UNITED STATES ENVIRONMENTAL PROTECTION AGENCY 

WASHINGTON, D.C. 20460 

MEMORANDUM 

Date: October 1, 2015 

OFFICE OF 

CHEMICAL SAFETY AND 

POLLUTION PREVENTION 

SUBJECT: Ethephon: Human Health Risk Assessment for Registration Review of Ethephon. 

PC Code: 09980 I DP Barcode: 423165 

Decision No.: 495942 Registration No.: NA 

Petition No.: NA Regulatory Action: Reg Review 

Risk Assessment Type: Human Health Risk Assessment Case No.: 0382 

TXR No.: NA CAS No.: 16672-87-0 

MRID No.: NA // l/J,_ /~R: §180.300 

FROM: Thurston G. Morton, Chemist tf:({~ /.1lf.f.! () '~ Kelly O'Rourke, Biologist I "'"'J /) /?71 - / _ 

Health 

Abdallah 

Effects 

Khasawinah

Division 

, PhD.

(7509P) 

, Toxicologist / / ~ 

THROUGH: Elissa Reaves, PhD, Branch Chief 

Risk Assessment Branch IV 

Health Effects Division (7509P) 

TO: Marquea King 

~~ 

Risk Management and Implementation Branch 5 

Pesticide Re-Evaluation Division (PRD) (7508P) 

Page 1of59 
1.0 Executive Summary ........................................................................................................... 4 

2.0 HED Recommendations .............................................................................. ...................... 7 

2.1 Data Deficiencies ..... ............... ........ ............................................................. ................. .. 7 

2.2 Tolerance Considerations ............................... ................... ...................................... .... .. 7 

2.2.1 Enforcement Analytical Method ........... ..... ... .... .... .... .... ... ...................... .......... ... .... .. 7 

2.2.2 International Harmonization ........ ..................... ....... ............................. ....... ... .......... 8 

2.2.3 Recommended Tolerances ........................................................................ ... .............. 8 

2.3 Label Recommendations ........................................... ....................................... ....... ....... 9 

2.3.1 Recommendations from Residue Reviews ................................................................ 9 

2.3.2 Recommendations from Occupational Assessment ................................................. 9 

2.3.3 Recommendations from Residential Assessment ................................... ................ I 0 

3.0 Introduction .............................................................. .... ....... .... ............................ .... ... ... ... I 0 

3.1 Chemical Identity .... ........................... ......... .... .... .... .... .... ....... .................. ... ... .... .......... IO 

3.2 Physical/Chemical Characteristics ............................................................................. l 0 

3.3 Pesticide Use Pattern ........ .... .... .................................................................................... l 0 

3.4 Anticipated Exposure Pathways ...................... .... ....................................................... I 0 

3.5 Consideration of Environmental Justice .................................................................... l l 

4.0 Hazard Characterization and Dose-Response Assessment .......................................... I 1 

4.1 Toxicology Studies Available for Analysis ................................................................. 11 

4.2 Absorption, Distribution, Metabolism, & Excretion (ADME) ................................. 12 

4.2.1 Dermal Absorption ... ................................................................................................ 12 

4.3 Toxicological Effects .................... .... ........................................... ................................. 12 

4.4 Safety Factor for Infants and Children (FQPA Safety Factor) ............................. .. 14 

4.4.1 Completeness of the Toxicology Database .............................................................. 14 

4.4.2 Evidence of Neurotoxicity ........................................................................................ 14 

4.4.3 Evidence of Sensitivity/Susceptibility in the Developing or Young Animal.. ...... 14 

4.4.4 Residual Uncertainty in the Exposure Database ................................................... l 5 

4.5 Toxicity Endpoint and Point of Departure Selections .............................................. 15 

4.5.1 Dose-Response Assessment ...................................................................................... 15 

4.5.2 Recommendation for Combining Routes of Exposures for Risk Assessment ..... 16 

4.5.3 Cancer Classification and Risk Assessment Recommendation ........ ... ... .... ... ....... 16 

4.5.4 Summary of Points of Departure and Toxicity Endpoints Used in Human Risk 

Assessment ..................................................................... .... ...................................................... 17 

4.6 Endocrine Disruption ....... .... ......................................................................... ....... ........ 17 

5.0 Dietary Exposure and Risk Assessment ......................................................................... 18 

5.1 Metabolite/Degradate Residue Profile ....................................................................... 18 

5.1.1 Summary of Plant and Animal Metabolism Studies ............................................. 18 

5.1.2 Summary of Environmental Degradation .............................................................. 19 

5.1.3 Comparison of Metabolic Pathways ......................... .................. ............................ 19 

5.1.4 Residues of Concern Summary and Rationale ... .... .... ............................ .... ... ....... . 19 

5.2 Food Residue Profile ............................ ........ ..... .... .... .... .... ... .... .... ................................ 20 

5.3 Water Residue Profile .......................................... .... .... .... ................................ ....... ..... 20 

5.4 Dietary Risk Assessment .... ................................................................................. ......... 22 

5.4.1 Description of Residue Data Used in Dietary Assessment .................................... 22 

5.4.2 Percent Crop Treated Used in Dietary Assessment .............................................. 22 

5.4.3 Acute Dietary Risk Assessment ........................................................................ ....... 22 

Page 2 of 59 
Page 3 of 59

5.4.4 Chronic Dietary Risk Assessment........................................................................... 23

5.4.5 Cancer Dietary Risk Assessment............................................................................. 23

6.0 Residential (Non-Occupational) Exposure/Risk Characterization ............................. 24

6.1 Residential Handler Exposure .................................................................................... 24

6.2 Post-Application Exposure .......................................................................................... 25

6.3 Residential Risk Estimates for Use in Aggregate Assessment.................................. 27

6.4 Residential Bystander Post-application Inhalation Exposure ................................. 27

6.5 Spray Drift.................................................................................................................... 28

7.0 Aggregate Exposure/Risk Characterization.................................................................. 29

7.1 Acute Aggregate Risk................................................................................................... 29

7.2 Short-Term Aggregate Risk ........................................................................................ 29

7.3 Intermediate-Term Aggregate Risk ........................................................................... 30

7.4 Chronic Aggregate Risk .............................................................................................. 30

7.5 Cancer Aggregate Risk ................................................................................................ 30

8.0 Cumulative Exposure/Risk Characterization ............................................................... 30

9.0 Occupational Exposure/Risk Characterization ............................................................ 31

9.1 Short- and Intermediate-term Handler Risk............................................................. 31

9.2 Short-/Intermediate-Term Post-Application Risk .................................................... 35

9.2.1 Occupational Post-application Inhalation Exposure/Risk Estimates.................. 35

9.2.2 Occupational Post-application Dermal Exposure/Risk Estimates....................... 35

10.0 References......................................................................................................................... 36

Appendix A. Toxicology Profile and Executive Summaries .................................................. 37

A.1 Toxicology Data Requirements................................................................................... 37

A.2 Toxicity Profiles............................................................................................................ 38

A.3 Hazard Identification and Endpoint Selection .......................................................... 44

Appendix B. Physical/Chemical Properties............................................................................. 46

Appendix C. Ethephon Use Pattern ......................................................................................... 47

Appendix D.................................................................................................................................. 58
Page 4 of 59

1.0 Executive Summary

Attached is Health Effects Division’s (HED) human health risk assessment status update for 

ethephon as part of the Registration Review process. The most recent risk assessment for 

ethephon was conducted in May, 2006 in support of the Tolerance Reassessment Eligibility 

Decision (TRED) which was issued in June, 2006. A Reregistration Eligibility Decision 

document (RED) was issued in April, 1995. 

Ethephon, an organophosphonate, is a plant growth regulator. It regulates phases of plant growth 

and development by application at various growth stages. Ethephon is registered on a number of 

terrestrial food, feed, and nonfood crops, greenhouse nonfood crops, and outdoor plants. 

Ethephon is used to promote fruit ripening, abscission, flower induction, and breaking of apical 

dominance (inhibition of the growth of lateral buds by the terminal bud of a shoot). Ethephon 

reacts to form ethylene gas which is an important component of the plant hormone complex. 

The production of ethylene by the plant occurs naturally as crops mature; ethylene triggers 

production of an enzyme that breaks down cellulose. Ethylene production by the plant can be 

slow during periods of unfavorable weather. Ethephon is used as a source of ethylene gas which 

is absorbed by the plant tissues and moderates the growth process. Ethephon formulations 

include emulsifiable concentrates and soluble concentrates. Application is by broadcast to plant 

foliage by either ground or aerial equipment. Ethephon may also be applied by hand sprayer to 

select home garden vegetables (i.e., tomatoes). 

Hazard Characterization

Ethephon is an organophosphorus/phosphonate compound; it is not an organophosphate. It does 

not have a leaving group as in the organophosphates which is required for the insecticidal mode 

of action. Humans appear to be more susceptible to the clinical toxicity of ethephon than 

experimental animals. Ethephon inhibits red blood cell and plasma cholinesterase (ChE) 

activities in experimental animals and may not be accompanied by clinical signs of toxicity until 

a high threshold level of exposure is reached. Brain ChE activity is not inhibited in vivo. In 

human subjects, plasma and RBC cholinesterase activities were slightly elevated in treated 

subjects but fell within the normal range. Because humans appear to be more susceptible to 

ethephon’s clinical toxicity than animals, a toxicity endpoint for risk assessment was selected 

from a human study.

The toxicology database for ethephon is complete for risk assessment. There is no quantitative or 

qualitative evidence of increased susceptibility following in utero or postnatal exposure in any of 

the developmental or reproductive studies. Developmental and post natal toxicity occurred at 

doses causing maternal/parental toxicity. Ethephon did not produce acute delayed neurotoxicity 

in hens after being dosed with nearly lethal doses. It produced clinical toxicity in rats following 

acute or subchronic neurotoxicity testing, but no neurobehavioral or neuropathological effects

were seen. Ethephon was mutagenic in bacteria but not in cultured mammalian cells. It was 

negative for cytogenic effects both in vitro and in vivo and did not cause unscheduled DNA 

synthesis. There was, however, evidence of mitotic gene conversion in yeast. Ethephon is 

rapidly absorbed from the gut and eliminated in the urine with minimum metabolic 

transformation.
Page 5 of 59

Ethephon was not carcinogenic in rats or mice at doses that were considered adequate. It was 

initially classified in 1994 as Group D for carcinogenicity based on insufficiency of the weight of 

the evidence (TXR # 0011195). However, based on the lack of carcinogenicity in rats and mice 

and mostly negative mutagenic effects, the HIARC in 2002, reclassified ethephon as a "Not 

Likely to be Carcinogenic to Humans” (TXR # 0051308). Ethephon exhibits low acute toxicity 

via the oral (Toxicity Category III), inhalation (Toxicity Category IV), and dermal (Toxicity 

Category III) routes of exposure. Ethephon is dermally corrosive and is a skin and eye irritant 

(Toxicity Category I). It is not a dermal sensitizer.

Endpoints and Uncertainty Factors for Risk Assessment

The point of departure for all exposure scenarios is derived from a 28-day human study with a 

LOAEL of 1.8 mg/kg/day and an uncertainty factor of 30 (10x for intraspecies variation, 

interspecies variation reduced to 1x for use of a human study and 3x for extrapolating from 

LOAEL to a NOAEL) (TXR 0051308). The clinical signs of toxicity in this human study 

occurred at 1.8 mg/kg/day (signs and symptoms are summarized in Table 4.5.4). This endpoint 

is conservative and is protective of any effects exhibited in experimental animals. This 28-day 

human study was reviewed by the Human Studies Review Board in 2006 and found acceptable. 

Dietary (Food and Water) Exposure and Risk

The established ethephon tolerance levels are adequate except for several where levels need 

revised to account for 2 significant figures. The tolerance expression for ethephon has been 

reviewed and should be should be updated based on HED’s Interim Guidance on Tolerance 

Expressions (S. Knizner, 5/27/09).

The tolerance expression for ethephon is harmonized with both Canada and Codex. There is 

harmonization with the Canadian ethephon Maximum Residue Level (MRL) levels for 

cantaloupe, grape, and pineapple. There is harmonization with the Codex ethephon MRL levels 

for apple, blueberry, cherry, and pineapple. Harmonization with the remaining commodity 

MRLs is not possible due to differences in the Good Agricultural Practices (GAP) or field trial 

residue levels used for MRL calculation.

 

Adequate field trial data for ethephon, following maximum application rates, have been 

submitted for all registered use sites. PDP data were available and used for grape and apple 

commodities. Processing factors from processing studies were used with the PDP monitoring 

data. Maximum percent crop treated (CT) was used in the acute dietary exposure analysis while 

the average percent CT was used in the chronic dietary exposure analysis. Use of PDP data, 

field trial data and calculated livestock anticipated residues (ARs) results in a dietary risk (food 

and water) estimate of 39% of the acute population adjusted dose (aPAD) for the U.S. Population 

and 170% for children 1-2 years, the most highly exposed population subgroup. Estimated 

chronic dietary (food and water) exposure is below HED’s level of concern for the general 

population and all subpopulations. Use of anticipated residues and %CT data results in a 
Page 6 of 59

maximum risk estimate of 3.5% of the cPAD for the U.S. Population and 24% of the cPAD for 

children 1-2 years, the most highly exposed subpopulation.

Aggregate risks from ethephon are of concern for Children 1-2 years old. For adults, the short 

term residential handler inhalation MOE estimated for Backpack Sprayer to Gardens /Trees, 

when aggregated with dietary exposure, is 990, which does not exceed HED’s level of concern 

(LOC = 30). For children, the aggregated MOE (incidental oral + dietary) MOE was 24 which 

exceeds HED’s level of concern (LOC = 30).

Spray Drift

The turf post-application assessment is considered protective of spray drift exposure based on the 

maximum application rate on crops and the existing turf application rates; therefore, a separate 

quantitative spray drift assessment was not conducted. 

Occupational Exposure and Risk

In the absence of systemic dermal toxicity, dermal handler and post-application exposure 

assessments were not conducted, and there is no risk associated with dermal exposure to 

workers. There are no occupational handler inhalation risk estimates of concern for the 

registered uses of ethephon at baseline (i.e., no respirator). Occupational inhalation margins of 

exposure (MOEs) ranged from 150 to 42,000 (LOC = 30) at baseline attire. The REI is based on 

the acute toxicity of ethephon and a 48 hour REI is adequate for the registered uses. 

Based on the Agency's current practices, a quantitative non-cancer occupational post-application 

inhalation exposure assessment was not performed for ethephon at this time. If new policies or 

procedures are put into place, the Agency may revisit the need for a quantitative occupational 

post-application inhalation exposure assessment for ethephon.

Residential Exposure 

There are no residential handler inhalation risk estimates of concern for the registered uses of 

ethephon; the MOEs range from 2,600 to 120,000 (LOC = 30). Regarding post-application 

exposure, the lowest incidental oral risk estimate for children (1 to < 2 year old) playing on 

treated turf (i.e., parks) is an MOE of 30, which does not exceed HED’s level of concern (LOC = 

30).

Human Studies Review

This risk assessment relies in part on data from studies in which adult human subjects were 

intentionally exposed to a pesticide or other chemical. These data, which include the human 

toxicity study (MRID 00036510 ) and studies from PHED 1.1; and the AHETF database are (1) 

subject to ethics review pursuant to 40 CFR 26, (2) have received that review, and (3) are

compliant with applicable ethics requirements. For certain studies, the ethics review may have 
Page 7 of 59

included review by the Human Studies Review Board. Descriptions of data sources, as well as 

guidance on their use, can be found at the Agency website1. 

2.0 HED Recommendations

No additional residue chemistry data are required for registration review. No label changes are 

required based on residue chemistry. Current tolerances need to be updated as previously 

discussed. 

HED calculated an aggregate risk estimate of concern (MOE of 24; LOC of 30) for short-term 

risk for children 1-2 years old from incidental oral and food and water. 

2.1 Data Deficiencies

ORE: In accordance with 40 CFR 158, turf transferable residue (TTR) data are required for all

occupational (e.g., sod farms, golf courses, parks, and recreational areas) or residential turf uses 

that could result in post-application exposure to turf. The existing uses for ethephon could result 

in residential post-application exposure; however, chemical-specific TTR data are not 

available. Since the highest estimated residential post-application exposure using default TTR 

values for ethephon is not minimal in comparison to the LOC (i.e., the calculated MOE is not 

greater than ten times higher than the LOC, MOE = 30 compared to the LOC of 30); EPA is 

requiring the 40 CFR TTR data to facilitate any necessary exposure assessments refinements and 

to further EPA’s general understanding of the availability of turf transferable pesticide residues.

2.2 Tolerance Considerations

2.2.1 Enforcement Analytical Method

Adequate methods for purposes of enforcement of ethephon tolerances in plant commodities, 

ruminant tissues and milk are available. The Amchem-Plant Method (PAM, VOL. II, Method I) 

is the recommended method for plant commodities and processed products other than wheat and 

barley straw. The Amchem-Cereal Method (forwarded to FDA for inclusion in the PAM, VOL. 

