### 1123/14 UNITED STATES ENVIRONMENTAL PROTECTION AGENCY

WASHING T ON

, D.C. 2 0460

O F FICE OF CHEM I CA L SAFETY

AND POLLUT I ON PREVENTION



### MEMORANDUM

SUB J ECT: 

### Fosetyi-Aiuminum: Regis t ration Review Preliminary Risk Assessment

PC Code: 12330 1 ; 0 416436



### PC Code: 123301


### Decision Nos. : 485 4 42


### Petition Nos.: NA 

### DP Barcodes: 416436 

### Registration Nos.: NA 

### Regulatory Action: Regis t ration Review



### Case No.: 0646

- 1 

### Risk Assessment Type: Sing l e Chemical Aggregate



### TXRNo.: NA 

### CAS No. : 39 1 48-24-8


### 40 CFR: 180.415 

### MRIDNo

. : NA

FROM:

THROUGH :

T O : DonnaS. Davis, Chemist & 

### Risk Assesso

Matthew Lloyd, CIH,

# Indu**rial** Hyg· nis t 

# i.-/.**tw_7 _**  Linda T ay l o r
, Toxicolog i st

## ~A-~C- Registra t ion Assessment B ch V II

H eat h Effects Div i sion (7509P)

Alexandra LaMay, Bio l ogis t

# ~~ MichaelS. Metzger, Branch Ch i ef Registration Assessment Branch

Healt h Effects D iv i sion (7509P)

Kelly Ba ll ard, Chemical Review Manager

Neil Anderson, Chief

Risk Managemen t and Implementation Branch I

Pesticide R e

- eva l uation D i vision (7508P)



## Attached please find t he Heal t h Effec t s Division's Preliminary Risk Assessment (PRA) fo r the

act i ve i n g r edient, fosetyl-Alum i num

.

Page 1 of36

### Page 2 of 36

EXECUTIVE SUMMARY

The Health Effects Division ( HED ) has evaluated the current databases for the active ingredient fosetyl

- aluminum ( fosetyl

- Al ) to support the registration re view of this active ingredient. Fosetyl

- Al is a systemic fungicide which is effective against diseases caused by the Oomycetes (phytophthora and downy mildews). It is registered for foliar use by ground and air application to a wide range of agricultural crops and for root dip, bark injection, and citrus trunk painting, as well as for use on pea as a seed treatment. Fosetyl

- Al is also registered for use on ornamental plants in residential areas

, and is registered for use on turf grass on golf courses, an d commercial turf areas where residential post application exposure may occur. The only new data considered in this assessment was a previously unreviewed succulent pea storage stability study. That study is scientifically acceptable and adequate to addre ss the standing storage stability data gap. No change to the current succulent pea tolerance is required based on these data. The toxicity, residue chemistry, and occupational/residential exposure databases are considered complete at

this time. The haza rd and exposure profiles for this active ingredient are adequately understood. There are no dietary (food and water), residential, aggregate

, or occupational risks of concern associated with fosetyl

- Al.

Regulatory Recommendation

There are no human health risks of concern identified for fosetyl

- Al.

HED has evaluated the current tolerances established for fosetyl

- Al and recommends the following revisions to the 40CFR 180.415 to harmonize with established international tolerances

and to reflect the most u pdated crop grouping definitions:

 The current caneberry subgroup 13A tolerance at 0.1 ppm should be replaced with a

tolerance for the caneberry subgroup 13

- 07A . HED recommends that the tolerance level for the crop group be reduced to 0.05 ppm to harmoniz e with Canadian MRLs and address U.S./Canadian grower priority for blueberries.

 The current bushberry subgroup 13B tolerance at 40 ppm should be replaced with bushberry subgroup 13

- 07B tolerance at 40 ppm.

 The current citrus fruit group 10 tolerance of 5.0 ppm should be replaced with a citrus fruit group 10

- 10 tolerance. HED has no objection to raising the tolerance from its current level of 5.0 ppm to 9 ppm to harmonize with the Canadian MRL.

 The current pome fruit group 11 tolerance of 10 ppm sh ould be replaced with a pome fruit group 11

- 10 tolerance at 10 ppm.

 Reduce the current ginseng tolerance of 0.1 ppm to 0.05 ppm to harmonize with the

Canadian MRL.

HED has evaluated the appropriate restricted en try interval (REI) for fosetyl

- A l and makes the following recommend revision to the product labels:

### Page 3 of 36

 Existing product labels should be amended to reflect a 48

- hour REI. Technical fosetyl

- Al falls into Toxicity Category I for primary eye irritation. Per the Worker Protection Standard (WPS), a 48

- ho ur REI is required for chemicals classified under Toxicity Category I.

For the seed treatment use (SLN ID

- 30001), HED recommends adding the appropriate seed treatment language. The labeling should state: Seed that has been treated with this product tha t is then packaged or bagged for future use must contain the following labeling on the outs ide of the seed package or bag:

"Treated Seed

- Do Not Use f or Food, Feed, or Oil Purposes. When opening this bag or loading/pouring the treated seed, wear a long

- s leeved shirt, long pants, shoes, socks, and chemical resistant gloves. After the seeds have been planted, do not enter or allow worker entry into treated areas during the

restricted

- entry interval (REI) of 48 hours. Exception: Once the seeds are planted

i n soil or other planting media, the Worker Protection Standard allows workers to

enter the treated area without restriction if there will be no worker contact with

the treated seeds in the soil or planting media."

INTRODUCTION

Fosetyl

- Al is a systemic fungicide which is effective against diseases caused by the Oomycetes (phytophthora and downy mildews ). The fungicide is currently registered for use on a wide variety of agricultural crops and on ornamental plants and turf.

The most rec ent comprehensive human health risk assessment s for fosetyl

- Al were developed to

support new uses on turnips, succulent peas, citrus fruit group, leeks, green onions and the bushberry subgroup ( D279163, M. Rust, 5/17/01). In 2007, HED completed a Scoping

D ocument that evaluated the available data and risk assessments for fosetyl

- Al (D340101, D. Davis, 8/15/07) and concluded that no new data were needed to support the registration review o f this active ingredient. The Sco ping D ocument did note that succulent pea storage stability data had been submitted to HED. This data needed review and the adequacy of the current succulent pea tolerance needed evaluation under registration review. These needs have been addressed in

th is risk assessment.

HAZARD CONSIDERATION S

No new toxicity and/or rat metabolism data have been received since the last risk assessment and scoping document were complete d . Neither of those documents identified any data deficiencies with respect to to xicology. However, based on the current 40 CFR Part 158 data requirements, an immunotoxicity study, a subchronic inhalation toxicity study, and acute and subchronic neurotoxicity studies may now be required for fosetyl

- Al

. As part of developing a prelimi nary risk assessment during registration review, t he Hazard and Science Policy Council (HASPOC)

reviewed the database for fosetyl

- Al and concluded that these studies are not required. (TXR

### Page 4 of 36

No. 0056809

, dated October 29, 2013 ). Consequently there have be en no changes to the toxicological endpoints and safety factors/uncertainty factors for human health risk assessment

from the most recent assessment referenced above.

The toxicological database for fosetyl

- Al is considered complete for characterization of potential developmental, reproductive, carcinogenetic, mutagenic, neurotoxic, and immunotoxic effects.

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 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 (cla ssified as not likely to pose a carcinogenic hazard 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 fosetyl

- Al toxicity profile tables are included in this memo in Appendix A. The toxicity endpoints for risk assessment are shown in Tables 1 and 2.

Table 1 . Summary of Toxicological Doses and Endpoints for Fosetyl

- Al for Use in Dietary and Non

Occupational Hum an 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 dose levels that exceed the limit dose.

### Page 5 of 36

Table 1 . Summary of Toxicological Doses and Endpoints for Fosetyl

- Al for Use in Dietary and Non

Occupational Hum an Health Risk Assessments

Exposure/

Scenario Point of

Departure Uncertainty/FQPA

Safety Factors RfD, PAD,

Level of

Concern for

Risk

Assessment Study and Toxicological Effects

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)

MROD 00098352 (1981) LOAEL = 600 mg/kg/day, based on decreased body weight gains in the F2b generation and urinary tract changes in

adults

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.

Inhalation Long

- Term (> 6 months) NOAEL =

250 mg/kg/day UF A 10x

UF H 10x

FQPA SF = 1x Residential

LOC for

MOE < 100 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) Cancer (oral, dermal, inhalation) Classification: Not likely to pose a carcinogenic hazard to humans

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. U F = 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 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.

Table 2. Summary of Toxicological Doses and Endpoints for Fosetyl

- Al for Use in Occupational Human

Health Risk Assessments

Exposure/

Scenario Point of

Departure Uncertainty

Factors Level of Concern

for Risk

Assessment Study and Toxicological Effects

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 dose levels that do not exceed the limit dose.

Inhalation (Short

- and

Intermediate

Term ) NOAEL =

300 mg/kg/day UF A 10x

UF H 10x

FQPA SF =

1x Occupational

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 trac t changes in adults.

### Page 6 of 36

Table 2. Summary of Toxicological Doses and Endpoints for Fosetyl

- Al for Use in Occupational Human

Health Risk Assessments

Exposure/

Scenario Point of

Departure Uncertainty

Factors Level of Concern

for Risk

Assessment Study and Toxicological Effects

Inhalation Long

- Term (> 6 months) NOAEL =

250 mg/kg/day UF A 10x

UF H 10x

FQPA SF =

1x Residential LOC

for MOE < 100 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) Cancer (oral, dermal, inhalation) Classification : Not likely to pose a carcinogenic hazard to humans

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 o bserved 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). MOE = margin of exposure. LOC = level of

c oncern.



