EPA REGISTRATION DIVISION COMPANY NOTICE OF FILING FOR
PESTICIDE PETITIONS PUBLISHED IN THE FEDERAL REGISTER

EPA Registration Division contact: [P.V. Shah 703

- 308

- 1846]

INSTRUCTIONS: Please utilize this outline in preparing the pesticide petit ion. 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., “ [ insert

company name ] ,” with the information specific to your action.

TEMPLATE:

[ Oro

- Agri Inc ]

[OA 1 ]

EPA has received a pesticide petition ( OA 1 ] ) from [Oro

- Agri Inc ]
, [ 990 Trophy Club Drive, Trophy C lub TX, 76262 ] proposing, pursuant to section 40 8(d) of the Federal Food, Drug, and Cosmetic Act (FFDCA), 21 U.S.C. 346a(d), to amend 40 CFR part 180.

to establish an exemption from the requirement of a tolerance for

[ Sweet Orange Peel Tincture
, CAS# 8028

- 48

- 6
, under 40CFR 180.910 for pre and p ost harvest crops when used as a surfactant and fragrance when contained at concentrations up to 10% in pesticide formulations and applied to agricultural

crops , preplant through post harvest]. EPA has determined that the petition contains

data or informa tion regarding the elements set forth in section 408 (d)(2) of FDDCA; however, EPA has not fully evaluated the sufficiency of the submitted d a ta at this time or whether the data supports granting of the petition. Additional data may be needed before

EPA ru les on the petition.

A. Residue Chemistry [ T his information is not available
, nor required for the establishment of a tolerance exemption .]

1. Plant metabolism. [ omit

- per above, not needed .]

2. Analytical method. [ omit

- per above, not needed .]

3. Magnitude of residues. [ omit

- per above, not needed .]2

B. Toxicological Profile [ Sweet Orange Peel Tincture is a cold press extract of orange peel, comprised of greater than 95% D

- Limonene (CAS# 5989

- 27

- 5) and other minor (<1%) components

. G iven the trace levels of these other components compared to D

limonene there is no expectation of contribution to the toxicological profile from

them. Pure D

- limonene is exempt from requirement of a tolerance when used as an inert ingredient in pesticide formulations on food (40 CFR 180.910). The EPA has conducted a thorough toxicological profile for D

- Limonene for use as an active ingredient a s a vertebrate repellent. Since Sweet Orange Peel Tincture is 95% or

more D

- Limonene, this profile represents Sw eet Orange Peel Tincture. ]

1. Acute toxicity

. [ The oral toxicity of limonene is relatively low. An oral

lethal dose for humans has been estimated at 1 oz.

- 1 pint. Limonene has been administered therapeutically to humans at doses of 20 g to dissolve ga llstones. Systemic toxicity from dermal exposure is anticipated to be lower than oral toxicity because dermal penetration is expected to be less than 100% and since local dermal irritation would occur at high exposure levels, causing discontinuation of exp osure. ]

2. Genotoxic i ty. [ Limonene is not mutagenic in numerous assays. Renal adenomas/ carcinomas in male rats administered limonene for 2 years (N ational

T oxicology P rogram study) are considered to be related to alpha 2u

- globulin

induced nephro pathy and therefore are not considered relevant to human risk assessment (Risk Assessment Forum document on alpha

- globulin nephropathy). ]

3. Reproductive and developmental toxicity. [ Limonene is not a developmental toxicant. Delayed ossification in bone d evelopment may be observed at high doses that also cause maternal toxicity. Several developmental toxicity studies were cited in the literature review of the NTP study. No developmental effects were observed in rabbits administered limonene up to 1,000 mg/ kg. ]

4. Subchronic toxicity

. [ In a N ational T oxicology P rogram study, toxicity of D

limonene administered by gavage in corn oil was assessed in CD rats and in B6C3F1
mice in 16

- day, 13

- week and 2

- year studies. In the 16

- day study, no effects were

obs erved in males at or below 825 mg/kg/day or in females at or below 1,650 mg/kg/day. Decreased body weights were observed in males at 1,650 mg/kg/day and in females at 3,300 mg/kg/day. Deaths occurred at 3,300 and 6,600 mg/kg/day among both males and femal es. In the 13

