Straight Chain Lepidopteran Pheromones Registration Review Case No. 8200 PC Codes: Multiple



### 1 UNITED STATES ENVIRONMENTAL PROTECTION AGENCY WASHINGTON, D.C. 20460

OFFICE OF CHEMICAL SAFETY & POLLUTION PREVENTION OFFICE OF PESTICIDE PROGRAMS



### MEMORANDUM

DATE: 19 November 2012

SUBJECT : Non-Target Organism Studies, Hazard Assessment, and Endangered Species Assessment for Straight-Chain Lepidopteran Pheromones (SCLPs) in Support of Registration Review.

Case No.: 8200 Chemical Class: Biochemical PC Codes: Multiple (see Table 1) CAS Nos. Multiple (see Table 1) Tolerance Exemptions: 40 CFR 180.1153



### FROM : Russell S. Jones, Ph.D., Senior Biologist /s/ 11/19/2012 Biochemical Pesticides Branch Biopesticides & Pollution Prevention Division (7511P)

TO : Colin Walsh, Regulatory Action Leader Biochemical Pesticides Branch Biopesticides & Pollution Prevention Division (7511P)

EXECUTIVE SUMMARY

Based on the expected very low exposure to aquatic organisms, low toxicity to birds, and on its use patterns and use instructions, the Agency has determined that Straight-Chain Lepidopteran Pheromones (SCLPs) will have “ No Effect ” on any currently listed, threatened, or endangered species or any designated critical habitat.

SCLPs are applied to the environment at concentrations much lower naturally occurring background levels and are applied in ways that are not readily accessible to nontarget organisms.Straight Chain Lepidopteran Pheromones Registration Review Case No. 8200 PC Codes: Multiple



### 2 They are volatile substances that induce highly species specific behavioral responses in males of the target pests. Specifically, they disrupt mating by the masking of, or misdirection from natural mating pheromone mating plumes emitted by females of the target species. The SCLPs are practically non-toxic to mammals, birds, and insects on an acute and dietary basis. In laboratory studies, SCLPs range from very highl y toxic to practically non-toxic to fish and aquatic invertebrates. The SCLPs, however, are practically insoluble in water and would never reach concentrations in water where toxicity would occur. In addition, SCLP products are not intended for application to aquatic sites. No data are available for plants, however, due to the low application rates, high relative volatility, and little to no measureable residues, effects on non-target plants are highly unlikely. No advers e effects have ever been reported on plants treated with SCLP products after several decad es of use in IPM programs for crop protection from insect pests.

DESCRIPTION OF THE ACTIVE INGREDIENTS

Semiochemicals include all substances emitted by plants, animals, and microorganisms that elicit behavioral responses in the receptor species. A semiochemical emitted by an individual of one species that effects the individuals of other species is defined as an allelochemical; a semiochemical emitted by an individual of a species that effects individuals of the same species is defined as a pheromone (see review by Jones, 2012).

Straight Chain Lepidopteran Pheromones (SCLPs ) are semiochemicals registered as mating disruptants for use on food crops and ornamentals. As defined by EPA at 40 CFR §158.2000, a pheromone is either a compound produced by a living organism, or is a synthetically derived structure that is structurally similar and functionally identical to a naturally occurring pheromone, that, alone or in combination with other such compounds, modifies the behavior of other individuals of the same species. EPA defines a Lepidopteran pheromone in 40 CFR § 158.2000 (a)(2)(ii) as an arthropod pheromone produced by a member of the insect order Lepidoptera and consist of an unbranched aliphatic chain ( between nine and eighteen carbons) ending in an alcohol, aldehyde, or acetate functional group. This group can contain up to three double bonds in the aliphatic backbone (40 CFR § 158.2000 ( a )(2)( i i i)).

Chemistry data are summarized below for three SCLPs that are representative of the classes of pheromones the Agency considers to be SCLPs. All SCLPs consist of an unbranched long chain of 9 to 18 carbons. They differ in the end functional group, which can be an alcohol, aldehyde, or acetate, and in the number of double bonds. The carbon chain may be unsaturated or contain up to three double bonds. For these reasons the SCLPs are structurally similar to one another and the product chemistry data follow similar patterns. While the Agency is satisfied with the existing product chemistry database, it does not exempt future registrations from being required to satisfy all biochemical product chemistry data requirements. Below are three tablesStraight Chain Lepidopteran Pheromones Registration Review Case No. 8200 PC Codes: Multiple



### 3 summarizing product chemistry data submitted for a specific SCLP from each of the three functional group classes.

Table 1. Biochemical Pesticides Product Chemis try Data for SCLP n-Tetradecyl Acetate.

