### UNITED STATES ENV IRO NMENTAL PROTECTION AGENCY WASHINGTON, D

. C

. 20460

OFFICE OF CHE MICA L SAFETY
AND POLL UTION PREVENTION



### MEMORANDUM

DAT E : Septe mb er 10

, 2014



### SUBJECT: Dikegulac S odium

. Hum an Health Scop ing Docum ent and Pr e liminary Risk
Assessment.



### PC C ode: 1 0960 1 

### DP Barcode: D 42 1171 

### Decision No.: 492549 

### Registration Nos.: 2217-932, 2217-776, 691 1 7-7 

### Petition No. : NA 

### Regulatory Action: Registration Review 

### C ase N o.: Risk Assessment Type : Single C hemical 

### TXRN o.: NA 

### CAS No.: 52 508- 35-7 

### MRIDNo .: NA 

### 40 CF R: NA

FROM: Bridgett Bo bowiec, Biologi s t

# ~**~** Yung Yan g , Ph.D.

, T oxicologist 

## 6-

- 

## 7--cl

P. Yvonne B arnes, Chemi st 

## -,?.a

....,___ 6**~** Risk Assessment Branch 6 Hea lth E ffects Division (750 9P)



### THROUGH: Shal u

# Shel~t**,** Indu_strial

# Hygieni~t**·~' ~~**  Q
1

# r.**~** Donna Dav1 s , Actmg Branch Chief ·

### (%lj~**~\/** Y r7 Risk Assessment Branch 6
H ealth Effect s Division ( 7509 P )



### TO: Ma tthew Manupella, Chemical Review Manager Cat hryn Britton, Team Leader
Ri s k Manageme n t and Implementation Branch
Pest i c ide Re- Evalu ation Division (7508P)

Page 1 of 1 2Executive Summary

To determine the scope o f work necessary to support Registration Review, Health Effects Division (HED) has considered updates to Agency's science policy and risk assessment methodologies and to the dikegulac sodium toxicity, exposure, and usage databases.

Dikegulac sodium is a plant growth regulator. It is registered to control folia r growth and

suppress nuisance fruiting for greenhouse and outdoor landscaping ornamentals, as well as for

tree farms. There are no agr i cultural uses associated with dikegulac sodium

. The current toxi cology and exposure databases for dikegulac sodium are considered complete to support a

non

- food use reg i stration. No residue chemistry data are required for a non-food use pesticide

. The most recen t dikegulac risk assessment took a qualitative approach to assessing risk, since this chemical does not pose a hazard at doses relevant to human exposure.

Dikegulac sodium has low acute toxicity for oral, dermal, and inhala t ion toxicity (all Toxicity Categories IV). The primary eye irritation study (§81-4) i s clas sified as Toxicity Category III. The chemical exhibits slight dermal irritation (Toxicity Category III) and is not a dermal sensitizer. No target organ toxicity i s iden t i fied in dogs and rat s following oral exposures and in rabbit s following dermal exposures at doses including and up to the Lim i t Dose (2': 1,000 mg/kg/day). The Hazard and Science Policy Council (HASPOC) waived the study requirements for subchronic inha la t ion, neurotoxicity (acute and subc hronic), immuno tox ici ty, and reproduction stu dies since there is no evidence of neuro -, developmental, immuno

- , or reproductive toxicity. Long -term rodent information regarding the chronic or carcinogenic potential of dikegulac sodium are not required for a non-food use chemica l. There is no concern for mu tage nici ty. HED has concluded that dikegulac sodium does no t pose a hazard at doses relevant to humans; therefore a qualitative risk assessment is appropriate for this chemical.

There are no registered or proposed residential handler uses for dikegulac sodium. Occupational handler and post-appl i cation exposure as well as residential pos tapplicatio n exposure are expected based on the registered use patterns, however, no endpoints of toxicological concern have been iden t ified for risk assessment purposes since dikegulac sodium does not pose a human
h ea lth hazard, there are no occupational risks or residential post-application risks associated with the registered use ofthis chemical.

No new data are r eq uired to s upport the registration review of this pesticide. There are no hazards associated with dikegulac sod ium at doses relevant to humans; therefore, a qualitative approach to ris k assessment i s appropriate. This document constitutes the preliminary risk

assessme n t for the purpose of registration review. HED concludes that ther e are no human health risks associated with the currently registered uses of dikegulac sodium.

