**,-~~,** 

# ... 8 tosr 4 ,.e · .s-·.,. UNITED STATES ENVIRONMENTAL PROTECTION AGENCY**~** 'i WASHINGTON, D.C. 20460**~ ~T/1** **~ .,.**  't.
.- 1),**~ -'~l** **Pno~(.v·**

MEMORANDUM OFFICE OF CHEMICAL
SAFETY AND
POLLUTION PREVENTION

Date: April 30, 2014

SUBJECT: Fosetyl-Aiuminum [Fosetyi-AI): Human Health Risk Assessment for th e Es tablishm en t of Tolerances with No U.S. Registration inion Pepper/eggplant, Subgroup 8-1 OB and Pepper, Non-bell (Chili), Dry Fruit.

PC Code: 12330 1

Decision No.: 479264

Petition No.: 3E8182 DP Barcode : 413728 Registration No.: NA Regulatory Action: Tolerance Petition

Case No.: NA Risk Assessment Type: Single Chemical Aggregate

TXRNo.: NA CAS No

. : 39148-24-8

40 CFR: 180.415 MRIDNo.: NA

FROM:

THROUGH:

TO: Matthew Lloyd, Risk Assessor

# /}'If~**~** /

William H. Donovan, Ph.D.,

## Chemi**~/~,/** 

## G

Linda Taylor, Toxicologist

### tv**)/~** Risk Assessment Branches 5 & 7 (RABV /V II)

Health Effec ts Division (7509P)

Alexandra LaMay,

# Chemis~**l ~** **~** Michael Metzger, Chief / · Risk Assessment Branches & 7 (RABV /V I

Health Effects Division (7509P)

Marcel Howard (RM20) Shaja Joyner (RM20) Fungicide Branch Registration Division (7505P)

This documen t provides th e Health E ffects Division' s (HED's) ri sk assessment conducted for the
request for toleranc es with no U.S. registration for Fosetyl-al: pepper/eggplant, s ubgroup 8-lOB and

pepper, non-bell (Chili), dry fruit.

Page 1 of23Page 2 of 23 Table of Contents
1.0 Executive Summary

................................ ................................ ................................ ............. 4
2.0 HED Recommendations

................................ ................................ ................................ ....... 5
2.1 Da ta Deficiencies

................................ ................................ ................................ ............. 5
2.2 Tolerance Considerations

................................ ................................ ................................ . 5
2.2.1 Enforcement Analytical Method

................................ ................................ ............... 5

2.2.2 Analytical Reference Standard

................................ ................................ ................. 6

2 .2.3 Recommended Tolerances

................................ ................................ ........................ 6

2.2.4 Revisions to Petitioned

- For Tolerances

................................ ................................ .... 6

2.2.5 International Harmonization

................................ ................................ ..................... 7

2.3 Label Recommendations

................................ ................................ ................................ .. 7
3.0 Introduction

................................ ................................ ................................ .......................... 7
3.1 Chemical Identity

................................ ................................ ................................ ............. 7
3.2 Physical/Chemical Characteristics

................................ ................................ ................... 8
3.3 Pesticide Use Pattern

................................ ................................ ................................ ........ 8
3.4 Anticipated Exposure Pathways

................................ ................................ ....................... 9
3.5 Consideration of Environmental Justice

................................ ................................ .......... 9
4.0 Hazard Characterization and Dose

- Response Assessment

................................ ................ 10
4.1 Toxicology Studies Available for Analysis

................................ ................................ ... 10
4.2 Absorption, Distribution, Metabolism, Excretion (ADME)

................................ .......... 11
4.3 Toxicological Effects

................................ ................................ ................................ ..... 11
4.4 Safety Factor for Infants and Children (FQPA Safety Factor)

................................ ....... 11
4.4.1 Completeness of the Toxicology Database

................................ ............................. 12

4.4.2 Evidence of Neurotoxicity

................................ ................................ ...................... 12

4.4.3 Evidence of Sensitivity/Susceptibility in the Developing or Young Animal

......... 12

4.4.4 Residual Uncertainty in the Exposure Database

................................ ..................... 13

4.5 Toxicity Endpoint and Point of Departure Selections

................................ .................... 13
4.5.1 Dose

- Response Assessment

................................ ................................ .................... 13

4.5.2 Recommendation for Combining Routes of Exposures for Risk Assessment

........ 13

4.5.3 Classification of Carcinogenic Potential

................................ ................................ . 14

4.5.4 Summary of Toxicological Doses and Endpoints for Fosetyl

- al for Use in Human
Health Risk Assessments

................................ ................................ ................................ ...... 14

5.0 Dietary Exposure and Risk Assessment

................................ ................................ ............ 15
5.1 Metabolite/Degradate Residue Profile

................................ ................................ ........... 15
5.1.1 Summary of Plant Metabolism Studies

................................ ................................ ... 15

5.1.2 Summary of Livestock Metabolism Studies

................................ ........................... 15

5.1.3 Comparison of Metabolic Pathways

................................ ................................ ....... 16

5.1.4 Residues of Concern Summary and Rationale

................................ ........................ 16Page 3 of 23

5.2 Food Residue Profile

................................ ................................ ................................ ...... 16
5.3 Water Profile

................................ ................................ ................................ ............... 17
5.4 Diet ary Risk Assessment

................................ ................................ ................................ 17
5.4.1 Description of Residue Data Used in Dietary Assessment

................................ ..... 17

5.4.2 Chronic Dietary Risk Assessment

................................ ................................ .......... 18

6.0 Residential (Non

- Occupational) Exposure/Risk Characterization

................................ .... 18
7.0 Aggregate Exposure/Risk Characterization

................................ ................................ ....... 19
7.1 Acute Aggregate Risk

................................ ................................ ................................ .... 19
7.2 Short

- Term Aggregate Risk

................................ ................................ ........................... 20
7.3 Intermediate

- Term Aggregate Risk

................................ ................................ ................ 20
7.4 Chronic Aggregate Risk

................................ ................................ ................................ . 20

7. 5 Cancer Aggregate Risk

................................ ................................ ................................ ... 20
8.0 Cumulative Exposure/Risk Characterization

................................ ................................ ..... 21
9.0 Occupational Exposure/Risk Characterization

................................ ................................ .. 21
10.0 References

................................ ................................ ................................ .......................... 21 Appendix A. Physical/Chemical Characteristics

................................ ................................ ......... 22 Appendix B: Review of Human Research

................................ ................................ ................ 23 Appendix C. International Residue Limits Table

................................ ................................ ........ 23Page 4 of 23

1 .0 E xecutive Summary

Fosetyl

- Al is a systemic fungicide which is effective against diseases caused by the Oomycetes (phytophthora and downy mildews ). The proposed action evaluated in this assessment is for the establishment of permanent tolerance, without U.S. registration fo r residues of fosetyl

- Aluminum
in/on pepper/eggplant subgroup 8

- 10B at 0.01 ppm

. The fungicide is currently registered for use on a wide variety of agricultural crops

, on ornamental plants and turf , and as a seed treatment use (SLN

ID

- 30001).