### RESIDUE CHEMISTRY CONSIDERATIONS

Fosetyl

- Al is registered on a wide variety of agricultural crops including: avocado; banana; blueberry; bushberries; caneberries; cranberry; citrus fruits; pome fruits; ginseng; hops; juneberry; leafy vegetable s; lingonberry; macadamia nuts; green and dry bulb onions; succulent peas; pineapple; salal; strawberry; tomato; turnip; cucurbits; and tobacco. Additionally, fosetyl

Al is regionally registered application on asparagus, avocado, strawberry, almond, walnu ts, pome fruit and hops, as well as for use as a bark injection on citrus and for use on pea seed. Formulations include wettable powder, water dispersible granules, emulsifiable concentrate and ready

- to

- use liquid. Typical application is multiple foliar applications of up to 4.0 lbs ai/A/application for seasonal totals ranging from 16 to 28 lbs ai/A with pre

- harvest intervals ( PHIs ) ranging from 60 days to 0 days.

The most recent residue chemistry reviews for fosetyl

- Al were developed to support new us es on turnips, succulent peas, and citrus (D272047, A. Acierto, 2/28/02), leeks and green onions (D279385, A. Acierto, 2/21/02) and on tobacco (D277604, N. Dodd, 8/2/05). No new residue chemistry data have submitted subsequen t to issuance of the HED Scopi ng D ocument in 2007. At the time of the scoping document, HED considered the residue chemistry database complete, but noted that succulent pea storage stability data submitted to the Agency should be reviewed to support the registration review of fosetyl

- Al

. The structure of fosetyl

- Al and the physical/chemical properties are contained in Appendix B, Table B1.

HED reviewed the submitted succulent pea storage stability data ( 45820301.der.doc, D. Davis,

1/16/14 ). The study was found to be scientifically a cceptable. Adequate documentation of the field and analytical phases of the study was provided. The storage stability period adequately reflects the duration of frozen storage of the original succulent pea field trial samples (MRID No.

45224702 )

. The data indicate that residues of fosetyl

- Al are not stable in pea seed stored at ≤

-

### Page 7 of 36

20°C for more than 30 days. After 90 days of frozen storage, residues in pea seed had declined by 41%.

HED considered the previously submitted succulent pea field trial data (MRID No. 45224702, D272047, A. Acierto, 2/28/02) in light of the new sto rage stability data to determine if the current succulent pea tolerance is adequate. Residues in pea samples from field trials (average of replicates) ranged from <0.05 ppm to 0.16 ppm. The residue data were developed using the maximum application rate, minimum retreatment intervals and minimum PHI . All pea samples

were stored for less than 90 days, the period of the submitted storage stability study. When the

maximum residue seen in the field trials was corrected for potential loss due to frozen storage,

the correct ed residue did not exceed th e current tolerance of 0.3 ppm. Furthermore, most of the

corrected residues from were significantly lower than the maximum residue val ue from the study. Therefore, HED concludes that the current tolerance for succulent pea is adequate and the tolerance may remain at 0.3 ppm, a value which is harmonized with the current Canadian MRL.

T he residue chemistry database is adequate to suppor t the registration review of the currently registered uses for fosetyl

- Al . Findings with respect to residue chemistry have not changed from the most recent residue chemistry summary documents. The nature and magnitude of the residue in plants, livestock and rotated crops is adequately understood . Adequate data have been provided on processed commodities

. A nalytical methods and reference standards are available to support the established tolerances.

INTERNATIONAL HARMONIZATION /TOLERANCE CONSIDERATION S

International Harmonization The International Residue Limits Status Sheet is attached to this memorandum in Appendix B.

There are no Codex MRLs for fosetyl

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

- Al based on the same tolerance expression. Actual tolerance/MRL values are harmonized for all crops with the exception of the following:

 Blackberries, loganberries, raspberries, wild raspberries. PMRA has established MRLs of 0.05 ppm for these crops; the U .S. has established a crop subgroup tolerance which includes these commodities at 0.1 ppm.

Blackberries have been identified as a US/Canadian grower priority; consequently, HED reviewed the available data used to support the original caneberry tolerance (MRID No. 4074701, M. Nelson, 4/19/89). All caneberry residues were less than the method limit of quantitation (<LOQ) of 0.05 ppm. Therefore, HED has no objection to lowering the U.S. tolerance for caneberry to 0.05 ppm in order to allow harmonization fo r all caneberries, including

black berries

.

 Citrus fruit crop group. PMRA has established an MRL of 9 ppm while the U

. S

. has a crop group tolerance of 5.0 ppm.

HED has no objection to increasing the tolerance on the citrus fruit crop group to 9 ppm in o rder

### Page 8 of 36

to harmonize tolerance/MRL levels with Canada. The increase is considered to be appropriate for international harmonization, but will have no impact on U.S. dietary exposure since the field trial data reflecting the maximum label application rate and a 0

- day PHI (D272047, A. Acierto, 2/28/02) are well below the current tolerance of 5.0 ppm and would not be expected to increase based solely on the increase in a tolerance level.

 Apples. PMRA has established an MRL of 1 for apples; the US has a pome fruit crop group tolerance, which includes apples at 10 ppm.

Residue data submitted to support the current U.S. tolerance include samples with residues in excess of the 1 ppm MRL established in Canada (PP8F3689, R. Cook, 2/21/89). Since residues

from the currently registered use are likely to exceed the Canadian MRL, harmonization is not possible at this time.

 Ginseng. PMRA has a ginseng root tolerance of 0.05 ppm, the U.S. has a ginseng

toler an ce of 0.1 ppm.

HED has reviewed the available residue data for ginseng. All ginseng residues were <LOQ of 0.05 ppm (1E3948, M. Nelson, 11/19/91). Therefore, HED has no objection to lowering the U.S. tolerance for ginseng to 0.05 ppm in order to allow harmonization with Canadian ginseng MRL.

Crop Group/Subgr oup Updates In order to update the 40 CFR to reflect the most recent crop grouping scheme, HED recommends the following crop group/subgroup revisions:

 The current caneberry subgroup 13A tolerance at 0.1 ppm should be replaced with a

tolerance for the cane berry subgroup 13

- 07A . HED recommends that the tolerance level for the crop group be reduced as noted above to 0.05 ppm.

 The current bushberry subgroup 13B tolerance at 40 ppm should be replaced with bushberry subgroup 13

- 07B tolerance at 40 ppm.

 The c urrent citrus fruit group 10 tolerance of 5.0 ppm should be replaced with a citrus fruit group 10

- 10 tolerance . HED has no objection to raising the tolerance from its current level of 5.0 ppm to 9 ppm to harmonize with the Canadian MRL.

 The current pom e fruit group 11 tolerance of 10 ppm should be replaced with a pome fruit group 11

- 10 tolerance at 10 ppm.

For all of the recommended crop subgroup/crop group updates, the representative commodities for the old groups/subgroups are the same as for the new groups/subgroups and the recommended tolerance level is the same or lower than previously established; therefore, no additional data are needed to make these changes.

### Page 9 of 36

DIETARY EXPOSURE AND RISK

The most recent dietary risk assessment was conducted to support Section 3 registration on turnips, succulent peas, citrus, green onions, and leeks (D278156, A. Acierto, 3/7/02).

There have been no changes to the residue inputs for this assessment since the 2002 dietary risk

assessment was conducted. All registered uses were included in the 2002 dietary risk assessment

at tolerance level residues and the assessment assumed 100% crop treated . During registration review, HED is recommending that several tolerances be lowered to allow for harmonization with Canadian MRLs. As noted above, HED is also recommending that the crop group tolerance for citrus fruit be increased from 5 ppm to 9 ppm. However, this increase is administrative in nature and is recommended only for purposes of tolerance harmonization. It is not as a result of an expected increase in residues above the previously established tolerance level which was the input value used in the 2002 dietary risk assessment.

The 2002 dietary risk assessment used the Dietary Exposure Evaluation Model DEEM

- FCID TM software version 7.73, which incorporates consumption data from USDA’s Continuing Surveys

of Food Intake by Individuals (CSFII), 1989

- 1992. HED is currently using the Dietary Exposure Evaluation Model software with the Food Commodity Intake Database (DEEM

- FCID) Version

3.16 . This is effectively the same software as used in the previous dietary assessment; however

it 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). HED has conducted evaluations to compare estimated risks using the two different consumptio n databases and results are generally comparable. Given the conservative inputs into the 2002 dietary risk assessment, the low risk estimates , and the low expected impact on overall results of the new consumption information, HED believes the previously c onducted dietary risk assessment is adequate to address dietary risks under registration review.

Food Exposure The inputs into the 2002 dietary assessment and findings from that assessment are briefly

summarized here. There is no hazard associated wit h acute exposure to fosetyl

- Al ; therefore only chronic dietary exposure is assessed for this active ingredient. A highly conservative chronic dietary exposure assessment was conducted using tolerance level residues, default processing factors, and 100% cr op treated for all commodities. At the time of the last dietary assessment, it was HED policy that drinking water could not be directly incorporated into dietary assessments; therefore, the assessment includes food residues only. Dietary (food only)

esti mated exposure for the U.S. population was 0.08 9 mg/kg/day

, which is equivalent to an estimated risk of 4% of the chronic Population Adjusted Dose (cPAD). The estimated exposure

of 0.1 9 mg/kg/day for children 1

- 6, the most highly exposed population subgro up
, is equivalent

to an estimated risk of 8% of the cPAD.

Drinking Water Exposure EFED has determined that an updated drinking water assessment is not required to support the registration review of fosetyl

- Al (email from J. Lin, EFED to D. Davis, HED da ted 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,

### Page 10 of 36

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. EFED noted that if fosetyl

- Al reached groundwater, it could persi st . The Screening

Concentration in Ground Wat er ( SCI

- GROW2 ) model estimated a concentration of less than 0.006 parts per billion (ppb) in groundwater

.

At the time of the 2001 risk assessment, HED policy dictated the calculation of “drinking water levels of concern” (DWLOCs) be used as a tool to as sess potential risk from drinking water. HED calculated DWLOCs for adults, young children (1

- 6 years old ) and infants (<1 year old). The DWLOC calculation looked at the risk cup for the chemical, subtracted food exposure and residential exposure, assumed a standard water consumption value and provided a “target” water value. If the estimated drinking water concentration was b e low the DWLOC, there were no risks of concern. The DWLOCs were 102,000 ppb for adults, 25,000 ppb for children 1

- 6 years old

, and 25,000 for infants. It is HED’s current policy is to directly input the modeled estimated drinking water concentrations into the dietary risk assessment which allows comparison with actual consumption data from the WWEIA survey. While differences do exi st between the standard consumption values used to calculate the DWLOCs and the current consumption information used to calculate drinking water estimated dietary risks, the estimated drinking water

concentration is orders of magnitude below exposure level s that might cause a concern ; therefore, HED concludes that there is no concern for risks associated with drinking water exposure. Further, directly incorporating modeled ground water estimated concentration of 0.006 ppb into the dietary risk assessment would not result in a risk of concern.

