1

UNITED STATES ENVIRONMENTAL PROTECTION AGENCY

 WASHINGTON, D.C. 20460

OFFICE OF PESTICIDES AND TOXIC SUBSTANCES 

MEMORANDUM

DATE: May 18, 2010

SUBJECT: Application for Experimental-Use Permit and temporary tolerance exemption for 

FAL 1800 (Prohydrojasmon)

EPA Reg. #: 62097-EUP-R

Chemical Class: Biochemical

 PC Code : 028000

CAS Number: 158474-72-7

MRID 47927801-43

FROM: Miachel Rexrode, Ph.D, Senior Biologist /S/ 05/18/2010

Biochemical Pesticides Branch

Biopesticides & Pollution Prevention Division (7511P)

TO: Gina Casciano, Regulatory Action Leader /S/ 05/18/2010

Biochemical Pesticides Branch

Biopesticides & Pollution Prevention Division (7511P) 

ACTION REQUESTED

The applicant, Fine Agrochemicals Ltd., has submitted a EUP application and supporting data for 

FAL 1800, a plant growth regulator to be used to enhance color formation in apples. The 

applicant is also requesting a temporary tolerance exemption.

Executive Summary

Prohydrojasmon is not naturally-occurring but is structurally similar to jasmonic acid (JA). JA is 

an intermediate in the pathway to plant abscisic acid synthesis and has ABA-like activity (i.e. 

growth inhibition, senescence, leaf abscission, as well as a role in wound response and systemic 

resistance). When plants are attacked by insects there is a release of JA, which inhibits the 

insect’s ability to digest protein.
2

The toxicological profile of Prohydrojasmon (FAL 1801) shows that this compound is practically 

non-toxic with a Toxicological Category IV for acute oral and acute inhalation and a Toxicology

Category III for acute dermal toxicity. Prohydrojasmon is a slight eye irritant (Toxicity Category

IV) and is not a skin sensitizer or a primary skin irritant (Toxicology Category IV). Assays for 

mutagenicity, chromosomal aberration, developmental toxicity, and subchronic oral did not 

present any clinical or toxicologically significant effects. This compound is relatively unstable in 

the environment with an aerobic soil half-life of 1.6 – 2.3 hours, and upon consumption breaks 

down under gastric condition with a half-life of 0.8 days.

All product chemistry, Tier I toxicology, and Tier I ecotoxicity studies submitted in support of the 

EUP for FAL 1800 (ai Prohydrojasmon) in support of an exemption from the Requirements of 

Tolerances are acceptable. There are no data gaps and no additional data are required at this time. 

No acute, subchronic, or chronic toxicity endpoints were identified in Guideline studies that were 

submitted and reviewed. Prohydrojasmon is not a sensitizer, not a mutagen or a developmental 

toxicant. There are no known endocrine effects via oral, dermal, or inhalation exposure and no 

significant exposure via drinking water. A temporary Tolerance Exemption is appropriate for this 

compound. There are no concerns for exposure to non-target organisms (aquatic and terrestrial 

species). The Agency has determined a no effect (NE) for threatened and endangered species 

when Prohydrojasmon is used in accordance with EPA-approved labeling. No efficacy data was 

submitted, but none were required for this non-public health use product.

RECOMMENDATIONS AND CONCLUSIONS

FATE AND DISTRIBUTION

FAL 1801 Prohydrojasmon (PDJ)

The fate and distribution information (Table 5.0) show that PDJ was fairly stable in an aquatic 

environment (pH 9 and 200C half-life was 17.7 days), photodegrades in water in about 58 hours, 

and degrades rapidly in soil (1.6 – 2.3 hours). Due to rapid metabolism and decomposition of PDJ 

the adsorption constant could not be calculated (does not bind to soil or sediment).

MRID 47927839: Adsorption/Desorption (OPPTS 835.1230). The laboratory study was 

conducted to determine the adsorption and desorption of prohydrojasmon (PDJ) in four different 

soils. PDJ was added to the soils at concentrations of 5, 1, 0.2, and 0.04 mg/L, with a test 

solution/soil ratio of 10 mL/2 grams. The soils were incubated at 25°C. After 16 hours, PDJ 

adsorption in the four soils ranged from 78.1 to 99.3%, and desorption ranged from 1.0 to 14.9%. 

The material balance for the four soils ranged from 13.7 to 71.2%. Due to the rapid metabolism 

and decomposition of PDJ and the low material balance percentages, the adsorption constant 

for PDJ could not be calculated. The study is classified as Acceptable.

MRID 47927840: Hydrolysis (OPPTS 835.2120). A laboratory study was conducted to 

determine the degradation of prohydrojasmon (PDJ) in water. Test solutions (2 mg/L) of PDJ 
3

were buffered to pH 9 and maintained at 20°C for 24 days or at 40°C for 72 hours. To determine 

degradation under gastric conditions, a treatment of pH 1.2 and 37°C for 32 hours was also 

included. The half-life of PDJ at pH 9 and 20°C was 17.7 days, and at pH 9 and 40°C was 2.0 to 

2.1 days. Based on these results, the Arrhenius equation was used to calculate the half-life at pH 9 

and 25°C as 10.7 days. Under gastric conditions, the half-life was 0.8 days. The major 

degradation product was dihydrojasmonic acid. The study is classified as Acceptable.

