### Page 2 of 36

the die tary, drinking water, residential (handler and post

- application)

, and occupational (handler and post

- application) routes for trifluralin

.

The toxicity database for trifluralin is substantially complete. An immunotoxicity study is required for registratio n review under the new data requirements for pesticides (40 CFR § 158). Following data evaluation, HED will determine if this study will impact the toxicity endpoints

for trifluralin. As part of the registration review risk assessment process, the need f or the required neurotoxicity battery (acute and subchronic neurotoxicity studies) w as discussed by the Hazard and Science Policy Council (HASPOC) on March 15, 2012. The available data on trifluralin and other structurally related dinitroaniline s did not indicate a concern for neurotoxicity. The HASPOC concluded that based on a weight

- of

- evidence approach

, considering all the available hazard and exposure information for trifluralin, the acute and subchronic neurotoxicity studies are not needed at this ti me. The requirement for the immunotoxicity study remains outstanding.

T rifluralin exhibits low acute toxicity in rats via the oral, dermal, and inhalation routes of exposure. In the rabbit studies, trifluralin has an LD 50 

### value of 5000 mg/kg when applied dermally (Toxicity Category IV). It is a slight eye irritant, but not a skin irritant; however, it was found to be a dermal sensitizer in guinea pigs. The kidney is the principal target organ.
However, s ubchronic oral studies in the rat and dog show tha t the liver is a lso a target organ with increased liver weights and changes in clinical chemistry parameters. The Agency classified trifluralin as a Group C

- “possible” human carcinogen. The Q 1 * 

### of 5.79 X 10 - 3 

### (mg/kg/day) - 1 

### was updated to 2.96 x 10 - 3 

### (mg/k g/day) - 1 

### in 2004 based on the Fischer 344 Rat Dietary 3⁄4’s scaling factor (May 11, 2004, TXR No. 0052534)

.

Tri fluralin is among the group of 58 pesticide active ingredients on the initial list to be screened

under the Endocrine Disruptor Screening Progra m ( EDSP ). Once all required Tier 1 and Tier 2 data have been received and reviewed, the endpoints and safety factors used for risk assessment purposes will be examined and a new risk assessment performed if necessary. For further

information on the status of the 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/

.

The existing residue che mistry database for trifluralin is adequate for risk assessment purposes. The qualitative nature of the residue in plants and animals has been adequately identified

, cha racterized and is understood. No additional data are required at this time; however, there are

some data that have been submitted by the registrant as a result of data call

- in ( DCIs ) requests
for trifluralin which were outlined in the most recent residue chemistry chapter (R. Griffin, D296627, 03/04/04) that will be review ed during the reg istration review process. Additionally,

t he Agency has recently responded to comments received from the registrant regarding the use of trifluralin on rapeseed forage; processing studies on mint, grape, and plum; and ruminant

metabolism and ruminant feedi ng studies. Based on the reassessed tolerances for alfalfa forage and hay, a new dietary burden was determined

. Due to the relatively low dietary burden for dairy cattle for trifluralin, no tolerances on livestock commodities are needed at this time (S. P iper, D399348,02/29/12)

.

### Page 3 of 36

In the most recent acute, chronic and cancer dietary assessment s ( 08/10/1994) results did not

exceed HED’s level of concern. New acute, chronic and cancer dietary exposure and risk

assessments may be required during registratio n review, which incorporate current consumption information, updated residue values and percent crop treated information while directly incorporating drinking water values into the assessment.

The residential exposure database is adequate to support the registration review process for trifluralin. In the 2004 risk assessment, all of the non

- cancer residential handler and post

application risk estimates were below the Agency’s level of concern. An updated residential exposure assessment may be required under registration review based upon revisions to HED’s

Resident ial SOPs.

The occupational exposure database is in adequate to support the registration review process for

trifluralin due to lack of Dislodgeable Foliar Residue (DFR) studies

. The 1996 RED assessed the potential for exposure to mixers, loaders, applicators, or other handlers arising from usage of the liquid and granular formulation and concluded that the cancer risk estimates for occupational

handlers did not exceed 1x10 - 5 

### (mg/kg/day) - 1



### . Non

- cancer occupational handler risk estimates were not reported in the RED. Also, the 1996 RED qualitatively assessed the potential post

application exposure from re

- entering treated turf, treated ornamentals, and food/fiber crop sites.

