### Page 3 of 18

obse rved thyroid effects in the rat because of several important quantitative dynamic

differences between rats a nd humans with respect to thyroid function (Interim Guidance on Thyroid Disrupting Pesticides, dated 11/ 0 1/ 20 05). The Points of Departures (PoDs) and endpoints of concern used for dietary and non

- dietary (occupational and residential) risk assessments are presented in Table 1

. The PoDs, endpoints , UFs, and FQPA Safety

Factors will be re

- evaluated during the preparati on of the registration review risk

assessment.

Endocrine Disruption Screening Program As required by FIFRA and FFDCA, EPA reviews numerous studies to assess potential adverse outcomes from exposure to chemicals. Collectively, these studies include acute, subchronic and chronic toxicity, including assessments of carcinogenicity, neurotoxicity, developmental, reproductive, and general or systemic toxicity. These studies include endpoints which may be susceptible to endocrine influence, including effec ts on endocrine target organ histopathology, organ weights, estrus cyclicity, sexual maturation, fertility, pregnancy rates, reproductive loss, and sex ratios in offspring. For ecological hazard assessments, EPA evaluates acute tests and chronic studies t hat assess growth, developmental and reproductive effects in different taxonomic groups. As part of its reregistration decision, EPA reviewed these data and selected the most sensitive endpoints for relevant risk assessment scenarios from the existing haz ard database. However, as required by FFDCA section 408(p), pendimethalin is subject to the endocrine screening part of the Endocrine Disruptor Screening Program (EDSP).

EPA has developed EDSP to determine whether certain substances (including pesticide active and other ingredients) may have an effect in humans or wildlife similar to an effect produced by a “naturally occurring estrogen, or other such endocrine effects as the Administrator may designate.” The EDSP employs a two

- tiered approach to making the statutorily required determinations. Tier 1 consists of a battery of 11 screening assays to identify the potential of a chemical substance to interact with the estrogen, androgen, or thyroid (E, A, or T) hormonal systems. Chemicals that go through T ier 1 screening and are found to have the potential to interact with E, A, or T hormonal systems will proceed to the next stage of the EDSP where EPA will determine which, if any, of the Tier 2 tests are necessary based on the available data. Tier 2 testi ng is designed to identify any adverse endocrine related effects caused by the substance, and establish a dose

- response relationship between the dose and the E, A, or T effect.

Under FFDCA section 408(p), the Agency must screen all pesticide chemicals. Be tween October 2009 and February 2010, EPA issued test orders/data call

- ins for the first group of 67 chemicals, which contains 58 pesticide active ingredients and 9 inert ingredients.

Pendimethalin is not among the group of 58 pesticide active ingredients on the initial list to be screened under the EDSP. Accordingly, as part of registration review, EPA will

issue future EDSP orders/data call

- ins, requiring the submission of EDSP screening assays for nitrapyrin. For further information on the status of t he EDSP, the policies and procedures, the list of 67 chemicals, future lists, the test guidelines and the Tier 1 screening battery, please visit our website: http://www.epa.gov/endo/

.

Residue Chemistry

### Page 4 of 18

The existing residue chemistry database for pendimethalin is adequate for risk assessment purposes. No additional data are required during the registration review process. The qualitative nature of the residue(s) of pendimethalin in plants and animals ha s been adequately identified/characterized and is understood. The residues of concern in plants

and animals for tolerance enforcement and risk assessment are pendimethalin and its 3,5

- dinitrobenzyl alcohol metabolite

.

Dietary Exposure and Risk Assessmen t

The pendimethalin dietary exposure database is adequate to support the existing registrations

. For the 2012 risk assessment, screening level acute and chronic dietary analyses were performed for pendimethalin using DEEM

- FCID and assuming 100% crop treated. The results of aggregate dietary (food + drinking water) analysis show that the

acute and chronic dietary risk for the general U.S. population and all population subgroups are below HED’s level of concern (<100% acute Population Adjusted Dos e (aPAD) and chronic Population Adjusted Dose (c PAD ) ) at the 95 th 

### percentile of the exposure distribution.

Residential Exposure and Risk Assessment

P endimethalin is currently registered for use on lawns, and landscape ornamentals and

for weed control on n on

- cropland areas by commercial applicators and homeowners

. Residen tial handler and post

- application exposures were assessed for the 2012 risk assessment to reflect changes to the Standard Operating Procedures, body weight parameters, and toxicological inf ormation

. Updated residential handler and post

application risk estimates do not exceed HED’s level of concern (MOEs ≥ 30).

