Document ID: EPA-HQ-OPP-2008-0513-0002
Agency: epa
Document Type: Supporting & Related Material
Title: 
Posted Date: 2009-03-18T04:00Z

UNITED STATES ENVIRONMENTAL PROTECTION AGENCY

WASHINGTON, DC  20460

OFFICE OF PREVENTION,

PESTICIDES AND TOXIC SUBSTANCES

MEMORANDUM

Date:		20 May 2008

Subject:	Pendimethalin.  Human Health Risk Assessment for the Proposed
Food/Feed Use of the Herbicide (Associated with Section 18 Registration)
on Bermuda Grass Pastures and Hay Fields in Texas.  

	PC Code:  108501					DP Barcode:  349723

	MRID Number:  (None)				Decision Number:  390012

	Petition Number:  08TX07				Registration Number:  241-418

	Assessment Type:  Single Chemical/Aggregate	Regulatory Action:  Section
18

	TXR Number:  (None)					Reregistration Case Number:  (None)

	Regulatory Citation:  40CFR §180.361		CAS Number:  40487-42-1

	Chemical Class:  Dinitroaniline Herbicide		Trade Name:  Prowl® H20

From:		William T. Drew, Chemist and Risk Assessor

		Shih-Chi Wang, Biologist and ORE Assessor 

		Registration Action Branch 2 (RAB2)

		Health Effects Division (HED), 7509P

Through:	Dennis McNeilly, Chemist

		Michael A. Doherty, PhD, Senior Scientist

		RAB2/HED, 7509P

To:		Stacey Groce and Daniel Rosenblatt, RM Team 5

		Risk Integration Minor Use & Emergency Response Branch (RIMUERB)

		Registration Division (RD), 7505P

1.0	Conclusions

	As summarized below, this Crisis Exemption/Section 18 use on Bermuda
grass in Texas will not affect the dietary burden or tolerances for
existing registered crop uses.  Since the aggregate exposures resulting
from currently registered pendimethalin uses are not of concern to HED,
the crisis exemption and proposed Section 18 use on Bermuda grass are
also not of concern to HED.  Occupational risks, in terms of margins of
exposure (MOEs), from the proposed use on Bermuda grass are all
estimated to be greater than 30 with baseline clothing, and are
therefore not of concern to HED.  

	The most recent Section 3 human health risk assessment for
pendimethalin is Pendimethalin.  Human Health Risk Assessment for the
Proposed Tolerance in/on Crayfish. (D350493; Christine L. Olinger; 31
March 2008).  Because details may be found in the above document, only
summary information regarding pendimethalin hazard characterization and
toxicity endpoints are included below in support of this Section 18
request.  Generally, information and/or conclusions which remain
unchanged from the previous risk assessment are not reiterated; instead,
a reference to the previous document is provided.  

	Inter-regional Research Project #4 (IR-4) has conducted 8 field trials
with pendamethalin on Bermuda grass (2 each in NC, TN, GA and TX), and
submitted summarized preliminary results in support of TDA’s petition
for a Section 18 registration.  HED has no objection to the
establishment (associated with Section 18 registration) of tolerances
for pendimethalin residues of 25 ppm in Bermuda grass forage, and 60 ppm
in Bermuda grass hay.  

	Environmental Justice Considerations

	Potential areas of environmental justice concerns, to the extent
possible, were considered for this human health risk assessment, in
accordance with US Executive Order 12898, Federal Actions to Address
Environmental Justice in Minority Populations and Low-Income Populations
(  HYPERLINK
"http://www.epa.gov/compliance/resources/policies/ej/exec_order_12898.pd
f" 
http://www.epa.gov/compliance/resources/policies/ej/exec_order_12898.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 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 the associated risks for adult applicators, and
for toddlers, youths, and adults entering or playing on treated areas
post-application are evaluated.  Further considerations are currently in
development as OPP has committed resources and expertise to the
development of specialized software and models that consider exposure to
bystanders and farm workers, as well as lifestyle and traditional
dietary patterns among specific subgroups.  

	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 B) have been determined to
require a review of their ethical conduct, have received that review,
and have been determined to be ethical.  

2.0	ACTION REQUESTED

	The State of Texas Department of Agriculture (TDA) is employing a
crisis exemption for the immediate use of the herbicide pendimethalin
(as Prowl H20) on Bermuda grass pastures and hay fields as a treatment
to control pre-emergent sandbur species in the State of Texas.  Prowl
H20 is an aqueous capsule suspension (CS) formulation.  TDA is
requesting a Section 18 registration for this use.  The request entails
application of an estimated 7.9 million gallons of product (30 million
lbs ai) to 10 million acres in Texas beginning 5 February 2008.  Human
exposures and risks are addressed in this document for chronic dietary
risk; exposure to and risk from pendimethalin residues in water;
residential exposure and risk; aggregate exposure and risk; and exposure
and risk to workers.  

