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

o FFICE PREVENTION,
PESTICIDES AND TOXIC SUBSTANCES



### MEMORANDUM July 28, 2010

SUBJECT : Summary of Ecotoxicity Data and Risk Assessment of three Nitrophenolates (Sodium 5-N itroguaiacolate, Sodium oNitrophenolate, Sodium p-Nitrophenola te) for the Registration Review
Decision Document.

EPA Reg No.: 64922-5 Registration Review
Case#: 6067 CAS No.: 67233-85-6; 824-39-5; 824-78-2. PC Code: 129075; 129076; 129077.



### FROM : Miachel Rexrode, Ph.D., Senior Biologist /s/ 07/28/2010
Biochemical Pesticides Branch Biopesticide & Pollution Pr evention Division (7511P)

TO: Driss Benmhend, Regulatory Action Leader
Biochemical Pesticides Branch Biopesticide & Pollution Pr evention Division (7511P)

THE FOLLOWING CONTAINS CONFID ENTIAL BUSINESS INFORMATION

ACTION REQUESTED

The following is a preliminary ecotoxicity assessment for the Nitrophenolates, Sodium 5- Nitroguaiacolate, Sodium o-Nitrophenolate, and Sodium p-Nitrophe nolate in support of the Registration Review Work Plan for Atonik PGR.

1

### RECOMMENDATIONS AND CONCLUSIONS

Executive Summary

Based on the available information for Atonik PGR, the Agency does not foresee the need for additional ecotoxicity data for a new risk assessment. All Tier I data requirements per 40 CFR 158.2060 have been fulf illed for the three active ingredients. Hazard and exposure data on these chemicals were evaluated against current standards established by the Agency’s scientific policie s and regulations. The unique characteristics of this product, its non-toxic mode of action, low use volumes (< 20g/A), and biodegradability (low to no pe rsistence) should minimize the risks to all non-targets. The Agency has reviewed the available ecotoxic ity data and completed a risk assessment using the maximum application of Atonik to an agricultural crop. Atonik is relatively nontoxic to honey bees and exposure of this pr oduct to non-target te rrestrial and aquatic species should not pose toxic risk. Since, At onik is intended for use as a plant growth enhancer and will be aerially applied to rice, soybean, and cotton crops; there is a possibility of drift to adjacent vegetative areas. The Agency, however, has evaluated the potential for indirect exposure to plants a nd concludes that this exposure will be minimal and not efficacious resulting in residue levels th at are 2-3 orders of magnitude below field levels that were found to not be effective (Bynum et al ., 2007). The Agency concludes that exposure of Atonik to fish and wildlife and to listed/threatened species and their supporting habitat will result in a No Effect (NE).

I. Background

Atonik is a plant growth regulat or (PGR), and is composed of three active ingredients, Sodium p-Nitrophenolate (0.3%); Sodium o- Nitrophenolate (0.2%); Sodium 5- Nitroguaiacolate. The three activ e ingredients are similar to each other in structure, function and toxicity and appear to enhance fertilizer uptake , crop growth and yield.

Currently, there are five products that are registered contai ning the biochemicals. One product is an end-use product (EP) that cont ains all three PGRs (EPA Reg. No.: 64922-1) as its active ingredients. Four products are manufactur ing-use products (MPs); one contains Sodium 5-Nitroguaiacolate (EPA Re g. No.: 64922-2) as its active ingredient, one contains Sodium p-Nitrophenolate (EPA Reg. No.: 64922-3) as its active ingredient, one contains Sodium o-Nitrophenolate (EPA Reg. No.: 64922-4) as its active ingredient, and the last contains all three active ingred ients (EPA Reg. No.: 64922-5). The EP is used on cotton, rice and s oybean plants.