Aggregate Exposure and Risk Assessment The acute aggregate risk estimates associated with exposure to pendimethalin are equivalent to the acute dietary risk estimates. The acute dietary risk estimates from the

2012 risk assessment do not exceed HED’s level of concern.

The short

- term aggregate risk assessment was conducted for pendimethalin. The short

term aggregate ( residential exposu r e was combined with background food and water exposure) risk estimates from the 2012 risk assessment do not exceed HED’s level of

concern (MOEs ≥ 30)

.

Chronic exposure is not expected for the residential exposure pathway. Therefore, the

chronic aggregate risk would be equivalent to the chronic dietary exposure estimate. The

chronic d ietary risk estimates from the 2012 risk assessment do not exceed HED’s level

of concern.

Occupational Exposure and Risk Assessment HED updated the occupational exposure assessment for the 2012 pendimethalin Section 3 for leaf lettuce, leafy brassica greens, melons, edamame, kiwi and other small fruit vines risk assessment to reflect current use information and policies. In addition to assessing risk estimates for the proposed uses, the 2012 risk assessment document also assessed all currently registered occupational uses for pendimethalin. The results of the occupational handler exposure assessment indicate that there are potential risk estimates of concern for three uses of pendimethalin. Risk estimates for the alfalfa, sugarcane, and the turf and

### Page 5 of 18

ornamental scenarios do not exceed HED’s level of concern (MOE ≥ 30) with gloves and/or respirators. However, for the dry bulk fertilizer use, no additional PPE can be assumed because the commercial impregnation takes into account a closed system.

I n accordance with the updated Part 158 data requirements (2007), one or more DFR studies are required when a pesticide has residen tial or occupational uses that could result in post

- application dermal exposure. As part of the recent revision to the Health Effects Division’s 2012 Standard Operating Procedures for Residential Pesticide Exposure

Assessment , HED analyzed a number of DFR studies and selected a new default value for the fraction of the application rate available to be dislodged after a foliar application (F AR 

### ). This default value is 25%. Of the analyzed DFR studies, the maximum F AR 

### value seen was 89% or 3.6 times higher than the default residue transfer value. Therefore, a calculated MOE of approximately 4 times higher than the LOC (i.e., an MOE > 120 for pendimethalin since the LOC = 30) using the default dislodged residue value would provide an adequate margin of safet y for any potentially higher residues seen in a

chemical

- specific DFR study.

P ost

- application worker risk estimates for all proposed and existing foliar uses were

asses sed in the 2012 risk assessment

. The existing DFR study (MRID 44969902) does

not rep resent foliar applications of pendimethalin and was, therefore, not used to calculate the post

- application risk estimates for foliar applications. Post

- application risk

estimates using the default F AR 

### value of 25% did not exceed HED’s level of concern (MO Es ≥ 30) however post

- application MOEs for alfalfa and ornamentals (handset irrigation activity) and green onions and onions (hand weeding activity) are less than 120

. 

### As a result, a DFR study is required for pendimethalin at this time. This approach is

documented in an HED HASPOC document entitled Guidance for Requiring/Waiving Turf Transferrable Residue (TTR) and Dislodgeable Foliar Residue (DFR) Studies (dated 6/7/12).

Human Studies

The 2012 pendimethalin r isk assessment rel ies in part on data from studies in which adult human subjects were intentionally exposed to a pesticide or other chemical. Studies such as the Pesticide Handlers Exposure Data base and the Agricultural Handler Exposure Task
Force, have been reviewed by the A gency and found on the basis of available evidence to have been neither fundamentally unethical nor significantly deficient relative to standards of ethical research conduct prevailing when they were conducted. There is no barrier in

EPA's "Protection of Human Subjects" R egulation to reliance on these studies.

P ublic Health and Pesticide Epidemiology Data An updat ed review of pendimethalin incident reports was rec ently prepared b y HED (S.

Recore , D 403507

, 0 7/10 /2012 ) . For this evaluation , the OPP Incident Data System (IDS) was consulted for pesticide incident data on the active ingredient pendimethalin

. Pendimethalin is i ncluded in the Agricultural Health Study (AHS) and therefore

information from the AHS on pendimethalin is included in the HED incident report.

