1

- Octanol DP Number: 423496 and 425328

PC Code: 079037 EPA File Symbol No.: 67727

- A and 3F8195 Type of Review: Product Chemistry, Human Health, Nontar get Organisms , Tolerance Exemption

OFFICE OF CHEMICAL SAFETY

AND POLLUTION PREVENTION UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
WASHINGTON, D.C. 20460

MEMORANDUM

DATE: February 23, 2015

SUBJECT : Science Review in Support of the Registration of 1,4Zap Technical

, Containing 99.0 %

1

- Octanol as its Active Ingredient

.

Decision Number: 482298

DP Number: 423496 and 425328

E PA File Symbol Number: 67727

- A

Chemical Class: Biochemical

PC Code: 079037

CAS Number: 111

- 87

- 5 Active Ingredient Tolerance/Exemption : Pending : petition # 3F8195

MRID Numbers: 48964401

- 48964402, 49458901

- 49458902 and 49545601

FROM: Angela L. Gonzales, Biologist

Biochemical Pesticides Branch Biopesticides & Pollution Prevention Division (7511P)

TO : Gina Burnett, M.S., Regulatory Action Leader

Biochemical Pesticides Branch Biopesticides & Poll ution Prevention Division (75 11P )

ACTION REQUESTED

In response to the Agency’s request for additional information discussed in the memorandum from A. L. Gonzales to L. Cole dated 7/23/14 and relayed in the deficiency letter to the applicant dated 7/29/14, the applicant has submitte d a revised Confidential St atement of Formula (CSF) dated 9/3/14, a revised label, information in the cover letter dated 9/3/14, product chemistry data and information in MRID 49458901 and mammalian toxicology data and information in MRID 49458902. In resp onse to the request for additional information discussed in the email from G. Burnett to A. Roberts dated 12/17/14, the applicant has submitted a revised CSF dated 1/16/15 and product chemistry data in MRID 49545601.1

- Octanol DP Number: 423496 and 425328

PC Code: 079037 EPA File Symbol No.: 67727

- A and 3F8195 Type of Review: Product Chemistry, Human Health, Nontarget Organisms , Tolerance Exemption

RECOMMENDATIONS AND CONCLUSIONS

1. The product chemistry submission is ACCEPTABLE, pending submission and review of the data listed

below.

MRID 4 9458901 : UPGRADEABLE MRID 49545601: ACCEPTABLE

a

. The applicant indicated that storage s tability and corrosion c haracteristics stud ies are in progress. These studies must be submitted upon completion.

b. All other product chemistry data requirements have been satisfied at this time. The CSF dated 1/16/15 is acceptable and supersedes all others.

2. The toxicology submission for the active ingredient is ACCEPTABLE

. MRID 4 9458902 : ACCEPTABLE

a. All mammalian toxicology data requirements have been satisfied at this time.

3. The nontarget organism toxicology submission is ACCEPTABLE.

a. The applicant submitted a revised labe l for the MP that indic ate s that the product is only to be formulated into

EPs for indoor

- use only.

4

. The petition for the exemption from the requirement of a tolerance for 1

- octanol is ACCEPTABLE.

a. Based on the data and information available , the re is adequate justification for an exemption from the requirement of a tolerance for 1

- octanol when used post

- harvest on stored root, tuber, and bulb crops

. This conclusion is based on the following:

i. Based on the data available to the Agency, no toxi c endpoints have been identified.

ii. Dietary exposure is anticipated to be negligible based on the volatility and expected rapid degradation of the active ingredient.

iii. Humans are already exposed to 1

- octanol as it is found naturally in foods, in fo ods to which it has been added as a food additive, in cosmetics and in air.

NOTE TO RAL :

1. The proposed MP label must be revised to include language that indicates the purpose of the MP (e.g.: for

formulation into end

- use products that are intended f or use as sprout inhibitors on stored root and tuber crops in

21

- Octanol DP Number: 423496 and 425328

PC Code: 079037 EPA File Symbol No.: 67727

- A and 3F8195 Type of Review: Product Chemistry, Human Health, Nontarget Organisms , Tolerance Exemption

storage facilities ). The label must also include language that EPs containing the proposed MP are to be applied from the outside of the building or storage facility. This requirement is based on the lack of exposure argument submitted by the applicant to satisfy the 90

- day dermal and 90

- day inhalation data requirements.