The most rec ent comprehensive human

- health risk assessment for fosetyl

- Al was prepared in January, 2 014 , and there have been no updates to the toxicological or exposure data bases since that risk assessment was completed

.

The toxicological database for fosetyl

- Al is considered complete for characterization of potential developmental, reproductive, carcinogenetic, mutagenic, neurotoxic, and immunotoxic effects. Based on a WOE approach considering all the available fosetyl

- Al hazard and exposure information,
the Haza rd and Science Policy Council ( HASPOC ) conclude d that acute and subchronic neurotoxicity studies , a 28

- day inhalation toxicity study , and an immunotoxicity study may be
waived for fosetyl

- al (TXR No. 0056809)

.

Fo setyl Al is rapidly metabolized following oral exposure and widely distributed

, and it is primarily
excreted via the respiratory route (as CO 2 ) and in the urine, mainly as phosphorous acid. The major target organs foll owing repeated oral exposure to fosetyl

- Al are the reproductive system in the d og (testicular degeneration: spermatocytic and/or spermatidic giant cells in the lumen of the seminiferous tubules) and the urinary system in the rat (histopathological changes in the kidney, impairment of calcium/phosphorus metabolism, calculi and hyperpl asia in the urinary tract, bladder tumors). There is no concern for increased quantitative or qualitative susceptibility of the young following in utero (rats and rabbits) and pre

- and post

- natal exposure (rats) to fosetyl

- Al . Also, there
is no evidence of developmental toxicity, reproductive toxicity, neurotoxicity, or immunotoxicity at dose levels that do not exceed the limit dose. The Food Quality Protection Act (FQPA) safety factor
has been reduced to 1X. Fosetyl

- Al is negative for carcinogenicity excep t at extremely high doses (>limit dose) in rats and mice, and it did not show any genotoxic potential (classified as not likely to
be carcinogenic to humans). Fosetyl

- Al is not acutely toxic via the oral, dermal, and inhalation routes. It produces severe e ye irritation, is not a dermal irritant, and is negative for dermal
sensitization.

The residue chemistry database is complete for purposes of setting fosetyl

- al residue tolerances for crop subgroup 8

- 10B . The nature of the residue in plants and livestock is adequately understood,
field trials were conducted to reflect worst

- case residues, and the residue data are supported by acceptable analytical methods and storage stability data. However, fresh reference standard should be provide d to the National Pesticide Standard Repository. A n up

- to

- date standard will need to be provided prior to the establishment of tolerances.

No acute dietary exposure and risk analysis was performed since there w as no toxicity attributable toPage 5 of 23

a single do se for either the general population or for f emales 13

- 49 years of age. Similarly, no cancer dietary exposure assessment was conducted because fosetyl

- Al is considered “n ot likely to be carcinogenic to humans .”

Conservative screening level chronic dietar y exposure (food and drinking water) assessments were conducted for all registered uses of fosetyl

- al, including the uses in/on crop subgroup 8

- 10B (pepper/eggplant subgroup)

. C hronic dietary risk estimates are below the level of concern (LOC) for all pop ulation subgroups. The estimated chronic dietary (food only) risk is equivalent to 3.6 % of the chronic population adjusted dose (cPAD) for the general U.S. population . The most highly exposed subpopulation is children 1

- 2 years old, with an estimated ris k level of 12% of the cPAD.

Dietary and non

- occupational exposure to fosetyl

- al are possible based on the registered and proposed use pattern ; aggregate exposure and risk estimates are not of concern (short

- term aggregate MOEs > 100 for children 1

- 2 years old [MOE = 540] and adults [MOE = 3

, 200])

.

Potential areas of environmental justice concerns, to the extent possible, were considered in this human health risk assessment (see Section 3.5).

2.0 HED R ecommendations

HED has no objection to the establishment of a permanent tolerance, without U.S. registration, for

res idues of fosetyl

- Aluminum in/on pepper/eggplant subgroup 8

- 10B at 0.01 ppm.

2.1 Data Deficie ncies

None.

2.2 Tolerance Considerations

2.2.1 Enforcement Analytical Method

Rhone

- Poulenc Method No. AR 154

- 97 underwent successfully independent laboratory validation for use as an enforcement analytical method. Although the tolerance expression includes only parent fosetyl

- Al, Method AR 154

- 97 was validated for both fosetyl

- Al and its metabolite, phosphorous acid. Briefly, this method involves residue extraction using a water:acetonitrile mixture (50:50, v/v), purification using an octadecyl (C18) cartridge and methylation using a (trimethylsilyl)

- diazomethane solution. Extrac ted residues are determined by Gas Chromatography on a DB Wax column using a Flame Photometric Detector (phosphorous mode; GC

- FPD). The method limit of quantitation (LOQ) for fosetyl

- Al residues in lettuce, bananas, and grapes ranged from 0.20

– 0.50

ppm.

In support of the pepper trials, the registrant made use of a data collection method, Method No. 00861/M001, which achieved a lower Limit of Quantitation (LOQ) than Method AR 154

- 97.
Method 00861/M001 is an HPLC

- MS/MS method that uses the same extract ion solvent as MethodPage 6 of 23

AR 154

- 97. Sufficient method validation data were submitted with the field trial data to support a LOQ of 0.01 ppm for fosetyl

- Al residues in pepper (bell and nonbell). As HED encourages the development of improved analytical method s and because both methods use the same extraction solvent, HED considers Method No. 00861/M001 to also be a suitable enforcement method for peppers. Thus, an adequate enforcement method is available to enforce tolerances for the proposed
new uses of fose tyl

- Al.

2.2.2 Analytical Reference Standard

The a nalytical standard for fosetyl

- Al (CAS # 39148

- 24

- 8 ) at the EPA National Pesticide Standards Repository currently has an expiration date of October 8, 2014 [personal communication from T.
Cole of ACB/BEAD to W. Donovan, 02/26/2014]. Fresh r eference standard should be provided to the Repo sitory prior to the expiration date. The reference standard should be sent to the Analytical Chemistry Lab, which is located at Fort Meade, to the attention of Theresa Co le at the following
address:

USEPA National Pesticide Standards Repository/Analytical Chemistry Branch/OPP 701 Mapes Road Fort George G. Meade, MD 20755

- 5350

The full 9 digit zip code is mandatory or the mail will be returned.

2 .2. 3 Recommended To lerances

T here are no issues that would preclude the establishment of tolerances for residues of fosetyl

- Al
in/ on the requested crop subgroup. The current tolerance expression for fosetyl

- Al is appropriate, but the tolerance table provided under [40 CFR §180.415(a)] should be amended to include the subgroup 8

- 10B tolerance indicated in the table below. Thus,

Tolerances are established for residues of the fungicide aluminum tris ( O

- ethylphosphonate)

, includin g its metabolites and degradates , in or on the commodities listed below. Compliance with the tolerance levels specified below is to be determined by measuring only fosetyl

- Al, [aluminum tris ( O

- ethylphosphonate)]

, in or on the commodity.