3.0	BACKGROUND

	Overview

	TDA has issued a crisis exemption that authorizes the use of
pendimethalin, with CAS name
N-(1-ethylpropyl)-3,4-dimethyl-2,6-dinitrobenzenamine, to control common
sandbur and other sandbur species (Cenchrus echinatus, et al) in Bermuda
grass pastures and hay fields in Texas.  The crisis program entails
application of the end-use product (EP), Prowl H20 (EPA Registration
Number 241-418), on a maximum of 10 million acres in the State of Texas.
 The counties of Texas affected by this crisis exemption include all
counties throughout the state.  Prowl H20 may be applied once per crop
season, by ground equipment only, at the rate of 2.0 to 3.0 pounds of
active ingredient per acre (lb ai/A), which is equivalent to 2.1 to 3.2
quarts of product per acre.  Application via aerial or chemigation
equipment is prohibited.  The maximum application rate is 3.0 lb ai/A
(3.2 quarts) per season, and the minimum pre-harvest interval (PHI) is
40 days.  The use period for the crisis exemption commenced 5 February
2008.  This HED human health risk assessment is intended to cover the
crisis exemption, as well as a request for the same use under Section 18
for the remainder of the season. 

	There are currently established tolerances for residues of
pendimethalin in many agricultural commodities, ranging from 0.10 ppm
(in multiple crops) to 4.0 ppm (in alfalfa hay), as cited in 40CFR
§180.361.  In addition to the establishment of tolerances for
pendimethalin residues in Bermuda grass forage and hay pursuant to this
Section 18 petition, there was the possibility that tolerances would be
necessary in cattle meat and milk.  However, the results of a 29-day
cattle feeding study (MRID #46591234) showed that pendimethalin residues
were not detected in either milk or tissues from cows which received the
100-ppm dose level.  The highest pendimethalin residues from IR-4's
Texas field trials on Bermuda grass were about 13 ppm at PHIs of 30 ± 2
days (in both forage and hay).  Since the previously calculated
theoretical dietary burden (TDB) to beef and dairy cattle was roughly 5
ppm, summing this with the maximum residues from the Texas Bermuda grass
field trials results in a TDB of approximately 18 ppm.  This estimated
TDB (in light of the fact that residues at the proposed PHI of 40 days
should be substantially lower than those seen at 30 days) indicates that
there should be no likelihood of quantifiable pendimethalin residues
appearing in either milk or beef tissues arising from grazing and/or
feeding of treated bermuda grass and/or hay to livestock.  Therefore,
there is no need to establish tolerances for pendamethalin in livestock
commodities.  

	There are currently no Codex maximum residue limits (MRLs) for
pendimethalin.  Mexico has established MRLs (expressed as pendimethalin
per se) for several crops, but not on Bermuda grass.  No Canadian MRLs
have been established for pendimethalin.  

	Occupational handler risks (MOEs) from the proposed use are all above
30, and do not cause concern to HED.  Because dermal exposure to
post-application workers is not expected for pendimethalin, occupational
post-application risks were not assessed.  

	Residential exposures are possible from pendimethalin products used on
lawns.  Residential post-application exposures were estimated for adults
and children, and all result in risks that are not of concern to HED.  

	Risk estimates associated with chronic dietary (food plus drinking
water) exposure to pendimethalin are significantly below HED’s level
of concern (LOC).  When dietary exposures are aggregated with
residential exposures, the resulting estimates of risk are not of
concern, either.  

	Hazard Characterization and Assessment

	The database adequately characterizes pendimethalin as having low acute
oral, dermal and inhalation toxicity.  It is Toxicity Category IV for
acute dermal toxicity, acute inhalation toxicity, and primary dermal
irritation; Toxicity Category III for acute oral and primary eye
irritation; and it is not a dermal sensitizer.  

	The thyroid is a target organ for pendimethalin.  Thyroid toxicity in
chronic and subchronic rat and mouse studies was manifested as
alterations in thyroid hormones (decreased Total T4 and T3, increased
percent of free T4 and T3), increased thyroid weight, and microscopic
thyroid lesions (including increased thyroid follicular cell height,
follicular cell hyperplasia, and follicular cell adenomas).  

	The toxicology database for pendimethalin is complete with regard to
pre-natal developmental toxicity in rats and rabbits.  The data provided
no indication of increased susceptibility following pre- or post-natal
exposure in the two-generation reproduction study in rats.  

