EPA BIOPESTICIDES AND POLLUTION PREVENTION DIVISION

COMPANY NOTICE OF FILING FOR PESTICIDE PETITIONS PUBLISHED IN

THE FEDERAL REGISTER

EPA Biopesticides and Pollution Prevention Division contact: [Linda Hollis. 703-

308-8733]

©1

INSTRUCTIONS: Please utilize this outline in preparing the pesticide petition. In

cases where the outline element does not apply, please insert "NA-Remove" and

maintain the outline. Please do not change the margins, font, or format in your

pesticide petition. Simply replace the instructions that appear in green, i.e., "j insert

company namel," with the information specific to your action.

SUBMISSION: E-mail the completed template to: hollis.iinda@epa.gov.

TEMPLATE:

[Fine Agrochemicals Ltd.]

[Insert petition numb erf

EPA has received a pesticide petition ([insert petition number]) from [Fine

Agrochemicals Ltd. c/o SciReg, Inc., 12733 Director's Loop, Woo el bridge, VA

22192] proposing, pursuant to section 408(d) of the Federal Food, Drug, and Cosmetic

Act (FFDCA), 2! U.S.C,346a(d):' to amend 40 CFR part J80. . •••"

(Options (pick one)

2. to establish un exemption from the requirement of a tolerance for

(Options (pick one)

2, biochemical pesticide [Prohydrojasmon]

•

Pursuant to section 4()8(d)(2)(A)(i) of FFDCA, as amended, [Fine •

Agrochemicals Ltd. c/o SciReg. Inc., 12733 Director's Loop, Woodbrktaft.Y^ •*• *

22192] has submitted the following summary of information, data, and cirgjnirJnfe in **

support of their pesticide petition. This summary was prepared b> [SciReg. Jiy.^and

iiPA has not fully evaluated the merits qf the pesticide petition. The sxinimai^n-Jay have

been edited by EPA if the lemiinoloav used was unclear; the summary coi»i»?iB»d ***. I

* — ' v "*•"• •

extraneous material, or the summary unintentionally made the reader conc.!ii*Jl>eil>:iat the '.

findings reflected EPA's position and not the position of the petitioner. t ••••
I, (Fine Agrochemicals Ltd. c/o SciReg, Inc., 12733 Director's Loop, Woodbridge,

VA 22192]'Petition Summary

llnsert petition number]

A. Product Name and Proponed Use Practices

I'FAL 1800, an end-use product containing 5.25% prohydrojasmon, is

tblJarly sprayed onto red apple varieties 7-28 days pre-harvest for fruit color

enhancement.] '

ft. Product Identity/Chemistry . '

i. Idenf'Uy of fhepesticide and corresponding residues. |Prohydrojasmqn is the

synthetic analog of methyl jasmonate, which is a natural derivative of jasmonic acid,

a naturally-occurring plant hormone. A petition for temporary tolerance exemption

accompanies this submission. Residue data are not applicable.]

2: Magnitude of residues ui the time of harvest and method used io determine the

residue. [No magnitude of residue (MOR) studies have been conducted with

prohydrojasmon based on the low toxicity of the active ingredient (see Toxicology

Profile, pages 2-6) and its structural similarity to a naturally-occurring plant

hormone.]

3. A statement of why an analytical method oj detecting and measuring ilu- levels

of the pesticide residue arc. not needed. [SciReg, Inc. is submitting a petition to

establish an exemption from the requirement of a tolerance and, therefore, an

analytical method is not required.]

«'.'. Mammalian lexicological Profile '' . ?

11 he full reports that support this petition and which are summarized in this

section were concurrently submitted to support the request for an Experimental Use

Permit. '

Prohydrojasmon Technical

1. Acute toxicity (oral, dermal, inhalation); OPPTS 870.1100, 870.1200, 870.1300

Acute oral toxicity, acute dermal toxicity, and acute inhalation toxicity studies

using SD rats were conducted with prohydrojasmon technical (PDJ). The acute

oral Lpso was >5000 mg/kg body weight in both male and female rats. The acute

dermal LDso of PDJ in male and female rats was >2000 mg/kg body-weight. The

acute inhalation LCso of PDJ Avas >2.8 mg/L in male and female rats.
2. Eye and dermal irritation, and skin sensitization; OPPTS 870.2400. 870.2500,

870.2600

Primary eye and dermal irritation studies were conducted using Japanese white

rabbits. Slight eye irritation was observed. No irritation was observed in the

dermal irritation study.