Guideline No. Physical and Chemical Properties Status 1 Value MRID/ Source 830.1100 Product Identity and Composition A --

830.1200 Description of starting materials, production and formulation process A CBI --

830.1400 Discussion of formation of impurities A CBI --

830.1700 Preliminary analysis A CBI -- 830.6302 Color A Pale Yellow 47423705 830.6303 Physical state A Liquid 47423705 830.6304 Odor A Fatty 47423705 830.6313 Stability to normal and elevated temperatures, metals and metal ions A Stable 47423705

830.7000 pH A 5.5-7.0 @20°C 47423705 830.7050 UV/Visible light absorption 290 nm A Molar Absorptivity ( ε ) 0.72 L mol-1cm-1 47423705

830.7200 Melting point/melting range A 2-4°C 47423705 830.7220 Boiling point/boiling range A 142-146°C @3 mmHg 47423705 830.7300 Density (specific gravity) A 0.866 @20°C 47423705 830.7520 Particle size, fiber length, and diameter distribution N/A -- 47423705

830.7550 830.7560 830.7570 Partition coefficient (nOctanol/Water) A Log P ow = 6.76 @25°C BRAD

830.7840 Water solubility A Insoluble 47423705 830.7950 Vapor pressure A 3.6-4.5x10 -4 mmHg @20°C 47423705

1. A=Acceptable. N/A=Not Applicable. CBI=Confidential Business Information.Straight Chain Lepidopteran Pheromones Registration Review Case No. 8200 PC Codes: Multiple



### 4 Table 2. Biochemical Pesticides Product Chemistry Data for SCLP (Z,Z,E)-7,11,13- Hexadecatrienal.
Guideline No. Physical and Chemical Properties Status 1 Value MRID/ Source 830.1100 Product Identity and Composition A --

830.1200 Description of starting materials, production and formulation process A CBI ----

830.1400 Discussion of formation of impurities A CBI --

830.1700 Preliminary analysis A CBI 830.6302 Color A Pale Yellow 47922801 830.6303 Physical state A Liquid 47922801 830.6304 Odor A Mild/waxy 47922801 830.6313 Stability to normal and elevated temperatures, metals and metal ions A Stable 47922801

830.7000 pH N/A insoluble 47922801 830.7050 UV/Visible light absorption 290 nm A λ max = 232 nm 47922801

830.7200 Melting point/melting range N/A -- 47922801 830.7220 Boiling point/boiling range A 341 ± 21°C 47922801 830.7300 Density (specific gravity) A 0.865 @25°C 47922801 830.7520 Particle size, fiber length, and diameter distribution N/A -- 47922801

830.7550 830.7560 830.7570 Partition coefficient (nOctanol/Water) N/A Log P ow > 5.35 @25°C 48231701 48231702 48231703 830.7840 Water solubility A Insoluble 47922801 830.7950 Vapor pressure A 8.23x10 -4 torr @25°C 47922801 1. A=Acceptable. N/A=Not Applicable. CBI=Confidential Business Information.Straight Chain Lepidopteran Pheromones Registration Review Case No. 8200 PC Codes: Multiple



### 5 Table 3. Biochemical Pesticides Product Chemistry Data for SCLP (Z)-11-Tetradecen-1-ol.
Guideline No. Physical and Chemical Properties Status 1 Value MRID/ Source 830.1100 Product Identity and Composition A --

830.1200 Description of starting materials, production and formulation process A CBI --

830.1400 Discussion of formation of impurities A CBI --

830.1700 Preliminary analysis A CBI -- 830.6302 Color A Pale Yellow 46832301 830.6303 Physical state A Liquid 46832301 830.6304 Odor A Fatty 46832301 830.6313 Stability to normal and elevated temperatures, metals and metal ions A Stable 46832301

830.7000 pH A 5.4 46832301 830.7050 UV/Visible light absorption A See MRID 46832301

830.7200 Melting point/melting range N/A 46832301 830.7220 Boiling point/boiling range A 138-140 @520 Pa 46832301 830.7300 Density (specific gravity) A 0.875 @20°C 46832301 830.7520 Particle size, fiber length, and diameter distribution N/A -- 46832301

830.7550 830.7560 830.7570 Partition coefficient (nOctanol/Water) A Log P ow = 4.6 @25°C 46832301

830.7840 Water solubility A <0.0004 g/l 46832301 830.7950 Vapor pressure A 0.16-0.20 Pa @20°C 46832301 1. A=Acceptable. N/A=Not Applicable. CBI=Confidential Business Information.



### EPA-REGISTERED END-USE PRODUCTS

Regulation of SCLPs predates the founding of the Agency. The first SCLP, (z,z)-11,13- hexadecadienal, was registered in July 1969. As of this document, the Agency has thirty five SCLPs with active registrations. On August 30, 1994, the Agency issued a final rule establishing an exemption from the requirement of a tolerance for residues from the use of straight chain lepidopteran pheromones in 40 CFR §180.1153. An SCLP Biopesticide Registration Action Document (BRAD) was issued in August 2001 and as new active ingredients have been registered the document has been amended with updated information.

The SCLPs with active registrations are summarized in Table 4 below. In some instances SCLPs have been registered concurrently and are always used together as a specificStraight Chain Lepidopteran Pheromones Registration Review Case No. 8200 PC Codes: Multiple



### 6 pheromone blend. These active ingredients are typically individual components of a specific, multi-component insect pheromone and are naturally grouped together.