	For detailed information, please refer to D350493; Christine L.
Olinger; 31 March 2008.  

	A summary of the LOCs for risk assessment is listed in Table 1 (below),
while the toxicological doses and hazard endpoints selected are
summarized in Table 2 (below).  The acute toxicity profile and the
subchronic/chronic toxicity profile for pendimethalin are provided in
the appendices.  

Table 1	Summary of Levels of Concern (LOCs) for Risk Assessment.

Route of Exposure	Duration of Exposure

	Short-Term

(1-30 Days)	Intermediate-Term

(1-6 Months)	Long-Term

(>6 Months)

Residential Exposure

Dermal	300	300	300

Inhalation	300	300	300

Incidental Oral	300	300	NA*

Occupational Exposure

Dermal	30	30	30

Inhalation	30	30	30

Incidental Oral	30	30	NA

* NA = Not Applicable.  

	FQPA Safety Factor

	Hormonal changes (alterations in thyroid weights, and histopathologic
lesions) were observed in several studies following oral administration
of pendimethalin, and it is likely that these changes 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
has recommended that a developmental thyroid assay be conducted to
evaluate the impact of pendimethalin on thyroid hormones, structure,
and/or thyroid hormone homeostasis during development.  Furthermore, HED
has recommended that a 10X database uncertainty factor (UFDB) be
retained pending receipt of the study for non-occupational exposure
scenarios.  

	The standard 10X intraspecies uncertainty factor, and 3X interspecies
factor are applicable to pendimethalin risk assessments.  The
interspecies uncertainty factor of 10X was reduced to 3X due to the
greater sensitivity of adult rats to thyroid effects compared to adult
humans.  Because of toxicodynamic differences in adult thyroid function
that result in greater sensitivity of the adult rat to hypothyroidism
compared to adult humans, the 3X (3.16) toxicodynamic part of the 10X
can be removed leaving the 3X (3.16) portion for toxicokinetic
interspecies differences (Interim Guidance on Thyroid Disrupting
Pesticides, 1 November 2005).  Thus, the usual 100X uncertainty factor
for intra- and interspecies differences is reduced to 30X.  The 10X
database uncertainty factor (UFDB) was retained pending submission of
the developmental thyroid toxicity study.  Therefore, the level of
concern (target MOE) for occupational exposure is 30 and the level of
concern for residential exposure is 300.  

	The 10X FQPA Safety Factor has been reduced to 1X, because thyroid
effects serve as the basis for endpoint selection for pendimethalin risk
assessment, 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 on the developing thyroid.  

  SEQ CHAPTER \h \r 1 TABLE 2	Toxicological Doses and Endpoints for
Pendimethalin Human Health Risk Assessments.  

Exposure

Scenario	Point of Departure 	Dose Used in Risk Assessment, UF	FQPA SF
and Level of Concern for Risk Assessment	Study and Toxicological Effects

Dietary Exposure

Acute Dietary

(females 13-49)

(general US population)	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	UFH = 10X 

UFA = 3X 

UFDB = 10X 

Total UF = 300X	FQPA SF = 1X

cPAD = Chronic RfD

              FQPA SF

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	UFH = 10X 

UFA = 3X 

UFDB  = 10X 

Total UF = 300X

	FQPA SF = 1X

Residential LOC = 300

Occupational LOC = 30	(Same as for chronic dietary.)  

Dermal Exposure

Dermal 

Short-Term

(1-30 days)

Intermediate-Term

(1-6 months)

Long-Term

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

UFA = 3X 

UFDB  = 10X 

Dermal Absorption = 3%	FQPA SF = 10X

Residential LOC = 300

Occupational LOC = 30	(Same as for chronic dietary.)  

Inhalation Exposure

Inhalation 

Short-Term

(1-30 days)

Intermediate-Term

(1 - 6 months)

Long-Term

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

UFA = 3X 

UFDB  = 10X 

Inhalation Absorption = 100% (equivalent to oral toxicity)	FQPA SF = 10X

Residential LOC = 300

Occupational LOC = 30	(Same as for chronic dietary.)  

Cancer

Cancer (oral, dermal, inhalation)	Pendimethalin is considered to be a
possible human carcinogen; the chronic dietary assessment using the cPAD
is considered to be protective of cancer effects.  	2-year
chronic/carcinogenicity study in rats.  

Point of Departure (POD) = a data point or estimated point derived from
observed dose-response data, which is used 	to mark the beginning of
extrapolation to determine risk associated with lower environmentally
relevant 	human exposures.  

  SEQ CHAPTER \h \r 1 UF = Uncertainty Factor.  