MRID 47927841: Photodegradation in Water (OPPTS 835.2240). The study author concluded 

that in this study, the mean half-life of PDJ under light-irradiated conditions was 54.0 hours in 

purified water and 57.8 hours in river water. Under light-shielded conditions, the mean half-life of 

PDJ was 685 hours in purified water and 247 hours in river water. The study is classified as 

Acceptable.

MRID 47927842: Aerobic soil metabolism (OPPTS 835-4100). The study author concluded 

that under aerobic conditions, the elimination of PDJ was similar in the Ibaraki and Osaka soils, 

with a half-life of 1.6 hours and 2.3 hours, respectively, and a DT80 of 3.7 hours and 5.3 hours, 

respectively. The major PDJ metabolite in both soils was DJA, believed to be the result of de-npropylation of PDJ, with CO2 generated as the final product. Under sterile conditions, the half-life 

of PDJ in Ibaraki and Osaka soils was extrapolated to be 102 days and 308 days, respectively. The 

study is classified as Acceptable.

Table 5.0 Fate and Distribution of FAL 1801(PDJ)

Data Requirement Results MRIDs Study Conclusion

Adsorption/Desorption

OPPTS 835.1230

Due to rapid 

metabolism and 

decomposition of 

PDJ and the low

material percentages, 

the adsorption 

constant for PDJ 

could not be 

calculated.

47927839 Acceptable

Hydrolysis

OPPTS 835.2120

Half-life of PDJ at 

pH 9 (200C) was 

10.7 days. Under 

gastric conditions the 

half-life was 

calculated at 0.8 

days. 

47927840 Acceptable

Photodegradation in Water

OPPTS 835.2240

Half-life in lightirradiated conditions 

was 54.0 hours in 

purified water 57.8 

hours and 57.8 hours 

in river water.

47927841

Acceptable

Aerobic Soil Metabolism

OPPTS 835.4100

Ibaraki and Osaka 

soils had half-lives 

of 1.6 and 2.3 hours, 

respectively.

47927842

Acceptable
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TOXICOLOGY

Test Material: FAL 1800 formulation containing 5.25% PDJ

The toxicological profile of FAL 1800 is summarized in Table 6.0 and shows that this compound 

is practically non-toxic mammals with a Toxicity Category IV as noted for acute oral and acute 

inhalation toxicity studies. The acute dermal toxicity study produced an LD50 > 2,000 mg/kg bw 

(Toxicity Category III) and the primary eye irritation study produced acute symptoms after the 

test material was administered, but were resolved by day 7 (Toxicity Category III). FAL 1800 is 

not a skin sensitizer or a primary skin irritant. 

1. Acute oral toxicity (OPPTS 870.1100): Acute oral toxicity study used SD rats. The acute 

oral LD50 was > 5000 mg/kg bw in both male and female rats.

2. Acute dermal toxicity (OPPTS 870.1200): Acute dermal toxicity study used SD rats. The 

acute dermal LD50 was > 2000 mg/kg bw in both male and female rats.

3. Acute inhalation toxicity (OPPTS 870.1300): Acute inhalation toxicity study used rats. The 

acute inhalation LC50 was > 5.0 mg/L in both male and female rats.

4. Primary eye irritation (OPPTS 870.2400): Primary eye irritation study used Japanese white 

rabbits. Acute symptoms were observed after test material administration, but were resolved 

by day 7. FAL 1800 produces reversible intense irritation in the eyes. The maximum average 

score for unwashed eyes was 52.0 one hour after test material instillation. The test material 

was severely irritating.

5. Primary skin irritation (OPPTS 870.2500): Primary skin irritation study used Japanese 

white rabbits. No irritation was noted on the skin.

6. Skin sensitization (OPPTS 870.2600): A skin sensitization study (Buehler method) used 

Hartley guinea pigs. No skin sensitization was observed.

Table 6.0 Toxicological Data for FAL 1800 (end product)

Data Requirement LD50 Toxicity 

Category

MRIDs

Acute Oral Toxicity

OPPTS 870.1100

>5000 mg/kg IV 47927818, 47927819

Acute Dermal Toxicity

OPPTS 870.1200

>2000 mg/kg III 47927818, 47927820

Acute Inhalation Toxicity

OPPTS 870.1300

LC50 > 5.0 mg/L IV 47927818, 47927821
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Table 6.0 Toxicological Data for FAL 1800 (end product)

Data Requirement LD50 Toxicity 

Category

MRIDs

Primary Eye Irritation

OPPTS 870.2400

Acute symptoms 

were observed after 

test material was 

administered, but 

resolved by day 7. 

FAL 1800 produces 

reversible intense 

eye irritation

III 47927818, 47927822

Primary Dermal Irritation

OPPTS 870.2500

No skin irritation. IV 47927818, 47927823

Dermal Sensitization

OPPTS 870.2600

Not a dermal 

sensitizer

- 47927818, 47927824

Test Material: FAL 1801 [prohydrojasmon (PDJ)

The toxicological profile of FAL 1801 is summarized in Table 7.0 and shows that this compound 

is practically non-toxic mammals with a Toxicological Category IV as noted for acute oral and 

acute inhalation toxicity studies. The acute dermal toxicity study produced an LD50 > 2,000 

mg/kg bw (Toxicity Category III). The primary eye irritation study produced slight acute 

symptoms after the test material was administered (Toxicity Category IV) and FAL 1801 proved 

to not be skin sensitizer or a primary skin irritant.

