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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: [Linda Holl is; (703) 308-8733]

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: Email the completed templa te to: hollis.linda@epa.gov.

TEMPLATE:

[D-I-1-4, Inc., a division of 1,4Group, Inc.]

[Insert petition number]

EPA has received a pesticide petition ([insert petition number]) from [D-I-1-4, Inc., a division of 1,4Group, Inc.], [PO Box 860, Meridian, ID 83360] requesting, 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 to establish an exemption from the requirement of a tolerance for the biochemical pesticide [1-octanol]

Pursuant to section 408(d)(2)( A)(i) of FFDCA, as amended, [D-I-1-4, Inc., a division of 1,4Group, Inc.] has submitted the following summary of information, data, and arguments in support of their pesticide petition. This summary was prepared by D-I-1-4, Inc., a division of 1,4Group, Inc.] and EPA has not fully evaluated the merits of the 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 position of the petitioner.

I. [D-I-1-4, Inc., a division of 1,4Group, Inc.] Petition Summary

[Insert petition number]

A. Product Name and Proposed Use Practices2



### [ 1-octanol will be applied post-harvest to stored potatoes and other sprouting root and tuber crops. It will be applied alone or in combinati on with the presently registered biochemical sprout inhibitor, 1,4-dimethylnaphthalene, by aerosol , through the buildings ventilation ducts. The product would be applied to the stored commodity when sprouting is first observed, usually several months after the commodity are harvested and are placed in storage. 

### ]

B. Product Identity/Chemistry

1. Identity of the pestic ide and corresponding residues. [ Active Ingredient: 1-octanol (CAS No. 111-87-5).

Information regarding the name, identity, chemical composition and natural occurrence

has been submitted to EPA and can be found in MRID No. 489644-01, and is

summarized as follows:

1-octanol (PC Code 79037) has been previ ously registered by EPA for use as a tobacco sucker control agent (first registered in 1972). Further, 1-octanol has been approved for use as an inert ingredient solvent in pes ticide formulations and exempted from the requirement of a tolerance at 180.9 20 (tolerance reassessed June 2006).

1-octanol has a number of non-pesticidal uses including perfumes, cosmetics, flavoring agents and industrial solvents. The ingredient is cleared by the FDA for use as a direct food additive per 21 CFR 172.230 in microcap sules for flavoring substances and per 21 CFR 172.515 as a synthetic flavoring substance and adjuvant.

1-octanol has been shown to be a natural c onstituent of plants and microbes. According to the NIH, 1-octanol has been found in green tea, grapefruit, dill, nectarines, apple juice, and bitter orange. Its presence has been qua ntified in certain foods, such as ice cream (0.91 ppm), candy (2.8 ppm), baked goods (3 .0 ppm), pudding (1.5 ppm), and chewing gum (16 to 57 ppm). It has also been identified as a volatile component of fried bacon, and has been found in chicken, pork, and beef.

Since 1-octanol is present as a natural compone nt of various fruits a nd vegetables, and is present as both a natural constituent found in foods and a constituent produced from cooking, it is clearly present in the human diet . Therefore, humans have been exposed to naturally occurring 1-octanol for centuries via th eir diet. The proposed use of 1-octanol would not significantly increase the total daily intake of the aliphatic alcohol.

Mode of Action: 1-octanol has been shown to be an effective plant growth regulator by controlling the growth of tobacco plant suck ers. As the tobacco plant matures, it produces a flower which, if allowed to open , reduces the plant’s ab ility to increase leaf size. The plant’s energy would go towards fl ower opening rather than to leaf growth. Thus, the flowers are removed as soon as th e buds begin to open in a process called topping. The plant, recognizing that it has lost its reproductive power, attempts to propagate by growing auxiliary buds called su ckers. If not eliminated, the suckers utilize critical nutrients and slow leaf growth. While suckers were previously removed by hand, two patents have been issued that describe th e application of aliphatic fatty acid alcohols to growing tobacco plants to control the grow th of the auxiliary buds (suckers). Both patents describe the successful use of 1-octa nol as a plant growth regulator to control sucker growth (5, 6), and there are regist ered pesticide products in the Registration3

Division with this active ingredient.

As a sprout inhibitor, 1-octanol functions in the same way to inhibit the growth of sprouts and peeps on stored potatoes and other post-harvest root and tuber crops.]



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

residue. [NA-Remove]

3. A statement of why an analytical method of detecting and measuring the levels of the pesticide residue are not needed. [ An analytical method for residues is not applicable. It is expected that, when used as proposed 1-oc tanol would not result in residues that are of toxicological concern.]



### C. Mammalian Toxicological Profile

[ 1) Acute Toxicity of 1-octanol.

Acute oral toxicity data is available and reports a LD50 >5,000 mg/kg (Toxicity Category IV) for pure 1-octanol and the same for a fo rmulated end-use product with 90% 1-octanol (MRID Nos. 489644-03 and 489645-09).