UFA = extrapolation from animal to human (interspecies).  

UFH = potential variation in sensitivity among members of the human
population (intraspecies).  

UFDB = to account for the absence of key data (such as the lack of a
critical study).  

FQPA SF = FQPA Safety Factor.  

NOAEL = No Observed Adverse Effect Level.  

LOAEL = Lowest Observed Adverse Effect Level.  

PAD = Population Adjusted Dose (a = acute, c = chronic).  

RfD = Reference Dose.  

MOE = Margin Of Exposure.  

LOC = Level Of Concern.  

NA = Not Applicable.  

	Dietary Exposure and Risk from Food and Drinking Water

	For detailed information, please refer to the dietary exposure
assessment memorandum Pendimethalin:  Chronic Dietary (Food and Drinking
Water) Analysis and Risk Assessment to Support a Tolerance in/on
Crayfish (D350492; Christine L. Olinger; 31 March 2008).  

	No acute endpoint was identified for pendimethalin, so a quantitative
assessment of acute dietary risk was not conducted. 

	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 the proposed tolerance
in/on crayfish.  The chronic dietary exposure analysis was based on the
following assumptions:  

(1) tolerance-level residues of pendimethalin in/on all current 				raw
agricultural commodities (RACs) in CFR40 §180.361, 				updated 16
November 2007) and proposed RACs; 

(2) empirical processing factors obtained from processing studies; 

(3) a maximum theoretical concentration factor of 8.0 for 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).  

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 in NY, at the rate of 6.0 lb ai/A) was the
highest modeling result calculated for either surface or groundwater
sources of drinking water, and is therefore conservative.  

	These assumptions result in conservative estimates of dietary exposure
and risk.  In calculating dietary risk estimates, HED has compared the
cPAD to the estimated dietary exposure.  Typically, HED 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 HED’s LOC.  

	From the chronic dietary assessment, the most highly exposed population
subgroup is children 1-2 years old.  The chronic exposure estimate,
0.004582 mg/kg/day, corresponds to approximately 15% of the cPAD.  The
risk estimate for the general US population is below HED’s LOC, as the
exposure (0.001526 mg/kg/day) utilizes 5% of the cPAD.  A summary of the
chronic dietary (food and water) exposure and risk estimates may be
found in Table 3, below.  

	The HED Cancer Peer Review Committee classified pendimethalin as a
possible human carcinogen, based on thyroid follicular cell adenomas in
rats.  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 3	Summary of Chronic Dietary Exposure and Risk Estimates for
Pendimethalin.  

Population Subgroup*

[Years of Age]	DEEM Chronic Dietary Analysis – Food and Drinking Water

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

General US Population	0.03	0.001526	5

All Infants [<1]	0.03	0.003037	10

Children [1-2]	0.03	0.004582	15

Children [3-5]	0.03	0.003724	12

Children [6-12]	0.03	0.002271	8

Youths [13-19]	0.03	0.001404	5

Adults [20-49]	0.03	0.001157	4

Adults [50+]	0.03	0.001053	4

Females [13-49]	0.03	0.001155	4

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

	Residential Exposure and Risk

	This residential exposure and risk assessment for pendimethalin is
based on the previous assessment (D325175; Margarita Collantes, Zaida
Figueroa; 2 April 2007).  In the previous assessment, dermal and oral
post-application exposures to residential turf were evaluated. 
Inhalation post-application was not assessed because there are no indoor
residential uses associated with pendimethalin products, and inhalation
exposure resulting from outdoor uses is expected to be negligible.  A
residential handler exposure assessment for applying pendimethalin to
residential turf was not performed because all turf labels appear to be
for commercial use only.  The dermal assessment performed in the
previous work included two scenarios:  

(1) children’s short-term dermal exposure to residential turf; and 

(2) adult’s short-term dermal exposure to residential turf.  

The oral assessment included three scenarios:  

(1) children's oral exposure from hand-to-mouth ingestion; 

(2) children's oral exposure from object-to-mouth; and 

(3) children's oral exposure from soil ingestion.  

Results of the previous assessment are summarized below.  

Dermal post-application exposure and risk:  The LOC for non-occupational
dermal exposure is an MOE of less than 300.  Using the turf transferable
residues (TTR) data for the Pendulum WDG formulation, children’s
short-term dermal MOEs (calculated with the use rate on Bermuda grass of
3.0 lb ai/A) ranged from 440 to 910 (see Table 4, below).  For adults,
short-term dermal MOEs ranged from 740 to 1500 (see Table 5, below). 
All dermal short-term MOEs are greater than 300, and therefore do not
exceed HED’s LOC.  