2 . Based on the acute toxicity category classification for 1

- octanol, the label signal word and precautionary language must be revised.

3 . The applicant should be notified that a complete copy of any reference cited should be submitted. In some

cases, in lieu of copies, hyperlinks were provided for references . These hyperlinks may become out of date in

the future and consequentl y difficult to find.

RISK ASSESSMENT AND STUDY SUMMARIES

I. Active Ingredient Characterization

1

- octano l, or octyl alcohol, is a linear saturated aliphatic alcohol containing eight carbons. The chemical has been registered as a plant growth regula tor (PGR) by EPA for use as a tobacco sucker control agent in pesticide products since 1980. In these products, 1

- o ctanol is combined with conventional pesticide chemicals. As a biopesticide, 1

- octanol is also considered a PGR and is intended for use as a sprout inhibitor in pesticide products to be applied post

- harvest on stored potatoes and other sprouting root and tuber crops. The chemical is approved for use by EPA as an inert ingredient in pesticide products for food (as a solvent or co

- solvent under

4 0 CFR 180.910), nonfood and fragrance uses.

There is a significant history of exposure to humans and the environment as 1

- octanol is found naturally in foods and in the environment and is also used as a food additive and as an ingredient in cosmetics. The chemical is approved by the FDA for use as a direct food additive under 21 CFR 172.230 in microcapsules for flavoring

substances and under 21 CFR 172.515 as a synthetic flavoring substance and adjuvant. It has been found in the

essential oils of green tea , grapefruit, California orange, bitter orange, Turkish rose and Bulgarian rose

. 1

- Octanol has been identified as a vol atile component of fried bacon, roasted filberts , raw and roasted earth

al monds, mutton, chicken, pork, raw beef, frankfurters, nectarin es
, apple juice, common guava, Gruyere cheese

and in foods pro cessed from Cassava root

. The amount of the chemical has been quantified in some foods. Fermented soybean curds were found to contain 164.8 to 337.1 ug/kg of 1

- octanol . Duck meat and duck fat we re found to contain the chemical as a volatile component at 8.88 ppb and 12.69 ppb

, respectively. 1

- octanol has also been detected (but not quantified) in air samples from inside some houses and in some suburban areas, rural areas and forests. (HSDB, 2014)

A. Product Chemistry (MRIDs 48964401, 49458901 and 49545601 )

31

- Octanol DP Number: 423496 and 425328

PC Code: 079037 EPA File Symbol No.: 67727

- A and 3F8195 Type of Review: Product Chemistry, Human Health, Nontarget Organisms , Tolerance Exemption

All product chemistry data requirements have been adequately satisfied per 40 CFR 158.2030

. Data Evaluation Records (DERs) were not created for the submitted MRIDs; however, the relevant data and information are summarized in Table 1 and in the subsequent sections. Refer to Table 1 below for summaries of physical and chemical properties data for 1,4Zap Technical containing 99.0% 1

- octanol. Refer to the Confidential Appendix (CA) below for more informatio n regarding product chemistry. The structure of 1

- octanol is below:

TABLE 1 . Physical and Chemical Properties of 1,4Zap Technical (99% 1

- octanol) (40 CFR § 158.2030)

OCSPP Guideline Property Description of Result MRID

830.6302 Color Colorless 49458901

830.6303 Physical State Liquid 49458901

830.6304 Odor Sweet, orange

- rose 49458901

830.6313 Stability to Normal and Elevated Temperatures, Metals and Met al

Ions Stable at normal and elevated temperatures. Will react with oxidizing material. No reported incompatibility with metals or metal ions. 49458901

830.6315 Flammability N/A: product does not contain combustible liquids 49458901

830.6317 Storage Stab ility A storage stability study is ongoing

830.6319 Miscibility N/A: product is not an emulsifiable liquid to be diluted with petroleum solvents 49458901

830.6320 Corrosion Characteristics A corrosion characteristics study is ongoing.

830.7000 pH 5.9 49458901

830.7050 UV/Visible Light Absorption 1.428

- 1.431 refractive index 49458901

830.7100 Viscosity < 10 cp 49458901

830.7200 Melting Point/Range

- 17 to

- 16°C 49458901

830.7220 Boiling Point/Range 194

- 195 °C 49458901

830.7300 Bulk Density 0.827 @ 2 0°C 49458901

830.7520 Particle Size, Fiber Length and

Diameter Distribution Not required: not a fibrous substance.