Introduction

HED has evaluated t he status of the human health assessme n t for dikegulac sodium to determine whether s u fficient data are avai l able and whether any updates are needed to support Registration Review. HED has considered the most recent human health risk assessment for dikegulac sodium. While ri s k and exposure assessment policies have been updated since the last risk

Page 2 of 12

### Page 3 of 12

assessment (DP317256, Y. Barnes, 10/31/2006 and addendum DP317852, S. Recore, 02/06/2007)

, HED is not recomme nding a new risk assessment as part of registration review due to the qualitative approach taken to assess risk for dikegulac sodium

Dikegulac sodium is structurally similar to natural products involved in the synthesis or biosynthesis of L

- ascorbic acid (vitamin C), naturally occurring pl ant cell wall components, and

to naturally occurring carbohydrates

. Dikegulac sodium is listed as a GRAS (Generally Recognized as Safe) chemical in 21 CFR §182 for use as a chemical preservative (§182 .3013), a dietary supplement (§182.5013), and a nutrient (§182.8013). The chemical identity and physicochemical properties of dikegulac sodium are attached in Tables 1.

There are two end

- use formulations for the growth regulator dikegulac sodium; soluble

concentrate s (2217

- 776 and 2217

- 932 ) and a Ready

- To

- Use (RTU) for mulation (69117

- 7). The soluble concentrate is applied to landscape ornamental s and to tree foliage using mechanically

pressur ized hand gun , backpack sprayers, airblast, manual pressurized h and wand, bark banding, and tree injection systems

. The maximum application rates range from of 0. 035 pounds active ingredient (ai) per gallon to 0. 835 lb ai/ gallon

. The corresponding dikegulac sodium acid equivalent (ae) rate ranged from 0.035 lb ae/gall on to 0.77 lb ae/gallon.

The current label for the soluble concentrate formulation of dikegulac sodium requires baseline dermal protection (long

- sleeved shirt, long pants, shoes plus socks ) and the addition of waterproof gloves

. T he RTU injection product requires the same PPE plus the protective

eyewear

. The injection product contain a requirement for protective eyewear due to the nature of the application and not due to the acute toxicity of the active ingredient

. Worker protective

sta ndard ( WPS ) language for early entry includes coveralls, shoes, socks, chemical

- resistant gloves ( of any waterproof material ) , and protective eyewear.

Most recently, there was a registrant request reviewed which petitioned the Agency to reduce the 12 ho ur restricted entry interval (REI) which is based on the acute toxicity of the chemical . HED determined that the registrant would need to supply EPA with specific information about the end use product containing dikegulac sodium to qualify for a reduced 4

- hou r REI requirement

. The
REI remains 12 hours pending registrant submission of end use product hypersensitivit y, adverse health effects, and incident information (D370143, A. Nielson, 02/04/2010 ).

Hazard Identification/Toxicology

The available toxicological data for dikegulac sodium are sufficient for hazard assessment. All submitted studies are detailed in the attached toxi cology tables (Table 3 through 5 ). The database consists of acute toxicity battery, developmental toxicity studies in rat s and rabbit s , subchronic (oral) toxicity studies in dog s and rat s, and a 21

- day dermal toxicity study in rabbit s

. Mutagenicity studies are available include Salmonella typhimurium , micronucleus, and gene mutation assays. The HASPOC considered all of the a vailable hazard and exposure information for dikegulac sodium and concluded that data requirements for subchronic inhalation toxicity

, reproduction, neurotoxicity (acute and subchronic), and immunotoxicity studies are waived at this time ( U. Habiba, TXR 0057022 , 07/31/2014)

. Since it is a non

- food use chemical, submitted

### Page 4 of 12

toxicity studies in combina tion of published literature are sufficient to assess the toxicity of dikegulac sodium.