Acute dermal toxicity data is available and reports a LD50 of >5,000 mg/kg (Toxicity Category IV) for pure 1-octanol and the same for a formulated end-use product with 90% 1-octanol (MRID Nos. 489644-02 and 489645-10).

Acute inhalation limit dose testing for an end- use product with 90% 1-octanol resulted in an LC50 of >5.10 mg/L (MRID No. 489645-11). 1-octanol has also been evaluated for developmental toxicity in pregnant rats whic h were exposed via the inhalation route. 1-

octanol demonstrated low mammali an toxicity when administered to pregnant rats daily via the respiratory route for eighteen days (MRID No. 489644-02).

Primary eye irritation data is available and re ports 1-octanol is irritating to eyes (Toxicity Category III) for pure 1-octanol and the same for a formulated end-use product with 90% 1-octanol (MRID Nos. 489644-02 and 489645-12).

Primary skin irritation data is available and re ports 1-octanol is slightly irritating to eyes (Toxicity Category IV) for pure 1-octanol and moderately irritation for a formulated enduse product with 90% 1-octanol (MRID Nos. 489644-02 and 489645-13).

Dermal sensitization data is available and reports 1-octa nol is not a skin sensitizer (Toxicity Category IV) for pure 1-octanol, but a contact sensitizer in a formulated enduse product with 90% 1-octanol (MRID Nos. 489644-02 and 489645-14).

2) Subchronic Toxicity, Teratogenicity a nd Genotoxicity of 1-octanol.

Subchronic Toxicity 1-octanol was administered daily to mice via oral gavage for one month at a dose of 180 mg/kg/day. No treatment-related adverse effects were reported by the scientists in their publication (MRID No. 489644-02).4

A ninety day dermal toxicity study was c onducted in rats with a blend of 57 percent decanol and 43 percent octanol. Doses applie d daily to the skin were 0, 100, 300, or 1000 mg/kg. While all three doses of the blend caused dermal irritation, which was observed as erythema, edema, and some exfo liation, body weight loss and hematological changes were observed only in the high dose an imals. A systemic NOEL was set at 1000 mg/kg/day based on clinical chemistry, hematology, and organ weights. Other than dermal irritation, histopathologic examination showed that the thirteen week exposure did not cause target organ toxicity, confirming the relatively low systemic toxicity of 1- octanol (MRID No. 437012-01).

Developmental Toxicity Pregnant rats received daily oral doses of 1- octanoic acid, the oxidized form of 1-octanol, on gestation days six through fifteen. The doses were 0, 1125, or 1500 mg/kg/day. While the highest dose caused significant maternal toxicity and maternal mortality, confirming that the Maximum Tolerated Dose was administered, there was no developmental toxicity in the exposed pups. Therefore, 1-octanoic acid did not demonstrate developmental toxicity (MRID No. 489644-02).

In a second developmental toxicity study, a bl end of two aliphatic alcohols containing 41 percent 1-octanol and 55 percent n-decanol was administered by oral gavage to pregnant rats from gestation day six through sixteen. The doses administered were 0, 125, 375, or 1000 mg/kg/day. While the high dose caused significant maternal toxicity, it did not cause developmental toxicity in the offspring (MRID No. 426093-01).

In a third developmental toxicity study, several aliphatic alcohols were individually administered to groups of pregnant rats via the inhalation route. The animals were exposed to the maximally attainable vapor concentration which, for 1-octanol, was 65 ppm (350 mg/m 3 ), seven hours per day, from gestation day one to gestation day nineteen. The maximally generated vapor concentration did not cause maternal toxicity, nor did it cause developmental toxicity (MRID No. 489644-02).

Mutagenicity 1-octanol was evaluated for mutagenic activit y in the Ames Test, along with sixty-two other food flavoring ingredients. Five st rains of Salmonella typhimurium were exposed to 1-octanol in the presence and absence of a metabolic activating system. The same laboratory evaluated these sixty three food ingredients in the Unscheduled DNA Synthesis Assay and the Mouse Lymphoma Test. 1-octanol did not demonstrate mutagenic activity in any of the three assays (MRID No. 489644-02).

In a second Ames Test, five strains of Salm onella typhimurium were exposed to six doses of a blend of 55 percent decanol and 41 pe rcent 1-octanol. The test, consisting of two independent trials, was conducted in the pr esence and absence of a metabolic activating system, using doses up to 500 ug per plate. The 1-octanol/n-decanol blend did not demonstrate mutagenic activity (MRID No. 42372-02).

The 55 percent n-decanol/41 percent 1-octanol blend was evaluated in a mouse lymphoma assay in the presence and absence of a metabolic activating system. Two independent assays were conducted, using doses sufficiently high to cause severe cytotoxicity. The alcohol blend did not demonstrate mutagenic activity in this assay (MRID No. 423720-03).5

A mouse micronucleus assay was conducted w ith the 55 percent n-decanol/41 percent 1-

octanol blend. Bone marrow cells were ha rvested 24 and 48 hours after treatment with three daily doses of 500, 1000, or 2000 mg/kg/ day. Treatment with the blend did not

induce the formation of micronuclei and thus the blend did not express mutagenic activity in this test. Although a high dose of 2000 mg/kg/day was administered, the blend did not cause signs of toxicity in any of the anim als, again demonstrating the relatively low systemic toxicity of the alcohol blend, and thus 1-octanol (MRID No. 423720-01).