Table 4	Children’s Short-Term Dermal Post-Application Exposure to
Pendimethalin.

State	TTR 1 (µg/cm2)	(mg/µg)	TC 2 (cm2/hr)	ET 3 (hrs)	Dermal
Absorption 	BW 4 (kg)	Daily Dose 5 (mg/kg/day)	NOAEL (mg/kg/day)	MOE 6

CA	1.1	0.001	5200	2	0.03	15	0.0228	10	440

PA	0.756

0.0157

640

FL	0.538

0.011

910

1. TTR = Turf Transferable Residues, based on Pendulum WDG TTR study
(MRID #44969901).  

2. TC = Transfer Coefficient, based on HED Residential SOPs.  

3. ET = Exposure Time, based on HED Residential SOPs.  

4. BW = Body Weight.  

5. Dose = [TTR (ug/cm2) x 0.001 (mg/ug) x TC (cm2/hr) x ET (hrs/day) x
dermal absorption] ÷ BW.  

6. Dermal MOE = [Short-term NOAEL (10 mg/kg/day)] ÷ Daily Dose.  

Table 5	Adult’s Short-Term Dermal Post-Application Exposure to
Pendimethalin.

State	TTR 1 (µg/cm2)	

(mg/µg)	TC 2 (cm2/hr)	ET 3 (hrs)	Dermal Absorption	BW 4 (kg)	Dose 5
(mg/kg/day)	NOAEL (mg/kg/day)	MOE 6

CA	1.1	0.001	14500	2	0.03	70	0.0136	10	740

PA	0.756

0.009

1100

FL	0.538

0.00668

1500

1. TTR = Turf Transferable Residues, based on Pendulum WDG TTR study
(MRID #44969901).  

2. TC = Transfer Coefficient, based on HED Residential SOPs.  

3. ET = Exposure Time, based on HED Residential SOPs.  

4. BW = Body Weight.  

5. Dose = [TTR (ug/cm2) x 0.001 (mg/ug) x TC (cm2/hr) x ET (hrs/day) x
dermal absorption] ÷ BW.  

6. Dermal MOE = [Short-term NOAEL (10 mg/kg/day)] ÷ Daily Dose.  

	Oral post-application exposure and risk:  The LOC for non-occupational
oral exposure is an MOE of less than 300.  All oral MOEs (hand-to-mouth,
object-to-mouth, and soil ingestion) were greater than 300, and
therefore are not of concern to HED.  The MOEs calculated for
hand-to-mouth exposures using the rate of 2.0 lb ai/A resulted in an MOE
of 7,700.  The MOEs for object-to-mouth and soil ingestion exposure were
130,000 and 100,000 respectively.  MOEs calculated for hand-to-mouth
exposures using the rate of 3.0 lb ai/A resulted in an MOE of 5,300. 
The MOEs for object-to-mouth and soil ingestion exposure were 85,000 and
67,000 respectively.  Calculations and MOEs are summarized in Table 6,
below.  

	Ingestion of pendimethalin granules is also a potential source of
exposure because children can eat them if they are found in treated
lawns or gardens.  This scenario is considered an episodic scenario by
the Agency (acute oral endpoints would be used to estimate the risk).  A
risk assessment for this exposure scenario for children was not
conducted since an acute oral toxicological endpoint of concern was not
identified for this pesticide.  

	Aggregate residential exposure:  An aggregate exposure estimate for
adults (consisting of dermal exposure only) resulted in a total MOE of
740 (see Table 7, below), which is greater than the LOC of 300, and
therefore not of concern to HED.  The adult total MOE of 740 was based
on using the TTR from the California test site, and a 3% dermal
absorption factor.  Since the California test site resulted in the
lowest dermal MOE, it was determined to represent the worst case
scenario.  In assessing the aggregate residential exposure for children,
HED also used the California TTR data, hand press data, and a 3% dermal
absorption factor for determining dermal exposure to children.  This
resulted in a total MOE (dermal + oral) of 410 for an application rate
of 2 lb ai/acre, or 400 for an application rate of 3 lb ai/acre (see
Table 7), which is greater than 300, and therefore not of concern.  



Table 6	Oral Post-Application Exposure to Pendimethalin.