Table 4. Straight Chain Lepidopteran Ph eromones with Active Registrations.
SCLP Name PC Code CAS Number Number of TGAI/MPs Number of EPs

(z,z)-11,13-hexadecadienal 000711 71317-73-2 2 5

lauryl alcohol 001509 112-53-8 1 13 myristyl alcohol 001510 112-72-1 1 7 (e,z,z)-3,8,11-tetradecatrienyl acetate 011472 163041-94-9 1 7
(z,z,e)-7,11,13-hexadecatrienal 029000 888042-38-4 1 1
(e)-5-decen-1-ol & (e)-5-decenyl
acetate 078038, 117703 56578-18-8, 38421-90-8 3 13

(z,e)-7,11-hexadecadien-1-yl acetate & (z,z)-7,11-hexadecadien-1-yl acetate 114101, 114102 53042-79-8, 52207-99-5 1 6

cis-7,8-epoxy-2-methyloctadecane 114301 29804-22-6 2 4

(z,e)-9,12-tetradecadienyl acetate 117203 31654-77-0 2 5

(e,z)-2,13-octadecadien-1-yl acetate & (e,z)-2,13-octadecadien-1-ol 117242, 117244 86252-65-5, 123551-47-3 1 1

(z)-11-hexadecenal 120001 53939-28-9 3 31
(z)-11-tetradecenal 120011 35237-64-0 0 1
(z)-4-tridecen-1-yl acetate & (e)-4- tridecen-1-yl acetate 121901, 121902 65954-19-0, 72269-48-8 2 4

(e,e)-9,11-tetradecadien-1-ol 128000 54664-98-1 1 8 n-tetradecyl acetate 128002 638-59-5 1 1

(z)-8-dodecen-1-yl acetate 128906 28079-04-1 4 24 (e)8-dodecen-1-yl acetate 128907 38363-29-0 4 24 (z)-8-dodecen-1-ol 128908 40642-40-8 4 24 (z)-11-tetradecenyl acetate & (e)-11- tetradecenyl acetate 128980, 129019 20711-10-8, 33189-72-9 2 13Straight Chain Lepidopteran Pheromones Registration Review Case No. 8200 PC Codes: Multiple



### 7 SCLP Name PC Code CAS Number Number of TGAI/MPs Number of EPs

(z)-9-dodecenyl acetate 129004 16974-11-1 1 2 (z)-11-tetradecen-1-ol 129021 34010-15-5 0 1
(e,e)-8,10-dodecadien-1-ol 129028 33956-49-9 5 29 (z)-6-heneicosen-11-one 129060 54844-65-4 0 1 (z)-11-hexadecenyl acetate 129071 34010-21-4 1 2 (z)-9-tetradecen-1-yl acetate 129109 16725-53-4 0 2
(e,z)-3,13-octadecadien-1-ol 129117 66410-28-4 1 1 (z,z)-3,13-octadecadien-1-ol 117241 66410-24-0 0 1 (z,e)-7,9-dodecadien-1-ol 011471 55774-32-8 0 1



### MODE OF ACTION

Lepidopteran pheromones are used to disrupt the mating behavior of certain moths and butterflies whose larvae destroy crops and trees via herbivory. Mating behavior in adults is disrupted by making it more difficult for males of the target species to locate mates via the masking of, or misdirection from the natural pheromone plumes emitted by females (Carde and Minks, 1995; Stelinsky, 2007). Mating disrup tion is a non-toxic mode of action.

Pheromones have a high degree of species specificity (see review by Ando et. al., 2004). Semiochemical pheromones, such as SCLPs, are “ odors” that bind to olfactory sensor receptors (OSRs) located in the antennae and maxillary palp s of receptor insect species (Sato and Touhara, 2009; Touhara and Vosshall, 2009). The OSRs are “narrowly tuned receptors” (i.e., have high species specificity) that are associated with olfactory sensory neurons (OSNs) (Touhara, 2009), which are “neural circuits in the [insect] brain” (Touhara and Voshall, 2009) involved with mating. Upon binding of a pheromone to an OSR, neuronal activity is triggered in the OSNs results in the mate-seeking behavioral responses of the receiver insect. No mortality occurs in the target species.

ENVIRONMENTAL FATE

The straight chain lepidopteran pheromones are applied to a variety of crops in various ways. The most common distribution methods are in dispensers (active and passive), flakes, microencapsulated beads, or granular formulations.Straight Chain Lepidopteran Pheromones Registration Review Case No. 8200 PC Codes: Multiple



### 8 The SCLPs are, as a group, insoluble in water and are of intermediate volatility. Volatility is key to the efficacy of SCLPs (Barth, 2001) and allows small amounts to be placed in the environment, resulting in low exposure to the active ingredient when used as a pesticide for mating disruption. Studies of the fate of SCLPs on moistened soil and water show rapid dissipation via volatilization and environmental degradation. Volatilization of the parent compounds occurs rapidly in water with half life varying from 29 hours to 7 days (Henson, 1977; Shaver, 1983). The SCLPs also readily undergo photo-oxidation (OECD, 2002) and are tran sformed by beta-oxidation of the double bonds in the carbon chain and other types of oxidative degradation. The enzymes operative during the degradation of SCLP residues are ubiquitous in nature (OECD, 2002).

