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      UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
       	     WASHINGTON, D.C. 20460
      		
      
      				OFFICE PREVENTION, 
   				PESTICIDES AND TOXIC SUBSTANCES       
   
                                         
   
   MEMORANDUM                                                                   December 05, 2012
   
   SUBJECT:	Ecotoxicity Scoping Document for Gibberellins Registration Review Decision Document.   
   
               EPA Reg No.:		62097-
               Registration Review 
               Case#:		               4110
               CAS No.:		77-06-5
               PC Code:		043801; 043802; 116902.
   
   FROM:	Michael Rexrode, Ph.D., Senior Biologist          /s/             12/05/2012
               Biochemical Pesticides Branch
               Biopesticide & Pollution Prevention Division (7511P)
   
   TO:		Menyon Adams, Regulatory Action Leader                         12/05/2012
               Biochemical Pesticides Branch
               Biopesticide & Pollution Prevention Division (7511P)
         
         
ACTION REQUESTED

The following is an ecotoxicity assessment for gibberellic acid in support of the Registration Review Work Plan. 


RECOMMENDATIONS AND CONCLUSIONS

Executive Summary

The following compounds will be considered collectively as Gibberellic acids (GA): Gibberellic acid (GA3) and related isomers known as gibberellins (GA4 and GA7). Gibberellic acids were first identified in Japan in 1935, as the metabolic byproduct of a fungal plant pathogen Gibberella fujikuroi. Since its discovery, GAs have been found in all plants and have been  used in agriculture as plant regulators to stimulate cell division and elongation that affects leaf, stem and fruit development. In addition to growth stimulation, gibberellic acids can hasten plant maturation and seed germination (Feng et al., 2008). 

GA stimulates the cells of germinating seeds to produce mRNA molecules that code for hydrolytic enzymes. Since GA regulates growth, applications of very low concentrations can have a profound effect while higher concentrations will have the opposite effect; therefore, the compounds are usually used in concentrations between 0.01 and 10 mg/L. GA is also widely used in the grape-growing industry as a hormone to induce the production of larger bundles and bigger grapes, especially Thompson seedless grapes (Univ. Davis website).

Based on a review of all available ecological data, exposure information, and gibberellic acids non-toxic mode of action, the Agency expects that label rate application of this plant growth regulator will pose minimal risk to nontarget wildlife and fish. The rational for this conclusion is as follows: 1) Gibberellic acid is produced in all plants as a growth stimulator; 2) Gibberellic acid is found in algae and seaweed that are natural components of fish diets; 3) Gibberellic acid is non-toxic to mammalian and avian species (LD50 > 2,250 mg/kg); 4) A review (11/27/12) of the Agency Environmental Incident Information System (EIISv2.1.1; 2012) showed that there were no reports of adverse effects from gibberellic acid exposure to non-target species.  Data waivers were also granted for Nontarget Insect Testing (885.4340) and Nontarget Plant Testing (885.4300) in July of 1995 as part of the RED development process because of the unique characteristics of this product, its non-toxic mode of action, low use volumes (< 2g/A), and biodegradability (low to no persistence). Based on the current use patterns and label directions, the non-toxic effects to terrestrial and aquatic plants and animals, the Agency finds that Gibberellic Acid use is a No Effect to endangered plant and animal species. 



Figure 1.0   Gibberellic Structure 





Method and Rates of Application:
Gibberellic Acid (GA ) may be applied by aircraft, irrigation systems, ground spray equipment, seed treatment or soil incorporation.

Chemical and Fate Properties
Table 1.0 shows that gibberellic acid is very water soluble (4,280 mg/L), has a very low potential for bioaccumulation (Log P = 0.72), is non-persistent (DT50 = 3.4 days soil; DT50 = 27 days hydrolysis), and photo degrades rapidly (DT50 = 0.2 days).

