UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
WASHINGTON, D.C. 20460
OFFICE OF
PREVENTION, PESTICIDES
AND
TOXIC SUBSTANCES
Fax On Demand
Item Number
January, 8 2001
PESTICIDE REGISTRATION (PR) NOTICE 2001-2
NOTICE TO MANUFACTURERS, PRODUCERS, FORMULATORS, AND
REGISTRANTS OF PESTICIDE PRODUCTS
ATTENTION: Persons Responsible for the Registration and Reregistration of Pesticides
Acute Toxicity Data Requirements For Granular Pesticide Products, Including Those
SUBJECT:
With Granular Fertilizers in the Product.
This PR Notice announces guidance intended to streamline the acute toxicity review and
classification process for certain granular pesticide products, including those products that contain
granular fertilizers. Based on OPP's extensive experience with granular pesticide products, the Agency
believes that an effective precautionary labeling policy can be implemented without testing of each
individual product. Please refer to Section IV on how OPP will implement this guidance. This
guidance is supported by a large toxicology data base and involves the application of sound scientific
principles. This guidance should achieve the following objectives: (1) significantly reduce the number
of animals subject to testing; (2) reduce the use of Agency resources while maintaining protection of
the public health and environment; and (3) decrease the time required to register qualifying granular
pesticide products. This notice is effective immediately, but comments will be accepted for 30 days,
after which the Agency may revise the notice.
Background
I.
FIFRA and Agency regulations require that each pesticide product bear on the label danger,
warning or caution statements. The signal word and precautionary statements are based on the acute
toxicity category of the pesticide, which is designed to protect the public health. This labeling informs
pesticide users/workers of the acute health hazards from exposure to the pesticides and what
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precautions should be taken to mitigate adverse effects. To determine the appropriate human hazard
signal word and label instructions the Agency evaluates six acute toxicological studies: acute oral
toxicity (870.1100), acute dermal toxicity (870.1200), acute inhalation toxicity (870.1300), eye
irritation (870.2400), dermal irritation (870.2500) and dermal sensitization (870.2600). The Series
870 numbers are the new guideline numbers which previously appeared in 40 CFR 158.340 as
guidelines 搂 81-1 through 搂 81-6.
Pesticide products are generally composed of the active ingredient(s) and inert ingredient(s).
This notice refers to those granular pesticide products that are composed of a registered source
product at less than 10% active ingredient, one or more clearly recognized innocuous (List 4) inert
carrier(s) and/or a fertilizer component(s) at greater than 90% and a sticker/binder (5% of the
formulation). Innocuous inerts (List 4) are carriers that are considered to be chemically inactive based
on available information and experience. Inerts in this category include corncobs, clay, limestone, sand
or food, etc.
This policy only applies to granular pesticide products and granular fertilizer pesticide products.
The Agency will not extrapolate for other products, because; 1) the LD50 is imprecise (dilution does not
always equal reduced toxicity); 2) a complete dose response curve, required at a minimum, is rarely
available; and 3) the Agency does not have a database that indicates that dilution always means
reduced toxicity.
II. Products Affected By the Guidance
A. Granular Pesticide Products
For purposes of this guidance, the Agency defines granular pesticide products to include those
products composed of less than 10% of a registered active ingredient(s), greater than 90% of List 4
inert carrier(s) (corn cobs, clay, limestone, sand, food) and a minimal amount of sticker/binder (5% or
less of the formulation).
If the acute toxicity profile of the registered source product(s) is in Category III or IV for all
endpoints, then the proposed pesticide product may use the acute toxicity profile of the registered
source product.
In addition, for systemic toxicity (i.e. acute oral, dermal and inhalation) endpoints, it is
acceptable to extrapolate Category III data down to Category IV. This extrapolation for acute
systemic toxicity is based on dilution. The assumption is that the innocuous inert does not contribute to
the toxicity, and thus acts as a diluent. If an extrapolated dose is borderline between two toxicity
categories, the Agency will label with the more restrictive toxicity category.