1. Acute oral toxicity (OPPTS 870.1100): Acute oral toxicity study used SD rats. The acute 

oral LD50 was > 5000 mg/kg bw in both male and female rats.

2. Acute dermal toxicity (OPPTS 870.1200): Acute dermal toxicity study used SD rats. The 

acute dermal LD50 was > 2000 mg/kg bw in both male and female rats.

3. Acute inhalation toxicity (OPPTS 870.1300): Acute inhalation toxicity study used rats. The 

acute inhalation LC50 was > 2.8 mg/L in both male and female rats.

4. Primary eye irritation (OPPTS 870.2400): Primary eye irritation study used Japanese white 

rabbits. Slight eye irritation was observed.

5. Primary skin irritation (OPPTS 870.2500): Primary skin irritation study used Japanese 

white rabbits. No irritation was noted on the skin.

6. Skin sensitization (OPPTS 870.2600): A skin sensitization study (Maximization method) 

used Hartley guinea pigs. No skin sensitization was observed.

Comments: The summary (MRID 47927818) seems to include the study results of PDJ (MRIDs 

47927819 to 47927824) and PDJ Formulation (MRIDs 47927825 to 47927830). 
6

Table 7.0 Toxicological Data for Prohydrojasmon (PDJ) FAL 1801

Guideline #

Test

Results/Toxicity 

Category

MRIDs Study Conclusion

Acute Oral Toxicity

OPPTS 870.1100

LD50 > 5000 mg/kg

IV

47927818, 

47927825

Acceptable

Acute Dermal Toxicity

OPPTS 870.1200

LD50 > 2000 mg/kg

III

47927818, 

47927826

Acceptable 

Acute Inhalation Toxicity

OPPTS 870.1300

LC50 > 5.0 mg/L

IV

47927818, 

47927827

Acceptable 

Primary Eye Irritation

OPPTS 870.2400

slight eye irritation

IV

47927818, 

47927828

Acceptable

Primary Dermal Irritation

OPPTS 870.2500

No skin irritation.

IV

47927818, 

47927829

Acceptable 

Dermal Sensitization

OPPTS 870.2600

Not a dermal 

sensitizer

47927818, 

47927830

Acceptable 

870.3100

90 day Oral Toxicity-Rat

NOEL=566-587 

mg/kg/day

47927831 Acceptable

870.3700

Prenatal Developmental 

Toxicity Study - Rat

Maternal NOEL >

500 mg/kg/day

Developmental 

NOEL > 500 

mg/kg/day

47927832 Acceptable 

870.5100

Bacterial Reverse 

Mutation Test

There was no 

evidence of induced 

mutant colonies over 

background

47927833 Acceptable

870.5375

In Vitro Mammalian 

Chromosome Aberration 

Tests

There was no 

evidence of cells 

with chromosomal 

abnormalities

47927834 Acceptable

Classification: Acceptable; no additional data are required. 

TOXICOLOGY STUDIES

FAL 1800 formulation containing 5.25% PDJ

MRID 47927819: Acute Oral Toxicity - Rats (OPPTS 870.1100)

The oral LD50 for males, females, and combined sexes of rats was greater than 5,000 mg/kg

suggesting that PDJ Formulation is a TOXICITY CATEGORY IV. This study is classified as 

Acceptable.

MRID 47927820: Acute Dermal Toxicity - Rats (OPPTS 870.1200)

The acute dermal LD50 for males, females, and combined sexes of rats was greater than 2000 

mg/kg placing PDJ Formulation in TOXICITY CATEGORY III. The study is classified as 

Acceptable.

MRID 47927821: Acute Inhalation Toxicity - Rats (OPPTS 870.1300)

The inhalation LC50 for males, females, and combined sexes of rats was > 5.0 mg/L placing DPJ 
7

Formulation in TOXICITY CATEGORY IV. The study is classified as Acceptable.

MRID 47927822: Acute Eye Irritation - Rabbits (OPPTS 870.2400)

Eye-unwashed group: Corneal opacity was noted on 6/6 rabbits one hour after test material 

instillation with persistence through day 4 with clearance by day 7. No iritis was noted on any

rabbit during the study. Positive conjunctival irritation was noted on 6/6 animals one hour after 

test material instillation with clearance by 24 hours. Eye-washed group: Corneal opacity was 

noted on 3/3 rabbits at one hour after test material instillation with resolution by day 4. No iritis 

was noted on any rabbit during the study. Positive conjunctival irritation was noted on 3/3 

animals at one hour after test material instillation with resolution by 24 hours The maximum 

average score for unwashed eyes was 52.0 at one hour after test material instillation. The 

maximum average score for washed eyes was 40.7 at one and 24 hours after test material 

instillation. PDJ Formulation was severely irritating and is in TOXICITY CATEGORY III. 

This study is classified as Acceptable. 