Rate

(lb ai/A)	SR 1	TTR 2 (µg/cm2)	Grt 2 (µg/cm2)	Srt 2 (µg/g)	(mg/µg) or
(g/ug)	SA (cm2/event)	IgR (cm2/day) or (mg/day)	FQ (events/

hr)	SEF	ET (hrs)	BW (kg)	Dose b (mg/kg/day) 	MOE

Hand-to-Mouth 3

2.0	22.4	0.049 a	NA*	NA	1E-3	20	NA	20	0.5	2	15	0.0013	7,700

3.0	33.6	0.74 a

0.0019	5,300

Object-to-Mouth 4

2.0	NA	NA	0.0471 a	NA	1E-3	NA	25	NA	NA	NA	15	0.0000785	130,000

3.0

	0.07 a

	0.0001178	85,000

Soil Ingestion 5

2.0	NA	NA	NA	15 a	1E-6	NA	100	NA	NA	NA	15	0.0001	100,000

3.0

22.5 a

0.00015	67,000

Total Oral Dose 6 and MOE 7

2.0

0.001479	6,800

3.0

0.00217	4,600

1. SR = Surface Residue = 2 (3) lb ai/A x 11.2 = 22.4 (33.6).  

2. TTR, Grt and Srt values are cited from ORE memo for pendimethalin
(D270528; Steven Weiss; 16 August 2001).  

3a. TTR = application rate (2 lb ai/A) x conversion factor (11.22
µg/cm2) x %transferability (0.0022) for gauze wipe.  

3b. Hand-to-mouth dose = [TTR t (ug/cm2) x SA (cm2/event) x SEF x FQ
(events/hr) x 1.0E-3 mg/ug x ET (hrs/day)] ÷ Body Weight (kg).  

4a. GRt = application rate (2 lb ai/A) x (11.22 µg/cm2) x
%transferability (0.0021) aerosol OT solution sample.  

4b. Object-to-mouth dose = [GR t (ug/cm2) x IgR (cm2/day) x 1.0E-3
mg/ug] ÷ Body Weight (kg).  

5a. Srt = application rate (2 lb ai/A) x (11.22 µg/cm2) x
%transferability (1.0) x 0.67 cm2/g soil.  

5b. Soil ingestion dose t = [SR t (ug/g) x IgR (100 mg/day) x CF1 (10-3
g/mg) x (10-3 mg/ug)] ÷ Body Weight (kg).  

6. Total dose = hand-to-mouth dose + object-to-mouth dose + soil
ingestion dose.  

7. Total oral MOE = 1/[(1/hand-to-mouth MOE) + (1/object-to-mouth MOE) +
(1/soil ingestion MOE)] = 

	[NOAEL (10 mg/kg/day)] ÷ [hand-to-mouth dose + object-to mouth dose +
soil ingestion dose].  

* NA = Not Applicable.  



Table 7	Aggregate Risk Resulting from Residential Exposure to
Pendimethalin.

Exposure Scenario	Population	TTR (ug/cm2) 1	Dermal Dose 2 (mg/kg/day)
Dermal MOE 3

	Inhalation MOE	Total Oral Dose4 (mg/kg/day)	Oral

MOE 5	Total Dose	Total MOE 6

Turf Grass	Adults	1.1 	0.0136 a	740 	NA 7	NA	NA	0.0136	740

	Children 

0.0228 b	440	NA	0.0015	6800	0.0243	410

0.0022	4600	0.025	400

1. TTR values are based on Pendulum WDG TTR study (MRID #44969901).  

2a. See Table 5.  

2b. See Table 4.  

3. Dermal MOE = average of dermal MOEs for adults and children
calculated from TTR data from CA, PA and FL (see Tables 4 and 5).  

4. Total oral dose = hand-to-mouth dose + object-to-mouth dose + soil
ingestion dose (see Table 6).  

5. Oral MOE = [NOAEL (10 mg/kg/day)] ÷ [hand-to-mouth dose + object-to
mouth dose + soil ingestion dose].  

6. Total MOE = 1/[(1/dermal MOE) + (1/oral MOE)] = [NOAEL (10
mg/kg/day)] ÷ [Dermal Dose + Total Oral Dose].  

7. NA = Not Applicable.  

	Occupational Exposure and Risk

	The proposed Section 18 emergency exemption requests the use of Prowl
H20 herbicide, which is a CS formulation (3.8 lb ai/gal), to control
sandbur species in Bermuda grass pastures and hay fields in Texas.  The
product will be applied (at a rate of 2.0 to 3.0 lb ai/A) by ground
equipment during winter dormancy, or in the spring prior to green-up. 
According to TDA, only one application per season will be made, and the
application shall not exceed 3.0 lb ai/A per crop season.  

	Handlers:  HED has determined that exposure to pesticide handlers is
likely during the occupational use of pendimethalin.  There are 2
handler scenarios that are expected to result in the highest exposure
for the proposed use:  

(1) Mixing/Loading Liquids for Ground Application; and 

(2) Applying Sprays Using Ground-Boom.  