II, Method II) is the recommended method for wheat and barley straw. The Union CarbideAnimal Method (forwarded to FDA for inclusion in the PAM, VOL. II, Method III) is the 

recommended method for milk and animal tissues. The currently recommended plant and animal 

analytical enforcement methods use diazomethane as a methylating agent. In the 1991 

Registration Update, HED required the registrant to revise the currently accepted enforcement 

methods to replace diazomethane with a safer methylating agent or provide documentation 

supporting the need for diazomethane if a suitable alternative is impractical. Rather than address 

Agency concerns about the use of diazomethane, Rhone-Poulenc submitted new plant and 

animal methods for enforcement purposes which principally involve the decomposition of 

ethephon to ethylene to determine the residues of ethephon in various commodities. The Agency 

reviewed the new proposed plant and animal enforcement methods and concluded they must also 

 

1 http://www.epa.gov/pesticides/science/handler-exposure-data.html and 

http://www.epa.gov/pesticides/science/post-app-exposure-data.html
Page 8 of 59

undergo a successful independent laboratory validation (ILV) (PR Notice 88-5, 7/15/88) 

followed by a successful method validation by the Agency. The ILV has been reviewed and 

found adequate by HED (T. Morton, 5/2/02, D280666). The method will be forwarded to the 

Agency laboratory for method validation. The registrant successfully radio-validated the animal 

residue analytical method using samples from the new poultry metabolism study (T. Morton, 

D227485, 2/21/02). 

2.2.2 International Harmonization

The tolerance expression for ethephon is harmonized with both Canada and Codex. There is 

harmonization with the Canadian ethephon MRL levels for cantaloupe, grape, and pineapple. 

There is harmonization with the Codex ethephon MRL levels for apple, blueberry, cherry, and 

pineapple. Harmonization with the remaining commodity MRLs is not possible due to 

differences in the GAP or field trial residue levels used for MRL calculation.

2.2.3 Recommended Tolerances

The 0.1 ppm tolerance for cucumbers was previously recommended for revocation (T. Morton, 

D280985, 6/20/01) but still remains in the CFR. This tolerance should be revoked.

The tolerance expression for ethephon has been reviewed and should be updated as follows 

based on HED’s Interim Guidance on Tolerance Expressions (S. Knizner, 5/27/09).

Tolerances are established for residues of ethephon, including its metabolites and degradates, in 

or on the commodities in the table below. Tolerance values in bold represent suggested changes. 

Compliance with the tolerance levels specified below is to be determined by measuring only 

ethephon (P)-(2-chloroethyl) phosphonic acid.

Table 2.2.3. Tolerance Summary for Ethephon

Commodity Tolerance (ppm) Comments; Correct Commodity Definition

Apple 5.0

Apple, juice 10.0

Barley, bran 5.0

Barley, grain 2.0

Barley, straw 10.0

Blackberry 30.0

Blueberry 20.0

Cantaloupe 2.0

Cattle, fat 0.02

Cattle, kidney 1.0

Cattle, meat 0.02

Cattle, meat byproducts, except kidney 0.20 2 significant figures

Cherry 10.0

Coffee, bean, green 0.50 Coffee, green bean; 2 significant figures

Cotton, gin byproducts 180.0

Cotton, undelinted seed 6.0

Cucumber 0.1 Revoke

Egg 0.002
Page 9 of 59

2.3 Label Recommendations

2.3.1 Recommendations from Residue Reviews

No label changes are recommended at this time based on the evaluation of residue chemistry

data.

2.3.2 Recommendations from Occupational Assessment

Labels vary with respect to requirements for work attire and personal protective equipment 

(PPE). For example, some labels do not specify any requirements for work attire, while others 

require respirators, chemical-resistant gloves and coveralls over long-sleeve shirt and long pants. 

Thus, label corrections/revisions should be consistently made to default to end-use product 

Goat, fat 0.02

Goat, kidney 1.0

Goat, meat 0.02

Goat, meat byproducts, except kidney 0.20 2 significant figures

Grape 2.0

Grape, raisin 12.0

Hazelnut 0.80 Filbert

Hog, fat 0.02

Hog, kidney 1.0

Hog, meat 0.02

Hog, meat byproducts, except kidney 0.20 2 significant figures

Horse, fat 0.02

Horse, kidney 1.0

Horse, meat 0.02

Horse, meat byproducts, except kidney 0.20 2 significant figures

Milk 0.01

Nut, macadamia 0.50 2 significant figures

Pepper 30.0

Pineapple 2.0

Poultry, fat 0.02

Poultry, liver 0.05

Poultry, meat 0.01

Poultry, meat byproducts, except liver 0.01

Sheep, fat 0.02

Sheep, kidney 1.0

Sheep, meat 0.02

Sheep, meat byproducts, except kidney 0.20

Sugarcane, molasses 1.5

Tomato 2.0

Walnut 0.50

Wheat, bran 5.0

Wheat, germ 5.0

Wheat, grain 2.0

Wheat, middlings 5.0

Wheat, shorts 5.0

Wheat, straw 10.0

Sugarcane3 0.10
Page 10 of 59

and/or technical grade active ingredient acute (ocular, dermal, oral, and inhalation) toxicity 

requirements; note that the technical grade of ethephon is corrosive to the skin (Toxicity 

Category I).

2.3.3 Recommendations from Residential Assessment

No label changes are needed for the residential assessment.

3.0 Introduction

3.1 Chemical Identity

Table 3.1 Test Compound Nomenclature

Chemical Structure

Empirical Formula C2H6ClO3P

Common Name Ethephon

IUPAC name 2-chloroethylphosphonic acid

CAS name (P)-(2-chloroethyl)phosphonic acid

CAS Registry Number 16672-87-0

End-use product/EP Ethephon 2, Florel, Ethrel, Quali-Pro

Chemical Class Plant Growth Regulator

3.2 Physical/Chemical Characteristics

Pure ethephon is a white waxy solid with a melting point of 74-75 0C. Ethephon is very soluble in 

water, alcohol, acetone, and propylene glycol, only slightly soluble in aromatic solvents such as 

benzene and toluene, and insoluble in kerosene and diesel oil. The vapor pressure of ethephon is 

<1 X 10-7 mm Hg at 25 0C. The octanol/water partition coefficient (p) is <0.603 ±0.0006 at 25 0C. 

The dissociation constant for ethephon is: K1 = 3.16 X 10-3and K2 = 6.31 X 10-8at 25 0C.

3.3 Pesticide Use Pattern

The ethephon use pattern can be found in Appendix C.

3.4 Anticipated Exposure Pathways

The Pesticide Re-Evaluation Division has requested a registration review assessment of human 

health risk for the registered uses of ethephon. Humans may be exposed to ethephon in food and 

drinking water, since ethephon may be applied directly to growing crops and application may 

result in ethephon reaching surface and ground water sources of drinking water. There are 

residential uses of ethephon, so there is likely to be exposure in residential or non-occupational 

settings during handling and post-application activities. In an occupational setting, applicators 
Page 11 of 59

may be exposed while handling the pesticide prior to application, as well as during application. 

There is a potential for post-application exposure for workers re-entering treated fields. 

3.5 Consideration of 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://www.epa.gov/compliance/environmentaljustice/resources/policy/exec_order_12898.pdf).

As a part of every pesticide risk assessment, OPP considers a large variety of consumer 

subgroups according to well-established procedures. In line with OPP policy, HED estimates 

risks to population subgroups 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 the USDA under the National Health and Nutrition Survey/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 analyzed 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 

appropriate, non-dietary exposures based on home use of pesticide products and associated risks 

for adult applicators and for toddlers, youths, and adults entering or playing on treated areas 

post-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.

4.0 Hazard Characterization and Dose-Response Assessment

4.1 Toxicology Studies Available for Analysis

The toxicology database for ethephon is complete for evaluating and characterizing its toxicity 

and selecting endpoints for purposes of this risk assessment. According to the revised 40 CFR 

Part 158 Toxicology Data Requirements, a subchronic inhalation toxicity study would be

required. However, based on the total weight of evidence, the HED/HASPOC determined that 

these data were not needed (TXR 0056295). A developmental neurotoxicity study was not 

conducted based on the unlikelihood that ethephon crosses the blood/brain barrier of offspring 

(See 4.4.3 for detail, TXR 0054221).

The following data are available:

 Acute- Oral rat, dermal rat, inhalation rat, eye irritation rabbit, dermal irritation rabbit, 

and skin sensitization guinea pig.

 Subchronic- mouse (30 day).

 Chronic- Oral rat, mouse and dog;

 Reproductive/developmental- Oral developmental rabbit and rat, 2-generation 

reproductive rat
Page 12 of 59

 Other- Oral rat and mouse cancer studies, 21-day dermal rabbit toxicity study, acute and 

subchronic neurotoxicity, acute delayed neurotoxicity, metabolism, mutagenicity screens, 

immunotoxicity, 28-day clinical oral human studies.

4.2 Absorption, Distribution, Metabolism, & Excretion (ADME)

No sex or dose-related differences were seen in pharmacokinetic parameters in an absorption, 

distribution, metabolism and excretion (ADME) study, where 14C- ethephon: 2-chloro (14C)ethyl 

phosphonic acid was administered to 6 groups of male and female Crl:CD(SD)BR rats 

(5/sex/dose) in four dosing schemes: 1) a single intravenous (iv) dose at 50 mg/kg, or 2) single 

oral doses at 50 or 3) 1000 mg/kg or 4) multiple daily oral doses (unlabeled ethephon) for 14 

days at 50 mg/kg/day followed by single oral dose (50 mg/kg/day) of the 14C-ethephon.

Low and high oral doses, and intravenous doses (dosing schemes 1-3) were rapidly absorbed and 

excreted in the urine accounting for 48-71% of the administered dose (AD). The oral Cmax was 

reached in 1.3 and 1.0 hours for the 50 mg/kg dose, 1.9 and 2.5 hours for the 1000 mg/kg dose in 

males and females, respectively. The half-life of blood clearance was 7 hours (alpha-phase) in 

both sexes at the low dose and 4 and 9 hours in females and males at the high dose, respectively. 

The iv dosing indicated that biliary excretion is minimal since less than 2% of the AD was 

recovered in the feces. Exhaled 14CO2 was <1%, 14C-ethylene was 10 to 20% of the AD and less 

than 7% of the AD was excreted in the feces. Residual radioactivity in tissues was less than 

0.1% of the AD. The highest tissue levels were found in the blood, liver, bone, kidney, and 

spleen with no differences between multiple and single dose administration. Total recovered 

radioactivity was 84-90%. Multiple dosing did not significantly alter the excretion pattern. 

Ethephon was not extensively metabolized. Ethephon as disodium salt accounted for 90% of the 

recovered radioactivity in the urine and feces with minor components of monosodium salt and 

other unidentified metabolites as less than 5%. The potential decomposition products, 

chloroacetic acid and chloroethanol were not reported or looked for. 

4.2.1 Dermal Absorption

Dermal absorption data were not required for ethephon. It is a severe skin irritant. 

4.3 Toxicological Effects

Ethephon (2-chloroethyl phosphonic acid) is a plant growth regulator used to promote fruit 

ripening, abscission, flower induction, breaking of apical dominance (inhibition of the growth of 

lateral buds by the terminal bud of a shoot), by production of ethylene gas which is an important 

component of the plant hormone complex. Ethephon is an organophosphorus/phosphonate

compound. It is not an organophosphate. It does not have a leaving group as in the 

organophosphates which is required for the insecticidal mode of action. 

 

Evidence in Laboratory Animals and In vivo and In vitro effects

Ethephon inhibits red blood cell and plasma cholinesterase (ChE) activities in experimental 

animals and may not be accompanied by clinical signs of toxicity until a high threshold level of
Page 13 of 59

exposure is reached. Brain ChE activity is not inhibited in vivo. At high doses (>250 mg/kg/day) 

it produces clinical signs of toxicity (ataxia, prostration, reduced activity, hypothermia, 

salivation, tremors and mortality). 

Anemia has been reported in dogs administered doses of 52 mg/kg/day. Reduced body weight 

gain is noticeable in experimental animals exposed to ethephon during their gestation period or 

during chronic exposure. There is no quantitative or qualitative evidence of increased 

susceptibility following in utero or postnatal exposure in any of the developmental or 

reproductive studies. Developmental and post natal toxicity occurred at doses causing 

maternal/parental toxicity. Ethephon did not produce acute delayed neurotoxicity in hens after 

being dosed with nearly lethal doses. It produced clinical toxicity in rats following acute or 

subchronic neurotoxicity testing, but no neurobehavioral or neuropathological effects were seen. 

Ethephon was mutagenic in bacteria but not in cultured mammalian cells. It was negative for 

cytogenic effects both in vitro and in vivo and did not cause unscheduled DNA synthesis. There 

was, however, evidence of mitotic gene conversion in yeast. 

Ethephon was not carcinogenic in rats or mice at doses that were considered adequate. It was 

initially classified in 1994 as Group D for carcinogenicity based on insufficiency of the weight of 

the evidence (TXR # 0011195). However, based on the lack of carcinogenicity in rats and mice 

and negative mutagenic effects, the HIARC in 2002, reclassified ethephon as a "Not likely to be 

Carcinogenic to Humans” (TXR # 0051308). In an immunotoxicity study in female mice, 

ethephon did not elicit systemic toxicity or immunotoxicity at the highest dose of 7000 ppm 

(1373 mg/kg/day, above the limit dose) tested.

Ethephon exhibits low acute toxicity via the oral (Toxicity Category III), inhalation (Toxicity 

Category IV), and dermal (Toxicity Category III) routes of exposure. Ethephon is dermally 

corrosive. It is a skin and eye irritant (Toxicity Category I). It is not a dermal sensitizer.

Human Evidence

Humans appear to be more susceptible to the clinical toxicity of ethephon than experimental 

animals. In a human clinical study that was reviewed by the Human Studies Review Board in 

2006 and found acceptable, five men and five women were given oral doses of 124 mg of 

ethephon (approximately 1.8 mg/kg/day) by capsule daily for 28 consecutive days. Three men 

and three women served as placebo controls. Treated subjects complained of diarrhea and 

increased urgency and frequency of urination. One treated man experienced loose stools for 2 

weeks and another one complained of stomach cramps or gas for the duration of the study. One 

control also reported increased urination. In human subjects, plasma and RBC cholinesterase 

activities were slightly elevated in treated subjects but fell within the normal range. Because 

humans appear to be more susceptible to ethephon toxicity than animals, HIARC relied on the 

human studies in selecting the toxic endpoint for risk assessments.
Page 14 of 59

4.4 Safety Factor for Infants and Children (FQPA Safety Factor)

The FQPA safety factor for increased susceptibility to infants and children is reduced to 1x for 

ethephon based on the following considerations. The toxicology database for ethephon contains 

acceptable guideline developmental and reproduction studies as well as acute and subchronic 

neurotoxicity studies. There is no quantitative or qualitative evidence of increased susceptibility 

following in utero or postnatal exposure in any of the developmental or reproductive studies. 

The RfDs and toxicity endpoints established are protective of pre/postnatal toxicity following 

acute and chronic exposures.

There are no residual uncertainties identified in the exposure databases. The dietary food 

exposure assessment includes anticipated residues calculated from field trial data conducted at 

maximum application rates, USDA Pesticide Data Program (PDP) monitoring data, processing 

factors, and available %CT information from BEAD (100%CT is assumed where BEAD data are 

not available). Dietary drinking water exposure is based on conservative modeling estimates of 

estimated drinking water concentrations from maximum application rates. These assessments 

will not underestimate the potential exposure to infants and children resulting from the use of 

ethephon.

4.4.1 Completeness of the Toxicology Database

The toxicological database for ethephon is complete for the purpose of this risk assessment. 

Based on a WOE approach considering all the available ethephon hazard and exposure 

information, the HASPOC concluded that a 28-day day inhalation toxicity study is not needed at 

this time (TXR 0056295).

4.4.2 Evidence of Neurotoxicity

Ethephon did not produce acute delayed neurotoxicity in hens after being dosed with nearly 

lethal doses. It produced clinical toxicity (mortality and cholinergic signs (abnormal respiratory 

sounds and breathing) in rats following acute or subchronic neurotoxicity testing, but no 

neurobehavioral or neuropathological effects were seen. No indication of abnormalities in the 

development of the fetal nervous system was observed in the prenatal developmental toxicity 

studies in either rats or rabbits, at maternally toxic oral doses up to 500 or 100 mg/kg/day, 

respectively. No neurotoxic effects were observed in the clinical observation data, brain weights, 

or histopathology of the nervous system in the chronic toxicity studies with ethephon in rats, 

mice or dogs. 

4.4.3 Evidence of Sensitivity/Susceptibility in the Developing or Young Animal

There is no evidence of susceptibility following in utero and/or postnatal exposure in the 

developmental toxicity studies in rats or rabbits, and in the 2-generation rat reproduction study. 

A developmental neurotoxicity study was not conducted based on the unlikelihood that ethephon 

crosses the blood/brain barrier of offspring (TXR 0054221). Ethephon is highly water soluble 

and no brain ChE activity was inhibited in adult mice, rats or dogs at the highest doses tested. 

Additionally, Watanabe et al. (1990, Placental and Blood-Brain Barrier Transfer Following 
Page 15 of 59

Prenatal and Postnatal Exposures to Neuro-active Drugs: Relationship with Partition Coefficients 

and Behavioral Teratogenesis. Toxicol. Appl. Pharmacol. 105:66–77), using C14-radiolabeled 

drugs demonstrated that blood brain barrier transfer of drugs depends on their lipophilicity. 

Highly lipophilic drugs (as measured by their partition coefficients) such as propranolol, 

chlorpromazine, haloperidol and atropine passed easily across the Blood-Brain Barrier (BBB) in 

adult rats (dams), their fetuses and their pups with a BBB transfer ratio (brain/plasma 

concentration ratio) ranging from 1-11. There was a tendency for atropine to pass at higher rate 

in the fetuses and the pups than in the dams. On the other hand low lipophilic drugs such as 

reserpine, dopamine, epinephrine, and norepinephrine passed poorly across the BBB (BBB 

transfer ratio less than 1) with no differences between the dams and their fetuses and their pups. 

