United States Prevention, Pesticides EPA-738-F-96-005
Environmental Protection And Toxic Substances December 1995
Agency (7508W)
R.E.D. FACTS
Gibberellic Acid
PGStJCJdG All pesticides sold or distributed in the United States must be
R0TGClistration 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 before November 1, 1984, 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 develops
mitigation measures or regulatory controls needed to effectively reduce 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 explains the basis
for its decision in a Reregistration Eligibility Decision (RED) document.
This fact sheet summarizes the information in the RED document for
reregistration case number 4110, Gibberellic Acid.
USG ProfilG F°r the purpose of this RED, the following compounds will be
considered collectively under the term "Gibberellic Acids": Gibberellic Acid
(GA3); related isomers known as Gibberellins (GA4 + GA7); and the salt of
the acid, Potassium Gibberellate.
Gibberellic Acids are naturally occurring plant hormones.
Gibberellic Acids are used in agriculture as plant regulators to stimulate
both cell division and cell elongation that affect leaves as well as stems
(eventually affecting fruit development and fruit set). Applications of
Gibberellic Acids can also hasten plant maturation and seed germination.
Because they are naturally occurring compounds and have a nontoxic mode
of action in target plants, Gibberellic Acid and related isomers have been
classified as biochemical pesticides.
Gibberellic Acids are applied to growing crops (field crops, small
fruits, vines and tree fruits), ornamental and shade tress, and ornamental
plants, shrubs and vines. The Agency has determined that the uses of
Gibberellic Acids, as currently registered, will not cause unreasonable risk
to humans or the environment. These uses are eligible for reregistration.
However, six of the uses currently on the labels are not covered by either
the exemption from tolerance (40 CFR 180.1098), or a numeric tolerance
-------
(40 CFR 180.224). The Agency plans to propose to exempt from tolerance
many plant regulators, including Gibberellic Acids, when used in low doses.
This exemption will apply only when application rates do not exceed 250
grams of ai/acre/year. The Agency believes this action does not present
unreasonable risks because it is based on Gibberellic Acid's low acute
mammalian toxicity, low use rates, naturally occurring exposure in the diet
from numerous plant sources, and minimal exposure in the diet derived
from consumption of treated commodities under the proposed maximum
label use rate.
Formulation Types Registered:
Formulations include tablets, soluble granules, and liquid concentrate.
Method and Rates of Application:
Gibberellic Acid (GA3) and Gibberellin Mixture (GA4 + GA7):
Gibberellic Acid (GA3) and Gibberellin Mixtures (GA4 + GA7)
may be applied by aircraft, irrigation systems, ground spray
equipment, seed treatment or soil incorporation.
Potassium Gibberellate:
Potassium Gibberellate may be applied by hand-held spray
equipment and as a seed treatment.
Regulatory
History
Use Practice Limitations
For terrestrial uses:
"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 apply through any type of irrigation system."
The plant regulator, Gibberellic Acid, was initially registered in
the United States in 1947 as PROVIDE GROWTH REGULATOR
SOLUTION (EPA Reg. No. 275-2) for applications to apple trees as a
means of controlling fruit russet fungus. Gibberellic Acids are naturally
occurring plant hormones that act as plant regulators, promoting cell
division and cell elongation leading to increased fruit set and crop yields.
During Phase 4 of the accelerated pesticide reregistration process, the
data base for Gibberellic Acids was evaluated and determined to be
inadequate in satisfying certain requirements for biochemical pesticides,
which include plant growth regulators. A DCI was issued in September
1993 to fill the outstanding data gaps.
-------
The biochemical data requirements for the reregistration of Gibberellic
Acids have been satisfied through the submission of data in response to the
1993 DCI. These data are adequate to support the registration of Gibberellic
Acids on all RAC's, as well as all of the currently registered uses.
Human Health Toxicity
AsS6SSm6nt In studies using laboratory animals, Gibberellic Acids generally have
been shown to be of low acute toxicity. The acute dermal toxicity
(LD50 > 2g/kg), acute inhalation (negative LC50 at 2.98mg/l and LC50
>5.9mg/l), eye irritation (all cleared in 7 days) place Gibberellic Acids in
Toxicity Category III (the second lowest of four toxicity categories).