Conclusions HED concludes that there are no dietary (food and water) drinking water risks associated with the registered uses of fosetyl

- Al

.

RESIDENTIAL EXPOSURE AND RISK

The most recent residential exposure asse ssment was conducted to support Section 3 registration

on turnips, succulent peas, citrus, green onions, and leeks (D279163, M. Clock

- Rust, 5/17/01). There have been no substantive changes to the residential turf application rate or registered use

pattern since that assessment . H owever, subsequent to that assessment substantial changes have occurred regarding the exposure methodology HED uses to conduct residential assessments; therefore, HED has reassessed residential handler and post

- application exposure to support registration review and to account for the 2012 Residential Standard Operating Procedures ( SOP )

revision.

Residential (Non

- Occupational) Exposure/Risk Characterization Fosetyl

- Al is registered for a variety of uses, including some use patterns that are relevant for residential exposure assessment. Fosetyl

- Al is registered for use on ornamental plants in

residential areas

, and is registered for use on turf grass on golf courses, an d commercial turf areas where residential post

- application exposure may occur. For residential handlers, exposure via the inhalation and dermal routes are anticipated, although no hazard has been identified for the dermal route of exposure. Therefore, only inhalation exposure has been quantitatively

### Page 11 of 36

assessed for residential handlers. Exposure durations consistent with short

- and intermediate

term exposure were assessed. For residential post

- application exposure, HED typically assesses adult dermal exposure and incidental oral exposure for children (1 < 2 years old)

. Since no

hazard ha s been identified for the dermal route of exposure for fosetyl

- al, quantitative

assessment for only children’s incidental oral exposure w as conducted

. In the case of fosetyl

- al, no chemical specific transfer data is available, so default values for trans ferable turf residues (TTR) are used to assess residential post

- application exposure

.

Residential Handler Exposure Based on the registered use patterns, s hort

- term inhalation exposure has been quantitatively assessed for residential handler exposure scen arios (i.e., application to lawns/turf and ornamental gardens) using handheld application equipment. The residential handler exposure assessment reflects a range of application rates depending on the use pattern; the maximum application rate

for fosetyl

- Al is up to 17.6 lbs ai/A for turf applications. The residential handler exposure and risk assessment findings are summarized in Table 3. Inhalation margins of exposure (MOEs) ranged from 120,000 to 7,100,000. Risk estimates exceed the level of concern (LO C) of 100; therefore no risks of concern are identified for residential handlers as a result of the registered

uses of fosetyl

- Al

.

Table 3 : Short

- Term Residential Handler Exposure and Risk Estimates for Fosetyl

- Al

Exposure Scenario Target

MOE Inhalation Unit Exposure Maximum Application

Rate a Amount

Treated

or Handled Daily b Inhalation

Dose c MOE d

Mixer/Loader/Applicator

Gardens/Trees
[ornamentals/spot

treatment lawn/turf]
Manually Pressurized

Handwand 100 0.018 0.04 lb ai/gallon 0.000045 6,700,000

Gardens/Trees
[ornamentals/spot

treatment lawn/turf]

Hose

- End Sprayer 100 0.0014 0.002 lb ai/ft2 0.000042 7,100,000

Lawn/turf
[liquid concentrate]

Hose

- end sprayer 100 0.022 17.6 lb ai/A 0.0024 120,000

Gardens/Trees
Ready

- to

- use

Hose

- end sprayer 100 0.034 0.004 lb ai/ft 2 0.001 150,000

a. Based on registered or existing product label s ( D279163

, Succulent Peas, Citrus Fruit Group (10), Leeks, Green Onions, and the Bushberry Subgroup (13B), Mary Rust et al,

05/17/2001 )

b. Exposure Science Advisory Council Policy #9.1

c. Inhalation Dose = Inhalation Unit Exposure (mg/kg) x Application Rate (lb ai/acre or gal) x A mount
Treated or Handled (A or gallons /day) /BW ( 80 kg)

d. Inhalation MOE = Inhalation NOAEL (mg/kg/day)/ Inhalation Dose (mg/kg/day)

### Page 12 of 36

R esidential Post

-

Application Exposure

Post

- application exposure and risk estimates were assessed us ing the maximum turf application

rate of 17.6 lbs ai/A

. The exposure and risk estimates presented below (Table 4) represent short

term incidental oral exposu re (children 1 < 2 years old ) to treated turf based on the 2012

Residential SOPs. In the case of fosetyl

- Al, o nly incidental oral exposure is quantitatively

assessed because no dermal hazard was identified

. Inhalation exposure is not quantitatively assessed for fosetyl

- al because the combination of low vapor pressure for fosetyl

- Al and dilution in outdoor air is likely to result in minimal inhalation exposure.

Chemical

- specific t ransferable turf residue (TTR) data are not available for use in exposu re assessment, so default TTR values included in the 2012 Residential SOP revision were used to assess residential post application exposure and risk.

The residential post application exposure and risk assessment findings are summarized in Table

4. The MOEs for children 1 < 2 years old ranged from 1,100 to 500,000. MOEs exce ed the

LOC of 100 ; therefore no risks of concern are identified for residential post

- application as a result of the registered uses of fosetyl

- Al.

Table 4 : Short

- term Residential Post A pplication Exposure and Risk Estimates for fosetyl

- Al

Lifestage Post A pplication Exposure Scenario Dose (mg/kg/day) MOEs

Child ren 1 < 2 years old Lawn/turf sprays Hand to Mouth 0.268 1,100
Object to Mouth 0.008 37,000

Incidental Soil Ingestion 6.0E

- 04 500,000



### Combined Residential Exposure

Recommendations for aggregate risk assessment are shown in Table 5.

 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 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 Residential Handler MOE = the MOEs associated with the highest residential handler doses . Total = 1 ÷ (1/D ermal MOE) +

(1/Inhalation MOE) [if both exposure routes are applicable].

3 Residential Post

- application Dose = the highest post

- application dose for each applicable lifestage of all post

- application scenarios

as sessed . 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). Table 5: 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) 4 Dermal Inhalation Dermal 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

Child ren 1 to < 2 years old N/A N/A N/A N/A N/A 0.268 0.268

### Page 13 of 36

Residential Bystander Post Application Inhalation Exposure Based on the Agency's current practices, a quantitative post

- application inhalation exposure assessment was not performed for fosetyl

- Al at this time primarily because of the low acute

inhalation t oxicity (Toxicity Category III and IV) and low vapor pressure ( 0.013 mPa at 25 °C )

. However, volatilization of pesticides may be a source of post

- application inhalation exposure to individuals nearby pesticide applications. The Agency sought expert advice and input on issues related to volatilization of pesticides from its Federal Insec ticide, Fungicide, and Rodenticide Act Scientific Advisory Panel (SAP) in December 2009, and received the SAP’s final report on March 2, 2010 ( http://www.epa.gov/scipoly/sap/meet ings/2009/120109meeting.html ). The Agency is in the process of evaluating the SAP report and may, as appropriate, develop policies and procedures to identify the need for and, subsequently, the way to incorporate post

application inhalation exposure into the Agency's risk assessments. If new policies or procedures are developed, the Agency may revisit the need for a quantitative post

- application inhalation exposure assessment for fosetyl

- Al

.

Spray Drift

Off

- target movement of pesticides can occur via man y types of pathways and it is governed by a variety of factors. Sprays that are released and do not deposit in the application area end up off

target and can lead to exposures to those it may directly contact. They can also deposit on

surfaces where conta ct with residues can eventually lead to exposures ( e.g. , children playing on lawns where residues have deposited next to treated fields). The potential risk estimates from these residues can be calculated using drift modeling coupled with methods employed for residential risk assessments for turf products.

The approach to be used for quantitatively incorporating spray drift into risk assessment include assessing exposures for children (1 to 2 years old) and adults who have contact with turf where

residues are assumed to have deposited via spray drift thus resulting in an exposure scenario. Aside from the predicted residues available for transfer, the routes of exposu re and assessment methodology are analogous to how exposures to turf products are consider ed in risk assessment.

Several fosetyl

- Al products have existing labels for use on turf, thus it was considered whether the risk assessment for turf may be considered protective of any type of exposure resulting from spray drift. If the maximum applicat ion rate on crops adjusted by the amount of drift expected is less than or equal to existing turf application rates, the existing turf assessment is considered protective of spray drift exposure. The proposed maximum single application rate of fosetyl

- Al

for turf is 17.6 lbs ai/A. The highest fraction of spray drift noted for any application method immediately adjacent to a treated field results in a deposition fraction of 0.26 1 

### of the application

rate. A quantitative spray drift assessment for fosetyl

- Al is not required because the max imum application rate for a crop/ta rget site multiplied by the adjustment factor for drift of 0.26 is less

than the maximum direct spray residential turf application rate of 17.6 lb ai/A for any fosetyl

- Al product s. The turf post

- application MOEs are protective for any potential exposures related to spray drift for fosetyl

- Al and have previously been discussed above

.