Ethephon is highly water soluble with low lipophilicity (lower than the drugs described in the 

Watanabe et al article). Thus, the ethephon properties described above make it less likely that 

younger children are more susceptible to any potential inhibitory activity of the brain ChE.

(TXR NO. 0054221).

4.4.4 Residual Uncertainty in the Exposure Database

There are no residual uncertainties in the exposure database. 

4.5 Toxicity Endpoint and Point of Departure Selections

4.5.1 Dose-Response Assessment

The point of departure for all exposure scenarios is derived from a 28-day human study with a 

LOAEL of 1.8 mg/kg/day and an uncertainty factor of 30 (10x for intraspecies variation, 

interspecies variation reduced to 1x for use of a human study and 3x for extrapolating from 

LOAEL to a NOAEL) (TXR 0051308). The 3X UF for extrapolating from a LOAEL to a 

NOAEL in the selected study (MRID 0051308) is adequate based on:

 The duration of the effects elicited by ethephon in the 28-day oral toxicity study in 

humans is consistent with a Cmax reaction i.e., compound concentration in the body 

quickly reaches a peak and declines very rapidly (~90% is eliminated within 24 hrs) so 

that every exposure appears as a single exposure).

 

 Mild clinical effects were observed in the 28-day human study.

 

 In a 29-day human study (MRID 00066931) at about one-third of the dose administered 

in the 28-day human study (0.5 mg/kg/day), no clinical signs were reported.

The use of the endpoint from the 28-day human study is considered appropriate since the 

toxicokinetic properties of this compound indicate a Cmax reaction in which repeated exposures 

do not lead to cumulative toxicity or progression of the effects.

In a 2005 HED document by Ray Kent (TXR 0053509) a weight of evidence comparison of 

human and animal toxicology studies and endpoints for ethephon is presented. After four 

different reviews by the HED HIARC (8/9/94, 4/1/98, 7/15/02 and 11/5/02) a 28-day human 

study was selected to assess all relevant exposure scenarios. 
Page 16 of 59

The clinical signs of toxicity in the 28-day human study occurred at 1.8 mg/kg/day. This 

endpoint is conservative and is protective of any effects exhibited in experimental animals. The 

28-day human study was reviewed by the Human Studies Review Board in 2006 and found 

acceptable. 

4.5.2 Recommendation for Combining Routes of Exposures for Risk Assessment

When there are potential residential exposures to a pesticide, the aggregate risk assessment must 

consider exposures from three major sources: oral, dermal, and inhalation exposures. The 

toxicity endpoints selected for these routes of exposure may be aggregated because of the 

common toxicity endpoint (clinical signs: diarrhea and increased urgency and frequency of 

urination, loose stools , stomach cramps) via these routes. 

4.5.3 Cancer Classification and Risk Assessment Recommendation

Ethephon was not carcinogenic in rats or mice at doses that were considered adequate. It was 

classified as Group D for carcinogenicity based on insufficiency of the weight of the evidence. 

An Ad Hoc Committee meeting on May 5, 1994 considered that the evidence from both rat 

studies and one of the mouse studies to be inadequate to support a positive carcinogenicity 

finding, while the evidence from one mouse study was equivocal (TXR # 0011195). However, 

based on the lack of carcinogenicity in rats and mice and negative mutagenic effects, the HIARC 

in 2002, reclassified ethephon as a "Not likely to be Carcinogenic to Humans” (TXR # 0051308).
Page 17 of 59

4.5.4 Summary of Points of Departure and Toxicity Endpoints Used in Human Risk 

Assessment

Table 4.5.4 Summary of Toxicological Dose and Endpoints for Ethephon for Use in Human Risk Assessment

Exposure Scenario Dose used in Risk 

Assessment

UF

FQPA SF and 

Endpoint for Risk 

Assessment

Study and Toxicological Endpoint

Acute Dietary

All populations

LOAEL = 1.8 

mg/kg/day

UF=30 

FQPA SF = 1

aPAD =

1.8

30

= 0.06 mg/kg/day

28-Day Human Clinical Study, MRID 00036510 

LOAEL = 1.8 mg/kg/day based on diarrhea and 

increased urgency and frequency of urination, loose 

stools, stomach cramps or gas

Chronic Dietary

All populations

LOAEL = 1.8 

mg/kg/day

UF = 30

FQPA SF = 1

cPAD =

1.8

30

= 0.06 mg/kg/day

28-Day Human Clinical Study, MRID 00036510 

LOAEL = 1.8 mg/kg/day based on diarrhea and 

increased urgency and frequency of urination, loose 

stools, stomach cramps or gas

Short/intermediate-Term 

Incidental Oral

(1day - 1 month)

LOAEL= 1.8 

mg/kg/day 

LOC for MOE= 30 28-Day Human Clinical Study, MRID 00036510 

LOAEL = 1.8 mg/kg/day based on diarrhea and 

increased urgency and frequency of urination, loose 

stools, stomach cramps or gas

Short-Term Dermal 

(1 day - 1 month)

Not Applicable - No exposure effects expected due to dermal corrosivity of ethephon. At dermal doses 

above 150 mg/kg/day, ethephon is corrosive to the skin. In a range finding study, dermally applied 

ethephon was lethal above 500 mg/kg/day and was a severe irritant at 500 mg/kg/day. In the main 21-

day rabbit dermal toxicity study ethephon produced no systemic toxicity at 150 mg/kg/day or less, but 

caused local dermal toxicity at doses of 25 mg/kg/day and above. Since ethephon is dermally corrosive, 

exposures at levels high enough to cause systemic toxicity are not expected. Therefore, risk assessment 

of dermal exposures to ethephon would not be applicable.

Short/intermed/longTerm

Inhalation

(1-30 days, 1-6 mos, > 6 

mos)

LOAEL= 1.8 

mg/kg/day 

LOC for MOE= 30

Short-Term for 

Residential 

and Occupational

28-Day Human Clinical Study, MRID 00036510 

LOAEL = 1.8 mg/kg/day based on diarrhea and 

increased urgency and frequency of urination, loose 

stools, stomach cramps or gas

Cancer Classification Not likely to be Carcinogenic to Humans (TXR # 0051308)

LOAEL = lowest observed adverse effect level. UF = uncertainty factor. FQPA SF = FQPA Safety Factor. PAD = 

population adjusted dose (a = acute, c = chronic). MOE = margin of exposure. LOC = level of concern. 

4.6 Endocrine Disruption

As required by FIFRA and FFDCA, EPA reviews numerous studies to assess potential adverse

outcomes from exposure to chemicals. Collectively, these studies include acute, subchronic and

chronic toxicity, including assessments of carcinogenicity, neurotoxicity, developmental,

reproductive, and general or systemic toxicity. These studies include endpoints which may be

susceptible to endocrine influence, including effects on endocrine target organ histopathology,

organ weights, estrus cyclicity, sexual maturation, fertility, pregnancy rates, reproductive loss,

and sex ratios in offspring. For ecological hazard assessments, EPA evaluates acute tests and

chronic studies that assess growth, developmental and reproductive effects in different

taxonomic groups. As part of its registration review decision for ethephon, EPA reviewed these 

data and selected the most sensitive endpoints for relevant risk assessment scenarios from the 

existing hazard database. However, as required by FFDCA section 408(p), ethephon is subject to 

the endocrine screening part of the Endocrine Disruptor Screening Program (EDSP).
Page 18 of 59

EPA has developed the EDSP to determine whether certain substances (including pesticide

active and other ingredients) may have an effect in humans or wildlife similar to an effect

produced by a “naturally occurring estrogen, or other such endocrine effects as the Administrator

may designate.” The EDSP employs a two-tiered approach to making the statutorily required

determinations. Tier 1 consists of a battery of 11 screening assays to identify the potential of a

chemical substance to interact with the estrogen, androgen, or thyroid (E, A, or T) hormonal

systems. Chemicals that go through Tier 1 screening and are found to have the potential to

interact with E, A, or T hormonal systems will proceed to the next stage of the EDSP where EPA

will determine which, if any, of the Tier 2 tests are necessary based on the available data. Tier 2

testing is designed to identify any adverse endocrine-related effects caused by the substance, and

establish a dose-response relationship between the dose and the E, A, or T effect. Under FFDCA 

section 408(p), the Agency must screen all pesticide chemicals. Between October 2009 and 

February 2010, EPA issued test orders/data call-ins for the first group of 67 chemicals, which 

contains 58 pesticide active ingredients and 9 inert ingredients. A second list of chemicals 

identified for EDSP screening was published on June 14, 20131and includes some pesticides 

scheduled for registration review and chemicals found in water. Neither of these lists should be 

construed as a list of known or likely endocrine disruptors. For further information on the status 

of the EDSP, the policies and procedures, the lists of chemicals, future lists, the test guidelines 

and the Tier 1 screening battery, please visit our website.2

1 See http://www.regulations.gov/#!documentDetail;D=EPA-HQ-OPPT-2009-0477-0074 for the final second list of

chemicals.

2 http://www.epa.gov/endo/

5.0 Dietary Exposure and Risk Assessment 

5.1 Metabolite/Degradate Residue Profile

5.1.1 Summary of Plant and Animal Metabolism Studies

The qualitative nature of the residue in plants is adequately understood based on tomato, 

cantaloupe, apple, fig, pineapple, tobacco, grape, walnut, filbert, cherry, tangerine, and lemon 

metabolism data. Ethephon degrades to ethylene, phosphate, and chloride. Data indicate that 

translocation of ethephon to fruits may occur following application to leaves. The residue of 

concern in plants is ethephon per se (T. Morton, D282695, 5/28/02). The qualitative nature of 

the residue in livestock is adequately understood based on goat and hen metabolism data. In 

ruminant tissues and milk, ethephon is incorporated into natural products (glutathione 

conjugates, protein, glycogen, triglycerides) and expired as 14CO2 and 14C-ethylene. No residues 

of ethephon were detected in the goat metabolism study; however, residues of ethephon were 

detected in ruminant tissues and milk in a ruminant feeding study which was conducted at 

exaggerated rates. The metabolic pathway for ethephon in poultry as proposed by the registrant

proceeds via initial cleavage of chlorine and formation of 2-hydroxy ethyl phosphonic acid 

(HEPA) followed by formation of intermediates that are incorporated into the amino acid and 

fatty acid biosynthetic pathways. The residue of concern in plants and livestock is ethephon per 

se (T. Morton, D282695, 5/28/02).
Page 19 of 59

5.1.2 Summary of Environmental Degradation

Ethephon (2-chloroethylphosphonic acid; CAS RN 16672-87-0) is nonvolatile, hydrophilic, and 

slightly-to-moderately mobile in soil, showing high variability in adsorption values across five 

tested soils. The compound is an anion (pKal = 2.5) in acidic environments and a double anion in 

alkaline environments (pKa2 = 7.2). Ethephon dissipates in the environment through both biotic 

and abiotic degradation and by leaching in soils that are low in organic carbon. The compound is

not expected to persist in aerobic soil (half-life of 9.1 days) or neutral to alkaline water bodies

(half-lives of 52.4 days). Ethephon’s persistence in acidic water bodies is uncertain. Ethephon

hydrolyzes with a half-life of 74 days at pH 5; however, data are not available with which to

directly estimate biodegradation rates in acidic water bodies. Susceptibility to biodegradation in

acidic, aerobic soil indicates that ethephon will degrade in acidic, aerobic water bodies; however,

ethephon biodegradation in acidic to alkaline anaerobic water was indiscernible when corrected

for hydrolysis. Terrestrial field dissipation data indicate that the chemical dissipates by degradation 

and leaching, with dissipation half-lives ranging from 7 to 25 days. The low end of this range is 

consistent with the results of the aerobic soil metabolism study, while the high end of this range is 

higher than expected with respect to the laboratory study results. Major degradates of ethephon 

identified in environmental fate studies include ethylene, phosphoric acid, and 2-

hydroxyethylphosphonic acid (HEPA), the latter of which is less mobile than the parent compound. 

Minor identified degradates include methylated phosphoric acid and carbon dioxide. Phosphoric 

acid, ethylene, and hydrochloric acid are expected to form in equal molar amounts during 

degradation; however, phosphate and chlorine were not quantified in degradation studies.

5.1.3 Comparison of Metabolic Pathways

In rats, parent ethephon is the major component with some formation of natural products such as 

CO2 and ethylene. The metabolic pathway in plants and livestock is similar with the production 

of natural products.

5.1.4 Residues of Concern Summary and Rationale

Table 5.1.4 Summary of Metabolites and Degradates to be included in the Risk 

Assessment and Tolerance Expression

Matrix Residues included in Risk 

Assessment

Residues included in 

Tolerance Expression

Plants

Primary Crop Ethephon Ethephon

Rotational Crop Ethephon Ethephon

Livestock

Ruminant Ethephon Ethephon

Poultry Ethephon Ethephon

Drinking Water Ethephon Not Applicable
Page 20 of 59

5.2 Food Residue Profile

All data for magnitude of the residue in plants have been evaluated and deemed adequate. 

Sufficient data are available to ascertain the adequacy of the established tolerances. 

The Agency has concluded that currently registered use of ethephon on cucumbers, squash, and 

pumpkins for hybrid seed production is a non-food use. The 0.1 ppm cucumber tolerance was 

previously recommended for revocation but still remains in the CFR. This tolerance should be 

revoked.

Adequate processing studies have been conducted on apples, barley, coffee, cottonseed, grapes, 

pineapple, tomato, and wheat to determine the extent to which residues of ethephon concentrate 

in food/feed items upon processing of the raw agricultural commodity. Data indicate that 

ethephon residues concentrate in apple juice, barley hulls, grape juice, raisins, blackstrap 

molasses, wheat bran, and wheat shorts and germ. Available processing data indicate that 

residues of ethephon do not concentrate in wet apple pomace, refined sugar of sugarcane, coffee 

roasted bean, freeze-dried coffee, cottonseed meal, cottonseed oil, tomato juice, tomato puree, 

wheat flour, pineapple juice, or tomato paste. Therefore, separate tolerances for these processed 

foods are not required.

The data requirements for magnitude of the residue in livestock are fulfilled. Acceptable 

livestock feeding studies have been submitted and evaluated. A new maximum dietary burden 

(MDB) estimate was calculated based on reassessed established/proposed tolerances of feed 

commodities and revised Table II of OPPTS 860 Guidelines (T. Morton, 6/20/02, D280985). 

Holstein dairy cows were dosed daily for 28 days with ethephon at levels of 0, 43, 129 and 430 

ppm in the diet (three cows per group). Milk samples were taken throughout the treatment 

period. Milk and tissue samples were analyzed with the ethylene release method. The estimated 

MDB in beef and dairy cows from established uses of ethephon based on a diet of cotton and 

wheat commodities is 46 ppm. Based on the estimated MDB, the dietary feeding levels in this 

study were 0.9X, 2.7X and 9X. The results of this feeding study were used to establish 

appropriate tolerances for meat and milk commodities. The registrant submitted data required to 

establish egg and poultry tissue tolerances (T. Morton, 5/7/02, D280983). Leghorn laying hens 

were dosed daily with ethephon at levels of 0, 2.3, 6.9 and 23 ppm in the diet. Each group had 

10 hens. Egg samples were taken throughout the treatment period. Egg and tissue samples were 

analyzed with the ethylene release method. Based on the estimated MDB of 4.3 ppm, the dietary 

feeding levels in this study were 0.5X, 1.6X and 5.3X. The results of this feeding study were 

used to establish tolerances for egg and poultry commodities. 

5.3 Water Residue Profile

The Environmental Fate and Effects Division (EFED) of the Office of Pesticide Programs (OPP) 

has completed a drinking water assessment for the registration review of ethephon (D423375, 

5/26/15, I. Abdel-Saheb). The chemical is a plant growth regulator registered for use on a variety 

of field and specialty crops (e.g., cotton, wheat, blueberries, and cucumbers), fruit and nut 

orchards, vineyards, ornamentals, and turf (e.g., golf courses and residential lawns). Applications 
Page 21 of 59

are made by ground or aerial spray. The maximum annual application rate is 20 pounds of active 

ingredient per acre (lb a.i./A) (turf).

EFED recommends that the Health Effects Division use the following surface water estimated 

drinking water concentrations (EDWC) resulting from modeling the Florida turf scenario:

 for peak (acute) of 25.7 ppb

 for the 365-day Avg (1-in-10 yr) 0.46 ppb

 Entire Simulation Mean 0.34 ppb. 

For groundwater, the model PRZM-GW yielded EDWCs for acute and chronic EDWCs less 

than 1 ppb (0.102 ppb).

Table 5.3. Tier II Estimated Drinking Water Concentrations (EDWCs) for surface water as 

a result of modeling with the Surface Water Concentration Calculator (SWCC).