The RED document suggested that the occupational post

- applications risk estimates were below the Agency’s level of concern

. Based on the 2011 BEAD memo, there are many use sites for

triflur al in that may have changed since the exposure and risk assessment to support the 19 96

RED. N e w occupational handler and post

- application assessment s may be necessary at the time of registration review to incorporate the most current registered uses, updated unit exposure data, and most current policies and guidelines for assessing occup ational exposure and risk estimates.

Introduction

HED evaluated the most recent human health risk assessment for trifluralin to determine if sufficient data are available, and if further updates are needed to support registration review.

The most rec ent human health risk assessment was performed in 2004 (R. Griffin, D296628) to support the Tolerance Reassessment Decision (TRED) document.

Trifluralin is a selective, pre

- emergence, dinitroaniline herbicide registered for the control of annual grasses a nd certain broadleaf weeds. Tolerances for residues of trifluralin (α,α, α

trifluoro

- 2,6

- dinitro

- N. N

- dipropyl

- p

- toluidine) in/ o n plant and processed commodities are currently expressed in terms of the residues of trifluralin

. T olerances are established for plant commodities under 40 CFR §180. 207 and tolerances range from 0.05 ppm to 2.0 ppm

. The current supported uses for t rifluralin are primarily for soybeans and cotton, but it is also registered for use on a variety of food and feed crops including: a lfalfa, asparagus, barley,

Brassica vegetables, bulb vegetables, celery, citrus fruits, corn (field), cotton, cucurbit vegetables, endive, flax, fruiting vegetables, grapes, hops, legume vegetables, peanuts, peppermint, root and tuber vegetables, rapeseed (canola), safflower, sorghum, spearmint, stone fruits, sugarcane, sunflower, tree nuts, and wheat. Tolerances for residues of trifluralin in /on

livestock commodities have not been established. The chemical structure and nomenclature of

### Page 4 of 36

trifluralin and it s metabolites and the physicochemical properties of technical grade trifluralin are presented in Tables 1 and 2

.

Hazard Identification/Toxicology

The toxicity database for triflural in is incomplete under the new 40 CFR Part 158 data requirements for con ventional pesticides, which require certain generic testing, including a n immunotoxicity study ( see Table 3 )

. Sub sequently, the Hazard and Science Policy Council (HASPOC) met on March 15, 2012 to discuss data requirements for the neurotoxicity battery (acu te and subchronic neurotoxicity studies) for the registration review risk assessment. The available data on trifluralin and other structurally related dinitroaniline s do not indicate a concern for neurotoxicity so the HASPOC concluded that these studies a re no longer required. The requirement for the immunotoxicity study remains outstanding.

As shown in Table 4 , t echnical trifluralin exhibits low acute toxicity in rats via the oral, dermal, and inhalation routes of exposure. In the rabbit studies, trifl uralin has an LD 50 

### value of 5000 mg/kg when applied dermally (Toxicity Category IV). It is a slight eye irritant, but not a skin irritant; however, it was found to be a dermal sensitizer in guinea pigs.

The toxicity profile for trifluralin is presented in Table 5 . Subchronic oral studies in the rat and dog show that the liver is a target organ with increased liver weights and changes in clinical chemistry parameters. However, the kidney is the principal target organ. These findings are

summarized in a peer review of trifluralin (April 11, 1986, TXR No. 0005578) and include the following observations: kidney and bladder tumors, decreased kidney weights, increased blood urea nitrogen ( BUN )

, increases in total protein, aspartate aminotransferase and lac tate dehydrogenase in the urine. Also, protein electrophoresis of urine samples showed α 1

- globulin

and α 2

- globulin, tubular hyaline casts in the kidneys, minimal cortical tubular epithelial regeneration observed microscopically, and increased incidence o f progressive glomerulonephritis. The Q 1 * 

