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EPA BIOPESTICIDES AND POLLUTI ON PREVENTION DIVISION

COMPANY NOTICE OF FILING FOR PE STICIDE PETITIONS PUBLISHED IN

THE FEDERAL REGISTER

EPA Biopesticides and Pollution Prevention Division contact: [Gina Burnett, (703) 605-0513]

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

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

maintain the outline. Please do not chan ge the margins, font, or format in your pesticide petition. Simply replace the instructions that appear in green , i.e., “ [insert company name] ,” with the information specific to your action.

SUBMISSION: E-mail the completed temp late to: hollis.linda@epa.gov.

TEMPLATE:

[Fine Agrochemicals Ltd. c/o SciReg, Inc., 12733 Director’s Loop, Woodbridge, VA 22192]

[1G7947]

EPA has received a pesticide petition ([1G7947]) from [Fine Agrochemicals Ltd. c/o SciReg, Inc.], [12733 Di rector’s Loop, Woodbridge, VA 22192] proposing, pursuant to section 408(d) of the Federal Food, Drug, and Cosmetic Act (FFDCA), 21 U.S.C. 346a(d), to amend 40 CFR part 180.

(Options (pick one)

to establish an amendment/expansion of an existing tolerance exemption for the

(Options (pick one)

biochemical pesticide [Prohydrojasmon (PDJ), propyl-3-oxo-2-pentylcyclopentylacetate ]

Pursuant to section 408(d)(2)( A)(i) of FFDCA, as amended, [Fine Agrochemicals Ltd. c/o SciReg, Inc.] has submitted the following summary of2

information, data, and arguments in support of their pe sticide petition. This summary was prepared by [Fine Agrochemicals Ltd. c/o SciReg, Inc.] and EPA has not fully

evaluated the merits of th e pesticide petition. The summary may have been edited by EPA if the terminology used was unclear, the summary contained extraneous material, or the summary unintentionally made the reader conclude that the findings reflected EPA’s position and not the positi on of the petitioner.

I. [Fine Agrochemicals Ltd. c/o SciReg, Inc.] Petition Summary

[1G7947]

A. Product Name and Proposed Use Practices

[FAL 1800, an end-use product contai ning 5.25% prohydrojasmon, is foliarly sprayed onto red apple varieties 7-42 days pre-harvest for fruit color

enhancement

. FAL 1810, an end-use product cont aining 10% prohydrojasmon, is foliarly sprayed onto grape varieties one week before veraison and one week after

veraison for fruit color enhancement. If a dditional color development is desired, up to two additional applications of FA L 1810 can be applied at 14-28 day spray intervals.]

B. Product Identity/Chemistry

1. Identity of the pestic ide and corresponding residues. [Prohydrojasmon 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 for grapes accompanies this submissi on. Residue data are not applicable.]

2. Magnitude of residues at the time of har vest and method used to determine the

residue. [No magnitude of residue (MOR) st udies have been conducted with prohydrojasmon based on the low toxicity of the ac tive ingredient (see Toxicology Profile) and its structural similarity to a naturally-occurring plant hormone.]

3. A statement of why an analytical method of detecting and measuring the levels of the pesticide residue are not needed. [ SciReg, Inc. is submitting a petition to establish an exemption from the requiremen t of a tolerance and, therefore, an analytical method is not required.]

C. Mammalian Toxicological Profile

[The full reports that support this peti tion and which are summarized in this section were previously submitted to EPA by Fine Agrochemicals Ltd.

Prohydrojasmon Technical

1. Acute toxicity (oral, dermal, inhalation); OPPTS 870.1100, 870.1200, 870.13003

Acute oral toxicity, acute dermal toxicit y, and acute inhalation toxicity studies using SD rats were conducted with prohydrojasmon technical (PDJ). The acute

oral LD 50 was >5000 mg/kg bodyweight in both male and female rats. The acute

dermal LD 50 of PDJ in male and female rats was >2000 mg/kg bodyweight. The

acute inhalation LC 50 of PDJ was >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 observ ed. 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 t oxicity (rats); OPPTS 870.3100

A 90-day subchronic dietary toxicity st udy was conducted using Fischer rats (10 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 relativ e 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 (N OAEL) in this study is considered to be 1000 ppm (male: 56.9 mg/kg body weight/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 supp ressed in the 120 mg/kg dose group. For fetuses, excessive rib growth was ob served with higher frequency in the 500 mg/kg dose group, but skeletal malfor mations were not observed. Malformation increases were not observed at 1000 mg/kg dose group in a preliminary study.4

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.

5. Genotoxicity; OPPTS 870.5100, 870.5300

An Ames bacterial reverse mutation te st and a chromosome aberration test using Chinese hamster lung cells were conducted. Both studies were negative. (Table 1) Prohydrojasmon is no t considered to be genotoxic.

Table 1. Summary of results
Test Sub j ect Dose levels Result

in vitro Reverse mutation test (±S9) S. typhimurium strains TA98, TA100, TA1535, TA1537 E. coli strain WP2 uvrA (-S9) TA100, TA1535, TA1537: 2.44, 4.88, 9.77, 19.5, 39.1, 78.1 μg/plate (+S9) TA100, TA1535, TA1537: 9.77, 19.5, 39.1, 78.1, 156, 313, 625 μg/plate

(-S9) TA98,
WP2 uvrA : 2.44, 4.88, 9.77, 19.5, 39.1, 78.1, 156 μg/plate (+S9) TA100, TA1535, TA1537: 39.1, 78.1, 156, 313, 625, 1250,
2500 μg / p late Negative

Chromosome aberration test (±S9) Chinese hamster lung cells (CHL/IU) (-S9): 10, 20, 40, 80 μg/ml (+S9): 1250, 2500,
5000 μg /ml Negative

Note: ±S9 = with and without metabolic activation.

