UNITED STATES ENVIRONMENTAL PROTECTION AGENCY

WASHINGTON

, D

. C. 20460



### MEMORANDUM

Date: May 1 4, 20 1 5 OFF I CE OF CHEM I CAL SA FET Y AND PO L L UTION PREVENTION



### SUBJECT : Thiab e ndazole: ID # l 5ID02

- Sect i o n 18 E m e r gency Exe mpti o n for th e Use of Thiabendazole as a Seed Tr eatme nt o n S u ccu l ent P eas in B onnev ill e and Latah Cou nt ies in Id aho

.

PC Co de: 060 I 0 I De c i s ion No. : 500376 Petiti o n No.: NA Ri s k Assessme nt T y pe: S in g l e Chemica l Aggregate TXR No. : NA MRID No. : NA DP Barcode: 425853 R eg i s tration No.: 151002 Regulator y Action: Sectio n 1 8 Case No.: 2670

CAS No.: 148

- 79 -8 40 CFR: 180. 242



### FROM: Jessica Kidwell

, Risk Assessor

# ~**~ ~~**  {'°"1\il,

-

# '(~ t<-,.--
Bonnie Cropp -K o hlli g i a n ,

## es**idu/Ch ~~i** **~t~** and Dietary Exposure

## Ass~~**~** 0 Abda ll a h Khasawinah

, PhD.

, Tox ic o l ogis t**~CC~** K elly O'Rourke

, Occupational/Residential Exposure Assessor

### --Y~ 

### Wl.0 ''f!cJL'-- Risk Assessmen t Branc h 4 H ea lth Effects Di vision (7509P)



### THROUGH: Elissa Reaves
, PhD

, Bran c h C hi Risk Assessmen t Branch 4 Health Effec t s Division (7509P)



### TO: Keri Grinstead

, Andrea Conra th

, a nd Tawanda Maignan

, RM09 Fungicide Branch Registration Division (7505P)

P age 1 of 25

### Thiabendazole / 060I0 1 Hu man Health Risk Assessme nt 04 25853

1.0 E xecut i v e Summary

......... ..... .. . .......... .. .. .. .......................................................... .. .............. 3 

### 2

. 0 H E D R eco mmendation s

. .. .. .. .............. . .. .. .............. .. . ... ...... . ... . ........ . .. .. .. . ........ .. .. . . . .. .......... 4 2.1 

### 2

. 2 2

. 2

. 1 2.2.2 2

. 2.3 2.2.4 2.3 Data Deficienci es

........................... ...... . ... ......... .. .. .. ....... . ...... . .. . .. ......... .. .... ............ . ... 4 To l erance Co n s id erat i ons

............ . .. . . ........... . ......................................... .... ............... 4 E nforcement A nal y tic a l Method

........................................ ... .................................. 4 Int e rnational H a rmoniz a tion

........ . .......................................................................... 4 R eco mmend e d To l erances

.. .. .. .. .. . ... ........................ ... ........ .. . .. .... ........ ............ . ..... .. .. 4 Revi s i ons to Petitioned-For Toleranc es

............ .. ............ .. ..................... ...... ........... 5 Labe l Recon1m e ndation s

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

### 3.0 3 .1 3.2 

### 3

. 3 Intr od u c tion

......... ........ .......... ................................... ....... . .. ...... ........ ................. ........ ....... .. 5 C hemical Identi ty

.... .. .. . .. .......... .. .. . ....................................... .. .. .. . .. .. . .. ......... .............. 5 Ph ys ical/Chemical C har acte ri s tics

...... . ..................... . ... . ... .. . ... . .. . ......... ..... ........ .. .... 6 Pe s ticid e Use P a ttern

.......................................................... .. . ... .......... . ............. .. .... .. 6 3.4 Anticipated Ex po s ure P a thw ays

.......... ....... ........... ................................... ..... .......... 7 3.5 Co n s id eratio n of E nvironmental Ju s tic e

. .. ........................................... .. ................ 7 4.0 Hazard C h a racterization and Do s e-Re s pon se Assess ment

.... ........ .. .... .. .. ........ .............. 8 5. 0 Di e tary Ex po s ur e an d Ri s k Assessment..

.................................... .. .... .... .. .. .................. ... 11 5.1 Metabo lit e/Deg rad a te R es i due Profil e

......... ......... ................................. ........ ....... 11 5

. 1.1 S ummary of Plant a nd An imal Meta b o li s m S tudi es

...... ... ..................... ....... ...... 11 5.1.2 S ummary of Environmenta l D eg r a dation

.... .. ...... ...... ..... . ... ................. ................ 11 5.1.3 Co mpari so n of Metabolic P at hway s

... ..... ........... ...................................... .. ........... 11 5 .1. 4 R esi du es of Co nc e rn Summary and Rationale

...................... ......... ........ .. ............ 1 2 5. 2 Foo d R es idu e Profi le

............................................................ .... ............... ... ............. 1 3 5.3 Water R es idu e Profile

........................................... . ............. ..... ............................... 1 4 5 .4 Di e tar y Risk Assessment

.................. .. ................ .......... .. .. .. .. .. ................................ 1 5 5 .4.1 De s cription of Re s idu e Data Use d in Dieta ry A ss e ss ment

.................... .... .......... 15 5.4.2 Percent Crop Treated Use d in Diet ary A ss e ss m e nt

.......... .. ................................. 

### 16 5 .4.3 Ac u te Diet ary Ri s k Assess ment

...................... .. ................ .. . .. ................................ 

### 16 5.4.4 C hronic Di e tary Ri s k Asse ss ment

.. .. .. .. ...... ........ ............. .. .... .................. .... .......... 17 5.4.5 Ca n cer Dietar y Risk Asse ss ment..

......................... ........ ......... ................ .... ........... 1 7 5.4.6 S ummary Tab l e

................................................................... .. . ... ........... .. . .. .............. 17 6.0 Re s identi a l (N on-Occupational) E xpo s ure / Ri s k C hara c t er iz a tion

............ ................ . 17 7. 0 Aggregate Ex po s ure / Ri s k C h aracterization

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

### 8.0 C umulative Ex po s ure/Risk C h aracte riz at i o n

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

### 9 .0 Occup a tional E xpo s ure / Ri s k C h aracter i zation

...... .. .................. .. ................................ 1 8 

### 9. 1 S h ort- and Intermediate-Term Hand l er Ri s k

........................................ .... .......... 18 9.2 S h ort

- /Inte rm ediate Po st-A pplication Ri s k

. .. .. ....................................... ...... ........ 21 

### 10.0 Reference s

........................ ..... .......................................................... ..... . .. . ... .. . . .. . .. .... . .. ..... . 2 1 Appe ndi x A. International Re s idue Limit s

.. .. ................. . .. ........ . .. .. .. .. .... ............... .. ................. 23 A pp e ndi x B. Physical/C h em i ca l Prop e rtie s

............................................. . ..... . .......... ........ ....... 24 A pp e ndix 

### C. S tudi es Reviewed for E thical Co ndu c t

...... .. .................... . ................................. 25



### P age 2of25

### Thiabendazole/060101 Human Health Risk Assessment D425853

Page 3 of 25 1.0 Executive Summary

The Idaho State Department of Agriculture has requested a Section 18 e mergency e xemption ( ID#15ID02 ) for the use of thiabendazole, formulated as the product Mertect 340

- F (EPA Reg No. 199

- 889)

, as a seed treatment on succulent shelled peas (English Peas) to control Fusarium and Ascochyta Blight in Bonneville and Latah Counties. The request entails application of 1.02 fluid ounces (0.03 lb a.i.) of Mertect 340

- F per 100 pounds of seed. A maximum of 239 gallons of Mertect 340

- F (980 lbs a.i.) may be applied in Bonneville and Latah Counties of Idaho between April 1 through June 15, 2015.