### of 5.79 X 10 - 3 

### (mg/kg/day) - 1 

### was updated to 2.96 x 10 - 3


### (mg/kg/day) - 

### in 2004 based on the Fischer 344 Rat Dietary 3⁄4’s scaling factor (May 11, 2004, TXR No. 0052534) and is still based on the incidence of male rat thyroid follicular cell combined adenoma, papillary adenoma, cystadenoma, and carcinoma tumors. It has been classified as a Group C (“Possible” Human Carcinogen). Extensive testing showed, however, that trifluralin is neither mutagenic nor genotoxic, and does not inhibit the polymerization of

microtubules in mammalian cells.

Endocrine Disruption Screening Program

"As required by FIFRA and FFDCA, EPA reviews numerous studies to assess potential adverse outcomes from exposure to chemicals. Collectivel y, 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 i nfluence, including effects 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 te sts and

### Page 5 of 36

chronic studies that assess growth, developmental and reproductive effects in different taxonomic groups. As part of the re registration decision for tri fluralin , EPA reviewed these data and selected the most sensitive endpoints for relevant risk a ssessment scenarios from the existing hazard database. However, as required by FFDCA section 408(p), tri fluralin is subject to the endocrine screening part of the Endocrine Disruptor Screening Program (EDSP)."

EPA has developed the EDSP to determine wheth er 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 EDS P 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) hormon al systems. Chemicals that go through Tier 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 bas ed on the available data. Tier 2 testing 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 m ust screen all pesticide chemicals. Between 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. Trif lur alin was includ ed

on that list and has been issued an order to conduct the Tier 1 testing. Once all required Tier 1 and Tier 2 data have been received and reviewed, the endpoints and safety factors used for risk assessment purposes will be examined and a new risk assessment perfor med if necessary. For further information on the status of the 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/

.

Conclusion The toxicity database for tri fluralin is complete except for a n immunotoxicity stud y required under the 2007 revised 40CFR Part 158 Toxicology Data R equirements. The endpoints, points of departure, and the FQPA Saf ety Factor for tri fluralin will be re

- evaluated during registration

review based on the submission and review of th ese outstanding data as well as all of the currently available data.

Residue Chemistry

The existing residue chemistry database for triflur alin is adequate for risk assessment purposes.

No additional data are required at this time; however, there are some submitted data received as a

result of a D ata C all

- I n (DCIs) request for trifluralin which was outlined in the most recent

residue chemist ry chapter (R. Griffin, D296627, 03/04/04) that will be review ed during the registration review process

. The qualitative nature of the residues of trifluralin in plants and animals has been adequately identified

, characterized and is understood.

### Page 6 of 36

The HE D Metabolism Assessment Review Committee (MARC) has reviewed the trifluralin toxicology and metabolism data ( 03 / 09 /04) and recommends that the tolerance expression for plant and livestock should include parent only

. The MARC also recommended that for the

p urposes of risk assessment estimates should be based on residue estimates of trifluralin and

metabolites TR

- 2, TR

- 4, TR

- 5, TR

- 6, TR

- 7, TR

- 14, TR

- 15, TR

- 42 and TR

- 44 for livestock

commodities and parent only for plant commodities. The Agency has determined that tolerances

for trifluralin residues in eggs and poultry tissue are not required based on the results of the respective poultry metabolism and feeding studies (CFR §180.6(a)(3)).

The Agency has provided responses to comments received from the regist rant regarding requests for residue data on rapeseed forage; processing studies on mint, grape, and plum; and ruminant

metaboli sm and ruminant feeding studies (S. Piper, D399348,02/29/12). Based on the reassessed tolerances for alfalfa forage and hay, a n ew dietary burden is needed. The potential dietary exposure of livestock to trifluralin residues was calculated using the recent Agency guidance on calculating dietary exposure from “reasonably balanced” livestock diets

. To determine the need

for toleran ces for residues trifluralin in milk and tissues, the anticipated secondary residues in cattle matrices were estimated using transfer coefficient factors calculated from the maximum

residues of trifluralin observed at the dose level closest to the reasonab le dietary burdens in the ruminant metabolism study. Based on the transfer coefficients for livestock tissues and the relatively low dietary burden for dairy cattle of 2.6 ppm for trifluralin, no tolerances on livestock

commodities are needed at this time

.