830.7550

830.7560

830.7570 Partition Coefficient (n

Octanol/Water) logP
ow = 2.54 49545601

830.7840 Water Solubility Insoluble 49458901

830.7950 Vapor Pressure 0.0794 mmHg @ 25°C 49458901

II. Human Health Assessment

41

- Octanol DP Number: 423496 and 425328

PC Code: 079037 EPA File Symbol No.: 67727

- A and 3F8195 Type of Review: Product Chemistry, Human Health, Nontarget Organisms , Tolerance Exemption

A. Toxicology (MRIDs 48964402 and 49458902 )

To satisfy the Tier I mammalian toxicology data requirements, data and information were submitted from the open scientific li terature and from publically

- available Agency documents. All toxicology data requirements have been satisfied per 40 CFR 158.2050. DERs were not created for the submitted MRIDs ; however, the

relevant data and information from these MRIDs are summarized in Table 2 and in the subsequent sections.

Table 2 . Mammalian Toxicology Data for 1,4Zap Technical (99% 1

- octanol) (40 CFR § 158.2050)

Study/OCSPP Guideline No. Results Toxicity Category/Description MRID

Acute oral toxicity (870.1100) LD 50 > 5

, 000 mg/k g (rat)

LD 50 = 1,800 mg/k g (mouse)

LD 50 = 4,135 mg/k g (rat) I II 48964402

WHO , 199 8

Acute dermal toxicity (rabbit) (870.1200) LD 50 > 5,00 0 mg/kg I V 48964402

Acute inhalation toxicity (rat) (870.1300) L C 50 > 6.4 mg/L after 1

- hour exposure (no deaths)

L C 50 > 5.6 mg/L after 4

- hour exposure (3 rats died within 2 days after exposure) IV HSDB, 2014

Primary eye irritation (rabbit) (870.2400) I rritating 1 I I 48964402 EPA, 2006 Primary dermal irr itation (rabbit) (870.2500) Slightly irritating IV 48964402

D ermal sensitization (guinea pig) (870.2600) Not a sensitizer N/A 49458902 EPA, 2006

90

- Day oral toxicity (870.3100) No adverse effects were reported when mice were dosed via gavage with 1

- octanol at 179 mg/kg body weight for 30 days. NOAEL > 179 mg/kg 4 8964402

90

- Day dermal toxicity (870.3250) Waived. Purposeful application and prolonged exposure to the human skin is not anticipated based

on the use pattern: 1

- octanol is intended to be applied inside crop storage facilities through ventilation
systems from outside of the facility. Per label instructions, buildings are sealed until fully ventilated and early reentry requirements include the use of appropriate PPE. Applicators and handlers are required to wear appropriate PPE during use of the pesticide w hich mitigates the potential for repeated exposure. Prolonged dermal exposure is also not anticipated as 1

- octanol is a volatile chemical (estimated half

- life of 3.5 minutes) and is not likely to remain on skin if exposure occurs. 48964402

49458902

51

- Octanol DP Number: 423496 and 425328

PC Code: 079037 EPA File Symbol No.: 67727

- A and 3F8195 Type of Review: Product Chemistry, Human Health, Nontarget Organisms , Tolerance Exemption

Table 2 . Mammalian Toxicology Data for 1,4Zap Technical (99% 1

- octanol) (40 CFR § 158.2050)

Study/OCSPP Guideline No. Results Toxicity Category/Description MRID

90

- Da y inhalation toxicity (870.3465) Waived. Significant repeat inhalation exposure to the active ingredient as a gas, vapor or aerosol is unlikely

. Significant inhalation exposure is not anticipated based on the use pattern: 1

- octanol is intended to be applie d inside crop storage facilities through ventilation systems from outside of the facility. Per label instructions, buildings are sealed until fully ventilated and early reentry requirements include the use of a respirator. Additionally, humans are already exposed to 1