The available acute toxicity studies indicate that dikegulac sodium h as very low oral, dermal and inhalation toxicity (Toxicity Categories IV). In July, 2008, EPA reclassified t he primary eye irritation study (§81

- 4) from Toxicity Category II to Toxicity Category III based on provided supportin g documents and a re

- evaluati on of the submitted Dikegulac sodium exhibited slight dermal irritation (Toxicity Category III) and is not a skin sensitizer

.
Acceptable/Guideline oral subchronic toxicity studies were conducted in dogs and rats. A 90

- day rat subchronic study revealed no toxicity, t he NOAEL is ≥ 2,000 mg/kg/day with no LOAEL being established. In a 13

- week dog toxicity study , beagle dogs were dosed at 0, 500, 1200 (via gelatin capsules), or 3000 mg/kg/day (via stomach tubes), diarrhea (presumable caused osmotically) was observed in the first week of treatment and especially in the high dose groups (1200 and 3000 mg/kg/day). However, this had no effect on the weight development of the dogs. The NOAEL is 1,200 mg/kg/day and the LOAEL is 3,000 mg/kg/day based on the relativ ely mild effects of profuse watery diarrhea and occasional vomiting

.
A rat developmental toxicity study revea led no developmental or embryotoxic effects based on fetal and maternal parameters. The maternal NOAEL is 700 mg/kg/day and the LOAEL is 2,000 mg/kg/day, based on clinical observations of light sedation following the first two treatments. The developmental NOAEL is > 2,000 mg/kg/day with no LOAEL being established

. In a rabbit developmental study, no treatment

- related developmental or embryotox ic effects were seen based on maternal clinical signs, liver enzymes, liver weights, gross pathology, litter size, numbers of live fetuses, dead fetuses, or resorptions, post implantation loss, sex ratio, fetal weight, or placental weight. The maternal NO AEL is 700 mg/kg/day and the LOAEL is 2,000 mg/kg/day, based on clinical observations of diarrhea and lack of body weight gain

. The developmental NOAEL is > 2,000 mg/kg/day with no LOAEL being established.

A 21

- day dermal toxicity study in rabbits result ed in slight erythema. However, no compound

related effects on mortality, body weight, body weight gain, food consumption, hematology, ophthalmology, or gross pathology were observed in the females. The dermal NOAEL is 600 mg/kg/day with no LOAEL being e stablished.

Available genotoxicity and mutagenicity studies were negative for reverse gene mutations in Salmonella typhimurium , not mutagenic in mouse lymphoma cell assays with/without activation at levels ranging from 500 to 5,000 μ g/ mL, and negative f or micronucleus induction in bone marrow cells of male and female CD

- 1 mice harvested 24, 48, and 72 hours post

- administration of a single dose o f 1,250, 2,500 or 5,000 mg/kg. For a non

- food use chemical, no long

- term rodent information regarding the carcinogenic potential of dikegulac sodium is required

.
Based on the available data, there is no evidence to suggest that dikegulac sodium causes increased susceptibility in infants and children. Furthermore, based on the low hazard concern from the avai lable studies, no endpoints of toxicological concern have been identified for risk assessment purposes.

### Page 5 of 12

Dietary Exposure

Dikegulac sodium does not have any agricultural or food production uses, as such it is designated and classified as a “non

- food” use chemical. Based on the low hazard concern from the available studies, no endpoints of toxicological concern have been identified. Due to t he hazard profile drinking water assessments are not needed. In addition

, because dikegulac sodium is not used on any agricultural food and/or feed commodities and is classified as a “non

- food” use chemical and metabolized to non

- toxic substances; a dieta ry risk assessment is not required.

Residential Exposure

Dikegulac sodium is used in small quantities by the professional landscaping industry, and is not marketed to homeowners. Residential post application exposure is possible from occupational applic ation to residential use sites h owever, due to the (very) low systemic toxicity of dikegulac sodium, a residential quanti tative risk assessment is not warranted for any type, or duration of

exposure.

Spray Drift and Volatility Since dikegulac does not pose a hazard, there are no risks associated with potential exposure to spray drift or exposure from volatility expected from this chemical.

Occupational Exposure Dikegulac sodium is registered for use as two end

- use product formulations (soluble concent rate and RTU injections). Table 6 summarizes the occupational handler use patterns and potential exposure scenarios

. While there are uses that could result in occupational handler and post

application exposure, due to the (very) low systemic toxicity of dikegulac sodium, a quanti tative occupational risk assessment is not warranted for any type, or duration of exposure.

Turf Transferable Residue (TTR) and Dislodgeable Foliar Residue (DFR) data are not required for dikegulac sodium based on the current us e patterns for this chemical.