MARC concluded that the confined rotational crop study is adequate and a plant back interval (PBI) of 100 days should be added to the labeling, as this shorter interval would lead to crop injury . Therefore, a PBI of 5 months should be added to EPA Reg . No 62719

- 97 in the directions for vegetable gardens, since no PBI appears on the label.

Conclusion

The database for trifluralin is considered adequate for risk assessment

. No new residue chemistry data requirements have been identified for trifluralin to support registration review ; however, there are some additional data for trifluralin that will be evaluated during the registration review process.

Dietary Exposure and Risks

A refined ( anticipated residues from field trials and percent crop treate d) dietary risk assessment was completed in 200 4 using DEEM

- FCIDTM ( S. Piper , D2 96628 , 0 8 / 1 0/0 4 ).

Acute An acute dietary endpoint was only identified for females 13

- 50 years of age. Estimated acute dietary risk for females age 13

- 50 associated with the use of trifluralin do not exceed the Agency’s level of concern. The acute dietary risk estimate for females 13

- 50 years of age is approximately < 1% of the acute population adjusted dose (aPAD) at the 9 9.9 th 

### percentile.

### Page 7 of 36

Chronic Chronic dietary risk estim ates associated with the use of trifluralin do not exceed the Agency’s level of concern for any population subgroup, including the most highly exposed subgroup

children 1

- 2 yrs . The chronic dietary risk for all population subgroups is <1% of the chronic

po pulation adjusted dose (cPAD)

.

Cancer

Cancer dietary risk esti mates for the general U.S. population is 1.64x 10 - 7 

### mg/kg/day for trifluralin which is below the Agency’s level of concern.

Drinking Water

A Tier II screening level drinking water assessment was conducted to support the tolerance reassessment eligibility decision for trifluralin. The recommended estimated drinking water concentrations (EDWCs) are based on the use parameters of soybean

. The estimates of 7.0 ppb for acute exposure, 0.4 ppb fo r chronic (cPAD) exposure, and 0.3 ppb for carcinogenic risk

estimates.

Conclusions The dietary exposure database is adequate to support the existing registration. However, it may be necessary for HED to conduct a new dietary exposure assessment for tr ifluralin including new and updated information and policies, which may include directly incorporating drinking water estimates into the dietary assessment. The revised assessment should include updated consumption information, any changes in the toxicolo gy endpoints, and utilize the latest version

of DEEM

- FCID.

Residential Exposure

Trifluralin is registered for a variety of non

- occupational use sites. Based on the BEAD Chemical Profile for Registration Memo (December 1, 2011), of the use sites for wh ich trifluralin is labeled, the following may result in residential exposure: ornamental lawns and turf, golf course turf, ornamental herbaceous and woody, turf farms, conservation reserve areas, fence rows, rights

- of

- way, pathways, pre

- paved areas, landsc ape plantings, septic drain fields, sidewalks, and tennis courts. The last Residential Exposure Assessment was completed in 2004 to support the Tolerance Reassessment Evaluation Decision (TRED) Document for Trifluralin (D296625, S. Recore, 5/6/2004).

R esidential Handlers

The 2004 Residential Exposure Assessment (D296625, S. Recore, 5/6/2004) assessed the following residential exposure scenarios:

o loading/applying granulars with a belly grinder, granulars with a push

- type spreader, granulars using a spo on, measuring scoop, shaker can, or via hand;

### Page 8 of 36 o mixing/loading/applying liquids with a hose

- end sprayer, liquids with low pressure handwand sprayer, liquids with backpack sprayer; and

o applying trifluralin impregnated fabric squares to soil.