The Health Effects Division (HED) has examined th e Section 18 emergency exemption request materials and availabl e data and has determined that the proposed use of thiabendazole on succulent shelled peas ( Pisum spp. , including English pea, garden pea and green pea) is adequately supported by available data and that a time

- limited tolerance based on the proposed
use p attern (i.e., 0.03 lbs a.i. per 100 pounds of seed) may be established

.
The most recent human health risk assessment ( D416471 , 8/26/2014) identified no risks of

concern

. T he addition of succulent shelled peas ( Pisum spp. , including English pea, garden pe a and green pea), treated according to the proposed Section 18 emergency exemption use rate

, did not change the findings of th is most recent risk assessment for drinking water, dietary (food and water), residential and aggregate exposure s; hence, updated a ssessments for these exposures were not needed

. However, a new occupational exposure and risk assessment was needed for this Section 18 emergency exemption request

. Based on the proposed use pattern, short

- /intermediate

- term durations of exposure are exp ected for occupational handlers. The estimates of exposure to pesticide seed treatment handlers (treatment and planting) are based upon ExpoSAC Policies 14, 15, and 15.1 and a memorandum from the Biological and Economic Analysis Division (BEAD), “Acres Pla nted Per Day and Seeding Rates of Crops Grown in the United States” (J. Becker, March 2011). Short

- / intermediate

- term exposure and risk for seed treatment resulted in total (combined dermal and inhalation) M argins of Exposure (M OEs ) ranging from 3,200 to 35,000 for primary handlers (seed treaters) and an MOE of 6,800 for secondary handlers (seed planters). Note that the short

and intermediate

- term Points of Departure ( PODs ) are the same, and the intermediate

- term exposure inputs are less conservative than the short

- term exposure inputs for seed treatment; therefore, short

- term exposure risk estimates are protective of intermediate

- term exposure risk estimates. These risk estimates are not of concern. A quantitative post

- application assessment is not requir ed for exposure to treated seeds that have already been planted.

### Thiabendazole/060101 Human Health Risk Assessment D425853

Page 4 of 25 2.0 HED Recommendations

HED concludes that a time

- limited tolerance for residues of thiabendazole and its regulated metabolite, benzimidazole, can be established for pea, succulent shelled for the proposed seed treatment use of thiabendazole on succulent shelled peas ( Pisum spp. , including English pea, garden pea and green pea). The specific tolerance recommendations are discussed in 2.2, and label modifications are discussed in section 2.3

.

2.1 Data Deficiencies

None for this action

.

2.2 Tolerance Considerations

2.2.1 Enforcement Analytical Method
HED Memo: D410807, 2/25/14, S. Hummel



### Acceptable enforcement analytical methods are available for thiabendazole and benzimidazole in plant commodities. Four spectrophotofluorometric methods for the determination of thiabendazole are published in the Pesticide Analytical Manual (PAM) Vol. II, a nd a high performance liquid chromatography (HPLC) method with fluorescence detection (FLD) for the determination of benzimidazole (free and conjugated) is identified in the U.S. EPA Index of Residue Analytical Methods under thiabendazole as Study No. 9302 0. The validated limits of detection (LODs) for the thiabendazole methods range from 0.05

- 0.1 ppm, and the validated limit of quantitation (LOQ) for the benzimidazole method is 0.1 ppm.

Thiabendazole is completely recovered using US Food and Drug Admini stration ( FDA )

m ultiresidue methods (MRMs) 302 and 404, but is not recovered using MRM 303. Thiabendazole residues are routinely generated by the Pesticide Data Program (PDP) of the US Department of Agriculture (USDA) using MRM s with very low LODs

. While MRM data submitted to EPA suggest that b enzimidazole and 5

- hydroxy

- thiabendazole are not recovered by the FDA MRMs , 5

- hydroxy

- thiabendazole residues are also routinely generated by PDP

.

2.2.2 International Harmonization

There is no issue with Internation al Harmonization (See Appendix A) . Neither CODEX nor Canada has established a maximum residue limit (MRL) for thiabendazole on the requested commodit y

. We note that the U.S. tolerance definition is not harmonized with Canada or CODEX.

2.2.3 Recommended Tolerances

The current permanent tolerance definition fo r residues of thiabendazole in/on plant commodities is for the combined residues of the fungicide thiabendazole (2

- (4

- thiazolyl)benzimidazole) and its metabolite benzimidazole (free and conjugated) a nd the current tolerance express i on is in accordance with the HED Interim Guidance on Tolerance Expressions (S. Knizner, 5/27/09)

.

### Thiabendazole/060101 Human Health Risk Assessment D425853

Page 5 of 25 Table 2.2.3.1 summarizes the recommended time

- limited tolerance level and commodity definition required to support the proposed new Section 18 emergency exemption use on pea, succulent shelled. This tolerance should be added to 40 CFR §180.242 (b) , using th e c urrent permanent tolerance definition and expression. Time

- limited tolerances in/on pea vines and hay will not be established for this Section 18 emergency exemption, given (1) that the proposed use is limited and prohibits the feeding of pea vines and hay grown from treated seed to livestock and (2) that the available soybean forage and hay data indicate that residues in/on these livestock feed commodities are not likely to be detectable. However, a Section 3 registration for use on peas, if that use in cludes field peas, would most likely require the establishment of tolerances in/on pea vines and hay and a restriction would not be appropriate

.

Table 2.2.3.1 Tolerance Summary for Thiabendazole.

Commodity Proposed Tolerance (ppm) Recommended

Tolerance (ppm) Comments; Correct Commodity Definition

Pea, succulent shelled Not Applicable 0.02 1 Pea, succulent shelled

1 Tolerance set at LOQ for both, thiabendazole and benzimidazole



### 2.2.4 Revisions to Petitioned

- For Tolerances

No tolerances were proposed by the petitioner.

2.3 Label Recommendations

The risk assessment supports the proposed thiabendazole seed treatment labels requiring only baseline level of clothing (i.e., long

- sleeve shirt, long pants, shoes/socks) without use of chemical

- resistant gloves. However, additional personal protective equipment (PPE) may be needed based on the acute toxicity of the end

- use product. HED recommends that the Registration Division (RD) ensure that the appropriate PPE (e.g., chemical

- r esistant gloves) be included on the final label if necessary.

3.0 Introduction

3.1 Chemical Identity

The chemical structure and nomenclature of thiabendazole and its regulated metabolites are presented in Table 3.1.

Table 3.1. Test Compound Nomenclature. Compound

Common name Thiabendazole Company experimental name None
IUPAC name 2

- (thiazol

- 4

- yl)benzimidazole
CAS name 2

- (4

- thiazolyl)

- 1 H

- benzimidazole

### Thiabendazole/060101 Human Health Risk Assessment D425853

Page 6 of 25 Table 3.1. Test Compound Nomenclature. CAS registry number 148

- 79

- 8
End

- use product (EP) 4.1 lb ai/gal FlC formulation (Mertect 34F; EPA Reg. No 100

- 889) Compound

Common name Benzimidazole
Chemical name 1H

- benzimidazole CAS registry number 51

- 17

- 2 Compound

Common name 5

- hydroxy

- thiabendazole
Chemical name 2

- (1,3

- thiazol

- 4

- yl)

- 1H

- benzimidazol

- 5

- ol)



### 3.2 Physical/Chemical Characteristics

Technical thiabendazole is a colorless crystalline solid with a melting point of 304

- 305 C, bulk density of 25

- 30 cc (tapped), octanol/water partition coefficient (K ow 

### ) of 240

- 285 at pH7, and has a low vapor pressure of 4 X 10

- 9 

### mm Hg at 25°C. Thiabendazole is sparingly soluble in water at 0.028

- 0.030 mg/mL at 25°C, and is soluble in several organic solvents. The physicochemical properties of the technical grade of thiabendazole are presented in Appendix B

.