Surface Water Modeling Results

Recommended EDWCs from the Florida Turf Scenario are in Bold

Crop Group Model

Scenario

1-in-10 year Acute 

concentration (ppb)

1-in-10 year 

annual 

average

30-year annual 

average

Berries OR berries 10.0 0.066 0.062

Cucurbits FL cucumber 8.26 0.01 0.006

Field crops & 

Tropical fruit

MS cotton

FL sugarcane

NC tobacco

23.2

6.86

12.4

0.2

0.063

0.11

0.10

0.036

0.05

Fruiting vegetables FL tomato

PA tomato

19.4

13.9

0.16

0.16

0.08

0.01

Grasses FL turf

ND wheat

25.7

2.51

0.46

0.032

0.34

0.027

Nuts OR filbert

GA Pecans

6.27

18.4

0.044

0.15

0.040

0.07

Ornamentals FL nursery

NJ nursery

CA nursery

25.6

23.3

6.87

0.19

0.21

0.040

0.12

0.10

0.038

Pome fruit NC apples 14.3 0.163 0.11

Stone fruit MI cherries 6.35 0.054 0.03
Page 22 of 59

5.4 Dietary Risk Assessment

5.4.1 Description of Residue Data Used in Dietary Assessment

Adequate field trial data for ethephon, reflecting maximum application rates and the appropriate 

PHI, have been submitted for all registered use sites. PDP data were available and used for 

grape and apple commodities. Data from PDP and crop field trials were used for the acute 

dietary analysis. Processing factors from processing studies were used with the PDP monitoring 

data. Anticipated residues were also used for the chronic dietary analysis.

5.4.2 Percent Crop Treated Used in Dietary Assessment

The following maximum percent crop treated estimates were used in the acute dietary risk 

assessment for the following crops that are currently registered for ethephon: apples: 25%; 

barley: 5%; blackberry: 51%; blueberry: 2.5%; cantaloupe: 2.5%; cherry: 30%; cotton: 70%; 

grapes (table): 60%; grape (raisin): 15%; grape (wine): 2.5%; peppers: 2.5%; tomato: 30%; and 

wheat: 2.5%. The following average percent crop treated estimates were used in the chronic 

dietary risk assessments for the following crops that are currently registered for ethephon: 

apples: 10%; barley: 5%; blackberry: 51%; blueberry: 1%; cantaloupe: 1%; cherry: 20%; 

cotton: 55%; grapes (table): 35%; grape (raisin): 10%; grape (wine): 1%; peppers: 2.5%; 

tomato: 15%; and wheat: 1%.

5.4.3 Acute Dietary Risk Assessment

An ethephon acute dietary exposure assessment was conducted using the Dietary Exposure 

Evaluation Model software with the Food Commodity Intake Database DEEM-FCIDTM, Version 

3.16, which incorporates consumption data from USDA’s National Health and Nutrition 

Examination Survey, What We Eat in America, (NHANES/WWEIA). This dietary survey was 

conducted from 2003 to 2008. The analyses was performed to support the registration review of 

ethephon. Results are reported at the 99.9th percentile of exposure because the assessment 

incorporated field trial and PDP data to estimate residue levels and estimates of %CT. Estimated 

acute dietary exposure is below HED’s level of concern for the General U.S. population and all 

population subgroups except Children 1-2 years old. Use of PDP data, field trial data and 

calculated livestock anticipated residues (ARs) results in a dietary risk (food and water) estimate 

at the 99.9th percentile of 39% of the acute population adjusted dose (aPAD) for the U.S. 

Population and 170% for children 1-2 years old, the most highly exposed population subgroup.
Page 23 of 59

Table 5.4.3. Results of Acute Dietary (Food and Water) Exposure Analysis

Population Subgroup

aPAD 

(mg/kg/

day)

95th Percentile 99th Percentile 99.9th Percentile

Exposure 

(mg/kg/day) % aPAD

Exposure 

(mg/kg/day) % aPAD

Exposure 

(mg/kg/day) % aPAD

General U.S. Population 0.06 0.001345 2.2 0.004843 8.1 0.023547 39

All Infants (< 1 year old) 0.06 0.002242 3.7 0.012833 21 0.053926 90

Children 

1-2 years old 0.06 0.005919 9.9 0.019392 32 0.102230 170

Children 3-5 years old 0.06 0.003911 6.5 0.012661 21 0.047986 80

Children 6-12 years old 0.06 0.001855 3.1 0.006242 10 0.030207 50

Youth 13-19 years old 0.06 0.000866 1.4 0.002804 4.7 0.011150 19

Adults 20-49 years old 0.06 0.001007 1.7 0.003332 5.6 0.014792 25

Adults 50-99 years old 0.06 0.001137 1.9 0.003841 6.4 0.018284 30

Females 13-49 years old 0.06 0.001020 1.7 0.003430 5.7 0.016453 27

The bolded %aPAD is the highest.

5.4.4 Chronic Dietary Risk Assessment

Estimated chronic dietary (food and water) exposure is below HED’s level of concern for the 

general population and all subpopulations. Use of tolerance level residues and %CT data results 

in a maximum risk estimate of 3.5% of the cPAD for the U.S. Population and 24% of the cPAD 

for children 1-2 years, the most highly exposed subpopulation.

Table 5.4.4. Results of Chronic Dietary (Food and Water) Exposure Analysis

Population Subgroup

cPAD

(mg/kg/day)

Exposure 

(mg/kg/day) % cPAD

General U.S. Population 0.06 0.002072 3.5

All Infants (< 1 year old) 0.06 0.006798 11

Children 1-2 years old 0.06 0.014585 24

Children 3-5 years old 0.06 0.008312 14

Children 6-12 years old 0.06 0.003248 5.4

Youth 13-19 years old 0.06 0.001244 2.1

Adults 20-49 years old 0.06 0.001060 1.8

Adults 50-99 years old 0.06 0.001136 1.9

Females 13-49 years old 0.06 0.001113 1.9

The bolded %cPAD is the highest.

5.4.5 Cancer Dietary Risk Assessment

Ethephon is classified as "Not likely to be Carcinogenic to Humans’' based on the lack of 

carcinogenicity in rats and mice and mostly negative mutagenic effects data (TXR # 0051308). 
Page 24 of 59

6.0 Residential (Non-Occupational) Exposure/Risk Characterization

Residential handler exposure from the registered residential ornamental uses of ethephon and 

residential post-application exposure from the registered occupational uses of ethephon on turf in 

parks have been reassessed in this documents to reflect updates to HED’s 2012 Residential 

SOPs2along with policy changes for body weight assumptions.

6.1 Residential Handler Exposure

HED uses the term “handlers” to describe those individuals who are involved in the pesticide 

application process. HED believes that there are distinct tasks related to applications and that 

exposures can vary depending on the specifics of each task. Residential handlers are addressed 

somewhat differently by HED as homeowners are assumed to complete all elements of an 

application without use of any protective equipment.

The quantitative exposure/risk assessment developed for residential handlers is based on the 

following scenarios:

Mixing/Loading/Applying

 Manually Pressurized Handwand: Gardens/Trees (around the home and garden) and 

ornamentals.

 Hose-end Sprayer: Gardens/Trees (around the home and garden) and ornamentals. 

 Backpack Sprayer: Gardens/Trees (around the home and garden) and ornamentals. 

Residential Handler Exposure Data and Assumptions

A series of assumptions and exposure factors served as the basis for completing the residential 

handler risk assessments. Each assumption and factor is detailed below.

Application Rate:

The highest application rate of 0.08 lb ai/gal for ornamentals (i.e., defoliation, tall hedge 

buckthorn) was used as a screening-level assessment. See Appendix C for specifics.

Unit Exposures and Area Treated or Amount Handled:

Unit exposure values and estimates for area treated or amount handled were taken from HED’s 

2012 Residential SOPs3and the draft September 2013 Aquatic use SOP. 

Exposure Duration: 

Residential handler exposure is expected to be short-term in duration. Intermediate-term 

exposures are not likely because of the intermittent nature of applications by homeowners.

Residential Handler Non-Cancer Exposure and Risk Estimate Equations

 

2 Available: http://www.epa.gov/pesticides/science/residential-exposure-sop.html

3 Available: http://www.epa.gov/pesticides/science/residential-exposure-sop.html
Page 25 of 59

The algorithms used to estimate exposure and dose for residential handlers can be found in 

Appendix A and/or the 2012 Residential SOPs4.

Summary of Residential Handler Non-Cancer Exposure and Risk Estimates

For all residential handler exposure scenarios, there are no risk estimates of concern associated 

with the use of ethephon (i.e., MOEs ≥ 30). Results of this assessment are summarized in Table 

6.1.1

Table 6.1.1. Residential Handler Non-cancer Exposure and Risk Estimates for Ethephon.

Exposure Scenario

Inhalation Unit 

Exposure 

(mg/lb ai)

Max. 

App.

Rate1

Area Treated or 

Amount Handled 

Daily2

Inhalation

Dose 

(mg/kg/day)3

MOE4

(LOC =30)

Mixer/Loader/Applicator (Soluble Concentrate)

Manually-pressurized 

Handwand/

Handgun to Gardens /Trees

0.018

0.08

lb ai/gal

5 gal 0.000090 20,000

Hose-end Sprayer to 

Gardens /Trees 0.0014 11 gal 0.000015 120,000

Backpack Sprayer to 

Gardens /Trees 0.14 5 gal 0.00070 2,600

1. Application rate is based on the highest rate for ornamentals (i.e., defoliation, tall hedge buckthorn) from Table 4.1. 

2. Based on HED’s Standard Operating Procedures for Residential Pesticide Exposure Assessment; Gardens/Trees and 

Ornamentals (Feb. 2012).

3. Inhalation Dose = daily unit exposure (mg/lb ai) x application rate (lb ai/area treated or amount handled) x Area treated or 

amount handled / body weight (80 kg).

4. Inhalation MOE = LOAEL (1.8 mg/kg/day) / daily dose (mg/kg/day). Level of concern = 30.

6.2 Residential Post-Application Exposure

In the absence of a point of departure for dermal toxicity, dermal post-application exposure 

assessments were not conducted. However, incidental oral exposure and risk was estimated for 

children (1 to < 2 year old) playing on treated turf (i.e., parks). The quantitative exposure/risk 

assessment for residential post-application exposures is based on the following scenarios: 

Recreational Turf (parks):

 Incidental Oral: Hand to mouth (HtM), Object to Mouth (OtM), and Soil Ingestion (SI)

Application Rate:

The maximum application rate of 0.09 lb ai/1,000 ft2(3.9 lb ai/A) for commercial turf (including 

parks) was used. See Appendix C.

Exposure Duration: 

Residential post-application exposure is expected to be short-term in duration.

Residential Post-application Non-Cancer Exposure and Risk Equations

 

4 Available: http://www.epa.gov/pesticides/science/residential-exposure-sop.html
Page 26 of 59

The algorithms used to estimate residential post-application exposure and dose can be found in 

the ORE exposure assessment as Appendix A and/or the 2012 Residential SOPs. 

Summary of Residential Post-application Non-Cancer Exposure and Risk Estimates

The residential post-application incidental oral exposure and risk estimates for children (1 to < 2 

year old) are summarized in Table 6.2.1. All incidental oral MOEs are ≥ 30.

Table 6.2.1. Residential Post-application Non-cancer Exposure and Risk Estimates for Ethephon.

Lifestage

Post-application Exposure Scenario Application 

Rate1

Dose 

(mg/kg/day)2 MOEs3

Use Site Route of Exposure/Activity

Children

(1 < 2) Turf (parks)

Incidental oral / hand to mouth

3.9 lb ai/A

0.060 30

Incidental oral / Object to 

mouth 0.0018 990

Incidental oral / soil ingestion 0.00013 14,000

1 Application rate is based maximum rate of 0.09 lb ai/1,000 ft2 (3.9 lb ai/A) for commercial turf (including parks) was used. See Table 4.1. 

2 Dose (mg/kg/day) equations provided in Appendix [A]. 

3 MOE = POD (1.8 mg/kg/day) ÷ Dose (mg/kg/day).

Turf Transferable Residue (TTR): In accordance with 40 CFR 158, TTR data are required for all 

occupational (e.g., sod farms, golf courses, parks, and recreational areas) or residential turf uses 

that could result in post-application exposure to turf. In the absence of chemical-specific TTR 

data, EPA uses default values. The 2012 Standard Operating Procedures for Residential 

Pesticide Exposure Assessment includes an analysis of all TTR data, available at the time, which 

resulted in the selection of revised liquid and granular default values for the fraction of the 

application rate available for transfer after a turf application (FAR). These values are based on 

an analysis of 59 TTR studies performed with the Modified California Roller Method (36 studies 

using liquids, 11 studies using wettable powders/water dispersible granules, and 12 studies using 

granules). The liquid results (N=131) indicate a range of FAR values from 0.0005% to 6.1 % 

and the granular results (N=37) indicate a range of 0.00064% to 0.69%. In both the liquid and 

granular data, a large range of transferability is observed and this variability can potentially be 

attributable to many factors such as active ingredient; formulation; field conditions in the studies; 

weather conditions (e.g., humidity); or many other difficult to quantify factors. Although 

witnessed across multiple chemicals, this range in FAR values is not expected when considering 

TTR data for a single chemical. 

HED selected 1% and 0.2% as high-end FAR default values for liquid and granular products, 

respectively. Because ethephon-specific TTR data are not available, EPA is using the default 

value of 1%. Although there may be a small degree of uncertainty in the use of the default TTR 

value for ethephon (i.e., there is a small chance that the FAR value may exceed the applicable 

default value), it is likely that the health-protective aspects of EPA’s residential post-application 

turf assessment methodology will more than compensate for this potential uncertainty (i.e., the 

methodology is likely to overestimate exposure by a factor greater than the factor than the 

highest measured FAR values exceed the defaults ). For example, when assessing residential 

post-application turf exposure, EPA assumes the following: exposures occur to zero-day (i.e., 

day of application ) residues every day of the assessed exposure duration (i.e., EPA assumes that 

no dissipation or degradation occurs, it doesn’t rain, the grass is not mowed, etc); individuals 
Page 27 of 59

perform the same post-application activities performed in the turf transfer coefficient study day 

after day (e.g., tumbling, playing on turf with toys, etc.); and individuals engage in these postapplication activities for a high-end amount of time every day that is represented by data 

reflecting time children spend outdoors and not specifically engaged in activities on turf, when in 

actuality children do not spend all of their outdoor time on turf and high-end levels of activity 

will not occur every day. Given the conservatisms discussed above and the potential 

compounding nature of these conservatisms, EPA is able to rely upon the calculated exposure 

estimates with confidence that exposure is not being underestimated. 

In the case of ethephon; default assumptions were used in all calculations. Since the estimated 

residential turf post-application exposure for residential turf (i.e., parks) using default TTR 

values for ethephon is not minimal in comparison to the level of concern (i.e., the calculated 

MOE is not greater than 10 times higher than the level of concern, MOE = 30 compared to the 

LOC of 30), future refinements of this post-application exposure for ethephon may be necessary 

due to increased use of ethephon or advances in EPA risk assessments. Therefore, EPA is 

requiring the 40CFR ethephon-specific TTR data to facilitate any necessary exposure assessment 

refinements and to further EPA’s general understanding of the availability of turf transferable 

pesticide residues.

6.3 Residential Risk Estimates for Use in Aggregate Assessment

Table 6.3.1 reflects the residential risk estimates that are recommended for use in the aggregate 

assessment for ethephon. The incidental oral scenarios for children 1 to < 2 years old (i.e., 

hand-to-mouth, object-to-mouth, and soil ingestion) are considered inter-related and it is likely 

that they occur interspersed amongst each other across time. Combining exposures from the

three incidental oral scenarios would compound the conservatism associated with each individual

scenario, so only the most protective one was selected. The target MOE for these exposures is 

30.

Table 6.3.1 Recommendations for the Residential Exposures for the ethephon Aggregate Assessment.

Lifestage Exposure 

Scenario

Dose (mg/kg/day)1 MOE 2

Dermal Inhalation Oral Total Dermal Inhalation Oral Total

Adult

Backpack 

Sprayer 

Treating 

Gardens/Trees

N/A 0.00070 N/A N/A N/A 2,600 N/A N/A

Child 

(1 to 2 

years old)

Hand to mouth 

activities on 

treated turf

N/A N/A 0.060 N/A N/A N/A 30 N/A

1. Dose = the highest dose for each applicable life stage and activity of all residential scenarios assessed. 

2. MOE = LOAEL (1.8 mg/kg/day) / dose. LOC = 30

6.4 Residential Bystander Post-application Inhalation Exposure

Volatilization of pesticides may be a source of post-application inhalation exposure to 

individuals nearby pesticide applications. The agency sought expert advice and input on issues 

related to volatilization of pesticides from its Federal Insecticide, Fungicide, and Rodenticide Act 
Page 28 of 59

Scientific Advisory Panel (SAP) in December 2009, and received the SAP’s final report on 

March 2, 2010 (http://www.epa.gov/scipoly/SAP/meetings/2009/120109meeting.html). The 

agency has evaluated the SAP report and has developed a Volatilization Screening Tool and a 

subsequent Volatilization Screening Analysis 

(http://www.regulations.gov/#!docketDetail;D=EPA-HQ-OPP-2014-0219). During Registration 

Review, the agency will utilize this analysis to determine if data (i.e., flux studies, route-specific 

inhalation toxicological studies) or further analysis is required for ethephon.

6.5 Spray Drift

Off-target movement of pesticides can occur via many types of pathways and it is governed by a 

variety of factors. Sprays that are released and do not deposit in the application area end up offtarget and can lead to exposures to those it may directly contact. They can also deposit on 

surfaces where contact with residues can eventually lead to indirect exposures (e.g., children 

playing on lawns where residues have deposited next to treated fields). The potential risk 

estimates from these residues can be calculated using drift modeling onto 50 feet wide lawns 

coupled with methods employed for residential risk assessments for turf products.