MRID 47927823: Primary Dermal Irritation - Rabbits (OPPTS 870.2500)

Very slight erythema was noted on 3/6 rabbits one hour after patch removal with clearance on two 

rabbits by 24 hours and on one rabbit by 48 hours. The primary irritation index was 0.2 

suggesting that the PDJ formulation was practically not irritating and is in TOXICITY 

CATEGORY IV. The study is classified as Acceptable.

MRID 47927824: Skin Sensitization - Guinea Pigs (OPPTS 870.2600)

After three consecutive weekly inductions, the test animals, control animals, and controls for 

positive control animals showed no signs of reactivity at 24 and 48 hours after challenge and the 

results for the DNCB positive control were appropriate. PDJ Formulation was not a dermal 

sensitizer. The study is classified as Acceptable.

FAL 1801 Prohydrojasmon (PDJ)

MRID 47927825: Acute Oral Toxicity - Rats (OPPTS 870.1100) 

The oral LD50 for males, females, and combined sexes of rats was greater than 5000 mg/kg 

placing PDJ in TOXICITY CATEGORY IV. The study is classified as Acceptable.

MRID 47927826: Acute Dermal Toxicity - Rats (OPPTS 870.1200)

The acute dermal LD50 for males, females, and combined sexes of rats was greater than 2000 

mg/kg placing PDJ in TOXICITY CATEGORY III. The study is classified as Acceptable.

MRID 7927827: Acute Inhalation Toxicity - Rats (OPPTS 870.1300)

The inhalation LC50 for males, females, and combined sexes of rats was > 2.8 mg/L placing DPJ 

in TOXICITY CATEGORY IV. This study is classified as Acceptable.

MRID 47927828: Acute Eye Irritation - Rabbits (OPPTS 870.2400) 

Eye-unwashed group: Corneal opacity was noted on 2/6 rabbits 24 hours after test material 

instillation with resolution by 48 hours. No iritis or positive conjunctival irritation was noted on 
8

any rabbit during the study. Eye-washed group: Corneal opacity was noted on 3/3 rabbits at one 

hour after test material instillation with resolution on two rabbits by 24 hours and on another 

rabbit by 48 hours. No iritis or positive conjunctival irritation was noted on any rabbit during the 

study. The maximum average score for unwashed eyes and washed eyes were 5.0 and 11.0, 

respectively, at one hour after test material instillation. The test material PDJ was minimally

irritating and is in TOXICITY CATEGORY IV. The study is classified as Acceptable. Note: 

PDJ Formulation was severely irritating.

MRID 47927829: Primary Dermal Irritation - Rabbits (OPPTS 870.2500)

No dermal irritation was noted for any rabbit during the study with a primary irritation index of

0.0. The test material PDJ was not irritating and is in TOXICITY CATEGORY IV. The study

is classified as Acceptable.

MRID 47927830: Skin Sensitization - Guinea Pigs (OPPTS 870.2600) After intradermal and 

topical inductions, the test, control, and control for positive control animals showed no signs of 

reactivity at 24, 48, and 72 hours after challenge. The DNCB positive control animals showed 

positive reactivity. The test material PDJ was not a dermal sensitizer. The study is classified 

as Acceptable.

MRID 47927831: Subchronic oral – rat (OPPTS 870.3100) No clinically or toxicologically 

significant effects were found in any treatment-group. Therefore, the reviewer establishes the 

NOAEL as the highest dose, 10,000 ppm (566 mg/kg bw/day for males and 587 mg/kg bw/day

for females). A LOAEL was not established suggesting that the test animals could have tolerated 

a higher dose (protocol calls for a high test level of at least 1,000 mg/kg). The study is classified 

as Acceptable although the LOAEL was not established. The Agency has calculated the 

possibility of dietary exposure and concludes that in a worst case scenario (no degradation) 

the PDJ residues consumed by a 70 kg person are four orders of magnitude below NOAEL 

that was calculated for this compound as noted in the risk assessment.

MRID 47927832: Prenatal Developmental toxicity – rat (OPPTS 870.3700) 

Maternal effects No treatment-related effects were found at necropsy in maternal animals nor 

were there effects on copra lutei, number of implantations, sex ratio, fetal body weight, or 

preimplantation embryonic mortality. The reviewer does not consider the transient decrease in 

body weight or food intake as adverse and establishes the NOAEL for the study as 500 mg/kg 

bw/day. A LOAEL was not identified. 

Developmental effects No treatment-related effects were found on external examination of the 

fetuses. Visceral examination showed a slight increase in the incidence of thymic remnants; 

however, the increase was within the historical background of the performing laboratory. 

Therefore, the Agency does not consider this a treatment-related effect. There was also a slight 

increase in the incidence of a 14th rib but this was not accompanied by an increased incidence of 

abnormal embryos either on external, skeletal, or visceral examination. Additonally, no increase 

in the incidence of litters with this effect was found. This effect is a common variation in this 

strain of rat and is therefore not considered an adverse effect. Based on the study results, the 

NOAEL for the study is the high-dose 500 mg/kg bw/day but a LOAEL was not identified. 

The study is classified as Acceptable although the LOAEL was not established. The Agency 
9

has calculated the possibility of dietary exposure and concludes that in a worst case scenario 

(no degradation) the PDJ residues consumed by a 70 kg person are four orders of 

magnitude below NOAEL that was calculated for this compound as noted in the risk 

assessment.