The following specific examples are illustrative of the rapid environmental degradation of SCLPs. The half-life of the Gypsy mo th pheromone, gossyplure [(Z,Z)- and (Z,E)- 7,11-Hexadecadien-1-ol acetate), was measured to be 1 day on soil and 7 days on water at 32 o 

### C (Henson, 1977). The half lives of the components of the tobacco budworm pheromone, (Z)-9-Tetradecenal and (Z)-11-Hexadecenal, were observed to be respectively, 29 and 50 hours in soil at 22 o 

### C, and 30 and 90 hours in water at 24 o 

### C (Shaver, 1983). In addition, a review of the existing data by OECD (2002) demonstrated that due to rapid volatilization and degradation, atmospheric concentrations of applied SCLPs are unlikely to exceed several ng/m3 in the aerial compartment in and around the treated crops.

Based on a large body of existing data, the Agency determined that additional environmental fate data are not required for registration SCLP produc ts intended for applications at a rate of no more than 150 grams active ingredient/acre/year per 40 CFR §158.2060, except those SCLP products expected to be available to avian species. This exception for products available to avian species applies to the SCLPs after they are formulated into end-use products and is used to address the potential toxicity of the other (inert) ingredients in the end-use products, not the SCLP active ingredients which have been demonstr ated to be practically non-toxic to birds on an acute and dietary basis (see Table 5 below). Environmental fate testing is typically required when results from Tier I TGAI testing indicate potential adverse effects. This has not been the case with the currently registered SCLPs.

EXPOSURE ASSESSMENT

SCLPs are formulated into end-use products at low concentrations that are intended for use as mating disruptants. The tolerance exemption for SCLPs in 40 CFR §180.1153 limits the application rate to 150 grams active ingredient/acre/year on growing crops and post-harvest treatments, or approximately 410 mg of pheromone per acre per day. For comparison, it has been estimated that in orchards infested with Codling moth, theStraight Chain Lepidopteran Pheromones Registration Review Case No. 8200 PC Codes: Multiple



### 9 females may emit up to 184 mg of mating pheromone per acre per day (Jones, 2012). Higher estimates (see review by Touhey, 1990) estimated that a Codling moth infestation may result in emission levels of up to 91.2 mg/A/hour (or 2188.8 mg/A/day). In any growing season, these values may vary but are likely significantly increased by the presence of multiple arthropod species emitting multiple pheromones in the same area (Jones, 2012).

The effectiveness of SCLP products are de pendent upon Lepidopteran olfactory receptor systems (i.e. the OSR/OSN complex) that are most sensitive to natural emission rates that are within a discrete range for the receptor species (Ando et. al., 2004). At higher rates of release, SCLP pheromones become much less, or even ineffective (Howse et. al., 1998). Therefore, in contrast to natural levels of SCLP emissions, exposure to humans and nontarget organisms from SCLP pesticide products is therefore expected to be much lower than from the collective natural background levels of lepidopteran pheromones. The SCLP pheromone delivery systems are designed to emit the active ingredients in the low nanogram range (Mayer and Mitchell, 1998).

The SCLP end-use products are typically applied via dispensers (active and passive), and foliar applications of microencapsulated flakes, beads, or granules. Residues on edible fruit (grapes) were undetectable when SCLPs were applied in the field via passive dispensers at up to 141 g a.i. per acre with a detection limit of 2-5 ppb (OECD, 2002). Unwashed tomatoes field-treated with an SCLP (tridecenyl acetate) formulated into 35 um microcapsules, had residues of 21-72 ppb on the day of application, declining to 0.9- 6.8 ppb by day 15 post-application, and 0.29-1.2 ppb by day 30 (OECD, 2002). Washing the tomatoes lowered the SCLP residues below the limits of detection. Even on the day of application, the highest residue levels were well below natural background levels of lepidopteran pheromones.

Straight chain lepidopteran pheromone products are not intended to be applied directly to aquatic environments and label language provides specific in structions to avoid direct applications to water. Regardless, the insolubility of SCLPs, together with their volatility (see Tables 1-3 above), renders exposure to aquatic organisms highly unlikely. For aquatic exposure, the Agency estimated environmental concentrations of (z,e)-7,11-hexadecadien-1-yl acetate and (z,z)-7,11-hexadecadien-1-yl acetate by applying a Tier I aquatic model, GENEEEC Version 2.0 (Appendix A). The GENEEC model predicts very low environmental concentrations, with a peak generic estimated environmental concentration of 308 ppt (parts per trillion), orders of magnitude below the lowest known endpoints for fish [96-hr LC 50 

### = 2.8 ppm (Bluegill sunfish) to 3.7 ppm (Rainbow trout) (Beroza et. al. 1975); and aquatic invertebrates [0.45 ppm to 1.3 ppm (Daphnids) (Touhey, 1990).Straight Chain Lepidopteran Pheromones Registration Review Case No. 8200 PC Codes: Multiple



### 10 HAZARD ASSESSMENT

According to 40 CFR §158.2060 (a)(2), SCLPs applied up to a maximum use rate of 150 grams active ingredient/acre/year in formulations not expected to be available to avian species are not required to address nontarget toxicity data requirements. In instances where the products are expected to be available to avian species, as in granular formulations, the Agency has typically required the registrant to submit Tier 1 Avian Testing as outlined in 40 CFR §158.2060 and/or other relevant data.

