UNITED STATES ENVIRONMENTAL PROTECTION AGENCY

WASHINGTON, DC  20460

OFFICE OF PREVENTION,

PESTICIDES, AND TOXIC SUBSTANCES

MEMORANDUM

Date:		22 August 2007

Subject:	Pendimethalin.  Human Health Risk Assessment for the Proposed Food Uses of the Herbicide on Artichoke, Globe; Asparagus; Brassica Head and Stem Vegetables, Subgroup 5A; and Grape (PP#6E7129).

			PC Code:			108501

			DP Number:			334062

			Regulatory Citation:		40CFR §180.361

			Chemical Class:		Dinitroaniline Herbicide

			Trade Names:			Prowl® 3.3 EC, Prowl® H2O

From:				Debra Rate, Ph.D., Biologist

			Alternative Risk Integration and Assessment (ARIA)

			Risk Integration, Minor Use, and Emergency Response Branch (RIMUERB)

			Registration Division (RD) (7505P)

Through:			William Cutchin, Acting Branch Senior Scientist

				ARIA

			RIMUERB/RD (7505P)

			And

	William T. Drew, Chemist

		Registration Action Branch 2 (RAB2)

		Health Effects Division (7509P)

To:		Barbara Madden/ Susan Stanton

		RIMUERB/RD (7505P)

Table of Contents

  TOC \f  1.0	Executive Summary	3

2.0	Ingredient Profile	7

2.1	Summary of Proposed Uses	7

2.2	Structure and Nomenclature	9

2.3	Physical and Chemical Properties	9

3.0	Hazard Characterization/Assessment	11

3.1	FQPA Hazard Considerations	13

3.1.1	Adequacy of the Toxicity Data Base	13

3.1.2	Evidence of Neurotoxicity	13

3.1.3	Developmental Toxicity Studies	14

3.1.4	Reproductive Toxicity Study	14

3.1.5	Additional Information from Literature Sources	14

3.1.6	Pre-and/or Postnatal Toxicity	14

<IP_ADDRESS>	Determination of Susceptibility	14

<IP_ADDRESS>	Degree of Concern Analysis and Residual Uncertainties for Pre and/or Post-natal Susceptibility	15

4.0	Public Health and Pesticide Epidemiology Data	15

5.0	Metabolism Assessment	15

6.0	Exposure Characterization/Assessment	15

6.1	Dietary Exposure/Risk Pathway	15

6.1.1	Drinking Water Residue Profile	15

6.1.2	Food Residue Profile	16

6.1.3	International Residue Limits	18

6.2.	Dietary Exposure and Risk	18

	6. 2.1	Acute Dietary Exposure and Risk	18

	6.2.2	Chronic Dietary Exposure and Risk	18

	6.2.3	Cancer Dietary Exposure and Risk	19

7.0	Residential (Non-Occupational) Exposure/Risk Characterization	19

7.1	Residential Handler Exposure	19

7.2.	Other (Spray Drift, etc.)	20

8.0	Aggregate Risk Assessments and Risk Characterization	20

8.1	Acute Aggregate Risk	21

8.2	Short-Term Aggregate Risk	21

8.3	Intermediate-Term Aggregate Risk	22

8.4	Long-Term Aggregate Risk	22

8.5	Cancer Risk	22

9.0	Cumulative Risk Characterization/Assessment	22

10.0	Occupational Exposure/Risk Pathway	22

10.1	Short-/Intermediate-/Long-Term/Cancer (if needed) Handler Risk	22

10.2	Short-/Intermediate-/Long-Term/Cancer (if needed) Postapplication Risk	24

11.0	Data Needs and Label Recommendations	25

11.1	Toxicology	25

11.2	Residue Chemistry	25

11.3	Occupational and Residential Exposure	25

References:	25

Appendix A:  Toxicology Assessment	27

A.1  Toxicology Data Requirements	27

A.2  Toxicity Profiles	27

Appendix B:  Metabolism Assessment	32

B.1	Metabolism Guidance and Considerations	29

Appendix C:  Tolerance Reassessment Summary and Table	33

Appendix D:  Review of Human Research	34

   SEQ CHAPTER \h \r 1 1.0	Executive Summary

A human health risk assessment has been conducted to support the proposed Section 3 registrations and associated tolerances for food uses of the herbicide pendimethalin on artichoke, globe; asparagus; Brassica head and stem vegetables, subgroup 5A; and grapes.  The end-use products (EPs) proposed for use on these crops include an emulsifiable concentrate (EC) formulation and an aqueous capsule suspension (CS) formulation.  Pendimethalin is a selective herbicide registered for control of broadleaf weeds and grassy weed species on a variety of agricultural crops, turf, and ornamentals.  It acts as a microtubule disruptor by inhibiting cell division and cell elongation in plants, and is generally applied early in the growing season.  Because a risk assessment reviewing requests for the use of pendimethalin   SEQ CHAPTER \h \r 1 on beans and peas has recently been completed (DP Num: 334766, 332747, W.Drew, 23/MAR/2007 and DP Num: 325176, M. Collantes, 03/MAR/2006), this current risk assessment document reviews and addresses changes in the dietary (food and drinking water), aggregate (residential plus dietary), and occupational exposures to pendimethalin arising from the proposed new uses.  In most cases, information or conclusions which remain unchanged from the previous risk assessment are not reiterated; instead, a reference to the previous document is listed.

Toxicology

The toxicology database is adequate to support the proposed uses for pendimethalin.  The scientific quality of the database for pendimethalin is relatively high, and the toxicity profile can be characterized for a wide range of effects, including potential developmental, reproductive, and neurotoxic effects.

No appropriate endpoint attributable to a single exposure was identified from the oral toxicity studies and developmental toxicity studies in rats and rabbits.  Therefore, an acute point of departure (aPOD) was not established.    SEQ CHAPTER \h \r 1 Three studies (a 92-day thyroid function study in rats, a 56-day thyroid function study in rats, and a 14-day intra-thyroid metabolism study in rats) were considered together to select the dose and endpoint for establishing the chronic population adjusted dose (cPAD) of 0.03 mg/kg/day. The cPAD is derived from the NOAEL of 10 mg/kg/day for thyroid effects, and a combined uncertainty factor of 300.

The same three studies conducted in rats were used for dose and endpoint selection for all durations of dermal and inhalation exposure.  A dermal absorption factor of 3%, and an inhalation absorption factor of 100% were used.  Since both dermal and inhalation endpoints were based on the same toxicological effects, these route-specific margins of exposure (MOEs) were combined into a total MOE.

(For more detailed information, refer to DP Num: 325176, M. Collantes, 03/MAR/2006.)

  SEQ CHAPTER \h \r 1 Residue Chemistry

The nature of the residue in plants, livestock, and rotational crops is adequately understood.  However, HED has previously requested a limited field accumulation study (OPPTS 860.1900) to determine the amount of pesticide residue uptake into rotational crops.  The limited field trials should reflect the maximum label use rate on rotatable crops of 4.0 lb ai/A, and should be conducted on a representative crop (as defined in 40CFR §180.41), at two trial sites per crop, for the following three crop groups:

	(1) root and tuber vegetables,

	(2) leafy vegetables, and

	(3) small grains (wheat, barley, oats, rye),

for a total of six trials.  The six trials should be conducted on crops which the petitioner intends to have as rotational crops on the label.  Samples should be analyzed for pendimethalin and its 3,5-dinitrobenzyl alcohol metabolite.

The residues of concern in plants (for both tolerance expression and risk assessment purposes) are the parent, pendimethalin, and its 3,5-dinitrobenzyl alcohol metabolite (CL202,347); in peanut hulls, the residues of concern also include the 2,4-dinitrobenzyl alcohol metabolite.  The residue of concern in drinking water is pendimethalin, per se.  ARIA has determined that there is no reasonable expectation of finite pendimethalin residues in animal commodities (40CFR §180.6[a][3]).  Tolerances for pendimethalin residues in animal commodities are therefore not needed at this time.

Adequate field trials, storage stability data, and analytical methods are available to support the proposed new uses.  In addition, adequate enforcement methods are available.  However, the grape processing study was not adequate and must be submitted at an exaggerated application rate (>5X) to adequately address the guideline 860.1520 Processed Food and Feed as it pertains to the proposed use on grapes.  In general, residue data indicate that pendimethalin and metabolite residues are low or non-detectable in food or feed crops.

  SEQ CHAPTER \h \r 1 Dietary Exposure

DEEM-FCID™), which uses food consumption data from the USDA’s Continuing Surveys of Food Intakes by Individuals (CSFII) from 1994 to 1996, and 1998.  Tolerance-level residues were assumed for all food commodities with current and proposed pendimethalin tolerances, and it was assumed that all of the crops included in the analysis were treated (100% crop treated).  The estimated drinking water concentration (EDWC) of 0.006 ppm was directly entered into the exposure model to assess the contributions from drinking water.  Acute dietary exposure estimates were not generated, because of the lack of an acute dietary endpoint and dose for risk assessment.

The most highly exposed population subgroup is children 1-2 years old.  The chronic exposure estimate of 0.004749 mg/kg/day corresponds to approximately 16% of the cPAD.  Risk estimates for the general US population and all other population subgroups are lower.

  SEQ CHAPTER \h \r 1 Residential (Non-Occupational) Exposure

The level of concern for oral, dermal and inhalation exposure is an MOE of less than 300.  The previous residential exposure estimate for adults (consisting of dermal exposure only) results in a total MOE of 740, and is therefore not of concern.  The residential exposure for children results in a total MOE (dermal + oral) of 410 at an application rate of 2 lb ai/acre, and an MOE of 400 for an application rate of 3 lb ai/acre.  Residential aggregate exposure is not of concern.

With regard to the proposed new uses, ARIA determined that there is no potential for residential exposure to pendimethalin.  Therefore, residential exposure/risk (associated with the proposed new uses) was not assessed for pendimethalin.

  SEQ CHAPTER \h \r 1 Aggregate Risk Estimate

ARIA has combined chronic dietary (food and water) and non-dietary (residential) sources of exposure to pendimethalin.  The resulting MOEs are all greater than 300 and, therefore, indicate that risk estimates for all population subgroups do not exceed ARIA’s level of concern.

Occupational   SEQ CHAPTER \h \r 1 Handler Exposure

Occupational handler exposure risk estimates were calculated for total (combined dermal and inhalation) short- and intermediate-term exposures.  A MOE of 30 is adequate to protect occupational pesticide handlers from exposures to pendimethalin.  Provided mixer/loaders wear protective gloves as directed on the labels, all MOEs are > 30 and therefore do not exceed ARIA’s level of concern.

Occupational Post-Application Exposure

Estimated occupational post-application risks, as calculated per ARIA default values, indicate that the risks from dermal exposure are not of concern (MOEs are above the level of concern of 30) on the day of treatment for all post-application tasks assessed.    SEQ CHAPTER \h \r 1 All pendimethalin proposed labels currently indicate a re-entry interval (REI) of 24 hours, and should therefore be adequate.