The approach to be used for quantitatively incorporating spray drift into risk assessment is based 

on a premise of compliant applications which, by definition, should not result in direct exposures 

to individuals because of existing label language and other regulatory requirements intended to 

prevent them.5 Direct exposures would include inhalation of the spray plume or being sprayed 

directly. Rather, the exposures addressed here are thought to occur indirectly through contact 

with impacted areas, such as residential lawns, when compliant applications are conducted. 

Given this premise, exposures for children (1 to 2 years old) and adults who have contact with 

turf where residues are assumed to have deposited via spray drift thus resulting in an indirect 

exposure are the focus of this analysis analogous to how exposures to turf products are 

considered in risk assessment. 

Several ethephon products have existing labels for use on turf, thus it was considered whether the 

risk assessment for that use may be considered protective of any type of exposure that would be 

associated with spray drift. It should be noted that the registered residential uses on turf result in 

exposure greater than potential exposure from spray drift; therefore, no new residential 

assessment needs to be completed. If the maximum application rate on crops, adjusted by the 

amount of drift expected, is less than or equal to existing turf application rates, the existing turf 

assessment is considered protective of spray drift exposure. The currently registered maximum 

single application rate of ethephon for crops is 2 lb ai/A. The highest degree of spray drift noted 

for any application method immediately adjacent to a treated field (Tier 1 output from the aerial 

application using fine to medium spray quality) results in a deposition fraction of 0.26 of the 

application rate. A quantitative spray drift assessment for ethephon is not required because the 

maximum application rate to a crop/target site, multiplied by the adjustment factor for drift of 

0.26, is less than the maximum direct spray residential turf application rate of 3.9 lb ai/A6for any

ethephon products. The turf post-application MOEs are based on the revised SOPs for 

Residential Exposure Assessment (i.e., see above in Section 5.2). 

 

5 This approach is consistent with the requirements of the EPA’s Worker Protection Standard.

6 2 lb ai/A x 0.26 ≤ 3.9 lb ai/A
Page 29 of 59

7.0 Aggregate Exposure/Risk Characterization

In accordance with the FQPA, when there are potential residential exposures to a pesticide, the 

Agency must aggregate risks based on exposures from three major routes: oral, dermal, and 

inhalation if the exposures share a toxicity endpoint. There are three sources for these types of 

exposures: food, drinking water, and residential uses. In an aggregate assessment, exposures 

from relevant sources are added together and compared to quantitative estimates of hazard (e.g., 

a NOAEL or PAD), or the risks themselves can be aggregated. When aggregating exposures and 

risks from various sources, HED considers both the route and duration of exposure. 

7.1 Acute Aggregate Risk

The acute exposure estimates provided in the Dietary Exposure Section represent acute aggregate 

exposure.

7.2 Short-Term Aggregate Risk

Short-term aggregate exposure takes into account residential exposure plus average exposure 

levels to food and water (considered to be a background exposure level). 

Table 7.2.1aggregates the short-term risk for toddlers from incidental oral and food and water (as 

a background). The short-term aggregate risk MOE of 24 for children 1 < 2 years old 

exceeds HED’s level of concern (LOC=30). This assessment is considered conservative in that 

the chronic dietary exposure estimate is based on tolerance level residues and average percent 

crop treated.

Table 7.2.1. Short-term Aggregate Risk Estimates to Ethephon for Children 1-2 years old

Exposure Scenario Target 

MOE

Route of 

Exposure Exposure LOAEL(mg/kg/day) MOE at Day 0 Combined MOE4

Average Food and Water N/A Oral 0.014585

1.8

120 2

24 Hand to mouth activities on 

treated turf

30 1 Oral 0.060 303

1 Target MOE= 30, LOAEL=1.8 mkd

2 MOE food = [(short-term oral LOAEL)/(chronic dietary exposure)] 

3 MOE oral = [(short -term oral LOAEL)/(hand-to-mouth residential exposure)] 

4 Aggregate Combined MOE (food, water, and residential) = 1÷ [(1÷MOE food and water) + (1÷MOE incidental oral)].

Table 7.2.2 aggregates the short-term risk for adults from residential handler exposure, and 

average food and water (as a background). The short-term aggregate risk MOE of 990 for adults 

does not exceed HED’s level of concern (LOC = 30). 
Page 30 of 59

Table 7.2.2: Short-term Aggregate Risk Estimates to Ethephon for Adults from Post-Application Activities

Exposure Scenario Target 

MOE

Route of 

Exposure

Exposure or

Daily dose

LOAEL

(mg/kg/day)

MOE at Day 0 Combined MOE4

Average Food and Water 

(As background)

N/A Food and 

water 0.001136

1.8

1600 2

990

Residential Handler (Backpack 

Sprayer Treating Gardens/Trees)

30 1Inhalation 0.00070 2600

3

1 Target MOE= 30, LOAEL = 1.8 mkd

2 MOE food and water = [(short-term oral NOAEL)/(chronic dietary exposure)] 

3 MOE inhalation = [(short -term inhalation NOAEL)/(high-end inhalation residential exposure)] 

4 Aggregate Combined MOE (food, water, and residential) = 1÷ [(1÷MOE food and water) + (1÷MOE handler inhalation)].

7.3 Intermediate-Term Aggregate Risk

No intermediate exposure scenarios were identified for ethephon, therefore, no intermediate

aggregate risk was calculated. 

7.4 Chronic Aggregate Risk

The chronic exposure estimates provided in the Dietary Exposure Section represent chronic 

aggregate exposure.

7.5 Cancer Aggregate Risk

Ethephon is classified as "Not likely to be Carcinogenic to Humans’' based on the lack of 

carcinogenicity in rats and mice and negative mutagenic effects (TXR # 0051308). No 

assessment was needed or conducted.

8.0 Cumulative Exposure/Risk Characterization

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 ethephon and any other substances and ethephon does not appear to produce a toxic metabolite 

produced by other substances. For the purposes of registration review, therefore, EPA has not 

assumed that ethephon has a common mechanism of toxicity with other substances. For 

information 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 Office of Pesticide Programs concerning common mechanism determinations 

and procedures for cumulating effects from substances found to have a common mechanism on 

EPA’s website at http://www.epa.gov/pesticides/cumulative/.
Page 31 of 59

9.0 Occupational Exposure/Risk Characterization

9.1 Short- and Intermediate-term Handler Risk

HED uses the term handlers to describe those individuals who are involved in the pesticide 

application process. HED believes that there are distinct job functions or tasks related to 

applications and exposures can vary depending on the specifics of each task. Job requirements 

(amount of chemical used in each application), the kinds of equipment used, the target being 

treated, and the level of protection used by a handler can cause exposure levels to differ in a 

manner specific to each application event. 

Based on the anticipated use patterns and current labeling, types of equipment and techniques 

that can potentially be used, occupational handler exposure is expected from the registered uses. 

The quantitative exposure and risk assessment developed for occupational handlers is based on 

the scenarios listed in Tables 9.1.1 and 9.1.2. 

Occupational Handler Exposure Data and Assumptions

A series of assumptions and exposure factors served as the basis for completing the occupational 

handler risk assessments. Each assumption and factor is detailed below on an individual basis.

Application Rate: The maximum single application rates are listed in Appendix C. As a 

screening-level assessment, the maximum application rate for a given scenario was used, and is

protective of all other crops with lower application rates. 

Unit Exposures: It is the policy of HED to use the best available data to assess handler exposure. 

Sources of generic handler data, used as surrogate data in the absence of chemical-specific data, 

include PHED 1.1, the AHETF database, or other registrant-submitted occupational exposure 

studies. Some of these data are proprietary (e.g., AHETF data), and subject to the data 

protection provisions of FIFRA. The standard values recommended for use in predicting handler 

exposure that are used in this assessment, known as “unit exposures”, are outlined in the 

“Occupational Pesticide Handler Unit Exposure Surrogate Reference Table7”, which, along with 

additional information on HED policy on use of surrogate data, including descriptions of the 

various sources, can be found at the Agency website8. 

Area Treated or Amount Handled: The area treated or amount handled is based on HED 

ExpoSAC Policy 9.1. The amount/area treated for each scenario is listed in the Occupational 

Handler Exposure Table (Tables 9.1.1 and 9.1.2). 

Exposure Duration: HED classifies exposures from 1 to 30 days as short-term and exposures 30 

days to six months as intermediate-term. Exposure duration is determined by many things, 

including the exposed population, the use site, the pest pressure triggering the use of the 

pesticide, and the cultural practices surrounding that use site. For most agricultural uses, it is 

reasonable to believe that occupational handlers will not apply the same chemical every day for 

 

7 Available: http://www.epa.gov/opp00001/science/handler-exposure-table.pdf

8 Available: http://www.epa.gov/pesticides/science/handler-exposure-data.html
Page 32 of 59

more than a one-month time frame; however, there may be a large agribusiness and/or 

commercial applicators who may apply a product over a period of weeks (e.g., completing 

multiple applications for multiple clients within a region). 

For ethephon, based on the registered use pattern, short- and intermediate-term exposures are 

expected. However, since the short- and intermediate-term inhalation POD is the same for both 

durations, the assessment is protective of both durations. 

Mitigation/Personal Protective Equipment: Estimated inhalation risks were calculated for the 

“baseline” level of PPE, defined as a single layer of clothing consisting of a long sleeved shirt, 

long pants, shoes plus socks, no protective gloves, and no respirator, as well as engineering 

controls, where applicable. According to the currently registered ethephon labels, occupational 

handlers must wear baseline attire and chemical-resistant gloves. 

Occupational Handler Non-Cancer Exposure and Risk Estimate Equations

The algorithms used to estimate non-cancer exposure and dose for occupational handlers can be 

found in Appendix A of the ORE memorandum (D428505).

Summary of Occupational Handler Non-Cancer Exposure and Risk Estimates

There are no occupational handler risk estimates of concern for the registered uses of ethephon at 

the baseline level of PPE. The level of concern (LOC) for occupational handler inhalation risk 

estimates is an MOE of 30. The occupational inhalation MOEs ranged from 150 to 42,000. A 

summary of risk estimates is provided in Tables 9.1.1 and 9.1.2.
Page 33 of 59

Table 9.1.1. Occupational Handler Non-Cancer Exposure and Risk Estimates for Ethephon.

Exposure Scenario Representative

Crop or Target1

Inhalation Unit 

Exposure (μg/lb ai)2 Maximum

Application 

Rate3

Area Treated or 

Amount Handled 

Daily4

Inhalation Risk Estimates4

(LOC = 30)

Baseline Baseline Dose

(mg/kg/day)5

Baseliene

MOE6

Mixer/Loader

Mixer/Loader Liquids for Aerial 

Application

Pineapple

0.219

2 350 0.00191 940

Cotton 2 1200 0.00658 270

Mixer/Loader Liquids for Airblast 

Application

Nursery 8 20 0.000438 4,100

Apple 2 40 0.000219 8,200

Mixer/Loader Liquids for 

Chemigation Application Pineapple 2 350 0.00191 940

Mixer/Loader Liquids for 

Groundboom Application

Nursery 8 60 0.00131 1,400

Pineapple 2 80 0.000438 4,100

Cotton 2 200 0.0011 1,600

Applicator

Applicator for Sprays via Aerial 

Application

Pineapple 0.0049

(engineering control; 

enclosed cockpit)

2 350 0.0000429 42,000

Cotton 2 1200 0.000148 12,000

Applicator for Sprays via Airblast 

Application

Nursery

4.71

8 20 0.00943 190

Apple 2 40 0.00471 380

Applicator for Sprays via 

Groundboom Application

Nursery

0.34

8 60 0.00204 880

Pineapple 2 80 0.00068 2,600

Cotton 2 200 0.0017 1,100

Flagger

Liquid Applications

Nursery

0.35

8 60 0.0021 860

Cotton 2 350 0.00306 590
Page 34 of 59

Table 9.1.2. Occupational Handler Non-Cancer Exposure and Risk Estimates for Ethephon.

Exposure Scenario Representative

Crop or Target1

Inhalation Unit 

Exposure (μg/lb ai)2 Maximum

Application 

Rate3

Area Treated or 

Amount Handled 

Daily4

Inhalation Risk Estimates4

(LOC = 30)

Baseline Baseline Dose

(mg/kg/day)5

Baseliene

MOE6

Mixer/Loader/Applicator

Liquid for Backpack Applications Nursery 140

0.08

lbs ai/gallon 40

gallons

0.0056 320

Liquids for Manually- Pressurized 

Handwand Nursery 30

0.08

lbs ai/gallon

0.0012 1,500

Liquids for MechanicallyPressurized Handgun

Greenhouse 120

0.008

lbs ai/gallon 1000

gallons

0.012 150

Nursery 3.9

0.08

lbs ai/gallon

0.0039 460

Landscaping 1.9 3.9 lb ai/A 5 acres 0.000464 3,900

1 Representative crop with highest application rate and area treated for each scenario – for screening-level assessment.

2 Based on the “Occupational Pesticide Handler Unit Exposure Surrogate Reference Table” (Feb 2015); Level of mitigation: Baseline and Eng. Controls (for aerial applicators only).

3 Based on registered labels (See Table 4.1). The rate for “Nursery” was based on 0.08 lb ai/gal for ornamentals (i.e., defoliation, tallhedge buckthorn), assuming 100 gallons of treatment solution per 

acre (i.e., 8 lb ai/A).

4 Exposure Science Advisory Council Policy #9.1 and assumptions in the Occupational Exposure Handler Spreadsheet (February 2015).

5 Inhalation Dose = Unit Exposure (μg/lb ai) × Conversion Factor (0.001 mg/μg) × Application Rate (lb ai/acre) × Area Treated (A/day) ÷ BW (80 kg).

6 Inhalation MOE = Inhalation LOAEL (1.8 mg/kg/day) ÷ Inhalation Dose (mg/kg/day).
Page 35 of 59

9.2 Short-/Intermediate-Term Post-Application Risk

HED uses the term post-application to describe exposures that occur when individuals are 

present in an environment that has been previously treated with a pesticide (also referred to as reentry exposure). Such exposures may occur when workers enter previously treated areas to 

perform job functions, including activities related to crop production, such as scouting for pests 

or harvesting. Post-application exposure levels vary over time and depend on such things as the 

type of activity, the nature of the crop or target that was treated, the type of pesticide application, 

and the chemical’s degradation properties. In addition, the timing of pesticide applications, 

relative to harvest activities, can greatly reduce the potential for post-application exposure.

9.2.1 Occupational Post-application Inhalation Exposure/Risk Estimates

There are multiple potential sources of post-application inhalation exposure to individuals 

performing post-application activities in previously treated fields. These potential sources 

include volatilization of pesticides and resuspension of dusts and/or particulates that contain 

pesticides. The agency sought expert advice and input on issues related to volatilization of 

pesticides from its Federal Insecticide, Fungicide, and Rodenticide Act Scientific Advisory Panel 

(SAP) in December 2009, and received the SAP’s final report on March 2, 2010 

(http://www.epa.gov/scipoly/SAP/meetings/2009/120109meeting.html). The agency has 

evaluated the SAP report and has developed a Volatilization Screening Tool and a subsequent 

Volatilization Screening Analysis (http://www.regulations.gov/#!docketDetail;D=EPA-HQOPP-2014-0219). During Registration Review, the agency will utilize this analysis to determine 

if data (i.e., flux studies, route-specific inhalation toxicological studies) or further analysis is 

required for ethephon.

In addition, the Agency is continuing to evaluate the available post-application inhalation 

exposure data generated by the Agricultural Reentry Task Force. Given these two efforts, the 

Agency will continue to identify the need for and, subsequently, the way to incorporate 

occupational post-application inhalation exposure into the agency's risk assessments.

9.2.2 Occupational Post-application Dermal Exposure/Risk Estimates

Occupational Post-application Dermal Exposure Data and Assumptions

No dermal toxicity point of departure was identified for ethephon, therefore a dermal postapplication risk assessment was not completed. 

Restricted Entry Interval

The REI specified on the registered labels is 48 hours. Ethephon is classified as Toxicity 

Category III via the dermal route and Category I for dermal and eye irritation (it is corrosive to 

the skin), but is not a skin sensitizer. Based on the acute toxicity of ethephon, a 48 hour REI is 

adequate.
Page 36 of 59

10.0 References

Ethephon. Occupational and Residential Exposure Assessment for Registration Review. D428505, 9/15/15, K. 

O’Rourke. 

Ethephon: Acute Probabilistic and Chronic Aggregate Dietary (Food and Drinking Water) Exposure and Risk 

Assessment Registration Review Risk Assessment. D428504, 10/1/15, T. Morton.

Ethephon: Drinking Water Assessment for Registration Review. D423375, 5/26/15, I. Abdel-Saheb.

PP#4E6835. Ethephon (099801): Ethephon in/on Filberts. D313792. 3/9/06. T. Morton.

PP#0E6205. Ethephon (099801): Ethephon in/on Coffee. D283033. 6/20/01. T. Morton

Tolerance Reassessment Eligibility Document (TRED) of Ethephon (PC Code 099801): Product and Residue 

Chemistry Considerations. D280985. 6/20/01. T. Morton.
Page 37 of 59

Appendix A. Toxicology Profile and Executive Summaries

A.1 Toxicology Data Requirements

The requirements (40 CFR 158.340) for Registration Review for Ethephon are in Table A.1. 

Study

Technical

Required Satisfied

870.1100 Acute Oral Toxicity.......................................................

870.1200 Acute Dermal Toxicity..................................................

870.1300 Acute Inhalation Toxicity..............................................

870.2400 Primary Eye Irritation....................................................

870.2500 Primary Dermal Irritation..............................................

870.2600 Dermal Sensitization .....................................................

yes

yes

yes

yes

yes

yes

yes

yes

yes

yes

yes

yes

870.3100 Oral Subchronic (rodent)...............................................

870.3150 Oral Subchronic (non-rodent) .......................................

870.3200 21-Day Dermal..............................................................