3.3 Pesticide Use Pattern

The petitioner has submitted a draft Section 18 emergency exemption label (not dated) for Mertect® 340

- F Fungicide (EPA Reg. No. 100

- 889) which includes proposed regionally restricted use directions for succulent shelled cultivars of pea ( Pisum spp. ) including English pea, garden pea and green pea. The proposed use directions are summarized in Table 3.3.1. See Section 2.3 for recommended modifications to the proposed label.

### Thiabendazole/060101 Human Health Risk Assessment D425853

Page 7 of 25 Table 3.3.1 Summary of Directions for Use of Thiabendazole

.

Applic. Timing, Type, and Equip. Formulation

[EPA Reg. No.] Applic. Rate Max. No. Applic
. per Season PHI Use Directions and Limitations

Pea, succulent shelled ( Pisum spp. ) including English pea, garden pea and green pea. Seed treatment, Seed treatment application equipment 4.1 lb ai/gal F

[100

- 889] 1.02 fl oz /100 lb seed

32.68 g ai/100 kg seed 0.033lb ai/100 lb seed Note: mg ai/seed not provided on label 1 N/A Restricted to use in Bonneville and Latah C ounties in the S tate of Idaho. For ready mix or slurry treaters, mix in adequate water to provide complete coverage. The minimum slurry volume is 4.0 fl oz/100 lb seed and more diluent may be required for completed coverage which is essential. Do not feed vines or hay grown from treated se ed to livestock



### 3.4 Anticipated Exposure Pathways

The Registration Division has requested an assessment of human health risk to support the proposed new seed treatment use of thiabendazole on pea, succulent shelled. Humans may be exposed to thiabendazole in food and drinking water. The proposed seed treatment uses of thiabendazole are not expected to result in residential (non

- occupational) exposures . However, residential exposure is possible via antimicrobial uses in products such as paints and sponges. Occupational exposure is expected for primary handlers (seed treaters) and secondary handlers (seed planters). Post application exposure is not expected for workers.

Risk assessments have been previously prepared for the existing uses of thia bendazole. This risk assessment considers all of the aforementioned exposure pathways based on the proposed new uses of thiabendazole, but also considers the existing uses as well.

3.5 Consideration of Environmental Justice

Potential areas of environm ental 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
p rocedures. 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 reside ntial setting. Extensive data on food consumption patterns are compiled by the USDA under the Continuing Survey of Food Intake by Individuals (CSFII) and are used in pesticide risk assessments for all registered food uses of a pesticide. These data are an alyzed and categorized by subgroups based on age, season of the year, ethnic group, and region of the country. Additionally, OPP is able to assess dietary exposure to smaller, specialized subgroups and exposure assessments are

### Thiabendazole/060101 Human Health Risk Assessment D425853

Page 8 of 25 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 patte rns among specific subgroups.

4.0 Hazard Characterization and Dose

- Response Assessment

The hazard characterization and dose response assessment were last updated in the 8/26/14 risk assessment (D416471). No updates were needed for this assessment. The toxicological endpoint selection table is presented below. Refer to the previous assessment (D416471) for any detailed information.

Table 4.1 Summary of Toxicological Doses and Endpoints for Thiabendazole for Use in Dietary and Non

Occupational Human Health Risk Assessments

Exposure/ Scenario Point of

Departure Uncertainty/FQ

PA Safety Factors RfD, PAD,

Level of Concern for Risk Assessment Study and Toxicological Effects

Acute Dietary (general population including females 13

– 49 years and children) NOAEL =

50 mg/kg UF A = 10X

UF H = 10X FQPA UF DB = 10X aRfD =

0.05mg/kg/day aPAD = 0.05 mg/kg Acute neurotoxicity Study (MRID 48996310)

LOAEL = 200 mg/kg based decreases in the FOB (reduced body temperature in males p<0.05, and reduced rearing in females ↓54%, p<0.01), reduced locomotor activity in males and females (↓37

- 46%, p<0.01), at time of peak effect (approximately 3 hours post

- dose). Reduced body weight gain (p<0.01) and food consumption (↓44%, p<0.01) o ccurred on day 1.

Chronic Dietary NOAEL =

10 mg/kg/day UF A = 3X

UF H = 10X FQPA UF DB = 10X cRfD =

0.033 mg/kg/day cPAD = 0.033 mg/kg/day 2

- Year chronic carcinogenicity in the Rat

(MRID 43593201) Chronic LOAEL = 30 mg/kg/day based on decreased body weight gains and liver hypertrophy. Thiabendazole induced thyroid adenomas in male rats at dosages of ≥30 mg/kg/day.

Supported by subchronic toxicity rat study (MRID 42942802)

Subchronic LOAEL = 40 mg/kg/ based on reduced body weight and body weight gains ((↓11%) and histopathological changes in the bone marrow (erythroid hyperplasia), liver (centrilobular hypertrophy), thyroid (follicular cell hypertrophy) and spleen (pigmented).

### Thiabendazole/060101 Human Health Risk Assessment D425853

Page 9 of 25 Table 4.1 Summary of Toxicological Doses and Endpoints for Thiabendazole for Use in Dietary and Non

Occupational Human Health Risk Assessments

Exposure/ Scenario Point of

Departure Uncertainty/FQ

PA Safety Factors RfD, PAD,

Level of Concern for Risk Assessment Study and Toxicological Effects

Incidental Oral (Short

– term (1

- 30 days) and intermediate

term (1

- 6 months) NOAEL= 10

mg/kg/day UF A = 3x

UF H =10x FQPA UF DB = 10x Residential

LOC for MOE = 300 Subchronic oral toxicity study

– rat

MRID 42942802 LOAEL = 40 mg/kg/day based on reduced body weight gains and histopathological changes in the bone marrow, liver and thyr oid

Dermal Short

- Term (1

- 30 day s) and Intermediate

term (1

- 6 months) DAF = 0.5% NOAEL= 10

mg/kg/day

DAF = 0.5% UF A = 3x

UF H =10 FQPA UF DB = 10x Residential

LOC for MOE = 300 Subchronic oral toxicity study

– rat

MRID 42942802 LOAEL = 40 mg/kg/day based on reduced body weight gains and histopathological changes in the bone marrow, liver and thyroid

Inhalation Short

- Term (1

- 30 days) and Intermediate

term (1

- 6 months) NOAEL= 10

mg/kg/day UF A = 3x

UF H =10x FQPA UF DB = 10x Residential

LOC for MOE = 300 Subchronic oral toxicity study

– rat

MRID 42942802 LOAEL = 40 mg/kg/day based on reduced body weight gains and histopathological changes in the bone marrow, liver and thyroid