Table 2

. 2.2 Tolerance Summary for Fosetyl

- Al, §180.415(a)

. Commodity Proposed Tolerance (ppm) Recommended

Tolerance (ppm) Comments; Correct Commodity

Definition
Pepper/Eggplant, Subgroup 8

- 10B 0.01 0.01 Pepper/eggplant subgroup 8

- 10B

Pepper, Non

- bell (Chili), dry fruit 0.01 None No separate tolerance needed since the dry commodity will be covered by the fresh pepper tolerance.

2.2. 4 Revisions to Petitioned

- For TolerancesPage 7 of 23

The recommended tolerance for subgroup 8

- 10B matches the proposed tolerance. No separate tolerance is needed for dried chili peppers since the fresh pepper tolerance will cover the dry commodity.

2.2. 5 International Harmonization

There are no Codex MRLs for fosetyl

- Al. The U.S. and Canada regulate residues of fosetyl

- Al based on the same tolerance expression. The fosetyl

- Al preliminary risk assessment document recently made several recommendations to achieve better harmonization between the Health Canada Pest Management Regulatory Agency (PMRA ) MRLs and the U.S. established tolerance levels ( D416436, D. Davis et. al. , 23

- JAN

- 2014)

.

The International Residue Limits Status Sheet relevant to the current petition is attached to this memorandum in Appendix D. Joint review of the current pepper petition with PMRA has resulted in
harmonization of the recommended Canadian M RL and U.S. tolerance level for crop subgroup 8

- 10B.

2.3 Label Recommendations

None

.

3.0 I ntroduction

Fosetyl

- Al is a systemic fungicide which is effective against diseases caused by the Oomycetes (phytophthora and downy mildews ). The proposed action evaluated in this risk assessment is for the establishment of permanent tolerance, without U.S. registration for residues of fosetyl

- Aluminum
in/on pepper/eggplant subgroup 8

- 10B at 0.01 ppm

. Fosetyl

- Al is currently r egistered for use on a wide variety of agricultural crops

, as a seed treatment, and on ornamental plants and turf.

The most recent comprehensive human

- health risk assessment for fosetyl

- Al was prepared in January, 2 014 1 and there have been no updates to the toxicological or exposure data bas e outside the proposal for tolerances in/on pepper/eggplant subgroup 8

- 10B

.

3.1 Chemical Identity

The chemical structure and nomenclature of fosetyl

- A l and the metabolite phosphorous acid is presented in Table 3.1.

1 D. Davis et al; Fosetyl

- Aluminum: Registration Review Preliminary Risk Assessment PC C ode: 123301; D416436Page 8 of 23

TABLE 3.1. Nomenclature of Fosetyl

- Al and Phosphorous Acid

. Compound Chemical Structure

Common name Fosetyl

- Aluminum or Fosetyl

- Al Phosphorous Acid

Company experimental names Not applicable Not applicable

IUPAC name Aluminum tris (O

- ethylphosphonate) P hosphonic acid

CAS name Aluminum tris (O

- ethylphosphonate) P hosphonic acid

CAS # 39148

- 24

- 8 13548

- 36

- 2

3.2 Physical/Chemical Characteristics

Fosetyl

- Al is a solid at environmental temperatures, with low volatility. The compound is very soluble in water and soluble in methanol ; however, it is relatively insoluble in acetonitrile , acetone,

n

- octanol, xylene, ethyl acetate and dichloro m ethane . Based on the Log K OW , fosetyl

- Al is unlikely to partition into fat or to bioaccumulate . Appendix A lists the physical/chemical properties of fosetyl

- Al.

3.3 Pesticide Use Pattern

The January 2014 Fosetyl

- Al Human Health Risk assessment referenced earlier provides a complete description of the agricultural, seed treatment, and commercial turf/ornamental uses . In order to assess the proposed establishment of tolerances, t ranslations of the Previcur® Energy labels from Mexico and Peru were provided. The overall use pattern specified by these labels is consistent wi th the use pattern tested in the crop field trials, particularly regarding application method and timing

. Table 3.3 describes the use pattern from the Previcur® Energy labels registered in Mexico and Peru

. Similarly, a use pattern table detailing the regis tered domestic uses of fosetyl

- Al is available in the January 2014 risk assessment. An important aspect of the use pattern referenced below in Table 3.3 is that the last foliar application to pepper seedlings is made no later than the BBCH 17 growth
stage, which is approximately 75

- 90 days prior to harvest. The late season applications are limited to soil drench or chemigation applications with a 7

- 14 day pre

- harvest interval (PHI). The use information provided is considered adequate for purposes of eva luating the submitted field trial data.

TABLE 3.3. Summary of Directions for Use for Fosetyl

- Al Formulations

.

Crop Application

Method/Timing No.

App./

Year Application Rate RTI (days) Spray
Volume Maximum

Seasonal Rate PHI

Previcur Energy: 310 g Fosetyl

- AL/L (FAL/L) + 530 g Propamocarb /L (PHY/L) (Peruvian label )Page 9 of 23

TABLE 3.3. Summary of Directions for Use for Fosetyl

- Al Formulations

.

Crop Application

Method/Timing No.

App./

Year Application Rate RTI (days) Spray
Volume Maximum

Seasonal Rate PHI

Pimiento Post

- transplant,

drench 1 FAL: 0.6

- 0.8 kg
a.i./ha

PHY: 1.1

- 1.3 kg
a.i./ha NA 300 L/ha FAL: 0.8 kg
a.i./ha

PHY: 1.3 kg
a.i./ha 7

Restrictions and Recommendations: Can be applied in a mixture with other pesticides and foliar fertilizers

Previcur E nergy 840 SL/Previcur Energy: 310 g FAL/L + 530 g PHY/L (Mexi can Label )

Chili Seedling treatment

in trays or nurseries (green house), 20 days post seed planting (or when
trays are extended) Up to

3 FAL: 0.3 1

- 0.6 2 g a.i./1L water

PHY: 0.5 3

- 1.1 g
a.i./1L water 10 0.3

- 0.5 L/tray FAL: 1.9 g a.i./1L

water (Max. 0.9 g a.i//tray)

PHY: 3

. 3 g a.i./1L

water (Max. 1.7 g a.i//tray) 3 A

Chili,

Tomato Drench applications;

or drip irrigation.
Make the first application between the first 10 days
after the transplantation. 3 FAL: 775

- 930 g a.i./
ha

PHY: 1.3

- 1.6 k g a.i./ ha 14 50

- 100 ml/plant FAL: 2.8 kg

a.i./ha

PHY: 4.8 k g a.i./ ha 14

Restrictions and Recommendations: This product is not compatible with copper and foliar fertilizers derived from nitrogen. It can be mixed with products registered for the same crop

- disease combination

Note: RTI = re

- treatment interval; No. = number; App. = applications. PHI = pre

- harvest interval.