Public Health and Pesticide Epidemiology Data

Because there are no incident cases reported for dikegulac sodium in either the Main or Aggregate Incident Data System ( IDS ) module

, Poison Control Centers (PCCs), California Department of Pesticide Regulation, National Pesticide Information Center(NPIC) and National Institute of Occupational Safety and Health’s Sentinel Event Notification System for Occupational Risks (NIOSH SENSOR) t here does not appear to be a concern at this time that would warrant further investigation (D 317857

, M

. Hawkins , 0 7 /2 5 /20 0 6 )

.

Environmental Justice

Potential areas of environmental justice concerns, to the extent possible, were considered in this human health risk assessment, in accordance with U.S. Executive Order 12898, "Federal Actions to Address Environmental Justice in Minority Populations and Low

- Income Populations," ( http://ww w.eh.doe.gov/oepa/guidance/justice/eo12898.pdf ). As a part of every pesticide risk

### Page 6 of 12

assessment, OPP considers a large variety of consumer subgroups according to well

- established procedures. In line with OPP policy, HED estimates risks to population subgro ups from pesticide exposures that are based on patterns of that subgroup’s food and water consumption, and activities in and around the home that involve pesticide use in a residential setting. Extensive data on food consumption patterns are compiled by t he United States Department of Agriculture’s (USDA’s) National Health and Nutrition Examination Survey (NHANES), What We Eat in America (NHANES/WWEIA) and are used in pesticide risk assessments for all registered food uses of a pesticide. These data are a nalyzed and categorized by subgroups based

on age and ethnic group. Additionally, OPP is able to assess dietary exposure to smaller, specialized subgroups and exposure assessments are performed when conditions or circumstances warrant. Whenever appropria te, non

- dietary exposures based on home use of pesticide products and associated risks for adult applicators and for children , youths, and adults entering or playing on treated areas following application are evaluated. Further considerations

are currently in development as OPP has committed resources and expertise to the development of specialized software and models that consider exposure to bystanders and farm workers as well as lifestyle and traditional dietary patterns among specific subgroups

.

Cumulative

Unlike other pesticides for which EPA has followed a cumulative risk approach based on a common mechanism of toxicity, EPA has not made a common mechanism of toxicity finding as

to dikegulac sodium and any other substances

. Dikegulac sodium does not appear to produce a toxic metabolite produced by other substances. For the purposes of this tolerance action, therefore, EPA has not assumed that dikegulac sodium has a common mechanism of toxicity with other substances. For inf ormation regarding EPA’s efforts to determine which chemicals have a common mechanism of toxicity and to evaluate the cumulative effects of such chemicals, see the policy statements released by EPA’s OPP concerning common mechanism determinations and proce dures for cumulating effects from substances found to have a common mechanism on EPA’s website at http://www.epa.gov/pesticides/cumulative/

.

Human Studies

This assessment does not rely on any data from studies in which human subjects were intentionally exposed to a pesticide.

Data Requirements

Residue chemistry data are not requir ed for a non

- food use chemical however the UV/visible absorption spectrum study is still outstanding. There are no outstanding toxicolog ical or exposure data requirements for the currently registered uses of dikegulac sodium

.
Preliminary Human Health Risk Assessment

The qualitative assessment discussed herein constitutes the preliminary risk assessment for dikegulac sodium. HED concludes that there are no human health risks associated with the currently register ed uses of dikegulac sodium.

### Page 7 of 12

References

Memoranda Relevant to Registration Review for Dikegulac Sodium

Author DP or TXR

Barcode Date Title

Y. Barnes D 317256 10/31/2006 Dikegulac Sodium. Human Health Considerations for the Reregistration Eligibility Decision

S. Recore D 317852 02/06/2007 Dikegulac Sodium: Addendum to HED Risk Assessment

U. Habiba TXR 0057022 07/31/2014 Dikegulac Sodium: Summary of Hazard and S cience Policy Council (HASPOC): subchronic inhalation , neurotoxicity (acute and subchronic), reproduction, and immunotoxicity studies

. M. Hawkins D317857 07/25/2006 Review of Dikegulac Sodium Incident Reports

A. Nielsen D370143 02/04/2010 Dikegulac Sodium: HED’s response to PBI/Gordon Corporation’s request to permit a
4

- hour restricted entry interval for the end use product Atrinal Plant Growth Regulator (EPA Reg. No. 2217

- 776)