Environmental Justice Considerations:

Potential areas of environmental justice concerns, to the extent possible, were considered in this human health risk assessment, in accordance with U.S. Executive Order 12898, "Federal Actions to Address Environmental Justice in Minority Populations and Low-Income Populations,"   HYPERLINK "http://www.eh.doe.gov/oepa/guidance/justice/eo12898.pdf"  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 procedures.  In line with OPP policy, HED estimates risks to population subgroups from pesticide exposures that are based on patterns of that subgroup’s food and water consumption, and activities in and around the home that involve pesticide use in a residential setting.  Extensive data on food consumption patterns are compiled by the 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 analyzed 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 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 postapplication are evaluated.  Further considerations are currently in development as OPP has committed resources and expertise to the development of specialized software and models that consider exposure to bystanders and farm workers as well as lifestyle and traditional dietary patterns among specific subgroups.

Review of Human Research:

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 (listed in Appendix D) have been determined to require a review of their ethical conduct, and have received that review.

Regulatory Recommendations and Proposed Tolerances

Pending the resolution of the following deficiencies, ARIA recommends that 40CFR §180.361 be revised to include tolerances for residues of pendimethalin (CAS name N-(1-ethylpropyl)-3,4-dimethyl-2,6-dinitrobenzenamine and CAS number 40487-42-1) and its metabolite (4-[(1-ethylpropyl)amino]-2- methyl-3,5-dinitrobenzyl alcohol) in or on the commodities listed in Table 1.0, below.

Table 1.0  Tolerance Summary for Pendimethalin.

Commodity	Proposed Tolerance (ppm)	Recommended Tolerance (ppm)

Brassica, head and stem, subgroup 5A	0.05	0.1

Artichoke, globe	0.05	0.1

Asparagus	0.1	0.15

Grape	0.05	0.1

Grape, raisin	---	0.50

Grape, juice	---	0.15

Residue Chemistry Deficiencies

860.1200  Directions for Use

1.  The product label should be amended to restrict use to a single application for each of the proposed crops.

2.  As previously requested by HED (DP Num: 329627, W. Drew, 12/JUL/2006), ARIA concludes that the registrant should impose PBIs of 90-days for rotated cereal grain crops, and 270-days for all other rotated crops, until limited field rotational crop studies (OPPTS 860.1900) have been conducted in order to determine if tolerances for residues of pendimethalin in rotational crops are needed.

860.1500  Crop Field Trials

Section F of the petition should be revised to reflect the recommended tolerance levels and correct commodity definitions listed in Table 1.0.

860.1520  Processed Food and Feed

The submitted grape processing study is not adequate.  A new study must be submitted using 5X the application rate or the petitioner must submit evidence of crop phytotoxicity at the 5X rate.  ARIA recommends for tolerances to be set at 0.50 ppm for raisins and 0.15 ppm for grape juice.  Once adequate studies have been received, these tolerances may be revised or withdrawn.

860.1900  Field Accumulation in Rotational Crops

HED has previously requested a limited field accumulation study (OPPTS 860.1900) to determine the amount of pesticide residue uptake into rotational crops.  The limited field trials should reflect the maximum label use rate on rotatable crops of 4.0 lb ai/A, and should be conducted on a representative crop (as defined in 40CFR §180.41), at two trial sites per crop, for the following three crop groups:

	(1) root and tuber vegetables,

	(2) leafy vegetables, and

	(3) small grains (wheat, barley, oats, rye),

for a total of six trials.  The six trials should be conducted on crops which the petitioner intends to have as rotational crops on the label.  Samples should be analyzed for pendimethalin and its 3,5-dinitrobenzyl alcohol metabolite.

2.0	Ingredient Profile

Pendimethalin is a selective dinitroaniline herbicide which acts as a microtubule disruptor by inhibiting cell division and cell elongation in plants.  IR-4 is proposing new uses of pendimethalin on artichoke, globe; asparagus; Brassica head and stem vegetables, subgroup 5A; and grapes (PP#6E7129).  The EP, Prowl® 3.3 EC Herbicide (EPA Reg. No. 241-337), is an EC formulation containing 37.4% ai (equivalent to 3.3 lb ai/gal), and Prowl® H2O Herbicide (EPA Reg. No. 241-418) is a CS formulation containing 38.7% ai (equivalent to 3.8 lb ai/gal).  Both have been proposed for use on the following crops, with the proposed maximum seasonal rates and preharvest intervals (PHIs) in parentheses:

(1) artichoke, globe (4.0 lb ai/A, 200 day PHI),

(2) asparagus (4.0 lb ai/A, 14 day PHI),

(3) Brassica head and stem vegetables, subgroup 5A (1.0 lb ai/A, 60 day PHI for broccoli, 70 day PHI for cabbage),

(4) grape (6.0 lb ai/A, 90 day PHI).

Both formulations can be applied as pre-emergence or post-emergence broadcast sprays directed to the soil surface using ground equipment.

  SEQ CHAPTER \h \r 1 2.1	Summary of Proposed Uses

Table 2.1.	Summary of Directions for Use of Pendimethalin.

Applic. Timing, Type, and Equip.	Formulation

(EPA Reg. No.)	Applic. Rate

(lb ai/A)	Max. No. Applic. per Season	Max. Seasonal Applic. Rate

(lb ai/A)	PHI1

(days)	Use Directions and Limitations

Artichoke

Apply as a broadcast spray directed to the soil surface 1-2 days prior to transplanting.	Prowl® 3.3 EC

(241-377)	9.7 pints/A

(4.0 lb ai/A)	1	9.7 pints/A

(4.0 lb ai/A)	200	Do not feed forage or graze livestock in treated fields.

Most effective when incorporated in the weed germination zone by rainfall or irrigation with 7 days of application.

Apply as a broadcast spray directed to the soil surface 1-2 days prior to transplanting.	Prowl® H20 (241-418)	8.2 pints/A

(4.0 lb ai/A)	1	8.2 pints/A

(4.0 lb ai/A)	200	Do not feed forage or graze livestock in treated fields.

Most effective when incorporated in the weed germination zone by rainfall or irrigation with 7 days of application.

Asparagus

Apply as soil directed broadcast spray at least 14 days before harvest, prior to spear emergence.	Prowl® 3.3 EC

(241-377)	9.7 pints/A

(4.0 lb ai/A)	1	9.7 pints/A

(4.0 lb ai/A)	14 	Do not feed forage or graze livestock in treated fields.

Most effective when incorporated in the weed germination zone by rainfall or irrigation with 7 days of application.

Apply as soil directed broadcast spray at least 14 days before harvest, prior to spear emergence.	Prowl® H20 (241-418)	8.2 pints/A

(4.0 lb ai/A)	1	8.2 pints/A

(4.0 lb ai/A)	14	Do not feed forage or graze livestock in treated fields.

Most effective when incorporated in the weed germination zone by rainfall or irrigation with 7 days of application.

Brassica Head and Stem Vegetables

Apply as broadcast foliar spray to 2-4 leaf vegetable transplants at 1 to 3 days after transplanting or of dierect seeded plants.	Prowl® 3.3 EC

(241-377)	2.4 pints/A

(1.0 lb ai/A)	1	2.4 pints/A

(1.0 lb ai/A)	60 broccoli, 70 cabbage	Do not feed forage or graze livestock in treated fields.

Most effective when incorporated in the weed germination zone by rainfall or irrigation with 7 days of application.

Apply as broadcast foliar spray to 2-4 leaf vegetable transplants at 1 to 3 days after transplanting or of dierect seeded plants.	Prowl® H20

(241-418)	2.1 pints/A

(1.0 lb ai/A)	1	2.1 pints/A

(1.0 lb ai/A)	60 broccoli, 70 cabbage	Do not feed forage or graze livestock in treated fields.

Most effective when incorporated in the weed germination zone by rainfall or irrigation with 7 days of application.

Grape

Apply as a soil directed broadcast spray underneath the canopy of grape vines at least 90 days before the harvest.	Prowl® 3.3 EC

(241-377)	14.5 pints/A

(6.0 lb ai/A)	1	14.5 pints/A

(6.0 lb ai/A)	90	Do not feed forage or graze livestock in treated fields.

Most effective when incorporated in the weed germination zone by rainfall or irrigation with 7 days of application.

Apply as a soil directed broadcast spray underneath the canopy of grape vines at least 90 days before the harvest.	Prowl® H20 (241-418)	12.3 pints/A

(6.0 lb ai/A)	1	12.3 pints/A

(6.0 lb ai/A)	90	Do not feed forage or graze livestock in treated fields.

Most effective when incorporated in the weed germination zone by rainfall or irrigation with 7 days of application.

1 PHI = Pre-harvest Interval

2.2	  SEQ CHAPTER \h \r 1 Structure and Nomenclature

TABLE 2.2.  Test Compound Nomenclature

Common name	Pendimethalin

Chemical Class	Dinitroaniline Herbicides

IUPAC name	N-(1-ethylpropyl)-2,6-dinitro-3,4-xylidine

CAS name	N-(1-ethylpropyl)-3,4-dimethyl-2,6-dinitrobenzenamine

CAS #	40487-42-1

End-use product/EP	Prowl® 3.3EC Herbicide (EPA Reg. No. 241-337), Prowl® H2O Herbicide (EPA Reg. No. 241-418)

Chemical Structure

  SEQ CHAPTER \h \r 1

2.3	Physical and Chemical Properties tc "2.4	Physical and Chemical Properties " \l 2

Pendimethalin is an orange-yellow crystalline solid with a melting point of 54-58ºC.  It is soluble in chlorinated hydrocarbons and aromatic solvents such as methylene chloride, acetone, and xylene, but relatively insoluble in water (<0.5 ppm) at 20ºC.  Pendimethalin is stable under acidic and alkaline conditions.

TABLE 2.3.  Physicochemical Properties of the Technical Grade Test Compound

Parameter	Valuea

Molecular Weight	281.3

Melting point	57.7 - 58ºC

Boiling point	330ºC

Vapor pressure	1.94 x 10-3 Pa @ 25°C

Henry’s Law Constant	2.728 x 10-3 KPa x m3/mol

Density 	0.85 g/cm3 @ 25°C

Vapor pressure	1.2x 10-5 Pa @ 25°C

Log10 KOW (Log P)	5.2 @ pH 7

Solubility	0.54 mg/L @ 20°C in water (pH 4)

0.33 mg/L @ 20°C in water (pH 7)

0.44 mg/L @ 20°C in water (pH 10)

48.9 g/L @ 20°C in n-hexane

66.08 mg/L @ 20°C in n-octanol

>800 g/L @ 20°C in ethyl acetate

>800 g/L @ 20°C in xylene

>800 g/L @ 20°C in acetone

>800 g/L @ 20°C in dichloromethane

Dissociation Constant	pKa = 2.8

aEuropean Commission Health & Consumer Protection Directorate-General, Directorate E – Pendimethalin 7477/ VI/98-final, 13 January 2000 (  HYPERLINK "http://ec.europa.eu/food/plant/protection/evaluation/existactive/list1- 35_en.pdf"  http://ec.europa.eu/food/plant/protection/evaluation/existactive/list1-3 5_en.pdf )

3.0	Hazard Characterization/Assessment tc "4.0  Hazard Characterization/Assessment"

For detailed information, please refer to DP Num: 325176; M. Collantes; 03/MAR/2006.