A Prior to transplant.

3.4 Anticipated Exposure Pathways

The Registration Division has requested an assessment of human health risk to support the proposed
new tolerance for fosetyl

- al in/on pepper/eggplant, subgroup 8

- 10B and pepper, non

- bell (Chili)

, dry fruit, with no U.S. registration. While the requested action for fosetyl

- al is non

- domestic, there is domestic potential for drinking water, occupational, and/or residential exposures based on the currently registered use pattern

. A new aggregate ris k assessment was completed to account for the proposed action along with the existing domestic registered use pattern.

3.5 Consideration of Environmental Justice

Potential areas of environmental justice concerns, to the extent possible, were considered in this human health risk assessment, in accordance with U.S. Executive Order 12898, "Federal Actions to Address Environmental Justice in Minority Populations and Low

- Income Populations," ( http://www.eh.doe.gov/oepa/guidance/justice/eo12898.pdf . As a part of every pesticide risk assessment, OPP considers a large variety of consumer subgroups according to well

- establishedPage 10 of 23

procedures. In line with OPP policy, HED estimates risks to popu lation subgroups from pesticide exposures that are based on patterns of that subgroup’s food and water consumption, and activities in and around the home that involve pesticide use in a residential setting. Extensive data on food consumption patterns are compiled by the U nited S tates D epartment of A griculture (USDA) under
the National Health and Nutrition Examination Survey, What We Eat in America (NHANES/WWEIA). These food consumption patterns are used in pesticide risk assessments for all registered foo d uses of a pesticide. These data are analyzed and categorized by subgroups based on

age and ethnic group. Additionally, OPP is able to assess dietary exposure to smaller, specialized subgroups and exposure assessments are performed when conditions or ci rcumstances warrant. Whenever appropriate, non

- dietary exposures based on home use of pesticide products and associated risks for adult applicators and for toddlers, youths, and adults entering or playing on treated areas post

- application are evaluated. Further considerations are currently in development as OPP has committed resources and expertise to the development of specialized software and models that consider exposure to bystanders and farm workers as well as lifestyle and traditional dietary
patter ns among specific subgroups.

4.0 Hazard Characterization and Dose

- Response Assessment

Fosetyl

- Aluminum: Reregistration Preliminary Risk Assessment PC Code: 123301; D. Davis, et al ; D416436

4.1 Toxicology Studies Available for Analysis

Dietary exposure is expected from food and water, and a route

- specific study was available for the chronic dietary assessment. An acute dietary endpoint was not selected because no appropriate endpoint attributable to a single exposure (dose) was identified from the oral toxicity studies, including developmental toxicity studies in rats and rabbits. The chronic dietary endpoint was selected from the chronic oral toxicity study in dogs and is based on an increased incidence of testicular degeneration (spermatocytic and/or s permatidic giant cells in the lumen of the seminiferous tubules). A 100X uncertainty factor was applied to account for inter

- and intra

- species variability.

For the incidental oral exposure risk assessment, a route

- specific study was available for risk

a ssessment. The endpoint (decreased body weight gains and urinary tract changes in adults) was
selected from the 3

- generation reproduction study in rats. A 100X uncertainty factor was applied to
account for inter

- and intra

- species variability.

Dermal and inhalation exposures are expected. No quantification of dermal risk is required , based on the lack of systemic effects following repeat dermal exposure of rabbits at dose levels up to 1500 mg/kg/day and the lack of developmental and reproductive concerns.

For the short

- term inhalation exposure risk assessment, a repeated dose study via the inhalation route of exposure is not available for fosetyl

- Al

. An oral endpoint (decreased body weight gains and urinary tract changes in adults) was selected from the 3

- generation reproduction study in rats. Since on oral study was selected, an inhalation absorption rate of 100% should be used in the route

- to

route extrapolation. A 100X uncertainty factor was applied to account for inter

- and intra

- speciesPage 11 of 23

variability.

Additionally, section 4.5.4 provides a summary of the toxicological doses and endpoints used in the human health risk assessment, along with the appropriate uncertainty factors and level of concern for each exposure route.

4.2 Absorption, Distribution, Metabolism, Excretion (ADME)

Fo setyl Al is rapidly metabolized following oral exposure and widely distributed

, and it is primarily
excreted via the respiratory route (as CO 2 ) and in the urine, mainly as phosphorous acid.

4.3 Toxicological Effects

The major target organs foll owing repeated oral exposure to fosetyl

- Al are the reproductive system in the dog (testicular degeneration: spermatocytic and/or spermatidic giant cells in the lumen of the seminiferous tubules) and the urinary system in the rat (hi stopathological changes in the kidney, impairment of calcium/phosphorus metabolism, calculi and hyperplasia in the urinary tract, bladder tumors).

The prenatal developmental studies in rabbits and rats and the 3

- generation reproduction study in
rats show ed no indication of increased susceptibility following in utero and/or postnatal exposure to fosetyl

- Al. Developmental toxicity was not observed in the rat at the limit dose or in the rabbit. Reproductive toxicity was not observed. The toxicology database for fosetyl

- Al does not show any
evidence of neurotoxicity

.

Fosetyl

- Al is classified as not likely to pose a carcinogenic hazard to humans since it was negative for carcinogenicity except at extremely high doses (>limit dose) in rats and mice, and it did not show any genotoxic potential.

Fosetyl

- Al is not acutely toxic via the oral, dermal, and inhalation routes, is not a skin irritant or dermal sensitizer, but is a severe eye irritant.

A repeated exposure study via the inhalation route is not available for fosetyl

- Al; however, the subchronic inhalation toxicity study has been waived based on a weight of evidence analysis indicating inhalation risks are not of concern (HASPOC TXR No. 0056809) . Although no neurotoxicity or immunotoxicity studies are available on fosetyl

- Al, there was no evidence of neurotoxicity or immunotoxicity following exposure to fosetyl

- Al, and these studies have been
waived (HASPOC TXR No. 0056809)

.

4.4 Safety Factor for Infants and Children (FQPA Safety Factor) The Food Quality Protection Act (FQPA) safety factor for the protection of infants and children has been reduced to 1X. There are no concerns and no residual uncertainties with regard to pre

- and/or postnatal toxicity. An FQPA Safety Factor of 1X is approp riate for the following reasons:Page 12 of 23

The database for prenatal developmental and reproductive toxicity is considered adequate to assess safety for infants and children. There is no evidence of increased qualitative or quantitative susceptibility in the develo pmental rat and rabbit studies or in the rat 3

- generation reproduction study. These studies have clearly defined NOAEL/LOAELs. There is a no evidence of neurotoxicity in any study on fosetyl

- Al.

