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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 - 8 733 ]
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 chang e the margins, font, or format in your pesti cide 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 template to: hollis . linda @epa.gov. TEMPLATE: [ EctoPharma Ltd. ] [ 4F8313 ] EPA has received a pesticide petition ( [ 4F8313 ] ) from [ EctoPharma Ltd. ] , [ Dunsdale Road, Selkirk, TD7 5EB, United Kingdom ] 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 to establish an exemption from the requirement of a tolerance for biochemical pesticide [ 1,2 - Octanediol ] . Pursuant to section 408(d)(2)(A)(i) of FFDCA, as amended, [ EctoPharma Ltd. ] has submitted the follow ing summary of information, data, and arguments in support of their pesticide petition. This summary was prepared by [ EctoPharma Ltd. ] and EPA has not fully evaluated the merits of the pesticide petition. The summary may have been edited by EPA if the term inology 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. [ EctoPharma Ltd. ] Petition Summary [ 4F8313 ] A. Product Name and Proposed Use Practices2 

### [ Product Name: 1,2
- Octanediol Technical (TGAI)

BiodiolTM Bioinsecticide (EP) Proposed Use Practice: 1,2
- Octanediol w ill be applied to growing crops to control insect pests such as a phids, whiteflies and thrips

. Mode of Action: 1,2
- octanediol acts to control insect pests by disrupting the insect cuticle leading to dehydration and death (MRID No. 493492

- 01). Importantly, this disruption is due to physical interactions rather than a n eurotoxic mechanism. 

### ] B. Product Identity/Chemistry 1. Identity of the pesticide and corresponding residues

. [ 1,2
- Octanediol (CAS No. 1117
- 86
- 8). Information regarding the name, identity, chemical composition and natural occurrence has been submitt ed to EPA and can be found in MRID No. 493492
- 01

. 1,2
- octanediol is used commercially in a wide variety of cosmetic products (for example, as an emollient in makeup, face wash, contact lens fluid, anti
- wrinkle creams, skin and hair conditioning products), and as a head lice treatment. 

### ] 2. Magnitude of residues at the time of harvest 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 1,2
- Octanediol would not result in residues that are of toxicological concern 

### .] C. Mammalian Toxicological Profile [ 1) Acute Toxicity of 1,2 - Oct anediol
. Acute Oral Toxicity
– An acute oral toxicity study on rats reported a LD50 of greater than 2,000 mg/kg bodyweight (MRID No. 493492

- 03). Five male and five female rats were given a single oral dose of test material as a suspension in arachis oi l BP at a dose level of 2,000 mg/kg bodyweight and observed for 14 days. There were no mortalities and animals appeared normal one to two days after dosing. All animals showed an expected weight gain. 1,2
- O ctanediol will be identified as Category II I for oral toxicity

. Acute Dermal Toxicity - In an acute dermal toxicity study five male and five fema le were dermally exposed to 1,2
- O ctanediol, moistened with sterile water , to an area that was approximately 10% of the total body surface, at a single dose o f 2000 mg/kg bw (MRID No. 493492

- 04). Test sites were covered with a gauze dressing for 24 hours. Animals were then observed for 14 days. There was no mortality in any of the animals on study and no signs of systemic toxicity. Two of the five females e xhibited a slight weight loss during the two week observation period and all males gained weight during the observation period. 1,2
- Octanediol will be identified as Toxicity Category III for the dermal toxicity.3

Acute Inhalation Toxicity - An acute i nhalation study on 1,2
- O ctanediol reported an LC50 for male rats greater than 2.08 mg/L, and an LC50 for female rats greater than 5.04 mg/L (MRID No. 493492