- octanol in the environment as it has been detected in air samples. Prolonged inhalation exposure is also not anticipated as 1

- octanol is a volatile chemical (estimated half

- life of 3.5 minutes) and degrades rapidly once introduced

into the env ironment. 48964402

Mutagenicity

- in vitro studies (870.5100) Not mutagenic with or without metabolic activation (Ames assay) 49458902

Mutagenicity

- in viv o micronucleus assay (870.5395 ) Not mutagenic with or without metabolic activation (mouse lymphoma assay) 49458902

Developmental toxicity (870.3700) No developmental adverse effects occurred when pregnant rats were exposed to 100 mg/m 3 1

- octanol (the max. achievable vapor) for 7 hours/day on gestation days 1

- 19.

No developmental adverse effects occ urred when pregnant rats were dosed via gavage with a blend of 55% decanol and 40.7% octanol at 0, 125, 375 and 1,000 mg/kg/day on gestation days 6

- 16. Maternal NOAEL = 375 mg/kg/day Maternal LOAEL = 1,000 mg/kg/day (increased incidence of salivation)

Dev elopmental NOAEL = 1,000 Developmental LOAEL = not established 48964402

49458902

1 The substance is classified as irritating because the available data indicate that 1

- octanol is “irritating” or “an irritant”, but information regarding the degree of seve rity is unavailable. Additionally, studies cited in the EPA 2006 memo indicate that: 1) exposure of rabbits to a 100% fatty a lcohol blend resulted in moderate to severe eye irritation (toxicity category II) and 2) exposure to varying levels of exposure to 1

- decanol (similar to 1

- octanol) resulted in varying levels of eye irritation, resulting in toxicity category classifications of I

- III. Because specific data on the eye irritation severity of 1

- octanol is unavailable and data on similar substances indicate varying levels of irritation from moderate to severe, a toxicity category II classification is appropriate at this time.

1 . Acute Toxicity

With the exception that it is an eye irritant, 1

- octanol is not considered to be acutely toxic based on the available data. The chemical is classified into toxicity category IV for acute dermal and inhalation toxicity and dermal irritation, toxicity category III for acute oral toxicity and toxicity category II for eye irritation. 1

- octanol is not

considered to b e a dermal sensitizer.

2. Subchronic Toxicity

61

- Octanol DP Number: 423496 and 425328

PC Code: 079037 EPA File Symbol No.: 67727

- A and 3F8195 Type of Review: Product Chemistry, Human Health, Nontarget Organisms , Tolerance Exemption

90

- Day Oral

The 90

- day oral data requirement is required to be addressed for uses of a pesticide on foods . In MRID 48964402, data were cited from the open scientific literature to satisfy the data requir ement. The study has been reviewed and cited by the World Health Organization’s (WHO) International Programme on Chemical Safety in

its assessment of 1

- octanol as a food additive. The study is also cited in the National Library of Medicine’s (NLM) Hazardou s Substances Database (HSDB) for 1

- octanol. Mice were administered the chemical via gavage at a dose of 179 mg/kg body weight for 30 days. No adverse effects were reported.

The metabolism in humans of 1

- octanol h as is well characterized. It is metabolize d into innocuous and endogenous substances. The alcohol is metabolized into its corresponding aldehyde which is then rapidly oxidized to the acid which is metabolized in the fatty acid and tricarboxylic acid pathways. (WHO , 1998)

90

- Day Dermal

The 90

- day dermal data requirement is conditionally required to support uses involving purposeful application to the human skin or uses that would result in prolonged dermal exposure and if data from a 90

- day oral study are not required or the active ingredient is k nown or expected to be metabolized differently by the dermal route of exposure than by the oral route and the metabolite is of toxicological concern. The Agency has waived this data requirement at this time. Purposeful application and prolonged exposure to the human skin is not anticipated based on the use pattern of the proposed product; 1

- octanol is intended to be applied inside crop storage facilities through ventilation systems from outside of the facility. Per label instructions, buildings are

sealed u ntil fully ventilated and early reentry requirements include the use of appropriate PPE which includes coveralls over long

- sleeved shirt, long pants, shoes plus socks, chemical resistant gloves, face

- sealing goggles and a respirator. During use of the pest icide, a pplicators and handlers are required to wear appropriate PPE (long

- sleeved shirt, long pants, shoes, socks, gloves and protective eyewear. These PPE requirements mitigate the potential for repeated dermal exposure. Add ition ally, p rolonged dermal ex posure is also not anticipated as 1

- octanol is a volatile chemical that is expected to degrade rapidly once introduced into the environment. The

chemical has an estimated half

- life of 3.5 minutes ( US EPA, 2007) and is not likely to remain on skin if

exposu re occurs.