A skin sensitization study (Maximization method) was conducted using Hartley

strain guinea pigs. No skin sensitization was observed.

3. 90-day subchronic dietary toxicity (rats); OPPTS 870.3100

A 90-day subchronic dietary toxicity study was conducted using Fischer rats (1.0

males and 10 females each per group) by administrating mixed food (technical

substance; 0,1000, 3000 and 10000 ppm, corresponding to 0, 56.9, 168 and 566

mg/kg bodyweight/day for males, and 0, 58.5,176 and 587 mg/kg

bodyweight/day for females).

In the 10000 ppm dose group, body weight gain suppression and relative adrenal

gland e weight increase were observed in males and females; Hb concentration

decreased; MCH decreased; total protein decreased; A/G ratio increased;

relative liver weight increased; and relative kidney weight increased in males, in

the 1000 ppm dose groups, food intake decreased; total cholesterol increased;

and serum chlorine decreased in males. In females, platelet number decreased;

nitrogen as urea in urine increased; and relative liver weight increased.

The No Observed Adverse Effect Level (NOAEL) in this study is considered to

be 1000 ppm (male: 56.9 mg/kg bodyweight/day; female: 58.5 mg/kg

bodyweight/day).

4. Developmental toxicity (rat); OPPTS 870.3700

A developmental toxicity study was conducted using SD rats (24 females each

per group) via gavage administration (technical substance; 0, 30, 120 and 500

mg/kg bodyweight/day) during days 6-15 of gestation.

In the 500 mg/kg dose group, body weight gain and food intake decreases were

observed, and body weight gain was suppressed in the 120 mg/kg close group.

For fetuses, excessive rib growth was observed with higher frequency in the 500

mg/kg dose group, but skeletal malformations were not observed. Malformation

increases were not observed at 1000 mg/kg dose group in a preliminary study.

Therefore, frequency of increase of excessive rib growth is not considered to be a

teratogenic effect of prohydrojasmon.

The NOAEL in this study is considered to be 80 mg/kg bodyweight/day for dams

and 300 mg/kg bodyweight/day for fetuses. No teratogenicity was observed.
Genotoxicity; OPPTS 870.5100, 870.5300

An Ames bacterial reverse mutation test and a chromosome aberration test

using Chinese hamster lung cells were conducted. Both studies were negative.

(Table 1) Prohydrojasmon is not considered to be genotoxic.

Table .1. Summary of results

Test

//•/ vitro

Reverse

mutation test

(±S9)

Chromosome

aberration

test (±S9)

Subject

S. tvphiiiiuiiiim strains

TA98, TA 100, TA 1535,

TA1 537

E. coli strain \\P2uvrA

Chinese hamster lung

cells (CHL/IU)

Dose levels

(-S9) TA100.

TAJ535, TA1537:

2.44, 4.88, 9.77,

19.5,39.1,78.1

ug/plate

(+S9)TA100,

TA J 535, TA 1537:

9.77,19.5,39.1,

78.1, 156,313,625

ug/plate

(-S9) TA98,

WP2/wv4: 2.44,

4.88,9.77, 19.5,

39.1,78.1, 156

ug/plate

(+S9) TA100.

TA1535, TAJ 537:

39.1,78.1. 156,

313, 625, 1250,

2500 ug/plate

(-S9): 10, 20. 40,

80 ng/ml

(+S9): 1250, 2500,

5000 jig/ml

Result

Negative

Negative

Note: ±S9 = with and without metabolic activation.

FAL 1800

1. Acute toxicity (oral/dermal/inhalation); OPPTS 870.11.00, 870.1200, 870.1300

Acute oral toxicity, acute dermal toxicity, and acute inhalation toxicity studies

using SD rats were conducted with FAL 1800 containing 5.25% PDJ. The acute

oral LDso was >5000 mg/kg bodyweight in both male and female rats. The acute

dermal LDso of FAL 1800 in male and female rats was >2000 mg/kg bodyweight.

The acute inhalation LCso of FAL 1800 was >5.0 mg/L in male and female rats.