Table 5 . Summary of Non-Target Organism Data

Study Type/OPPTS Guideline SCLP Test Substance LD 50 /LC 50 /EC 50 Results Toxicity Category Reference or MRID Acute Oral Toxicity(rat)
/OPPTS 870.1100 All known tested LD 50 >5,000 mg/kg IV Practically non-toxic 

### FR Notice 1/26/94

Avian Acute Oral Toxicity
/OPPTS 850.2100 (Z)-11-Hexadecanal (91.9%) (Z)-9-Tetradecenal (6.1%) LD 50 >2000 ppm (Bobwhite quail) Practically non-toxic Touhey, 1990

(Z)-11-Hexadecen-1-ol (0.01%) 1-Tetradecenal (8.25%) (Z)-9-Tetradecenal (8.82%)

1-Hexadecenal (17.4%) (Z)-7-Hexadecanal (0.63%) (Z)-9-Hexadecanal (0.63%) (Z)-11-Hexadecanal (62.3%) LD 50 >2000 ppm (Mallard duck) Practically non-toxic Touhey, 1990 & MRID 00073644

(Z)-9-Dodecen-1-ol acetate (80%) (E)-9-Dodecen-1-ol acetate (20%) LD 50 >2000 ppm (Mallard duck) Practically non-toxic Touhey, 1990

(Z)-4-Tridecen-1-ol acetate (4%) (E)-4-Tridecen-1-ol acetate (96%) LD 50 >2000 ppm (Mallard duck) Practically non-toxic Touhey, 1990

(Z,Z)-7,11-Hexadecadien-1-ol acetate (49.8%) (Z,E)-7,11-Hexadecadien-1-ol acetate (47.2%) LD 50 >10000 ppm (Mallard duck) Practically non-toxic Touhey, 1990 & MRID 00070563

Avian Dietary Toxicity
/OPPTS 850.2150 (Z,Z)-7,11-Hexadecadien-1-ol acetate (49.8%) (Z,E)-7,11-Hexadecadien-1-ol acetate (47.2%) 8-day LD 50 >10000 ppm (Mallard duck) Practically non-toxic Touhey, 1990 & MRID 00083062 (Z,Z)-7,11-Hexadecadien-1-ol acetate (49.8%) (Z,E)-7,11-Hexadecadien-1-ol acetate (47.2%) 8-day LD 50 >10000 ppm (Bobwhite quail) Practically non-toxic Touhey, 1990 & MRID 00083062 (Z)-7-Dodecen-1-ol LC 50 = 3.7ppm (Rainbow trout) LC 50 = 2.8 ppm (Bluegill sunfish) Highly toxic Beroza et. al., 1975Straight Chain Lepidopteran Pheromones Registration Review Case No. 8200 PC Codes: Multiple



### 11 Study Type/OPPTS Guideline SCLP Test Substance LD 50 /LC 50 /EC 50 Results Toxicity Category Reference or MRID

Freshwater Fish Acute Toxicity, 96 hr
/OPPTS 850.1075 (Z)-7-Dodecen-1-ol acetate LC 50 >100 ppm (Rainbow trout) LC 50 >100 ppm (Bluegill sunfish) Practically non-toxic Beroza et. al., 1975 (Z)-11-Hexadecanal (91.9%)

(Z)-9-Tetradecenal (6.1%) LC 50 = 320 ppm (Rainbow trout) Practically non-toxic Touhey, 1990

(Z)-9-Dodecen-1-ol acetate (80%) (E)-9-Dodecen-1-ol acetate (20%) LC 50 >300 ppm (Bluegill sunfish) Practically non-toxic Touhey, 1990

(Z)-4-Tridecen-1-ol acetate (4%) (E)-4-Tridecen-1-ol acetate (96%) LC 50 >300 ppm (Bluegill sunfish) Practically non-toxic Touhey, 1990

(E)-11-Tetradecen-1-yl acetate (9.5%) (E,E)-9,11- Tetradecen-1-yl acetate (0.5%) LC 50 >187 ppm (Rainbow trout) LC 50 >187 ppm (Fathead minnow) Practically non-toxic USDA/APHIS, 2011

Aquatic Freshwater Invertebrate Toxicity, 48-hr
/OPPTS 850.1010 (Z)-11-Hexadecanal (91.9%) (Z)-9-Tetradecenal (6.1%) LC 50 >0.45 ppm ( Daphnia magna ) 1 Very highly toxic Touhey, 1990

(Z)-9-Dodecen-1-ol acetate (80%) (E)-9-Dodecen-1-ol acetate (20%) LC 50 = 1.3 ppm ( Daphnia magna ) 1 Highly toxic Touhey, 1990

(Z,Z)-7,11-Hexadecadien-1-ol acetate (49.8%) (Z,E)-7,11-Hexadecadien-1-ol acetate (47.2%) LC 50 = 6.8 ppm ( Daphnia magna ) Highly toxic Touhey, 1990.