II. Toxicity Profile

Avian Toxicity Studies

An acute oral toxicity study using the technical grade of th e active ingredient (TGAI) is required to establish the toxicity of th e plant stimulant, Atonik PGR (sodium 5- nitroguaiacolate; Sodium o-ni trophenolate; Sodium p-Nitrophenolate) to birds. The

2

### preferred test species is either mallard duck ( Anas platyrhynchos ; a waterfowl) or Bobwhite quail ( Colinus virginianus ; an upland game bird). Re sults of these studies are
summarized below in Table 1.0. Atonik PGR ha s been shown to be practically non-toxic to avian species as noted in the Bobwhite qua il acute and dietary studies where toxicity ranges from LD 50 

### > 2,000 mg/kg to LC 50 

### = 5,620 ppm. One exception was Sodium oNitrophenolate that is consid ered slightly toxic at LD 50 

### = 1,046 mg/kg. The results of these studies suggest that Atonik PGR shoul d not cause any adverse effects to avian
wildlife.

Table 1.0 Summary of Avian Toxicity for Atonik PGR Species Sodium 5- Nitroguaiacolate Sodium oNitrophenolate Sodium pNitrophenolate MRID No.

850.2100
Acute Oral Bobwhite quail (Colinus virginianus) LD 50 >2,000 mg/kg

Practically nontoxic LD 50 = 1,046 mg/kg

Slightly toxic LD 50 = 2,000 mg/kg

Practically nontoxic 41852201
41854802
41868505

850.2200 Acute Dietary Bobwhite quail (Colinus virginianus) LC 50 >5,620 ppm

Practically nontoxic LC 50 >5,620 ppm

Practically nontoxic LC 50 >5,620 ppm

Practically nontoxic 41868506
41854803
41852202



### Mammal Studies

Summaries of the most sensitive toxicity va lues (acute) for mammals are shown in Table 2.0. The acute oral toxicity was found to ranged from LD 50 

### = 345.5 – 960.1 mg/kg suggesting slight toxicity. Exposure to these compounds should not result in acute dermal effects (2,000 mg/kg) or significant acute inhalation eff ects (>1.2-2.3 mg/L). Studies on prenatal development showed maternal NOEL and LOEL at 300 and 600 mg/kg/day and developmental NOEL = 600 mg/kg (no toxicity). The results of these studies suggest that Atonik PGR should not cause any a dverse effects to mammalian
wildlife

Table 2.0 Summary of Mammalian Toxicity Studies for Atonik PGR

Test Sodium 5- Nitroguaiacolate Sodium oNitrophenolate Sodium pNitrophenolate MRID
No.
870.1100 Acute Oral Toxicity LD 50 = 716 mg/kg
Tox Cat
III LD 50 = 960.1 mg/kg
Tox Cat
III LD50 = 345.5 mg/kg
Tox Cat
II 41897901
41868401
41868501
870.1200
Acute Dermal > 2,000 mg/kg
Tox Cat
III > 2,000 mg/kg
Tox Cat
III > 2,000 mg/kg
Tox Cat
III 41868602
41868402
41868502
870.1300
Acute Inhalation >2.3 mg/L
Tox Cat
IV >1.24 mg/l
Tox Cat
III >1.2 mg/L
Tox Cat
III 43070307
43072007
43071907
870.3700
Prenatal Developmental Maternal NOEL =300 mg/kg/day;
Maternal LOEL=600 Maternal NOEL =300 mg/kg/day;
Maternal LOEL=600 Maternal NOEL =300 mg/kg/day;
Maternal LOEL=600 43070203
43070203
43070203



### 3Test Sodium 5- Nitroguaiacolate Sodium oNitrophenolate Sodium p- MRID Nitrophenolate No. mg/kg/day; Developmental
NOEL = 600 mg/kg/day (no toxicity ) mg/kg/day; Developmental
NOEL = 600 mg/kg/day (no toxicity ) mg/kg/day; Developmental
NOEL = 600 mg/kg/day (no toxicity )



### Honey Bee Toxicity

Atonik PGR appears to be nontoxi c to honey bees as noted in acute contact studies with
LD 50 

### = 100 – 111 ug/bee (Table 3.0). The results of these studies suggest that Atonik PGR should not cause any adverse e ffects to beneficial insects.