Cancer (oral, dermal, inhalation) Likely to be carcinogenic at doses high enough to cause a disturbance of the thyroid hormonal balance

but not likely to be carcinogenic at doses lower that those which could cause a disturbance of this hormonal balance (TXR 0050554). Quantification of cancer risk is not required. 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 ob served adverse effect level. LOAEL = lowest observed adverse effect level. UF = uncertainty factor. UF A = extrapolation from animal to human (interspecies). UF H = potential variation in sensitivity among members of the human population (intraspecies). UF DB = to account for the absence of key data (i.e., lack of a critical study). 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. DAF = dermal absorption factor (TXR 0055373)

### Thiabendazole/060101 Human Health Risk Assessment D425853

Page 10 of 25 Table 4..2 Summary of Toxicological Doses and Endpoints for Thiabendazole 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 Short

Term (1

- 30 day s) and Intermediate

term (1

- 6 months) DAF = 0.5% NOAEL= 10

mg/kg/day

DAF = 0.5% UF A = 3x

UF H =10 UF DB = 10x Occupational l

LOC for MOE = 300 Subchronic oral toxicity study

– rat

MRID 42942802 LOAEL = 40 mg/kg/day based on reduced body weight gains and histopathological changes in the bone marrow, liver and thyroid

Inhalation Short

- Term (1

- 30 days) and Intermediate

term (1

- 6 months) NOAEL= 10

mg/kg/day UF A = 3x

UF H =1 0x UF DB = 10x Occupational

LOC for MOE = 300 Subchronic oral toxicity study

– rat

MRID 42942802 LOAEL = 40 mg/kg/day based on reduced body weight gains and histopathological changes in the bone marrow, liver and thyroid
Cancer (oral, dermal, inhalation) Likely to be carcinogenic at doses high enough to cause a disturbance of the thyroid hormonal

balance but not likely to be carcinogenic at doses lower that those which could cause a disturbance of this hormonal balance (TXR 0050554). Quantifica tion of cancer risk is not required. 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 re levant human exposures. NOAEL = no observed adverse effect level. LOAEL = lowest observed adverse effect level. UF = uncertainty factor. UF A = extrapolation from animal to human (interspecies). UF H = potential variation in sensitivity among members of the human population (intraspecies). UF L = use of a LOAEL to extrapolate a NOAEL. UF S = use of a short

- term study for long

- term risk assessment. UF DB = to account for the absence of key data (i.e., lack of a critical study). MOE = margin of exposure. LOC = level of concern. N/A = not applicable. DAF = dermal absorption factor (TXR 0055373)

### Thiabendazole/060101 Human Health Risk Assessment D425853

Page 11 of 25 5.0 Dietary Exposure and Risk Assessment

5.1 Metabolite/Degradate Residue Profile

5.1.1 Summary of Plan t and Animal Metabolism Studies

The nature of the residue in plants is understood based on acceptable plant metabolism studies conducted in wheat, soybean, and sugar beet. In the three plant metabolism studies submitted, the parent compound and benzimidaz ole (free and conjugated) were the major residues. In the confined rotational crop study, thiabendazole (TBZ) , benzimidazole (BNZ) , and 5

- hydroxy thiabendazole ( 5

- OH

- TBZ ) were identified. The residues of concern in primary and rotational crops for purposes of tolerance enforcement and risk assessment are thiabendazole and its metabolite benzimidazole (free and conjugated). The nature of the residue in livestock is understood based on acceptable hen and goat metabolism studies. The major metabolite in goat

m ilk and tissues is the 5

- OH

- TBZ compound (and its conjugates); BNZ and TBZ are also present. TBZ degrades predominantly to 5

- OH

- TBZ and its conjugates in hens. Varying amounts of BNZ and unchanged TBZ are also present in eggs and hen tissues. The residues of concern in livestock commodities are thiabendazole, 5

- hydroxy

- thiabendazole (free and conjugated), and benzimidazole.

5.1.2 Summary of Environmental Degradation

Environmental fate studies show that thiabendazole is persistent and immobile. Thiabenda zole is stable to hydrolysis and soil photolysis and degrades slowly in aerobic (half

- life ~ 700 days) and anaerobic soil environments (>200 days). Aquatic photolysis, with a half

- life of 1.2 days in clear water, appears to be the only significant degradat ion pathway. Under anaerobic aquatic conditions thiabendazole showed no evidence of abiotic or biotic degradation but moved rapidly from water phase to the sediment phase. Thiabendazole binds tightly to soil due to its high soil/water partitioning coeffici ents (K oc 

### s > 1,000 mL/g oc 

### ), thus limiting the amount available for leaching into ground water and for solution phase runoff into surface water. With the high sorption capacity, thiabendazole would be transported on eroded sediment. Sorption was weakly

corr elated to organic carbon. Terrestrial field dissipation studies showed thiabendazole to be extremely persistent with no observable leaching. Vapor pressure and Henry’s Constant indicate that thiabendazole has a low potential to volatilize from soil and wat er.

5.1.3 Comparison of Metabolic Pathways

In the plant metabolism studies submitted, the parent compound and benzimidazole (free and conjugated) were the major residues when foliar application was used. Although 5

- hydroxy thiabendazole is a major metabolite in rats and livestock, it is minor in pl ants. In the confined rotational crop study, thiabendazole, benzimidazole, and 5

- hydroxy thiabendazole were identified. The major metabolite in livestock is the 5

- OH

- TBZ compound (and its conjugates); BNZ and TBZ are also present.

### Thiabendazole/060101 Human Health Risk Assessment D425853

Page 12 of 25 5.1.4 Residues of Concern Summary and Rationale

Residues of Concern: The qualitative nature of the residue in plants is adequately understood based on soybean, sugar beet and wheat metabolism studies reflecting foliar treatments. The HED Metabolism Assessment Review Commi ttee (MARC) determined that residues of concern in plants for regulation and dietary risk assessment include thiabendazole and its metabolite benzimidazole (free and conjugated). No residues of 5

- hydroxythiabendazole were identified in these plant metaboli sm studies. [Note: The 5

- hydroxythiabendazole metabolite was identified as a minor residue in rotational crops.] Post

- harvest treatments are expected to result in the highest potential residues of thiabendazole per se in/on plant commodities and potentia l residues of benzimidazole (free and conjugated) are unlikely to contribute significantly to the total thiabendazole residues of concern for these uses. Based on re

- evaluation of the available foliar metabolism data, the reviewer has determined that maxim um total thiabendazole residues of concern in soybean (foliage, immature plant, straw and seed), sugar beet roots, sugar beet tops and wheat (foliage, forage, straw and grain) may be estimated by multiplying the thiabendazole residue level by 1.5x, 1.4x, 1 .8x and 1.8x, respectively.

The qualitative nature of the residue in animals is adequately understood based on acceptable ruminant and poultry metabolism studies. The HED Metabolism Committee determined that residues of concern in livestock for regulati on and dietary risk assessment include thiabendazole, 5

- hydroxythiabendazole (free and conjugated), and benzimidazole.