The IDS includes reports of alleged human health incidents from various sources, including mandatory Federal Insecticide, Fungicide and Rodenticide Act (FIFRA) Section 6 (a) (2) reports from registrants, other federal and state he alth and environmental

### Page 6 of 18

agencies and individual consumers. IDS contain reports from across the U.S. and most incidents have all relevant product information recorded. Reports submitted to the IDS represent anecdotal reports or allegations only, unless oth erwise stated in the report. IDS records incidents resulting in higher severity outcomes in more detail, in a module called the Main IDS module. This system stores incident data for death, major and moderate incidents, and it includes more details about the location, date and nature of the incident.

In Aggregate IDS, from January 1, 2007 to February 22, 2012, there were 111 minor reported incidents involving pendimethalin . For the Main IDS, from January 1, 2007 to February 22, 2012, there were 24 incidents reported in the database. One incident w as classified as major severity. Upon further review this incident involved more than one product; however, the other products were not identified. In addition, there was one more incident reported that involved pendimethalin and other chemicals. Overall, there are few incidents involving pendimethalin reported to IDS.

The AHS is a high quality

, prospective epidemiology study evaluating the link between pesticide use and various health outcomes including cancer. The AHS includes private

and commercial pesticide applicators and their spouses

. The AHS includes information on use of 50 different pesticide active ingredients commonly used in agriculture

. T here are AHS findings relevant to a pendimet halin that were summarized in the incident

report.

Within the AHS, there are several published investigations relevant to the hazard and exposure characterization of pendimethalin. Studies have noted a potential link of pendimethalin exposure related to various cancers and myocardial infarction. Of t he

studies discussed in the incident report, the authors of Hou et al. (2006) reported no compelling evidence that pendimethalin use was related to all cancers combined, or with many specific anatomical canc er sites including prostate cancer and melanoma. Alavanja et al. (2004) authors reported a significantly reduced risk of lung cancer when comparing all AHS participants with the general populations of the respective study states, but

identified a 4

- fold s ignificantly increased risk of lung cancer among pendimethalin users. However, authors could not rule out a role of residual confounding by smoking in estimating the association, though, it is notable that this potential link with lung cancer

has now been observed in two studies within the AHS, at two points in time, using similar data to measure exposure and co

- variables including smoking. Authors also noted a significant association between users and pancreatic cancer, however, authors

note there was no a priori hypothesis for this association, and many statistical tests were performed and not adjusted in final analyses. Additionally, an AHS study observed an association between users and myocardial infarction. Given the small number of pendimethalin ex posed cases of MI, the correlated nature of many pesticides used by cohort members which is difficult to disentangle in statistical analyses only, and the lack

of an a priori hypothesis and no known or hypothesized mechanism of action, these results should be interpreted with caution.

Based on the low frequency and generally low severity of incident cases reported for pendimethalin , there does not appear to be a concern at this time tha t would warrant further investigation based upon acute poisoning incident data . The Agency will continue to monitor the incident information and if a concern is triggered, additional analysis will

### Page 7 of 18

be included in the risk assessment.

Tolerance Assessment a nd International Harmonization

Tolerances are established under 40 CFR §180. 440 for residues of pendimethalin

, including its metabolites and degradates, in or on a variety of commodities

. The Codex

Alimentarius Commission and Mexico have not established m aximum residue limits (MRLs) for pendimethalin. Included in Table 5 are the MRLs harmonized with Canada. Any pendimethalin tolerances reassessed during the registration review process will be considered for possible harmonization with international MRLs should they be

established. (see Table 5 )

The current tolerance expression as listed in the 40 CFR§180. 361 (a ) has been updated to reflect current HED policies and thus will not need to be revised during the reg istration review process.

Environmental J ustice Potential areas of environmental justice concerns, to the extent possible, were considered in this human health risk assessment, in accordance with U.S. Executive Order 12898, "Federal Actions to Address Environmental Justice in Minority Populations and Low

Income Populations," http://www.epa.gov/compliance/resources/policies/ej/exec_order_12898.pdf

. 

### The Office of Pesticide Programs (OPP) typically considers the h ighest potential exposures from the legal use of a pesticide when conducting human health risk assessments, including, but not limited to, people who obtain drinking water from sources near agricultural areas, the variability of diets within the U.S., and people who may be exposed when harvesting crops. Should these high exposures indicate potential risks of concern, OPP will further

refine the risk assessments to ensure that the risk estimates are based on the best available

information.