  Table 1.0 Chemical and Fate Properties for Gibberellic Acid[1]
                             OPPTS Guideline No. 
                                   Property
                             Description of Result
                                   830.6302
Color
White
                                   830.6303
Physical State
White crystalline solid
                                   830.7200
Melting point/Range
Decomposes before melting
                                   830.7220
Boiling point/Range
Decomposes before boiling
                                   830.7300
Bulk density (g/ml)/Specific gravity
1.49
                                   830.7550
                                   830.7560
                                   830.7570
Partition Coefficient (n-
Octanol/Water)
P = 5.25     
 Log P = 0.72
                                   830.7840
Water Solubility
4,280 mg/L at 20[0]  C
                                   830.7950
Vapor Pressure
0.1 mm Hg @ 25°C 

                                   830.7370
Dissociation constant at 25[0]  C
pKa = 4.0
                                   835.3300
Aerobic Soil Degradation  (days)
DT 50 = 3.4
                                   835.2240
Aqueous Photolysis (Days at pH 7)
DT50 = 0.2
                                   835.2130
Aqueous Hydrolysis (days at 200  C pH 7)
DT50 = 27
 [1] BPBD : biopesticide data base University of Hertfordshire
Aquatic Risk Assessment
The available aquatic data shows that gibberellic acid is practically non-toxic to fish (rainbow trout LC50 > 150 ppm) and aquatic invertebrates (Daphnia magna LC50 > 143 ppm) (Table 2.0). 

Table 2.0   Gibberellic Acid Aquatic Toxicity Data
Test
Results
MRID
Freshwater Fish LC50 (Trout)
 850.1075
LC50 > 150 ppm;
NOEL = 143 ppm
Practically non-toxic
42167401

Freshwater Invertebrate (Daphnia)
 850.1010
LC50 > 143 ppm
NOEL = 143 ppm
Practically non-toxic
42084402

In order to assess any potential risk to aquatic life from runoff to an aquatic area, the Agency has evaluated the potential for risk through a Tier I single event model, (Parker et al., 1995) GENEEC (GENeric Estimated Exposure Concentration). This model assumes that one single large rainfall/runoff event occurs that removes a large quantity of pesticide from a field to an adjacent body of water at one time. Longer-term, multiple-day average concentration values are calculated based on the peak day value and subsequent values considering degradation processes. Table 3.0 shows the estimated environmental concentrations (EECs) that could be expected from a worst case (0.5221 lbs ai/A) runoff event from a blueberry field into an aquatic area. The Agency calculated risk quotients (RQ) as an exposure/hazard ratio in order to determine the potential ecological risk from gibberellic acid exposure to non-target aquatic species. Assuming that the fish LC50 is = 150 ppm and that the invertebrates EC50 =143 ppm, the respective RQ values were found to range from 0.00  -  0.0002 ppm. These projected RQs are below the Agency's level of concern (LOC) (0.05  -  0.5) for risk to non-target aquatic organisms, as well as, aquatic endangered/threatened species (Appendix A). The acute risk from gibberellic acid exposure to non-target and listed aquatic organisms is low.

Table 3.0 GENEEC Version 1.0 Estimated Environmental Concentrations Calculated for Gibberellic Acid Runoff (PPM) from a Blueberry Field after a Maximum Application of 0.52911 lbs. ai/A, one Applications/Years
Peak EEC 
RQ values
Max. 4 day average EEC
RQ values
Max. 21 day average EEC
RQ values
Max. 60 day average EEC
RQ values
Max. 90 day average EEC
RQ values
0.031
0.0002
0.027
0.0002
0.016
0.00
0.007
0.00
0.004
0.00

Terrestrial Risk Assessment
The acute terrestrial toxicity profile for gibberellic acid shows that this compound is practically non-toxic to mammalian (LD50 > 5,000 mg/kg) and avian species (LD50 >2,250 mg/kg; LC50 > 4,640 mg/kg), as well as, non-target insects (Table 4.0). 