The exposure s cenarios included the maximum application rates for both the non

- cancer and cancer assessments, with the exception of one use. The assessment used 3 lbs ai/acre as the typical rate for the cancer ornamentals assessment. The assessment assumed adult handl ers weighted 70 kg and represent a handler wearing typical residential clothing attire of short

sleeved shirt, short pants, socks, shoes, and no gloves. The amounts handled or treated were

based on the 2001 Standard Operating Procedure 12: Recommended Rev isions to the Standard Operating Procedures for Residential Exposure Assessment. The unit exposures were based on

data from the Pesticide Handlers Exposure Database (PHED) Version 1.1, two ORETF Handler

studies: Homeowner Push

- Type Spreader (OMA003) ; Home owner Hose

- end and Hand

- held Sprayer; and a proprietary study: Worker Exposure Study During Application of Regent 20GR

In Banana Plantation

, EPA MRID 452507

- 02 (Fipronil Study).

For residential handlers, the calculations of short

- term inhalation non

- canc er risk indicate that

the MOEs are greater than 100 for all residential handler scenarios (MOE range 61,000 to 70,000,000). The calculations of residential handler cancer risk indicate that all scenarios have a

cancer risk estimate of less than 1x10 - 6



### .

R esidential Post Application

The 2004 Residential Exposure Assessment (D296625, S. Recore, 5/6/2004) addressed the following post

- application exposure scenarios:

o dermal exposure from residue on lawns (adult and toddler), on golf course turf grass (adult and youth); on home gardens (adult and youth);

o hand

- to

- mouth transfer of residue on lawns (toddler);

o object

- to

- mouth transfer of residues on lawns (toddler);

o incidental ingestion of soil from pesticide treated residential areas (toddler); and

o incident al ingestion of granules from pesticide

- treated residential areas (toddler)

The exposure scenarios include the TTR value from a trifluralin

- specific turf transferable residue study (MRID 457456

- 01). The assessment assumed non

- cancer residential risks fo r both adults and children were based generally on maximum application rates and parameters specified in the

2001 Standard Operating Procedure 12: Recommended Revisions t o t he Standard Operating

Procedures f

or Residential Exposure Assessment. The transfe r coefficients were utilized from SOPs for residential exposure, draft SOPs for golfer exposure assessment, and the Agricultural Default Transfer Coefficient SOP. The cancer risk estimates were based on the assumption that adults may be exposed on day of application following both the permitted applications each year. Exposure durations, length, and frequency were assumed to be worst case.

### Page 9 of 36

The risk estimates indicated that the MOEs are greater than 100 for all post

- application scenarios (MOEs range: 11 0,000 to 680,000,000). The calculations of residential post

- application cancer

risk indicate that all scenarios have a cancer risk estimate of less than 1x10 - 6



### .

Conclusions

Currently registered residential uses appear to be similar to those previously a ssessed; however, the Standard Operating Procedures and related parameters for performing residential exposure and risk assessments have changed since the 2004 assessment. R evised residential handler and
post

- application assessments may be needed to incor porate the changes to the Standard Operating Procedures of Residential Pesticide Exposure Assessment (February 2012 or most current version), body weight parameter changes, and any toxicological information that may be updated at the time of registration r eview.

Spray Drift/Bystander Exposure Estimates Residential bystander inhalation exposures resulting from off

- site transport (e.g., spray drift or volatilization) may occur as a result of applications of trifluralin . The Agency is in the process of

eva luating these types of exposures and may, as appropriate, develop policies and procedures to identify the need for and, subsequently, the way to incorporate post

- application inhalation exposure into the Agency's risk assessments. The need for a bystander inhalation risk

assessment for trifluralin should be examined during registration review.

Aggregate Risk Assessment

The 2004 Residential Exposure Assessment (D296625, S. Recore, 5/6/2004) assessed the

combined cancer risk values for residential handler a nd residential post

- application exposures associated with turf applications. The combined handler plus post

- application cancer risk associated with applications to residential turf grass is 5.4 x10 - 7 

### . A new aggregate risk

assessment may be needed at the time of registration review to incorporate the most current dietary and drinking water uses with the updated residential exposure and risk estimates.

Conclusion Updated aggregate exposure and risk assessments may be required under registration review

bas ed on the need for directly incorporating drinking water into the dietary exposure estimates. Revised aggregate exposure and risk assessment may also be needed if toxicological endpoints change or other new data are received by the Agency which impact exp osure estimates.