- 05). In this study, 5 male and 5 female Sprague

- Dawley rats were exposed in a nose
- only chamber to 5.04 mg/L 1,2
- O ctanediol for 4 hours and then monitored for 14 days. The particle mass median aerodynamic diameter (MMAD) was 2.43 μm and the geometric standard deviation (GSD) was 2.13μm. Two of the 5 males at this high dose died and so 5 additional males were exposed to 2.08 μm for 4 hours. The MMAD for this lower exposure was 2.11 μm, and the GSD was 2.06 μm. None of the male rat s died at the 2.08 μm exposure concentration. The low toxicity following acute inhalation exposure to 1,2
- octanediol indicates that 1,2
- O ctanediol is not expected to be particularly toxic by the inhalation route. 1,2
- Octanediol will be identified as Toxi city Category III for inhalation toxicity. Primary Eye Irritation - The eye irritation potential for 1,2

- Octanediol was assessed in a bovine corneal opacity and permeability assay (MRID No. 493492

- 06) and the ingredient was considered to be a severe e ye irritant. Further, the proposed end use product, BiodiolTM Bioinsecticide, which is a 20% formulation of 1,2

- O ctanediol, was characterized as corrosive to the eye of a rabbit in a Primary Eye Irritation study (MRID No. 493493

- 07). 1,2

- O ctanediol will be identified as Category I for eye irritation. Primary Dermal Irritation
– In a primary dermal irritation study, three male or female New Zealand White rabbits were dermally exposed to 0.5 g of 1,2
- O ctanediol that was moistened with aqua ad injectionem and applied to approximately 6 cm 2 on the left side of the dorsal area (MRID No. 493492

- 07)

. The test item was applied first to a gauze patch, which was then applied to the skin and held in place with non
- irritating tape. Test sites were covered with a semi
- o cclusive dressing for 4 hours. Residual test article was removed with tap water from animal 1 after the 4

- hour exposure, but test article was not removed from animals 2 and 3. Animals were then observed for 9

- 14 days. Irritation was scored based on the s everity of erythema and eschar formation, and edema formation. In this study, 1,2
- Octanediol wa s mildly or slightly irritating to the skin based on slight erythema at 72 hours. 1,2
- Octanediol will be identified as Toxicity Category IV for skin irritation

. Dermal Sensitization
– In a dermal sensitization study with 1,2
- O ctanediol guinea pigs were tested using the method of maximization. Mercapobenzothiazole (>98% purity) was used as the positive control substance for the reliability check in October 2013 (6 months earlier). Ten animals were in the test group, 5 were in the negative control group and 6 were in the dose range finding study. All animals in the test and control groups survived throughout the test period. There was no evidence of sensitization in either group and the percentage of sensitized animals was 0%. The sensitization rate after application of the positive control substance was 100%. 1,2
- Octanediol is not a contact dermal sensitizer. 2) Subchronic Toxicity, Teratogenicity and Genotoxic ity of 1,2 - Octanediol. Subchronic Toxicity4 Two repeated dose studies have shown minimal toxicity following oral exposure to 1,2
- octanediol. In the first study, groups of male and female Wistar rats were exposed by gavage to 0, 50, 300 or 1,000 mg/kg 1,2
- octanediol daily for 28 days (MRID No. 493492

- 12). There were no test article

- related effects on mortality, clinical signs, functional observational battery, food consumption, body weight, hematology or clinical biochemistry. An increase in mean abso lute and relative liver and kidney weights was reported in rats treated with 1000 mg/kg/day. Histopathologic changes were seen in the stomach of rats treated with 300 and 1000 mg/kg/day. These effects were indicative of portal of entry irritation by the te st item on the pars non glandularis of the stomach. The no observed adverse effect level (NOAEL) was identified as 300 mg/kg/day based on the consideration that the findings noted in the stomach were local effects due to irritation by 1,2 octanediol. In the second study, groups of male and female rats were exposed by gavage to 0, 50, 150 or 300 mg/kg 1,2

- octanediol daily for 90 days (MRID No. 493492

- 13). Treatment
- related findings identified in the trachea and lungs were determined to be due to accident al inhalation of the test item (basophilic foreign material) by regurgitation. These effects in the lungs and trachea represent a local artifact of the gavage dosing and were not considered a systemic test item effect. The 1,2