Table 4.0 Gibberellic Acid Terrestrial Toxicity Data
Test
Results
MRID
Rat Acute Oral 
870.1100
LD50 > 5,000 mg/kg
00153783
Avian Acute Oral (Bobwhite Quail)
850.2100
LD50 > 2,250 mg/L;
Noel +2,250 mg/L
Practically non-toxic
42084401
Avian Dietary (Bobwhite Quail) 
 850.2200
LC50 > 4,640 ppm
Practically non-toxic
00121075

Non-target Insects
Non-toxic to honey bees 
> 25 ug/bee
43370201

In order to quantitatively evaluate the potential for toxic exposure of gibberellic acid residues to avian and mammalian organisms, the Agency used a worst case agricultural scenario on blueberries along with mammalian toxicity and avian toxicity data. Using the Terrestrial Residue Exposure Model (T-REX) Version 1.4.1. in order to calculate expected residues, the Agency performed a terrestrial risk assessment that included numerous calculations of dietary exposure for multiple weight class animals (Appendix B). Expected residues were calculated for avian and mammalian food items along with dissipation rate of a chemical applied to foliar surfaces (single application) in order to estimate acute and chronic RQs relative to weight class for various sized birds and mammals. The upper bound (Table 5.0) Kenega values show that exposure to gibberellic acid (0.5291 lbs/A ai) has a low potential for toxic impact to birds (RQ = 0.00  -  0.09) and mammals (RQ= 0.00- 0.01) that may be feeding in the area of application. The low toxic risk of gibberellic acid to terrestrial organisms, the short environmental half life (4 days) and an understanding of the ubiquitous nature of gibberellic acid (produced in all plants) show that there is a very low potential for toxic risk to birds and mammalian species, including listed species.

Table 5.0  T-REX Estimated Environmental Concentrations and RQ Values for Gibberellic Acid Application to a Blueberry Field after a Maximum Application of 0.52911 lbs. ai/A, one Applications/Years

Dose-Based 
                   Mammalian Classes and Body Weight (grams)

                      15                                                 35                                                  1000

EEC
RQ
EEC
RQ
EEC
RQ
Short grass
121.07
0.01
83.68
0.01
19.40
0.01
Tall grass
55.49
0.01
38.35
0.00
8.89
0.00
Broadleaf plants
68.10
0.01
47.07
0.01
10.91
0.00
Fruit/pods
7.57
0.00
5.23
0.00
1.21
0.00
Arthropods
47.42
0.00
32.77
0.00
7.60
0.00
Seeds
1.68
0.00
1.16
0.00
0.27
0.00








Dose-Based
                     Avian Classes and Body Weight (grams)

                       20                                                 100                                                 1000

EEC
RQ
EEC
RQ
EEC
RQ
Short grass
144.62
0.09
82.47
0.04
36.92
0.01
Tall grass
66.29
0.04
37.80
0.02
16.92
0.01
Broadleaf plants
81.35
0.05
46.39
0.02
20.77
0.01
Fruit/pods
9.04
0.01
5.15
0.00
2.31
0.00
Arthropods
56.64
0.03
32.30
0.02
14.46
0.00
Seeds
2.01
0.00
1.15
0.00
0.51
0.00




Endangered Species
The unique characteristics of gibberellic acid, its non-toxic mode of action, low use volumes, and biodegradability (low to no persistence) should minimize the risks to threatened and endangered species. The Agency has calculated the potential risk to terrestrial and aquatic species by relying on Individual Effects Model Version 1.1 that predicts the chance of individual effect at about 1 in 294,000 for terrestrial animals (Table 6.0) and 1 in 418,000,000 for aquatic species (Table 7.0). Based on the ecological toxicity data that has been submitted on the active ingredients, there should not be toxic risk to endangered/ threatened species from exposure to the end use product. Gibberellic acid should present a No Effect to terrestrial and aquatic threatened or endangered species, if used in accordance with approved labeling.