90

- Day Inhalation

The 90

- day inhalation data requirement is conditionally required if there is a likelihood of significant levels of repeated inhalation exposure to the pesticide as a gas, vapor or aerosol

. The Agency has waived this data

requ irement at this time. Significant inhalation exposure is not anticipated based on the use pattern: 1

- octanol is intended to be applied inside crop storage facilities through ventilation systems from outside of the facility. Per label instructions, building s are sealed until fully ventilated and early reentry requirements include the use of a respirator. Add ition ally, prolonged inhalation exposure is also not anticipated as 1

- octanol is a volatile chemical that is expected to degrade rapidly once introduced into the environment. The chemical has an estimated half

71

- Octanol DP Number: 423496 and 425328

PC Code: 079037 EPA File Symbol No.: 67727

- A and 3F8195 Type of Review: Product Chemistry, Human Health, Nontarget Organisms , Tolerance Exemption

life of 3.5 minutes ( US EPA, 2007). Furthermore, humans are already exposed to 1

- octanol in the environment as it has been detected in air samples (HSDB, 2014)

.

3. Developmental Toxicity

Develop mental toxicity data are required for to support food uses and are available for 1

- octanol. In MRIDs 48964402 and 49458902, data were cited from the open scientific literature and from studies previously

submitted to the Agency to satisfy the data requirem ent. The cited studies have already been reviewed and used in previous Agency risk assessments ( US EPA, 2006). No adverse effects (maternal or developmental) were

observed i n a developmental toxicity study where pregnant rats were exposed to 100 mg/m 3 1

- oc tanol (the maximum achievable vapor) for seven hours per day on gestation days 1

- 19. No developmental toxicity occurred in a study were pregnant rats were dosed via gavage with a blend of 55% decanol and 40.7% octanol at 0, 125, 375 and 1,000 mg/kg/day on gestation days 6

- 16 . Increased salivation was observed in dams at the highest dose. The m aternal NOAEL = 375 mg/kg/day and the maternal LOAEL = 1,000 mg/kg/day. In this study, increased salivation is not considered a toxic endpoint; the effect occurred at the highest dose tested (the

limit dose ) which is a ver y high dose to which humans are extremely unlikely to be exposed. The d evelopmental NOAEL = 1,000 . The developmental LOAEL was not established because there were no adverse effects at the highest dose tested.

4. Mutagenicity

Mutagenicity data are required to support food uses and are available for 1

- octanol

. In MRID 4 9458902 , data from the open scientific literature were cited to satisfy the mutagenicity data requirements. In an Ames assay,

five st rains of Salmonella typhimurium were exposed to 2,000 nl/plate of 1

- octanol with or without metabolic

activation. 1

- octanol was not considered mutagenic in the assay. In a mouse lymphoma assay (L5178Y TK+/

- )

, cells were exposed to 100 μg/ml 1

- octanol with or without metabolic activation. 1

- octanol was not considered mutagenic in the assay.

5 . Effects on the Endocrine System

As required under FFDCA section 408(p), EPA has developed the Endocrine Disruptor Screening Program (EDSP) to determine whether cer tain substances (including pesticide active and other ingredients) may have an effect in humans or wildlife similar to an effect produced by a “naturally occurring estrogen, or other such endocrine effects as the Administrator may designate.” The EDSP emp loys a two

- tiered approach to making the statutorily required determinations. Tier 1 consists of a battery of 11 screening assays to identify the potential of a chemical substance to interact with the estrogen, androgen, or thyroid (E, A, or T) hormonal sy stems. Chemicals that go through Tier 1 screening and are found to have the potential to interact with E, A, or T hormonal systems will proceed to the next stage of the EDSP where EPA will determine which, if any, of the Tier 2 tests are necessary based o n the available data. Tier 2 testing is designed to identify any adverse endocrine related effects caused by the substance, and establish a dose

- response relationship between the dose and the E, A, or T effect.