If the primary eye and dermal irritation effects are classified in Category III and/or IV, the
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categories of the source registered product may be used for the proposed pesticide product and the
toxicity profile will be complete.
EXAMPLE 1:
Source Product Study Toxicity Category Toxicity Category for Granular Product
Acute oral LD50 III IV
Acute dermal LD50 III IV
Acute inhalation LD50 III IV
Primary Eye Irritation III III
Primary Skin Irritation III III
Skin Sensitization Non-sensitizer Non-sensitizer
If the acute LD50, dermal LD50, Inhalation LD50, primary dermal and/or eye irritation effects for
the registered product(s) are classified in Category I and/or II, then the Agency will not accept
calculations that bridge down from these categories and additional data would be required for the
proposed pesticide product. Either these studies would need to be submitted, or the registrant would
need to cite data on a substantially similar product.
EXAMPLE 2:
Source Product Study Toxicity Category Toxicity Category for Granular Product
Acute oral LD50 II II
Acute dermal LD50 II II
Acute inhalation LD50 I I
Primary Eye Irritation III III
Primary Skin Irritation III III
Skin Sensitization Non-sensitizer Non-sensitizer
For dermal sensitization, if a granular product contains any ingredient which is a known
sensitizer, the formulated product would be labeled as a sensitizer. If the product is not a dermal
sensitizer, and there are no known dermal sensitizers in the product, a dermal sensitization study may be
waived and the product will not require sensitization labeling. If dermal sensitization data on a
substantially similar product indicates no dermal sensitization at low concentrations, these data may be
cited in support of the product. This determination will be made with data on the active ingredient or
information provided by the registrant on an inert (e.g., Material Safety Data Sheet - MSDS). If the
registrant knows there is a sensitizing component and can justify the finding, the Agency will not require
testing.
B. Granular Fertilizer Pesticide Products
For purposes of this guidance, EPA defines granular fertilizer pesticide products to include
those products composed of less than 10% of a registered active ingredient(s), greater than 90%
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granular fertilizer components plus clearly recognized innocuous (List 4) inert carrier(s), and a minimal
amount of sticker/binder (5% or less of the formulation).
The fertilizer components of these products are considered analogous to the innocuous inert
described above with the exception of eye irritation. In some cases, fertilizer products are more
irritating to the eye than the comparable non-fertilizer granular products. Therefore, the primary eye
irritation results may not be bridged under this guidance. A separate eye irritation study is expected to
be performed with the pesticide/fertilizer formulation containing the highest free level of nitrogen. If, at
some point, the nitrogen content of the fertilizer component is increased above the tested level, a new
primary eye irritation study will be required.
III. Exclusions To This PR
Rodenticide baits are not included in this policy. In the Agency's experience, rodenticide baits
are often more toxic than would be predicted using the bridging methods outlined above. In general,
the Agency will continue to allow similar baits to use one set of data for purposes of precautionary
labeling.
IV. What Registrants And Applicants Should Do
The registrant should submit the following information with the application: (1) request in writing
that the Agency apply this guidance to their product; (2) the acute toxicity profile (with corresponding
MRID Numbers) for the registered product(s); and (3) the current label for the registered product(s).
The Agency will use this information to determine an acute toxicity profile for the product.
VI. Non-Binding Statement
This PR Notice provides guidance to EPA and to pesticide registrants. This notice is not
binding on either EPA or pesticide registrants, and EPA may depart from the guidance provided in
individual circumstances. Likewise. pesticide registrants may assert that the guidance is not appropriate
for a specific pesticide or situation.
VI. Additional Information
You may contact: John Redden
Registration Division (7505C), USEPA
401 M Street, SW
Washington, DC 20460
(703) 305-1969
redden.john@epa.gov
James J. Jones, Director
Registration Division
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