Exposure estimates (food and water) are not likely to unde restimate risk

. F urther details of the dietary risk assessment are available in Section 5.4.

4.4.1 Completeness of the Toxicology Database

The toxicology database for fosetyl

- Al is complete. Acceptable rat and rabbit developmental toxicity
studies and a rat 3

- generation reproduction study are available. The HED’s Hazard and Science Policy Council (HASPOC) determined that the acute and subchronic neurotoxicity studies may be
waived (HASPOC Memo, TXR No. 0056809, 10/29/13).

All other required toxicology studies have been submitted and are considered acceptable.

4.4.2 Evidence of Neurotoxicity There is no concern for neurotoxicity resulting from exposure to fosetyl

- Al, based on a lack of evidence of neurotoxicity in any study on fosetyl

- Al. There is no concern for developmental neurotoxicity.

4.4.3 Evidence of Sensitivity/Susceptibility in the Developing or Young Animal There is no evidence of increased susceptibility [qualitative and quantitative] following in utero exposure to fosetyl

- Al in either the rat (at dose levels that do not exceed the limit dose) or rabbit developmental toxicity stud y, and there is no evidence of increased susceptibility [qualitative or quantitative] following in utero and/or pre

- /post

- natal exposure in the 3

- generation reproduction study in rats.

Fosetyl

- Al has been evaluated for potential developmental effects in the rat and rabbit (gavage administration). Maternal toxicity in the rat included mortality, decreased body weight gain, and increased incidence of total resorptions at 4 times greater than the limit dose . Maternal toxicity in the
rabbit included decrease d body weight gain. Decreased fetal body weight and litter size, and an increased incidence of total resorptions, fetal malformations

, and fetal skeletal variations were
observed in the rat at 4 times the limit dose but not at the limit dose , whereas there were no developmental effects in the rabbit at the highest dose tested (half the limit dose)

. Decreased pup body weight gain and reduced litter and pup body weights in mid and late lactation (all generations), increased incidence of pathological changes i n the urinary tract (F1b and F2b generations), associated with an increased incidence of deaths in F1b and F2b males, and crystal or calcium

- type deposits in the lumen of the urinary bladder of most animals were observed in the reproduction study
at a dose level greater than the limit dose. Reproductive toxicity was not observed.Page 13 of 23

4.4.4 Residual Uncertainty in the Exposure Database

There are no residual uncertainties w i th regard to dietary (food and water ) or residential exposure s

. T he food exposure assessments are based on high

- end tolerance residue levels (that account for the

par ent compound ) and conservative water modeling results

. Actual risks from exposure to fosetyl

Al will likely be lower than those presented in this risk assessment

.

4.5 Toxicity Endpoint and Point of Departure Selections

4.5.1 Dose

- Response Assessment

A detailed description of the toxicity studies used for selecting toxicity endpoints and points of departure for various exposure scenarios is presented in A ppendix A of the January 2014 human
health risk assessment referenced in this document.

An acute dietary endpoint was not selected because no appropriate endpoint attributable to a single exposure (dose) was identified from the oral toxicity studies, including d evelopmental toxicity
studies in rats and rabbits.

The chronic dietary endpoint was selected from the 2

- year oral chronic toxicity study in dogs with a NOAEL of 250 mg/kg/day. At the study LOAEL of 500 mg/kg/day, testicular degeneration (spermatocytic an d/or spermatidic giant cells in the lumen of the seminiferous tubules) was observed. A 100X uncertainty factor was applied to account for inter

- and intra

- species variability resulting in a chronic reference dose (cRfD) of 2.5 mg/kg/day. Since the FQPA f actor is reduced to 1X, the RfD is equivalent to the chronic population adjusted dose (cPAD).

Short

- term and intermediate

- term inhalation endpoints for risk assessment were selected from the 3

- generation re production study in rats with a N OAEL of 300 mg/k g /day. A t the L OAEL of 600 mg/kg /day, decreased body weight gains in the F2b generation and urinary tract changes in adults
were observed. A 10 X uncertainty factor was applied (10X to account for inter

- species variability,
10X to account for intra

- speci es variability, and a 1X FQPA Safety Factor)

.

No quantification of dermal risk is required. Although the dermal toxicity study did not evaluate developmental endpoints, (1) there was no dermal or systemic toxicity observed following repeated dermal appli cations to rabbits at a dose greater than the limit dose (1500 mg/kg/day); (2) there was

no quantitative or qualitative susceptibility observed in the developmental or reproductive toxicity studies; ( 3) although developmental toxicity was observed in the r at, it occurred only at 4000 mg/kg/day, which is 4 times the limit dose, and developmental toxicity was not observed in the rat at the limit dose (1000 mg/kg/day); and (4) developmental toxicity was not observed in the rabbit.

4.5.2 Recommendation for Combining Routes of Exposures for Risk Assessment

In the case of import tolerances with no U.S. registration, there is no potential for domestic residential or occupational exposure. However, fosetyl

- Al is currently registered for use on turf andPage 14 of 23

ornamentals. Therefore, Section 7 details the aggregation of residential and dietary exposure for the appropriate exposure routes

.

4.5.3 Classification of Carcinogenic Potential

Fosetyl

- Al is classified as “not likely to be carcinogenic to humans.” HE D’s Carc inogenicity Peer Review Committee concluded that the effects produced by fosetyl

- Al in rats occurred at extremely high doses, under conditions not anticipated to occur outside of the experimental lab. It was determined that pesticidal use of fosetyl

- Al is unlikely to pose a carcinogenic hazard to humans

. Additionally, no genotoxic potential was observed in the available studies

.

4.5.4 Summary of Toxicological Doses and Endpoints for Fosetyl

- al for Use in Human Health
Risk Assessments

The fosetyl

- Al toxicity profile tables are available in Appendix A of the January, 2014 HED

Human Hea l th Risk Assessment. The toxicity endpoints and points of departure used for risk

assessment purposes are summarized Tables 4.5.4

.

Table 4.5.4 . Summary of Toxicological Doses and Endpoints for Fosetyl

- Al for Use in Dietary and Non

Occupational Human Health Risk Assessments

Exposure/
Scenario Point of

Departure Uncertainty/FQPA

Safety Factors RfD, PAD,

Level of
Concern for
Risk
Assessment Study and Toxicological Effects

Acute Dietary (All populations) No hazard or appropriate acute endpoint was identified in the database. There are no developmental

concerns. HASPOC determined that an ACN is not required (TRX No. 0056809, dated October 29,
2013 ).

Chronic Dietary (All Populations) NOAEL =

250 mg/kg/day UF A 10x

UF H 10x

FQPA SF = 1X cRfD =

2.5mg/kg/day

cPAD = 2.5 mg/kg/day Chronic oral toxicity (dog)

MRID 00098340 ( 1981) LOAEL = 500 mg/kg/day, based on an
increased incidence of testicular degeneration ( spermatocytic and/or spermatidic giant cells in the lumen of the seminiferous tubules)

Dermal (All durations) No potential hazard via the dermal route, based on the lack of systemic effects following repeat

dermal exposure of ra bbi ts at dose levels up to 1 5 00 mg/kg/day, which is greater than the limit dose. The endpoints of concern were all assessed in this study, and there is no developmental or reproductive concern at do se levels that exceed the limit dose.