Ecological Effects Summary
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 this plant growth regulator will pose minimal to no risk to non-target wildlife and fish. The rational for this conclusion is as follows: 1) Gibberellic acid is produced in all plants as a growth stimulator; 2) Gibberellic acid is found in algae and seaweed that are natural components of fish diets; 3) Gibberellic acid is non-toxic to mammalian and avian species (LD50 > 5,000 mg/kg); 4) A review (11/27/12) of the Agency Environmental Incident Information System (EIISv2.1.1; 2012) showed that there were no reports of adverse effects from gibberellic acid exposure to non-target species; 5) Gibberellic acid is not toxic to bees (< 25 ug/bee). Data waivers were also granted for Nontarget Insect Testing (885.4340) and Nontarget Plant Testing (885.4300) in July of 1995 as part of the RED development process because of the unique characteristics of this product, its non-toxic mode of action, low use volumes (< 2g/A), and biodegradability (low to no persistence). Based on the current use patterns, the non-toxic effects to terrestrial and aquatic plants and animals, the Agency finds that Gibberellic Acid use is a No Effect to endangered plant and animal species. 

















Reference

BPBD : biopesticide data base University of Hertfordshire http://sitem.herts.ac.uk/aeru/bpdb/Reports/371.htm

Gibberellin and Flame Seedless Grapes from a University of California, Davis website

Feng, S., Martinez C., Gusmaroli, G., Wang, Y., Zhou, J., Wang, F., Chen, L., Yu, L.,  Iglesias-Pedraz, J.M., Kircher, S., Eberhard, S., Fu, X., Fan, L-M., and Deng, X.W.  2008.  Coordinated regulation of Arabidopsis thaliana development by light and gibberellins. Nature 451:475-479.

Parker, R.D., R.D. Jones and H.P. Nelson., 1995. GENEEC: A Screening Model for Pesticide Environmental Exposure Assessment in Proceedings of the International Exposure Symposium on Water Quality Modeling; American Society of Agricultural Engineers, pp. 485-490; Orlando, Florida

U.S. EPA.  1998.  Guidance for Ecological Risk Assessment.  Risk Assessment Forum.  EPA/630/R-95/002F, April 1998.

U.S.EPA  2004. Individual Effects Chance Model Version 1.1. EFED/OPP/USEPA.

U.S.EPA  2008. Terrestrial Residue Exposure Model (T-REX) Version 1.4.1. EFED/OPP/USEPA.
























Appendix A   GENEEC Model

Table A.1   Gibberellic Acid Residues to an Aquatic Area after One Application to Blueberries (GENEEC)
INPUT VALUES *
  --------------------------------------------------------------------
   RATE (#/AC)   No.APPS &     SOIL    SOLUBIL    APPL TYPE      NO-SPRAY INCORP
    ONE(MULT)    INTERVAL    Koc       (PPM )        (%DRIFT)               (FT)          (IN)
  --------------------------------------------------------------------------------------------------------------------------
  .529(   .529)            1   1           10.0         4280.0         GRHIFI(  6.6)           .0              .0
  FIELD AND STANDARD POND HALFLIFE VALUES (DAYS)
  ---------------------------------------------------------------------------------------------------------------------------
  METABOLIC   DAYS UNTIL      HYDROLYSIS   PHOTOLYSIS   METABOLIC   COMBINED
   (FIELD)            RAIN/RUNOFF          (POND)         (POND-EFF)          (POND)          (POND)
  --------------------------------------------------------------------------------------------------------------------------
     3.40                       0                                N/A             .20-  24.80               6.00                 4.83

  GENERIC EECs (IN MICROGRAMS/LITER (PPB)     Version 2.0 Aug 1, 2001
  ---------------------------------------------------------------------------------------------------------------------------
      PEAK      MAX 4 DAY            MAX 21 DAY         MAX 60 DAY        MAX 90 DAY
      GEEC      AVG GEEC              AVG GEEC            AVG GEEC            AVG GEEC
  ----------------------------------------------------------------------------------------------------------------------------
      30.74             27.51                         15.68                           6.72                         4.52



























Appendix B   Gibberellic Acid Residues to Terrestrial Area after One Application to Blueberries (T-REX) 



Table B.1 T-REX Upper Bound Residues and RQ Calculations for mammalian and Avian Exposure to Gibberellic Acid














