Gibberellins PC Code: 043801, 043802 and 116902

Type of Review: Toxicology (Registration Review)

OFFICE OF CHEMICAL SAFETY

AND POLLUTION PREVENTION

UNITED STATES ENVIRONMENTAL PROTECTION AGENCY

WASHINGTON, D.C. 20460

 

MEMORANDUM

DATE: December 31, 2012

SUBJECT: Human Toxicology Scoping Document for the Registration Review of Gibberellins.

Registration Review Case #: 4110

PC Code: 043801, 043802 and 116902

CAS #: 77-06-5, 125-67-7 and 8030-53-3, respectively

Chemical Class: Biochemicals

FROM: Angela L. Gonzales, Biologist /s/

Biochemical Pesticides Branch

Biopesticides & Pollution Prevention Division (7511P)

TO: Leonard Cole, Senior Regulatory Specialist

Biochemical Pesticides Branch

Biopesticides & Pollution Prevention Division (7511P)

ACTION REQUESTED

In support of the development of the Final Workplan for Registration Review, the following scoping document 

contains the human health assessment for the following biopesticide active ingredients: 1) gibberellic acid; 2) 

gibberellic acid, monopotassium salt; and 3) gibberellin A4 mixture with gibberellin A7.

Executive Summary

All human health assessment data requirements under 40 CFR 158.2050 have been fulfilled for the active 

ingredients. Since the last registration review of these active ingredients, the Agency has received some 

additional mammalian toxicology data for which Agency reviews could not be located. Also, according to the 

Agency’s Incident Data System, there have been reports of human incidents resulting from the use of pesticide 

products containing gibberellic acid as the active ingredient. During the course of registration review, the 

Agency will review of all of these data and determine if a reevaluation of the current risk assessments is 

warranted. 

I. Background
Gibberellins PC Code: 043801, 043802 and 116902

Type of Review: Toxicology (Registration Review) 

 

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Gibberellic Acid (A3)

As a pesticide, gibberellic acid is a plant growth regulator (PGR) used to promote flowering and elongation of 

stems and roots and to stimulate fruit growth and maturation. The chemical naturally occurs in plants and in 

some microbes. (Gibberellins Fact Sheet, 2001)

The chemical was first registered by the Agency in 1971. There are currently 65 registered products containing 

the active ingredient; 35 products contain gibberellic acid as the sole active ingredient, 29 products contain the 

chemical along with one or more other plant growth regulators and 1 product contains the chemical and a 

microbial active ingredient. There are 10 manufacturing-use products (MPs) and 55 end-use products (EPs) that 

contain gibberellic acid as an active ingredient.

Gibberellic Acid, Monopotassium Salt

Currently, there are no pesticide products registered by the Agency containing this active ingredient, thus a 

review of the available data and risk assessments will not be conducted for this chemical.

Gibberellin A4 Mixture with Gibberellin A7

Gibberellin A4 (GA4) and gibberellin A7 (GA7) are isomers of gibberellic acid and thus are significantly similar 

in structure and function. The mixture of the two gibberellins is used as a PGR in pesticide formulations for the 

same purposes as GA3.

The GA4 and GA7 mixture was first registered by the Agency in 1994. There are currently 14 registered 

products containing the active ingredients; 7 products contain the mixture as the sole active ingredient and 7 

products contain the mixture along with one or more other PGRs. There are 2 MPs. 

II. Tolerances

40 CFR § 180.1098 Gibberellins [Gibberellic Acids (GA3 and GA4 + GA7), and Sodium or Potassium 

Gibberellate]; exemption from the requirement of a tolerance.

An exemption from the requirement of a tolerance is established for residues of gibberellins [gibberellic acids 

(GA3 and GA4 + GA7), and sodium or potassium gibberellate] in or on all food commodities when used as 

plant regulators on plants, seeds, or cuttings and on all food commodities after harvest in accordance with good 

agricultural practices. [64 FR 31505, June 11, 1999]

III. Incidents
Gibberellins PC Code: 043801, 043802 and 116902

Type of Review: Toxicology (Registration Review) 

 

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Gibberellic Acid (A3)

According to the Incident Data System, there have been six reports of human incidents resulting from the use of 

pesticide products containing GA3 as the active ingredient. During the course of registration review, the Agency

will conduct an assessment of the incident data to determine if the current risk assessments will need to be 

reevaluated.

Gibberellin A4 Mixture with Gibberellin A7

According to the Incident Data System, there have been no reports of incidents resulting from the use of 

pesticide products containing GA4 and GA7 mixture as the active ingredient.

IV. Toxicity Profile

Because GA3 and the GA4 and GA7 mixture are significantly similar in structure and function, they are 

considered collectively in the toxicity assessment. Sufficient data have been provided to fulfill the biochemical 

pesticide data requirements under 40 CFR 158.2050 for the current use patterns for the active ingredients. The 

data available to the Agency are summarized in Table 1 below. Several mutagenicity studies and a skin 

sensitization study have been submitted to the Agency since the last review of these active ingredients. The 

reviews of these studies were not able to be located, thus they will be reviewed during the course of registration 

review.
Gibberellins PC Code: 043801, 043802 and 116902

Type of Review: Toxicology (Registration Review) 

 

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Table 1. Human Health Assessment Data Requirements for Gibberellins (40 CFR § 158.2050)

Study/OCSPP Guideline No. Results Toxicity 

Category/Description MRID

Acute oral toxicity (rat)

(870.1100)