(E)-11-Tetradecen-1-yl acetate (9.5%) (E,E)-9,11- Tetradecen-1-yl acetate (0.5%) 96-hr LC 50 >187 ppm ( Ceriodaphnia dubia ) Practically non-toxic USDA/APHIS, 2011

Non-target Plants

- No direct toxicity reported or expected for any product due to low application rates, high volatility, and minimal to no measurable residues . Practically non-toxic USDA/APHIS, 2011

Non-target Insects (Honey Bee Acute Oral Toxicity, 48-hr)/OPPTS 850.3020 (E)-11-Tetradecen-1-yl acetate (9.5%) (E,E)-9,11- Tetradecen-1-yl acetate (0.5%) No mortality with contact exposure of up to 0.91 g/300bee (1.0% soln); up to 10x the field app. rate Practically non-toxic Monheit et. al., 2008

Non-target Insects (Honey Bee Contact Toxicity, 48- hr)/OPPTS 850.3020 (E)-11-Tetradecen-1-yl acetate (9.5%) (E,E)-9,11- Tetradecen-1-yl acetate (0.5%) No mortality with contact exposure of up to 1.13g/300bee (0.1% soln) ); up to 10x the field app. rate Practically non-toxic Monheit et. al., 2008

1. Mortality likely due to entrapment of test organisms in oily surface filmStraight Chain Lepidopteran Pheromones Registration Review Case No. 8200 PC Codes: Multiple



### 12 RISK ASSESSMENT

Risk Quotients (RQs) and Levels of Concern (LOCs) were assessed using the highest known values for SCLP residues on field-treated crops via active and passive dispensers: unwashed tomatoes field-treated with an SCLP (tridecenyl acetate) formulated into 35 um microcapsules,had residues of 21-72 ppb on the day of application, declining to 0.9-6.8 ppb by day 15 postapplication, and 0.29-1.2 ppb by day 30 (OECD, 2002). The residue value of 72 ppb (0.072 ppm) was used for all subsequent calculations on terrestrial taxa.

Terrestrial vertebrates : Numerous studies have demonstrated that SCLPs are practically nontoxic (Toxicity Category IV) in acute oral and acute dermal routes of exposure (LD 50 

### > 5000 mg/kg) (see review by OECD, 2002; & USEPA, 2007 & 2008). Mammalian RQs are estimated

as: Mammalian RQ = 0.072/5000 <0.01

The RQ for mammals are well below any levels of concern for non-target mammals, including threatened and endangered species.

Birds : It has been demonstrated that SCLPs are practically non-toxic to birds on both an acute (>2000 mg/kg to > 10000 mg/kg) (Table 5). Using the lowest non-definitive endpoint for birds exposed to residues via active/passive dispensers, RQs are estimated as:

Avian RQ = 0.072/2000 <0.01 (acute and dietary)

Oral exposure to birds via flakes or granules is not expected to be a significant route of exposure to SCLPs (which make up only a tiny percentage of the products on a w/w basis). Based on the low exposure and minimal toxicity (Table 5), the Agency has exempted the requirements for non-target bird data for granular product, except for end-use formulations (see 40 CFR 158.2060). This requirement is used to assess the potential for effects on birds resulting from the inert ingredients in the granular products, not fo r the active ingredient. Effects on birds resulting from potential consumption of granular end-use formulations will be assessed on a case-by-case basis as these products are reviewed for registration. Otherwise, the RQs are well below any levels of concern for non-target birds, including threatened and endangered species.

Fish and Aquatic Invertebrates : Effects on fish in laboratory studies are somewhat variable, but the majority of studies indicate that SCLPs are practically non-toxic to fish (> 100 ppm; Beroza, 1975), except for one study using the SCLP (Z)-7-Dodecen-1-ol as a test substance which reported LD 50 

### s respectively of 3.7 ppm and 2.8 ppm for Rainbow trout and Bluegill sunfish (both Highly toxic) (Beroza, 1975). Effects on aquatic invertebrates also were variable, ranging from >0.45 ppm to 6.8 ppm (Very highly toxic to Highl y toxic) in laboratory studies (Touhey, 1990; USDA/APHIS, 2011; Table 5). For aquatic exposure, the Agency estimated environmentalStraight Chain Lepidopteran Pheromones Registration Review Case No. 8200 PC Codes: Multiple



### 13 concentrations of (Z,E)-7,11-hexadecadien-1-yl acetate and (Z,Z)-7,11-hexadecadien-1-yl acetate by applying a Tier I aquatic model, GENEEEC Version 2.0 (Appendix A). The GENEEC model predicts very low environmental concentrations, with a peak generic estimated environmental concentration of 308 ppt (parts per trillion; or 0.000308 ppm). Based on the lowest known LD 50 

### for fish (2.8 ppm for Bluegill sunfish), the RQ is estimated as:

Fish RQ = 0.000308/2.8 <0.01

Similarly, based on the lowest known LD 50 

### for aquatic invertebrates (0.45 ppm for Daphnia), the RQ is estimated as: Aquatic invertebrate RQ = 0.000308/0.45 <0.01

The RQs are well below any levels of concern for non-target aquatic organisms, including threatened and endangered species.