1 Tier 1 output from the aerial application using fine to medium spray quality based on AgDrift output files

### Page 14 of 36

AGGREGATE EXPOSURE AND RISK

No aggregate risk issues were identified in the most recent human health risk assessment cited above. As previously noted, food and water exposures have not changed substantially from the prior dietary exposure assessment. The residential risk assessment has also not changed substantially. Adult residential exposure was 0.0021 mg/kg/day in the 2001 assessment, and has been updated to 0.0024 mg/kg/day. Residential exposure to children has been decreased from 2001 where it was 0.34 ppm, and has been reassessed to be 0.27 mg/kg/day. In 2001 aggregate

risks were conduct ed by using the appropriate POD and the LOC to calculate the maximum allowable exposure in mg/kg/day. The dietary (food only) and residential exposure were

subtracted from that maximum, and the remaining exposure was allocated to water and a

DWLOC was cal culated. If the estimated drinking water concentrations were below the DWLOCs, then the maximum allowed exposure was not exceeded and there were no aggregate risks of concern. While this aggregate methodology varies from the current practice of directly including water in the dietary risk assessment, and combining dietary (food and water) with residential and comparing to the appropriate NOAEL, the 2001 assessment is acceptable for the purposes of registration review as it clearly demonstrates that there will be no aggregate risks of concern for fosetyl

- Al. As noted above, the calculated DWLOCs were 102,000 ppb for adults and 25,000 for children. The drinking water estimated concentration of 0.006 ppb is substantially below those DWLOCs. Even though the re have been some slight changes in exposure values, all the assessments included in the 2001 human health risk assessment use conservative, health protective inputs, and are likely to have over

- estimated risk. Even with small changes, there will be no ri sks of concern identified if a quantitative update of the aggregate risk were completed. HED considers the current information sufficient to demonstrate that there are no aggregate risks associated with the registered uses of fosetyl

- Al.

OCCUPATIONAL EXP OSURE AND RISK (Agricultural Crops)

The most recent occupational exposure assessment was conducted to support Section 3 registration on turnips, succulent peas, citrus, green onions, and leeks (D279163, M. Clock

- Rust, 5/17/01). Additionally, HED assessed occupational exposure to fosetyl

- al in 2 separate actions in 2005; 1) Occupational Risk Assessment to Support Request for a Section 3 Re gistration of Fosetyl

- Al on Tobacco

, D317831. B. O’Keefe, 7/1/2005. ; and 2) Fosetyl

- Al (Aliette® WDG Fungicide). Proposed Label Amendment to Reduce REI , D313651 & D315276. B. O’Keefe,

7/1/2005.

Although there ha ve not been substantive use pattern changes since the above exposure and risk assessments, HED has reassessed occupational handler and post application exposure to support registration review and to account for updated unit exposure data. EPA has updated the occupational inhalation risk assessment for fosetyl

- Al to reflect current HED policy and available unit exposure data, registered use pattern information, appropriate exposure duration (short

- and intermediate

- term), and endpoint selection. No risk is expected via the dermal route of exposure b ecause no hazard was observed [ 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 15 of 36

Fosetyl

- Al is registered for ground/airblast application on a wid e variety of agricultural crops (see Residue Chemistry section for additional information).

Commercial applicators may also be exposed to fosetyl

- Al due to the registered use pattern on ornamental plants in residential areas

, turf grass on golf courses, sod farms, and other commercial turf areas. Rates range from 6.6 to 8.7 pounds ai/acre with an application interval of 14 days and 13.3 to 17.4 pounds ai/acre with an application interval of 21 days. There is potential

for shor t

- and intermediate

- term occupational exposure to fosetyl

- Al during handling (mixing, loading, applying) of liquid and wettable powder formulations with airblast equipment. Personal Protective Equipment (PPE) for fosetyl

- Al product includes chemical

- resist ant gloves and eye protection because it is a severe eye irritant. Available product labels indicate applicators

should wear goggles or a face shield.

Short

- /Intermediate Occupational Handler Risk

Table 6 shows the calculated short

- and intermediate

- term risk estimates for occupational inhalation exposure based on the registered use pattern and formulations of fosetyl

- Al. No risk estimates of concern (i.e., MOEs<100) were identified.

Fosetyl

- Al is also registered as an injectable fungicide (EPA Reg. No: 264

- 504; 

### bark injection of citrus trees). At this time, HED does not have appropriate unit exposure values to represent the tree injection exposure scenario; however, HED believes that the occupational exposure from the tree injection use is lower than tho se scenarios quantitatively assessed below given the label directions, label

- specified personal protective equipment and agricultural practices.

Table 6. Baseline Short

- and Intermediate

- Term Occupational Exposures and Risk Estimates for Fosetyl

- Al

.

Exposure Scenario Application

Rate a Area

Treated Daily b ST/IT

Baseline

Inhalati

on UEs c ST/IT

Baseline Inhalation

Dose d ST/IT

Baseline Inhalation

MOE e

lb a i /A acres μg/lb ai mg/kg/day ST LOC = 100

Mixer/Loader

Aerial Mixer/Loader Dry Flowable/Water Dispersable Granule

Formulation Orchard/field crop 4 350 8.96 0.156 1,900

Aerial Mixer/Loader Dry Flowable/Water Dispersable Granules

Formulation

nursery 4 60 8.96 0.0269 11,000

Aerial Mixer/Loader

Wettable Powders

nursery 4 60 43 0.129 2,300

Aerial Mixer/Loader liquid formulations Orchard/field crop 4 350 0.219 0.00384 78,000

Aerial Mixer/Loader liquid formulations

nursery 4 60 0.219 0.000658 460,000

### Page 16 of 36

Table 6. Baseline Short

- and Intermediate

- Term Occupational Exposures and Risk Estimates for Fosetyl

- Al

.

Exposure Scenario Application

Rate a Area

Treated Daily b ST/IT

Baseline

Inhalati

on UEs c ST/IT

Baseline Inhalation

Dose d ST/IT

Baseline Inhalation

MOE e

lb a i /A acres μg/lb ai mg/kg/day ST LOC = 100

Airblast Mixer/Loader Dry Flowable/Water Dispersable Granule

Formulation

orchard 6 40 8.96 0.0269 11,000

Airblast Mixer/Loader Dry Flowable/Water Dispersable Granule

Formulation

nursery 4 20 8.96 0.00896 33,000

Groundboom

Mixer/LoaderBroadcast

– golf course 17.6 40 0.34 0.00299 100,000

Groundboom

Mixer/Loader liquid formulations Field crop, typical 4 80 0.219 0.000876 340,000

Groundboom

Mixer/Loader liquid formulations

nursery 4 60 0.219 0.000658 460,000

Flagger

Flagger Field crop/orchard 4 350 0.35 0.00613 49,000

Applicator

Groundboom applicator Liquid sprays 4 80 0.34 0.00136 220,000

Aerial applicator

nursery (engineering controls) 4 60 0.0049 0.0000148 20,000,000

Aerial applicator Field crop/orchard (engineering controls) 4 350 0.0049 0.0000858 3,500,000

Applicator

Airblast (macadamian nuts) 6 40 4.71 0.0141 21,000

Golf course (fairways, tees, greens) 17.6 40 4.71 0.00943 32,000

Golf course (tees and greens only) 17.6 5 4.71 0.000374 800,000

a Application Rates based on existing or registered uses for fosetyl

- Al ).

b Acres Treated Per Day is taken from Exposure Science Advisory Council (ExpoSAC) Policy No. 9.1.

c UEs = Unit Exposures based on PHED Version 1.1, ORETF, or AHETF data. Baseline = no gloves, no respirator.

d Dose (mg/kg/day) = daily unit exposure (μg/lb ai) × application rate (lb ai /acre) × amount handled/day (acres/day) x conversion factor (1 mg/1,000 μg) × absorption factor (%) ÷ body weight (80 kg). No inhalation absorption factor.

e MOE = NOAEL ÷ Dose (mg/kg/day). ST/IT Inhalation NOAEL = 100 mg/kg/day. ST/IT level of concern = 100.

### Page 17 of 36

Short

- and Intermediate

- Term Occupational Dermal Post

- Application Risk Post application exposure is possible for workers entering fosetyl

- Al treated fields. A dermal occupational post application risk assessment was not performed, because fosetyl

- Al does not pose a dermal hazard.

Technical fosetyl

- Al falls into Toxicity Ca tegory I for primary eye irritation. Per the Worker Protection Standard (WPS), a 48

- hour REI is required for chemicals classified under Toxicity Category I. Therefore, the existing product labels should be reviewed for the appropriate REI for compliance with WPS. Existing product labels should be amended to reflect a 48

- hour REI.

Inhalation Occupational Post Application Risk Based on the Agency's current practices, a quantitative post

- application inhalation exposure assessment was not performed for fosetyl

- Al at this time primarily because of the low acute inhalation toxicity (Toxicity Category III and IV) , and low vapor pressure ( 0.013 mPa at 25 °C ). However, there are multiple potential sources of post

- application inhalation exposure to individuals p erforming post

- application activities in previously treated fields. These potential sources include volatilization of pesticides and resuspension of dusts and/or particulates that contain pesticides. The Agency sought expert advice and input on issues rel ated to volatilization of pesticides from its Federal Insecticide, Fungicide, and Rodenticide Act Scientific Advisory Panel (SAP) in December 2009, and received the SAP’s final report on March 2, 2010 ( http://www.epa.gov/scipoly/sap/meetings/2009/120109mee ting.html ). The Agency is in the process of evaluating the SAP report as well as available post

- application inhalation exposure data generated by the Agricultural Reentry Task Force and may, as appropriate, develop policies and procedures, to identify the need for and, subsequently, the way to incorporate occupational

post

- application inhalation exposure into the Agency's risk assessments. If new policies or procedures are put into place, the Agency may revisit the need for a quantitative occupational

pos t

- application inhalation exposure assessment for fosetyl

- Al

.

Although a quantitative occupational post application inhalation exposure assessment was not performed, an inhalation exposure assessment was performed for occupational/commercial

handlers. Han dler exposure resulting from application of pesticides outdoors is likely to result in higher exposure than post application exposure. Therefore, it is expected that these handler inhalation exposure estimates would be protective of most occupational post

- application inhalation exposure scenarios.

As fosetyl

- Al is registered for use on tree nuts (e.g. walnuts, almonds, etc.) , inhalation exposure during dusty mechanical activities such as shaking and mechanical harvesting is another potential source of pos t

- application inhalation exposure. However, the airblast applicator

scenario (See Table 6) is believed to represent a reasonable worst case surrogate estimate of post application inhalation exposure during these dusty mechanical harvesting activities.