S. Recore D 317852 02/06/2007 Dikegulac Sodium: Addendum to HED Risk Assessment Acid Equivalent Rates

Attachment s

Table 1. Chemical Identity of Dikegulac Sodium Table 2. Physicochemical Properties of Technical Grade Dikegulac Sodium Table 3

. Satisfaction of Dikegulac Sodium Toxicology Data Requirements Table 4

. Dikegulac Sodium Acute Toxicity Profile Table 5

. Dikegulac Sodium Subchronic, Chronic, and Other Toxicity Profiles Table 6

. Summary of Representative Occupational Use Patterns, Formulations, and App Rates

### Page 8 of 12

Attachment s

Chemical Identity and Physicochemical Properties T able s

Table 1. Chemical Identity of Dikegulac Sodium

Chemical Structure

Common Name Dikegulac Sodium
PC Code 10 9601

CAS Name sodium 2,3:4,6

- bis

- O

- (1

- methylethylidene)

- α

- L

- xylo

- 2

- hexulofuranosonate

IUPAC Name sodium 2,3:4,6

- di

- O

- isopropylidene

- α

- L

- xylo

- 2

- hexulofuranosonate

CAS No. 52508

- 35

– 7 Registration Review Case No. 3061 Chemical Class` Acid herbicide Molecular weight 235.02 g/mol

Table 2. Physicochemical Properties of Technical Grade Dikegulac Sodium

Parameter Value Reference

Molecular Weight 296.25 grams MSDS

Melting range > 300 o C MSDS

Density 9.12 lbs/gal MSDS

Water solubility (20°C) 590 g/L, soluble Merck Index 12 th Edition

Solvent solubility (20°C) methanol 390 g/L ; ethanol 230 g/L ; chloroform 60 g/L ; acetone <10 g/L ; hexane <10 g/L; cyclohexanone <10 g/L Merck Index 12 th Edition

Vapor pressure 3.08E

- 12 mm Hg at 25 ° C SRC: Neely, WB & Blau, GE (1985)

Dissociation constant, pKa Not reported Data Required Octanol/water partition coefficient, log K OW (25°C) Log P =

- 2.05 SRC: Meylan, Wm. Howard ,PH (1995)
UV/visible absorption spectrum Not reported Data Required

### Page 9 of 12

Table 3

. Toxicology Data Requirements for Dikegulac Sodium

Study Technical Required Satisfied
870.1100 Acute Oral Toxicity 870.1200 Acute Dermal Toxicity 870.1300 Acute Inhalation Toxicity 870.2400 Acute Eye Irritation 870.2500 Acute Dermal Irritation 870.2600 Skin Sensitization yes yes yes yes yes yes yes

yes yes yes yes yes 870.3100 90

- Day Oral Toxicity in Rodents 870.3150 90

- Day Oral Toxicity in Non

- Rodents 870.3200 21/28

- Day Dermal Toxicity 870.3250 90

- Day Dermal Toxicity 870.3465 90

- Day Inhalation Toxicity yes CR a
yes CR a (no) CR a ( yes ) y es

yes yes

--- waived b
870.3700 Prenatal Developmental Toxicity Study (Rodent) 870.3700 Prenatal Developmental Toxicity Study (Non

- Rodent) 870.3800 Reproduction and Fertility Effects yes yes yes y es

yes waived b
870.4100 Chronic Toxicity (Rodent) 870.4200 Carcinogenicity (Two Rodent Species; Rat and Mouse) 870.4300 Combined Chronic Toxicity/Carcinogenicity CR a (no) CR a (no)

--- y es

yes

--- 870.5100 Bacterial Reverse Mutation Test yes y es 870.5300 i n vitro Mammalian Cell Gene Mutation Test 870.5375 i n vitro Mammalian Chromosome Aberration Test 870.5385 Mammalian Bone Marrow Chromosomal Aberration Test 870.5395 Mammalian Erythrocyte Micronucleus Test yes yes yes yes y es

yes yes yes 870.6200 Neurotoxicity Screening Battery (Acute, Rat) 870.6200 Neurotoxicity Screening Battery (Subchronic, Rat) 870.6300 Developmental Neurotoxicity Study yes yes CR a (no) waived b

waived b

--- 870.7200 Companion Animal Safety 870.7485 Metabolism and Pharmacokinetics 870.7600 Dermal Penetration 870.7800 Immunotoxicity CR a (no) CR a (no) CR a (no)

yes ---

yes

--- waived b

a CR = conditionally required. b Waived by Hazard and Science Policy Council (HASPOC) on ( TXR )

.