Table 3.A  Summary of Levels of Concern for Risk Assessment.

Route of Exposure	Duration of Exposure

	Short-Term

(1 - 30 Days)	Intermediate-Term

(1 - 6 Months)	Long-Term

(> 6 Months)

Occupational (Worker) Exposure

Dermal	30	30	30

Inhalation	30	30	30

Residential Exposure

Dermal	300	300	300

Inhalation	300	300	300

Incidental Oral	300	300	---

  SEQ CHAPTER \h \r 1 TABLE 3.B	Toxicological Doses and Endpoints for Pendimethalin Human Health Risk Assessments.

Exposure

Scenario	Point of Departure	Dose Used in Risk

Assessment, UF 	RfD, PAD, Level of Concern for Risk Assessment	Study and Toxicological Effects

	Dietary Exposure

Acute Dietary

(Females 13-49)

(General US Pop.)	NA	NA	NA	No appropriate acute endpoint identified for these groups.  There were no toxic effects attributable to a single dose.

Chronic Dietary

(all populations)	NOAEL = 10 mg/kg/day

Chronic RfD= 0.03 mg/kg/day	UF = 10X (intraspecies)

           3X (interspecies)

         10X (database UF)

Total UF = 300X

	Chronic RfD= 0.03 mg/kg/day

cPAD = Chronic

                 RfD

cPAD = 0.03 mg/kg/day	92-day thyroid function study in rats; 56-day thyroid study in rats; 14-day intra thyroid metabolism study in rats.

LOAEL= 31 mg/kg/day based on hormonal and histopathological changes in the thyroid.

Incidental Oral Exposure

Incidental Oral Short-Term

(1 - 30 days)

Intermediate-Term

(1 - 6 months)	NOAEL = 10 mg/kg/day

	UF = 10X (intraspecies)

           3X (interspecies)

         10X (database UF)

Total UF = 300X

	Residential LOC = 300

Occupational LOC = 30	92-day thyroid function study in rats; 56-day thyroid study in rats; 14-day intra thyroid metabolism study in rats.

LOAEL= 31 mg/kg/day based on hormonal and histopathological changes in the thyroid.

Dermal Exposure

Dermal

Short-Term

(1 - 30 days)

Intermediate-Term

(1 - 6 months)

Long-Term

(> 6 months)	NOAEL = 10 mg/kg/day

	UF = 10X (intraspecies)

           3X (interspecies)

         10X (database UF)

Total UF = 300X

Dermal Absorption = 3%	Residential LOC = 300

Occupational LOC = 30	92-day thyroid function study in rats; 56-day thyroid study in rats; 14-day intra thyroid metabolism study in rats.

LOAEL= 31 mg/kg/day based on hormonal and histopathological changes in the thyroid.

Inhalation Exposure

Inhalation

Short-Term

(1 - 30 days)

Intermediate-Term

(1 - 6 months)

Long-Term

(> 6 months)	NOAEL = 10 mg/kg/day

	UF = 10X (intraspecies)

           3X (interspecies)

         10X (database UF)

Total UF = 300X

Inhalation Absorption = 100%	Residential LOC = 300

Occupational LOC = 30	92-day thyroid function study in rats; 56-day thyroid study in rats; 14-day intra thyroid metabolism study in rats.

LOAEL= 31 mg/kg/day based on hormonal and histopathological changes in the thyroid.

Cancer

Cancer (oral, dermal, inhalation)	Pendimethalin is considered to be a possible human carcinogen; quantitative estimate of cancer risk is not required.  	2-year chronic/carcinogenicity study in rats.

Point of Departure (POD) = A data point or an estimated point that is derived from observed dose-response data and  used to mark the beginning of extrapolation to determine risk associated with lower environmentally relevant human exposures.  NOAEL = no observed adverse effect level.  LOAEL = lowest observed adverse effect level.  UF = uncertainty factor.  UFA = extrapolation from animal to human (interspecies).  UFH = potential variation in sensitivity among members of the human population (intraspecies).  UFL = use of a LOAEL to extrapolate a NOAEL.  UFS = use of a short-term study for long-term risk assessment.  UFDB = to account for the absence of key date (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.

3.1	FQPA Hazard Considerations  tc "4.2	FQPA Hazard Considerations " \l 2

3.1.1	Adequacy of the Toxicity Data Base  tc "4.2.1	Adequacy of the Toxicity Data Base " \l 3

The toxicology database for pendimethalin is adequate for purposes of risk assessment.  However, based on the hormonal changes (alterations in thyroid weights and histopathological lesions) observed in several studies following oral administration of pendimethalin, it is likely that pendimethalin may cause disruption in the endocrine system.  There is concern that perturbation of thyroid homeostasis may lead to hypothyroidism, and possibly result in adverse effects on the developing nervous system. Consequently, HED recommends that a developmental thyroid assay be required to evaluate the impact of pendimethalin on thyroid hormones, structure, and/or thyroid hormone homeostasis during development.  Furthermore, HED has recommended that the 10X database uncertainty factor (UFDB) be retained pending receipt of the developmental thyroid study.

3.1.2	Evidence of Neurotoxicity  tc "4.2.2	Evidence of Neurotoxicity " \l 3

There were no neurotoxicity studies available for pendimethalin.  Furthermore, there was no evidence of neurotoxic clinical signs, changes in brain weight, or histopathology of the nervous system in any study with pendimethalin.  Neurotoxicity studies for pendimethalin are not required based on the chemical characteristics.

3.1.3	Developmental Toxicity Studies  tc "4.2.3	Developmental Toxicity Studies " \l 3

In the rat, the pendimethalin NOAELs for developmental and maternal toxicity are both 500 mg/kg/day (highest dose tested).  There were no maternal or developmental effects noted at any dose level tested.  However, the study is considered adequate, and a new study is not required because in other rat studies, thyroid toxicity was seen at significantly lower doses (31 mg/kg/day) than the highest dose tested in this study, and because if thyroid parameters had been measured, maternal toxicity would likely have been demonstrated.

A rabbit toxicity study with pendimethalin did not demonstrate maternal toxicity at doses up to 60 mg/kg/day (highest dose tested).  The NOAEL for developmental toxicity was 60 mg/kg/day (HDT).  Since neither maternal nor developmental toxicity was seen at the highest dose tested, potential for increased sensitivity of the offspring could not be determined.

3.1.4	Reproductive Toxicity Study  tc "4.2.4	Reproductive Toxicity Study " \l 3

A 2-generation reproduction study (MRID# 41725203) with pendimethalin was reviewed by HED.  The pendimethalin RED and the Data Evaluation Report (DER), concluded that the parental systemic NOAEL was 172 mg/kg/day [M] and 216 mg/kg/day [F] (2500 ppm), based on decreased body weight gain and food consumption at the LOAEL of 346 mg/kg/day [M] and 436 mg/kg/day [F] (5000 ppm).  The reproductive/offspring NOAEL was 172 mg/kg/day [M] and 216 mg/kg/day [F] (2500 ppm), based on decreased pup weight at the LOAEL of 346 mg/kg/day [M] and 436 mg/kg/day [F] (5000 ppm).  The mg/kg/day were calculated from actual intake of chemical specific data in the DER.

Conclusions for the same 2-generation reproduction study (MRID# 41725203) with pendimethalin in the HIARC (4/18/2000) indicated that the parental systemic NOAEL was 25 mg/kg/day (500 ppm), based on decreased body weight gain and food consumption at the LOAEL of 125 mg/kg/day (2500 ppm).  The reproductive/offspring NOAEL is 25 mg/kg/day (500 ppm), based on decreases in the number of pups born and pup weight at the LOAEL of 125 mg/kg/day (2500 ppm).  Parental and reproductive NOAELs and LOAELs were based on a generic ratio (1:20) of dietary intake of chemical.

3.1.5	Additional Information from Literature Sources  tc "4.2.5 Additional Information from Literature Sources " \l 3

There was no additional information available from the literature.

3.1.6  Pre-and/or Postnatal Toxicity  tc "4.2.6  Pre-and/or Postnatal Toxicity " \l 3

HED has concluded there is potential for pre- and/or postnatal toxicity (thyroid) in developing offspring resulting from exposure to pendimethalin.

<IP_ADDRESS>	Determination of Susceptibility  tc "<IP_ADDRESS>	Determination of Susceptibility " \l 4

There was no indication of pre-/or postnatal qualitative or quantitative increased susceptibility in the developmental studies in rats and rabbits or the 2-generation reproduction studies in rats.  However, because developmental LOAELs could not be determined in the developmental studies, HED has requested developmental thyroid toxicity data, in order to determine potential thyroid toxicity following pre- and/or post-natal exposure to pendimethalin.

<IP_ADDRESS>	Degree of Concern Analysis and Residual Uncertainties for Pre and/or Post-natal Susceptibility  tc "<IP_ADDRESS>	Degree of Concern Analysis and Residual Uncertainties for Pre and/or Post-natal Susceptibility " \l 4

HED performed a Degree of Concern Analysis because the developmental studies were not adequate to fully address the potential for susceptibility.  The purpose of the Degree of Concern analysis is (1) to determine the level of concern for the effects observed when considered in the context of all available toxicity data; and (2) identify any residual uncertainties after establishing toxicity endpoints and traditional uncertainty factors to be used in the risk assessment.

If residual uncertainties are identified, then HED determines whether these residual uncertainties can be addressed by a special FQPA safety factor and, if so, the size of the factor needed.

In the case of pendimethalin, the developmental studies in rats and rabbits were acceptable but not adequate to determine the potential for thyroid toxicity during development.  Consequently, there is concern for potential increased sensitivity or susceptibility in offspring regarding thyroid effects.  A developmental thyroid toxicity study has been required, and the registrant has met with the Agency to discuss the conduct of the ongoing study.  Pending receipt of the study, a 10X database uncertainty factor (UFDB) has been retained.  The 10X special FQPA Factor has been reduced to 1X, however, since thyroid effects serve as the basis for endpoints for risk assessment for pendimethalin, since there were no developmental effects observed in the rat and rabbit developmental toxicity studies, and since the 10X UFDB has been retained for the lack of data in the developing thyroid.

Public Health and Pesticide Epidemiology Data

Please refer to DP Num: 325176; M. Collantes; 03/MAR/2006.

5.0	Metabolism Assessment tc "3.0	Metabolism Assessment"

Please refer to D325176; M. Collantes; 3/MAR/2006.

6.0	Exposure Characterization/Assessment

6.1	Dietary Exposure/Risk Pathway

6.1.1	Drinking Water Residue Profile

The drinking water residues used in this chronic dietary risk assessment were provided by the EFED in a memorandum (DP Num: 334061, J. Breithaupt; 08/MAY/2007), and incorporated directly into the dietary assessment.  Water residues were entered into the DEEM-FCID input file under the food categories “water, direct, all sources” and “water, indirect, all sources.”

