellent for use
on humans. Formulations include ready-to-use solutions, emulsifiable
concentrates, granulars and impregnated material. Limonene is applied by
hand as needed, both indoors and outdoors. Use practice limitations include
a label prohibition against use on weanling kittens and a caution against use
of undiluted product.
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Regulatory
History
Human Health
Assessment
Limonene was first registered as a insecticide in the U.S. in 1958. It
was registered as an antimicrobial in 1971, and as a dog and cat repellent in
1983. In May 1988, EPA announced that limonene is considered an inert
rather than an active ingredient when used in antimicrobial products (please
see 40 CFR 153.139(a)). In April 1994, limonene was granted an
exemption from the requirement of a tolerance (or maximum residue limit)
when it is an inert ingredient used as a solvent or fragrance in pesticide
formulations (please see 40 CFR 180.1001 (c), (e)). The Food and Drug
Administration (FDA) lists limonene as Generally Recognized as Safe
(GRAS) as a food additive or flavoring and a fragrance additive (please see
21 CFR 182.60). Currently, 15 limonene pesticide products are registered.
Limonene is among those pesticide active ingredients for which a
reduced set of generic data requirements is appropriate for registration or
reregistration. Limonene is naturally occurring, has been established as an
inert, is exempt from the requirement of a tolerance, and is recognized as
safe by FDA. Its effects are well known and documented in scientific
literature; additional testing would not likely provide any new findings.
Adequate information is available to characterize its risks to humans and
animals.
Toxicity
Limonene is of relatively low acute toxicity taken orally. It is a
dermal irritant when applied at high concentrations and may cause dermal
sensitization. A 90-day dermal toxicity study using the formulated product
is required as confirmatory data to support reregistration of the insect
repellent that is to be applied directly to human skin.
A subchronic study by the National Toxicology Program (NTP) using
rats and mice resulted in decreased body weights, kidney disease and
mortality at the highest dose tested. A chronic toxicity study by NTP using
rats resulted in decreased body weight, kidney disease and kidney tumors,
which occurred due to a species-specific mechanism. Limonene is not
considered a human carcinogen, a developmental toxicant or mutagenic.
Dietary Exposure
Limonene occurs naturally in citrus and other fruits, vegetables, meats
and spices. It also is used in a variety of foods and beverages (as well as in
soaps and perfumes) to add lemon-like flavor and aroma. FDA considers
limonene Generally Recognized as Safe (GRAS) as a food additive or
flavoring, and as a fragrance additive. EPA has granted limonene an
exemption from the requirement of a tolerance when it is used as an inert
ingredient in pesticide formulations, and when used as an insect repellent
tablecloth.
As a pesticide active ingredient, limonene is not registered for food or
feed crop uses and is not expected to result in dietary exposure.
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Environmental
Assessment
Occupational and Residential Exposure
People and pets may be exposed to limonene during and after
application in household settings. Human exposure may occur during
application of pet flea products, animal repellent granules or insecticide
sprays, or during use of insect repellent impregnated tablecloths.
Toxicologic concerns for humans from these exposures include skin
irritation and sensitization. Ocular irritation also may occur if limonene
products accidentally enter the eye and are not washed away.
Limonene is used in several shampoo, dip and spray products applied
dermally to domestic animals to control fleas and ticks. Adverse reactions
have been reported in a small percentage of animals, especially cats,
following exposure to limonene products. Kittens and young cats seem to
be most sensitive. Product labels bear precautionary statements warning of
the potential for dermal irritation, prohibiting use on weanling kittens, and
cautioning against use of undiluted product on pets.
Human Risk Assessment
Dietary exposure to limonene is not a concern. Limonene occurs
naturally in foods, is used as a flavoring agent, is generally recognized as
safe by FDA, and has only one food-related pesticide use (as an insect
repellent impregnating tablecloths) that EPA has exempted from tolerance
requirements.
People may be exposed to limonene when applying flea and tick
control shampoos, dips or sprays to their pets, when applying animal
repellent granules or insecticide sprays, or when using impregnated
tablecloths. Skin irritation and sensitization or eye irritation may occur
from these uses. In addition, adverse reactions may occur in some pets,
especially cats, treated with the flea and tick control products. Additional
precautionary statements are required on limonene product labeling to
reduce the potential for adverse effects among users and treated pets.
Environmental Fate
Limonene is insoluble and is expected to be stable in water.