The results of toxicity testing on 1-octanol a nd its long history of safe human exposure from natural occurrence in foods, and from use in perfu mes, as a flavoring agent and as a direct food additive show there is no risk to human health from 1-octanol. Both dietary and non-dietary exposures would not be expected to pose any quantifiable risk due to a lack of residues of toxicological concern. 

### ]

D. Aggregate Exposure

1. Dietary exposure.

i. Food. [ Dietary exposure from use of 1-octanol, as proposed, is minimal. The intended use of 1-octanol is indoor application to post- harvest crops. 1-octanol is not considered persistent based on its characteristics, pr operties or known degradation pathways.

Acute toxicity studies have shown that 1-oc tanol is not toxic during acute, subchronic, and teratology studies. Further, 1-octanol is not mutagenic as demonstrated in multiple studies The results of toxicity testing on 1-octanol a nd its long history of safe human exposure from natural occurrence in foods, and from use in perfu mes, as a flavoring agent and as a direct food

additive show there is no risk to human health from 1-octanol. Dietary exposures would not be expected to pose any quantifiable risk due to a lack of residues of toxicological concern. 

### ]

ii. Drinking water. [ Similarly, exposure to humans from residues of 1-octanol in consumed drinking water would be unlikely. Potential exposure to surface water would be negligible and exposure to drinking wa ter (well or ground water) would be impossible

to measure. The intended use of 1-octanol is indoor application to post-harvest crops. The ingredient is not applied directly to water.

Acute toxicity studies have shown that 1-octanol is not toxic during acute, subchronic and chronic studies. Further, 1- octanol is not mutagenic as demonstrated in multiple studies. The results of toxicity testing on 1-octanol and its long history of safe human exposure from natural occurrence in foods, and from use in perfumes, as a flavoring agent and as a direct food additive show there is no risk to human health from 1-octanol. Drinking water exposures would not be expected to pose any quantifiable risk due to a lack of residues of toxicological concern. 

### ]

2. Non-dietary exposure

. [ The potential for non-dietary exposure to the general population, including infants and children, is unlikely as the proposed use sites are indoor and agricultural. The intended use of 1-octa nol is application to post-harvest crops. 1- octanol is not considered persistent based on its characteristics, properties or known degradation pathways.

Acute toxicity studies have shown that 1-octa nol is not toxic during acute, subchronic and6

chronic studies. Further, 1-octanol is not mu tagenic as demonstrated in multiple studies. The results of toxicity testing on 1-octanol and its long history of safe human exposure from natural occurrence in foods, and from use in perfumes, as a flavoring agent and as a

direct food additive show there is no risk to human health from 1-octanol. Non-dietary exposures would not be expected to pose any quantifiable risk due to a lack of residues of toxicological concern 

### .]

E. Cumulative Effects

[ It is not expected that, when used as proposed , 1-octanol would result in residues that are of toxicological concern. The intended use of 1-octanol is application to post harvest crops. 1-octanol is not consid ered persistent based on its ch aracteristics, properties or known degradation pathways.

Acute toxicity studies have shown that 1-octa nol is not toxic during acute, subchronic and chronic studies. Further, 1-octanol is not mu tagenic as demonstrated in multiple studies. The results of toxicity testing on 1-octanol and its long history of safe human exposure from natural occurrence in foods, and from use in perfumes, as a flavoring agent and as a

direct food additive show there is no risk to human health from 1-octanol. 

### ]

F. Safety Determination

1. U.S. population. [ The results of toxicity testing on 1-octanol and its long history of safe human exposure from natural occurrence in foods, and from use in perfumes, as a flavoring agent and as a direct food additive show there is no risk to human health from

1-octanol. The intended use of 1-octanol is a pplication to post-harvest crops. There is a reasonable certainty of no harm to the gene ral US population from exposure to this active ingredient



### . ]

2. Infants and children

. [ As mentioned above, it is not expected that, when used as proposed, 1-octanol would result in residues that are of toxicological concern. There is a reasonable certainty of no harm for infant s and children from exposure to 1-octanol from the proposed uses. 

### ]

G. Effects on the Immune and Endocrine Systems

[ To date there is no evidence to suggest that 1-octanol functions in a manner similar to any known hormone, or that it acts as an endocrine disrupter 

### .]

H. Existing Tolerances

[ There is an exemption from the requirement of a tolerance for 1-octanol when used as a solvent inert ingredient in pesticid e formulations applied to food at 40 CFR 180.920 (tolerance
reassessed June 2006) 

### .]

I. International Tolerances7



### [ A Codex Alimentarium Commission Maximum Residue Level (MRL) is not established

for 1-octanol 

### .]