It was determined that the parent, pendimethalin, is the only significant non-volatile residue, therefore, the EDWCs were calculated for pendimethalin only.  For surface water sources of drinking water, the acute (peak) water concentration is 77.7 ppb (0.0777 ppm), 6.0 ppb (0.006 ppm) for chronic (non-cancer) and 4.8 ppb (0.0048 ppm) for cancer.  The groundwater screening concentration for non-cancer chronic exposure ranged from 0.006 to 0.036 ppb.  The EDWC of 0.006 ppm ((the 1 in 10 year annual mean concentration in surface water, as calculated by PRZM-EXAMS modeling) was directly entered into the exposure model to assess the contributions from drinking water.  This EDWC (resulting from a single application of pendimethalin to grapes (NY) at the rate of 6.0 lb ai/A) was the highest chronic modeling result calculated for either surface or groundwater sources of drinking water, and is therefore conservative.

Table 6.1.1	Summary of Estimated Surface Water and Groundwater Concentrations for Pendimethalin.

	[Chemical]

	Surface Water Conc., ppb a	Groundwater Conc., ppb b

Acute	77.7	0.036c

Chronic (non-cancer)	6.0	0.036c

Chronic (cancer)	4.8	0.036c

a From the Tier II PRZM-EXAMS - Index Reservoir model.  Input parameters are based on ...

b From the SCI-GROW model assuming a maximum seasonal use rate of 6.0 lb ai/A, a Koc of 15,000, and a half-life of 172 days.                                                                                c EFED does not expect residue concentrations to exceed this level.

Food Residue Profile

As of July 1, 2007, tolerances are currently established (40CFR §180.361) for the combined residues of the herbicide pendimethalin and its metabolite in or on the following raw agricultural commodities (RACs):

Commodity	Parts per million

Alfalfa, Forage	3.0

Alfalfa, Hay	4.0

Alfalfa, Seed	0.10

Almond, hulls	0.4

Apple, wet pomace	0.20

Bean, lima, seed	0.1

Bean, lima, succulent	0.1

Bean, forage	0.1

Bean, hay	0.1

Carrots	0.5

Citrus, oil	0.5

Corn, field, forage	0.1

Corn, field, grain	0.1

Corn, field, stover	0.1

Corn, pop, grain	0.1

Corn, sweet, forage	0.1

Corn, sweet, kernel plus cob with husks removed	0.1

Corn, sweet, stover	0.1

Cotton, undelinted seed	0.1

Fruit, citrus, group 10	0.1

Fruit, pome, group 11	0.10

Fruit, stone, group 12	0.10

Garlic	0.1

Juneberry	0.10

Leek	0.20

Nut, tree, group 14	0.1

Onion, dry bulb	0.1

Onion, green	0.20

Onion, welsh	0.20

Pea, succulent	0.1

Peanut	0.1

Peanut, hay	0.1

Peppermint, oil	1.0

Peppermint, tops	0.2

Pistachio	0.1

Pomegranate	0.10

Potato	0.1

Rice, grain	0.1

Rice, straw	0.1

Shallot	0.2

Sorghum, forage	0.1

Sorghum, grain, grain	0.1

Sorghum, grain, stover	0.1

Soybean, forage	0.1

Soybean, hay	0.1

Soybean, seed	0.1

Spearmint, oil	1.0

Spearmint, tops	0.2

Strawberry	0.10

Sugarcane, cane	0.1

Sunflower, seed	0.1

Vegetable, fruiting, group 8	0.10

Wheat, grain	0.10

Wheat, forage	3.0

Wheat, hay	0.60

Wheat, straw	0.30

  SEQ CHAPTER \h \r 1 The residue chemistry data submitted to support the proposed uses (and associated tolerances) on artichoke, globe; asparagus; Brassica head and stem vegetables, subgroup 5A; and grapes are adequate with respect to field trials, analytical methods, and storage stability data.  The grape processing study was not adequate (2x application rate) and therefore ARIA recommends in favor of establishing tolerances for pendimethalin in/on grape, juice and grape, raisin.  ARIA also recommends in favor of establishing tolerances for pendimethalin in/on these commodities, however the previously requested limited field accumulation study (DP Num: 271502, W. Drew, 12/JUL/2006) has yet to be submitted for review.  In general, residue data indicate combined residues of parent pendimethalin and its metabolite are very low or non-detectable in food or feed items.  However, residues concentrate in some processed commodities, most significantly citrus oil and mint oil.

6.1.3	International Residue Limits

There are currently no Canadian , Mexico or Codex maximum residue limits (MRLs) for pendimethalin on the proposed commodities.  See the residue chemistry chapter (DP Num: 340343, D. Rate, 02/AUG/2007) for the International Residue Limit Status sheet.

6.2	Dietary Exposure and Risk

6.2.1	Acute Dietary Exposure/Risk  TC \l3 "5.2.1  Acute Dietary Exposure/Risk

Due to a lack of an acute dietary endpoint and dose for risk assessment, an acute dietary risk assessment was not generated and is not required for this chemical.

6.2.2	Chronic Dietary Exposure/Risk  TC \l3 "5.2.2  Chronic Dietary Exposure/Risk

A chronic dietary risk assessment was conducted using the Dietary Exposure Evaluation Model (DEEM-FCID™, Version 2.03) which uses food consumption data from the US Department of Agriculture’s Continuing Surveys of Food Intakes by Individuals (CSFII) from 1994 to 1996, and 1998.  The analysis was performed to support Section 3 registration requests from IR-4 proposing tolerances for pendimethalin in/on artichoke, globe; asparagus; Brassica head and stem vegetables, subgroup 5A; and grape.  Acute and cancer dietary risk assessments are not required for this chemical.

The chronic dietary exposure analysis was based on the following assumptions:

(1) Tolerance-level residues of pendimethalin in/on all current RACs (e-CFR 40 §180.361, Updated July 1, 2007) and proposed RACs.

(2) Empirical processing factors obtained from processing studies (when available; including citrus commodities).  Grape processing studies were not adequate, and tolerances for grape commodities (grape, raisin and grape, juice) were recommended and no processing factor was used in the dietary analysis.

(3) A processing factor of 8 for the processed commodities of wheat bran and wheat germ and 1.4 for wheat flour.

(4) DEEM 7.81 default processing factors were used for the remaining processed commodities.

(5) 100% crop treated (CT), and

(6) 0.006 ppm pendimethalin estimated drinking water concentration (EDWC).

These assumptions result in conservative estimates of dietary exposure and risk.  In calculating dietary risk estimates, ARIA has compared the cPAD to the estimated dietary exposure.  Typically, ARIA has concerns regarding dietary risk when the exposure estimates exceed 100% of the cPAD.  Even with the conservative assumptions noted above, risk estimates associated with chronic dietary exposure to pendimethalin are significantly below ARIA’s level of concern.

In the chronic dietary assessment, the most highly exposed population subgroup is children 1-2 years old.  The chronic exposure estimate, 0.004749 mg/kg/day, corresponds to approximately 16% of the cPAD.  Risks for the general US population were 5% of the cPAD.

Cancer Dietary Risk  TC \l3 "5.2.3  Cancer Dietary Risk

 The HED Cancer Peer Review Committee classified pendimethalin as a “Group C” (possible human) carcinogen, based on thyroid follicular cell adenomas in rats.  The committee recommended a non-quantitative approach (non-linear, RfD approach).  The chronic dietary risk assessment is considered to be protective of any cancer effects; therefore, a separate quantitative cancer dietary risk assessment is not required.

TABLE 6.2.3	Summary of Chronic Dietary Exposure and Risk Estimates for Pendimethalin.

Population Subgroup*

[Years of Age]	DEEM Chronic Dietary Analysis

	cPAD (mg/kg/day)	Exposure Estimate (mg/kg/day)	% cPAD

General US Population	0.03	0.001548	5

All Infants [<1]	0.03	0.003081	10

Children [1-2]	0.03	0.004749	16

Children [3-5]	0.03	0.003819	13

Children [6-12]	0.03	0.002304	8

Youths [13-19]	0.03	0.001417	5

Adults [20-49]	0.03	0.001166	4

Adults [50+]	0.03	0.001065	4

Females [13-49]	0.03	0.001164	4

* Values for the population with the highest risk are in bold type.

Residential (Non-Occupational) Exposure/Risk Characterization

7.1	Residential Handler Exposure

As there are no new residential exposures as a result of the newly proposed uses, please refer to previously reviewed residential exposure in memorandum DP Num: 325176; M. Collantes; 03/MAR/2006.  With regard to residential pendimethalin uses previously reviewed, HED combined all non-dietary sources of handler and post-application exposure to obtain an estimate of potential aggregate exposure.  The scenarios used were short-term in duration and consisted of dermal (for adults and children) and oral (hand-to-mouth, object-to-mouth, and soil ingestion, for children only) exposure.  HED combined risk values resulting from separate exposure scenarios when it was likely they could occur simultaneously, based on the use-pattern and the behavior associated with the exposed population.

The level of concern for oral, dermal and inhalation exposure is an MOE of less than 300.  The residential exposure estimate for adults (consisting of dermal exposure only) results in a total MOE of 740, and is therefore not of concern.  The residential exposure for children results in a total MOE (dermal + oral) of 410 at an application rate of 2 lb ai/acre, and an MOE of 400 for an application rate of 3 lb ai/acre.  Residential aggregate exposure is not of concern.

With regard to the proposed new uses, ARIA has determined that there no potential for residential exposure to pendimethalin.  However, proposed label instructions specify that pendimethalin be applied (pre- or early transplant) directly to the soil surface14 to 90 days before harvest.  Based upon these factors, residential exposure during pick-your-own strawberry activities was determined to be unlikely to occur and, therefore, residential exposure/risk (associated with the proposed new uses) was not assessed for pendimethalin.

  SEQ CHAPTER \h \r 1 TABLE 7.1	Aggregate Risk Resulting from Residential Exposure to Pendimethalin (Tier 1).

Exposure Scenario	Popu-lation	TTR 1 (µg/cm2)	Dermal Dose (mg/kg/day) Dermal MOE 2

	Total Oral Dose 3 (mg/kg/day)	Oral

MOE 4	Total Dose	Total MOE 5

Turf Grass	Adults	1.1	0.0136	740	NA	NA	0.0136	740

	Children

0.0228	440	0.0015	6800	0.0243	410

	0.0022	4600	0.0250	400

  SEQ CHAPTER \h \r 1 1 TTR values are based on Pendulum WDG TTR study (MRID #44969901).

2 Dermal MOE = average of dermal MOEs for adults and children (calculated from TTR data in CA, PA, and FL).

3 Oral Dose = hand-to-mouth dose + object-to-mouth dose + soil ingestion dose.

4   SEQ CHAPTER \h \r 1 Oral MOE = 1/(  SEQ CHAPTER \h \r 1 hand-to-mouth MOE + object-to-mouth MOE + soil ingestion MOE).