OCCUPATIONAL EXPOSURE AND RISK (Seed Treatment)

Besides for the agricultural and commercial turf applications addressed above, fosetyl

- al is registered as a Special Local Need (SLN) in Idaho for use on succulent peas as a seed treatment. Occupational seed treatment handlers may experience short

- and intermediate

- term exposure to

### Page 18 of 36

fosetyl

- al while performing seed treatment activities in commercial settings. In addition, occupational secondary handlers may experience short

- and intermediate

- term exposure whi le planting fosetyl

- al treated seeds. No chemical

- specific handler exposure data were submitted in support of this use pattern. For assessing commercial seed treatment and seed planting activities, unit exposure data were taken from HED ExpoSAC Policy 14: SOPs for Seed Treatment. The

amount of active ingredient handled depends on the application rate (lb ai/lb seed) and the pounds of seed treated in a day (or the pounds of seed that can be planted in a day), all of which

vary depending upon the seed type. Values for the amount of seed treated and planted per day

were obtained from HED ExpoSAC Policy 15 .1 . The results are presented in Table s 7 and 8

. All the calculated risk estimates exceed an MOE of 28,000 (range: 28,000

– 390,000).

Treating Seed (Primary Handler)

P otential occupational exposure scenarios from the use of fosetyl

- al as a commercial seed

treatment include:

 Mixing, loading, applying liquid formulations;

 Bagging treated seed;

 Sewing bags; and

 Multiple activities

.

Typically

, for large

- scale commercial seed treatments, workers perform only those specific individual tasks listed above; however, it is assumed that workers also may perform multiple activities throughout the day. As a result a “multiple activities” scenario (i.e. wher e one worker performs all seed treatment tasks such as loading/applying, sewing, bagging, cleaning, calibration, repair, forklift driver, etc.) w as addressed.

Planting Treated Seed (Secondary Handler)

P otential occupational exposure scenarios from the use of fosetyl

- al as a commercial seed

treatment include p lanting treated seed (secondary handler)

.

Planting treated seed consists of the farmer purchasing bags of treated seed, placing the seed in the hop pe r and applying seed to fields ( considered a secondary handler exposure scenario )

.

Exposure Data, Factors, and Assumptions

The following are exposure factors and assumptions used to calculate exposure and risk in the occupational assessment for commerci al seed treatment scenarios.

Unit Exposures

Chemical

- specific data for assessing exposure during commercial seed treatment and seed planting were not submitted to the Agency in support of this risk assessment

. In the absence of

chemical

- specific data, u nit exposures are from ExpoSAC Policy 14: SOPs for Seed Treatment ( May 1, 2003). Unit exposure values from ExpoSAC Policy 14 are based on data for open

### Page 19 of 36

mixing/loading/application systems. HED SOP 15.1 provides guidance to exposure assessors on

the amoun t of commercial seed treated per day.

Amount of Seed Treated Per Day (Primary Handler)

The amount of seed treated per day at a commercial facility i s summarized below for the relevant exposure duration (short

- and intermediate

- term)

.

 Dry beans and pea s (for succulent pea)

– 281,250 lbs (ST), and 200,000 lbs (IT)

Amount of Seed Planted Per Day (Secondary Handler)

HED has worked closely with OPP’s Biological and Economic Analysis Division (BEAD) to define the amount of seed planted per day. The appropr iate value is shown below.

 Dry beans and peas (for succulent pea)

– 16,000 lbs

Application Rates

The succulent pea seed treatment rate is 0.0001 9 lb ai/lb seed for seed treatment.

Body Weight

The average adult weight of 80 kg was used for estimating inhalation exposure since the endpoint was based on not based on developmental effects.

Exposure Duratio n

It is anticipated that occupational fosetyl

- al exposures will generally occur in short

- (1

- 30 days)

an d intermediate

- (1

- 6 months) term durations.

Absorption Factor

Since no inhalation absorption data are available, toxicity by the inhalation route is considered to be equivalent to the estimated toxicity by the oral route of exposure (100% absorption fac tor).

Seed Treatment Handler Exposure and Risk Summary

Primary Handler

A summary of the inhalation risk estimates for the succulent pea seed treatment exposure scenario is presented in Table 7 for short

- term and intermediate

- term inhalation exposures. Dermal exposure and risk estimates are not calculated because no dermal hazard was identified. The results of the occupational handler exposure and risk assessment indicate that inhalation risk

estimates are not of concern ( MOEs ≥ 100) at baseline exposure

.

H ED is currently in the process of revising ExpoSAC Policy 15 in efforts to update the daily

amount of seed treated in commercial seed treatment fac ilities. With the increasing demand for hybridized treated seeds, there have been modifications not only in the seed treatment

### Page 20 of 36

equipment, but in the market shares of new and currently registered pesticide products. HED

understands that d ue to the high co st of produc ing hybrid seeds, direct seeding is done in a precision manner which requires lower volumes of seed per acre. However, this does not provide a direct correlation to the amount of seed which is treated in the commercial seed

treatment facilitie s.

Seed Treatment Occupational Post

- Application Exposures and Risks

The potential for post

- application exposures following the planting of fosetyl al treated seeds is unlikely because s ustained levels of contact with treated seed after it has been placed in the soil or other planting media would not be expected because no routine cultural practice required for the production of agricultural commodities involves such an activity as define d in the no/low

contact criteria in the Worker Protection Standard (WPS)

. Therefore, no quantitative post

application assessment is required for exposure to treated seeds that have already been planted

.

The labeling should state: Seed that has been trea ted with this product that is then packaged or bagged for future use must contain the following labeling on the outside of the seed package or bag.

"Treated Seed

- Do Not Use f or Food, Feed, or Oil Purposes. When opening this bag or loading/pouring the tr eated seed, wear a long

- sleeved shirt, long pants, shoes, socks, and chemical resistant gloves. After the seeds have been planted, do not enter or allow worker entry into treated areas during the

restricted

- entry interval (REI) of 48 hours

. Exception: Onc e the seeds are planted in soil or other planting media, the Worker Protection Standard allows workers to

enter the treated area without restriction if there will be no worker contact with

the treated seeds in the soil or planting media."

Table 7

. Summary of Short

- and Intermediate

- Term Handler Exposures and Risks for Fosetyl al (Seed Treatment Only).

Seed Type Dermal

UE a 

### Inhal

UE a 

### Max App

Rate b 

### Amt

Treated c 

### Inhal

Dose d 

### Inhal

MOE e


### mg/lb mg/lb lb ai/lb seed lb seed/day mg/kg/day LOC = 100 LOADER/APPLICATOR (single layer, gloves)

Succulent Peas (ST) N/A

0.00034 0.0001 9 281,250 0.00 23 170



### , 000



### Succulent Peas (IT) N/A 200,000 0.001 6 2 8 0



### , 000



### SEWER (single layer, NO gloves)

Succulent Peas (ST) N/A

0.00023 0.0001 9 281,250 0.001 5 2 0 0



### , 000



### Succulent Peas (IT) N/A 200,000 0.00086 350



### , 000

### Page 21 of 36

Table 7

. Summary of Short

- and Intermediate

- Term Handler Exposures and Risks for Fosetyl al (Seed Treatment Only).

Seed Type Dermal

UE a 

### Inhal

UE a 

### Max App

Rate b 

### Amt

Treated c 

### Inhal

Dose d 

### Inhal

MOE e


### mg/lb mg/lb lb ai/lb seed lb seed/day mg/kg/day LOC = 100

BAGGER (single layer, NO gloves)

Succulent Peas (ST) N/A

0.00016 0.0001 9 281,250 0.00 11 28 0



### , 000



### Succulent Peas (IT) N/A 200,000 0.000 8 390



### , 000



### MULTIPLE ACTIVITIES (combination of loader/applicator with gloves + no coveralls,

sewer without gloves, stacker without gloves)

Succulent Peas (ST) N/A

0.0016 0.00019 281,250 0.0 11 28



### , 000



### Succulent Peas (IT) N/A 200,000 0.00 8 39



### , 000

a Unit Exposures from HED Exposure Science Advisory Council Policy 14 (baseline inhalation = no respirator).

b Application Rates based on proposed label uses for fosetyl al.

c HED default for lb seed treated per day from HED Exposure Science Advisory Council Policy 15.

d Daily Inhalation Dose (mg/kg/day) = daily inhalation unit exposure ( m g/ lb ai) x a pplication rate (lb ai/lb seed) x amount planted (lb seed/day) x absorption factor (100%) / body weight (8 0 kg adult).

e Inhalation MOE = NOAEL ( 300 mg/kg/day for short

- and intermediate

- ter m exposure ) / Inhalation Dose (mg/kg/day) . Level of concern = 100.



### Table 8. Summary of Secondary Handler (Planter) Exposures and Risks for Fosetyl al ( Single Layer, Gloves for Loading O nly)

.

Seed Type Dermal

UE a 

### Inhal

UE a 

### Max App

Rate b 

### Amt of Seed

Planted/Day c 

### Inhal ation

Dose d 

### Inhalation

MOE e



### mg/lb mg/lb lb ai/lb

seed lb seed/day mg/kg/day LOC =

100

Beans and Peas N/A 0.0034 0.0001 9 1 6 ,000 0.001 2 3 0,000

a Unit Exposures from HED Exposure Science Advisory Council Policy 14: Standard Operating Procedures for Seed Treatment.

b Application Rates based on proposed label uses for fosetyl

- al.

c HED default for lb seed planted per day from HED Exposure Science Advisory Council Policy 15 .1

. d Dai ly Inhalation Dose (mg/kg/day) = daily inhalation unit exposure ( m g/ lb ai) x a pplication rate (lb ai/lb seed) x amount planted (lb seed/day) x absorption factor (100%) / body weight (8 0 kg adult).

e Inhalation MOE = NOAEL ( 300 mg/kg/day for short

- and i ntermediate

- term exposure ) / Inhalation Dose (mg/kg/day) . Level of concern = 100.

### Page 22 of 36

Appendix A. Toxicity Information

Table A .1 Acute Toxicity Profile

– Fosetyl

- Al

Guideline

No. Study Type MRID Guideline No. Guideline No.