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

Matrix Residues included in Risk Assessment Residues included in Tolerance Expression

Plants Primary Crop thiabendazole and benzimidazole (free and conjugated) thiabendazole and benzimidazole (free and conjugated)

Rotational Crop thiabendazole and benzimidazole (free and conjugated) thiabendazole and benzimidazole (free and conjugated)

Livestock Ruminant thiabendazole, 5

- hydroxy

thiabendazole (free and conjugated), and benzimidazole thiabendazole, 5

- hydroxy

thiabendazole (free and conjugated), and benzimidazole

Poultry thiabendazole, 5

- hydroxy

thiabendazole (free and conjugated), and benzimidazole thiabendazole, 5

- hydroxy

thiabendazole (free and conjugated), and benzimidazole Drinking Water thiabendazole Not Applicable

### Thiabendazole/060101 Human Health Risk Assessment D425853

Page 13 of 25 5.2 Food Residue Profile
HED Memo: D410807/D410833/D313507, 2/25314, S. Hummel



### To support the Section 18 e mergency e xemption request for use of thiabendazole as a seed
treatment on succulent shelled peas ( Pisum spp. , including English pea, garden pea and green pea), the Idaho application i ncluded two new field trial data reports but not the full studies. The preliminary report of pea/bean field trial data from trials conducted by Syngenta Crop Protection, LLC (hereafter referred to as Syngenta) at an exaggerated rate, support pr eviously su bmitted soybean field trial data which are deemed adequate to support the proposed use and these data are discussed briefly below. The preliminary report of fresh peas from Sleepy Eye, MN is consistent with the data above but provides too little detail to be of use and will not be discussed fur ther.

Syngenta reportedly conducted thirty

- five field trials in the United States on peas and beans (succulent shelled, edible

- podded and dried shelled varieties) using Mertect® 340

- F, containing 4.1 lb ai/gal thiabendazole, at a nominal seed treatment rate of 0.2 mg ai/seed. This rate is approximately 2x the proposed maximum use rate estimated by the reviewer at 0.11 mg ai/seed (use rate 0.033 lb ai/100 lb seed) and BEAD 1 

### estimated 1361

- 2800 garden pea seed/lb of seed). Samples were collected at normal harvest timing and stored frozen for up to 19 months prior to analysis. Samples were analyzed using the liquid chr o matography with tandem mass spectrometry (LC

- MS/MS) method GRM040.01A which has been previously deemed acceptable for data

- collection; the l imit of quantitation (LOQ) determined as the lowest level of method validation (LLMV) is 0.01 ppm for both th i abendazole and benzimidazole, for a combined LOQ of 0.02 ppm. Residues of thiabendazole and benzimidazole were reportedly less than the LOQ (<0.0 1 ppm

, for each analyte ) in/on succulent shelled peas/beans (6 pea trials and 6 bean trials), edible

- podded peas/beans (3 peas trials and 6 bean trials) and dry shelled peas/beans (5 pea trials and 9 bean trials). These reported data are consistent with th e previously submitted/reviewed soybean data discussed below.

Syngenta previously submitted soybean field trial data reflecting seed treatment use of thiabendazole which were reviewed by HED (D410807). E ighteen independent field trials were conducted in the United States during the 2010 growing season. Mertect® 340

- F was applied to the seeds at a nominal rate calculated by the original reviewer of 0.06 mg ai/seed (based on use rate of 0.04 lb ai/ 100 lb seed and BEAD estimated 3,000 seeds/lb of seed). Fo r each trial site, samples of treated seeds were planted within 3

- 30 days of treatment. Samples of soybean forage and hay were harvested from all trials 46

- 94 days after planting (DAP); seed was harvested 109

- 153 DAP. Hay samples were dried to approximat ely 10

- 20% moisture content; drying intervals were not reported. Samples of soybean were stored frozen from collection to analysis for 221

- 273 days (7.3

- 9.0 months) for forage, 222

- 274 days (7.3

- 9.0 months) for hay, and 181

- 224 days (6.0

- 7.4 months) for s eed. Samples were analyzed for residues of thiabendazole and benzimidazole using the LC/MS/MS method GRM040.01A deemed adequate for data

- collection.

1 Becker, J. and Ratnayake, S. 3/24/11. No DP Barcode. Acres Planted per Day and Seeding Rates of Crops Grown in the United States.

### Thiabendazole/060101 Human Health Risk Assessment D425853

Page 14 of 25 Residues of thiabendazole and benzimidazole were each below the LOQ (<0.01 ppm) in/on all samples of soyb ean seed, forage and hay.

Acceptable storage stability data are available indicating that residues of both analytes are stable during frozen storage for up to 22 months in/on soybean forage, hay, and seed (DP# 280701, 12/9/10, T. Morton). These data are adequate to support the sample storage conditions and durations for the field trials discussed above.

5.3 Water Residue Profile
EFED Memo: D410805, 2/24/14, J. Wolf. (Drinking Water Assessment (DWA))



### An updated drinking water assessment is not needed for this Section 18 e mergency e xemption request for use of thiabendazole on succulent shelled peas ( Pisum spp. , including English pea, garden pea and green pea). The most recent drinking water assessment (D410805) provided Tier 1 estimated drinking water concentrations (EDWCs) resulting from the currently registered seed treatment use rate estimated for wheat at 0.20 lb ai/A which is higher than the estimated maximum proposed seed treatment use rate for su cculent peas at 0.14 lb ai/A (calculated by the reviewer based on the proposed use rate of 0.033 lb ai/100 lb seed and the BEAD 2 

### estimated 1361

- 2800 garden pea seed/lb of seed and BEAD estimated seeding rate for garden peas of 560,057 seed/A). The finding s of the most recent drinking water assessment (D410805) are reiterated below.

The drinking water estimates used in the dietary risk assessment were provided by the Environmental Fate and Effects Division (EFED; D410805). EFED conducted a Tier I drinki ng water assessment for thiabendazole in surface water using the FQPA Index Reservoir Screening Tool (FIRST) model and in ground water using the Pesticide Root Zone Model for GroundWater (PRZM

- GW). The highest Estimated Drinking Water Concentrations (EDWC s) resulted from the currently registered use of thiabendazole on wheat as a seed treatment and not from the proposed new uses or requested soybean use rate increase. Surface water estimates were higher than ground water estimates. The highest EDWCs for peak and annual mean were 3.80 and 0.47 μg/L (ppb), respectively. The peak concentration of 0.0038 ppm and annual mean of 0.00047 ppm were used in the acute and chronic dietary exposure analyses, respectively. See Table 5.3 below for details.

2 Becker, J. and Ratnayake, S. 3/24/11. No DP Barcode. Acres Planted per Day and Seeding Rat es of C rops Grown in the United States.

### Thiabendazole/060101 Human Health Risk Assessment D425853

Page 15 of 25 Table 5.3. Summary of Tier 1 Estimated Drinking Water Concentrations in Surface and Ground Water for the New Uses and Previously Assessed Wheat Use.

New Uses and Reassessment Thiabendazole Peak Concentration Annual Average Surface Water Crop (app rate lb a.i./A) Model μg/L

New Uses (0.15) FIRST 2.85 0.35 Wheat (0.20) FIRST 3.80 0.47 From RED Peak Concentration 56

- day Average Wheat (0.20) GENEEC 2.40 1 1.55 1 Groundwater Highest Daily Concentration Average Concentration after Breakthrough New Uses (0.15) PRZM

- GW 0.46

- Wheat (0.20) PRZM

- GW 0.62

- 1 The highest EDWCs in surface water for thiabendazole were previously prepared for the 2002 Reregistration Eligibility Decision (RED), using the Tier 1 GENEEC model (which has since been replaced by the FIRST model) for surface water and the SCI

- GROW mode l (which has since been replaced with PRZM

- GW) for groundwater. The peak concentrations are higher than previously determined for the RED primarily due to changes in the conceptual model (GENEEC vs. FIRST) (e.g., differences of field size and shape and th e implementation of the Index Reservoir) and difference in fate input values for modeling. The chronic EDWCs are lower than before due the inclusion of the Index Reservoir (e.g., size and flow through the reservoir).



### The drinking water models and their de scriptions are available at the EPA internet site: http://www.epa.gov/oppefed1/models/water/

.