- octanediol NOAEL was the hi gh dose tested, 300 mg/kg/day. Rationales for no further testing have been submitted for the conditionally required 90
- day Dermal and 90
- day Inhalation data requirements based on the facts that 1) 1,2

- Octanediol is demonstrated to be of low dermal and in halation toxicity; 2) significant repeated dermal or inhalation exposure is not expected form the intended use patters; 3) metabolism of 1,2

- Octanediol is expected to follow the same pathways for both oral and dermal exposure; 4) 28

- day and 90
- day rat stud ies of repeat oral exposure to 1,2

- Octanediol resulted in minimal adverse effects; 5) systemic levels of 1,2

- Octanediol in oral studies are expected to be higher following oral rather than dermal or inhalation exposure; and 6) a 90

- day inhalation study con ducted on a compound that is structurally similar to 1,2
- Octanediol reported no test article related adverse effects at 2.2 mg/L (MRID No. 493492
- 20). Developmental Toxicity In a developmental toxicity study 1,2
- O ctanediol was administered to groups of 24 female Wistar rats/dose by gavage at dose levels of 0, 150, 300 or 1000 mg/kg bw/day from Days 5 through 19 of gestation (MRID No. 493492

- 14)

. Daily administration of the test item did not result in any mortality, clinical signs of toxicity or gross necr opsy findings in the dams at any dose level. Overall, no maternal toxicity was observed except of lower gravid uterine weights at 300 and 1000 mg/kg bw/day correlating with lower mean fetus weights at 1000 mg/kg/day. Under the conditions of this study, t he maternal NOAEL of the test item, 1,2
- octanediol, was 150 mg/kg bw/day based on the occurrence of lower gravid uterine weights at the LOAEL of 300 mg/kg bw/day and at 1000 mg/kg bw/day. The NOAEL for developmental toxicity was 300 mg/kg bw/day based on the5 occurrence of lower fetus weights at the LOAEL of 1000 mg/kg bw/day correlating with an increased incidence of a 14 th accessory rib. On the basis of the results of this study, the test item 1,2

- octanediol was considered to have no teratogenic potentia l in Wistar rats up to a dose level of 1000 mg/kg bw/day. Mutagenicity 1,2
- Octanediol was evaluated for mutagenic activi ty in the “Ames Test” (MRID No. 493492
- 09). Four strains of Salmonella typhimurium and one of Escherichia coli were exposed to 1,2
- Oc tanediol in the presence and absence of a metabolic activating system. The test material was considered to be non
- mutagenic under the conditions of the test

. 1,2
- Octanediol was evaluated in an in vitro chromosome aberration test using mammalian culture c ells (MRID No. 493492

- 10). The study was designed to examine a clastogenic potential of the test material in the chromosome aberration test system using Chinese Hamster lung cell (CHL0IU). Study results demonstrated that 1,2
- Octanediol did not show the c hromosome aberrations without and with metabolic activation system under the conditions of the study. Finally, 1,2
- Octanediol was evaluated in a gene mutation assay in Chinese hamster V79 cells in vitro (MRID No. 493492

- 11). The assay was performed in tw o independent experiments, using two parallel cultures each. The first experiment was performed with and without liver microsomal activation and a treatment period of 4 hours. The second experiment was performed with a treatment time of 4 hours with and 24 hours without metabolic activation. No substantial and reproducible dose depend increase of the mutation frequency was observed in both experiments, this it was stated that under the experimental conditions the test material did not induce gene mutatio ns. The results of toxicity testing on 1,2
- Octanediol and its long history of safe human exposure from cosmetic and personal care product uses show there is no risk to human health from 1,2
- Octanediol

. Both dietary and non
- dietary exposures would not b e expected to pose any quantifiable risk due to a lack of residues of toxicological concern. 