The HED occupational LOC is an MOE of less than 30.  No MOEs for
handlers exceed the LOC at the single layer level (MOE for mixer/loader
= 33, and MOE for applicator = 2,600).  Single layer consists of
long-sleeve shirt and long pants (or coveralls), and no respirator. 
Because the MOE for mixers/loaders is so close to the LOC, an assessment
of risk for mixers/loaders with single layer plus gloves was conducted. 
For this scenario, the mixer/loader MOE was 1500.  A summary of the
exposures and risks for handlers is presented in Table 8, below.  

	The handler exposure estimates in this assessment are based on a
central tendency estimate of unit exposure, and an upper-percentile
assumption for the application rate, and are assumed to be
representative of high-end exposures.  The uncertainties associated with
this assessment stem from the use of surrogate exposure data
(differences in use scenario, and data confidence), and assumptions
regarding the amount of chemical handled.  The estimated exposures are
believed to be reasonable high-end estimates, based on observations from
field studies, and professional judgement.  

	Post-application:  The post-application exposure and risk assessment is
not required because the application is made direct to the soil (the
product must be applied using a low boom), and the application is made
during winter dormancy, or in the spring prior to green-up.  Dermal
exposure to post-application workers is not expected under these
conditions.  

	The technical material has a Toxicity Category IV for skin irritation
and acute dermal toxicity, and a Category III for eye irritation.  Per
the Worker Protection Standard (WPS), a 12-hour restricted entry
interval (REI) is required.  The 24-hour REI appearing on the label is
adequate.  



Table 8	Non-Cancer Occupational Risks for Pendimethalin Handlers.

Exposure Scenario	Mitigation Level 1	Dermal Unit Exposure 2 (mg/lb ai)
Inhalation Unit Exposure 3   (ug/lb ai)	Use Rate

(lb ai/A)	Acres Treated 4

(A/day)	Daily

Dermal

Dose 5 (mg/kg/day)	Daily

Inhalation

Dose 6 (mg/kg/day)	Combined Daily Dose 7 (mg/kg/day)	Total

MOE 8

Mixer/Loader

Mixing/Loading       Liquids for Ground Application	Single Layer

(No Gloves)	2.9	1.2	3	80	0.2983	0.0041	0.3024	33

	Single Layer

Plus Gloves	0.023	1.2	3	80	0.0024	0.0041	0.0065	1,500

Applicator

Applying Sprays Using

Ground-Boom	Single Layer

(No Gloves)	0.014	0.74	3	80	0.0014	0.0025	0.0039	2,600

1. Single layer = long-sleeve shirt + long pants or coveralls, and no
respirator.  

2. Dermal unit exposure represents long pants and long-sleeved shirt,
with either no gloves or plus gloves.  

3. Inhalation unit exposure represents no respiratory protection, open
mixing, loading, applying. 

4. Daily acres treated values are EPA estimates of area that could be
treated per day for each exposure scenario of concern (ExpoSAC Policy 9,
5 July 2000).  

5. Daily dermal dose (mg/kg/day) = [unit dermal exposure (mg/lb ai) x
application rate (lb ai/A) x DA (0.03) x daily acres treated] ÷ body
weight (70kg).  

6. Daily inhalation dose (mg/kg/day) = [unit exposure (µg/lb ai) x
(1mg/1000 µg) conversion x use rate (lb ai/A) x daily acres treated] ÷
body weight (70kg).  

7. Combined daily dose = daily dermal dose (mg/kg/day) + daily
inhalation dose (mg/kg/day).  

8. Total MOE = NOAEL (10 mg/kg/d) ÷ combined daily dose.  

	Residue Chemistry and Tolerance Assessment

	There are currently no Codex maximum residue limits (MRLs) for
pendimethalin.  Mexico has established MRLs (expressed as pendimethalin
per se) for several crops, but not on Bermuda grass.  No Canadian MRLs
have been established for pendimethalin.  

	Residue analytical methods:  Adequate methods are available for
tolerance enforcement.    SEQ CHAPTER \h \r 1 Methods I through IV in
the Pesticide Analytical Manual (PAM) Volume II are gas chromatography
with electron capture detection (GC/ECD) methods with LOQs of 0.05 ppm
each for the parent and its 3,5-dinitrobenzyl alcohol metabolite (both
of which are included in the tolerance expression).  Currently, all
pendimethalin tolerances for RACs are established at the combined LOQ of
0.1 ppm.  A confirmatory GC with mass spectrometry detection (GC/MS)
method has been submitted (with a petition on carrots), and has been
found adequate to determine residues of pendimethalin and its
3,5-dinitrobenzyl alcohol metabolite.  