Incidental Oral (Short

- and
Intermediate

Term) NOAEL =

300 mg/kg/day UF A 10x

UF H 10x

FQPA SF = 1x Residential

LOC for
MOE < 100 3

- generation reproduction (rat)

MR I D 00098352 (1981) LOAEL = 600 mg/kg/day, based on decreased body weight gains in the F2b generation and urinary tract changes in
adultsPage 15 of 23

Table 4.5.4 . Summary of Toxicological Doses and Endpoints for Fosetyl

- Al for Use in Dietary and Non

Occupational Human Health Risk Assessments

Exposure/
Scenario Point of

Departure Uncertainty/FQPA

Safety Factors RfD, PAD,

Level of
Concern for
Risk
Assessment Study and Toxicological Effects

Inhalation (Short

- and
Intermediate

Term) NOAEL =

300 mg/kg/day UF A 10x

UF H 10x

FQPA SF = 1x Residential

LOC for
MOE < 100 3

- generation reproduction (rat)

MRID 00098352 (1981) LOAEL = 600 mg/kg, based on decreased body weight gains in the F2b generation and urinary tract changes in adults. Cancer (oral, dermal, inhalation) Classification: Not likely to pose a carcinogenic hazard to humans

5 Point of Departure (POD) = A data point or an estimated point that is derived from observed dose

- response data and used to mark the beginning of extrapolation to determine risk associated with lower environmentally relevant human exposures. NOAEL = no observed adverse effe ct level. LOAEL = lowest observed adverse effect level. UF = uncertainty factor. UF A = extrapolation from animal to human (interspecies). UF H = potential variation in sensitivity among members of the human population (intraspecies). FQPA SF = FQPA Saf ety Factor. PAD = population adjusted dose (a = acute, c = chronic). RfD = reference dose. MOE = margin of exposure. LOC = level of concern. N/A = not applicable.

5.0 D ietary Exposure and Risk Assessment

The dietary exposure assessment includes contributions from the proposed use in/on imported pepper/eggplant subgroup 8

- 10B plus all registered food uses for fosetyl

- Al. Thus, contributions from drinking water are also included in the dietary risk assessm ent, as described below.

5.1 Metabolite/Degradate Residue Profile

5.1.1 Summary of Plant Metabolism Studies

No plant metabolism studies were submitted with the present petition. Based on studies which were previously submitted, the residue of concern in plants is parent fosetyl

- Al (see Memo, W. Cutchin, D219153, 5/13/96). This conclusion was based on results o f metabolism studies performed on the following commodities: pineapples and grape vines (PP#2F2702, 6/13/83), tomatoes (PP#1F4014, 11/4/91), citrus (PP#5F3267, 9/27/85), and apples (PP#8F3689, 2/21/89). The metabolism of fosetyl

- Al in plants proceeds thro ugh the hydrolytic cleavage of the ester bond. Phosphorous acid is detected as the major metabolite ( See Table 3.1 for additional information )

.

5.1. 2 Summary of Livestock Metabolism Studies

This topic is not relevant to the current petition since there are no livestock feedstuffs from peppers. A ruminant (goat) metabolism study was previously submitted and reviewed in conjunction with PP#8F3689 in/on pome fruit (PP#8F3689, D180622, R.W. Cook, 12/10/93). HED concluded that the nature of fosetyl

- Al in li vestock is adequately understood , with the r esidue of concern identifiedPage 16 of 23

as parent fosetyl

- Al (PP#8F3689, D180622, R.W. Cook, 12/10/93; D198393, M. Nelson, 4/6/94). Furthermore, since detectable residues of fosetyl

- Al are not likely to occur in meat or mi lk,
tolerances for residues in livestock commodities are not required.

5.1. 3 Comparison of Metabolic Pathways

The available data are sufficient to provide an understanding of fosetyl

- Al metabolism by plants,

rats, and ruminants. These data indicate that the primary plant metabolite is phosphorous acid, a chemical which has been exempted from the requirement for a tolerance as listed in 40 CFR § 180.1210. Goat metabolism results in the parent being extensively broken down, with the radioactivity being incorporated into natural products or eliminated through respiration . Similarly, in the rat, fosetyl

- Al is readily absorbed and extensively metabolized to carbon dioxide, which is exhaled. Aluminum does not appear to be absorbed to a significant extent from the gastrointestinal

tract.

5.1

. 4 Residues of Concern Summary and Rationale

The qualitative nature of fosetyl

- Al residues in plants and livestock is understood based on the results of previously submitted metabolism studies. The regulated residue of concern is parent fosetyl

- Al, as summarized in Table 5.1.4

Table 5.1.4. Summary of Metabolites and Degradates to be included in the Risk Asessment and Tolerance Expression

Matrix Residues included in Risk

Assessment Residues included in Tolerance Expression

Plants Fosetyl

- Al Fosetyl

- Al

Livestock Fosetyl

- Al Fosetyl

- Al

Drinking Water Fosetyl

- Al Not Applicable

5.2 Food Residue Profile

Adequate residue chemistry data have been provided to support the requested fosetyl

- Al tolerance for crop subgroup 8

- 10B. Field trials are of adequate number and geographic representation, as trials were conducted in the US, Mexico, and Peru. Data analys es employed validated analytical methods, and suitable enforcement methods are available. There are no processed commodities or livestock feedstuffs associated with peppers. Rotational crop considerations are not relevant to uses
that do not include US r egistrations. The field trial data show that no residues of fosetyl

- Al are found when following the intended use pattern. This finding is consistent with expectation since the foliar applications are restricted to early season uses when the plants are st ill seedlings (no later thanPage 17 of 23

BBCH 17). The late season treatments are limited to soil

- based treatments, where fosetyl

- Al residues are known to degrade quickly. Thus the only residues detected were identified as the phosphorous acid metabolite, which is no t a residue of concern for tolerance enforcement or risk assessment. Although pepper storage stability data were not provided and translation from related crops is not appropriate, because use pattern considerations suggest that no detectable fosetyl

- Al

r esidues are likely at harvest, a pepper storage stability study will not be required at this time. Should the pepper use pattern be changed to permit a late season foliar application, a supporting pepper storage stability study may be required.