5.4 Dietary Risk Assessment HED Memo: D416470, 3/10/14, B. Cropp

- Kohlligian



### An updated dietary risk assessment is not needed for this Section 18 e mergency e xemption request for use of thiabendazole on succulent shelled peas ( Pisum spp. , including English pea, garden pea and green pea). Based on the supporting residue chemistry dat a, the combined residues of th i abendazole and benzimidazole in/on succulent shelled peas ( Pisum spp. , including English pea, garden pea and green pea) is estimated at 0.01 ppm (i.e., 1⁄2 LOQ for each analyte) for the proposed Section 18 e mergency e xemption u se. The previous drinking water estimates (D410805) are deemed adequate for the proposed use on succulent shelled peas. The addition of succulent shelled peas ( Pisum spp. , including English pea, garden pea and green pea) and the assumption of 100% of succ ulent shelled peas treated did not change the findings of the most recent dietary exposure and risk assessment (D416470) which are reiterated below.

5.4.1 Description of Residue Data Used in Dietary Assessment

With regards to food, refined acute probab ilistic and chronic dietary exposure assessments were conducted for thiabendazole using anticipated residue estimates for all existing uses except, cereal grains, citrus oil/peel, dried beans/peas and soybeans. Established/recommended tolerances were used for cereal grains (corn tolerance at the method limit of quantitation; estimated at 1⁄2 LOQ), citrus oil/peel, dried beans, soybeans and the proposed new seed treatment uses. Maximum residues based on field trial data were used for dried peas. Anticipated re sidue estimates for carrot, potato, sweet potato, cantaloupe, orange, apple, pear baby food, strawberry,

### Thiabendazole/060101 Human Health Risk Assessment D425853

Page 16 of 25 mushrooms, avocado, banana, mango, and papaya were based on USDA PDP monitoring data for thiabendazole and translated, as appropriate to yams, other ci trus fruits, other pome fruits and plantains. Because USDA PDP monitoring data did not include benzimidazole (free and conjugated), an additional factor based on available metabolism data reflecting foliar use was applied to sweet potato/yam, avocado, cant aloupe, strawberry and mushrooms to account for this residue.

There is no reasonable expectation of finite residues of thiabendazole in poultry and eggs. Anticipated residue estimates in meat and milk considered exposure from thiabendazole

- treated feedst uffs as well as from the use of thiabendazole as an animal drug, regulated by FDA. Anticipated residue estimates in tissues with the exceptions of beef meat and beef fat were based on feeding study data. Anticipated residue estimates in the meat and fat o f beef were based on tolerances established under 21 CFR §556.730 for residues of thiabendazole at 0.1 ppm for negligible residues of thiabendazole in tissues. The anticipated residue estimate in milk was based on USDA PDP data for parent and available fee ding study data for its metabolite, 5

- hydroxythiabendazole (free and conjugated). All estimates were supported by available ruminant metabolism data.

DEEM default processing factors were used for all commodities except potato chips/granules/flakes and whe at processed commodities which relied on empirical data demonstrating that residues do not concentration in these processed commodities. Also, the maximum theoretical concentration factor for citrus peel (3.3x) was applied to orange and lemon peel, since t he use on citrus is post

- harvest and most of the residues should be found in/on the peel.

5.4.2 Percent Crop Treated Used in Dietary Assessment

The available percent crop treated (%CT or PCT) data for the currently registered seed treatment uses of thiabendazole on soybeans and wheat (SLUA report 2/22/13) were used in the acute and chronic dietary assessments. The following maximum percent crop treated estimates were used in the acute dietary risk assessment for the following crops that are currently registered for thiabendazole: soybeans 2.5% and wheat 2.5%. The following average percent crop treated estimates were used in the chronic dietary risk assessment for the following crops that are currently registered for thiabendazole: soybeans 1% and whea t 1%. The available %CT data for the currently registered seed treatment use of thiabendazole on potatoes was not use d since there is also a post

- harvest use on potatoes. No other %CT data are available according to BEAD (Email dated 12/12/13 from S. Hadda d (BEAD) to T. Morton (HED)) and, therefore, 100% crop treated was assumed for all other existing/proposed uses.

5.4.3 Acute Dietary Risk Assessment

Estimated acute and chronic dietary exposures to thiabendazole from food and drinking water are below H ED’s level of concern for all population subgroups . The c ombined acute dietary exposure from food and drinking water at the 99.9 th 

### percentile of exposure is estimated at 0.012953 mg/kg/day for the general population, equivalent to 26% of the aPAD. The popu lation subgroup with the highest estimated acute dietary exposure is children 1

- 2 years, with an

### Thiabendazole/060101 Human Health Risk Assessment D425853

Page 17 of 25 estimated exposure at the 99.9 th 

### percentile of 0.034322 mg/kg/day, equivalent to 69% of the aPAD.

5.4.4 Chronic Dietary Risk Assessment

Chronic dietary exposure estimates for food and drinking water are well below HED’s level of concern (<100% CPAD) for all population subgroups. The dietary exposure is estimated at 0.000379 mg/kg/day for the general population (1.1% of the cPAD) and 0.001 562 mg/kg/day (4.7% of the cPAD) for Children 1

- 2 years old, the population subgroup with the highest estimated chronic dietary exposure. The results for all populations are summarized in Table 5 below.

5.4.5 Cancer Dietary Risk Assessment

Since thiab endazole is classified as “ Likely to be carcinogenic at doses high enough to cause a disturbance of the thyroid hormonal balance but not likely to be carcinogenic at doses lower that those which could cause a disturbance of this hormonal balance,” a cancer dietary exposure assessment is not required. HED is currently regulating chronic dietary risk with a chronic RfD that reflects a dose level below dose levels at which thyroid hormone balance is impacted and consequently is also being protective of potenti al carcinogenic effects. Therefore, a cancer dietary assessment was not performed.

5.4.6 Summary Table

Table 5.4 6 Summary of Dietary (Food and Drinking Water) Exposure and Risk for Thiabendazole.

Population Subgroup Acute Dietary (99.9 Percentile) Chronic Dietary Cancer
Dietary Exposure (mg/kg/day) % aPAD* Dietary Exposure (mg/kg/day) % cPAD* Dietary Exposure (mg/kg/day) Risk

General U.S. Population 0.012953 26 0.000379 1.1 All Infants (<1 year old) 0.021098 42 0.000612 1.9



### N/A N/A Children 1

- 2 years old* 0.034322 69 0.001562 4.7
Children 3

- 5 years old 0.028211 56 0.001081 3.3
Children 6

- 12 years old 0.017865 36 0.000597 1.8
Youth 13

- 19 years old 0.009042 18 0.000295 0.9
Adults 20

- 49 years old 0.007528 15 0.000267 0.8
Adults 50

- 99 years old 0.007786 16 0.000276 0.8
Females 13

- 49 years old 0.007789 16 0.000256 0.8 *The population subgroup(s) with the highest risk estimates.



### 6.0 Residential (Non

- Occupational) Exposure/Risk Characterization (AD memo of 6/23/10, T. Leighton, D379421)



### The proposed seed treatment use of thiabendazole is not expected to result in residential (non

occupational) exposures . However, residential exposure is possible via antimicrobial uses in

### Thiabendazole/060101 Human Health Risk Assessment D425853

Page 18 of 25 products such as paints and sponges. The Antimi crobials Division has previously conducted an assessment of these uses (D379421, T. Leighton, 6/23/10). No risks of concern were identified.