MRID 47927833: Salmonella/Escherichia/mammalian activation assay (OPPTS 870.5100)

The investigator concluded that PDJ was not mutagenic to the tested bacterial strains under the 

conditions used in this study. Using doses of the test article up to those that were cytotoxic, both 

without and with activation, there was no dose that caused at least a 2-fold increase in the number 

of revertants compared to the corresponding solvent control. There was also no test condition 

which caused any dose-dependent and reproducible increase in the number of revertants. All 

positive controls, without and with activation, gave appropriate. This is study is classified as 

Acceptable.

MRID 47927834: In vitro Mammalian Chromosome Aberration Test (OPPTS 870.5375)

PDJ was tested up to cytotoxic dose levels (80 μg/mL, based on reduced mitotic activity) without 

S9 activation, and up to the limit concentration of 5000 μg/mL with S9 activation. None of the 

test concentrations induced a significant increase in the incidence of cells with chromosomal 

abnormalities, either in the absence or presence of S9 activation. In both experiments, the 

fraction of cells with chromosomal aberrations was below 5%, which indicated a negative 

response. There was also no indication of any dose-response effect either without or with 

activation. All of the negative, solvent and positive controls gave appropriate responses.

This study is classified as Acceptable.

ECOTOXICITY STUDIES

FAL 1801 Prohydrojasmon (PDJ)

Ecotoxicity studies (Table 8.0) show that prohydrojasmon (PDJ) is moderately toxic to fish and 

aquatic invertebrates (LC50 and EC50 = 3.3 and 9.54 mg/L, respectively) and practically non-toxic 

to avian species (LD50 >2,000 mg/kg; LC50 >5,000 ppm). This compound is relatively unstable 

in the environment with an aerobic soil half-life of 1.6 – 2.3 hours, and upon consumption breaks 

down under gastric condition with a half-life of 0.8 days.

Table 8.0. Ecotoxicity Data for Prohydrojasmon (PDJ)

Guideline #

Test

Results/Toxicology

Category

MRID Study 

Conclusion

Aquatic Species Testing

850.1010

Acute Toxicity Test, Daphnids 

EC50 = 9.54 mg/L.

Moderately toxic

47927838 Acceptable

850.1075 

Acute Toxicity Freshwater Fish

Cyprinus carpio

96 hr LC50 = 3.3 mg/L.

Moderately toxic

47927837 Acceptable

Avian Species Testing

850.2100

Avian Acute Oral Toxicity 

Bobwhite (Colinus virginianus) 

LD50 >2000 mg/kg

Practically non-toxic

47927835 Acceptable
10

Table 8.0. Ecotoxicity Data for Prohydrojasmon (PDJ)

Guideline #

Test

Results/Toxicology

Category

MRID Study 

Conclusion

850.2200

Avian Dietary Toxicity 

Japanese quail (Colinus virginianus)

LC50 >5000 ppm

Practically non-toxic

47927836 Acceptable

FAL 1801 Prohydrojasmon (PDJ)

MRID 47927835: Avian Acute Oral Toxicity (OPPTS 850.2100) The acute Northern Bobwhite 

(Colinus virginianus) oral nominal LD50 was >2,000 mg a.i./kg. The no-mortality concentration 

and the no-observed-effect concentration were 2,000 mg a.i./kg. This study is classified as 

Acceptable.

MRID 47927836: Avian Dietary Toxicity (OPPTS 850.2200) In a five-day dietary toxicity test, 

a group of 10-day-old Japanese quail was administered prepared diet containing a nominal dose 

5000 ppm PDJ (a.i., 98.08% n-propyl dihydrojasmonate), followed by three days of untreated 

basal diet. A control group was fed untreated basal diet only. There were no treatment-related 

mortalities, and all birds appeared normal during the test. Mean body weight, body weight gain, 

feed intake, and feed conversion were comparable between the control and test material groups. 

The measured concentration of the test material in the prepared diet was 4721 ± 255.1 ppm, 

94.4% of the nominal concentration. The 5-day dietary study produced an LC50 > 5,000 ppm and 

the NOEC of 5,000 ppm. This study is classified as Acceptable.

MRID 47927837: Fish Acute Toxicity Testing (OPPTS 850.1075) Based on the mean measured 

concentrations, the 96-hour LC50 for PDJ Technical in common carp (Cyprinus carpio) was 3.3

mg a.i./L with the LOEC of 2.76 mg a.i./L, and the NOEC of 1.42 mg a.i./L. This study is 

classified as Acceptable.

MRID 47927838: Aquatic Invertebrate Acute Toxicity Testing (OPPTS 850.1010).

Based on the mean measured concentrations, the 24-hour EC50 was 9.54 mg/L (95% a.i., 7.62-

12.0 mg/L), and the 48-hour EC50 was 2.13 mg/L (95% a.i., 1.64-2.70 mg/L). The study is 

classified as Acceptable.
11

Risk Assessment

HUMAN HEALTH

Chronic Exposure and Oncogenicity:

None of the results of the submitted studies triggered the need for chronic exposure or 

oncogenicity testing. No morphologic effects (e.g. hyperplasia or metaplasia) in any organ that 

could potentially lead to neoplastic change. Assays for mutagenicity, chromosomal aberration, 

developmental toxicity, and subchronic oral did not present any clinical or toxicologically

significant effects.

