### UNITED STATES ENVIRONMENTAL PROTECTION AGENCY **WASHINGTON, D.C. 20460**

**O FFICE 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 : Mi chael Rexrode, Ph.D., Senior Biologist /s/ 12/ 05 /2012

Biochemical Pesticides Branch Biopesticide & Pollution Prevention Division (7511P) **TO:** Menyon Adams, Regulatory Action Leader 12/05/20 12 Biochemical Pesticides Branch Biopesticide & Pollution Prevention Division (7511P)
**ACTION REQUESTED** The following is an ecotoxicity assessment for gibberelli c 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 (GA 3 

### ) and related isomers known as gibberellins (GA4 

### and GA 7 

### ). Gibberellic acids were first identified in Japan in 1935, as the metabolic by product of a fungal plant pathogen Gibberella fujikuroi . Since its discovery , GA s have been found in all plants and have been used in agriculture as plant regulators to stimulate cell division and elongation that affect s leaf, stem and fruit development. Inaddition 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

hydrol ytic enz ym es . 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 concentr ations between 0.01 and 10 mg/L

. GA is also widely used in the grape

- growing industry as a hormo ne 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 Agenc y 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 (LD 50 

### > 2,2 50 mg/kg); 4) A review (11/27/12) of the Agency Environmental Incident Information System (E IISv2.1.1; 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, it s non - toxic mode of action, low use volumes (< 2 g/A), and biodegradability

(low to no persistence)

. Based on the current use patterns and label directions , the non

- toxic effec ts 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 Gibberell** **ic Structure** 

### Method and Rates of Application:

**Gibberellic Acid (GA )** may be applied b y aircraft, irrigation s ys tems, 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 (DT 50 

### = 3.4 day s soil; DT 50 

### = 27 day s hydrol ys is), and photo degrades rapidly (DT 50 

### = 0.2 day s). **Tab le 1.0 Chemical and Fate Properties for Gibberellic Acid**  **1 OPPTS Guideline**  **No. Property**  **Description of Result** 830.6302 Color **White** 830.6303 Phy sical State White crystalline solid 830.7200 Melting point/Range Decom poses before melting 830.7220 Boiling point/Range Decom poses before boiling 830.7300 Bulk d ensity (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) DT 50 = 0.2 835.2130 Aqueous Hydrolysis (days at 20 0 C pH 7) DT 50 = 27 1 BPBD : biopesticide data base University of Hertfordshire 

### Aquatic Risk Assessment The available aquatic data shows that gibberellic acid is practicall y non - toxic to fish (rainbow trout L C 50 

### > 150 ppm) and aquatic invertebrates ( Daphnia magna LC 50 

### > 143 ppm) (Table 2 .0). **Table 2.0 Gibberellic Acid Aquatic Toxicity Data**  Test Results MRID Freshwater Fish L C 50 (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 (GENeri c 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 L C 50 

### is = 1 5 0 ppm and that the invertebrates EC 50 

### = 1 43 ppm , the respective RQ

value s were found to range from 0.00

– 0.000 2 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 expos ure 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**  **Fi eld after a Maximum Application of**  **0.5291 1 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 practicall y non - toxic to mammalian (LD 50 

### > 5,000 mg/kg) and avian species (LD 50 

### >2,250 mg/kg; L C 50 

### > 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 LD 50 > 5,000 mg/kg 00153783 Avian Acute Oral (Bobwhite Quail) 850.2100 LD 50 > 2,250 mg/L; Noel +2,250 mg/L Practically non

- toxic 42084401
Avian Dietary (Bobwhite Quail) 850.2200 LC 50 > 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 s how that exposure to gibberellic acid ( 0.5291 lbs/A ai) has a low potential for toxic impact to birds (RQ = 0.0 0

– 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 day s) 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**  **0.5291 1 lbs. ai/A,**  **one Applications/Years** 
**Dose**
**- Based**  **Mam malian 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 b y relying on In dividual Effects Model Version 1.1 that predicts the chance of individu al 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 submitte d 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 wil l pose minimal to no risk to non

- target wildlife and fish. The rational for this conclusion is as follows: 1) G ibberellic acid is produced in all plants as a growth stimulator; 2) Gibberellic acid is found in algae and seaweed that are natural components o f fish diets; 3 ) Gibberellic acid is non

toxic to mammalian and avian species (LD 50 

### > 5,000 mg/kg) ; 4 ) A review (11/27/12) of the Agency Environmental Incident Information S ys tem (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 char acteristics of this product, it s non - toxic mode of action, low use volumes (< 2 g/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 b y 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)

-------------------------------------------------------------- ------------------------------------------------------ ------ .52 9( .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 4.8 3 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 Ch**  **emic al N**  **am e:**  **U se**  **For mu**  **lat io**  **n Ap**  **pl ica**  **ti on**  **Ra te**  **0. 5291**  **lb s**  **a. i./ac**  **re**

**Ha lf** **-l if**  **e 3.**  **4 da**  **ys Ap**  **pl ic**  **at io**  **n Int er** 

**va l**  **0 da**  **ys Ma**  **ximu m #** 

**A pps** **./Y ear**  **1 Le**  **ngth of**

**Simula ti**  **on 1**  **ye ar**  **Va ria**  **bl e ap**  **pl ic**  **at io**  **n ra te**  **s? no** 

**Bo bw**  **hite q**  **ua il**  **LD 50**  **(m g/k** **g-bw )**  **2250. 00** 

**Bo bw**  **hite q**  **ua il**  **LC 50**  **(m g/**  **kg-die t)**  **0.00 Ma**  **llar d duc**  **k NOAEL**  **(m g/k** **g-bw )**  **0.00**

