,-~~, ... 8

tosr4,.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 the 

Establishment 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 

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

TXRNo.: NA CAS No.: 39148-24-8 

MRIDNo.: NA 40 CFR: 180.415 

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 /VII) 

Health Effects Division (7509P) 

Alexandra LaMay, Chemis~l ~ ~ Michael Metzger, Chief / · 

Risk Assessment Branches & 7 (RABV /VI 

Health Effects Division (7509P) 

Marcel Howard (RM20) 

Shaja Joyner (RM20) 

Fungicide Branch 

Registration Division (7505P) 

This document provides the Health Effects Division's (HED's) risk assessment conducted for the 

request for tolerances with no U.S. registration for Fosetyl-al: pepper/eggplant, subgroup 8-lOB and 

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

Page 1 of23 
Page 2 of 23

Table of Contents

1.0 Executive Summary............................................................................................................. 4

2.0 HED Recommendations....................................................................................................... 5

2.1 Data 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........................................................ 16
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5.2 Food Residue Profile...................................................................................................... 16

5.3 Water Profile............................................................................................................... 17

5.4 Dietary 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 ........................................................................ 23
Page 4 of 23

1.0 Executive 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 for 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 recent comprehensive human-health risk assessment for fosetyl-Al was prepared in 

January, 2014, and there have been no updates to the toxicological or exposure databases 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 Hazard and Science Policy Council (HASPOC) concluded 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). 

Fosetyl Al is rapidly metabolized following oral exposure and widely distributed, and it is primarily 

excreted via the respiratory route (as CO2) and in the urine, mainly as phosphorous acid. The major 

target organs following 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 (histopathological changes in the kidney, 

impairment of calcium/phosphorus metabolism, calculi and hyperplasia 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 except 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 eye 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 provided to the National Pesticide Standard Repository. An 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 was no toxicity attributable to 
Page 5 of 23

a single dose for either the general population or for females 13-49 years of age. Similarly, no 

cancer dietary exposure assessment was conducted because fosetyl-Al is considered “not likely to be 

carcinogenic to humans.”

Conservative screening level chronic dietary 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). Chronic dietary risk estimates are below the level of concern (LOC) for 

all population 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 risk 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 Recommendations

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

residues of fosetyl-Aluminum in/on pepper/eggplant subgroup 8-10B at 0.01 ppm.

2.1 Data Deficiencies

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. Extracted 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 extraction solvent as Method 
Page 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 methods 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 fosetyl-Al.

2.2.2 Analytical Reference Standard

The analytical 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 reference standard should be provided to

the Repository 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 Cole 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 Tolerances

There 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),

including 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 Tolerances
Page 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 MRL and U.S. tolerance level for crop subgroup 8-

10B.

2.3 Label Recommendations

None.

3.0 Introduction

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 registered 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, 20141and there have been no updates to the toxicological or exposure data base outside the 

proposal for tolerances in/on pepper/eggplant subgroup 8-10B.

3.1 Chemical Identity

The chemical structure and nomenclature of fosetyl-Al and the metabolite phosphorous acid is

presented in Table 3.1. 

 

1 D. Davis et al; Fosetyl-Aluminum: Registration Review Preliminary Risk Assessment PC Code: 123301; D416436
Page 8 of 23

TABLE 3.1. Nomenclature of Fosetyl-Al and Phosphorous Acid.

Compound Chemical Structure

Al

3

C2H5O P

H

O

O

Common name Fosetyl-Aluminum or Fosetyl-Al Phosphorous Acid

Company experimental names Not applicable Not applicable

IUPAC name Aluminum tris (O-ethylphosphonate) Phosphonic acid

CAS name Aluminum tris (O-ethylphosphonate) Phosphonic 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 dichloromethane. Based on the Log KOW, 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, translations of the Previcur® Energy labels from 

Mexico and Peru were provided. The overall use pattern specified by these labels is consistent with 

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 registered 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 evaluating 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 Energy 840 SL/Previcur Energy: 310 g FAL/L + 530 g PHY/L (Mexican Label)

Chili

Seedling treatment 

in trays or nurseries 

(green house), 20 

days post seed 

planting (or when 

trays are extended)

Up to 

3

FAL: 0.31-0.62 g 

a.i./1L water 

PHY: 0.53-1.1 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 kg 

a.i./ha

14 50-100 

ml/plant

FAL: 2.8 kg 

a.i./ha 

PHY: 4.8 kg 

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 risk 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-established 
Page 10 of 23

procedures. In line with OPP policy, HED estimates risks to population 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 United States Department of Agriculture (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 food 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 circumstances 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 

patterns 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 spermatidic 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 

assessment. 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-toroute extrapolation. A 100X uncertainty factor was applied to account for inter- and intra-species 
Page 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)

Fosetyl Al is rapidly metabolized following oral exposure and widely distributed, and it is primarily 

excreted via the respiratory route (as CO2) and in the urine, mainly as phosphorous acid.

4.3 Toxicological Effects

The major target organs following 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 (histopathological 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 showed 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 appropriate 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 developmental 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 underestimate risk. Further 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 study, 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 decreased 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 in 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 with regard to dietary (food and water) or residential exposures. 