Effects on the Endocrine System:

No data are available regarding the effects of Prohydrojasmon on endocrine systems via oral, 

dermal, or inhalation exposure. No significant treatment-related effects were observed for prenatal 

developmental or maternal testing.

Dose Response Assessment:

No toxicological endpoints were identified; therefore a dose response assessment was not 

required.

Dietary Exposure:

The most likely dietary route of exposure of humans to Prohydrojasmon is via exposure to treated 

fruit or foliage (e.g. apples). Table 9.0 shows possible Prohydrojasmon residues on various 

matrices after one maximum application of 0.009 lbs ai/A (200 ppm ai/A). The dietary-based 

estimated environmental concentrations range from 0.77 to 0.06 ppm on the day of application 

and decline to 0.0 by Day 2. This compound is relatively unstable in the environment with an 

aerobic soil half-life of 1.6 – 2.3 hours, and upon consumption breaks down under gastric 

condition with a half-life of 0.8 days. 

The Agency has calculated the possibility of risk to humans through dietary exposure by

using a worst case scenario of maximum application and no degradation. These calculations 

(Appendix A) show that the Prohydrojasmon residues consumed by a 70 kg person are 

about seven orders of magnitude below Developmental Toxicity NOAEL > 500 mg/kg and 

about eight orders of magnitude below the Acute Oral toxicity value (LD50 > 5,000 mg/kg), 

suggesting no dietary or sublethal risk
12

Table 9.0 Estimated Prohydrojasmon Residues on Terrestrial Matrices Using the Terrestrial 

Exposure Model (T-REX ; USEPA )

Terrestrial Matrix Dietary-based Estimated Environmental Concentrations 

(ppm)

0 days after application 2 days after first application

Short Grass 0.77 0.0

Tall Grass 0.32 0.0

Broadleaf Plant Foliage 0.41 0.0

Fruits, Pods, and Seeds 0.06 0.0

Drinking Water Exposure and Risk Characterization: 

No significant exposure via drinking water is expected when Prohydrojasmon is used in 

accordance with EPA-approved product labeling. The end product is not to be applied directly to 

water or to areas where surface water is present. In the unlikely event that exposure via drinking 

water did occur, the health risk would be expected to be minimal, based on low acute oral and 

dermal toxicity of Prohydrojasmon.

The Agency estimated environmental concentrations (EECs) to an aquatic site from 

Prohydrojasmon runoff (spray to apple trees) using the GENeric Estimated Environmental 

Concentration model (GENEEC; EPA, 2001). The model assumed 2 maximum applications of 

end product at 0.009lbs ai/A (4g ai/A) at 7 day intervals, a 10.7 day aquatic half-life, a 57.8 hours 

photodegradation half-life in water, and a 1.6 – 2.3 hour half-life in aerobic soil. The peak aquatic 

EEC was calculated at about 0.00048 ppm with a decline to 0.000024 ppm after 21 days (Table 

10.0). No acute or subacute endpoints were identified through mammalian testing and the 

expected concentrations in surface water are well below (6 to 7 orders of magnitude) the 

maximum doses used in laboratory testing (e.g. Acute Oral Toxicity LD50 > 5,000 mg/kg; 

Developmental Toxicity NOAEL > 500 mg/kg).

Table 10.0 Generic Estimated Environmental Concentrations (EECs) of Prohydrojasmon in Aquatic 

Sites using the GENEEC Model, ver 2.0 (EPA, 2001) in Parts Per Million (ppm)

Peak EEC Max 4 Day

Avg EEC

Max 21 Day

Avg EEC

Max 60 day

Avg EEC

Max 90 Day

Avg EEC

0.00048 0.00013 0.000024 0.000008 0.000006

Occupational Exposure:

Occupational exposure to Prohydrojasmon is mitigated as long as the end-use product is used in 

accordance with EPA-approved labeling. Occupational exposures are not included under the 

Federal Food, Drug, and Cosmetic Act (FFDCA) in the assessment of aggregated exposures for 

the purpose of establishing tolerances and exemptions from tolerance.

Residential, school and Day Care Exposure and Risk Characterization:

Significant human exposure to Prohydrojasmon is highly unlikely in residential, school and day 
13

care areas when the end use product is used in accordance with EPA-approved labeling. The 

product is only intended for commercial use as a plant growth regulator on apples.

Aggregated Exposure from Multiple Routes Including Dermal, Oral and Inhalation:

There is reasonable certainty that no harm to the U.S. population will result from aggregate 

exposure to residues of Prohydrojasmon. This included all exposures for which there is reliable 

information. The Agency arrived at this conclusion based on the low toxicity and rapid breakdown of the compound. The risk from aggregate exposure via oral, dermal, and inhalation are a 

compilation of three low-risk exposure scenarios (oral, dermal, and inhalation) and are negligible. 

Since there are no threshold effects of concern for this compound, and no known toxic endpoints, 

the provision requiring an additional margin of safety does not apply.

Cumulative Effects:

Residues of Prohydrojasmon will not reach levels that are of toxicological concern if the 

compound is used as proposed. Because of its low toxicity and low level of exposure, cumulative 

effects with other substances that share a common mechanism of toxicity are not expected.