The Agency notes that the LD 50 

### s reported in laboratory studies, where the test substance was artificially rendered water soluble via the use of solvents, are at concentrations that are well above the solubility of SCLPs (practically insol uble in water) in a natural aquatic environment.

Non-Target Plants : Exposure to plants is expected to be minimal and would occur via contact resulting from atmospheric exposure to SCLPs vola tilized from active and passive dispensers, or volatilized from foliarly applied flakes or granules containing SCLPs. Residues on edible fruit (grapes) were undetectable when SCLPs were applied in the field via passive dispensers at up to141 g a.i. per acre with a detection limit of 2-5 ppb (OECD, 2002). Unwashed tomatoes fieldtreated with an SCLP (tridecenyl acetate) formulated into 35 um microcapsules, had residues of 21-72 ppb on the day of application, declining to 0.9-6.8 ppb by day 15 post-application, and 0.29-1.2 ppb by day 30 (OECD, 2002). Due to the low application rates, high relative volatility, and little to no measureable residues, effects on non-target plants are highly unlikely. No adverse effects have ever been reported on plants treated with SCLP products after several decades of use in IPM programs for crop protection from insect pests. There are no concerns for non-target plants, including threatened and endangered species.

Non-Target Insects : Lepidopteran pheromones are used to disrupt the mating behavior of certain moths and butterflies whose larvae destroy crops and trees via herbivory. Mating behavior in adults is disrupted by making it more difficult for males of the target species to locate mates via the masking of, or misdirection from the natural pheromone plumes emitted by females (Carde and Minks, 1995; Stelinsky, 2007). Mating disrupti on is a non-toxic mode of action. Unique suites of pheromones exist for each species of insect (Ando et. al. 2004; Roelofs, 1995; Stelinsky, 2007) and pheromones eliciting a response in one species are highly unlikely to elicit a response in an unrelated species.Straight Chain Lepidopteran Pheromones Registration Review Case No. 8200 PC Codes: Multiple



### 14 Few studies have been conducted to determine contact or oral toxicity to insects. One available study (Monheit et. al., 2008), demonstrated that the SCLP used in the control of Light Brown Apple moth (LBAM) (Table 5), was non-toxic to honey bees on a dietary and on a a contact basis at up to 10x the field applied rate. The Agen cy notes that dietary exposure to bees or other pollinators via nectar or pollen is highly unlikely because SCLPs are not systemic in plants.

There are no concerns for non-target insects, including threatened and endangered species.

Overall Risk Assessment : Based on the application methods of end-use products containing straight chain lepidopteran pheromones as their active ingredient, there is little or no exposure of SCLPs to nontarget terrestrial and aquatic organisms. As discussed above, SCLPs are applied to the environment at concentrations lower than that found naturally and are presented in the environment in ways that are not readily accessible to nontarget organisms.

Based on the expected very low exposure to aquatic organisms, low toxicity to birds, and on its use patterns and use instructions, the Agency has determined that it will have “ No Effect ” on any currently listed, threatened, or endangered species or any designated critical habitat.

REFERENCES

Ando, T., S. Inomata, and M. Yamamoto. 2004. Lepidopteran sex pheromones. Topics in Current Chemistry 239: 51-96.

Barth, F.G and A. Schmid. 2001. Ecology of Sensing

. Springer.

Beroza, M., M. N. Inscoe, P. H. Schwartz, M. L. Keplinger, and C. W. Mastri. 1975. Acute toxicity studies with attractants. Toxicology and Applied Pharmacology 31: 421-429.

Carde, R. T. and A. K. Minks. 1995. Control of moth pests by mating disruption: successes and constraints. Annual Review of Entomology 40: 559-585.

Esmeralda, R., C. Barata, J. Damásio, and M. P. Bosch, and A. Guerrero. 2006. Aquatic ecotoxicity of a pheromonal antagonist in Daphnia magna and Desmodesmus subspicatus

. Aquatic Toxicology 79: 296-303.

Jones, R. S. 2012. Biochemical Pesticides: Green Chemistry Designs by Nature. In: Green Processes Volume 9: Designing Safer Chemicals. R. Boethling and A. Voutchkova, eds. WileyVCH, 2011. pp. 329-347.Straight Chain Lepidopteran Pheromones Registration Review Case No. 8200 PC Codes: Multiple



### 15 Henson, R. D. 1977. Environmental fate of gossyplure. Environmental Entomology 6: 821- 822.

Howse, P. E., I. D. R. Stevens, and O. T. Jones. 1998. Insect Pheromones and their Use in Pest Management. Chapman and Hall, London, 369 pp.

Mayer, M. S. and E. R. Mitchell. 1998. Rapid measure of sex pheromone emission from plastic rope dispensers: example of utility in sexual communication disruption of the Diamondback moth, Plutella xylostella . Phytoparasitica 26(2): 1-9.