870.3250 90-Day Dermal..............................................................

870.3465 90-Day Inhalation..........................................................

no

yes

yes

no

waived*

-

yes

yes

-

-

870.3700a Developmental Toxicity (rodent) ..................................

870.3700b Developmental Toxicity (non-rodent)...........................

870.3800 Reproduction .................................................................

yes

yes

yes

yes

yes

yes

870.4100a Chronic Toxicity (rodent)..............................................

870.4100b Chronic Toxicity (non-rodent) ......................................

870.4200a Oncogenicity (rat)..........................................................

870.4200b Oncogenicity (mouse) ...................................................

870.4300 Chronic/Oncogenicity ...................................................

yes

yes

yes

yes

yes

yes

yes

yes

yes

yes

870.5100 Mutagenicity—Gene Mutation - bacterial.....................

870.5300 Mutagenicity—Gene Mutation - mammalian................

870.5xxx Mutagenicity—Structural Chromosomal Aberrations...

870.5xxx Mutagenicity—Other Genotoxic Effects.......................

yes

yes

yes

yes

yes

yes

yes

yes

870.6100a Acute Delayed Neurotoxicity (hen)...............................

870.6100b 90-Day Neurotoxicity (hen) ..........................................

870.6200a Acute Neurotoxicity Screening Battery (rat).................

870.6200b 90-Day Neurotoxicity Screening Battery (rat) ..............

870.6300 Develop. Neurotoxicity .................................................

yes

no

yes

yes

waived**

yes

-

yes

yes

-

870.7485 General Metabolism ......................................................

870.7600 Dermal Penetration........................................................

870.7800 Immunotoxicity .............................................................

yes

no

yes

yes

-

yes

Special Studies for Ocular Effects

Acute Oral (rat)...........................................................

Subchronic Oral (rat)..................................................

Six-month Oral (dog)..................................................

no

no

no

-

-

-

* TXR 0056295

** TXR 0054221
Page 38 of 59

A.2 Toxicity Profiles

Table A.2.1 Acute Toxicity Data on Ethephon

Guideline

No. Study Type MRID #(S). Results Toxicity Category

870.1100 Acute Oral 41154501 (1989) LD50 = 3030 mg/kg III

870.1200 Acute Dermal 41154502 (1989) LD50 = 1560 mg/kg III

870.1300 Acute Inhalation 41154504 (1989) LC50 = 4.53 mg/L IV

870.2400 Primary Eye Irritation Not required Assumed Corrosive I

870.2500 Primary Skin Irritation 00029514 (1979) Corrosive I

870.2600 Dermal Sensitization 41154503 (1989) Non-sensitizer Non-sensitizer

Table A.2.2: Ethephon: Toxicity Profile - Toxicological Studies

Guideline No./ Study Type MRID No. (year)/ 

Classification /Doses

Results

870.3100

90-Day oral toxicity rats

00029516 (1979)

Unacceptable/Guideline

75% a.i.

0, 50, 100 or 200 

mg/kg/day 

LOAEL = 200 mg/kg/day for systemic toxicity based on decreased 

ovary weight, ovarian/body weight ratio and liver/body weight ratio 

in females with a NOAEL of 100 mg/kg/day. 

The ChE inhibition activity findings were inconsistent and not in 

agreement with other ethephon studies. Plasma ChE activity was 

inhibited at all dose levels, RBC ChE activity was not affected at 

any dose. This is also the only study that reports brain ChE 

inhibition following treatment with ethephon.

Non-guideline

30-day oral feeding study

Mice

00087920 (1978)

Acceptable/NonGuideline

Purity not reported

0, 225, 450, 900 or 3600 

ppm (0, 34, 68, 135, or 540 

mg/kg/day)

LOAEL for systemic toxicity is 3600 ppm (540 mg/kg/day) based 

on a significant depressed male relative liver weight and the 

NOAEL is 900 ppm (135 mg/kg/day). 

870.3150

90-Day oral toxicity dog

See one and two year dog studies

870.3200

21-Day dermal toxicityrabbit 

Range-finding study- rabbit

41295901 (1989)

Acceptable/Guideline

72.2% a.i.

0, 25, 75, or 150 

mg/kg/day, 5 days/week 

for 3 weeks

LOAEL = 25 mg/kg/day for dermal effects based on the incidence 

and severity of erythema of the treated skin and the NOAEL is <25 

mg/kg/day.

LOAEL = >150 mg/kg/day for systemic effects based on the lack of 

toxic effects and the NOAEL is 150 mg/kg/day. 

Doses were based on a range finding study at 0, 125, 250, 500, 750, 

or 1000 mg/kg/day applied to shaved skin of one rabbit/sex/group; 

two highest doses caused mortality or moribundity within 2-6 days; 

animals exhibited low food consumption, hypothermia, prostration, 

ataxia, salivation tremors and dyspnea. Mild irritation was exhibited 

at 125 and 250 mg/kg/day and severe dermal irritation at higher 

doses.

870.3465

90-Day inhalation toxicity

Waived, HASPOC TXR 0056295

870.3700a

Prenatal developmental in 

rodents-rats

00063745 (1980)

Acceptable/guideline

0, 200, 600 or 1800 

mg/kg/day

Maternal Toxicity

LOAEL = 1800 mg/kg/day based on excessive maternal mortality 

(56%), gastroenteritis, respiratory disease, and necrotic hepatitis an 

the NOAEL is 600 mg/kg/day. 

Developmental Toxicity

LOAEL = 1800 mg/kg/day based on slightly reduced pup weight 

and the NOAEL is 600 mg/kg/day.
Page 39 of 59

Table A.2.2: Ethephon: Toxicity Profile - Toxicological Studies

Guideline No./ Study Type MRID No. (year)/ 

Classification /Doses

Results

870.3700a

Prenatal developmental in 

rodents- rat

41103001 (1989)

Acceptable/guideline

71.7% 

0, 125, 250 or 500 

mg/kg/day

Range Finding I. 0, 450, 

900, 1350, or 1800 

mg/kg/day 

Range Finding II. 0, 300, 

600 and 1200 mg/kg/day

Maternal Toxicity

LOAEL = 600 mg/kg/day based on the maternal mortality noted in 

the range finding study and the NOAEL is 500 mg a.i./kg/day. 

Developmental Toxicity

LOAEL = >500 mg/kg/day (the highest dose tested; the NOAEL is 

500 mg/kg/day

870.3700b

Prenatal developmental in 

rodents- rabbit

00085755 (1981)

Acceptable/guideline

0, 50, 100 or 250 

mg/kg/day

Maternal Toxicity

LOAEL = 100 mg/kg/day, based on mortality.

NOAEL = 50 mg/kg/day. 

Developmental Toxicity

LOAEL = 100 mg/kg/day based on decreased fetal viability. 

NOAEL = 50 mg/kg/day

870.3700b

Prenatal developmental in 

nonrodents - rabbit

41557201 (1990)

Acceptable/guideline

71.9-72.2% purity

0, 62.5, 125, or 250 

mg/kg/day

Maternal Toxicity

LOAEL = 250 mg/kg/day, based on mortality, clinical toxicity 

(ataxia, prostration, reduced activity) and significant body weight 

gain decrease during the dosing period. 

NOAEL = 125 mg/kg/day. 

Developmental Toxicity

LOAEL = 250 mg/kg/day based on decreased live fetuses/doe and 

increased early resorptions and post implantation loss.

NOAEL = 125 mg/kg/day.

870.3800

Reproduction and fertility 

effects

2-generation, rat

41508701 (1990)

Acceptable/guideline

71.14 - 72.14% purity

dietary dose levels of 0, 

300, 3,000 or 30,000 ppm

Parental Toxicity

LOAEL = 3000 ppm (245 mg a.i./kg/day) based on decrements in 

adult female pre-mating body weight, reduced food consumption 

and relative food utilization. 

NOAEL = 300 ppm (24 mg a.i. mg/kg/day)

Offspring Toxicity

LOAEL = 3000 ppm (245 mg a.i./kg/day) based on body weight 

decrement. 

NOAEL = 300 ppm ((24 mg a.i. mg/kg/day).

870.4100b

2-Year Chronic toxicity –

dogs

00060359 (1977)

Acceptable/guideline

75.6% purity

0, 30, 300 or 3000 ppm (0, 

0.75, 7.5, 75 mg/kg/day)

LOAEL for systemic toxicity is >1500 ppm (>37.5 mg/kg/day) 

based on lack of toxicity at this dose. The NOAEL = 1500 ppm 

(37.5 mg/kg/day).

870.4100b

1-Year Chronic toxicity 

dogs

41135001 (1989)

Acceptable/guideline

71.14% a.i. (Adjusted to 

100% a.i.) Main Study:

0, 100, 300, 1000 or 2000 

ppm (0, 2.7, 8.2, 28.5 and 

52.1 mg/kg/day)

Main Study

LOAEL = 2000 ppm (52.1 mg/kg/day) for systemic toxicity 

(decreased body weight, decreased spleen weight and anemia in 

males). ChE not measured in Main Study.

NOAEL = 1000 ppm (28.5 mg/kg/day). 

Range Finding Study

No mortalities or clinical signs were observed. The females 

receiving the 3000 and 10000 ppm and the male receiving the 10000 
Page 40 of 59

Table A.2.2: Ethephon: Toxicity Profile - Toxicological Studies

Guideline No./ Study Type MRID No. (year)/ 

Classification /Doses

Results

2-week Range Finding 

Study: 30, 100, 30, 1000, 

3000, or 10000 ppm (0.8, 

2.7, 8.2, 28.5, 85.5, 285 

mg/kg/day)

ppm had weight losses. Plasma ChE activity was inhibited at all 

dose levels (36-93% at one week and 41-94% at two weeks in males 

and 27-94% at one week and 33-95% at two weeks in females). 

RBC ChE activity was inhibited at levels of 1000 ppm and above 

(47-90% at one week and 56-95% at two weeks) in males and 300 

ppm and above in females (22-93% at one week and 27-98% at two 

weeks).

870.4200

18-Month Carcinogenicity 

Mouse

00081634 (1981)

Unacceptable

75% a.i.: 0, 30, 300, or 

1000 ppm (0, 4.5, 45, 150 

mg/kg/day)

The study was inconclusive in establishing a LOAEL and NOAEL

for ethephon toxicity. 

Not definitive for oncogenicity findings

870.4200

18-Month Carcinogenicity 

Mouse

41050801 (1988)

Acceptable/guideline

70.6-72.1% a.i.

0, 100, 1000, 10,000 or 

50,000 ppm

(0, 15.5, 156, 1630, 7750 

mg/kg/day

LOAEL = 10000 ppm (1630 mg/kg/day) based on body weight and 

body weight gain depression in females. NOAEL = 1000 ppm (156 

mg/kg/day). 

The 50,000 ppm group was terminated at 12 days due to excessive 

mortality and moribundity and clinical signs of tremors and 

dehydration.

Negative for carcinogenicity

870.4300

24-Month Carcinogenicity

Rats

00060358 (1978)

Acceptable/guideline

75.6% purity

0, 30, 300, or 3,000 ppm 

(0, 1.5, 15, 150 mg/kg/day)

LOAEL = >3,000 ppm (150 mg/kg/day) for systemic toxicity, the 

highest dose tested, based on the lack of clinical toxicity and 

treatment related histopathological findings. 

NOAEL = 3000 ppm (150 mg/kg/day).

There was a significant increase in pancreatic islet cell tumors at the 

3000 ppm dose level that were within the historical range.

870.4300

24-Month Carcinogenicity

Rats

41139001 (1989) 

Acceptable/guideline

70.6-72.1% a.i.

0, 300, 3000, 10000, or 

30000 ppm

(Males:0, 13, 131, 446, 

1465 mg/kg/day, 

Females 0, 16, 161, 543, or 

1794 mg/kg/day)

LOAEL = 10,000 ppm (446 mg/kg/day) for systemic toxicity based 

on reduction in mean body weight and mean body weight gain in 

males and the NOAEL is 3000 ppm (131 mg/kg/day).

The test material was not carcinogenic at the doses tested. 

Gene Mutation

870.5100

Bacterial reverse mutation

00077065 (1980)

Acceptable/guideline

21.6% formulation

50 to 5000 μg/plate

tested up to cytotoxic dose

Positive: Increased the number of revertant colonies (0.4-0.7 over 

the number of the spontaneous reversion rate) in strain TA1535 at 

concentrations of 50, 166, 500 and 1666 μg/plate but not at 5000 

μg/plate.

Gene Mutation

870.5100

Bacterial reverse mutation

40412401 (1987)

Acceptable/guideline

72.3% purity

0.1 to 50 μl/plate

tested up to cytotoxic dose.

Positive: 40% or greater reduction in histidine+ colonies of strains 

TA1537, TA 1538, and TA98 exposed to 50 μl/plate ± activation. 

In TA1535 strain, a dose related increase in reversion ranging from 

1.5 at 5.0 μl/plate to 4-fold at 50 μl/plate in the absence of S9 

activation and 2-fold at 10 and 25 μl/plate and 3.5 fold at 50 μl/plate 

+ activation. A repeat test confirmed that the test material is 

mutagenic in the TA1535 strain. 

Other Effects 

870.5300

870.5300

40498101 (1988)

Acceptable/guideline

40555301 (1988)

Acceptable/guideline

Negative: Ethephon did not induce forward mutations in CHO cells. 

The 5.0 mg/ml dose was 100% cytotoxic
Page 41 of 59

Table A.2.2: Ethephon: Toxicity Profile - Toxicological Studies

Guideline No./ Study Type MRID No. (year)/ 

Classification /Doses

Results

870.5395

870.5500

870.5500

870.5575

00077061 (1981)

Acceptable/guideline

40555201 (1988)

Acceptable/guideline

41255601 (1984)

Acceptable/guideline

00077066 (1980)

Acceptable/guideline

Negative: Ethephon did not induce chromosomal aberrations in 

CHO cells in the presence or absence of microsomal metabolic 

activation at doses reaching subtoxic levels of 2000 μg/mL.

Negative: Ethephon did not produce a statistical significant increase 

in the number of micronuclei per 1000 polychromatic erythrocytes 

in the treated animals when compared to the control group. 

Ethephon is not mutagenic in this micronucleus test.

Negative: Concentrations of the test material below the cytotoxic 

dose of 2000 μg/mL did not induce unscheduled DNA synthesis.

Negative: for inducing Unscheduled DNA Synthesis at 

concentrations up to and including 1000 μg/well.

Doses above 1000 μg/well were cytotoxic

Positive: Increased mitotic gene conversion in strain D7 at doses of 

42 and 45 mg/ml without metabolic activation. Was not tested with 

metabolic activation. 

870-5575 00077063 (1980)

Mitotic gene conversion 

assay (Saccharomyces 

cerevisiae), July 15, 1980

21.6% formulation

1/3, 1/10, 1/30, 1/100 

dilution of a high dose that 

caused 50% survival of the 

yeast cells.

Ethrel formulation 21.6% did not induce mutation in Saccharomyces 

cerevisiae cells under the conditions of the test.

Unacceptable/Non-guideline: actual concentrations not given. 

Ethrel was not tested with metabolic activation. The test was not 

performed on levels beyond the 50% survival rate

870.5450 00029494 (1979)

Dominant lethal assay in 

rats: 

oral gavage at 0, 250, 500 

or 1000 mg/kg/day for 5 

days

Inconclusive. The study protocol is not consistent with the current 

guidelines. Purity not given. unacceptable

870.6200a

Acute neurotoxicity 

44000802 (1996)

Acceptable/guideline

72.4% a.i.

Single doses at 0, 500, 

1000 or 2000 mg/kg

sacrificed on Day 15

LOAEL = 500 mg/kg bw (the lowest dose tested) based on pinpoint 

pupils in all ethephon treated groups which lasted throughout the 

observation period. A NOAEL was not established. Pupillary 

constriction, increased urination (males only), reduced food 

consumption and body weight, decreased body temperature (females 

only), and reduced motor activity and mortality at the mid- and the 

high-dose level. No neuropathological lesions were seen that were 

attribute to treatment. ChE inhibition was not evaluated.

870.6100

Acute Delayed 

Neurotoxicity - Hen 

00144559 (1983)

Acceptable/guideline

70.75%

single oral gavage 3160 or 

3850 mg/kg, administered 

another dose of 2370 

mg/kg on day 21, 

sacrificed on day 42.

Mortality 28/30 & 10/30 birds at 3850 & 3160 mg/kg, respectively 

during the first 21 day period. Body weight & food consumption 

reduced. Lethargy and anorexia 3-5 hours after dosing and lasted 

for up to 72 hours. No signs of ataxia in any of the birds. A low 

incidence of lesions in the nerves in controls and ethephon treated 

groups, but none appeared to be treatment related, except in the 

positive control (TOCP) where various lesions were noted.
Page 42 of 59

Table A.2.2: Ethephon: Toxicity Profile - Toxicological Studies

Guideline No./ Study Type MRID No. (year)/ 

Classification /Doses

Results

Ethephon did not produce acute delayed neurotoxicity in hens after 

being dosed with nearly lethal doses.

Non-guideline

2-week range finding 

neurotoxicity study

rats

44283001 (1997)

Acceptable/non-guideline

72.5% a.i.