### Page 10 of 12

Table 4 . Acute Toxicity Data for Dikegulac Sodium

Guideline No. Study Type MRID Results Toxicity Category

870.1100 81

- 1 Acute oral [rat]

Acceptable/guideline 44093901

No deaths, no clinical signs LD50 >5000 mg/kg. IV Acute oral [rat]

Unacceptable/guideline 43064604

43064605

43064606

43064607

43064608

870.1200 81

- 2 Acute dermal [rat]

Acceptable/guideline 43064612 3 deaths, no clinical signs LD50 >2000 mg/kg III

Acute dermal [rabbit]
Acceptable/guideline 43064610 LD50 >1000 mg/kg II

44093902 No deaths, no clinical signs. LD50 >5000 mg/kg IV

870.1300 81

- 3 Acute inhalation [rat]

Acceptable/guideline 43064613 No deaths. LC50 >2 mg/L III

44093903 IV

870.2400 81

- 4 Acute eye irritation [rabbit]

Acceptable/guideline 43064614 Conjunctival redness was persistent for 48 and 72 hours. IV

44093904 No corneal effects were observed. Conjunctival redness, swelling or discharge returned to normal within 72 hours. II I a

870.2500

81

- 5 Acute dermal irritation [rabbit]

Unacceptable/guideline 43064615 Slight dermal irritation/ slight erythema was apparent 72 hours after application III

Acute dermal irritation [rabbit]
Acceptable/guideline 44093905 Slight erythema and edema observed IV

870.2600

81

- 6 Acute dermal sensitization [guinea

pig]
Unacceptable/guideline 43064616 All animals survived. No adverse clinical signs. Not a dermal sensitizer N/A

870.2600

81

- 6 Acute dermal sensitization [guinea

pig]

Acceptable/guideline 44093906 All animals survived. No adverse clinical signs. Not a dermal sensitizer N/A

870.2500

81

- 5 Acute dermal irritation [rabbit]

Acceptable/guideline 44093905 Slight erythema and edema observed IV

870.2600

81

- 6 Acute dermal sensitization [guinea

pig]
Unacceptable/guideline 43064616 All animals survived. No adverse clinical signs. Not a dermal sensitizer N/A

870.2600

81

- 6 Acute dermal sensitization [guinea

pig]

Acceptable/guideline 44093906 All animals survived. No adverse clinical signs. Not a dermal sensitizer N/A

a The toxicity category on eye irritation was revised to III (TXR 0054936, 2008)

### Page 11 of 12

Table 5 : Subchronic, Developmental, and Other Toxicity Profile on Dikegulac Sodium
Guideline#/ Study Type MRID# (year)/ Classification /Doses Results

870.3100 82

- 1a

90

- Day Subchronic toxicity (rat) 42957701 (1975)

Acceptable/guideline

22 Fullinsdorf albino rats/sex/dose of 0, 200, 700, 2000 mg/kg/day for 13 weeks Mortality, clinical signs, food consumption, body weight, hematology, urinalysis, organ weights, gross and microscopic pathology were unaffected by treatment.
The NOAEL is ≥ 2000 mg/kg/day. The LOAEL was not established.

870.3100 82

- 1b

90

- Day Subchronic toxicity (dog) 42957702 (1975)

Acceptable/guideline
4 beagle dog sex/dose of 0, 500

, 1200 , 3000 mg/kg bw/day for 13 weeks Mortality, clinical signs, body weight, hematology, urinalysis, organ weights, gross and microscopic pathology were unaffected by treatment.

The NOAEL is 1200 mg/kg/day. The LOAEL is 3000 mg/kg/day based on relatively mild effec ts of profuse watery diarrhea and occasional vomiting.

870.3250 82

- 3 21

- Day dermal toxicity 42957703 (1975)

Acceptable/Guideline

5 New Zealand White rabbits /sex/ dose of 0, 3% or 30% seven days a week for 21 days. Slight erythema occurred in three male and three female control rabbits during the treatment period.

The dermal NOAEL is 600 mg/kg/day, no LOAEL being established.