FAL 1800 (BLUSH)

1. Acute toxicity (oral/derm al/inhalation); OPPTS 870.1100, 870.1200, 870.1300

Acute oral toxicity, acute dermal toxicit y, and acute inhalation toxicity studies using SD rats were conducted with FAL 1800 containing 5.25% PDJ. The acute

oral LD 50 was >5000 mg/kg bodyweight in both male and female rats. The acute

dermal LD 50 of FAL 1800 in male and female rats was >2000 mg/kg bodyweight.

The acute inhalation LC 50 of FAL 1800 was >5.0 mg/L in male and female rats.5

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 Draize grading method was 52.0 in th e non eye-washed group. Classification

of irritation effects based on this value and according to the Kay and Calandra method revealed that the degree of irritati on 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 ir ritation in the eyes of rabbits under the conditions of this study.

No irritation was observed in the skin.

A skin sensitization study (Buehler meth od) was conducted using Hartley strain guinea pigs. No skin sensitization was observed.

FAL 1810

1. Acute toxicity (oral/derm al/inhalation); OPPTS 870.1100, 870.1200, 870.1300

The acute oral LD 50 is estimated to be >500 mg/kg bodyweight and <5.000 mg/kg bodyweight.

The acute dermal LD 50 of FAL 1810 is estimated to be >2000 mg/kg bodyweight and <5.000 mg/kg bodyweight.

The acute inhalation LC 50 of FAL 1810 is estimated to be >0.5 mg/L and <2 mg/kg bodyweight.

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

870.2600

The primary eye and dermal irritation potentials of FAL 1810 are estimated to place the product into Toxicity III.

FAL 1810 is not believed to be a skin sensitizer.]

D. Aggregate Exposure

1. Dietary exposure. [The potential for non-occ upational, dietary, and nondietary exposure to prohydrojasmon by th e general population, including infants and children, is likely throug h ingestion of treated fruit.]6

i. Food. [Dietary exposure to prohydrojasmon should not be of concern due to its low toxicity shown across the en tire toxicological profile (see above).]

ii. Drinking water. [Prohydrojasmon does not pose a risk to drinking water, as agricultural practice prohibits direct applic ation of the end-use products directly to water. Further, based on the environmenta l fate studies submi tted to support the Experimental Use Permit, prohydrojasmon rapidly degrades in the environment.]

2. Non-dietary exposure

. [Non-dietary exposure to prohydrojasmon will be much more likely through handling by formul ators and applicators, but in light of the subject chemical’s toxicological pr ofile, should be of little concern. There are no non-pesticidal uses of prohydrojasmon. Th ere are no residential, indoor, school or day care uses proposed for this active ingredient. The proposed use pattern is for agricultural food crops (apples and grapes). Therefore, there is no potential for nonoccupational exposure to the general population.]

E. Cumulative Effects

[Section 408(b)(2) of the FFDCA requires that, when considering whether to establish an exemption from a tolerance, the Agency consider available information concerning the cumulative effects of the pa rticular ingredient’s residues and other

substances that have a common mechanism of toxicity. These considerations include the possible cumulative effects of such resi dues 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 will occur through their use.]

F. Safety Determination

1. U.S. population. [With respect to the potential for harmful effects of prohydrojasmon to the U.S. population, the toxicity and exposure data are sufficient to adequately address potential exposu re to prohydrojasmon. There is reasonable certainty that no harm will result to the U.S. population, including infants and children, from aggregate exposure to residue s 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 othe r exposures for which there is reliable information. This chemical will be applied as a plant growth regulator to apples and grapes.]

2. Infants and children

. [It is believed that the potential exposure of infants and children to residues of prohydrojasmon through its use to enhance the color of red apple and grape varieties is no great er than that of the general population. Available information does not suggest that infants and children are more susceptible to the effects of pr ohydrojasmon than are adults.]

G. Effects on the Immune and Endocrine Systems7

[No specific studies have been conducted with prohydrojasmon to determine whether it may have an effect in humans th at is similar to an effect produced by a naturally-occurring estrogen or other endocri ne-affecting substance. However, it is not likely that prohydrojasmon would have estrogen or endocrine effects since it is structurally similar to a naturally-occurri ng plant hormone, it has demonstrated low mammalian toxicity, and there is no ev idence that prohydrojasmon affects the immune system, functions in a manner sim ilar to any known hormone, or that it acts as an endocrine disruptor.]

H. Existing Tolerances

[There is an existing U.S. tolerance exemption for prohydrojasmon on apples (40 CFR 180.1299)

. ]

I. International Tolerances

[ Codex Maximum Residue Level. No maximum residue le vels (MRLs) 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. 396/2005.

The Japanese Ministry of Agriculture, Farming and Fisheries (JMAFF) has assigned an MRL for prohydrojasmon of 0.05 ppm in apples and grapes.]