0, 100, 300, 600, or 

1000 mg/kg/day, gavage. 

LOAEL = 600 mg/kg/day based on mortality and cholinergic signs 

(abnormal respiratory sounds and breathing) and body weight loss. 

The NOAEL for systemic toxicity is 300 mg/kg/day. 

Plasma ChE activity was inhibited at all dose levels but not RBC 

ChE activity. Brain ChE activity was not evaluated.

Mortality at 1000 mg/kg/day (6/6 males, 5/6 females died between 

Days 3 and 10), and 600 mg/kg/day (2/6 males, 4/7 females died 

between Days 2 and 9). Rats in the 1000 and 600 mg/kg/day 

treatment groups had mean body weights 27-34 and 13-19% lower, 

respectively, than the controls (days 8-12), and a mean food 

consumption 23-48% lower than the controls during the first week 

of the study. 

870.6200b

Subchronic neurotoxicity 

screening battery

Rats

44283002 (1997)

Acceptable/non-guideline

72.5% a.i.

0, 75, 150 or 400/300 

mg/kg/day for 13 weeks.

LOAEL for neurotoxic effects (abnormal respiratory sounds, 

vocalization in males, cold to touch in males and mortality) is 

400/300 mg/kg/day, the highest dose tested. The NOAEL for 

neurotoxic effects is 150 mg/kg/day. Inhibition of plasma and/or 

RBC ChE activity at the lower dose levels was not accompanied by 

cholinergic and/or clinical signs and is not considered relevant to the 

human response to ethephon. Brain ChE activity was not inhibited 

at any of the dose levels.

870.6300

Developmental 

neurotoxicity rats

A developmental neurotoxicity study was not conducted based on the unlikelihood that ethephon 

crosses the blood/brain barrier of offspring (TXR 0054221).

870.7800

Immunotoxicity Study –

Mice

49037903 (2012)

Ethephon 70.8% a.i.

0, 1000, 3000 or 7000 ppm 

(0, 187, 575, 1373 

mg/kg/day for 28 days

LOAEL for systemic and immunotoxicity is > 7000 ppm (>1373 

mg/kg/day).

NOAEL for systemic and immunotoxicity = 7000 ppm (1373 

mg/kg/day).

870.7485

Metabolism and 

pharmacokinetics

Rats

41906101 (1990)

Acceptable/guideline

single intravenous doses at 

50 mg/kg, or single oral 

doses at 50 or 1000 mg/kg 

or in multiple daily oral 

doses (unlabeled ethephon) 

for 14 days at 50 

mg/kg/day followed by 

single oral dose of the 14Cethephon to groups of male 

and female Crl:CD(SD)BR 

rats (5/sex/dose)

Oral and IV doses were rapidly absorbed and excreted in the urine 

accounting for 48-71% of the administered dose (AD). The iv 

dosing indicated that biliary excretion is minimal since less than 2% 

of the AD was recovered in the feces. Exhaled 14CO2 was <1%, 14Cethylene was 10 to 20% of the AD. Less than 7% of the AD was 

excreted in the feces. Residual radioactivity in tissues was less than 

0.1% of the AD. Total recovered radioactivity was 84-90%. There 

were no significant differences in the pharmacokinetics between the 

sexes. Multiple dosing did not significantly alter the excretion 

pattern. 

Ethephon was not extensively metabolized. Ethephon as disodium 

salt accounted for 90% of the recovered radioactivity in the urine 

and feces with less than 5% as monosodium salt and other 

unidentified metabolites. The potential decomposition products, 

chloroacetic acid & chloroethanol were not reported or analyzed for. 

870.7600

Dermal penetration

NA, Not required. Ethephon is a severe skin irritant

Special studies

Human Oral Study

00036510 (1972)

Acceptable/nonguideline

0 (3/sex) or 1.8 mg/kg/day 

(5/sex) for 28 days

LOAEL = 1.8 mg/kg/day based on diarrhea and increased urgency 

and frequency of urination, loose stools, stomach cramps or gas.

NOAEL = <1.8 mg/kg/day
Page 43 of 59

Table A.2.2: Ethephon: Toxicity Profile - Toxicological Studies

Guideline No./ Study Type MRID No. (year)/ 

Classification /Doses

Results

Special studies

Human Oral Study

00066931 (1977)

Unclassifiable

0 (6 males and 4 females) 

or 0.5 mg/kg/day (10/sex) 

for 16 days with 29 day 

recovery period.

No clinical symptoms were reported. Hematological, clinical 

chemistry values and urinalysis parameters were comparable to the 

placebo controls. 

Plasma and RBC ChE activities were significantly inhibited in both 

placebo and test groups. Therefore, this finding makes any 

conclusions regarding the effects attributable to ethephon 

administration impossible. This is in contradiction to the study 

authors overall conclusion that a daily ethephon oral dosage of 0.5 

mg/kg/day produces significant plasma ChE inhibition which is 

reversible in 15 days.
Page 44 of 59

A.3 Hazard Identification and Endpoint Selection

A.3.2 Acute Reference Dose

The HIARC selected an acute RfD of 0.06 mg/kg from a 28 day human clinical study based upon 

cholinergic signs in humans of both sexes following daily bolus dosing (capsule) at the Lowest 

Observed Adverse Effect Level (LOAEL) of 1.8 mg/kg/day. Plasma and RBC cholinesterase 

were slightly elevated in treated subjects but fell within the normal range. The study is 

considered appropriate for selection of an acute endpoint because clinical signs were generally 

seen between days 1 and 4. A UF of 10 for intraspecies variation is adequate for this risk 

assessment. The conventional UF of 10x for interspecies extrapolation was not applied because 

of the use of a human study. An additional traditional 3X factor is applied for the lack of a 

NOAEL in the selected study (MRID 0051308). The 3X UF for extrapolating from a LOAEL to 

a NOAEL is adequate based on:

 The duration of the effects elicited by ethephon in the 28-day oral toxicity study in 

humans are consistent with a Cmax reaction (i.e., compound concentration in the body 

quickly reaches a peak and declines very rapidly (~90% is eliminated within 24 hrs) so 

that every exposure appears as a single exposure).

 Mild clinical effects seen in the 28-day human study. Another 29-day human study 

(MRID 00066931 )at one third of the dose (0.5 mg/kg/day) no clinical signs were 

reported.

 The use of this endpoint/study is considered appropriate since the toxicokinetic properties 

of this compound indicate a Cmax reaction in which repeated exposures do not lead to 

cumulative toxicity or progression of the effects.

The HIARC recommended a (UF) of 30x for the general population and all population subgroups 

except infants <1 year old and children 1-6 years. The HIARC recommended that an additional 

3X factor be applied to dietary exposure assessments for infants <1 year old and children 1-6 

years old for lack of data indicating that ethephon does not cross the blood brain barrier in the 

young. As previously noted, the 3X UF has been removed based HED’s reevaluation of the 

FQPA factor in light of additional data. The Acute RfD is: 

aRfD for general population =

1. 8 mg/kg (LOAEL)

10 (UF) 3 (SF)

= 0. 06 mg/kg

A.3.3 Chronic Reference Dose

The HIARC selected a chronic RfD of 0.06 mg/kg from a 28 day human clinical study based 

upon cholinergic signs in humans of both sexes following daily bolus dosing (capsule) at the 

Lowest Observed Adverse Effect Level (LOAEL) of 1.8 mg/kg/day. The same study is 

considered appropriate for selection of a chronic endpoint because metabolism studies (MRID 

41906101) in rats have shown that ethephon is rapidly excreted in urine (48-71% of the 

administered dose) as disodium salt of the parent, and exhalation (10-20% of the AD) as ethylene 

and is not retained in the body. Therefore chronic exposures would not lead to accumulative 

effects and the short term study selected would be appropriate for the chronic exposure. The 
Page 45 of 59

same uncertainty factors recommended for the acute RfD are considered appropriate for the 

chronic RfD for the same reasons. The ChronicRfD is: 

cRfD for general population =

1. 8 mg/kg (LOAEL)

10 (UF) 3 (SF)

= 0. 06 mg/kg

A.3.4 Incidental Oral Exposure - All Durations

The HIARC selected a chronic RfD of 0.06 mg/kg from a 28 day human clinical study based 

upon cholinergic signs in humans of both sexes following daily bolus dosing (capsule) at the 

Lowest Observed Adverse Effect Level (LOAEL) of 1.8 mg/kg/day. However, exposure via 

incidental ingestion was not assessed because the current limited residential use pattern of 

ethephon is unlikely to result in exposure via this route.

A.3.5.1 Dermal Exposure - All Durations

At dermal doses above 150 mg/kg/day, ethephon is corrosive to the skin. In a range finding 

study, dermally applied ethephon was lethal above 500 mg/kg/day and was a severe irritant at 

500 mg/kg/day. In the main 21-Day rabbit dermal toxicity study ethephon produced no systemic 

toxicity at 150 mg/kg/day or less, but cause local dermal toxicity at doses of 25 mg/kg/day and 

above. Since ethephon is dermally corrosive, exposures at levels high enough to cause systemic 

toxicity are not expected. Therefore, risk assessment of dermal exposures to ethephon would 

not be applicable.

A.3.5.2Dermal Absorption

Dermal absorption data are not available and also not applicable for risk assessment purposes. 

A.3.6 Inhalation Exposure - All Durations

The HIARC selected a dose for inhalation risk assessment of 0.06 mg/kg from a 28 day human 

clinical study based upon cholinergic signs in humans of both sexes following daily bolus dosing 

(capsule) at the Lowest Observed Adverse Effect Level (LOAEL) of 1.8 mg/kg/day. Absorption 

via the inhalation route is considered to be equivalent to the oral route.
Page 46 of 59

Appendix B. Physical/Chemical Properties

Table C1. Physico-Chemical Properties

Parameter Value Reference

Molecular Weight 144.5

R. Daiss, D327932, 5/10/2006

pH

Water solubility (20°C) readily soluble in water

Solvent solubility (20°C to 25°C)

very soluble in water, 

alcohol, acetone, and 

propylene glycol, only 

slightly soluble in 

aromatic solvents such 

as benzene and toluene, 

and insoluble in 

kerosene and diesel oil

Vapor pressure (25°C) <1 x 10-7 mmHg at 25 C

Dissociation constant, pKa K1 = 3.16 X 10-3

and K2

= 6.31 X 10-8at 25 C

Octanol/water partition coefficient, log KOW

(25°C) <0.603 ±0.0006 at 25 C
Page 47 of 59

Appendix C. Ethephon Use Pattern

Table 4.1. Summary of Directions for Use of Ethephon.

Site

Application Type

Application Timing

Application Equipment

Formulation

(EPA Reg No.)

Maximum Single

Application Rate 

(lb ai/A)

Maximum 

Seasonal 

Rate (lb ai/A)

PHI

(days)

Reentry 

Interval 

(Hours) Use Limitations

Crop Uses

Apple

Foliar

Ground equipment

2 lb/gal SC/L

(228-660)

(264-267)

(66330-262)

(85678-9)

2 2 7 48 A 30-day plant-back interval is specified. Do 

not apply through irrigation system.

Foliar

 Ground and aerial

 equipment

3 lb/gal EC

(5905-595)

2 2 7 48 A 30-day plant-back interval is specified. Do 

not apply through irrigation system.

Barley

Foliar, broadcast

Ground and aerial 

equipment

2 lb/gal SC/L

(228-660)

(66330-262)

(85678-9)

0.5 0.5 40 48 Apply ground and aerial applications in a 

minimum of 7 and 3 gal/A, respectively. 

Grazing or foraging by livestock or cutting 

for hay or silage are prohibited. Mature straw 

at normal harvest may be consumed by 

animals. A 30-day plant-back interval is 

specified.

Foliar, broadcast

Early to late boot stage 

prior to awn emergence

Ground and aerial 

equipment

4 lb/gal SC/L

(264-377)

0.5 0.5 40 24 Apply ground and aerial applications in a 

minimum of 7 and 3 gal/A, respectively. 

Grazing or foraging by livestock or cutting 

for hay or silage are prohibited.3 Mature 

straw at normal harvest may be consumed by 

animals. A 30-day plant-back interval is 

specified. 

 Foliar, broadcast

 Ground and aerial

 equipment 

3 lb/gal EC

(5905-595)

0.5 0.5 40 48 Not for use in CA. Grazing or foraging by 

livestock or cutting for hay or silage are 
Page 48 of 59

Table 4.1. Summary of Directions for Use of Ethephon.

Site

Application Type

Application Timing

Application Equipment

Formulation

(EPA Reg No.)

Maximum Single

Application Rate 

(lb ai/A)

Maximum 

Seasonal 

Rate (lb ai/A)

PHI

(days)

Reentry 

Interval 

(Hours) Use Limitations

prohibited. A 30-day plant-back interval is 

specified.

Blackberry

 Foliar, broadcast

 Ground equipment

2 lb/gal SC/L

(228-660)

(264-267)

(66330-262)

(85678-9)

2 2 3 48 For use on blackberries in OR and WA only. 

A 30-day plant-back interval is specified.

Foliar

 Ground and aerial

 equipment 

3 lb/gal EC

(5905-595)

2 2 3 48 For use on blackberries in OR and WA only. 

A 30-day plant-back interval is specified.

Blueberry

 Foliar, broadcast

 Ground and aerial

 equipment 

2 lb/gal SC/L

(228-660)

(264-267)

(66330-262)

(85678-9)

2 2 NS 48 Apply ground and aerial applications in a 

minimum of 100-200 gal/A and 10 gal/A, 

respectively. A 30-day plant-back interval is 

specified.

 Foliar, broadcast

 Ground and aerial

 equipment 

3 lb/gal EC

(5905-595)

2 2 NS 48 Not registered for use in CA.

Cantaloupe

Foliar

Aerial or ground 

equipment

2 lb/gal SC/L

(228-660)

(264-267)

(66330-262)

(85678-9)

0.75 0.75 2 48 AZ, CA, and TX only. Ground and aerial 

applications can be made in a minimum of 40 

and 10 gal/A, respectively. Ground 

equipment may be used for application in CA 

and AZ. Aerial or ground applications are 

allowed in TX only. A 30-day plant-back 

interval is specified.

Foliar 3 lb/gal EC

(5905-595)

0.75 0.75 2 48 AZ, CA, and TX only. Ground and aerial 

applications can be made in a minimum of 40 
Page 49 of 59

Table 4.1. Summary of Directions for Use of Ethephon.

Site

Application Type

Application Timing

Application Equipment

Formulation

(EPA Reg No.)

Maximum Single

Application Rate 

(lb ai/A)

Maximum 

Seasonal 

Rate (lb ai/A)

PHI

(days)

Reentry 

Interval 

(Hours) Use Limitations

Ground and aerial 

equipment

and 10 gal/A, respectively. Ground 

equipment may be used for application in CA 

and AZ. Aerial or ground applications are 

allowed in TX only. A 30-day plant-back 

interval is specified.

Cherry (sweet and tart)

Foliar

Ground equipment

2 lb/gal SC/L

(228-660)

(264-267)

(66330-262)

(85678-9)

1 (sweet)

0.25 (tart)

1 7 48 This use is not permitted in CA. Apply in a 

minimum of 50 gal/A. A 30-day plant-back 

interval is specified.

Foliar

Ground and aerial 

equipment

3 lb/gal EC

(5905-595)

1 (sweet)

0.25 (tart)

1 7 48 This use is not permitted in CA. 

Cotton

Foliar, Broadcast

Ground equipment

Aerial equipment also*

2 lb/gal SC/L

(66330-262)

2.28 lb/gal SC

(228-607)

(34704-911)*

6 lb/gal EC

(228-659)*

(228-709)*

(228-727)*

(264-418)*

(264-703)*

(9779-349)*

(34704-856)*

(55467-16)*

(66222-136)*

2 2 7 48 A 30-day plant-back interval is specified. 

EPA Reg. No. 264-703 specifies 3 gal/A by 

air and 10 gal/A by ground. A 30 day plantback interval is specified for all crops. Do 

not apply through irrigation equipment. 

Apply in a minimum of 2 gal/A by air. In AZ 

and CA, aerial spray volume must be at least 

5 gal/A. 
Page 50 of 59

Table 4.1. Summary of Directions for Use of Ethephon.

Site

Application Type

Application Timing

Application Equipment

Formulation

(EPA Reg No.)

Maximum Single

Application Rate 

(lb ai/A)

Maximum 

Seasonal 

Rate (lb ai/A)

PHI

(days)

Reentry 

Interval 

(Hours) Use Limitations

(66330-250)*

(66330-273)*

(83222-33)*

(83520-35)*

(84009-16)*

(84930-31)*

(85678-5)*

(89167-8)*

Foliar

Ground and aerial 

equipment

3 lb/gal EC

(5905-595)

2 2 7 48 Apply in a minimum of 3 gal/A by air. In AZ 

and CA, aerial spray volume must be at least 

5 gal/A. A 30-day plant-back interval is 

specified.

Grape

 Foliar

 Ground equipment

2 lb/gal SC/L

(228-660)

(264-267)

(66330-262)

(85678-9)

0.5 0.5 14 48 For use on table grapes in AZ and CA only. 

Also for use on Thompson seedless for raisin 

production. A 30-day plant-back interval is 

specified.

Foliar

 Ground and aerial

 equipment 

3 lb/gal EC

(5905-595)

0.5 0.5 14 48 For use on table grapes in AZ and CA only. 

Also for use on Thompson seedless for raisin 

production. A 30-day plant-back interval is 

specified.