Table 3.0 Summary of Honey B ee Toxicity for Atonik PGR

Test Species Sodium 5- Nitroguaiacolate Sodium oNitrophenolate Sodium pNitrophenolate MRID No.

880.4350 Honey bee (Aphis LD 50 = 100 ug/bee

Nontoxic LD 50 = 100 ug/bee

Nontoxic LD 50 = 111 ug/bee

Nontoxic 41868509
41852205
41854805



### Non target Plant Testing

Plant testing of biological pest control agents is conditionally required if incidents have occurred or if there is published informa tion that the compound is toxic to plants. Therefore, to the best of our knowledge none of these compounds are known to be phytotoxic.

Aquatic Toxicity Studies

The Agency has summarized available acute aquatic studies and concluded that Atonik PGR is slightly toxic to fish with LC 50 

### = 25.0 – 69.0 mg/L and sli ghtly toxic to aquatic
invertebrates with 48 hr EC 50 

### = 27.7 – 84.5 mg/L (Table 4.0).

Table 4.0 Summary of Aquatic T oxicity Studies for Atonik PGR Species Sodium 5- Nitroguaiacolate Sodium oNitrophenolate Sodium pNitrophenolate MRID No.

Fish
850.1075
Rainbow trout ( Oncorhynchus mykiss ) 96 hr LC 50 = 37.4 mg/L

Slightly toxic 96 hr LC 50 = 69.0 mg/L

Slightly toxic 96 hr LC 50 = 25.0 mg/L

Slightly toxic 41944701
41852203
41868507

Aquatic Invertebrates
850.1010 Daphnia magna 48 hr EC 50 84.5 mg/L

Slightly toxic 48 hr EC 50 68.8 mg/L

Slightly toxic 48 hr EC 50 27.7 mg/L

Slightly toxic 41854804
41852204
41868508



### 4Species Sodium 5- Nitroguaiacolate Sodium o- Sodium p- MRID No. Nitrophenolate Nitrophenolate



## Ecological Assessment Ecotoxicity Risk

Aquatic Atonik (nitrophenolates) is used as a plant growth regulator to enhance fertilizer uptake and crop yield on soybeans, rice, and cotton. The three nitrophenol ates compounds that make-up Atonik are applied at a total rate of 20 g ai/A pe r application and are rapidly absorbed and converted to compounds that ar e naturally found in plants. In order to assess potential risk to aquatic ecosystem s the Agency has estimated environmental concentrations (EECs) of Atonik from runoff af ter applications to te rrestrial crops. Using
the GENeric Estimated Environmental Con centration model (GENEEC; EPA, 2001) the Agency assumed 2 maximum applications of end product at 0.004lbs a i/A (4g ai/A) at 7 day intervals, assume a one day aquatic half-l ife, a one day photodegr adation half-life in water, and a one day half-life in aerobic so il. The peak aquatic EEC was calculated at a about 0.000031 ppm which declined to about 0.000005 ppm after 21 days (Table 5.0).
Since the LC 50 

### values for fish and aquatic inverteb rates is 37.4mg/L and 84.5mg/L this would result in Risk Quotients (RQs) of 0.00 and 0.00, respectively, well below the Agency’s Levels of Concern (LOCs = 1.0 - 0.5), suggesting no risk concerns for aquatic species

.

Table 5.0 Generic Estimated Environmental Concentrations (EECs) of Atonik in Aquatic Sites using the GENEEC Model, ver 2.0 (EPA, 2001) in Parts Per Trillion (pptr)


### Table Peak EEC Max 4 Day Avg EEC Max 21 Day Avg EEC Max 60 Day Avg EEC Max 90 Day Avg EEC

31.22 20.64 4.97 1.74 1.16



### Terrestrial In order to evaluate risk of Atonik (nitroph enolates) exposure to terrestrial species, the Agency has estimated RQ values using the Terrestrial Residue Exposure Model (T-REX)
Version 1.4.1. A terrestrial risk assessment in cludes calculated expected residues, as well as, numerous calculations of dietary expos ure for multiple weight class animals (Appendix B). Expected residues were calcul ated for avian and mammalian food items along with dissipation rate of a chemical applied to foliar surfaces (single or multiple applications) in order to estimate worst case acute RQs relative to weight class for
various sized birds and mammals. These calc ulations showed upper bound Kenega values and that exposure to Atonik (0.004lbs ai/A) has a low potential for toxic impact to birds (RQ = 0.00) and mammals (RQ= 0.00) that may be feeding in the area of application as noted in Appendix B. The unique characterist ics of this product, the non-toxic mode of action, biodegradability and low pot ential for exposure will result in no risk to all nontarget terrestrial organisms.