81

- Octanol DP Number: 423496 and 425328

PC Code: 079037 EPA File Symbol No.: 67727

- A and 3F8195 Type of Review: Product Chemistry, Human Health, Nontarget Organisms , Tolerance Exemption

Between October 2009 and February 2010, EPA issued test orders/data call

- ins for the first group of 67 chemicals, which contains 58 pesticide active ingredients and 9 inert ingredients. This list of chemicals was selected based on the potential for human exposure through pathways such as food and w ater, residential activity, and certain post

- application agricultural scenarios. This list should not be construed as a list of known or likely endocrine disruptors.

1

- octanol is not among the group of 58 pesticide active ingredients on the initial list to be screened under the EDSP. Under FFDCA sec. 408(p) the Agency must screen all pesticide chemicals. Accordingly, EPA anticipates issuing future EDSP test orders/data call

- ins for all pesticide active ingredients

.

For further information on the statu s of the EDSP, the policies and procedures, the list of 67 chemicals, the test guidelines and the Tier 1 scr eening battery, please visit the website: http://www.epa.gov/endo/.

B. Dose Response Assessment

Based on the data available to the Agency, there is insufficient hazard concern to warrant a dose

- response assessment as no toxic endpoints have been identified for 1

- octanol. This conclusion is in accord with previous Agency conclusions regarding the risk assessment of 1

- octanol as a conventional pestic ide chemical.

C. Food Quality Protection Act (FQPA) Considerations

1. Dietary Exposure and Risk Characterization

Human exposure to 1

- octanol via dietary exposure to treated commodities is unlikely . Based on this and the low hazard concern (lack of to xic endpoints), a quantitative risk assessment is not necessary. Therefore, a qualitative

assessment is appropriate for 1

- octanol

. T he Agency has determined that there is reasonable certainty of no

harm to humans when 1

- octanol is use d according to label i nstructions. T his conclusion is based on the following: 1) toxic endpoints have not been identified for 1

- octanol based on the available data and information ; 2) residues on food commodities are not anticipated as the chemical is expected to degrade rapidl y once applied and 3) humans are already exposed to 1

- octanol in air, in foods that naturally contain the chemical, and in foods

to which the chemical has been added as food additive. A detailed discussion of how the Agency arrived at its conclusion is pro vided in the subsequent paragraphs.

For a discussion of the toxicology data available for the active ingredient refer to the section entitled, “ II.

Human Health Assessment ” above. At this time, no toxic endpoints have been identified for risk assessment

p urposes for 1

- octanol.

Dietary exposure from the proposed use of 1

- octanol on root, tuber and bulb crops is not anticipated because the chemical is expected to degrade rapidly once applied. The half

- life of 1

- octanol is estimated to be from 3.5

minutes ( US EPA, 2007) to 1.3 days (HSDB, 2014). The chemical is volatile and is expected to degrade in the

91

- Octanol DP Number: 423496 and 425328

PC Code: 079037 EPA File Symbol No.: 67727

- A and 3F8195 Type of Review: Product Chemistry, Human Health, Nontarget Organisms , Tolerance Exemption

atmosphere by reaction with photochemically

- produced hydroxyl radicals (HSDB, 2014). Residues of the pesticide are not anticipated on treated commodities at the time of consumption.

As discussed previously in this document, humans are already exposed to 1

- octanol in the air, in the diet and in

cosmetics. Dietary exposure, if any, of 1

- octanol when used as a pesticide on root, tuber and bulb crops is expected to be negligible. Additionally, no endpoints of toxicological concern have been identified for the purposes of this risk assessment. In consideration of the available information, unreasonable risks to humans from dietary exposure (if any) are unlikely. T his conclusion is also in accord with previous Agency conclusions regarding the risk assessment of 1

- octanol as a conventional pesticide chemical. Further, no safety concerns for

1

- octanol have been identified thus far by the FDA or by the WHO in their ass essments of the chemical as a

food additive.