**Bo bw**  **hite q**  **ua il**  **NOAEC (m**  **g/ kg-d**  **ie t)**  **2250. 00** 

**5000. 00**  **0.00 0.00**  **0.00**
**Ke na**  **ga Va**  **lu es**  **Short Gra ss**  **126. 98**  **Ta ll G**  **ra ss**  **58. 20**  **Broa dl**  **eaf**

**pla nts**  **71. 43**  **Frui ts**  **/pods /s**  **eed s**  **7. 94**  **Arthropods 49.**  **74** 

### Up **per Bound**  **Kenaga Re**  **si dues**  **For RQ** **C al**  **cul at**  **io n** 



### Di **et ar**  **y- based EECs**  **(p pm)**  **NOAEL (**  **mg/k g-bw**  **) NOAEC**  **(m g/**  **kg-d ie**  **t)** 

### Ma **mmal s**  **LD 50**  **(m g/k** **g-bw )**  **LC 50**  **(m g/**  **kg-die t)**  **gi bbe**  **re llic** **ac id**  **grow th**  **r eg**  **ula tor**  **0**



### Av **ia n**  **Endpoi nt** **s sm**  **all mid**  **la rge**  **20 100**  **1000 Short Gra**  **ss 144.**  **62 82.**  **47 36.**  **92 Ta**  **ll Gras**

**s 66.**  **29 37.**  **80 16.**  **92 Br** **oadleaf**

**pla nt**  **s 81.**  **35 46.**  **39 20.**  **77 Fruits**  **/pods 9.**  **04 5.15**  **2. 31**  **Ar thropods**  **56. 64**  **32. 30**  **14. 46**  **Se eds**  **2. 01**  **1.15 0.**  **51**

**20 100**  **1000 Short Gra**  **ss 0.**  **09 0.04**  **0. 01**  **Ta ll Gras** 

**s 0.**  **04 0.02**  **0. 01**  **Br oadleaf** 

**pla nt**  **s 0.**  **05 0.02**  **0. 01**  **Fruits /pods**  **0. 01**  **0.00 0.**  **00 Ar**  **thropods 0.**  **03 0.02**  **0. 00**  **Se eds**  **0. 00**  **0.00 0.**  **00** 

### Di **et ary-**  **ba sed**  **R Qs**  **(D ie**  **tary-based EEC/LC50 or Acu**  **te Chroni**  **c Short Gra**  **ss #DIV/0!**  **0.06 Ta**  **ll Gras**

**s #DIV/0!**  **0.03 Br** **oadleaf**

**pla nt**  **s #DIV/0!**  **0.03 Fruits**  **/pods /s**  **eed s**  **#DIV/0! 0.00**  **Ar thropods**  **#DIV/0! 0.02** 
No te: T o prov ide ris k ma nagement with th e max imum pos sib le information, it is rec ommended th at b ot h th e dos e-bas ed and co nc ent rat io n-bas ed RQs be ca lculated when dat a are av ailable 

### Dose-based EECs **(m g/**  **kg -bw**  **) Avi**  **an C**  **la sse**  **s and B**  **ody Weig**  **ht s**  **(gra ms** **)**



### Do **se-based R** **Qs (D**  **ose- based**  **EEC/**

**adj usted LD50)** 

**RQ s**  **Av ia**  **n Acute R**  **Qs Si**  **ze C**  **la ss (grams)** 

**15 35**  **1000 Short Gra**  **ss 121.**  **07 83.**  **68 19.**  **40 Ta**  **ll Gra ss**  **55. 49**  **38. 35**  **8.89 Broa**  **dle af** 

**plants 68.**  **10 47.**  **07 10.**  **91 Fruits**  **/pods 7.**  **57 5.**  **23 1.21**  **Arthropods 47.**  **42 32.**  **77 7.60**  **Seeds 1.**  **68 1.**  **16 0.27** 

**15 gra**  **ms 35**  **gra ms**  **1000 gra**  **ms Acute**  **Chronic Acute**  **Chronic Acute**  **Chroni c**  **Short Gra ss**  **0. 01**  **#DI V/0**  **! 0.01**  **#DI V/0**  **! 0.**  **01 #DI**  **V/0! Ta**  **ll Gra ss**  **0. 01**  **#DI V/0**  **! 0.00**  **#DI V/0**  **! 0.**  **00 #DI**  **V/0! Broa**  **dle af** 

**plants 0.**  **01 #DI**  **V/0 !**  **0.01 #DI**  **V/0 !**  **0. 00**  **#DI V/0!**  **Fruits /pods**  **0. 00**  **#DI V/0**  **! 0.00**  **#DI V/0**  **! 0.**  **00 #DI**  **V/0! Arthropods**  **0. 00**  **#DI V/0**  **! 0.00**  **#DI V/0**  **! 0.**  **00 #DI**  **V/0! Seeds**  **0. 00**  **#DI V/0**  **! 0.00**  **#DI V/0**  **! 0.**  **00 #DI**  **V/0! Me**  **dium mammal La**  **rge mammal**  

### Do **se-b ased**  **R Qs**  **(D ose-**  **based EEC/ LD50**  **or Sma**  **ll mammal** 

### Dos **e-Based EECs (m**  **g/kg-bw )**  **(g ra**  **ms )**  **Ma mmalian**  **C las** 

**se s**  **an d B**  **ody w eig**  **ht**