Monheit, S., E. C. Mussen, and M. L. Johnson. 2008. Effects of Contact and exposure to formulated CheckMate and LBAM-F and unformulated LBAM mating pheromones on honey bees, Apis mellifera (Hymenoptera: Apidae). Final Report, Nov 18. http://www.cdfa.ca.gov/plant/pdep/lbam/docs/HoneyBee_Checkmate_ToxicityRpt%20_Nov_08. pdf

Organisation for Economic Cooperation and Development (OECD). 2002. Guidance for registration requirements for pheromones and other semiochemicals used for arthropod pest control. OECD Series on Pesticides, No. 12. Environmental Directorate, Joint Meeting of the Chemical Committee and the Working Party on Chemicals, Pesticides, and Biotechnology. ENV/JM/MONO(2001)12. Roelofs, W. L. 1995. Chemis try of sex attractants. Proceedings of the Ntional Academy of Sciences 92: 42-49.
Roelofs, W. L. 1995. Chemistry of sex attractants. Proceedings of the National Academy of Sciences 92: 42-49.

Sato, K. and K. Touhara. 2009. Insect olfaction: receptors, signal transduction, and behavior. Chemosensory Systems in Mammals, Fishes, and Insects, Results and Problems in Cell Differentiation 47:121-138.

Shaver, T. N. 1983. Environmental fate of (Z)-11-hexadecenal and (Z)-9-tetradecenal, components of a sex pheromone of the tobacco budworm (Lepidoptera: Noctuidae). Environmental Entomology 12: 1802-1804.
Stelinsky, L. L. 2007. On the physiological and behavioral mechanisms of pheromone-based mating disruption. Pestycydy 3-4: 27-32.
Touhey, J. G. 1990. White Paper. A review of the current bases for the United States Environmental Protection Agency’s policies for the regulation of pheromones and other semiochemicals, together with a review of the available relevant data which may impact the assessment of risk for these classes of chemicals. Part No. I. Straight chain alcohols, acetate esters and aldehydes. (USEPA, unpublished).Straight Chain Lepidopteran Pheromones Registration Review Case No. 8200 PC Codes: Multiple



### 16 Touhara, K. 2009. Insect olfactory receptor complex functions as a ligand-gated ionotrophic channel. New York Academy of Sciences 1170: 177-180. (Abstract Only).
Touhara, K. and L. B. Voshall. 2009. Sensing odorants with pheromones and chemosensory receptors. Annual Review of Physiology 71: 307-332.
USDA/APHIS. 2011. Ecological risk assessment for European grapevine moth control in nurseries and noncommercial applications. http://www.aphis.usda.gov/plant_health/ea/downl oads/2011/EGVMPesticideEnvironmentalRisk Assessment.pdf

USEPA. 2007. Quarantine Exemptions for Light Brown Apple Moth Pheromones. http://www.epa.gov/region9/pesticides/light-brown-moth.html

USEPA. 2008. Straight Chain Lepidopteran Pheromones, Biopesticide Registration Action Document. http://www.epa.gov/pesticides/chem_search/reg_actions/registration/decision_G109_02-Oct-08.pdf
Weatherson, I. and A. K. Minks. 1995. Regulation of semiochemicals - global aspects.. International Pest Management Review 1: 1-13.

Welter, S.C., C. Pickel, J. Millar, F. Cave, R. A. Van Steenwyk, and J. Dunley. 2005. Pheromone mating disruption offers management options for key pests. California Agriculture 59(1): 16-22 (2005).

cc: R. S. Jones, C. Walsh, BPPD Subject File/IHAD R. S. Jones, Sr. Biologist, FT, OPY: 11/19/2012Straight Chain Lepidopteran Pheromones Registration Review Case No. 8200 PC Codes: Multiple



### 17 Appendix A:

GENEEC Run for (z,e)-7,11-hexadecadien-1-y l acetate and (z,z)-7,11-hexadecadien-1-yl acetate

RUN No. 3 FOR 114101 ON cotton * INPUT VALUES *

-------------------------------------------------------------------- RATE (#/AC) No.APPS & SOIL SOLUBIL APPL TYPE NO-SPRAY INCORP ONE(MULT) INTERVAL Koc (PPM ) (%DRIFT) (FT) (IN)

-------------------------------------------------------------------- .022( .022) 10 25 .0 120.0 GRANUL( .0) .0 .0

FIELD AND STANDARD POND HALFLIFE VALUES (DAYS)

-------------------------------------------------------------------- METABOLIC DAYS UNTIL HYDROLYSIS PHOTOLYSIS METABOLIC COMBINED (FIELD) RAIN/RUNOFF (POND) (POND-EFF) (POND) (POND)

-------------------------------------------------------------------- 1.00 2 N/A .00- .00 2.00 2.00

GENERIC EECs (IN NANOGRAMS/LITER (PPTr)) Version 2.0 Aug 1, 2001

-------------------------------------------------------------------- PEAK MAX 4 DAY MAX 21 DAY MAX 60 DAY MAX 90 DAY GEEC AVG GEEC AVG GEEC AVG GEEC AVG GEEC

-------------------------------------------------------------------- 308.88 237.37 83.20 29.66 19.77