5   SEQ CHAPTER \h \r 1 Total MOE = 1/[(1/  SEQ CHAPTER \h \r 1 dermal MOE) + (1/  SEQ CHAPTER \h \r 1 oral MOE)]

7.2	Other (Spray Drift, etc.) TC \l2 "6.3	Other (Spray Drift, etc.)

Spray drift is always a potential source of exposure to residents nearby to spraying operations.  This is particularly the case with aerial application, but, to a lesser extent, could also be a potential source of exposure from the ground application method employed for pendimethalin.  The Agency has been working with the Spray Drift Task Force, EPA Regional Offices and State Lead Agencies for pesticide regulation and other parties to develop the best spray drift management practices.  On a chemical by chemical basis, the Agency is now requiring interim mitigation measures for aerial applications that must be placed on product labels/labeling.  The Agency has completed its evaluation of the new database submitted by the Spray Drift Task Force, a membership of U.S. pesticide registrants, and is developing a policy on how to appropriately apply the data and the AgDRIFT computer model to its risk assessments for pesticides applied by air, orchard airblast and ground hydraulic methods.  After the policy is in place, the Agency may impose further refinements in spray drift management practices to reduce off-target drift with specific products with significant risks associated with drift.

It is noted that the 3.0 lb ai/acre application rate for turf was modeled to estimate postapplication residential exposure of toddlers.  As this rate is equal to or higher than many of agricultural application rates, this scenario is protective of any exposure of farm children via spray drift from agricultural pendimethalin applications.

  SEQ CHAPTER \h \r 1 8.0	Aggregate Risk Assessments and Risk Characterization

In an aggregate assessment, exposures from relevant sources are combined, and compared to quantitative estimates of hazard (such as a NOAEL or PAD).  When aggregating exposures and risks from various sources, ARIA considers both the route and duration of exposure.

In evaluating the proposed uses of pendimethalin, ARIA has combined dietary (food and drinking water) and non-dietary (turf grass) sources of exposure to obtain an estimate of potential aggregate exposure.  The non-dietary scenarios in the aggregate assessment include dermal exposure for adults and children, as well as incidental oral exposures (hand- and object-to-mouth transfer of residues and ingestion of soil) for children only.

ARIA acknowledges that the aggregate exposure and risk estimates for children are likely to overestimate actual exposures since our estimates assume simultaneous, constant exposures from dietary and non-dietary sources.  An assessment that takes into account the timing of source-specific exposures and the likelihood of their co-occurring would be expected to produce more realistic and lower exposure and risk estimates.

  SEQ CHAPTER \h \r 1 8.1	Acute Aggregate Risk

No toxic effects attributable to a single dose were identified for pendimethalin.  Therefore, an acute risk assessment is not warranted for this chemical.

  SEQ CHAPTER \h \r 1 8.2	Short-Term Aggregate Risk

In estimating short-term aggregate risk, ARIA combines the chronic dietary (food and drinking water) exposure estimate and the total non-dietary (residential) exposure estimate for adults and children.  The chronic dietary exposure estimate reflects average dietary exposure, and serves as an estimate of dietary exposure that co-occurs with potential short-term non-dietary exposure to adults and children.  Short-term aggregate risk estimates for pendimethalin are summarized in Table 8.2, below.  The level of concern for oral, dermal, and inhalation exposure is an MOE of less than 300.  The short-term aggregate exposure estimate for adult males results in an aggregate MOE of 650, while the short-term aggregate exposure estimate for adult females results in an aggregate MOE of 580.  The aggregate exposure estimate for children results in a total MOE of 410 at an application rate (to residential turf) of 2 lb ai/acre, and a total MOE of 390 for an application rate of 3 lb ai/acre.  Aggregate exposure is therefore not of concern for any of the population subgroups.

  SEQ CHAPTER \h \r 1 TABLE 8.2	Short-Term Aggregate Risk Calculations.

Population	Short-Term Scenario

	NOAEL

(mg/kg/day)	Target

MOE 1	Average

Dietary Exposure Estimate 2

(mg/kg/day)	Residential Exposure Estimate 3

(mg/kg/day)	Aggregate MOE 4

(Dietary and

Residential)

Adult Male

(US Population)	10	300	0.0015	0.014	650

Adult Female

(Females 13+)	10	300	0.0012	0.016	580

Child

(Children 1-2 yrs)	10	300	0.0050	0.024 5	410

0.025 6	390

  SEQ CHAPTER \h \r 1 1. Target MOE = 300, based on a total UF of 100 (10X intraspecies, 3X interspecies, 10X Database).

2. Dietary exposure = [food exposure + drinking water exposure].

3. Residential exposure = [oral exposure + dermal exposure + inhalation exposure].

4. Aggregate MOE = [NOAEL ÷ (average dietary exposure + residential exposure)].

5. Based on an application rate of 2 lb ai/A.

6. Based on an application rate of 3 lb ai/A.

8.3	Intermediate-Term Aggregate Risk  tc "7.3	Intermediate-Term Aggregate Risk " \l 2

Based on the currently requested uses, there are no scenarios that are likely to result in intermediate-term exposure (30 to 180 days, continuous).  Therefore, ARIA has not conducted an intermediate-term risk assessment for pendimethalin.

8.4	Long-Term Aggregate Risk  tc "7.4	Long-Term Aggregate Risk " \l 2

The dietary exposure (food and drinking water) pathway is the only source of exposure to pendimethalin that is expected to be of long term (180 to 365 days).  Therefore, the long-term aggregate exposure and risk estimates are equivalent to the chronic dietary exposure and risk estimates discussed in Section 6.1.3, and do not exceed ARIA’s level of concern.

8.5	Cancer Aggregate Risk

The HED Cancer Peer Review Committee classified pendimethalin (18/MAR/1992 and re-affirmed 01/NOV/1999) as a “Group C” (possible human) carcinogen based on a statistically significant increased trend and pair-wise comparison between the high dose group and controls for thyroid follicular cell adenomas in male and female rats.  The committee recommended a non-quantitative approach (non-linear, RfD approach) since mode of action studies are available that demonstrate that the thyroid tumors are due to a thyroid-pituitary imbalance, and also since pendimethalin was shown to be non-mutagenic in mammalian somatic cells and germ cells.  The chronic risk assessment is considered to be protective of any cancer effects; therefore, a separate quantitative cancer aggregate risk assessment is not required.

9.0	Cumulative Risk Characterization/Assessment

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 pendimethalin and any other substances and pendimethalin does not appear to produce a toxic metabolite produced by other substances.  For the purposes of this tolerance action, therefore, EPA has not assumed that pendimethalin 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 statements released by EPA’s Office of Pesticide Programs concerning common mechanism determinations and procedures for cumulating effects from substances found to have a common mechanism on EPA’s website at   HYPERLINK http://www.epa.gov/pesticides/cumulative/. http://www.epa.gov/pesticides/cumulative/.

 	Occupational Exposure/Risk Pathway

For detailed information, please refer to DP Num: 334174; M. Dow; 09/JAN/2007.

10.1	Occupational Pesticide Handler Exposure

HED ExpoSAC SOP Number 12 (29 March 2000)

ARIA has determined that exposure to pesticide handlers is likely during the occupational use of pendimethalin.  Based upon the proposed use patterns, applications are likely only to be made by ground-boom sprayers.  For the proposed new uses, the most highly exposed occupational pesticide handlers will be mixer/loaders using open-pour loading of liquid formulations and applicators using open-cab, ground-boom sprayers.  The agricultural products, Prowl® 3.3 EC and Prowl® H2O, have been assessed for occupational exposures associated with the proposed new uses.

Since there is only one application/season and the treatment blocks (i.e., areas treated) are relatively small for the proposed new crop uses (as compared to typical field crops such as cotton, corn, soybeans or wheat), ARIA believes pesticide handlers will be exposed to short-term duration (1 - 30 days) exposures but not to intermediate-term (1 - 6 months) duration exposures.  In other words, it is unlikely that pesticide handlers would be exposed continuously for 30 days or more.  Estimates of intermediate-term exposures are, however, presented.

No chemical specific data were available with which to assess potential exposure to pesticide handlers.  The estimates of exposure to pesticide handlers are based upon surrogate study data available in the PHED (v. 1.1, 1998).  For pesticide handlers, it is HED standard practice to present estimates of dermal exposure for “baseline” that is, for workers wearing a single layer of work clothing consisting of a long sleeved shirt, long pants, shoes plus socks and no protective gloves as well as for “baseline” and the use of protective gloves or other PPE as might be necessary.  The PPE to be used with these two products includes long-sleeved shirt, long pants, shoes plus socks and chemical resistant gloves.

On 7 March 2005, the Agency issued a memorandum which contains toxicological endpoints for use in risk assessment (DP Num: 278047, C. Swartz, 07/MAR/2005).  The Agency identified short-term (1 - 30 days), intermediate-term (1 - 6 months) and long-term (> 60 months) dermal and inhalation toxicological endpoints from a 56 - day thyroid study in the rat, a 14 day intra thyroid metabolism study in the rat and a 92 - day thyroid function study in the rat.  The effects seen were hormonal and histopathological changes in the thyroid.  The No Observable Adverse Effects Level (NOAEL) for each exposure duration of dermal and inhalation exposure is 10.0 mg ai/kg bw/day.  The Agency identified a 10.0 % dermal absorption factor for use in exposure estimates.  ARIA assumes 100 % absorption via the inhalation route of exposure.

Since the dermal and inhalation toxicological endpoints are the same and are identified from the same studies, the dermal and inhalation exposures are summed then divided into the NOAEL to derive the Margin of Exposure.

Subsequent to the 7 March 2005 hazard memorandum (DP Num: 278047, C. Swartz, 07/MAR/2005), the Agency conducted the two most recent risk assessments for assorted new uses of pendimethalin (DP Num: 325176; M. Collantes; 03/MAR/2006 and DP Num: 329627; W. Drew; 12/JUL/2006).  The March and July assessments used the same dermal and inhalation toxicological endpoints (i.e. 10 mg ai/kg bw/day) however modifications were made to the dermal absorption factor and to the uncertainty factors.  The dermal absorption factor was adjusted to 3.0 %.  Regarding the uncertainty factors the Agency stated:  HED has recommended retaining a 10X UFDB (database uncertainty factor) for pendimethalin to account for the lack of a developmental thyroid toxicity study.  The standard 10X intraspecies uncertainty factor and a 3X interspecies factor are applicable to pendimethalin risk assessments.  The interspecies uncertainty factor of 10X is reduced to 3X due to the greater sensitivity of the adult rat thyroid effects compared to adult humans.  Therefore, the level of concern (target MOE) for occupational exposure is 30X.  See Table 10.1 for a summary of estimated exposures and risks to occupational pesticide handlers.