870.1100 Acute oral [rat] 00247160 LD 50 > 5000 mg/kg I V

870.1200 Acute dermal [rat] 00247160 LD 50 > 3 000 mg/kg III

870.1300 Acute inhalation [rat] 00247160 LC 50 > 1.73 mg/L I II

870.2400 Acute eye irritation [rabbit] 00247160 Severe eye irritant I

870.2500 Acute dermal irritation [rabbit] 00247160 not an irritant IV

870.2600 Skin sensitization [guinea pig] 00247160 not a dermal sensitizer N/A

Table A .2 Subchronic, Chronic and Other Toxicity Profile

– Fosetyl

- Al

Guideline No./ Study Type MRID No. (year)

Classification /Doses Results

No guideline

4

- week study MRID 00 098341 (1981)

0, 10000, 20000, 40000 ppm acceptable/non

- guideline

TXR0004140 mechanistic study; determination of c alcium and phosphorus in the s erum, u rine and f eces ; fosetyl

- Al induced alterations of the calcium/p hosphorus excretion, as evidenced by a dose related increased calciuria in both sexes, a slight decrease in urinary excretion of phosphorus at all dose levels, a questionable increase in fecal calcium excretion in high

- d ose males, a significant increase in fecal phosphorus excretion in mid

- and high

- dose males. Histological examination showed mild dose related alterations of the epithelial cells of the renal tubules.

870.3100

90

- Day oral toxicity [ Sprague

Dawley Crl:CD® (SD) BR rat] MRID 41315201 (1989)

0, 8000, 30000, 50000 ppm Males 0, 500, 2100, 3500 mg/kg/day Females 0, 600, 2500, 4200 mg/kg/day Acceptable/non

- guideline

TXR#0008207 NOAEL = 500 mg/kg/day LOAEL = 2100 mg/kg/day, based on histopathological changes in urinary bladder seen in

2

- year study related to calculi formation in bladder [calculi in kidneys, ureters, urinary bladder; calculi formation nearly always associated with transitional cell hyperplasia in kidneys, ureters, and bladder]

870.3150

13

- week oral toxicity in

nonrodent [dog] MRID 00098337 (1977)

0, 2000, 10000, 50000 ppm

Males 0, 58, 274, 1309 mg/kg/day

Females 0, 58, 272, 1446 mg/lg/day

acceptable/guideline NOAEL = 10000 ppm [274/272 mg/kg/day] LOAEL = 50000 ppm [1309/1446 mg/kg/day], based on decreased serum potassium but no histopathological changes.

870.3200

21

- Day dermal toxicity ( rabbit) MRID 0009 8338 (1979)

0, 380, 750, 1500 mg/kg/day

acceptable/guideline NOAEL (systemic) = 15 00 mg/kg/day

L OAEL ( systemic ) >1 50 0 mg/kg/day (HDT)

870.3465

90

- day inhalation toxicity Study requirement waived HASPOC memo TXR No. 0056809, dated 10/29/13

### Page 23 of 36

Table A .2 Subchronic, Chronic and Other Toxicity Profile

– Fosetyl

- Al

Guideline No./ Study Type MRID No. (year)

Classification /Doses Results

870.3700a

Prenatal developmental in

rodent (CFY strain SPF rat) MRID 00114091 (1977)

MRID 00247174 () 0, 500, 100, or 4000 mg/kg/day

GD 6

- 15

acceptable/guideline Maternal toxicity NOAEL = 1000 mg/kg/day Maternal toxicity LOAEL = 4000 mg/kg/day, based

on mortality, decreased body weight gain, and an increase in total resorptions

D evelopmental toxicity NOAEL = 1000 mg/kg/day Developmental toxicity LOAEL = 4000 mg/kg/day,

based on decreased litter size and fetal body weight,

increased incidence of fetal malformations and

skeletal variations , and an increase in total resorptions

. 870.3700b

Prenatal developmental in nonrodent ( New

Zealand White

Ju/RP rabbit) MRID 00098347 (19 76 )

MRID 00247174 0, 125

, 250 , or 50 0 mg/kg/day

GD 6

- 16

acceptable/guideline Materna l toxicity NOAEL = 125 mg/kg/day Maternal toxicity LOAEL = 250 mg/kg/day, based

on d ecreased body weight gain; at 500 mg/kg/day, similar findings Developmenta l toxicity NOAEL > 500 mg/kg/day Developmental toxicity LOAEL not identified

870.3800 Reproduction and fertility effects ( CFY strain SPF rats) MRID 00098348/00114091

(19 82 /19 77 )

0, 60 00, 12 000, 2 4 000 ppm 0, 300, 600, 1200 mg/kg/day (std conversion)

acceptable/guideline Parental toxicity NOAEL = 6000 ppm ( 300 mg/kg/day) Parental toxicity LOAEL = 12 000 ppm [ 6 00 mg/kg/day], based on decreased body weight gains of F2b generation and urinary tract changes in adults

Reproductive NOAEL = 24000 ppm [1200 mg/kg/day (HDT)]

Offspring NOAEL = 6 000 ppm [ 300 mg/kg/day] Offspring LOAEL = 1 2000 ppm [ 600 mg/kg/day,

based on reduced litter and pup body weights in both matings of each generation

At 24000 ppm [1200 mg/kg/day], retarded bod y weight gain and lower litter and mean pup body weight in mid and late lactation; increased incidence of pathological changes in urinary bladder (F1b/F2b)

870. 4100a Chronic toxicity rodents ( Charles

River CD

- 1 rat) See below under 870.4200

870.4100b Chronic toxicity nonrodent (dog) MRID 00098340 ( 19 81 )

0, 10000 , 20000, or 40000 ppm (0, 250, 500, 1000 mg/kg/day)

acceptable/guideline NOAEL = 100 0 0 ppm [ 250 mg/kg/day] LOAEL = 20000 ppm [500 mg/kg/day], based on testicular degeneration (spermatocyte and/or spermatidic giant cells in the lumen of the seminiferous tubules); similar findings at 1000 mg/kg/day

870.4 2 00 Carcinogenicity

mice (Charles

River CD

- 1

mouse ) MRID 00098353 (19 8 1)

MRID 00247168 0, 250 0, 100 00, 20000/30 000 ppm 0, 357, 1429, or 2857/4286 mg/kg/day for 24 months

acceptable/guideline NOAEL = 30000 ppm (4286 mg/kg/day )

LOAEL was not determined No compound

- related effects on survival, body weight, histopathology other than hematology findings (↓segmented neutrophils, ↑ lymphocytes, ↓reticulocyte counts.

No evidence of tumors.

### Page 24 of 36

Table A .2 Subchronic, Chronic and Other Toxicity Profile

– Fosetyl

- Al

Guideline No./ Study Type MRID No. (year)

Classification /Doses Results

870.4 3 00

C ombined chronic toxicity/

c arcinogenicity (Charles River

CD

- 1 rat ) MRID 00098339/00098352 (19 82 )

MRID 00247162

- 166 (1981) 0, 2 0 00, 8 000, or 4 0000 /30000 ppm 0, 100, 400, 1500 mg/kg/day (std conversion) for 24 months

acceptable/guideline NOAEL = 8000 ppm (400 mg/kg/day) LOAEL = 40000/30000 ppm (1500 mg/kg/day), based on an increase in protein (urinalysis), and transitional epithelial cell tumors (adenomas/ carcinomas) in the urinary bladder NOTE: Tumors considered likely due to prolonged mechanical irritation by bladder calculi, which

appear to be present as a result of the calcium

phosphorus imbalance at high doses (in excess of the limit dose).

870.5 100

Gene Mutation

- Ames assay MRID 00098342 (1977)

MRID 002471 73 (1977)

Salmonella typhimurium

TA1535, TA1537, TA98, TA100

1, 10, 100, 1000 μg/plate and 125, 250, 500, 1000 μg/plate without S9

125, 250, 500, 1000 μg/plate with S9; Spot test at 5 μg/disc (+S9/

- S9)

Acceptable/guideline N ot mutagenic in the battery of Salmonella typhimurium strains when tested in the Ames procedure with and witho ut S9 or in the spot test.

870.5 100

Gene Mutation

- Ames assay MRID 00 098343 (1981)

Salmonella typhimurium (TA1535, TA1537, TA1538, TA98, TA100) 125, 250, 500, 1000 μg/plate ±S9

Acceptable/guideline N o mutagenic activity in the basic battery of Salmonella typhimurium strains treated up to precipitation (with and without S9)

870.5385

Micronucleus

assay Swiss mouse MRID 00098344 (1977)

MRID 00247173 (1977 )

1 000, 2000, 4 000 m g/kg ( fosetyl

- Al and hydrated monosodium phosphite) Acceptable/guideline Fosetyl

- Al and hydrated monosodium phosphite were neither clastogenic nor aneugenic up to lethal doses ( fosetyl

- Al ) or at doses > limit dose (metabolite); no increase in frequency of micronuclei in polychromatic erythrocytes at 1000 and 2000 mg/kg fosetyl or 1000, 2000, 4000 mg/kg phosphite metabolite. All mice at 4000 mg fosetyl Al/kg died.