Cumulative Risk 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 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 stateme nts released by EPA’s Office of Pesticide Programs concerning common mechanism determinations and procedures for cumulating effects from substances found to have a common

mechanism on EPA’s website at http://www.epa.gov/pesticides/cumulative/

.

Data Requirements HED requires a Dislodgeable Foliar Residue study to be submitted to refine the post

application exposure risk estimates for foliar applications of pendimethalin. HED does

not anticipate that additional residue chemistry or toxicology data will be required for the pendimethalin registration review process

.

### Page 8 of 18

Barring submission of any data that would impact the outcome of the 2012 risk assessment, HED does not anticipate the nee d for any updates to the pendimethalin risk assessment during registration review.

### Page 9 of 18

Table 1 : Toxicological Doses and Endpoint s for Pendimethalin Human Health Risk

Assessment (D390457; July 2012)

Exposure/Scenario Point of Departure Uncertainty/FQPA

Safety Factors RfD, PAD, Level of Concern

for Risk Assessment Study and Toxicological

Effects Acute Dietary (Females 13

- 49) No appropriate endpoint was identified including developmental toxicity studies in rats and rabbits.

Acute Di etary ( General population including infants and

children ) NOAEL=100 mg/kg UF A = 10 X

UF H = 10 X FQPA SF = 1X

Total UF = 10 0X Acute RfD = 1

mg/kg/day

a PAD = Acute RfD FQPA SF

= 1 mg/kg/day Acute neurotoxicity study (MRID 48695601). The LOAEL=300 mg/kg

, based on reduced motor activity for

males and females on Day 0.

Chronic Dietary (all populations) NOAEL = 10 mg/kg/day UF A = 3 X

UF H = 10 X FQPA SF = 1X

Total UF = 30X Chronic RfD = 0.3 mg/kg/day

cPAD = Chronic RfD FQPA SF

= 0. 3 mg/kg/day 92

- Day thyroid function study in rats (MRID 42054601); 56

- day thyroid study in rats (MRID 43135001); 14

- day intra thyroid metabolism study in rats (MRID 43135003). LOAEL = 31 mg/kg/day based

on hormonal and histopathological changes in the thyroid. Incidental Oral Exposure

Oral

Short

- Term (1

- 30 days)

Intermediate

– Term (1

- 6 months) NOAEL = 10 mg/kg/day UF A = 3 X

UF H = 10 X FQPA SF = 1X

Total UF = 30X Residential LOC = 30 Occupational LOC = 30 The same as the chronic dietary.

Dermal Exposure

Dermal

Short

- Term (1

- 30 days)

Intermediate

– Term (1

- 6 months)

Long

– Term (>6 months) NOAEL = 10 mg/kg/day UF A = 3 X

UF H = 10 X FQPA SF = 1X

Total UF = 30X

Dermal Absorption =

3% Residential LOC = 30

Occupational LOC = 30 The same as the chronic dietary.

Inhalation Exposure

Inhalation

Short

- Term (1

- 30 days)

Intermediate

– Term (1

- 6 months)

Long

– Term (>6 months) NOAEL = 10 mg/kg/day UF A = 3 X

UF H = 10 X FQPA SF = 1X

Total UF = 30X

Inhalation Absorption = 100% Residential LOC = 30 Occupational LOC = 30 The same as the chronic dietary.

Cancer Cancer (oral, dermal, inhalation) 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. A non

- quantitative approach (i.e., non

- linear, RfD approach) was recommended by th e Cancer Peer Review Committee since mode of action studies are available

. UF = uncertainty factor, 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. UF A = extrapol ation from animal to human (inter species), UF H = potential variation in sensitivity among membe rs of the human population (intra

- species). UF DB = to account for the absence of key data (i.e., lack of a critical study).

### Page 10 of 18

TABLE 2: Subchronic, Chronic and Other Toxicity Profile for Pendimethalin. (D390457; July 2012)

Guideline

Number Study Type MRID Number

& Classification Dose Levels Results

870.3100 Subchronic oral

[Rat] (30

- day) 000106754

Supplementary 0, 800, 1600, 3200 ppm

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

based on increased liver weight.

870.3100 Subchronic oral

[Rat] (13

- week) 00156081 0, 100, 500, 5000 ppm

0, 10, 50, 500 m g/kg/day 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 0, 25, 50, 100, 500, 2500

ppm

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

LOAEL was not determined.