5

### Endangered Species Risk Assessment

Terrestrial and Aquatic Animals The unique characteristics of this product, At onik PGR, its non-toxic mode of action, low use volumes (< 20g/A), and biodegradability (l ow to no persistence) should minimize the risks to all non-targets, including threaten ed and endangered aqua tic and terrestrial animal species. Due to the non-toxic mode of action and/or lack of exposure to nontargets by this product, and Risk Quotient (RQ) calculated at 0.00 for terrestrial and aquatic non-target species toxi c risk and/or exposure to lis ted and endangered/threatened species will be at or near zero. The Agency ’s Individual Effects Chance Model Version 1.1 (Table 6 and 7) was used to further es timate the chance of risk to endangered/ threatened avian and aquatic species from expos ure to Atonik. These values (avian risk at 1 in 294,000 and aquatic risk at 1 in 418,000,000) show that Atonik will not cause toxic risk to these endangered/threatened species. The mode of action of Atonik is to enhance plant growth, however, calculat ed residues from an expected drift scenario shows that
these levels will be minimal and non efficaci ous (refer to Plant section) and will not
cause an indirect effect in terrestrial and aquatic habitat. The Agency concludes that Atonik exposure is a No Effect (NE) for terrestrial and aquatic species

.

Table 6.0 Individual Effects Chance Model Version 1.1 (Terrestrial Species)

Enter LC 50 or LD 50 2000

Enter desired threshold 0.1 Enter slope of dose-response 4.5
z score result -4.5 Probability associated with z 3.40E-06 Chance of individual effect, ~1 in . . . 2.94E+05



### Table 7.0 Individual Effects Chance Model Version 1.1 (Aquatic Species)

Enter LC 50 or LD 50 27.7

Enter desired threshold 0.05 Enter slope of dose-response 4.5
z score result -5.85463498 Probability associated with z 2.39E-09 Chance of individual effect, ~1 in . . . 4.18E+08



### Plants Plant testing of biological pest control agents is conditionally required if incidents have occurred or if there is published informa tion that the compound is toxic to plants. Therefore, to the best of our knowledge Atonik is not known to be phytotoxic. Positive effects, however, are problematic when it comes to measurement or observation in the field and thresholds will be different for various plant species relative to
environmental conditions. Since Atonik is inte nded for use as a plant growth enhancer

6

### and will be aerially applied to rice, soybean, and cotton crops, there is a possibility of drift to adjacent vegetative areas. This indi rect exposure, however, is minimal and not efficacious. The Agency has made this conclu sion by noting that the direct application scenario for target plants can result in expected residues of 0.02 – 1.1 g ai/A (T-REX). Bynum et a l., (2007) found that the use of n itrophenolates (Chaperone) on cotton increased yield after application of 0.69 g ai/A, but was not efficacious at 0.17 – 0.34 g ai/A. In evaluating Atonik aerial application to a crop the Agency has assumed a worst
case scenario of about 5% drift from the target site onto adjace nt areas that can result in expected residues ranging from 0.001 – 0.06 g ai/A with significan t decreases farther from the target site. These values are a bout 2 -3 orders of magnitude below the non efficacious levels found by Bynum et al., (2007) and illustrates that indirect exposure of Atonik to non-target plants (listed threatened or enda ngered plant species or any designated critical habi tat) will result in No Effect (NE ).