Table 10.1  Summary of Exposure & Risk for Occupational Handlers Applying Pendimethalin

Unit Exposure1

mg ai/lb handled	Applic. Rate2

lb ai/unit	Units Treated3	Avg. Daily Exposure4

mg ai/kg bw/day	MOE5

Mixer/Loader Using Open Pour of Liquid Formulations

Dermal:

SLNoGlove       2.9 HC

SLWithGlove    0.023 HC

Inhal.               0.0012 HC	6.0 lb ai/A	200 A/day	Dermal:

SLNoGlove      1.49

SLWithGlove   0.012

Inhal.                0.021	SLNoGlove

7

SLWithGlove

303

Applicator Using Open-Cab Ground-boom Sprayer

Dermal:

SLNoGlove       0.014 HC

SLWithGlove    0.014 MC

Inhal.               0.00074 HC	6.0 lb ai/A	200 A/day	Dermal:

SLNoGlove     0.0072

SLWithGlove  0.0072

Inhal.               0.013	SLNoGlove

495

SLWithGlove

495

1.  Unit Exposures are taken from “PHED SURROGATE EXPOSURE GUIDE”, Estimates of Worker Exposure from The Pesticide Handler Exposure Database Version 1.1, August 1998.   Inhal. = Inhalation.  Units = mg a.i./pound of active ingredient handled.  Data Confidence: LC = Low Confidence, MC = Medium Confidence, HC = High Confidence.   Dermal SLNoglove = dermal exposure with a single layer of work clothing (long pants, long sleeved shirt and shoes + socks) and NO protective gloves;  Dermal SLWithGlove = dermal exposure with a single layer of work clothing AND the use of protective gloves.  Inhal.  = inhalation exposure.

2.  Applic. Rate. = Taken from the

3.  Units Treated are taken from “Standard Values for Daily Acres Treated in Agriculture”; SOP  No. 9.1.   Science Advisory Council for Exposure;  Revised 5 July 2000;

4.  Average Daily Dose (ADD) = Unit Exposure * Applic. Rate * Units Treated  * absorption factor ( 3.0 % dermal, 100 % inhalation) ( Body Weight (70 kg)

5.  MOE = Margin of Exposure = No Observable Adverse Effect Level (NOAEL) (10 mg ai/kg bw/day)  ( ADD.  ADD = dermal exposure + inhalation exposure.

Occupational handler exposure risk estimates were calculated for total (combined dermal and inhalation) short- and intermediate-term exposures.  MOEs are above the LOC of 30 for all exposure scenarios at single-layer (with gloves) level of risk mitigation, and are, therefore, not of concern to ARIA, as long as there is a label requirement for the use of PPE.

10.2	Occupational Post-Application Exposure

It is possible for agricultural workers to have post-application exposure to pesticide residues during the course of typical agricultural activities.  HED in conjunction with the Agricultural Re-entry Task Force (ARTF) has identified a number of post-application agricultural activities that may occur and which may result in post-application exposures to pesticide residues.  HED has also identified transfer coefficients (TC) (cm²/hr) relative to the various activities which express the amount of foliar contact over time, during each of the activities identified (ExpoSAC SOP 3.1, Agricultural Transfer Coefficients, Rev. 7 Aug. 2000).

With the exception of broccoli and cabbage, applications for the proposed new uses are to be applied to the soil and incorporated with rainfall, irrigation or light mechanical incorporation.  For broccoli and cabbage, applications are to be broadcast foliar, at the 2 - 4 leaf stage of crop development.  Under the circumstances of the proposed new use pattern and according to the SOP 3.1, the uses with the highest TCs are broccoli and cabbage with a TC of 2,000 cm2/hr for hand weeding in minimal foliage development.

Therefore, as a screening level assessment, ARIA uses the maximum rate of application (1.0 lb ai/A) for broccoli and cabbage and a TC of 2,000 cm2/hr to assess postapplication exposure to agricultural workers.  A screening level assessment is considered to be conservative i.e., protective.

A MOE of 30 is adequate to protect agricultural workers from post-application exposures to pendimethalin applied as described above.  The calculated MOE is 666.  Since the calculated MOE is > 30, the proposed uses do not exceed ARIA’s level of concern.

10.3  Restricted Entry Interval (REI)

In the Agency's 3 March 2006 risk assessment (DP Num: 325176, M. Collantes, 03/MAR/2006), the Agency classified pendimethalin in Toxicity Category IV for acute dermal, acute inhalation toxicity and primary dermal irritation.  It is classified in Toxicity Category III for primary eye irritation and it is not a dermal sensitizer.  Except for broccoli and cabbage, all proposed applications are to be made directly to the soil. The current pendimethalin labels list a REI of 24 hours which is adequate to protect agricultural workers from post-application exposures.

11.0	Data Needs and Label Requirements tc "10.0	Data Needs and Label Requirements"

11.1	Toxicology  tc "10.1	Toxicology " \l 2

HED has previously requested the submission of developmental thyroid toxicity data for adult rats and young rats following pre- and post-natal exposure to pendimethalin.  This study is still required.

11.2	Residue Chemistry  tc "10.2	Residue Chemistry " \l 2

Please refer to the Residue Chemistry Deficiencies portion of the Executive Summary (Section 1.0).

11.3	Occupational and Residential Exposure  tc "10.3	Occupational and Residential Exposure " \l 2

ARIA reiterates the label requirement for PPE.

References

Endpoint Selection Document

Pendimethalin: REVISED HED Human Health Risk Assessment to Support Section 3 Registration for use on Carrots, Mint, Citrus, and Tree Nuts. PC Code: 108501; DP Num: 325176; M. Collantes; 03/MAR/2006.

Pendimethalin.  Addendum to Human Health Risk Assessment (D329627) of 7/12/2006: Inadvertently Omitted Tolerances (on Various Beans and Peas), Review of BASF’s Proposal for Reduction of Citrus Fruit Pre-Harvest Interval, and Revision of the Chronic Toxicity Profile; DP Num: 334766; W. Drew; 27/MAR/2007  SEQ CHAPTER \h \r 1 .

Dietary Exposure Memorandum

Pendimethalin: Chronic Dietary (Food and Drinking Water) Analysis and Risk Assessment to Support the Section 3 Registration for New Food Uses of the Herbicide on Artichoke, Asparagus, Brassica Head and Stem Vegetables, Subgroup 5A, and Grape; DP Num: 334173; D. Rate; 02/AUG/2007.

Drinking Water Memorandum

Drinking Water Assessment for Pendimethalin for Cabbage, Asparague, Bearing Grapes, and Artichoke; DP Num: 334061, J. Breithaupt; 08/MAY/2007.

Product Chemistry Memorandum

European Commission Health & Consumer Protection Directorate-General, Directorate E – Pendimethalin 7477/ VI/98-final, 13 January 2000 (  HYPERLINK "http://ec.europa.eu/food/plant/protection/evaluation/existactive/list1- 35_en.pdf"  http://ec.europa.eu/food/plant/protection/evaluation/existactive/list1-3 5_en.pdf

Residue Chemistry Data Reviews

Pendimethalin.  Tolerance Petition   SEQ CHAPTER \h \r 1 Requesting Section 3 Registration for Food/Feed Use of the Herbicide on Alfalfa.  Summary of Analytical Chemistry and Residue Data.  PP#5F6961.; DP Num: 319412; W. Drew; 12/JUL/2006.

Pendimethalin.  Petitions for Tolerances on Brassica Head and Stem Vegetables, Subgroup 5A, Asparagus, Grape and Articoke.  Summary of Analytical Chemistry and Residue Data.  Petition Number 6E7129.; DP Num: 340343; D. Rate; 02/AUG/2007.

Occupational and Residential Exposure Memorandum

PENDIMETHALIN - Human Non-Dietary Risk Assessment for the Proposed Use of Pendimethalin on Artichoke, Asparagus, Broccoli, Cabbage and Grape; DP Num: 334174; M. Dow; 09/JAN/2007.

Re-registration Eligibility Document

Pendimethalin Re-registration Eligibility Document; DP Num: 221532; J. Leahy; 20/FEB/1996.

Appendices

APPENDIX A:  TOXICOLOGY DATA REQUIREMENTS

HED has requested the submission of developmental thyroid toxicity data for adult rats and young rats following pre- and post-natal exposure to pendimethalin.

Table A.1	Acute Toxicity Profile - Pendimethalin

Guideline No.	Study Type	MRID(s)	Results	Toxicity Category

870.1100	Acute oral [Rat]	00026657	LD50=1250 mg/kg (m)

        =1050 mg/kg (f)	III

870.1200	Acute dermal [Rabbit]	00026657	LD50 = > 5000 mg/kg	IV

870.1300	Acute inhalation [Rat]	00073342	LC50 = 32 mg/L	IV

870.2400	Acute eye irritation [Rabbit]	00026657	slight conjunctival irritation	III

870.2500	Acute dermal irritation [Rabbit]	00026657	no dermal irritation IV

870.2600	Skin sensitization [Guinea pig ]	00153767	non-sensitizer	-

Table A.2 Subchronic, Chronic and Other Toxicity Profile for Pendimethalin.

Guideline No.	Study Type	MRID No./ Classification	Dose Levels	Results

870.3100	Subchronic oral rat (30-day)	000106754 Supplementary	ppm = 0, 800, 1600, 3200

mg/kg/day =

0, 80, 160, 320	NOAEL = 160 mg/kg/day

LOAEL = 320 mg/kg/day based on increased liver weight.

870.3100	Subchronic oral rat (13-week)	00156081	ppm = 0, 100, 500, 5000

mg/kg/day =

 0, 10, 50, 500	NOAEL = 50 mg/kg/day

LOAEL = 500 mg/kg/day based on decreased body weight gain and food consumption, decreased hematocrit and hemoglobin w/ increases in platelets in males, increased liver weight, red thyroids, and hypertrophy of the liver.