870.3100 Subchronic oral

[Rat] (13 week) 00059469

Supplementary 0, 2500 ppm

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

LOAEL was not determined.

870.3100 Subchronic oral

[Rat] (92

- day) 42054601 0, 100, 5000 ppm

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

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

870.3100 Subchronic oral

[Rat] (56

- day) 43135001 0, 500, 5000 ppm

0, 31, 292 mg/kg/day NOAEL was not determined. LOAEL = 31 mg/kg/day, based on thyroid effects.

870.3100 Subchronic oral

[Rat] (14

- day) 43135003 0, 100, 500 ppm

0, 10, 500 mg/kg/day NOAEL = 10 mg/kg/day. LOAEL = 500 mg/kg/day, based on thyroid effects.

870.3100 Subchronic oral

[Dog] (90

- day) 00026672

Supplementary 0, 62.5, 250, 1000

mg/kg/day 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 0, 500, 1000, 2000 ppm

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

LOAEL was not determined.

870.3200 21

- Day dermal

toxicity [Rat] 00026663 0, 250, 500, 1000 mg/kg/day NOAEL = 1000 mg/kg/day.

LOAEL was not determined.

870.3700a Prenatal

developmental toxicity [Rat] 00025752

Supplementary, but satisfactory

when considered 0, 125, 250, 500

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

### Page 11 of 18

TABLE 2: Subchronic, Chronic and Other Toxicity Profile for Pendimethalin. (D390457; July 2012)

Guideline

Number Study Type MRID Number

& Classification Dose Levels Results

with the rabbit developmental. Developmental NOAEL = 500 mg/kg/day (highest dose tested).

870.3700b Prenatal

developmental toxicity [Rabbit)] 00117444

Supplementary, upgradeable. 0, 15, 30, 60 mg/kg/day 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 Acceptable 0, 500, 2500, 5000 ppm

0, 34/43, 172/216, 346/436 mg/kg/day (M/F)

HED RED

0, 25, 125, 250 mg/kg/day

HIARC Document

Note: Doses were obtained

from an HED pendimethalin RED, and a

HIARC document (4/18/2000) which resulted

in different dose

calculations fo r 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).

LOAEL = 125

- 172/216 (M/F) mg/kg/day (25 00 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

Acceptable 0, 500, 5000 ppm

0, 25, 250 mg/kg/day Parental/Systemic

NOAEL = 25 mg/kg/day.

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.

870.4100b Chronic toxicity [Dog]

(2

- year oral) 00058657 0, 12.5, 50, 200 mg/kg/day NOAEL = 200 mg/kg/day.

LOAEL was not established.

### Page 12 of 18

TABLE 2: Subchronic, Chronic and Other Toxicity Profile for Pendimethalin. (D390457; July 2012)

Guideline

Number Study Type MRID Number

& Classification Dose Levels Results

870.4200 Chronic toxicity/

carcinogenicity [Rat]

(2

- year oral) 40174401

Acceptable 0, 100, 500, 5000 ppm

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

Acceptable 0, 1250, 2500, 3750, 5000

ppm

0, 51, 103, 154, 213 mg/kg/day 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

Acceptable 0, 100, 500, 5000 ppm

0, 12.3/15.6, 62.3/78.3, 622.1/806.9 mg/kg/day (M/F) 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 50, 158, 500, 1581, 5000 μg/plate 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 25, 50, 100, 250, 500, 750 μg/plate 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 50, 100, 250, 500, 750 μg/plate Negative

870.5300 Mammalian cell gene

mutation [Chinese hamster ovary] 43177802 1, 5, 7.5, 10, 20, 30, 40, 50 μg/plate (

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

870.5375 Chromosomal

aberration [Chinese hamster ovary] 00153770 Doses ranging from 5

- 50 μg/ml Negative

870.5395 Micronucleus study

[Mouse] 42027801 313, 625, 1250 mg/kg Negative

870.5550 Alkaline elution assay

[Rat] 43135007 1250, 2500, 5000 mg/kg Negative

870.6200 Acute neurotoxicity 48695601

Acceptable 0, 100, 300, or 1000 mg/kg NOAEL=100 mg/kg,

LOAEL= 300 mg/kg, based on reduced motor activity for males and females (↓19 and ↓51%,

### Page 13 of 18

TABLE 2: Subchronic, Chronic and Other Toxicity Profile for Pendimethalin. (D390457; July 2012)

Guideline

Number Study Type MRID Number

& Classification Dose Levels Results

respectively, on Day 0.