Ecological Effects Summary

The Agency has reviewed the available ecotoxicity data and completed a risk assessment using the maximum application of Atonik to an agricultural crop. Atonik is relatively nontoxic to honey bees and exposure of this pr oduct to terrestrial and aquatic animal species (non-target or listed /threatened species) should not pose a toxic risk. Since, Atonik is intended for use as a plant growth enha ncer and will be aeri ally applied to rice, soybean, and cotton crops; there is a possibility of drift to adjacent vegetative areas. The Agency, however, has evaluated the potential for indirect exposure to plants and concludes that this exposure will be mini mal and not efficacious resulting in residue levels that are 2-3 orders of magnitude be low field levels that were found to not be effective (Bynum et al ., 2007). The Agency concludes that exposure of Atonik to fish and
wildlife and to listed /threatened species and their s upporting habitat will result in a No Effect (NE).

III. References

Bynum, J.B., Cothren, J.T., Lemon, R.G., Fromm, D.D., Boman, R.K. 2007. Field evaluation of nitrophenolate plant growth re gulator (Chaperone) fo r the effect on cotton lint yield. J. Cotton Sci. 11: 20-25.

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 Modelin g; American Society of Agricultural Engineers, pp. 485-490; Orlando, Florida.

U.S. EPA Fact Sheet for Sodium 5-Nitrogua iacolate (129075), Sodium o-Nitrophenolate (129076), Sodium p-Nitrophenolate (129077). Issued August, 2001.

7

### U.S. EPA. Federal Register: Octobe r 26, 2007 (Volume 72, Number 207) Page 61008-
61011.

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 Ch ance Model Version 1.1. EFED/OPP/USEPA.

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

8

### Appendix A

GENEEC Model Output for Aton ik Application to Soybeans

ATONIK SOYBEANS * INPUT VALUES *

-------------------------------------------------------------------- RATE (#/AC) No.APPS & SOIL SOLUBIL APPL TYPE NO-SPRAY INCORP ONE(MULT) INTERVAL Kd (PPM ) (%DRIFT) ZONE(FT) (IN)

------------------------------------------------------------------------------------------------------- .004( .004) 2 7 100.0 100.0 ERL_B( 13.0) .0 .0

FIELD AND STANDARD PO ND HALFLIFE VALUES (DAYS)

-------------------------------------------------------------------- METABOLIC DAYS UNTIL HYDROLYSIS PHOTOLYSIS METABOLIC COMBINED (FIELD) RAIN/RUNOFF (POND) (POND-EFF) (POND) (POND)

-------------------------------------------------------------------------------------------------------------------- 1.00 0 N/A 1.00- 124.00 1.00 .9 9

GENERIC EECs (IN NANOGRAMS/LITER (PPTr)) 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

--------------------------------------------------------------------------------------------------------- 31.22 20.64 4.97 1.74 1.16



### 9

### Appendix B TREX Output for Terrestr ial Exposure and Risk from Atonik Application to Soybeans

Avian Results

Avian Body Ingestion (Fdry) Ingestion (Fwet) % body wgt FI
Class Weight (g) (g bw/day) (g/day) consumed (kg-diet/day)

Small 20 5 2 3 114 2.28E-02

Mid 100 13 65 65 6.49E-02 Large 1000 58 291 29 2.91E-01

Avian Body A djusted LD50

Weight (g) (mg/kg-bw)

20 1038.45
100 1322.00
1000 1867.37

small mid large 20 g 100 g 1000 g

Short Grass 1.10 0.63 0.28
Tall Grass 0.51 0.29 0.13 Broadleaf plants/sm Insects 0.62 0.35 0.16 F ru i ts / po d s / see d s /l g i nsects 0.07 0.04 0.02

20 g 100 g 1000 g

Short Grass 0.00 0.00 0.00
Tall Grass 0.00 0.00 0.00 Broadleaf plants/sm insects 0.00 0.00 0.00 Fruits/pods/seeds/lg insects 0.00 0.00 0.00

Acute Chronic

Short Grass 0.00 #DIV/0!
Tall Grass 0.00 #DIV/0! Broadleaf plants/sm Insects 0.00 #DIV/0! Fruits/pods/seeds/lg insects 0.00 #DIV/0! RQs 