870.5385

Micronucleus

assay CD

- 1 mouse MRID 00098345

MRID 00247186 (1981)

CD

- 1 mice 600, 1200, 2400, 3600 mg/kg

1 dose ( bone marrow collected at 30 hours); 2 doses ( collected at 48 hours) Acceptable/guideline No increase in the incidence of micronuclei in polychromatic erythrocytes (MPCE) up to lethal

doses

870.5550 DNA repair test

– MRID 00247173 (1981)

- S9: 12.5, 25, 50, 100 μg/plate

+S9: 6.25, 12.5, 25, 50, 100 μg/plate Negative with and without S9

870.5550 DNA repair test

– E. coli MRID 00247186 (1981)

62.5, 125, 250, 500, μg/plate

Acceptable Negative at concentrations up to 500 μg/plate

without S9

### Page 25 of 36

Table A .2 Subchronic, Chronic and Other Toxicity Profile

– Fosetyl

- Al

Guideline No./ Study Type MRID No. (year)

Classification /Doses Results

Phage induction

test MRID 00098346 (1978)

0.05, 0.1, 0.5, 1, 5, 10, 50, 100, 500,
1000 μg/mL



### . Escherichia coli K12 harboring lambda prophage was utilized for the assay: Strain

GY4015 was used as an indicator strain; GY5027 (lysogenic for lambda papa ) was used to measure inducer activity; and strain GY5029 ( lysogenic for lambda c1857 ) was used to measure toxicity to phage development. Unacceptable/non

- guideline Fosetyl

- Al inhibited phage development in the I.P.L.M. (preincubation) test with strain GY5029 at 50 μg/plate without metabolic activation (

- S9), but

no inhibition occurred at the same concentration in the presence of activation (+S9). The same effect was produced in the P.I. (plate) test with strain GY5027, confirming detoxication by S9. No inducing activity was detected

Phage induction

test MRID 00098346 (1978)

MRID 002471 73 (1978)

1, 5, 10, 50, 100, 500, 1000, and

2000 μg



### . Escherichia coli K12 harboring lambda prophage was utilized for the assay: Strain

GY4015 was used as an indicator strain; GY5027 (lysogenic for lambda papa ) was used to measur e inducer activity; and strain GY5029 (lysogenic for lambda c1857 ) was used to measure toxicity to phage development. Acceptable Fosetyl

- Al inhibited phage development in the I.P.L.M. (preincubation ) test with strain GY5029 at 50 μg/plate without metabolic activation (

- S9), but

no inhibition occurred at the same concentration in the presence of activation (+S9). The same effect was produced in the P.I. (plate) test with strain GY5027, confirming de toxication by S9. No inducing activity was detected

870.6200a

Acute neurotoxicity screening battery Study requirement waived HASPOC memo TXR No. 0056809, dated 10/29/13

870.6200b

Subchronic neurotoxicity screening battery Study requirement waived HASPOC memo TXR No. 0056809, dated 10/29/13

870.6300 Developmental neurotoxicity Not required

870.7485

Metabolism and pharmacokinetics (Sprague

- Dawley rat) MRID 00099355 (1976)

MRID 00247183 (1976)

14 C

- fosetyl

- Al 250 mg/kg/day for 7 days Fosetyl

- Al is rapidly metabolized/hydrolyzed to give ethanol and phosphite; ethanol is oxidized to mainly

CO 2 (60%), which is excreted in exhaled air; ≈26%

is excreted via urine (metabolite phosphorous acid, which is not oxidized to phosphate); 3%

- 4% was

excreted vi a feces

870.7600

Dermal penetration MRID 00143578 (1984)

4μg/cm 2 (human)

Acceptable Rate of penetration <1% in 6

- 16 hour period

870.7800 Immunotoxicity Study requirement waived HASPOC memo TXR No. 0056809, dated 10/29/13

### Page 26 of 36

Appendix B. Physical/Chemical Properties

Table B 1

. Physical/Chemical Properties of Fosetyl

- Al 1

Structure

Common Name Fosetyl

- Al

IUPAC Name Aluminum ethyl hydrogen phosphonate

CAS Name Aluminum tris ( O

- ethyl phosphonate)

CAS Number 39148

- 24

- 8 Melting Point Range >200 °C

pH, 1% aqueous suspension not available

Density not available

Water solubility 120 g/L @ 20 o C

Solvent solubility in g/L @

20 o C Methanol = 920; acetone = 13; propylene glycol =80; ethyl acetate = 5; acetonitrile = 5; hexane = 5.

Vapor pressure <0.013 mPa (25 o C)

Dissociation constant, pK

a 0.8

Octanol/water partition

coefficient - 2.7 (pH 4)

UV/visible absorption
spectrum not available

### Page 27 of 36

Appendix C . International Residue Limit Status



## International Residue Limits

Fosetyl

- Al uminum ( 123301 ; 9/29/13 )

Summary of US and International Tolerances and Maximum Residue Limits Residue Definition :
US Canada Mexico 1 

### Codex

40 CFR 180.4 15 : Plant: Parent only [Aluminum tris (O

ethylphosphonate)]

Livestock: None aluminum tris( O

- ethylphosphonate) None



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

US Canada Mexico 1 

### Codex

Avocado 25 25

Banana 3.0 Bushberry subgroup 13B 40 40 aronia berries, buffalo currants, Chilean guavas, currants, elderberries, European barberries, gooseberries, highbush blueberries, highbush cranberries honeysuckle, huckleberries, jostaberries, lingonberries, lowbush blueberries, native currants, sala l berries, saskatoon berries (juneberries), sea buckthorn Caneberry subgroup 13A 0.1 0.05 blackberries, loganberries, raspberries, wild raspberries Cranberry 0.5 Fruit, citrus, group 10 5.0 9 Australian (desert limes, finger limes, round limes), brown river finger limes, calamondin, citrus citron, citrus hybrids, grapefruits, kumquats, lemons, limes,

Mediterranean m andarin, m ount w hite lime, New Guinea wild limes, oranges, pummelos, Russell R iver limes, s atsuma
mandarins sweet limes, t achibana oranges, Tahiti limes, tangelos

, t angerines, t angors
, t rifoliate oranges, u niq fruits Fruit, pome, group 11 10 1 Apples Ginseng 0.1 0.05 ginseng roots Hop, dried cones 45 Juneberry 40 40 Lingonberry 40 40
Nut, macadamia 0.20 0.2
Onion, bulb 0.5 0.5 dry bulb onions Onion, green 10.0 10 green onions
Pea, succulent 0.3 0.3 succulent shelled (english peas, garden peas, green peas, peas, pigeon peas) Pineapple 0.1 0.1

Salal 40 40 salal berries Strawberry 75 75

Tomato 3 3 Turnip, greens 40 40 turnip tops

### Page 28 of 36

Summary of US and International Tolerances and Maximum Residue Limits Residue Definition :
US Canada Mexico 1 

### Codex
Turnip, roots 15 15 Vegetable, brassica, leafy, group 5 60 60 bok choy Chinese cabbages, broccoli, cabbages, cauliflower s , Chinese broccoli, mustard greens Vegetable, cucurbit, group 9 15 15 cantaloupes, cucumbers, squash

Vegetable, leafy, except brassica, group 4 100 100 celery, lettuce, spinach



### MRLs With No US Equivalent

Fat of ( cattle , goats, hogs, horses, and sheep) 0.05

Meat of ( cattle , goats, hogs, horses, and sheep) 0.05

Meat byproducts of ( cattle , goats, hogs, horses, and sheep) 0.05

Milk 0.02 Rutabaga roots 15

Completed: M. Negussie; 10/17/13

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

(c) Tolerances with regional registrations. Tolerances with regional registration, as defined in § 180.1(l), are established for residues of the fungicide aluminum tris ( O

- ethylphosphonate), including its metabolites and degradates, in or on the commodit ies in the table in this paragraph. Compliance with the tolerance levels specified in this paragraph is to be determined by measuring only aluminum tris ( O

- ethylphosphonate), in or on the commodity.

Commodity Parts per million Asparagus 0.1

Grape 10

### Page 29 of 36

Appendix D. Occupational and Residential Exposure Algorithms

Occupational (agricultural) :

The exposure methodology used to calculate inhalation exposure assessment for occupational handlers is detailed on the Agency website: http://www.epa.gov/pesticides/science/handler

exposure

- data.html

The unit exposures used to calculate handler inhalation exposure are presented in the March 2013 Occupational Pes ticide Handler Unit Exposure Surrogate Reference Guide, also available at the Agency website: http://www.epa.gov/pesticides/science/handler

- exposure

- table.pdf

Occupational (see d treatment): Occupational Handler Non

- Cancer Exposure and Risk Estimate Equations

Potential daily exposures for occupational handlers were calculated using the following

formulas:

Daily Exposure (mg ai /day) = UE ( mg ai / lb of seed ) * AR (lb ai /

100 lbs of seed

) * AT (A mount of seed treated /day) * 1E

- 3 mg/μg

W here :

Daily Exposure = Amount (mg ai/day) that is available for dermal or inhalation absorption,

UE = Unit Exposure (μg ai / lb ai)

, AR = maximum application rate according to proposed label (lb ai / 100lbs of seed ) , and

AT = daily amount treated ( lbs/day )

.



### The daily doses were calculated using the following formula:

Average Daily Dose (mg ai/kg/day) = [Daily Exposure (mg ai/day) * Absorption (%)] Body Weight (kg)

W here: Average Da ily Dose = Absorbed dose received from exposure to a pesticide in a given scenario (mg pesticide active ingredient/kg body weight/day), Daily Exposure = Amount (mg ai/day) that is available for dermal or inhalation absorption, Absorption Factor = A meas ure of the amount of chemical that crosses a biological boundary such as the skin and lungs (%) , and Body Weight = Body weight determined to represent the population of interest in a risk

assessment (kg)

.

MOE = POD (typically a NOAEL in mg/kg/day) ADD (mg/kg/day)



### W here:

MOE = Margin of Exposure: value used by HED to represent risk or risk estimates (unitless),

PO D = Point of Departure,

NOAEL = No Observed Adverse Effect Level (mg/kg/day): Dose level in a toxicity study, where no

observed adverse effects occurred in the study, and

ADD = Average Daily Dose (mg/kg/day) : the absorbed dose received from exposure to a pesticide in a given scenario

.

### Page 30 of 36

Residential:

The exposure methodol ogy used to calculate residential exposure is detailed on the Agency

website: http://www.epa.gov/pesticides/science/residential

- exposure

- sop.html Additional detail is provided below.

1.1.1 Turf, Gardens and Trees

Dermal and Inhalation Handler Exposure Algorithm Daily dermal and inhalation exposure (mg/day) for residential pesticide handlers, for a given

formulation

- application method combination, is estimated by multiplying the formulation

application method

- specific unit exp osure by an estimate of the amount of active ingredient handled in a day, using the equation below:

E = UE * AR * A

where:

E = exposure (mg/day); UE = unit exposure (mg/lb ai); AR = application rate (e.g., lb ai/ft 2 

### , lb ai/gal); and

A = area treated or amount handled (e.g., ft 2 

### /day, gal/day).

1.2 Residential Handler Dose Calculations

Dermal and/or inhalation absorbed doses normalized to body weight are calculated as:

D = E *AF / BW

where:

D = dose (mg/kg

- day); E = exposure (mg/day); AF = absorption factor (dermal and/or inhalation); and BW = body weight (kg).