7.0 Aggregate Exposure/Risk Characterization HED Memo: D416471, 8/26/14, J. Kidwell, et al

. 

### An updated dietary exposure and risk assessment is not needed for this Section 18 e mergency

e xemption request for use of thiabendazole on succulent shelled peas ( Pisum spp. , including English pea, garden pea and green pea). Hence, an updated aggregate expo sure and risk assessment is not needed. The most recent aggregate exposure and risk assessment (D416471) did not result in any risks of concern

. From the most recent aggregate assessment, the MOEs were 2000 for painters and 1400 (children 1

- 2 years) to 730 0 (general population) for sponges and

, th erefore, were not of concern.

8.0 Cumulative Exposure/Risk Characterization

Unlike other pesticides for which EPA has followed a cumulative risk approach based on a common mechanism of toxicity, EPA has not made a common mechanism of toxicity finding as to thiabendazole and any other substances and thiabendazole does not appear to produce a toxic metabolite produced by other substances. For the purposes of this tolerance action, therefore, EPA has not assumed tha t thiabendazole has a common mechanism of toxicity with other substances. 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 stat ements released by EPA’s Office of Pesticide Programs concerning common mechanism determinations and procedures for cumulating effects from substances found to have a common mechanism on EPA’s website at http://www.epa.gov/pesticides/cumulative/.

9.0 Occu pational Exposure/Risk Characterization

9.1 Short

- and Intermediate

- Term Handler Risk

HED uses the term handlers to describe those individuals who are involved in the pesticide application process. HED believes that there are distinct job functions or ta sks related to applications and exposures can vary depending on the specifics of each task. Job requirements (amount of chemical used in each application), the kinds of equipment used, the target being treated, and the level of protective gear or controls used by a handler can cause exposure levels to differ in a manner specific to each application event.

Based on the proposed seed treatment use , occupational handler exposure is expected. Occupational seed treatment handlers may experience short

- and intermediate

- term exposure to thiabendazole while performing seed treatment activities in commercial settings (mixing, loading, applying liquid formulations; bagging treated seed; sewing bags; and multiple activities) . In addition, occupational handlers ma y experience short

- and intermediate

- term exposure while planting thiabendazole

- treated seeds (for the purposes of regulatory seed treatment, planting treated seeds are referred to as ‘secondary handlers’). However, since the same dermal and inhalation en dpoints were selected for short

- and intermediate

- term exposure durations, short

- term exposure and risk estimates are considered to be protective of intermediate

-

### Thiabendazole/060101 Human Health Risk Assessment D425853

Page 19 of 25 term exposure. While the number of days treating the proposed seed crops could potentially

exc eed the typical intermediate

- term duration used in HED’s occupational assessments, HED has no information to indicate that the same chemical is used consecutively for a long

- term duration. Therefore, chronic occupational handler exposure for seed treatmen t was not assessed. Dermal and inhalation risk estimates were combined in this assessment because the toxicological effects for these exposure routes were similar.

This risk assessment relies in part on data from studies in which adult human subjects we re intentionally exposed to a pesticide or other chemical. These data, listed in Appendix C, are (1) subject to ethics review pursuant to 40 CFR 26, (2) have received that review, and (3) are compliant with applicable ethics requirements.

The results of the occupational handler exposure and risk assessment indicate that short

- / intermediate

- term dermal and inhalation risks are not of concern (i.e., MOEs ≥ 300) . Total MOEs range from 3,200 to 35,000 for seed treaters and for seed planters , the MOE is 6,80 0

. (Tables 9.1.1 and 9.1.2).

### Thiabendazole/060101 Human Health Risk Assessment D425853

Page 20 of 25 Table 9.1.1 Summary of Short

- /Intermediate

- Term Handler Exposures/Risks for Thiabendazole Seed Treatment

Seed Type Max

Application Rate 1 Unit Exposure 2

(mg/lb ai) Amount

of Seed Treated 3 Absorbed Dose

(mg/kg/day) 4 MOE 5 Total MOE 6 lb ai/lb seed Dermal Inhal. lb seed/day Dermal Inhal. Dermal Inhal.
LOADER/APPLICATOR (single layer, no gloves) succulent
pea 0.00 033 0.079 0.00034 339,500 5.5 E

- 0 4 4.7 E

- 0 4 18,000 21,000 9,800
SEWER (single layer, no gloves) succulent
pea 0.00 033 0.0062 0.00023 339,500 4.3 E

- 05 3 .2E

- 04 230 ,000 31 ,000 28 ,000
BAGGER (single layer, no gloves) succulent
pea 0.00 033 0.0091 0.00016 339,500 6.3 E

- 0 5 2.2 E

- 04 16 0,000 45 ,000 35 ,000

MULTIPLE ACTIVITIES (combination of loader/applicator without gloves + no coveralls, sewer without gloves, stacker without gloves) succulent
pea 0.000 33 0.134 0.0016 339,500 9.3 E

- 0 4 2.2 E

- 03 11

, 0 00 4

, 5 00 3

, 2 00

1 Application Rate based on proposed label use for thiabendazole (see Table 3.3.1 ). 2 Unit Exposures from HED Exposure Science Advisory Council Policy 14: Standard Operating Procedures for Seed Treatment. In cases where a vailable data represents workers wearing chemical

- resistant gloves. Unit exposures representing workers without chemical

- resistant gloves were calculated by increasing exposure to the hands

- only portion of the total dermal exposure measurement assuming chemical

- resistant gloves provide 90% protection (i.e., dividing non

- gloved hand exposures by 0.1), the standard protection factor assumption for chemical

- resistant gloves. 3 HED default for lb seed treated per day from HED Exposure Science Advisory Council Interim Policy 15.1 and the BEAD memo “Acr es Planted Per Day and Seeding Rates of Crops Grown in the United States” (J. Becker, March 2011). 4 Daily Absorbed Dose (mg/kg/day) = daily unit exposure (mg/ lb ai) × application rate (lb ai/lb seed) × amount treated (lb seed/day) × Absorption (0.5 % for dermal) ÷ body weight (80 kg. 5 MOE = NOAEL (dermal = 10 mg/kg/day for short

- /intermediate

- term expo sure; inhalation = 10 mg/kg/day for short

- /intermediate

- term ) ÷ Absorbed Dose (mg/kg/day). LOC = 300. 6 Total MOE = 1 ÷[(1 ÷ Dermal MOE) + (1 ÷ Inhalation MOE)]

Table 9.1.2. Summary of Secondary Handler (Planter) Exposures and Risks for Thiabendazole ( Single Layer, No Gloves during Loading Only)

.