### Dietar y -based RQs

(Dietary-based EEC/LC50 or
NOAEC ) Avian Acute RQs 

### Dose-based RQs

(Dose-based EEC/adjusted LD50) Avian Classes and Body Weights Dose-based EECs

(mg/kg-bw)



### 10Mammalian Results

Mammalian Body Ingestion (Fdry) Ingestion (Fwet) % body wgt FI
Class Weight (g bwt/day) (g/day) consumed (kg-diet/day)
15 3 14 95 1.43E-02
Herbivores/ 35 5 23 66 2.31E-02
insectivores 1000 31 153 15 1.53E-01
15 3 3 21 3.18E-03
Grainvores 35 5 5 15 5.13E-03
1000 31 34 3 3.40E-02

Mammalian Body A djusted A djusted

Class Weight LD50 NOAEL
15 759.35 659.35
Herbivores/ 35 614.40 533.48
insectivores 1000 265.74 230.75
15 759.35 659.35
Grainvores 35 614.40 533.48
1000 265.74 230.75

15 g 35 g 1000 g 15 g 35 g 1000 g

Short Grass 0.92 0.64 0.15
Tall Grass 0.42 0.29 0.07 Broadleaf plants/sm Insects 0.52 0.36 0.08 Fruits/pods/seeds/lg insects 0.06 0.04 0.01 0.01 0.01 0.00

Acute Chronic A cute Chronic Acute Chronic

Short Grass 0.00 0.00 0.00 0.00 0.00 0.00
Tall Grass 0.00 0.00 0.00 0.00 0.00 0.00 Broadleaf plants/sm insects 0.00 0.00 0.00 0.00 0.00 0.00 Fruits/pods/lg insects 0.00 0.00 0.00 0.00 0.00 0.00 Seeds (granivore) 0.00 0.00 0.00 0.00 0.00 0.00

Acute Chronic

Short Grass #DIV/0! 0.00
Tall Grass #DIV/0! 0.00 Broadleaf plants/sm insects #DIV/0! 0.00 Fruits/pods/seeds/lg insects #DIV/0! 0.00 

### Dietar y -based RQs

(Dietary-based EEC/LC50 or NOAEC) Mammal RQs 15 g mammal 35 g mammal 1000 g mammal 

### Dose-based RQs

(Dose-based EEC/LD50 or NOAEL) Granivores Mammalian Classes and Body weight Dose-Based EECs

( m g /k g -bw ) Herbivores/ insectivores



### 11

### Appendix C Risk Conclusions for Li sted Threatened/Endangered Species

Table C-1. Summary of risk co nclusions for listed threatened and endangered species that may be exposed to Atonik 

### Species Risk Conclusion Presumptions

Aquatic Animal Species No Effect Occurs in habitat that may be affected by appli cation. Toxicity values indicate no potential direct (acute and chronic effects) or indirect (changes in water quality parameters; loss of cover/food)
effects. Residue levels are not
efficacious.

Terrestrial Animal Species No Effect Occurs in habitat that may be affected by appli cation. Toxicity values indicate no potential direct (acute and chronic effects) or indirect (changes in water quality parameters; loss of cover/food)
effects. Residue levels are not
efficacious.

Terrestrial Animal Species No Effect Occurs in habitat that may be affected by appli cation. Toxicity values indicate no potential direct (acute and chronic effects) or indirect (changes in water quality parameters; loss of cover/food)
effects. Residue levels are not
efficacious.

Terrestrial Plants No Effect Occurs in habitat that may be affected by appli cation. Toxicity values indicate no potential direct (acute and chronic) effects.
Indirect effects from drift are not expected because residues are 2-3 orders of magnitude below levels
that were found to not be
efficacious.

Aquatic Plants
No Effect Occurs in habitat that may be affected by appli cation. Toxicity values indicate no potential direct (acute and chronic) effects.
Indirect effects from drift are not expected because residues are 2-3 orders of magnitude below levels
that were found to not be
efficacious.



### 12