5.3 Wat er Profile

EFED has determined that an updated drinking water assessment is not required for fosetyl

- Al (email from J. Lin, EFED to D. Davis, HED dated 9/23/13). There are no monitoring data for fosetyl

- Al; therefore, EFED provided modeled surface and gr oundwater estimated drinking water values. (ID# 0E06090, T. Steeger and J. Breithaupt, 6/8/01). Environmental fate properties suggest that fosetyl

- Al is not likely to reach ground or surface water under most conditions, and if it does
reach surface water , it is expected to degrade rapidly. In the case that fosetyl

- Al reached groundwater, environmental persistence could be a concern. T he Screening Concentration in Ground Water (SCI

- GROW) model estimated a concentration of less than 0.006 parts per billion (ppb) in groundwater. Thus, the estimated drinking water concentration (EDWC) of 0.006 ppb was directly incorporating into the chronic dietary risk assessment.

5. 4 Dietary Risk Assessment

A chronic aggregate dietary food and drinking water exposure and risk assessment was conducted using the Dietary Exposure Evaluation Model software with the Food Commodity Intake Database (DEEM

- FCID) Version 3.1 6. This software uses 2003

- 2008 food consumption data from the U.S. Department of Agriculture’s (USDA’s) National Health and Nutrition Examination Survey, What We Eat in America, (NHANES/WWEIA). Dietary risk assessment incorporates both exposure and toxicity of a given pesticide. For chronic dietary assessments, the risk is expressed as a percentage
of a ma ximum acceptable dose (i.e., the dose which HED has concluded will result in no unreasonable adverse health effects). This dose is referred to as the chronic population adjusted dose ( c PAD). The c PAD is equivalent to the chronic reference dose ( c RfD) div ided by the combined uncertainty factors retained due to missing data or concerns for susceptibility. For chronic exposures, HED is concerned when estimated dietary risk exceeds 100% of the cPAD. The analysis
was conducted in support of an import use of fosetyl

- aluminum (fosetyl

- Al) in/ on crop subgroup 8

- 10B (pepper/eggplant subgroup) and included all registered uses of fosetyl

- Al.

No acute dietary exposure and risk analysis was performed since there were no appropriate studies
that demonstrated evidenc e of toxicity attributable to a single dose for either the general population
or for f emales 13

- 49 years of age. Similarly, no cancer dietary exposure assessment was conducted because fosetyl

- Al is considered “ n ot likely to be carcinogenic to humans .”

5. 4 .1 Description of Residue Dat a Used in Dietary AssessmentPage 18 of 23

The unrefined chronic analysis is based on tolerance

- level residues and 100% crop treated (%CT) assumptions. Default processing factors were used for all crops except for citrus where processing studies showed no residue concentration; thus, the processing factor was set to one for processed
citrus commodities.

5.4.2 Chronic Dietary Risk Assessment

A screening level chronic dietary (food and drinking water ) exposure analysis was performed for the general U.S. population and various population subgroups. Chronic dietary risk estimates are not of concern for the general U.S. population or other population subgroups. The estimated non

- cancer chronic dietary (food only) risk is equivalent to 3.6 % of the chronic population adjusted dose (cPAD) for the general U.S. population. The most highly exposed subpopulation is children 1

- 2 years old , with an estimated risk level of 12 % of the cPAD. A summary of the chro nic dietary risk estimates is provided in Table 5. 4

. 2

.

Table 5. 4

. 2

. Summary of Estimated Dietary (Food + Drinking Water) Exposures and Risk for Fosetyl

- Aluminium

Population Subgroup cPAD, mg/kg/day Chronic Estimates

Dietary Exposure (mg/kg/day) % cPAD U.S. Population

2.5 0.090 623 3.6 All infants (< 1 year old) 0.1240 45 5.0

Children 1

- 2 yrs old* 0.2891 12 12
Children 3

- 5 yrs old 0.205 470 8.2

Children 6

- 12 yrs old 0.1063 13 4.3

Youth 13

- 19 yrs old 0.0620 27 2.5

Adults 20

- 49 yrs old 0.0740 41 3.0

Adults 50

- 99 yrs old 0.082 512 3.3

Females 13

- 49 yrs old 0.0787 45 3. 1 *The subpopulation with the highest risk estimates

.

6.0 R esidential (Non

- Occupational) Exposure/Risk Characterization There are currently registered use patterns of fosetyl

- Al that may result in residential exposure. The January 2014 risk assessment provides a complete overview of residential handler and residential post

- application exposure. The residential handler assessment quantitatively evaluated inhalation expos ure and no dermal point of departure was identified because there were no systemic
effects observed 2 and no developmental or reproductive concerns were identified at dose levels that
exceed the limit dose. All the MOEs for residential handlers greatly exce ed the target MOE of 100
and are therefore not of concern.

There is the potential for short

- term post

- application exposure for individuals exposed as a result of being in an environment that has been previously treated with fosetyl

- al (based on contact with

2 No potential hazard via the dermal route, based on the lack of systemic effects following repeat dermal exposure of

ra bbi ts at dose levels up to 1 5 00 mg/kg/day, which is greater than the limit dose.Page 19 of 23

treated turf at the maximum turf application rate of 17.6 lbs ai/A)

. No risk concerns were identified with incidental oral MOEs all exceeding the LOC of 100.

Residential post

- application exposure was also assessed based on contact with treated turf a t the maximum turf application rate of 17.6 lbs ai/A. Only incidental oral exposure is quantitatively
assessed because no dermal hazard was identified. No risk concerns were identified with incidental oral MOEs all exceeding the LOC of 100.

Based on the r esidential exposure assessment, Table 6 identifies the residential risk estimates for use in the aggregate assessment. These scenarios include:

 The recommended residential exposure for use in the adult aggregate assessment reflects
inhalation exposure from the hose end sprayer for turf applications.

 The recommended residential exp osure for use in the children 1 to < 2 years old aggregate
assessment reflects incidental oral exposure from post

- application exposure to treated turf.

1 Residential Handler Dose = the highest handler dose for each applicable lifestage of all residential handler scenarios assessed . Total =

dermal + inhalation (where applicable)

. 2 Total Residential Exposure = the dose associated with the highest residentia l handler doses

. 3 Residential Post

- application Dose = the highest post

- application dose for each applicable lifestage of all post

- application scenarios assessed

.

Total = dermal + inhalation + incidental oral (where applicable).
4 Residential Post

- application MOE = the MOEs associated with the highest post

- application doses . Total = Dermal MOE + Inhalation MOE

+ Incidental Oral MOE (where applicable).

7.0 A ggregate Exposure/Risk Characterization

In accordance with the FQPA, HED must aggregate (add) pesticide exposures and risks from three major sources: food, drinking water, and residential exposures. In an aggregate assessment, exposures from relevant sources are added together and compared to quantitative estimates of hazard ( e.g., a NOAEL or PAD), or the risks themselves can be aggregated. When aggregating exposures and risks from various sources, HED considers both the route and duration of exposure. Fosetyl

- Al is registered for use in residential settings as well as for us e on food (both domestic uses and the proposed establishment of a tolerance without a U.S. registration) ; therefore, an aggregate risk was conducted which combined average food residues with non

- occupational estimates of exposure.