Human Risk Characterization:

The Agency considered human exposure to Prohydrojasmon in light of relevant safety factors in 

FQPA and FIFRA. A determination has been made that no unreasonable adverse effects to the 

U.S. population in general, and to infants and children in particular, will result from the use of 

Prohydrojasmon when used in accordance with EPA-approved labeling.

Ecological Assessment

ECOTOXICITY RISK

Terrestrial

Prohydrojasmon is not naturally-occurring but is structurally similar to jasmonic acid (JA). JA is 

an intermediate in the pathway to plant abscisic acid synthesis and has ABA-like activity (i.e. 

growth inhibition, senescence, leaf abscission, as well as a role in wound response and systemic 

resistance). When plants are attacked by insects there is a release of JA, which inhibits the 

insect’s ability to digest protein.

In order to evaluate risk of Prohydrojasmon exposure to terrestrial species, the Agency has 

estimated RQ values using the Terrestrial Residue Exposure Model (T-REX) Version 1.4.1. A 

terrestrial risk assessment includes calculated expected residues, as well as, numerous calculations 

of dietary exposure for multiple weight class animals (Appendix B). Expected residues were 

calculated for avian and mammalian food items along with dissipation rate of a chemical applied 

to foliar surfaces (single or multiple applications) in order to estimate worst case acute RQs 

relative to weight class for various sized birds and mammals. These calculations showed upper 

bound Kenega values and that exposure to Prohydrojasmon (0.009lbs ai/A) has a low potential for 
14

toxic impact to birds (RQ = 0.00) and mammals (RQ= 0.00) that may be feeding in the area of 

application as noted in Appendix B. The unique characteristics of this product, Prohydrojasmon, 

and the non-toxic mode of action, biodegradability and low potential for exposure will result in 

no risk to all non-target terrestrial organisms.

Aquatic

Prohydrojasmon exposure to aquatic species should result in no toxicity effects. Estimated 

environmental concentrations (EECs) in aquatic sites from Prohydrojasmon runoff after 

application to terrestrial crops were estimated using the GENeric Estimated Environmental 

Concentration model (GENEEC; EPA, 2001). The model assumed 2 maximum applications of 

end product at 0.009lbs ai/A (4g ai/A) at 7 day intervals, a 10.7 day aquatic half-life, a 57.8 hours 

photodegradation half-life in water, and a 1.6 – 2.3 hour half-life in aerobic soil. The peak aquatic 

EEC was calculated at a peak of about 0.00048 ppm which declined to 0.000024 ppm after 21 

days (Table 10.0). Since the LC50 values for fish and aquatic invertebrates is 3.3 mg/L and 9.54 

mg/L this would result in Risk Quotients (RQs) of 0.0001 and 0.00005, respectively, which are

about three and four orders of magnitude below the Agency’s levels of concern (LOCs = 0.1),

suggesting no risk concerns for aquatic species. 

Endangered Species

The Agency’s Individual Effects Chance Model Version 1.1 was used to estimate to the chance of 

risk to endangered/threatened avian and aquatic species from exposure to Prohydrojasmon. These 

values (avian risk at 1 in 294,000 and aquatic risk at 1 in 418,000,000) suggest that

Prohydrojasmon should not cause toxic risk to endangered/threatened species. In evaluating risk 

to aquatic endangered species the calculated RQs are about two and three orders of magnitude 

below the aquatic endangered species LOC = 0.05 resulting in no effect (NE) to aquatic 

endangered species. The calculated RQ values for terrestrial species are 0.00 resulting in a no 

effect (NE) to endangered/threatened terrestrial organisms.
15

Appendix A Human Toxicity Calculations

Polyhydrojasmon (PDJ) is to be sprayed on red apples in order to promote fruit color change. The 

product is to be applied to tree canopies with 1-2 applications of 100-200 ppm at 7-14 day

intervals, 7-28 days prior to anticipated harvest. The active ingredient (PDJ) amounts to 50 grams 

per liter of end product (FAL 1800). The maximum amount of FAL 1800 that can be applied per 

acre is 52 oz. or 2.73 oz. ai (5.25% ai in product). 

Given: 50 g ai/L or 50 g ai/33.8oz;

 52oz of formulation/A or 2.73oz ai/A (5.25 % ai in FAL 1800);

 

 X 2.73 oz = 4g ai/A or 0.009 lbs. ai/A to be sprayed at each application.

50g 33.8 oz

Information on apple production:

300 – 400 trees/A (Minnesota) can produce about 300 – 500 bushels of apples/A1; One bushel = 

42 lbs of apples1. Weight of 10 apples is 3.5 lbs., 3.5 lbs. ÷ 10 apples = .35 lbs./apple1. Human 

consumption is about 42 lbs. of apples/year or about 120 apples1. Therefore if we project a worst 

case scenario (no degradation and maximum application) this will result in 4g ai/A (0.009 lbs 

ai/A) and 0.013g ai/bushel x 2 applications = 0.026g ai/bushel of apples (no degradation).

Risk Scenario

In order to evaluate toxic risk to humans the Agency calculated acute and sublethal chronic 

effects in combination with an extrapolated possible exposure scenario. The acute oral toxicity

was calculated at > 5,000 mg/kg (MRID 47927825) while a sublethal NOAEL > 500 mg/kg/day

(MRID 47927832). The worst case scenario of maximum application and no degradation was 

used as an exposure component that amounted to 26mg ai/42lbs apples or about 0.07 mg ai/apple. 