Occupational Exposure

Based on the BEAD Chemical Profile for Registration memorandum (December 1, 2011), of the use sites for which trifluralin is labeled, many may result in occupational exposure. These use

sites include but are not limited to the following: a variety of agricultural vegetable, fruit, grain and fiber use sites, ornamental lawns and turf, golf course turf, ornamental herbaceous and woody, turf farms, conservation reserve areas, fence rows, rights

- of

- way, pathways, pre

- paved areas, landscape plantings, septic drain fields, sidewalks, and tennis courts. Application methods

### Page 10 of 36

include chemigation, and aerial as well as ground applications (banded, broadcast, spot,

broadcast and hand

- held granular, and soil incorporated). Th e last occupational exposure and risk assessment was completed as part of the 1996 Registration Eligibility Document (RED).

Occupational Handlers

The 1996 RED assessed the potential for exposure to mixers, loaders, applicators, or other handlers arising from usage of the liquid and granular formulations. The applications varied and include aerial, groundboom, granular spreader, as well as push

- type and handheld equipment. The last assessment assumed that handlers donned baseline clothing except for the granular row planter scenario and the mixer/loaders of liquid formulations. Additional PPE such as coveralls

and chemical

- resistant gloves were assessed. The row

- planter handlers were also assumed to have enclosed cabs. Based on use patterns and PPE ass umptions, the 1996 RED concluded that the cancer risk estimates for occupational handlers did not exceed 1x10 - 5 

### (mg/kg/day) - 1 

### . Non

cancer occupational handler risk estimates were not reported in the 1996 RED.

Based on the 2011 BEAD memo, use sites for t rifluralin may have changed since the exposure and risk assessment to support the 1996 RED. The most current use sites should be assessed as part of registration review. Additionally, r ecommended unit exposures for occupational handler assessments have g enerally been derived only from PHED. However, recently both the ORETF and AHETF have produced pesticide handler exposure monitoring data that the Agency is using in place of PHED ( http://www.epa.gov/pesticides/science/handler

- exposure

- data.html ). As more reliable data become available (such as that from the AHETF and ORETF), the Agency will continue to replace existing data. HED will incorporate new exposure monitoring data, as necessary, during Registration Review. A new occupational handler assessment may be necessary at the time of registration review to incorporate the most current registered uses, updated unit exposure data, and will reflect the most current policies and guidelines for assessing occupational exposure and risk estimates.

Occupational Post Application

The 1996 RED qualitatively assessed the potential post

- application exposure from re

- entering treated turf, treated ornamentals, and food/fiber crop sites. The 1996 RED document suggested that the occupational post

- applications would be no higher than the exposure to the occupational handlers. Therefore, the Agency did not anticipate that the exposure and risk estimates for the

post

- application scenarios wo uld exceed 1x10 - 5 

### (mg/kg/day) - 1



### .

Based on the 2011 BEAD memo, use sites may have changed since the 1996 RED document. The most current use sites should be assessed as part of reregistration review. Additionally, HED has recently updated the Agricultural Transfer Coefficient Policy 3 document to reflect the adoption of all Agricultural Reentry Exposure Task Force (ARTF) data. These data were reviewed in 2008 by the FIFRA SAP. As more reliable data become available the Agency will continue to replace exi sting data. A new occupational post

- application assessment may be necessary at the time of registration review to incorporate the most current registered uses, updated transfer coefficient data, and reflect the most current policies and guidelines for

ass essing occupational exposure and risk estimates.

### Page 11 of 36

Conclusions

The occupational exposure database is in adequate to support the registration review process for trifluralin due to lack of Dislodgeable Foliar Residue (DFR) studies. In accordance with the

u pdated Part 158 data requirements (2007), o ne or more DFR studies are required when a pesticide has residential or occupational uses that could result in post

- application dermal

exposure. Since trifluralin is registered for use at these sites, the se studi es are required. Updated

occu pational handler exposure assessments may be required under registration review based upon revisions to the Agency’s s cenario

- specific surrogate handler exposure data ( http://www.epa.gov/pesticides/science/handler

- exposure

- table.pdf ). An occupational post

application assessment will also be required under registration review to incorporate revisions to the transfer coefficient policy ( http://www.epa.gov/pesticides/science/exposac_policy3.pdf ) and inclusion of DFR studies submitted to support registration review for trifluralin

. Additionally

,

r evised assessments may be needed t o incorporate the changes to body weight parameter changes and any toxicological information that may be updated at the time of registration review.