2.0 Residential Post

- application

2.1 Turf/Physical Activities on Turf

Post

- application Dermal Exposure Algorithm

– Physical Activities on Turf Exposure resulting from contacting previously treated turf while performing physical activities is calculated as shown below. Residential post

- application exposure assessment must include calculation of exposure on the day of application. Therefore, though an assessment can present exposures for any day “t” following the application, it must include “day 0” exposure.

### Page 31 of 36 E = TTRt * CF1 * TC * ET

where:

E = exposure (mg/day);

TTR t 

### = turf transferable residue on day t (μg/cm 2 

### ); CF1 = weight unit conversion factor (0.001 mg/μg);

TC = transfer coefficient (cm 2 

### /hr); and ET = exposure time (hr/day).

If chemical

- specific TTR data are available, then surface residues from the day of application should be used (assume that individuals could be exposed to residues immediately after application). However, if dat a are not available, then TTR t 

### can be calculated using the following

formula:

TTR t 

### = AR * F * (1

- FD) t 

### * CF2 * CF3

where:

TTRt = turf transferable residue on day t (μg/cm 2 

### ); AR = application rate (lbs ai/ft 2 

### or lb ai/acre);

F = fraction of ai as transfera ble residue following application (unitless); FD = fraction of residue that dissipates daily (unitless);

t = post

- application day on which exposure is being assessed; CF2 = weight unit conversion factor (4.54 x 10 8 

### μg/lb); and

CF3 = area unit conversion fa ctor (1.08 x 10 - 3 

### ft 2 

### / cm 2 

### or 2.47 x 10 - 8 

### acre/cm 2 

### ).

Dermal absorbed doses are calculated as:

where:

D = dose (mg/kg

- day);

E = exposure (mg/day);

AF = absorption factor (dermal); and

BW = body weight (kg).

Table D

- 1 : Turf (Physical Activities)

-- Inputs for Residential Post

- application Dermal Exposure

Algorithm Notation Exposure Factor (units) Point Estimate(s)

AR Application rate (mass active ingredient per unit area) Up to 17.6 lbs ai/A

### Page 32 of 36

Table D

- 1 : Turf (Physical Activities)

-- Inputs for Residential Post

- application Dermal Exposure

Algorithm Notation Exposure Factor (units) Point Estimate(s)

F Fraction of AR as TTR

following application (if

chemical

- specific data is unavailable) L/WP/WDG 0.01

F D Daily residue dissipation

(if chemical

- specific data is unavailable) (fraction) L/WP/WDG 0.1

TC Transfer

Coefficient (cm 2 /hr) L/WP/WDG Adults 180,000

Children 1 < 2 years old 49,000

Granules Adults 200,000

Children 1 < 2 years old 54,000

ET Exposure Time

(hours per day) Adults 1.5 Children 1 < 2 years old 1.5

BW Body Weight (kg) Adults 80

Children 1 < 2 years old 11 L/WP/WDG = Liquids/Wettable Powders/Water

- dispersible Granules



### Post

- application Hand

- to

- Mouth Exposure Algorithm

– Physical Activities on Turf Exposure from hand

- to

- mouth activity is calculated as follows (based on the algorithm utilized in

the SHEDS

- Multimedia model ):

E = [HR * ( F

M 

### * SA H 

### ) * (ET * N_Replen) * (1

- (1

- SE ) (Freq_HtM/N

- Replen) 

### )]

where:

E = exposure (mg/day); HR = hand residue loading (mg/cm 2 

### ); FM = fraction hand surface area mouthed / event (fraction/event); SAH = typical surface area of one hand (cm 2 

### ); ET = exposure time (hr/day); N_Replen = number of replenishment intervals per hour (intervals/hour); SE = saliva extraction factor (i.e., mouthing removal efficiency); and Freq_HtM = number of hand

- to

- mouth contacts events per hour (events/hour).

and

where:

HR = hand residue loading (mg/cm 2 

### );

Fai hands 

### = fraction ai on hands compared to total surface residue from dermal transfer coefficient study (unitless);

### Page 33 of 36

DE = dermal exposure (mg); and

SA H 

### = typical surface area of one hand (cm 2 

### ).

Dose, normalized to body weight, is calculated as:

where:

D = dose (mg/kg

- day);

E = exposure (mg/day); and

BW = body weight (kg).

Table D

- 2 : Turf (Physical Activities)

– Inputs for Residential Post

- application Hand

- to

- Mouth Exposure Algorithm

Notation Exposure Factor (units) Point Estimate(s)

Fai hands Fraction of ai on hands

from dermal transfer coefficient study (unitless) Liquid formulations 0.06

Granular formulations 0.027

DE Dermal exposure (mg) Calculated (0.268)

SA H Typical surface area of one hand (cm 2 ), children 1 < 2 years old 150

AR Application rate

(mass active ingredient per unit area) 17.6 lbs ai/A

HR Residue available on the hands (mg/cm 2 ) Calculated via (DE * Fai hands )/SA H

F M Fraction hand surface area mouthed (fraction/event) 0.127

N_Replen Replenishment intervals per hour (intervals/hr) 4

ET Exposure time (hrs/day) 1.5

SE Saliva extraction factor (unitless) 0.48

Freq_HtM Hand

- to

- mouth events per hour (events/hr) 13.9

BW Body Weight

(kg) Children 1 < 2 years old 11



### Post

- application Object

- to

- Mouth Exposure Algorithm

– Physical Activities on Turf Exposure from object

- to

- mouth activity is calculated as follows (based on the algorithm utilized

in SHEDS

- Multimedia):

E = [OR* CF1 * SAM O 

### * (ET * N_Replen) * (1

- (1

- SE O 

### ) (Freq_OtM/N_Replen) 

### )]

where:

E = exposure (mg/day);

### Page 34 of 36

OR = chemical residue loading on the object on day “t” (ug/cm 2 

### ); CF1 = weight unit conversion factor (0.001 mg/μg);

SAM O 

### = area of the object surface that is mouthed (c m 2 

### /event); ET = exposure time (hr/day); N_Replen = number of replenishment intervals per hour (intervals/hour);

SE O 

### = saliva extraction factor (i.e., mouthing removal efficiency); and Freq_OtM = number of object

- to

- mouth contact events per hour (events/hour).

and

OR = AR * F O 

### * CF2 * CF3

where:

OR = chemical residue loading on the object (μg/cm 2 

### ); AR = application rate (lbs ai/ft 2 

### or lb ai/acre);

F O 

### = fraction of residue available on the o bject (unitless); CF2 = weight unit conversion factor (4.54 x 10 8 

### μg/lb); and CF3 = area unit conversion factor (1.08 x 10 - 3 

### ft 2 

### /cm 2 

### or 2.47 x 10 - 8 

### acre/cm 2 

### ).

Dose, normalized to body weight, is calculated as:

where:

D = dose (mg/kg

- day);

E = exposure (mg/day); and

BW = body weight (kg).

Table D

- 3 : Turf (Physical Activities)

– Inputs for Residential Post

- application Object

- to

- Mouth Exposure
Algorithm

Notation Exposure Factor (units) Point Estimate(s)

AR Application rate (to turf)

(mass active ingredient per unit area) Up to 17.6 lbs ai/A

F O Fraction of AR as OR following application 1 0.01

SAM O Surface area of object mouthed (cm 2 /event) 10

N_Replen Replenishment intervals per hour (intervals/hour) 4

SE O Saliva extraction factor (fraction) 0.48

ET Exposure time (hours per day) 1.5

Freq_OtM Object

- to

- mouth events per hour (events/hr) 8.8

BW Body Weight (kg) Children 1 < 2 years old 11

1 This SOP assumes that all of the residue on the turf could be transferred to the object (e.g., object residue is equal to turf transferable residue).

### Page 35 of 36

Post

- application Incidental Soil Ingestion Exposure Algorithm

– Physical Activities on Turf Exposure from incidental soil ingestion is calculated as follows:

E = SRt * SIgR * CF1

where: E = exposure (mg/day); SRt = soil residue on day "t" (μg/g); SIgR = ingestion rate of soil (mg/day); and CF1 = weight unit conversion factor (1 x 10 - 6 

### g/μg).

and

SRt = AR * FS * (1

- F D 

### ) t 

### * CF2 * CF3 * CF4

where:

SR t 

### = soil residue on day "t" (μg/g); AR = application rate (lbs ai/ft 2 

### or lb ai/acre); FS = fraction of ai available in uppermost cm of soil (fraction/cm);

F D 

### = fraction of residue that dissipates daily (unitless); T = post

- application day on which exposure is being assessed; CF2 = weight unit conversion factor (4.54 x 10 8 

### μg/lb); CF3 = area unit conversion factor (1.08 x 10 - 3 

### ft 2 

### /cm 2 

### or 2.47 x 10 - 8 

### acre/cm 2 

### ); and CF4 = soil volume to weight unit conversion factor (0.67 cm 3 

### /g soil).

Dose, normalized to body weight, are calculated as:

where :
D = dose (mg/kg

- day);

E = exposure (mg/day); and

BW = body weight (kg).

Table D

- 4 : Turf (Physical Activities)

– Inputs for Residential Post

- application Incidental Soil Ingestion Exposure
Algorithm

Notation Exposure Factor (units) Point Estimate(s)

AR Application rate

(mass active ingredient per unit area) Up to 17.6 lbs ai/A

FS Fraction of AR available in uppermost 1 cm of soil (unitless) 1

F D Daily residue dissipation (fraction) 0.1

SIgR Soil ingestion rate (mg/day) 50

### Page 36 of 36

Table D

- 4 : Turf (Physical Activities)

– Inputs for Residential Post

- application Incidental Soil Ingestion Exposure

BW Body weight (kg) Children 1 < 2 years old 11