- week study, no effects were observed in
females at or below 600 mg/kg/day. At 1,200 and 2,400 mg/kg/day clinical signs (lethargy, salivation) were observed in males and females. Decreased body weight
was observed in males at 1,200 mg/kg/day and females at 2,400 mg/kg/day. Lacrimation, rough coat and lethargy were noted at 1,200 mg/kg/day. Nephropathy related to alpha

- 2u globin accumulation was observed in male rats at all doses (150 mg/kg/day above).3

Mortality was increased in males and fem ales at 2,400 mg/kg/day (highest dose tested). ]

5. Chronic toxicity. [ In a 2

- year study, male rats were given 75 or 150 mg/kg/day and females 300 or 600 mg/kg/day limonene. At 150 mg/kg/day males had slightly decreased body weight but at both doses dev eloped alpha

- globulin nephrotoxicity and renal 2u adenoma/adenocarcinoma. Females showed no effects at 300 mg/kg/day but at 600 mg/kg/day had slightly decreased body weight and increased mortality. Mice given limonene at the same doses in the 16

- day and 1 3

- week studies also showed limited evidence of toxicity at high doses, although some body weight decrease in males was observed at all doses. Mice were given 250 or 500 mg/kg/day (males) or 500 or 1000 mg/kg/day (females) in the 2

- year study.
Females at 10 00 mg/kg/day had decreased body weight. No treatment

- related nephropathy or renal adenomas/carcinomas were observed in either sex in the 2

- year study. ]

6. Animal metabolism. [ NA

- Remove ]

7. Metabolite toxicology

. [ NA

- R emove ]

8. Endocrine disrup tion

. [ The Agency has no information that suggests Sweet Orange Peel Tincture in general will have an effect on the immune or endocrine system. ]

C. Aggregate Exposure

1. Dietary exposure. [ Dietary exposure to sweet orange peel tincture is possibl e through ingestion of citrus fruit (oranges). D

- Limonene, the constituent which comprises 95% of sweet orange peel tincture, is naturally occurring in fruits, vegetables, meats and spices. ]

i. Food. [ D

- Limonene occurs naturally in fruits (especially citrus fruits, vegetables, meats, and spices). As an additive it is found in a variety of foods and beverages. According to the National Toxicology Program report of 1992, approximately 254,000 kg are consumed annually. All of the orange peel tincture

con stituents are found in common foods. The exposures from residues of orange peel tincture applied to crops as an inert ingredient will constitute a negligible
addition to diet. ]

ii. Drinking water

. [ The peel extract are nonsoluble oils and terpenes . The contamination of drinking water is highly improbable. ]

2. Non

- dietary exposure

. [ The primary route of exposure to these chemicals4

from their use as inert ingredients in pesticide products would most likely be through consumption of food to which pesticide products containing them have been applied. Dermal and inhalation exposures are also possible for workers from use of pesticide products containing this inert ingredient. However, the quantitative exposure assessment via inhalation and dermal ro utes of exposure has not been determined but is not expected to be of significance. ]

D. Cumulative Effects

[ Unlike other pesticide ingredients 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 Sweet Orange Peel Tincture and any other substances. For the purposes of this tolerance action, therefore, EPA has not assumed that Sweet Orange Peel Tincture has a common mechanism of toxicity with oth er substances. ]

E. Safety Determination

1. U.S. population. [ D

- Limonene occurs naturally in fruits (especially citrus fruits, vegetables, meats, and spices). As an additive it is found in a variety of foods and beverages. According to the National T oxicology Program report of 1992, approximately 254,000 kg are consumed annually. All of the orange peel tincture constituents are found in common foods. The exposures from residues of orange peel tincture applied to crops as an inert ingredient will con stitute a negligible
addition to diet. ]

2. Infants and children

. [ EPA concluded that the F QPA safety factor can be set to 1X for Sweet Orange Peel Tincture for the following reasons: There is sufficient data to assess the toxicity of sweet orange peel tincture.

The data presented in the assessment on D

- Limonene, the primary constituent, constituting greater than 95% of the product, are adequate to characterize the expected behavior of the subject extract. Studies have shown that this natural terpen e does not pose a teratogenic, developmental or mutagenic effect. All of the peel extract components can be found in food (fruit) commonly consumed by children. The incidental residues possible from application of this product are significantly less

than the natural exposure of infants and children through ingestion of fruit (especially citrus fruit). ]

F. International Tolerances

[ There are no CODEX or international tolerance exemptions established for the subject inert ingredient at this time. ]