The food exposure assessments are based on high-end tolerance residue levels (that account for the 

parent compound) and conservative water modeling results. Actual risks from exposure to fosetylAl 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 Appendix 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 developmental 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 and/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 factor 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 reproduction study in rats with a NOAEL of 300 mg/kg/day. At the LOAEL of 600 

mg/kg/day, decreased body weight gains in the F2b generation and urinary tract changes in adults

were observed. A 10X uncertainty factor was applied (10X to account for inter- species variability, 

10X to account for intra-species 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 applications 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 rat, 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 and 
Page 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.” HED’s Carcinogenicity 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 Health 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 NonOccupational 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

UFA 10x

UFH 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 rabbits at dose levels up to 1500 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 dose levels that exceed the limit dose.

Incidental Oral

(Short- and 

IntermediateTerm)

NOAEL = 

300 

mg/kg/day

UFA 10x

UFH 10x

FQPA SF = 1x

Residential

LOC for

MOE < 100

3-generation reproduction (rat)

MRID 00098352 (1981)

LOAEL = 600 mg/kg/day, based on 

decreased body weight gains in the F2b 

generation and urinary tract changes in 

adults
Page 15 of 23

Table 4.5.4. Summary of Toxicological Doses and Endpoints for Fosetyl-Al for Use in Dietary and NonOccupational 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 

IntermediateTerm) 

NOAEL = 

300 

mg/kg/day

UFA 10x

UFH 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 effect level. LOAEL = lowest observed adverse effect level. 

UF = uncertainty factor. UFA = extrapolation from animal to human (interspecies). UFH = potential variation in 

sensitivity among members of the human population (intraspecies). FQPA SF = FQPA Safety 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 Dietary 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 assessment, 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 of 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 through 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 livestock is adequately understood, with the residue of concern identified 
Page 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 milk, 

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 analyses 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 registrations. 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 still seedlings (no later than 
Page 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 not 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 

residues 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 Water 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 groundwater 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. The 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 3.16. 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 maximum 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 

(cPAD). The cPAD is equivalent to the chronic reference dose (cRfD) divided 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 evidence of toxicity attributable to a single dose for either the general population 

or for females 13-49 years of age. Similarly, no cancer dietary exposure assessment was conducted 

because fosetyl-Al is considered “not likely to be carcinogenic to humans.”

5.4.1 Description of Residue Data Used in Dietary Assessment
Page 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 chronic 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

0.090623 3.6

All infants (< 1 year old) 0.124045 5.0

Children 1-2 yrs old* 0.289112 12

Children 3-5 yrs old 0.205470 8.2

Children 6-12 yrs old 0.106313 4.3

Youth 13-19 yrs old 0.062027 2.5

Adults 20-49 yrs old 0.074041 3.0

Adults 50-99 yrs old 0.082512 3.3

Females 13-49 yrs old 0.078745 3.1

*The subpopulation with the highest risk estimates.

6.0 Residential (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 exposure and no dermal point of departure was identified because there were no systemic 

effects observed2and no developmental or reproductive concerns were identified at dose levels that 

exceed the limit dose. All the MOEs for residential handlers greatly exceed 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 

rabbits at dose levels up to 1500 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 at 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 residential 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 exposure 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 residential 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 Aggregate 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 use 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 Intermediate-Term Residential Exposures for the Fosetyl-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) Dermal 4

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 0.268
Page 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 fosetyl-Al.

7.2 Short-Term Aggregate Risk

Short-term aggregate assessments include exposures of one to thirty days 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 sprayer. For children, the appropriate scenario was incidental oral postapplication exposure from contacting treated lawns. Table 7.2.1 presents the 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

LOC1

Max 

Allowable 

Exposure2

mg/kg/day

Average 

Food and 

Water 

Exposure 

mg/kg/day

Residential 

Exposure 

mg/kg/day3

Total 

Exposure 

mg/kg/day4

Aggregate 

MOE (food, 

water, and 

residential)5

Adult Male

300 100 3

0.090623 0.0024 0.0930 3,200

Adult Female 0.090623 0.0024 0.0930 3,200

Child (1-<2yr) 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 applicable)]. 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 Chronic Aggregate Risk

Chronic or long-term aggregate assessments include exposures that will exceed six (6) months. 

Since there are no chronic non-occupational (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 Cumulative Exposure/Risk Characterization

Although fosetyl-Al shares a similar chemical structure with many OPs, there is no evidence of 

neurotoxicity or evidence 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 chemicals 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 website3.

9.0 Occupational Exposure/Risk Characterization

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

10.0 References

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. Summary of Analytical Chemistry and Residue Data; W. Donovan, D418702; 29-

APR-2014.

Fosetyl-Aluminum: Chronic Aggregate Dietary (Food and Drinking Water) Exposure and Risk 

Assessments for the Pepper/eggplant Subgroup 8-10B Import Tolerance. W. Donovan; D418703; 

26-MAR-2014.

NAFTA Guidance Document on Data Requirements for Tolerances 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/cm3) (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 (pKa) 4.7 (Al3+ < -- >AlOH2+)

Octanol/water partition coefficient, Log 

(Kow)

-2.11 (22 C)

UV/Visible Absorption Spectrum No significant absorption at wavelengths 190 –

800 nm
Page 23 of 23

Appendix B: Review of Human Research

This risk assessment did not rely 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 Mexico2 Codex

40 CFR 180.415:

Plant: aluminum tris (Oethylphosphonate) 

aluminum tris(Oethylphosphonate)None

Commodity1 Tolerance (ppm) /Maximum Residue Limit (mg/kg)

US Canada Mexico2 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.