Gibberellic Acids acute toxicity (LD50 > 5g/kg), dermal irritation (mild to
slight), and dermal sensitization (mild sensitizer) place it in Toxicity
Category IV (the lowest of four toxicity categories).
[NOTE: For acute oral, dietary, mammalian/avian/aquatic toxicity:
Category I = very highly or highly toxic
Category II = moderately toxic
Category III = slightly toxic
Category IV = practically non-toxic]
Subchronic Toxicity
Two subchronic oral toxicity studies for Gibberellic Acids were
reviewed in connection with the RED process. In the first subchronic
dietary study there was a NOEL of 10,000 ppm and a LOEL of 50,000 ppm
based on the occurrence of soft stools in both sexes of rats and increased
BUN levels, liver and kidney weights in females. In the second study, there
was a NOEL of 10,000 ppm and a LOEL of 25,000 ppm based on
alterations in clinical chemistry, decreased food consumption, decreased
body weights, increases in relative organ weights (brain, kidney, testis) and
gross histopathological changes in the kidney.
Developmental Toxicity
Two developmental toxicity studies for Gibberellic Acids were
reviewed for this RED. In the first study, rats were dosed at 0, 100, or
1,000 mg/kg/day for 8 weeks without significant chemical, hematological or
pathologic evidence of toxicity. The maternal toxicity NOEL was greater
than 1,000 mg/kg/day (HTD). In the second study, rabbits were dosed at 0,
300, or 1,000 mg/kg/day; the highest concentration caused increased
mortality, abortion rates, clinical signs of toxicity, and gross pathological
observations. The maternal and developmental NOELs were established at
300 mg/kg/day.
-------
Mutagenicity
Gibberellic Acid (GA3) Salmonella typhimurium test strains TA 98, TA
100, TA 1535, TA 1537, and TA 1538 at concentrations ranging from 0 to
10,000 ug/plate with negative test results up to limit dose of 5,000 and 10,000
ug/plate. The mutagenicity of Gibberellins (GA4 + GA7) was tested in an Ames
assay with Salmonella typhimurium test strains TA 98, TA 100, TA 1535, TA
1537, and TA 1538 at concentrations ranging from 0 to 10,000 ug/plate. Test
results were negative up to 10,000 ug/plate in the standard set of five histidine
negative strains of Salmonella typhimurium LT2.
A mouse-micronucleus assay on Gibberellins (GA4 + GA7) indicated that no
increased incidence of micronucleated-polychromatic erythrocytes (m-PCE) were
found at levels up to 1200 mg/kg.
An unscheduled DNA synthesis in rat hepatocytes conducted with
Gibberellins technical 90% (GA4 + GA7) was negative for induction of UDS up to
1260 ug/ml, the limit of solubility (MRID 40261603). A second unscheduled
DNA synthesis in rat hepatocytes conducted with Gibberellins also was negative.
Dietary Exposure
People may be exposed to residues of Gibberellic Acids through the diet.
Tolerances or maximum residue limits have been established for Gibberellic Acid
(GA3) and Gibberellins (GA4 + GA7)for the following commodities (refer to 40
CFR 180.224).
Gibberellic Acid (0.15 ppm) Gibberellin Mixture (0.5 ppm)
Artichokes Leafy vegetables Apples
Blueberries Stone fruits
Citrus fruits Sugarcane
Grapes Sugarcane fodder
Hops Sugarcane forage
-------
An exemption from the requirement of a tolerance (40 CFR 180.1098) has
been established for Gibberellins (specifically GA3) when used as a plant regulator
at less than 20g ai/acre in or on the following RAC's:
Barley Cucumbers Oranges Strawberries
Beans Grapefruit Peanuts Squash
Beets (sugar) Lemons Peppers Sugarcane
Broccoli Lettuce Potatoes Tomatoes
Brussels sprouts Melons Rice Turnips
Cabbage Mints Rye Watercress
Cauliflower Mustard greens Sorghum (milo) Wheat
Corn (all) Oats Soybean
Cotton Onions Spinach
The Agency plans to propose an exemption from the requirements of a
tolerance for certain Gibberellic Acids (specifically Gibberellic Acid (GA3), a
mixture of Gibberellins (GA4 + GA7), and Potassium Gibberellate) for all RAC's
when treated with application rates under 250 g ai/acre/year. The Agency believes
this action does not present unreasonable risks because it is based on Gibberellic
Acids' low mammalian toxicity, low use rates, natural background dietary
exposure and minimal exposure in the diet derived from consumption of treated
commodities under the proposed use rates.