870.6200 Subchronic

neurotoxicity 42054601

Acceptable 0, 42.0/50.1, 126.5 / 151.9,

386.8/423.1 mg/kg bw/day [M/F] NOAEL= 386.8/423.1 mg/kg/day (HDT).

LOAEL not established.

870.7800 Immuotoxicity 48608901

Acceptable 0, 38, 72, 276 mg/kg/day NOAEL=276 mg/kg/day (HDT)

LOAEL not established.

870.7485 Metabolism and

pharmacokinetics
[Rat] 00046275

Acceptable NA* Pendimethalin is eliminated from the body within 24 hours, with 70% being excreted in feces (primarily the parent compound),

and 20% in urine.

Non

guideline Developmental

Thyroid Study 48695603

Acceptable 0, 31, 62 or 186 mg/kg /day

(GD 6

- PND 21) Developmental thyroid function, The thyroid function in fetuses or post partum day (PND 4) was not affected by the treatment of pendimethalin.

Parental thyroid function,

Decreased thyroxine (T4) levels were observed in pregnant dams

and PND 21 male and female pups at 31 mg/kg/day (LOAE L)

.

### Page 14 of 18 TABLE 3 : Toxicology Data Requirements for Pendimethalin.

Test Technical

Required Conducted

870.1100 Acute Oral Toxicity 870.1200 Acute Dermal Toxicity 870.1300 Acute Inhalation Toxicity 870.2400 Primary Eye Irritation

870.2500 Primary Dermal Irritation

870.2600 Dermal Sensitization yes

yes

yes

yes

yes

yes yes

yes

yes

yes

yes

yes

870.3100 Oral Subchronic (rodent) 870.3150 Oral Subchronic (non

- rodent)

870.3200 21/28

- Day Dermal

870.3250 90

- Day Dermal

870.3465 90

- Day Inhalation yes

yes

yes

no

no yes

yes

yes

no

no

870.3700a Developmental Toxicity (rodent) 870.3700b Developmental Toxicity (non

- rodent) 870.3800 Reproduction yes

yes

yes yes

yes

yes

870.4100a Chronic Toxicity (rodent)

870.4100b Chronic Toxicity (non

- rodent) 870.4200a Oncogenicity (rat) 870.4200b Oncogenicity (mouse) 870.4300 Chronic/Oncogenicity yes

yes

yes

yes

yes yes

yes

yes

yes

yes

870.5100 Mutagenicity

— Gene Mutation (bacterial) 870.5300 Mutagenicity

— Gene Mutation (mammalian) 870.5375 Mutagenicity

— Structural Chromosomal Aberrations 870.5395 Mutagenicity

— Other Genotoxic Effects 870.5500 Mutagenicity

— Other Genotoxic Effects yes

yes

yes

yes

yes yes

yes

yes

yes

yes

870.6100a Acute Delayed Neurotoxicity (hen)

870.6100b 90

- Day Neurotoxicity (hen) 870.6200a Acute Neurotoxicity Screening Battery (rat)

870.6200b 90

- Day Neurotoxicity Screening Battery (rat) 870.6300 Developmental Neurotoxicity no

no

yes

yes

no no

no

yes

yes

no

870.7485 General Metabolism

870.7600 Dermal Penetration 870.7800 Immunotoxicity yes

no

yes yes

yes

yes

### Page 15 of 18 Table 4 : Physicochemical Properties of Pendimethalin.

Parameter Value Reference

Melting point/range 54

- 58 °C (TGAI) Product Chemistry Chapter of Pendimethalin RED, DP# 221531, 12/8/1995, B. Cropp

- Kohlligian

pH 4.7 (TGAI) CB# 789, 06/13/1986, G. Makhijani

Density 1.461 g/cm 3 (at room temperature) DP#s 271502 and 317053,
07/12/2006, W. Drew

Water solubility of PAI 0.275 ppm at 25 °C CB# 789, 06/13/1986, G. Makhijani

Solvent solubility of TGAI Solvent g/100 mL at 25 oC

n

- Heptane 11.2

2

- Propanol 6.1

Acetone 161.0

Toluene 128.4 Methyl alcohol 5.5 Dimethyl sulfoxide 21.4 Methylene chloride 232.0 CB# 789, 06/13/1986, G. Makhijani