Seed Type Max

Application Rate a Unit Exposure b

(mg/lb ai) Amount of

Seed Planted Per Day c Absorbed Dose

(mg/kg/day) d MOE e Total MOE f

lb ai/lb seed Dermal Inhal. lb seed/day Dermal Inhal. Dermal Inhal. succulent pea 0.00 033 1.51 0.0034 3 2

, 96 0 1.0 E

- 0 3 4 .6E

- 04 9

, 9 00 22 ,000 6
, 8 00

a Application Rate based on proposed label use for thiabendazole (see Table 3.3.1 ). b Unit Exposures from HED Exposure Science Advisory Council Policy 14: Standard Operating Procedures for Seed Treatment. Available data represents workers wearing chemical

- resistant gloves. Unit exposures representing workers without chemical

- resistant glo ves were calculated by increasing exposure to the hands

- only portion of the total dermal exposure measurement assuming chemical

- resistant gloves provide 90% protection (i.e., dividing non

- gloved hand exposures by 0.1), the standard protection factor assump tion for chemical

- resistant gloves.

c HED default for lb seed planted per day from HED Exposure Science Advisory Council Interim Policy 15 and the BEAD memo “Acres Planted Per Day and Seeding Rates of Crops Grown in the United States” (J. Becker, March 2011). d Daily Absorbed Dose (mg/kg/day) = daily unit exposure (mg/ lb ai) × application rate (lb ai/lb seed) × amount treated (lb seed/day) × Absorption (0.5% for dermal) ÷ body weight (80 kg).

e MOE = NOAEL (dermal = 10 mg/kg/day for short

- /intermediate

- term exposure; inhalation = 10 mg/kg/day for short

- /intermediate

- term ) ÷ Absorbed Dose (mg/kg/day). LOC = 300. f Total MOE = 1 ÷ [(1 ÷ Dermal MOE) + (1 ÷ Inhalation MOE)]

### Thiabendazole/060101 Human Health Risk Assessment D425853

Page 21 of 25 9.2 Short

- /Intermediate Post

- Application Risk

HED uses the term post

- application to describe exposures that occur when individuals are present in an environment that has been previously treated with a pesticide (also referred to as re

entry exposure). Such exposures may occur when workers enter previously treated areas to perform job functions, including activities related to crop production, such as scouting for pests or harv esting. The potential for dermal and inhalation post

- application exposures following the planting of thiabendazole

- 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 defined in the no/low contact criteria in the WPS. Therefore, while the requirement of a 12 hour restricted entr y interval (REI) for potential contact with treated seed following planting applies based on the acute toxicity of technical thiabendazole, so does the potential exception to this requirement per WPS guidance for situations where contact with residue is no t expected.

Similarly, a post

- application inhalation exposure assessment is not required, as exposure is expected to be negligible. However, the seed treatment handler assessments provide quantitative inhalation exposure assessments for seed treaters and planters, both of which would be protective of most post

- application inhalation exposure scenarios.

10.0 References

Becker, J. and Ratnayake, S. 3/24/11. No DP Barcode. Acres Planted per Day and Seeding Rates of Crops Grown in the United States.

Cropp

- Kohlligian, B. 3/10/14. D416470. Thiabendazole : Acute Probabilistic and Chronic Aggregate Dietary (Food and Drinking Water) Exposure and Risk Assessments for Section 3 Registration for New Seed Treatment Uses on Assorted Vegetables/Small Grains and I ncreased Seed Treatment Use Rate on Soybean.

Hummel, S. 2/25/14 . D410807, D410833, D313507. Thiabendazole. PP# 3F8166. New Seed Treatment Uses on Assorted Vegetables and Small Grains (vegetable, root (except sugar beet); subgroup1B, onion, bulb, subgrou p 3

- 07A; Brassica, head and stem, subgroup 5A; vegetable, cucurbit group 9; alfalfa; spinach (including baby); and small grains (wheat, barley, oats, rye, and triticale). Summary of Analytical Chemistry and Residue Data. Multiresidue Method Data.

Kidwel l, J et al . 8/26/14. D416471. Thiabendazole: Human Health Risk Assessment for the Requested Increase in the Currently Registered Seed Treatment Use Rate on Soybeans and the New Section 3 Uses of Thiabendazole for Seed Treatment on Assorted Vegetables and S mall Grains Including: Vegetable, Root (Except Sugar Beet), Subgroup1B; Radish Tops; Onion, Bulb, Subgroup 3

- 07A; Brassica , Head and Stem, Subgroup 5A; Vegetable, Cucurbit Group 9; Alfalfa; Spinach; and a Number of Small Grains (Barley, Oats, Rye, and Tri ticale).

Leighton, T. 6/23/10. D379421. Thiabendazole: Antimicrobial Residential Uses for Consideration in the Aggregate Assessment to be Developed by USEPA/OPP/HED.

### Thiabendazole/060101 Human Health Risk Assessment D425853

Page 22 of 25 O’Rourke, K. 2/19/14. D416472. Thiabendazole: Occupational/Residential Exposure Assessm ent for Proposed Seed Treatment Uses on Alfalfa, Brassica , Bulb Vegetables, Cucurbits, Root Vegetables, Small Grain Cereals, Spinach and Soybeans.

Wolf, J., Hetrick, J., et al. 2/24/14. D410805. Thiabendazole: Drinking Water Assessment for Proposed New Us es of the Fungicide Mertect® 340

- F (EPA Reg. No. 100

- 889) as a Seed Treatment.

### Thiabendazole/060101 Human Health Risk Assessment D425853

Page 23 of 25 Appendix A. International Residue Limits

Thiabendazole (PC Code 060101) Summary of US and International Tolerances and Maximum Residue Limits Residue Definition : US Canada Mexico 1 Codex 2
40 CFR 180.242 Plants: 2

- (4

- thiazolyl) benzimida zole) and its metabolite benzimidazole (free and conjugated) 2

- (4

- thiazolyl)benzimidazole Plants: thiabendazole

Commodity Tolerance (ppm) /Maximum Residue Limit (mg/kg) US Canada Mexico 1 Codex 2 Pea, succulent shelled 0.02 Completed: M. Negussie; 03/17/15

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

2 * = absent at the limit of quantitation; Po = postharvest treatment, such as treatment of stored grains. PoP = processed postharvest treated commodity, such as processing of treated stored wheat. (fat) = to be measured on the fat portion of the sample. MRLs indicated as proposed have not been finalized by the CCPR and the CAC.

### Thiabendazole/060101 Human Health Risk Assessment D425853

Page 24 of 25 Appendix B

. Physical/Chemical Properties

Table C1. Physicochemical Properties of the Technical Grade Test Compound: Thiabendazole.
Parameter Value Reference Melting point/range 304

- 305 °C Thiabendazole RED 10/02 pH 5.16

- 5.97 Thiabendazole RED 10/02 Density 25

- 30 cc (tapped) Thiabendazole RED 10/02 Water solubility 0.028

- 0.030 mg/mL at 25 °C Thiabendazole RED 10/02 Solvent solubility
acetone benzene chloroform dimethylformamide dimethyl sulfoxide ethanol ethyl acetate methanol 25 oC

4.2 g/L 230 mg/L 80 mg/L 39 g/L 80 g/L 7.9 g/L 2.1 g/L (R.T.) 9.3 g/L The Pesticide Manual, 8 th edition

Vapor pressure 4 x 10

- 9 mm Hg at 25 °C Thiabendazole RED 10/02 Dissociation constant, pK a pK a1 = 4.73; pK a2 = 12.00 Thiabendazole RED 10/02 Octanol/water partition coefficient Log(K OW ) = 240

- 285 at pH 7 Thiabendazole RED 10/02 UV/visible absorption spectrum Neutral solution 32,170 L/mol*cm 3 at 205.5 nm Acidic solution 41,520 L/mol*cm 3 at 303.5 nm Neutral solution 40,553 L/mol*cm 3 at 215.5 nm MRID 46286801 1

1 Data were referenced in MRID 47705121.

### Thiabendazole/060101 Human Health Risk Assessment D425853

Page 25 of 25 Appendix C . Studies Reviewed for Ethical Conduct

This risk assessment relies in part on data from studies in which adult human subjects were intentionally exposed to a pesticide or other chemical. These studies were determined to require a review of their ethical conduct, have received that review and have been determined to be ethical.

HED Exposure Science Advisory Council Policy 14: Standard Operating Procedures for Seed Treatment.