870.3700a 83

- 3a Developmental Toxicity (rat) 43064617 (1977)

Acceptable/Guideline

40 female Fullinsdorf albino rats/dose of (by gavage) 0, 200, 700 or 2000 mg a.i./kg/day (GD 7

- 16) The maternal NOAEL is 700 mg/kg/day. The maternal LOAEL is 2000mg/kg/day, based on clinical observations of light sedation following the first two

treatments.

The developmental NOAEL is > 2000 mg/kg bw/day. No developmental LOAEL was established

.

870.3700a 83

- 3a
Developmental Toxicity (rabbit) 43064618 (1977)

Acceptable/Guideline

20 female yellow

- sliver rabbits/dose of 0, 200, 700 or 2000 mg a.i./kg/day (GD 7

- 1 9) The maternal NOAEL is 700 mg/kg/day. The maternal LOAEL is 2000 mg/kg /day, based on clinical observations of diarrhea and lack of body weight gain.

The developmental NOAEL is > 2000 mg/kg /day. No developmental LOAEL was observed.

Gene Mutation 84

- 2 870.5100 ( Salmonella typhimurium ) 440393907 (1995)

Acceptable/Guideline

100, 333, 1000, 3330 and 5000 μg/ plate Negative for reverse gene mutations in Salmonella typhimurium TA98, TA100, TA1535 and TA1537 in presence or absence of S9 activation to doses from 100 to 5000 μg/plate. Cytotoxicity was not observed at any dose levels.

Gene Mutation 870.5300 84

- 2 (mouse lymphoma cells) 440393908 (1995)

Acceptable/Guideline

500 to 5000 μg/mL Not mutagenic in assays with/without S9activation.
Cytotoxicity was not observed at any dose levels.

Micronucleus 870.5395 84

- 2 (mouse) 440393909 (1995)

Acceptable/Guideline

1250, 2500, or 5000 mg/kg Negative for micronucleus induction in bone marrow cells of Male and Female CD

- 1 mice harvested 24, 48, and 72 hrs. post

- administration of single doses of 1250, 2500, or 5000 mg/kg/day. No overt toxicity in any treated animal or target organ in any treatment group.

### Page 12 of 12

Oc cupati onal Exposure Use Pattern Table

Table 6 . Summary of Maximum Application Rates for Registered Dikegulac

- Sodium Uses

EPA Reg. No Crop Target % ai. Maximum Application
Rate Application Equipment Amount

Handled Daily Use Directions and Limitations

Soluble Concentrate

ATRINAL® NURSERY AND GREENHOUSE 2217

- 932 Greenhouse

and nursery

o rnamentals

, tree farms (chemical pinching)

Foliar

Spray, bark banding, soil drench 18.5 % 0.052 lb

ai/gal lon

(0.048 lb

ae 1 /gal lon) Mechanically

pressurized hand gun 1,000

gallons

N ot for use on green ash, red oak, conifers, trailing and weeping lantana, Christmas tree farms , and evergreens in California. Do not apply through any type of irrigation system. Do not use on food or fodder crops. PPE includes baseline dermal protection. Direct inj ections to trees, applicators must wear protective eyewear Manually pressurized handwand 40

gallons
B ackpack

ATRINAL® PLANT GROWTH REGULATOR 2217

- 776 Landscape

Ornamentals

-- shrubs, hedges, trees, and groundcover (growth control) 4.26 lb ai/A

or 0.039 lb ai/ga l l on (0.035 lb

ae /gal lon) Mechanically

pressurized hand gun 1,000

gallons

Manually pressurized handwand 4 0

gallons
B ackpack

Use with medium or coarser spray nozzles. Do

not apply through any type of irrigation system. Do not use on food or fodder crops. PPE includes baseline dermal protection. Direct injections to trees, applicators must wear protective eyewear Fruiting Landscape Trees and Shrubs (suppression of flower and fruit formation) 7.1 lb ai/A

or 0.065 lb ai/gal lon (0.060 lb

ae /gal lon) H andgun 1,000 gallons Manually pressurized handwand 40

gallons
B ackpack

Broadleaf trees in rights

- of

way, parks Tree

injection 0.09 lbs

a.i./tree or 0.835 lb ai/gal lon

(0.77 lb ae/gallon) I njection

system NA

Ready to Use
Pinscher® PGR 69117

- 7 Ornamental

trees Tree injection 18.5 % 0.0016 lb

a.i./ tree I njection

system NA Apply in spring prior to flower. Do not apply to

foo bearing plants
1 ae= acid equivalent.