870.3100	Subchronic oral rat (13-week)	00059468

Supplementary	ppm = 0, 25, 50, 100, 500, 2500

mg/kg/day =

0, 2.5, 5, 10, 50,  250	NOAEL = 250 mg/kg/day

LOAEL was not determined

870.3100	Subchronic oral rat (13 week)	00059469

Supplementary	ppm = 0, 2500

mg/kg/day = 0, 250	NOAEL = 250 mg/kg/day

LOAEL was not determined

870.3100	Subchronic oral rat (92-day)	42054601	ppm = 0, 100, 5000

mg/kg/day =

0, 4.98, 245.4	NOAEL = 4.98 mg/kg/day

LOAEL = 245.4 mg/kg/day based on thyroid effects

870.3100	Subchronic oral rat (56-day)	43135001	ppm = 0, 500, 5000

mg/kg/day =

0, 31, 292	NOAEL was not determined

LOAEL = 31 mg/kg/day based on thyroid effects

870.3100	Subchronic oral rat (14-day)	43135003	ppm = 0, 100, 500

mg/kg/day =

0, 10, 500	NOAEL = 10 mg/kg/day

LOAEL = 500 mg/kg/day based on thyroid effects

870.3100	Subchronic oral dog (90-day)	00026672

Supplementary	mg/kg/day =

0, 62.5, 250, 1000	NOAEL = 62.5 mg/kg/day

LOAEL = 250 mg/kg/day based on body weight loss

870.3150	Subchronic oral mouse (30-day)	000106754

Supplementary	ppm = 0, 500, 1000, 2000

mg/kg/day =

0, 75, 150, 300	NOAEL = 300 mg/kg/day

LOAEL was not determined

870.3200	21-Day dermal toxicity (rat)	00026663	mg/kg/day =

0, 250, 500, 1000	NOAEL = 1000 mg/kg/day

LOAEL was not determined

870.3700a	Prenatal Developmental Toxicity (Rat)	00025752

Supplementary; but satisfactory when considered w/ rabbit developmental mg/kg/day =

0, 125, 250, 500	Maternal NOAEL = 500 mg/kg/day (highest dose tested)

Maternal LOAEL was not determined

Developmental NOAEL = 500 mg/kg/day  (highest dose tested)

Developmental LOAEL was not determined

870.3700b

	Prenatal Developmental Toxicity (Rabbit)	00117444

Supplementary; Upgradeable	mg/kg/day =

 0, 15, 30,  60	Maternal NOAEL = 60 mg/kg/day (highest dose tested)

Maternal LOAEL was not determined

Developmental NOAEL = 60 mg/kg/day (highest dose tested)

Developmental LOAEL was not determined

range finding study indicated doses ≥125 mg/kg/day associated with increased mortality

870.3800	Reproduction and fertility effects

(2-Generation Reproduction in Rats)	41725203

	ppm = 0, 500, 2500, 5000

mg/kg/day (M/F) =

0, 34/43, 172/216, 346/436

HED RED

mg/kg/day =

0, 25, 125, 250

HIARC Document

Note: Doses were obtained from  a HED pendimethalin RED and a HIARC document (4/18/2000) which resulted in different dose calculations for mg/kg/day.  Consequently, doses

are given as a range, based on calculations from

actual chemical intake and a generic ratio (1:20) of dietary intake. Parental/Systemic NOAEL = 25-34/43 (M/F)  mg/kg/day (500 ppm)

Parental /Systemic LOAEL = 125-172/216 (M/F) mg/kg/day (2500 ppm) based on decreased body weight gain and food consumption.

Reproductive/Offspring NOAEL = 25-34/43 (M/F)  mg/kg/day (500 ppm)

Reproductive/Offspring LOAEL = 125-172/216 (M/F) mg/kg/day (2500 ppm) based on decreases in the number of pups born and pup weights.

870.3800	Reproduction and fertility effects

3-Generation Reproduction in Rats	00026671, 0040304, 00059470	ppm = 0, 500, 5000

mg/kg/day =

0, 25, 250	Parental/Systemic NOAEL = 25 mg/kg/day.

Parental/Systemic LOAEL = 250 mg/kg/day based on decreased body weight.

Reproductive/Offspring NOAEL = 25 mg/kg/day

Reproductive/Offspring LOAEL = 250 mg/kg/day based on decreased pup body weight gain and possible decreased pups born alive and pup survival.

870.4100a	Chronic toxicity

(Mouse)	40909901	ppm = 0, 100, 500, 5000

mg/kg/day (M/F) =

0, 12.3/15.6, 62.3/78.3, 622.1/806.9

	NOAEL = 62.3/78.3 mg/kg/day

LOAEL = 622.1/806.99 mg/kg/day

based on mortality, body weight decrease, organ weight changes and amyloidosis.

870.4100b	Chronic toxicity

(2-year Oral Dog)	00058657	mg/kg/day =

0, 12.5, 50, 200	NOAEL = 200 mg/kg/day

LOAEL was not established. 2

870.4200	Chronic Toxicity/Carcino-genicity

(2-year Oral Rat)	40174401	ppm = 0, 100, 500, 5000

mg/kg/day =

0, 5, 25, 250	NOAEL = 25 mg/kg/day

LOAEL = 250 mg/kg/day based on decreased survival, body weight gain and decreased food consumption, increased gamma glutamyl transferase, cholesterol and liver weights and thyroid effects.

870.4200	Chronic Toxicity

(2-year Oral Rat)	42027802	ppm = 0, 1250, 2500, 3750, 5000

mg/kg/day =

0, 51, 103, 154, 213	NOAEL was not determined

LOAEL = 51 mg/kg/day based on non-neoplastic thyroid follicular cell changes.

870.4300

	Carcinogenicity

(18-month Oral Mouse)	40909901	ppm = 0, 100, 500, 5000

mg/kg/day (M/F) =

0, 12.3/15.6, 62.3/78.3, 622.1/806.9

	NOAEL = 62.3/78.3 mg/kg/day

LOAEL = 622./806.9 mg/kg/day  based on mortality, body weight decrease, organ weight changes and amyloidosis.

870.5100	Reverse Gene Mutation Assay in Bacteria strains of S. typhimurium	00153768	50, 158, 500, 1581, 5000 µg/plate	Positive

Evidence of a 2-fold increase in number of induced mutant colonies over background at all doses from 50 to 5000 µg/plate

870.5100	Reverse Gene Mutation Assay in Escherichia coli WP2	43177801 25, 50, 100, 250, 500, 750 µg/plate	Negative

870.5100	Reverse Gene Mutation Assay in Escherichia coli WP2	43135005 50, 158, 500, 1581, 5000 µg/plate or 1000 µg/paper disk/plate  Negative

870.5100	Reverse Gene Mutation Assay in Escherichia coli WP2	43135006 50, 100, 250, 500, 750 µg/plate 	Negative

870.5300	Mammalian Cell Gene Mutation in Chinese hamster ovary	43177802 1, 5, 7.5, 10, 20, 30, 40, 50 µg/ml (-S9)

10, 25, 50, 75, 100, 125, 150, 175 µg/ml (+S9)	Negative

870.5375	Chromosomal Aberration (CHO)	00153770	Doses ranging from 5-50 µg/ml	Negative

870.5395	Mouse Micronucleus Study	42027801	313, 625, 1250 mg/kg	Negative

870.5550	Alkaline Elution Assay in Rats	43135007	1250, 2500, 5000 mg/kg/bw	Negative

870.7485	Metabolism and pharmacokinetics in Rat	00046275	n/a Pendimethalin is eliminated from body with 70% being excreted in feces primarily parent compound and 20% in urine within 24 hours.

Some of the  LOAELs/NOAELS in Table 4.1b were previously denoted as LOELs/NOELS in Data Evaluation Records (DERs), the language was updated to comply with current standards without re-examining effects.  As new uses for pendimethalin are submitted, DERs will be re-reviewed and updated.

APPENDIX B:	METABOLISM CONSIDERATION

The nature of the residue in plants, livestock and rotational crops is adequately understood.

Metabolism studies identified and discussed in the 13/MAY/1996 RED chapter support the currently proposed uses.  Rotational crop tolerances are not needed, provided labels specify rotational crop PBIs of 90-days for cereal grains, and 270 days for all other crops.

As a result of the proposed increase in seasonal application rate (pursuant to the alfalfa petition) which may be applied to rotatable food/feed crops (from 2.0 lb ai/A to 4.0 lb ai/A), HED is requesting a limited field accumulation study (OPPTS 860.1900) to determine the amount of pesticide residue uptake into rotational crops.  HED concludes that the registrant should impose PBIs of 90-days for rotated cereal grain crops, and 270-days for all other rotated crops, until the limited field rotational crop study has been conducted.

APPENDIX C:	TOLERANCE ASSESSMENT SUMMARY AND TABLE

(DP Num: 334173; D. Rate; 02/AUG/2007)

The Residue Chemistry Chapter for the Pendimethalin RED concluded that the residues of concern in plants are pendimethalin   SEQ CHAPTER \h \r 1 [N-(1-ethylpropyl)-3,4-dimethyl-2,6-dinitrobenzenamine] and its metabolite, 4-[(1-ethylpropyl)amino]-2-methyl-3,5-dinitrobenzyl alcohol (CL202,347).  The chemical names and structures of pendimethalin and CL202,347 are depicted in Appendix I. The proposed tolerance expression is consistent with 40CFR §180.361.

A summary of tolerance assessments, following ARIA’s review of submitted field and processing studies, is presented in Table 7.  ARIA recommends tolerances of 0.10 ppm for the commodities listed in Table 7 which were not entered in a Tolerance/MRL Harmonization Spreadsheet (all proposed commodities except asparagus), because all of the samples treated at the proposed 1X application rate bore residues below the method LLMV (or LOQ) (<0.050 ppm) for each analyte.  Following application at 1X, the combined residues were <0.1 ppm in all samples of artichoke (n = 6 samples), broccoli (n = 12), cabbage (n = 7) and grape (n = 18).  The residues observed in all but two samples of asparagus (n = 12) treated at 1X were also <0.050 ppm for each analyte.  The proposed tolerance for asparagus was calculated using the maximum limit estimator (MLE) and the maximum residue limit (MRL) spreadsheet.  Without ignoring lognormality, a value of 0.15 ppm was recommended for asparagus using the 95th percentile of EU method I.

There are currently no Canadian , Mexico or Codex maximum residue limits (MRLs) for pendimethalin on the proposed commodities.  An International Residue Limit Status sheet is appended at the end of this document in Appendix II.

Pendimethalin tolerances are not required for milk, meat, poultry, nor eggs for the purpose of evaluating the subject IR-4 petition.

Pending submission of a revised Section F to reflect appropriate tolerance levels, there are adequate residue data to support the establishment of pendimethalin tolerances on artichoke, globe; asparagus; Brassica head and stem vegetables, subgroup 5A; and grape.

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Proposed Tolerance (ppm)	Recommended Tolerance (ppm)	Comments1;

Correct Commodity Definition

Brassica, head and stem, subgroup 5A	0.05	0.1	Adequate field trial data are available.  All combined residues were <0.1 ppm.

Artichoke, globe	0.05	0.1	Adequate field trial data are available.  All combined residues were <0.1 ppm.

Asparagus	0.1	0.15	Adequate asparagus field trial data are available and the tolerance was calculated using the MLE and MRL spreadsheets.

Grape	0.05	0.1	Adequate grape field trial data are available.  All residues in the field studies were below the combined residue LLMV (<0.1 ppm).

Grape, juice	--	0.15	Adequate grape processing studies were not provided.  The study must use an application rate of at least 5X or the petitioner may show that the exaggerated rate is phytotoxic to the crop.  Once adequate studies have been reviewed, the tolerance may be revised or withdrawn.

Grape, raisin 	--	0.50

1 MLE = Maximum Limit Estimater; MRL = Maximum Residue Limit

APPENDIX D:  REVIEW OF HUMAN RESEARCH

No MRID - PHED Surrogate Exposure Guide

	Page   PAGE  1  of   NUMPAGES  34


[Federal Register Volume 85, Number 137 (Thursday, July 16, 2020)]
[Proposed Rules]
[Pages 43193-43195]
[FR Doc No: 2020-14652]

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ENVIRONMENTAL PROTECTION AGENCY

40 CFR Part 300

[EPA-HQ-SFUND-1990-0013; FRL-10011-27-Region 6]

National Oil and Hazardous Substances Pollution Contingency Plan;
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ACTION: Proposed rule; notice of intent.