Human Studies

Previous assessments relied in part on data from studies in which adult human subjects w ere intentionally exposed to a pesticide or other chemical. These data, which include studies from the Pesticide Handlers Exposure Database Version 1.1 (PHED 1.1), are subject to ethics review pursuant to 40 CFR 26, have received that review, and are comp liant with applicable ethics requirements. Future assessments will rely on the most current and updated data from a variety of sources. All future data used are subject to ethics review pursuant to 40 CFR 26. Descriptions of data sources as well as guid ance on their use can be found at http://www.epa.gov/pesticides/science/handler

- exposure

- data.html and http://www.epa.gov/pesticides/science/post

- app

- exposure

- data.html

.

Public Health and Pesticide Epidemiology Data

An updated review of trifluralin incident report was recently prepared by HED (S. Recore, D397847, 03/14/2012). For this evaluation, t he OPP Incident Data System (IDS)

indicated moderately high frequency of incidents involving trifluralin. Although most of these

incidents w ere of low severity, it appears exposures to trifluralin have the potential to result in high severity outcomes. Con sequently, based on the frequency of exposures and the potential for exposures to result in high severity outcomes, these incident data may warrant further analysis in the preliminary risk assessment phase of Registration Review.

With respect to the epid emiological research from the Agricultural Health Study, there are two notable preliminary reports from the Agricultural Health Study (AHS) relating to colon cancer and to myocardial infarction. The Agency will continue to monitor AHS research reports with respect to trifluralin. If a concern is triggered, additional analysis will be included in the risk

assessment

. F ollow

- up studies from the AHS and other sources will be evaluated (if available) at

the time of the risk assessment

.

### Page 12 of 36

Tolerance Assessment a nd International Harmonization

Tolerances are established under 40 CFR §180. 207 for residues of the herbicide and plant growth regulator tri fluralin in or on a variety of food and feed crops ( see Table 7 ). These tolerances are based on the residue analysi s of tri fluralin . There are currently no established or proposed Codex, Canadian, or Mexican maximum residue limits (MRLs) for tri fluralin

.

“Tolerances are established under 40 CFR §180. 207 for residues of the herbicide and plant growth regulator tri flu ralin , including its metabolites and degradates, in or on the commodities in

Table 7 . Compliance with the tolerance levels specified is to be determined by measuring only

trifluralin ( α
, α, α

- trifluoro

- 2,6

- dinitro

- N,N

- dipropyl

- p

- toluidine)

, in or on the commodity

. ”

Environmental Justice

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/p olicies/ej/exec_order_12898.pdf

. 

### The Office of Pesticide Programs (OPP) typically considers the highest 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 assessmen ts to ensure that the

risk estimates are based on the best available information.

Cumulative Risk Assessment

At this time, EPA does not have available data to determine whether tri fluralin has a common mechanism of toxicity with other substances. EPA has not made a common mechanism of toxicity finding as to tri fluralin or any other substances, and tri fluralin does not appear to produce a toxic metabolite produced by other substances, which have tolerances in the U.S. Therefore, EPA has not assumed that tr i fluralin has a common mechanism of toxicity with other

substances.

Data Requirements

HED does not anticipate that additional residue chemistry, toxicology, or occupational/ residential exposure data will be required for the registration review process o f tri fluralin with the exception of the following studies listed below:

Immunotoxicity Study (OPPTS guideline 870.7800) Dislodgeable Foliar Residue Studies (OPPTS guideline 875.2100)

### Page 13 of 36

Data Call

- In

The registrant submitted studies in response to a data call

- in ) requests for trifluralin which were outlined in the most recent residue chemistry chapter (R. Griffin, D296627, 03/04/04) that will be reviewed during the registration review process. These studies include a magnitude of residue studies on aspara gus, carrots, grapes and wheat (D240693), alfalfa (D231299), cotton gin by

product (D240093), and an analytical method (D273840).