7.1 Acute Aggregate Risk Table 6: Short

- and Interme diate

- Term Residential Exposures for the F osetyl

- Al Combined
Residential Risk Calculations

Population Handler Exposure

(mg/kg/day) 1 Residential

Handler Total Exposure (mg/kg/day) 2 Postapplication

Exposure (mg/kg/day) 3 Residential Postapplication
Total Exposure (mg/kg/day) 4 Dermal Inhalation Derm
al Inhalation Oral

Short

- Term
Adult Male N/A 0.0024 0.0024 N/A N/A N/A N/A

Adult Female N/A 0.0024 0.0024 N/A N/A N/A N/A

Children 1 to < 2 years old N/A N/A N/A N/A N/A 0.268 0.268Page 20 of 23

An acute aggregate assessment was not conducted because an endpoint attributable to a single dose
was not identified from the available data for f osetyl

- A l

.

7.2 Short

- Term Aggregate Risk

Short

- term aggregate assessments include exposures of one to thirty d ays duration, and aggregate the most protective short

- term residential exposure scenarios with average food and water exposures

. The exposure scenario used for adults was the adult residential handler applying liquid concentrates
to turf via hose

- end spra yer . For children, the appropriate scenario was incidental oral post

application exposure from contacting treated lawns . Table 7.2.1 presents t he short

- term aggregate risk estimates which were not of concern for adults or children.

Table 7.2.1 Short

- Term Aggregate Risk Calculations

Population Short

- Term Scenario

NOAEL mg/kg/d

ay LOC 1 Max

Allowable Exposure 2 mg/kg/day Average

Food and
Water Exposure mg/kg/day Residential

Exposure mg/kg/day 3 Total

Exposure mg/kg/day 4 Aggregate

MOE (food, water, and residential) 5

Adult Male

300 100 3 0.0 90623 0.0024 0. 0930 3

, 2 00
Adult Female 0.0 90623 0.0024 0.0930 3

, 2 00 Child ( 1

- < 2y r) 0. 289112 0.268 0.557112 540

1 For LOC calculation a 10x standard inter

- species, 10x intra

- species and 1× FPQA uncertainty factors are included.

2 Maximum Allowable Exposure (mg/kg/day) = NOAEL/LOC

3 Residential Exposure = [Oral exposure + Dermal exposure + Inhalation Exposure (as ap plicable) ]. Values from Table 6

4 Total Exposure = Avg Food & Water Exposure + Residential Exposure)

5 Aggregate MOE = [NOAEL / (Avg Food & Water Exposure + Residential Exposure)]

7.3 Intermediate

- Term Aggregate Risk

Intermediate

- term exposures to fosetyl

- al are not likely because of the intermittent nature of applications by homeowners

.

7.4 C hronic Aggregate Risk

Chronic or long

- term aggregate assessments include exposures that will exceed six (6) months.
Since there are no chronic non

- occupat ional (residential) exposures, the chronic aggregate assessment only includes food and drinking water exposures. Refer to section 5.4. 2 for a detailed discussion of the chronic dietary assessment.

7.5 Cancer Aggregate Risk

HED has classified fosetyl

- al as “ not likely to be carcinogenic to humans” ; no quantification of cancer risks is required.Page 21 of 23

8 .0 C umulative Exposure/Risk Characterization

Although fosetyl

- Al shares a similar chemical structure with many OPs, there is no evidence of neurotoxicity or evidenc e of cholinesterase inhibition following exposure to fosetyl

- Al at dose levels at and greater than the limit dose. EPA has concluded that fosetyl

– Al is a member of the OP cumulative group. For information regarding EPA’s efforts to determine which chemica ls have a common mechanism of toxicity and to evaluate the cumulative effects of such chemicals, see the policy statements released by EPA’s Office of Pesticide Programs concerning common mechanism determinations and procedures for cumulating effects from substances found to have a common
mechanism on EPA’s website 3

.

9.0 O ccupational Exposure/Risk Characterization

There are no new domestic agricultural or occupational applications associated with this action.

10 .0 R eferences

Fosetyl

- Aluminum [Fosetyl

- Al]

. Petition for the Establishment of Permanent Tolerances for Residues in/on Pepper/Eggplant Subgroup 8

- 10B and Dried Chili Pepper, Without a U.S. Registration. Sum mary of Analytical Chemistry and Residue Data ; W. Donovan , D4 18702 ; 29

- APR

- 201 4.

Fosetyl

- Aluminum: Chronic Aggregate Dietary (Food and Drinking Water) Exposure and Risk Assessments for the Pepper/eggplant Subgroup 8

- 10B Import Tolerance. W. Donovan ; D41 8703 ; 26

- MAR

- 2014.

NAFTA Guidance Document on Data Requirements for Tolerance s on Imported Commodities in the United States and Canada; December 2005; US Environmental Protection Agency Office of Pesticide Programs and Health Canada Pest Management Regulatory Agency.

Fosetyl

- Aluminum: Registration Review Preliminary Risk Assessment; D. Davis, M. Lloyd, and L.Taylor; D416436; 23

- JAN

- 2014.

3 http://www.epa.gov/pesticides/cumulative/.Page 22 of 23

Appendix A . Physical/Chemical Characteristics

TABLE A

. Physicochemical Properties of Fosetyl

- Al

. Parameter Value Reference

Melting point/range 215 °C

MRID 49072901 pH 3.1 @ 25 °C

Density (g/cm 3 ) (20°C) 1.529

Water solubility (20°C) 111 g/L (pH 6)

Solvent solubility (at 20 °C) Solvent Solubility (mg/L)
Methanol 807
Acetone 6 Ethyl acetate <1
Acetonitrile 1
Dichloromethane 4

N

- octanol 10 Xylene 1

Vapor pressure > 10

- 7 Pa
Dissociation constant (pK a ) 4.7 ( Al 3+ <

-- >AlOH 2+ )
Octanol/water partition coefficient, Log (K ow ) - 2.11 (22  C)

UV/Visible Absorption Spectrum No significant absorption at wavelengths 190

– 800 nmPage 23 of 23

Appendix B : Review of Human Research

This risk assessment did not rel y on data from studies in which adult human subjects were intentionally exposed to a pesticide or other chemical.

Appendix C

. International Residue Limits Table

Table C

. Summary of US and International Tolerances and Maximum Residue Limits for Fosetyl

- Aluminum (123301) Residue Definition :
US Canada Mexico 2 Codex

40 CFR 180.415:
Plant: aluminum tris ( O

ethylphosphonate) aluminum tris( O

ethylphosphonate) None

Commodity 1 Tolerance (ppm) /Maximum Residue Limit (mg/kg)

US Canada Mexico 2 Codex
Pepper/eggplant subgroup 8

- 10B 0.01

Completed: M. Negussie; 02/28/14

1 Includes only commodities of interest for this action. Tolerance values should be the HED recommendations and not those proposed by the applicant.

2 Mexico adopts US tolerances and/or Codex MRLs for its export purposes.