Vapor pressure 1.24 x 10 - 8 Pa at 20 °C DP#s 271502 and 317053, 07/12/2006, W. Drew

Dissociation constant, pK

a Too small to measure CB# 789, 06/13/1986, G. Makhijani

Octanol/water partition coefficient, Log(K OW ) 5.18 DP#s 271502 and 317053,
07/12/2006, W. Drew

UV/visible absorption

spectrum UV molecular extinction =

3.81 x 10 4 at 234 nm,

1.93 x 10 4 at 280 nm. DP#s 271502 and 317053,
07/12/2006, W. Drew

### Page 16 of 18

Table 5: Summary of US and International Tolerances and Maximum Residue Limits

Residue Definition :
US Canada Mexico 1 

### Codex

40 CFR 180.361:

Plant: pendimethalin, [ N

- (1

- ethylpropyl)

- 3,4

- dimethyl

- 2,6

- dinitrobenzenamine], and its metabolite, 4

- [(1

- ethylpropyl)amino]

- 2

- methyl

- 3,5

- dinitrobenzyl alcohol, calculated as the

stoichiometric equivalent of pendimethalin benzenamine, N

- (1

- ethylpropyl)

- 3,4

- dimethyl

2,6

- dinitro

- , including the

metabolite benzenemethanol, 4

- [(1

- ethylpropyl)amino]

- 2

- methyl

- 3,5

- dinitro

None



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

US Canada Mexico 1 

### Codex
Alfalfa, forage 3.5 Alfalfa, hay 4.0
Alfalfa, seed 0.10
Almond, hulls 0.4 Apple, wet pomace 0.20 Artichoke, globe 0.1 Asparagus 0.15

Beans 0.10 Beans, forage 0.10 Beans, hay 0.10

Brassica head and stem, subgroup 5

- A 0.1

Carrot 0.5
Citrus, oil 0.5 Corn, field, forage 0.1 Corn, field, grain 0.1 0.1 field corn
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, gin byproducts 3.0
Cotton, undelinted seed 0.1 Crayfish 0.05 Fruit, citrus, group 10 0.1 Fruit, pome, group 11 0.10 0.1 apples Fruit, stone, group 12 0.10 0.1 apricots, nectarines, peaches, sweet cherries, tart cherries

Garlic 0.1 Grape 0.1 Grass forage, fodder, and hay crop group 17, forage 20

Grass forage, fodder, and hay crop group 17, hay 13

Grass forage, fodder, and hay crop group 17, straw 4.0

Juneberry 0.10

Leek 0.20 Nut, tree, group 14 0.1

Olive 0.1
Onion, bulb 0.1 0.1 dry bulb onions Onion, green 0.20
Onion, welsh 0.20

### Page 17 of 18

Table 5: Summary of US and International Tolerances and Maximum Residue Limits

Residue Definition :
US Canada Mexico 1 

### Codex

Peanut 0.1 Peanut, hay 0.1 Peas (except field peas) 0.10 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 0.1 dry soybeans 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 Completed by: M. Negussie; 08/03/2012

(b) Section 18 emergency exemptions . Time

- limited tolerances specified in the following table are established for combined residues of the herbicide pendimethalin, [ N

- (1

- ethylpropyl)

- 3,4

- dimethyl

- 2,6

- dinitrobenzenamine], and its metabolite 4

- [(1

- ethylpropyl)amino]

- 2

- methyl

- 3,5

- dinitrobenzyl alcohol, in or on the specified agricultural commodities, resulting from use of the pesticide pursuant to FIFRA section 18

emergen cy exemptions. The tolerances expire and are revoked on the date specified in the table.

Commodity Parts per million Expiration/revocation date

Bermuda grass, forage 25 12/31/10

Bermuda grass, hay 60 12/31/10

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



### Table 6 : HED Memoranda Relevant to Registration Review

Author Barcode/TXR # Date Title

### Page 18 of 18 Table 6 : HED Memoranda Relevant to Registration Review

Author Barcode/TXR # Date Title

S. Shelat D 390457 0 7 / 25 / 2012 REVISED: Pendimethalin: Human Health Risk Assessment for Proposed Use on Leaf lettuce; Leafy brassica greens; Melons; Edamame; Kiwi and

other small fruit vines

S. Recore D 4 03507 0 7/10 /2012 Pendimethalin: Review of Human

Incidents