Therefore, if the average 70kg human consumes about 120apples/year1the annual body burden of 

ai would amount to 8.4mg (120 x 0.07mg = 8.4mg). A 70kg human would have to consume >

35,000mg ai/day in order to approach the sublethal NOAEL > 500 mg/kg/day or 350,000mg ai to 

approach the acute oral dietary of 5,000mg/kg.

1

http://www.rma.usda.gov/handbooks/25000/2001/0
16

Appendix B. TREX Output for Terrestrial Exposure and Risk from Prohydrojasmon

Application to Apples

Avian Body Ingestion (Fdry) Ingestion (Fwet) % body wgt FI

Class Weight (g) (g bw/day) (g/day) consumed (kg-diet/day)

Small 20 5 23 114 2.28E-02

Mid 100 13 65 65 6.49E-02

Large 1000 58 291 29 2.91E-01

Avian Body Adjusted LD50

Weight (g) (mg/kg-bw)

20 1038.45

100 1322.00

1000 1867.37

small mid large

20 g 100 g 1000 g

Short Grass 2.46 1.40 0.63

Tall Grass 1.13 0.64 0.29

Broadleaf plants/sm Insects 1.38 0.79 0.35

Fruits/pods/seeds/lg insects 0.15 0.09 0.04

20 g 100 g 1000 g

Short Grass 0.00 0.00 0.00

Tall Grass 0.00 0.00 0.00

Broadleaf plants/sm insects 0.00 0.00 0.00

Fruits/pods/seeds/lg insects 0.00 0.00 0.00

Acute Chronic

Short Grass 0.00 #DIV/0!

Tall Grass 0.00 #DIV/0!

Broadleaf plants/sm Insects 0.00 #DIV/0!

Fruits/pods/seeds/lg insects 0.00 #DIV/0!

Dietary-based RQs RQs

(Dietary-based EEC/LC50 or

NOAEC)

Avian Acute RQs Dose-based RQs 

(Dose-based EEC/adjusted LD50)

Avian Classes and Body Weights Dose-based EECs 

(mg/kg-bw) 
17

Mammalian Body Ingestion (Fdry) Ingestion (Fwet) % body wgt FI

Class Weight (g bwt/day) (g/day) consumed (kg-diet/day)

15 3 14 95 1.43E-02

Herbivores/ 35 5 23 66 2.31E-02

insectivores 1000 31 153 15 1.53E-01

15 3 3 21 3.18E-03

Grainvores 35 5 5 15 5.13E-03

1000 31 34 3 3.40E-02

Mammalian Body Adjusted Adjusted

Class Weight LD50 NOAEL

15 10989.15 1098.92

Herbivores/ 35 8891.40 889.14

insectivores 1000 3845.80 384.58

15 10989.15 1098.92

Grainvores 35 8891.40 889.14

1000 3845.80 384.58

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

Short Grass 2.06 1.42 0.33

Tall Grass 0.94 0.65 0.15

Broadleaf plants/sm Insects 1.16 0.80 0.19

Fruits/pods/seeds/lg insects 0.13 0.09 0.02 0.03 0.02 0.00

Acute Chronic Acute Chronic Acute Chronic

Short Grass 0.00 0.00 0.00 0.00 0.00 0.00

Tall Grass 0.00 0.00 0.00 0.00 0.00 0.00

Broadleaf plants/sm insects 0.00 0.00 0.00 0.00 0.00 0.00

Fruits/pods/lg insects 0.00 0.00 0.00 0.00 0.00 0.00

Seeds (granivore) 0.00 0.00 0.00 0.00 0.00 0.00

Acute Chronic

Short Grass 0.00 0.00

Tall Grass 0.00 0.00

Broadleaf plants/sm insects 0.00 0.00

Fruits/pods/seeds/lg insects 0.00 0.00

Dose-Based EECs 

(mg/kg-bw)

Herbivores/ insectivores Granivores

Mammalian Classes and Body weight

15 g mammal 35 g mammal 1000 g mammal Dose-based RQs 

(Dose-based EEC/LD50 or NOAEL)

Dietary-based RQs 

(Dietary-based EEC/LC50 or 

NOAEC)

Mammal RQs
18

References

1. Parker, R.D., R.D. Jones and H.P. Nelson., 1995. GENEEC: A Screening Model for 

Pesticide Environmental Exposure Assessment., in Proceedings of the International 

Exposure Symposium on Water Quality Modeling; American Society of Agricultural 

Engineers, pp. 485-490; Orlando, Florida.

2. U.S. EPA. 1998. Guidance for Ecological Risk Assessment. Risk Assessment Forum. 

EPA/630/R-95/002F, April 1998.

3. U.S.EPA 2008. Terrestrial Residue Exposure Model (T-REX) Version 1.4.1. 

EFED/OPP/USEPA.

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

5. U.S. EPA. 2004. Overview of the Ecological Risk Assessment Process in the Office of 

Pesticide Programs. Office of Prevention, Pesticides, and Toxic Substances. Office of 

Pesticide Programs. Washington, D.C. January 23, 2004.