Ecological Effects
Technical limonene is practically nontoxic to birds on a subacute
dietary basis, and is slightly toxic to freshwater fish and invertebrates on an
acute basis. The formulated product is practically nontoxic to birds on an
acute and subacute dietary basis. It is practically nontoxic to freshwater fish
and slightly toxic to freshwater invertebrates on an acute basis. Based on
acute toxicity data using rats, limonene is practically nontoxic to mammals.
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Additional Data
Required
Product Labeling
Changes Required
Ecological Effects Risk Assessment
Potential risk to birds might occur from ingesting limonene granules
spread on lawns, sidewalks or driveways, or from consuming insects
contaminated with limonene. However, based on the lack of toxicity of
limonene to birds, little risk is anticipated.
Similarly, mammals are not likely to ingest a sufficient quantity of
limonene granules to be at risk, particularly since limonene is practically
nontoxic to mammals.
The mosquito larvicide use of limonene produces an oily film that is
expected to dissipate rapidly, posing no major ecological concern for
freshwater invertebrates or other aquatic species. Minimal risks to aquatic
species, including endangered aquatic species, are expected from runoff into
pond water from applications of the granular product.
EPA is requiring a 90-day dermal toxicity study for the recently
registered limonene personal insect repellent product, to confirm its
regulatory assessments and conclusions. The Agency also is requiring
product-specific data including product chemistry and acute toxicity studies,
revised Confidential Statements of Formula (CSFs) and revised labeling for
reregistration.
All limonene end-use products must comply with EPA's current
pesticide product labeling requirements, and with the following:
Environmental Hazard Statements
End-use products with the mosquito larvicide use must bear the following
statement:
"Do not contaminate water when disposing of equipment washwater or
rinsate. Consult with your State Agency in charge of fish and game
before applying to public waters to determine if a permit is needed."
End-use products without the mosquito larvicide use must bear the following
statement:
"Do not apply directly to water, or to areas where surface water is
present or to intertidal areas below the mean high-water mark. Do not
contaminate water when disposing of equipment washwater or
rinsate."
Precautionary Statements
To reduce the risk of adverse effects which occasionally occur in pets
exposed to limonene flea and tick control products, and to reduce risks of
skin irritation/ sensitization to product users, the following strengthened
statements are required on labels of products intended for use on domestic
animals:
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Regulatory
Conclusion
For More
Information
Add: "Applicators of flea and tick dip (concentrates), spray or
shampoo products are to use protective gloves to reduce the risk of
dermal irritation or dermal sensitization."
Add: "Flea dip concentrates may harm animals when used at greater
strength than specified on the label."
Change the age for product use on kittens/puppies to several months
or a year.
Change the statement, "Use with care on nursing animals," to "Do not
use on nursing animals or any animal which is in poor health."
Provide a list of symptoms which may occur when animals are
sensitive to the product, to the precautionary statement, "Individual
animals may be more sensitive to the product."
The use of currently registered pesticide products containing limonene
in accordance with approved labeling will not pose unreasonable risks or
adverse effects to humans or the environment. Therefore, all uses of these
products are eligible for reregistration.
These limonene products will be reregistered once the required
confirmatory data, product-specific data, revised Confidential Statements of
Formula and revised labeling are received and accepted by EPA.
EPA is requesting public comments on the Reregistration Eligibility
Decision (RED) document for limonene during a 60-day time period, as
announced in a Notice of Availability published in the Federal Register. To
obtain a copy of the RED document or to submit written comments, please
contact the Pesticide Docket, Public Response and Program Resources
Branch, Field Operations Division (7506C), Office of Pesticide Programs
(OPP), US EPA, Washington, DC 20460, telephone 703-305-5805.
Following the comment period, the limonene RED document will be
available from the National Technical Information Service (NTIS), 5285
Port Royal Road, Springfield, VA 22161, telephone 703-487-4650.
For more information about EPA's pesticide reregistration program,
the limonene RED, or reregistration of individual products containing
limonene, please contact the Special Review and Reregistration Division
(7508W), OPP, US EPA, Washington, DC 20460, telephone 703-308-8000.
For information about the health effects of pesticides, or for assistance
in recognizing and managing pesticide poisoning symptoms, please contact
the National Pesticides Telecommunications Network (NPTN). Call toll-
free 1-800-858-7378, between 8:00 am and 6:00 pm Central Time, Monday
through Friday.
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