### ] D

. Aggregate Exposure 1. Dietary exposure. i. Food. [ The intended use of 1,2
- Octanediol is application to food crops, so there is a potential for diet ary exposure
. Acute toxicity studies have shown that 1,2
- Octanediol is not toxic during acute or subchronic testing. Further, 1,2
- Octanediol is not mutagenic as demonstrated in multiple studies. The results of toxicity testing on 1,2
- Octanediol and i ts long history of safe human exposure from cosmetic and personal care products show there is no risk to human health from 1,2
- Octanediol

. 1,2
- Octanediol is not considered persistent based on its characteristics, properties or known degradation pathways. D ietary exposures would not be expected to pose any quantifiable risk due to residues of toxicological concern. 

### ]6


### ii. Drinking water
. [ Similarly, exposure to humans from residues of 1,2
- Octanediol in consumed drinking water would be unlikely. Potential exposure to surface water would be negligible and exposure to drinking water (well or ground water) would be impossible to measure. The intended use of 1,2
- Octanediol is application to growing crops

. The ingredient is not applied directly to water. Acut e toxicity studies have shown that 1,2
- Octanediol is not toxic during acute or subchronic testing. Further, 1,2
- Octanediol is not mutagenic as demonstrated in multiple studies. The results of toxicity testing on 1,2
- Octanediol and its long history of safe human exposure from cosmetic and personal care products show there is no risk to human health from 1,2
- Octanediol

. 1,2
- Octanediol is not considered persistent based on its characteristics, properties or known degradation pathways. Dietary exposures wo uld not be expected to pose any quantifiable risk due to 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 sit es are agricultural. T he intended use of 1,2
- Octanediol is application to food crops

. Acute toxicity studies have shown that 1,2
- Octanediol is not toxic during acute or subchronic testing. Further, 1,2
- Octanediol is not mutagenic as demonstrated in m ultiple studies. The results of toxicity testing on 1,2
- Octanediol and its long history of safe human exposure from cosmetic and personal care products show there is no risk to human health from 1,2
- Octanediol

. 1,2
- Octanediol is not considered persiste nt based on its characteristics, properties or known degradation pathways. Non
dietary exposures would not be expected to pose any quantifiable risk due to residues of toxicological concern 

### .] E . Cumulative Effects [ It is not exp ected that, when used as proposed, 1,2
- Octanediol would result in residues that are of toxicological concern. The intended use of 1,2
- Octanediol is application to growing crops to control insect pests

. 1,2
- Octanediol is not considered persistent based on its characteristics, properties or known degradation pathways

. Acute toxicity studies have shown that 1,2
- Octanediol is not toxic during acute or subchronic. Further, 1,2
- Octanediol is not mutagenic as demonstrated in multiple studies. The results of t oxicity testing on 1,2
- Octanediol and its long history of safe human exposure from cosmetic and personal care products show there is no risk to human health from 1,2
- Octanediol 

### .] F . Safety Determination 1. U.S. population. [ Acute toxicity studies ha ve shown that 1,2
- Octanediol is not7 toxic during acute or subchronic testing. Further, 1,2
- Octanediol is not mutagenic as demonstrated in multiple studies. T he results of toxicity testing on 1,2
- Octanediol and its long history of safe human exposure from cosmetic and personal care products show there is no risk to human health from 1,2
- Octanediol

. 1,2
- Octanediol is not considered persistent based on its characteristics, properties or known degradation pathways. There is a reasonable certainty of no harm to the general US population from exposure to this active ingredient 

### .] 2. Infants and children

. [ As mentioned above, it is not expected that, when used as proposed, 1,2
- Octanediol would result in residues that are of toxicological concern. There is a rea sonable certainty of no harm for infants and children from exposure to 1,2
- Octanediol from the proposed uses 

### .] G. Effects on the Immune and Endocrine Systems [ To date there is no evidence to suggest that 1,2
- Octanediol function s in a manner similar to any known hormone, or that it acts as an endocrine disrupter 

### .] H. Existing Tolerances [ There are no existing tolerances under 40 CFR for 1,2

- Octanediol. 

### .] I . International Tolerances [ A Codex Alimentarium Commission Ma ximum Residue Level (MRL) is not established for 1,2
- Octanediol 

### .]