2

. Drinking Water Exposure and Risk Characterization

Residues of 1

- octanol in drinking water are not expected when products are used according to label ins tructions. The active ingredient is a volatile compound that is already present in the environment

. Additionally, 1

- octanol is expected to degrade rapidly once applied. The pesticide will be used indoors only on stored root, tuber and bulb crops and will not be applied directly to water. Therefore, res idues of 1

- octanol in drinking water are unlikely.

3. Acute and Chronic Dietary Risks for Sensitive Subpopulations Particularly Infants and Children

The Agency has determined that there are no foreseeable dietary risks to sensitive subpopulations, incl uding infants and children, from the use of 1

- octanol when labe l instructions are followed. This conclusion is based on the following : 1) no toxic endpoints have been identified and there is no evidence to suggest that 1

- octanol causes increased susceptibi lity in infants and children; 2) significant dietary exposure is not anticipated when

label instru ctions are followed and 3 ) humans are already exposed to 1

- octanol in the diet, in the environment

and in cosmetics.

D. Occupational, Residential, School an d Day Care Exposure and Risk Characterization

1

. Occupational Exposure and Risk Characterization

An occupational exposure assessment was not conducted for sarmentine. Based on the proposed use pattern and toxicity data available to the Agency, anticipa ted exposure is not likely to result in unreasonable risk to applicators/handlers. Significant occupational exposure is not anticipated because applicators and handlers are required to wear PPE that will mitigate exposure to the active ingr edient. Addition ally, 1

- octanol is anti cipated to degrade rapidly once applied which would preclude significant post

- application exposure. No toxic endpoints

have been identified and significant exposure in an occupational setting is not expected if label instructions are

followed.

101

- Octanol DP Number: 423496 and 425328

PC Code: 079037 EPA File Symbol No.: 67727

- A and 3F8195 Type of Review: Product Chemistry, Human Health, Nontarget Organisms , Tolerance Exemption

2

. Residential, School and Day Care Exposure and Risk Characterization

A residential, school and day care exposure assessment was not conducted for 1

- octanol

. Significant exposure to

the chemical is not anticipated in residential, sch ool, a nd day care settings, as product s cont aining this active ingredient are intended for indoor use only on crops in storage facilities

.

E. Aggregate Exposure from Multiple Routes Including Dermal, Oral, and Inhalation

The Food Quality Protection Act amendm ents to the Federal Food, Drug, and Cosmetic Act (FFDCA, Section 408(b)(2)(A)(ii)) require “that there is a reasonable certainty that no harm will result from aggregate exposure to pesticide chemical residue, including all anticipated dietary exposures and other exposures for which there are reliable information.” Aggregate exposure will typically include exposures from food, drinking water, residential uses of a pesticide, and other nonoccupational sources of exposure.

In consideration of the above inform ation, the Agency has determined the risk from aggregate exposure (via oral, dermal, and inhalation exposures) is negligible; there is reasonable certainty that no harm will result to the general population or to infants and children from ag gregate exposur e to 1

- octanol

. No toxic endpoints have been identified and exposure for all routes of exposure is anticipated to be insignificant. Therefore, an aggregate exposure assessment is not necessary for 1

- octanol.

F. Cumulative Effects

EPA has considered the potential for cu mulative effects of 1

- octanol and other substances in relation to a common mechanism of toxicity. Unlik e other pesticides for which EPA has followed a cumulative risk approach based on a c ommon mechanism of toxicity, the Agency has not mad e a common mechanism of

toxicit y finding for 1

- octanol and any other substances and 1

- octanol does not appear to produce a toxic metabolite produced by other substances. The active ingredient is a biopesticide that has a nontoxic mode of

action. For inform ation regarding EPA’s efforts to determine which chemicals have a common mechanism of toxicity and to evaluate the cumulative effects of such chemicals, see the pol icy statements released by the Agency’s Office of Pesticide Programs concerning common mecha nism determinations and procedures for cumulating effects from substances found to have a common mechanism on EPA’s website at http://www.epa.gov/pesticides/cumulative/.