Occupational and Residential Exposure
Based on the application methods listed on the product labels, the potential
for eye, dermal, and inhalation exposure to agricultural workers does exist.
However, the lack of acute toxicity (i.e., Gibberellic Acids are in Toxicity
Categories III and IV) does not trigger additional requirements for evaluation of
worker exposure over the existing precautionary labeling currently required under
the provisions of the Worker Protection Standards.
Human Risk Assessment
Since exposures and subsequent risks from Gibberellic Acids are not
expected, any potential risks from exposures to treated plants will be mitigated by
use of baseline personal protective equipment required by the Worker Protection
Standards, supplemented by specific precautionary labeling required by this RED.
Post-application reentry workers are required to observe a 12 hour Restricted
Entry Interval. Because of Gibberellic Acid's low mammalian toxicity, however it
is a candidate for a reduced reentry interval from 12 hours to 4 hours.
-------
Environmental
Assessment
Based on a review of all available ecological data, exposure
information, and Gibberellic Acids non-toxic mode of action, the Agency
expects that applications of Gibberellic Acids will pose minimal risk to
nontarget wildlife and fish.
Environmental fate studies for biochemicals are not imposed unless
adverse effects are observed in ecological effects data. Since no adverse
effects are anticipated, the Agency will not, at this time, impose any
environmental fate data requirements for the currently registered uses of
Gibberellic Acids.
Additional Data
Required
Product Labeling
Changes
Required
Regulatory
Conclusion
For More
Information
EPA is requiring the a revised Confidential Statement of Formula
(CSF) and revised product labeling for reregistration.
The Agency has reexamined the toxicological data base for
Gibberellic Acid s and concluded that the current precautionary labeling
(i.e., Signal Word , Statement of Practical Treatment, and other label
statements associated with mitigating risks) adequately mitigate any risks
associated with the use of this plant regulator.
Based on the reviews of the generic data for Gibberellic Acid, the
Agency has sufficient information on health effect and potential for causing
adverse effects to human s or the environment. Therefore, the Agency
concludes that the use of currently registered products containing
Gibberellic Acids in accordance with approved labeling will not pose
unreasonable risks or adverse effects to humans or the environment. Certain
uses of Gibberellic Acids that have neither a tolerance or an exemption from
tolerance requirements (i.e., food use/commodities not listed in 40 CFR
180.224 or 40 CFR 180.1098) will become eligible for reregistration when
the proposed tolerance exemption is issued as a final rule in 1996.
EPA is requesting public comments on the Reregistration Eligibility
Decision (RED) document for [name] 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.
Electronic copies of the RED and this fact sheet can be downloaded
from the Pesticide Special Review and Reregistration Information System at
703-308-7224. They also are available on the Internet on EPA's gopher
server, GOPHER.EPA. GOV, or using ftp on FTP.EPA.GOV, or using
WWW (World Wide Web) on WWW.EPA.GOV.
Printed copies of the RED and fact sheet can be obtained from EPA's
National Center for Environmental Publications and Information
-------
(EPA/NCEPI), PO Box 42419, Cincinnati, OH 45242-0419, telephone
513-489-8190, fax 513-489-8695.
Following the comment period, the Gibberellic Acid RED document
also 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 Gibberellic Acid RED, or reregistration of individual products
containing Gibberellic Acid, please contact the Biopesticides and Pollution
Prevention Division (7501W), OPP, US EPA, Washington, DC 20460,
telephone 703-308-8712.
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 9:30 am and 7:30 pm Eastern Standard
Time, Monday through Friday.
------- |