2. Eye and dermal irritation, and skin sensitization; OPPTS 870.2400, 870.2500,

870.2600

Primary eye and dermal irritation studies were conducted using Japanese white

rabbits. In the eye study, the maximum of the weighted mean score according to
the Drai/e grading method was 52.0 in the non eye-washed group. Classification

of irritation effects based on this value and according to the Kay and Calandr a

method revealed that the degree of irritation of the test substance was "severely

irritating." However, in both the non eye-washed group and the eye-washed

group, similar acute symptoms were observed after administration, but were

resolved by day 7 after administration. In view of these results, it was concluded

that FAL 1800 produces reversible intense irritation in the eyes of rabbits under

the conditions of this study.

No irritation was observed in the skin.

A skin sensitization study (Buehler method) was conducted using Hartley strain

guinea pigs. No skin sensiti/ation was observed.)

/). Aggregate Exposure

i. Die/an' exposui'e. (The potential for non-occupational, dietary, and nondietary exposure to Prohydrojasmon by the general population, includin g infants

and children, is likely through ingestion of treated fruit.)

1. Food. [Dietary exposure to Prohydrojasmon should not be of concern due

to the low toxicity shown across the entire toxicological profile (see above).]

ii. Drinking 'water. (Prohydrojasmon does not pose a risk to drinking water, as

agricultural practice prohibits direct application of the end-use product directly to

water. Further, based on the environmental fate studies submitted to support the

Experimental Use Permit, Prohydrojasmon rapidly degrades in the environment.|

2. Nat'.-dittarv exposure. (Non-dietary exposure to prohydrojasmon will be

much more likely through handling by formula tors and applicators, but in light of

the subject chemical's toxicological profile, should be of little concern. There are no

non-pesticidal uses of prohydrojasmon. There are no residential, indoor, school or

clay care uses proposed for this product. The proposed use pattern is for

agricultural food crops (apples). Therefore, there is no potential for nonoccupational exposure to the general population.)

/•'. ("I'liuilative Effects

(Section 408(b)(2) of the FFDCA requires that, when considering \vhether to

establish an exemption from a tolerance, the Agency consider available information

concerning the cumulative effects of the particular ingredient's residues and other

substances that have a common mechanism of toxicity. These considerations include

the possible cumulative effects of such residues on infants and children. There is the

possibility that the human population may be cumulatively exposed to other plant

hormones; however, based on the ubiquitous nature of these hormones, it is unlikely

that detrimental effects to the human population wil l occur through their use.)
1. U.S. population. [With respect to the potential for harmfu l effects of

prohydrojasmon in the U.S. population, the toxicity and exposure data are sufficient

to adequately address potential exposure to prohydrojasmon. There is reasonable

certainty that no harm will result to the U.S. population, includin g infants and

children, from aggregate exposure to residues of prohydrojasmon as a result .of

preharvest uses, as toxicity and exposure is expected to be minimal. This includes all

anticipated dietary exposures and all other exposures for which there is reliable

information. This chemical will be applied as a plant growth regulator to apples.]

2, Infant's and children. |l.t is believed that the potential exposure of infants

and children to residues of prohydrojasmon through its use to enhance the color of

red apple varieties is no greater than that of the general population. Available

information does not suggest that infants and children are more susceptible to the

effects of prohydrojasmon than are adults.|

(.'•>. Effi'cis uu I he'Immune and Endocrine Syxu-ms

[No specific studies have been conducted with prohydrojasmon to determine

whether it may have an effect in humans that is similar to an effect produced by a

naturally-occurring estrogen or other endocrine-affecting substance. However, it is

not likely that prohydrojasmon would have estrogen or endocrine effects since it is

structurally similar to a naturally-occurring plant hormone, it has demonstrated

low mammalian toxicity, and there is no evidence that prohydrojasmon affects the

immun e system, functions in a manner similar to any known hormone, or that it

acts as an endocrine disruptor.j

.'/. /'."v.'}///7g Tolerance

[There are no U.S. tolerances or tolerance exemptions for prohydrojasmon.]

/ International Tolerances

\CodexMaximum Residue Level. No maximum residue levels (iMRLs) have

been established for prohydrojasmon by the Codex Alimentarius Commission

(CODEX).

The European Union (EU) has assigned a default MRL for prohydrojasmon of 0.01

mg/kg according to Article 18(1 )(b) Reg. 39672005.

The Japanese Ministry of Agriculture, Farming and Fisheries (JMAFF) has

assigned an iVlRL for prohydrojasmon of 0.05 ppm in apples and grapes.]