Macadamia Nut

Foliar

Prior to harvest

Ground equipment

4 lb/gal SC/L

(HI100005)

0.7 lb ai/100 gal 1 5 24 SLN No. HI100005 permits one application 

to leaves and nuts in HI only at 100-200 

gal/A. Grazing and foraging of cover crops 

is not permitted.

Pepper
Page 51 of 59

Table 4.1. Summary of Directions for Use of Ethephon.

Site

Application Type

Application Timing

Application Equipment

Formulation

(EPA Reg No.)

Maximum Single

Application Rate 

(lb ai/A)

Maximum 

Seasonal 

Rate (lb ai/A)

PHI

(days)

Reentry 

Interval 

(Hours) Use Limitations

Foliar

Ground and aerial 

equipment

2 lb/gal SC/L

(228-660)

(264-267)

(66330-262)

(85678-9)

1 1 5 48 A 30-day plant-back interval is specified.

Foliar

Ground and aerial 

equipment

3 lb/gal EC

(5905-595)

1 1 5 48 Not for use in CA. A 30-day plant-back 

interval is specified.

Pineapple

Foliar broadcast

Ground equipment

2 lb/gal SC/L 

(264-267)

(66330-262)

(85678-9)

2 3 2 48 Apply in a minimum of 100 gal/A. Grazing 

of pineapple forage is not permitted. 

Foliar

Ground and aerial 

equipment

3 lb/gal EC

(5905-595)

2 3 2 48 Not for use in CA. A 30-day plant-back 

interval is specified.

Sugarcane

Foliar, broadcast

Aerial equipment

2 lb/gal SC/L 

(264-267)

(66330-262)

0.5 0.5 2 

months

48 Application permitted in HI only. Grazing of 

sugarcane forage is not permitted.

Foliar

Ground and aerial 

equipment

3 lb/gal EC

(5905-595)

0.5 0.5 2 

months

48 Not for use in CA. A 30-day plant-back 

interval is specified.

Tobacco (Flue-cured only) 1

Foliar, directed

Foliar, broadcast

Ground equipment

2 lb/gal SC/L

(228-660)

(264-267)

(264-292)

(66330-262)

2 2 2 48 A 30-day plant-back interval is specified.
Page 52 of 59

Table 4.1. Summary of Directions for Use of Ethephon.

Site

Application Type

Application Timing

Application Equipment

Formulation

(EPA Reg No.)

Maximum Single

Application Rate 

(lb ai/A)

Maximum 

Seasonal 

Rate (lb ai/A)

PHI

(days)

Reentry 

Interval 

(Hours) Use Limitations

(85678-9)

Foliar, directed

Foliar, broadcast

Ground equipment

6 lb/gal EC

(228-659)

(228-709)

(264-418)

(34704-856)

(55467-16)

(66222-136)

(66330-250)

(66330-273)

(83222-33)

(83520-35)

(84009-16)

(84930-31)

(85678-5)

(89167-8)

2 2 2 48 A 30-day plant-back interval is specified.

Foliar, broadcast

Ground and aerial 

 equipment 

3 lb/gal EC

(5905-595)

2 2 2 48 Not for use in CA.

Tomato (fresh market)

Foliar, broadcast

Aerial and ground 

equipment

2 lb/gal SC/L

(228-660)

(264-267)

(66330-262)

(85678-9)

1.25 1.25 3 48 This use is permitted only in CA. A 30-day 

plant-back interval is specified.

Foliar, broadcast

 Aerial and ground

 equipment 

3 lb/gal EC

(5905-595)

1.24 1.63 3 48 Do not use on greenhouse tomatoes.

Tomato (for processing)

Foliar, broadcast 2 lb/gal SC/L 1.63 1.63 3 48
Page 53 of 59

Table 4.1. Summary of Directions for Use of Ethephon.

Site

Application Type

Application Timing

Application Equipment

Formulation

(EPA Reg No.)

Maximum Single

Application Rate 

(lb ai/A)

Maximum 

Seasonal 

Rate (lb ai/A)

PHI

(days)

Reentry 

Interval 

(Hours) Use Limitations

Aerial and ground 

equipment

(228-660)

(264-267)

(66330-262)

(85678-9)

Apply in a minimum of 20 (ground) and 10 

(air) gal/A. A 30-day plant-back interval is 

specified. Do not use on greenhouse 

tomatoes.

Foliar, broadcast

 Aerial and ground

 equipment 

3 lb/gal EC

(5905-595)

1.63 1.63 3 48 Do not use on greenhouse tomatoes.

Tomato (Greenhouse)

Foliar, broadcast

Ground equipment

2 lb/gal SC/L

(264-267)

1.25 1.25 2 48 Do not apply through irrigation system.

Tomato (Home Garden)

Foliar, broadcast

 Ground equipment

0.33 lb/gal SC/L

(264-543)

(66330-284)

0.018 lb ai/gal NS 14 NS Thoroughly wet leaves and fruit.

Walnut

Foliar

Ground Equipment

2 lb/gal SC/L

(228-660)

(264-267)

(66330-262)

(85678-9)

1.25 1.25 5 48 A 30-day plant-back interval is specified. For 

use in CA only.

Foliar, broadcast

 Aerial and ground

 equipment 

3 lb/gal EC

(5905-595)

1.25 1.25 5 48 A 30-day plant-back interval is specified. For 

use in CA only.

Wheat

Foliar, broadcast

Ground and aerial 

equipment

2 lb/gal SC/L

(228-660)

(66330-262)

(85678-9)

0.5 0.5 40 48 Apply ground and aerial applications in a 

minimum of 7 and 3 gal/A, respectively. 

Grazing or foraging by livestock or cutting 

for hay or silage are prohibited.3 Mature 

straw at normal harvest may be consumed by 
Page 54 of 59

Table 4.1. Summary of Directions for Use of Ethephon.

Site

Application Type

Application Timing

Application Equipment

Formulation

(EPA Reg No.)

Maximum Single

Application Rate 

(lb ai/A)

Maximum 

Seasonal 

Rate (lb ai/A)

PHI

(days)

Reentry 

Interval 

(Hours) Use Limitations

animals. A 30-day plant-back interval is 

specified.

 Foliar, broadcast

 Ground and aerial

 equipment 

3 lb/gal EC

(5905-595)

0.5 0.5 40 48 Not for use in CA. Grazing or foraging by 

livestock or cutting for hay or silage are 

prohibited. A 30-day plant-back interval is 

specified.

Foliar, broadcast

Early to late boot stage 

prior to awn emergence

Ground and aerial 

equipment

4 lb/gal SC/L

(264-377)

0.5 0.5 40 24 Apply ground and aerial applications in a 

minimum of 7 and 3 gal/A, respectively. 

Grazing or foraging by livestock or cutting 

for hay or silage are prohibited.4 Mature 

straw at normal harvest may be consumed by 

animals. A 30-day plant-back interval is 

specified.

Ornamental Fruit Trees (Apple, carob, crabapple, cottonwood, elm, flowering pear, horse chestnut, maple, oak, olive, pine, sour orange, sweetgum, sycamore) 

for Fruit Elimination2

 Foliar, broadcast

 Ground equipment 

2 lb/gal SC/L

(228-660)

(264-267)

(53883-314)

(66222-151)

(66330-262)

(70506-288)

(85678-9)

0.33 lb/gal SC/L

(264-263)

(264-543)

(54705-8)

(66330-284)

0.009 lb ai/gal NS NA 48 Apply as a foliar spray but not to runoff. No 

REI on the residential product 264-543.

 Foliar, broadcast

 Ground equipment

3 lb/gal EC

(5905-595)

0.1875 NS NA 48

Ornamentals (ornamental conifers, Douglas fir ornamentals, and ornamental deciduous trees) for Mistletoe Removal
Page 55 of 59

Table 4.1. Summary of Directions for Use of Ethephon.

Site

Application Type

Application Timing

Application Equipment

Formulation

(EPA Reg No.)

Maximum Single

Application Rate 

(lb ai/A)

Maximum 

Seasonal 

Rate (lb ai/A)

PHI

(days)

Reentry 

Interval 

(Hours) Use Limitations

 Foliar, broadcast

 Ground equipment 

2 lb/gal SC/L

(228-660)

(264-267)

(53883-314)

(66222-151)

(66330-262)

(70506-288)

(85678-9)

0.33 lb/gal SC/L

(264-543)

(54705-8)

(66330-284)

0.05 lb ai/gal NS NA 48 0.05 lb ai/gal rate is for deciduous trees.

0.025 lb ai/gal rate is for ornamental conifers.

0.0125 lb ai/gal rate is for ornamental douglas 

fir.

 Foliar, broadcast

 Ground equipment

3 lb/gal EC

(5905-595)

0.05 lb ai/gal 0.5 40 48 0.05 lb ai/gal rate is for deciduous trees.

0.025 lb ai/gal rate is for ornamental conifers.

0.0125 lb ai/gal rate is for ornamental douglas 

fir.

Ornamental Bromeliads for Flower Induction

 Foliar, broadcast

 Ground equipment

2 lb/gal SC/L

(228-660)

(85678-9)

0.33 lb/gal SC/L

(264-263)

(54705-8)

(66330-283)

0.02 lb ai/gal

0.125 lb ai/10 ft2

NS NA 48 Avoid overspraying to runoff. The 0.125 lb 

ai/10 ft2is for greenhouse bench or outdoor 

bed area.

Ornamental Defoliation (roses, tallhedge buckthorn, and apple nursery stock in WA)

 Foliar, broadcast

 Ground equipment

2 lb/gal SC/L

(228-660)

(85678-9)

0.33 lb/gal SC/L

(264-263)

0.008 lb ai/gal roses

0.08 lb ai/gal 

tallhedge buckthorn

0.0017 lb ai/gal 

apple nursery stock

0.0033 lb 

ai/gal for 

apple nursery 

stock

NA 48 Apply to thoroughly wet foliage.
Page 56 of 59

Table 4.1. Summary of Directions for Use of Ethephon.

Site

Application Type

Application Timing

Application Equipment

Formulation

(EPA Reg No.)

Maximum Single

Application Rate 

(lb ai/A)

Maximum 

Seasonal 

Rate (lb ai/A)

PHI

(days)

Reentry 

Interval 

(Hours) Use Limitations

(54705-8)

(66330-283)

Increased Lateral Branching on Ornamentals (see label for species)

 Foliar, broadcast

 Ground equipment

2 lb/gal SC/L

(228-660)

(85678-9)

0.33 lb/gal SC/L

(264-263)

(54705-8)

(66330-283)

0.004 lb ai/gal 

except azalea

0.04 lb ai/gal for 

azalea

NS NA 48 Apply to thoroughly wet foliage but not to 

runoff.

Reduction of Hyacinth Stem Topple and Daffodil Plant Height

 Foliar, broadcast

 Ground equipment

2 lb/gal SC/L

(228-660)

(85678-9)

0.33 lb/gal SC/L

(264-263)

(54705-8)

(66330-283)

0.033 lb ai/gal NS NA 48

Hybrid Seed Production (cucumber, squash, and pumpkins)

 Foliar, broadcast

 Ground equipment

2 lb/gal SC/L

(228-660)

0.33 lb/gal SC/L

(264-263)

(66330-283)

(85678-9)

0.08 lb ai/A 

cucumber and 

squash

0.25 lb ai/A 

pumpkins (IL only)

0.25 lb ai/A 

pumpkins, squash, 

cucumbers (CA 

only)

16

1.5

1.5

NS

42

60

48 Do not harvest any treated cucumbers, 

squash, or pumpkins for human or livestock 

consumption. Seed production only.
Page 57 of 59

Table 4.1. Summary of Directions for Use of Ethephon.

Site

Application Type

Application Timing

Application Equipment

Formulation

(EPA Reg No.)

Maximum Single

Application Rate 

(lb ai/A)

Maximum 

Seasonal 

Rate (lb ai/A)

PHI

(days)

Reentry 

Interval 

(Hours) Use Limitations

 Foliar, broadcast

 Ground equipment

0.33 lb/gal SC/L

(54705-8)

0.25 lb ai/A 

cantaloupe, 

pumpkin, squash, 

cucumber (CA 

only)

0.08 lb ai/A 

cantaloupe, 

cucumber, and 

squash

0.25 lb ai/A 

pumpkins

1.5 60

42

48

Commercial Turf (golf course, parks and sports turf)

 Foliar, broadcast

 Ground equipment

2 lb/gal SC/L

(264-267)

(228-660)

(432-1230)

(53883-314)

(66222-151)

(66330-262)

(70506-288)

(85678-9)

0.09 lb ai/1000 ft2 0.47 lb 

ai/1000 ft2

NA 48 No REI specified on 432-1230.

 Foliar, broadcast

 Ground equipment

3 lb/gal EC

(5905-595)

0.08 lb ai/1000 ft2 0.47 lb 

ai/1000 ft2

NA 48

1 Non-food use.

2 Label directions for apples, crabapples, carob, and olives that are for ornamental use only must be clearly designated as such on all pertinent labels.

3 These label restrictions are no longer appropriate since the Agency has determined that barley and wheat forage and hay are not under grower/farmer 

control (OPPTS 860 Guidelines), therefore, are not practical or enforceable.
Ethephon Human Health Risk Assessment DP No. D423165

Page 58 of 59

Appendix D.

Ethephon (PC Code 099801; 08/10/15)

Summary of US and International Tolerances and Maximum Residue Limits 

Residue Definition: 

US Canada Mexico1 Codex2

40 CFR 180.300:

Plant/Livestock: Compliance with the tolerance 

levels specified below is to be determined by 

measuring only ethephon [(2-chloroethyl) 

phosphonic acid]

(P)-(2-

chloroethyl)phosphon

ic acid

Ethephon

Commodity Tolerance (ppm) /Maximum Residue Limit (mg/kg)

US Canada Mexico1 Codex2

Apple 5.0 3 5

Apple, juice 10.0 6

Barley, bran 5.0

Barley, grain 2.0 0.5 1

Barley, straw 10.0 5 barley straw and 

fodder, dry

Blackberry 30.0 20

Blueberry 20.0 10 20

Cantaloupe 2.0 2 1

Cattle, fat 0.02

Cattle, kidney 1.0 0.2 (*)

Cattle, meat 0.02 0.1 (*)

Cattle, meat byproducts, except 

kidney 0.2 0.2 (*) 

Cherry 10.0 8 sweet cherries

2 tart cherries

10

Coffee, bean, green 0.5 1

Cotton, gin byproducts 180.0

Cotton, undelinted seed 6.0 7 2

Cucumber 0.1

Egg 0.002 0.2 (*) chicken eggs

Goat, fat 0.02

Goat, kidney 1.0 0.2 (*) edible offal 

Goat, meat 0.02 0.1 (*)

Goat, meat byproducts, except 

kidney 0.2 0.2 (*) edible offal 

Grape 2.0 2 1

Grape, raisin 12.0 5 5 dried grapes (=currants, 

raisins and sultanas)

Hazelnut 0.80 0.2

Hog, fat 0.02

Hog, kidney 1.0 0.2 (*) edible offal 

Hog, meat 0.02 0.1 (*)

Hog, meat byproducts, except 

kidney 0.2 0.2 (*) edible offal 

Horse, fat 0.02

Horse, kidney 1.0 0.2 (*) edible offal 

Horse, meat 0.02 0.1 (*)

Horse, meat byproducts, except 

kidney 0.2 0.2 (*) edible offal 

Milk 0.01 0.05 (*) milk of cattle, 

goats, sheep

Nut, macadamia 0.5 0.01
Ethephon Human Health Risk Assessment DP No. D423165

Page 59 of 59

Summary of US and International Tolerances and Maximum Residue Limits 

Residue Definition: 

US Canada Mexico1 Codex2

Pepper 30.0

5 bell peppers, nonbell peppers5 peppers

50 peppers chili, dried

Pineapple 2.0 2 2

Poultry, fat 0.02

Poultry, liver 0.05 0.2 (*) poultry edible 

offal of

Poultry, meat 0.01 0.1

Poultry, meat byproducts, except 

liver 0.01 0.2 (*) poultry edible offal of 

Sheep, fat 0.02

Sheep, kidney 1.0 0.2 (*) edible offal 

Sheep, meat 0.02 0.1 (*)

Sheep, meat byproducts, except 

kidney 0.2 0.2 (*) edible offal 

Sugarcane, molasses 1.5 1.5

Tomato 2.0 2 2

Walnut 0.5 0.3 black walnuts, 

English walnuts

0.5

Wheat, bran 5.0 2.2

Wheat, germ 5.0

Wheat, grain 2.0 2 1

Wheat, middlings 5.0

Wheat, shorts 5.0

Wheat, straw 10.0 5 wheat straw and 

fodder, dry

MRLs with NO US Equivalents

Figs, dried or dried and candied 3 figs 10

Rye 1

Rye straw and fodder, dry 5

Barley milling fractions, 

excluding flour

2

Citrus fruits 1

Cranberries 2

Completed: M. Negussie; 08/24/2015

1 Mexico adopts US tolerances and/or Codex MRLs for its export purposes.

2 * = absent at the limit of quantitation; Po = postharvest treatment, such as treatment of stored grains. PoP = 

processed postharvest treated commodity, such as processing of treated stored wheat. (fat) = to be measured on the 

fat portion of the sample. MRLs indicated as proposed have not been finalized by the CCPR and the CAC.

(c) Tolerances with regional registrations. A tolerance with regional registration, as defined in §180.1(m), of 0.1 

part per million is established for residues of the plant regulator ethephon [(2-chloroethyl)phosphonic acid] in or on 

the food commodity sugarcane.