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and information in these repositories, including the deletion docket,
has not been updated with hardcopy or electronic media. For further
information and updates on EPA Docket Center services, please visit us
online at https://www.epa.gov/dockets.
    The EPA continues to carefully and continuously monitor information
from the Centers for Disease Control and Prevention (CDC), local area
health departments, and our Federal partners so that we can respond
rapidly as conditions change regarding COVID.

FOR FURTHER INFORMATION CONTACT: Michael Torres, Remedial Project
Manager, U.S. Environmental Protection Agency, Region 6, Superfund and
Emergency Management Division (R6 SED-RL); 1201 Elm Street, Suite 500;
Dallas, Texas 75270,<PHONE_NUMBER>, email<EMAIL_ADDRESS>
SUPPLEMENTARY INFORMATION:

Table of Contents

I. Introduction
II. NPL Deletion Criteria
III. Deletion Procedures
IV. Basis for Site Deletion

I. Introduction

    EPA Region 6 announces its intent to delete the Tulsa Fuel and
Manufacturing Superfund Site from the National Priorities List (NPL)
and requests public comment on this proposed action. The NPL
constitutes Appendix B of 40 CFR part 300 which is the National Oil and
Hazardous Substances Pollution Contingency Plan (NCP), which EPA
promulgated pursuant to section 105 of the Comprehensive Environmental
Response, Compensation and Liability Act (CERCLA) of 1980, as amended.
EPA maintains the NPL as the list of sites that appear to present a
significant risk to public health, welfare, or the environment. Sites
on the NPL may be the subject of remedial actions financed by the
Hazardous Substance Superfund (Fund). As described in 40 CFR
300.425(e)(3) of the NCP, sites deleted from the NPL remain eligible
for Fund-financed remedial actions if future conditions warrant such
actions.
    EPA will accept comments on the proposal to delete this site for
thirty (30) days after publication of this document in the Federal
Register.
    Section II of this preamble explains the criteria for deleting
sites from the NPL. Section III of this preamble discusses procedures
that EPA is using for this action. Section IV of this preamble
discusses where to access and review information that demonstrates how
the deletion criteria have been met at the Tulsa Fuel and Manufacturing
Superfund Site.

II. NPL Deletion Criteria

    The NCP establishes the criteria that EPA uses to delete sites from
the NPL. In accordance with 40 CFR 300.425(e), sites may be deleted
from the NPL where no further response is appropriate. In making such a
determination pursuant to 40 CFR 300.425(e), EPA will consider, in
consultation with the State, whether any of the following criteria have
been met:
    i. Responsible parties or other persons have implemented all
appropriate response actions required;
    ii. all appropriate Fund-financed response under CERCLA has been
implemented, and no further response action by responsible parties is
appropriate; or
    iii. the remedial investigation has shown that the release poses no
significant threat to public health or the environment and, therefore,
the taking of remedial measures is not appropriate.
    Pursuant to CERCLA section 121(c) and the NCP, EPA conducts five-
year reviews to ensure the continued protectiveness of remedial actions
where hazardous substances, pollutants, or contaminants remain at a
site above levels that allow for unlimited use and unrestricted
exposure. EPA conducts such five-year reviews even if a site is deleted
from the NPL. EPA may initiate further action to ensure continued
protectiveness at a deleted site if new information becomes available
that indicates it is appropriate. Whenever there is a significant
release from a site deleted from the NPL, the deleted site may be
restored to the NPL without application of the hazard ranking system.

III. Deletion Procedures

    The following procedures apply to deletion of the Site:
    (1) EPA consulted with the State before developing this Notice of
Intent to Delete.
    (2) EPA has provided the state 30 working days for review of this
action prior to publication of it today.
    (3) In accordance with the criteria discussed above, EPA has
determined that no further response is appropriate.
    (4) The State of Oklahoma, through the Oklahoma Department of
Environmental Quality, has concurred with deletion of the Site from the
NPL.
    (5) Concurrently with the publication of this Notice of Intent to
Delete in the Federal Register, a notice is being published in a major
local newspaper, the Tulsa World. The newspaper notice announces the
30-day public comment period concerning the Notice of Intent to Delete
the site from the NPL.
    (6) The EPA placed copies of documents supporting the proposed
deletion in the deletion docket and made these items available for
public inspection and copying at the Site information repositories
identified above.
    If comments are received within the 30-day public comment period on
this action, EPA will evaluate and respond appropriately to the
comments before making a final decision to delete. If necessary, EPA
will prepare a Responsiveness Summary to address any significant public
comments received. After the public comment period, if EPA determines
it is still appropriate to delete the Site, the Regional Administrator
will publish a final Notice of Deletion in the Federal Register. Public
notices, public submissions and copies of the Responsiveness Summary,
if prepared, will be made available to interested parties and in the
site information repositories listed above.
    Deletion of a site from the NPL does not itself create, alter, or
revoke any individual's rights or obligations. Deletion of a site from
the NPL does not in any way alter EPA's right to take enforcement
actions, as appropriate. The NPL is designed primarily for
informational purposes and to assist EPA management. Section
300.425(e)(3) of the NCP states that the deletion of a site from the
NPL does not preclude eligibility for future response actions, should
future conditions warrant such actions.

IV. Basis for Site Deletion

    The EPA placed copies of documents supporting the proposed deletion
in the deletion docket. The material provides explanation of EPA's
rationale for the deletion and demonstrates how it meets the deletion
criteria. This information is made available for public inspection in
the docket identified above.

List of Subjects in 40 CFR Part 300

    Environmental protection, Air pollution control, Chemicals,
Hazardous waste, Hazardous substances, Intergovernmental relations,
Penalties, Reporting and recordkeeping requirements, Superfund, Water
pollution control, Water supply.

    Authority: 33 U.S.C. 1251 et seq.

    Dated: July 1, 2020.
Kenley McQueen,
Regional Administrator, Region 6.
[FR Doc. 2020-14652 Filed 7-15-20; 8:45 am]
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[Federal Register Volume 78, Number 205 (Wednesday, October 23, 2013)]
[Notices]
[Pages 63181-63182]
[FR Doc No: 2013-24793]

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ENVIRONMENTAL PROTECTION AGENCY

[EPA-HQ-OECA-2013-0340; FRL-9901-67-OEI]

Information Collection Request Submitted to OMB for Review and
Approval; Comment Request; NESHAP for Stationary Reciprocating Internal
Combustion Engines (Renewal)

AGENCY: Environmental Protection Agency (EPA).

ACTION: Notice.

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SUMMARY: The Environmental Protection Agency has submitted an
information collection request (ICR), ``NESHAP for Stationary
Reciprocating Internal Combustion Engines (Renewal)'' (EPA ICR No.
1975.09, OMB Control No. 2060-0548) to the Office of Management and
Budget (OMB) for review and approval in accordance with the Paperwork
Reduction Act (44 U.S.C. 3501 et seq.). This is a proposed extension of
the ICR, which is currently approved through November 30, 2013. Public
comments were previously requested via the Federal Register (78 FR
33409) on June 4, 2013 during a 60-day comment period. This notice
allows for an additional 30 days for public comments. A fuller
description of the ICR is given below, including its estimated burden
and cost to the public. An Agency may not conduct or sponsor and a
person is not required to respond to a collection of information unless
it displays a currently valid OMB control number.

DATES: Additional comments may be submitted on or before November 22,
2013.

ADDRESSES: Submit your comments, referencing Docket ID Number EPA-HQ-
OECA-2013-0340, to: (1) EPA online, using www.regulations.gov (our
preferred method), by email to<EMAIL_ADDRESS>or by mail to: EPA
Docket Center, Environmental Protection Agency, Mail Code 28221T, 1200
Pennsylvania Ave. NW., Washington, DC 20460; and (2) OMB via email to
<EMAIL_ADDRESS>Address comments to OMB Desk Officer for
EPA.
    EPA's policy is that all comments received will be included in the
public docket without change including any personal information
provided, unless the comment includes profanity, threats, information
claimed to be Confidential Business Information (CBI) or other
information whose disclosure is restricted by statute.

FOR FURTHER INFORMATION CONTACT: Learia Williams, Monitoring,
Assistance, and Media Programs Division, Office of Compliance, Mail
Code 2227A, Environmental Protection Agency, 1200 Pennsylvania Ave.
NW., Washington, DC 20460; telephone number:<PHONE_NUMBER>; fax
number:<PHONE_NUMBER>; email address<EMAIL_ADDRESS>
SUPPLEMENTARY INFORMATION: Supporting documents which explain in detail
the information that the EPA will be collecting are available in the
public docket for this ICR. The docket can be viewed online at
www.regulations.gov or in person at the EPA Docket Center, EPA West,
Room 3334, 1301 Constitution Ave. NW., Washington, DC. The telephone
number for the Docket Center is<PHONE_NUMBER>. For additional
information about EPA's public docket, visit http://www.epa.gov/dockets.
    Abstract: The respondents to this information collection are owners
or operators of existing spark ignition (SI) engines that have a site
rating of less than or equal to 500 brake hp and located at major
sources of hazardous air pollutants (HAP) and existing stationary SI
engines located at area sources of HAP emissions. The information is
requested by the Agency to determine compliance with the rule. The
information will then be used by enforcement agencies to verify that
sources subject to the standards are meeting the emission reductions
mandated by the Clean Air Act (CAA). Other sizes/types of stationary
reciprocating internal combustion engines (RICE) have been regulated
under previous actions. Thus, this final action fulfills the
requirements of section 112 of the CAA, which requires EPA to
promulgate standards for stationary RICE, by adding requirements for
the remaining engines.
    Form Numbers: None.
    Respondents/affected entities: Owners or operators of stationary
reciprocating internal combustion engines (RICE).
    Respondent's obligation to respond: Mandatory (40 CFR part 63,
subpart ZZZZ).
    Estimated number of respondents: 902,791 (total).
    Frequency of response: Initially, quarterly, semiannually, and
annually.
    Total estimated burden: 3,427,264 hours (per year). Burden is
defined at 5 CFR 1320.3(b).
    Total estimated cost: $424,877,556 (per year), includes $27,854,429
annualized capital or operation & maintenance costs.
    Changes in the Estimates: There is a decrease in the total
estimated burden as currently identified in the OMB Inventory of
Approved Burdens. The decrease is a result of merging the reporting and
recordkeeping requirements for the initial and amendment NESHAP and
removing any duplicative burden items. This ICR combines the original
final rule and the 2006, 2008, and 2010 amendments, which were
previously covered under EPA ICR Number 1975.04, 1975.05, 1975.06,
1975.07, and 1975.08. In addition, this ICR incorporates the
requirements for emergency engines as set forth in the January 2013
Final Rule amendment. This resulted in several changes in the total
estimated burden and costs.

John Moses,
Director, Collection Strategies Division.
[FR Doc. 2013-24793 Filed 10-22-13; 8:45 am]
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