	Crop field trials:  IR-4 has conducted field trials with pendamethalin
on Bermuda grass, and submitted summarized preliminary results in
support of TDA’s petition for a Section 18 registration.  Residues in
forage and hay were determined at 5 PHIs (30, 35, 40, 45, and 50 days). 
Because the proposed PHI is 40 days, only residue data from samples
harvested at this PHI were entered into the tolerance spreadsheet to
determine the recommended tolerances.  The spreadsheet results recommend
tolerances for pendimethalin residues of 25 ppm in Bermuda grass forage,
and 60 ppm in Bermuda grass hay.  

FIGURE 1	Bermuda Grass Forage

 

		y = 1.4151x - 0.2426				R2 = 0.9196

FIGURE 2	Bermuda Grass Forage

 

FIGURE 3	Bermuda Grass Hay

 

		y = 1.5465x + 0.4923				R2 = 0.9532

FIGURE 4	Bermuda Grass Hay

 

4.0	REFERENCES

Risk Assessment Memorandum

	Pendimethalin.  Human Health Risk Assessment for the Proposed Tolerance
in/on Crayfish.; D350493; Christine L. Olinger; 31 March 2008.  

Dietary Exposure Memorandum

	Pendimethalin:  Chronic Dietary (Food and Drinking Water) Analysis and
Risk Assessment to Support a Tolerance in/on Crayfish; D350492;
Christine L. Olinger; 31 March 2008.  

Occupational and Residential Exposure Memorandum

	Pendimethalin: REVISED Occupational and Residential Exposure Assessment
for Proposed Section 3 Registration for Use on Mint, Citrus Fruits, Tree
Nuts, and Carrots.; D325175; Margarita Collantes, Zaida Figueroa; 2
April 2007.  

AppendiX A:  Toxicology Assessment

Toxicity Profiles TC \l2 "A.2  Toxicity Profiles 

Table A.1	Acute Toxicity Profile for Pendimethalin.

Guideline Number	Study Type	MRID Number	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.	NA*

* NA = Not Applicable.  

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

Guideline Number	Study Type	MRID Number & 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 with 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 with the rabbit
developmental.	mg/kg/day = 

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

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

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).

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

Note: a range finding study indicated doses ≥125 mg/kg/day associated
with increased mortality.

870.3800	Reproduction and fertility effects [Rat]

(2-generation reproduction)	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 an 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 [Rat]

(3-generation reproduction)	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 [Dog] (2-year oral)	00058657	mg/kg/day =

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

LOAEL was not established. 

870.4200	Chronic toxicity/carcino-genicity [Rat]

(2-year oral)	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 and body weight gain,
decreased food consumption, increased gamma glutamyl transferase,
cholesterol and liver weights, and thyroid effects.

870.4200	Chronic toxicity  [Rat] (2-year oral)	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 [Mouse] (18-month oral)	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 [Bacterial strains of S.
typhimurium]	00153768	µg/plate = 50, 158, 500, 1581, 5000	Positive 

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

870.5100	Reverse gene mutation assay [Escherichia coli WP2]	43177801
µg/plate = 25, 50, 100, 250, 500, 750	Negative

870.5100	Reverse gene mutation assay [Escherichia coli WP2]	43135005	50,
158, 500, 1581, 5000 µg/plate or 1000 µg/paper disk/plate 	Negative

870.5100	Reverse gene mutation assay [Escherichia coli WP2]	43135006
µg/plate = 50, 100, 250, 500, 750	Negative

870.5300	Mammalian cell gene mutation [Chinese hamster ovary]	43177802
µg/plate = 1, 5, 7.5, 10, 20, 30, 40, 50 (-S9)

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

870.5375	Chromosomal aberration [Chinese hamster ovary]	00153770	Doses
ranging from 5-50 µg/ml	Negative

870.5395	Micronucleus study [Mouse]	42027801	mg/kg = 313, 625, 1250
Negative

870.5550	Alkaline elution assay [Rat]	43135007	mg/kg/bw = 1250, 2500,
5000	Negative

870.7485	Metabolism and pharmacokinetics [Rat]	00046275	NA*
Pendimethalin is eliminated from the body within 24 hours, with 70%
being excreted in feces (primarily the parent compound), and 20% in
urine.

* NA = Not Applicable.  

Note:  Some of the LOAELs/NOAELS 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:  Human Research REFERENCE



	



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 Exposure Database, Version 1.1 (Electronic Database); The PHED Task
Force, 1995; (Task Force members: Health Canada, US Environmental
Protection Agency, and the National Agricultural Chemicals Association);
released February, 1995.  

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