G. Risk Characterization

The Agency has considered human exposure to 1

- octanol in l ight of the relevant safety factors in FQPA and FIFRA. A determination has been made that no unreasonable adverse effects to the U.S. population in general, and to infants and children in particular, will result from the use of 1

- octanol as a pesticide whe n label

instructions are followed.

111

- Octanol DP Number: 423496 and 425328

PC Code: 079037 EPA File Symbol No.: 67727

- A and 3F8195 Type of Review: Product Chemistry, Human Health, Nontarget Organisms , Tolerance Exemption

III. Environmental Assessment

A. Nontarget Organism Toxicology

Based on the indoor

- only use pattern of EPs containing the proposed MP, 1,4Zap Technical, all nontarget organism toxicology data requirements have been w aived. Significant exposure to nontarget organisms is not anticipated. The pesticide will be applied in indoor storage facilities. Once applied, if 1

- octanol is released into the outside air via ventilation systems, environmental fate data and information indicate that the chemical will degrade rapidly. The half

- life of 1

- octanol is estimated to be from 3.5 minutes ( US EPA, 2007) to 1.3 days (HSDB, 2014). The chemical is volatile and is expected to degrade in the atmosphere by reaction with photochemically

- produced hydroxyl radicals (HSDB, 2014).

B. Environmental Fate and Groundwater Data

Environmental fate and groundwater data are not required at this time because the results of the nontarget organism toxicity assessment (Tier I data requirements) did not trigger these Tier II data requirements.

C. Ecological Exposure and Risk Characterization

A risk assessment was not conducted for nontarget organisms, including endangered/threatened organisms due to the unlikelihood of exposure based on the indoor

- on ly use pattern of end

- use products containing the MP, 1,4Zap Technical. Exposure and risk to nontarget organisms are not anticipated when products are used according to label instructions.

D. Endangered Species Assessment

The Agency has not conducted a risk assessment that supports a complete endangered species determination. The ecological risk assessment planned during registration review will allow the Agency to determine whether

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- octanol’s use has “no effect” or “may effect” federally listed threa tened or endangered species (listed species) or their designated critical habitats. When an assessment concludes that a pesticide’s use “may affect” a listed species or its designated critical habitat, the Agency will consult with the U.S. Fish and Wildli fe Service and/or National Marine Fisheries Services (the Services) as appropriate.

121- Octanol DP Number: 423496 and 425328

PC Code: 079037 EPA File Symbol No.: 67727

- A and 3F8195 Type of Review: Product Chemistry, Human Health, Nontarget Organisms , Tolerance Exemption

REFERENCES

HS DB, 2014. Hazardous Substances Data Bank. National Library of Medicine. Search Term: 1 -octanol. <http://toxnet.nlm.nih.gov/cgi- bin/sis/search2/f?./temp/~lUFAi6:1 >

US EPA, 2006. Memorandum from Elissa Reaves and Shanna Recore to Tawanda Spears. Aliphatic Alcohols: Human Health Chapter of the Reregistration Eligibility Decision (RED) Document. Reregistration Case Number 4004. June 20, 2006.

US EPA, 2007. Reregistration Eligibility Decision (RED) for Aliphatic Alcohols (Document EPA 738-07-004; March 2007). Docket number EPA- HQ

- OPP -2007-0134 at http://www.regulations.gov

.

WHO, 1998. International Programme on Chemical Safety, Safety Evaluation of Certain Food Additives and Contaminants, Series 40, Saturated Aliphatic Acyclic Linear Primary Alcohols, Aldehydes and Acids.

Geneva. http ://www.inchem.org/documents/jecfa/jecmono/v040je10.htm

.

CONFIDENTIAL APPENDIX

STUDY SUMMARIES

I. Active Ingredient Characterization

A. Product Chemistry (MRIDs 48964401 and 49458901)

131- Octanol DP Number: 423496 and 425328

PC Code: 079037 EPA File Symbol No.: 67727

- A and 3F8195 Type of Review: Product Chemistry, Human Health, Nontarget Organisms , Tolerance Exemption

c c: A. L. Gonzales, G. Burnett, BPPD Science Review Fil e, IHAD/ARS

A. L. Gonzales, Biologist, FT, PY

- S: 2-23-15

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