LD50 > 5,000 mg/kg (GA3) IV 44081306

LD50 > 5,000 mg/kg (GA4 and GA7 mixture) IV 40873201

LD50 > 5,000 mg/kg (GA4 and GA7 mixture) IV 44264705

Acute dermal toxicity (rabbit)

(870.1200)

LD50 > 2,000 mg/kg1(GA3) III 44081307

LD50 > 2,000 mg/kg1(GA4 and GA7 mixture) III 40873202

LD50 > 2,000 mg/kg1(GA4 and GA7 mixture) III 44264706

Acute inhalation toxicity (rat)

(870.1300)

LC50 > 4.94 mg/L (GA3) IV 44081308

LC50 > 2.98 mg/L2(GA4 and GA7 mixture) III 40873203

LC50 > 5.44 mg/L (GA4 and GA7 mixture) IV 44264707

Primary eye irritation (rabbit)

(870.2400)

Mildly irritating-effects cleared within 7 days (GA3) III 44081309

Moderately irritating-effects cleared within 7 days 

(GA4 and GA7 mixture) III 40873204

Mildly irritating-effects cleared within 7 days (GA4 

and GA7 mixture) III 44264708

Primary dermal irritation (rabbit)

(870.2500)

Non-irritating (GA3) IV 44081310

Non-irritating (GA4 and GA7 mixture) IV 40873205

Non-irritating (GA4 and GA7 mixture) IV 44264709

Dermal sensitization (guinea pig)

(870.2600)

Not a sensitizer (GA3) 44081311

Mildly sensitizing (GA4 and GA7 mixture) 40873206

Not a sensitizer (GA4 and GA7 mixture) 44264710

90-Day oral toxicity 

(870.3100)

NOAEL = 10,000 ppm in rats

LOAEL = 25,000 ppm based on alterations in clinical 

chemistry, decreased food consumption, decreased 

body weight, increases in relative organ weights (brain, 

kidney and testis) and gross and histopathological 

changes in the kidney (GA4 and GA7 mixture)

41616601

NOAEL = 10,000 ppm in rats

LOAEL = 50,000 ppm based on occurrence of soft 

stools in both males and females, increased blood urea 

nitrogen (BUN) levels and increased liver and kidney 

weights in females. (GA3)

41617501

NOAEL = 600 mg/kg/day in male dogs, 1,000 

mg/kg/day in female dogs

LOAEL = 1,000 mg/kg/day in males based on a 

reduction in body weight gain and food efficiency, 

increased liver weight and gross and histopathological 

changes in the thymus and adrenal glands. 

45695901

90-Day dermal toxicity

(870.3250)

Waived. Products containing the active ingredients are 

not purposefully applied to the skin and prolonged 

exposure is not anticipated based on the active 

ingredients’ use pattern as PGRs. 

90-Day inhalation toxicity

(870.3465)

Waived. Significant repeated inhalation exposure as a 

gas, vapor or aerosol is not expected based on the use 

pattern of the active ingredients.

Mutagenicity

(Bacterial reverse mutation test; 870.5100)

Not mutagenic under the conditions of the studies 

(GA3 and GA4 and GA7 mixture)

40261601

40873207

44264711

Mutagenicity

(Unscheduled DNA synthesis in 

mammalian cells; 870.5550)

Not mutagenic under the conditions of the studies. 

(GA3 and GA4 and GA7 mixture)

40261603

40873209

Mutagenicity

(In vivo mammalian erythrocyte 

micronucleus test; 870.5395)

Not mutagenic under the conditions of the study. (GA4 

and GA7 mixture) 40873208

Mutagenicity

(In vitro mammalian cell gene mutation 

test; 870.5300)

Not mutagenic under the conditions of the study. (GA4 

and GA7 mixture) 44264712
Gibberellins PC Code: 043801, 043802 and 116902

Type of Review: Toxicology (Registration Review) 

 

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Table 1. Human Health Assessment Data Requirements for Gibberellins (40 CFR § 158.2050)

Study/OCSPP Guideline No. Results Toxicity 

Category/Description MRID

Mutagenicity

(In vitro mammalian chromosome 

aberration test; 870.5375

Evidence of clastogenic activity observed at ≥ 1,000 

μg/ml without S9 activation and at ≥ 2,000 μg/ml with 

S9 activation.3(GA4 and GA7 mixture)

44264713

Developmental toxicity

(870.3700)

Maternal NOAEL > 1,000 mg/kg/day1in rats. 

Developmental NOAEL is not available. (GA3)

40155201

40746801

Maternal and developmental NOAEL = 300 mg/kg/day 

in rabbits.

Maternal and developmental LOAEL = 1,000 

mg/kg/day based on increased mortality, increased 

abortion rates, clinical signs of toxicity and gross 

pathological observations (GA4 and GA7 mixture)

41143201

1Highest dose tested.

2Highest respirable dose achieved.

3Although clastogenic activity was observed in this in vitro study, the active ingredients are considered not likely to be mutagenic. 

This conclusion is based on the negative results observed in all of the other mutagenicity studies, one of which was an in vivo study. 

VI. References

U.S. EPA Biochemical Fact Sheet for Gibberellins. Issued January, 2001. 

<http://www.epa.gov/opp00001/chem_search/reg_actions/registration/fs_G-106_01-Jan-01.pdf>

cc: A. L. Gonzales, L. Cole, BPPD Science Review File, IHAD/ARS

 A. L. Gonzales, FT, PY-S: 12/31/12