### Page 14 of 36

Table 1 . Trifluralin Nomenclature

Chemical structure

Common name Trifluralin

Molecular Formula C 13 H 16 F 3 N 3 O 4
Molecular Weight 335.3

IUPAC name α,α,α

- trifluroro

- 2,6

- dinitro

- N,N

- dipropyl

- p

- toluidine

CAS name 2,6

- dinitro

- N,N

- dipropyl

- 4

- (trifluoromethyl)benzenamine

CAS # 1582

- 09

- 8

PC Code 036101



### Table 2. Physicochemical Properties of Trifluralin

Parameter Value Reference

Melting point/range 42

- 49 C Trifluralin Update dated 10/29/91

pH 5.9 ± 0.1 saturated aqueous solution D207577, 4/9/97, K. Dockter

Density or specific gravity (22 C) 1.36 g/mL D207577, 4/9/97, K. Dockter

Water solubility (25 C) <1 ppm D207577, 4/9/ 97, K. Dockter

Solvent solubility (25 C) readily soluble in organic solvents such as acetone, acetonitrile, chloroform, dichloromethane, ethyl acetate, and toluene at >100 g/100 mL, and in

hexane at 5

- 6.7 g/100 mL or

methanol at 3.3

- 4 g/100 mL D207577 , 4/9/97, K. Dockter

Vapor pressure (25 C) 6.1 x 10 - 3 Pa D207577, 4/9/97, K. Dockter

Dissociation constant (pK

a ) not required; does not dissociate D207577, 4/9/97, K. Dockter

Octanol/water partition coefficient (log K

ow ; 20 C) 4.83 D207577, 4/9 /97, K. Dockter

UV/vis absorption spectrum not available

### Page 15 of 36

Table 3 : Toxicology Data Requirements for Trifluralin

Test Technical

Required Satisfied

870.1100 Acute Oral Toxicity

................................ ...................... 870.1200 Acute Dermal Toxicity

................................ ................. 870.1300 Acute Inhalation Toxicity

................................ ............. 8 70.2400 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 (nonrodent)

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

870.3700 Developmental Toxicity (rodent)

................................ . 870.3700 Developmental Toxicity (nonrodent)

........................... 870.3800 Reproduction

................................ ................................ yes

yes

yes yes

yes

yes

870.4100 Chronic Toxicity (rodent)

................................ ............. 870 .4100 Chronic Toxicity (nonrodent)

................................ ....... 870.4200 Oncogenicity (rat)

................................ ......................... 870.4200 Oncogenicity (mouse)

................................ .................. 870.4300 Chronic/Oncogenicity (mouse)

................................ ..... 870.4500 Chronic/Oncogenicity (rat)

................................ ........... yes

yes

yes

yes

yes

yes yes

yes

yes

yes

yes

yes

870.5100 Mutagenicity

— Gene Mutation

- bacterial

.................... 870.5300 Mutagenicity

— Gene Mutation

- mammalian

............... yes

yes yes

yes

870.5375 Mutagenicity

— Structural Chromosomal Aberrations

.. 870.5385 Mutagenicity

— Structural Chromosomal Aberrations

.. 870.5395 Mutagenicity

— Other Genotoxic Effects

...................... 870.5550 Mut agenicity

— Other Genotoxic Effects

...................... yes

yes

yes

yes Yes

yes

yes

yes

870.6100 Acute Delayed Neurotox. (hen)

................................ .... 870.6100 90

- Day Neurotoxicity (hen)

................................ .......... 870.6200 Acute Neurotox. Screening Battery (rat)

...................... 870.6200 Chronic Neurotox. Screening Battery (rat)

................... 870.6300 Develop. Neuro

................................ ............................. yes

no

yes

yes

no y es

---

n o a

n o a

---

870.7485 General Metabolism

................................ ..................... 870.7600 Dermal Penetration

................................ ....................... 870.7800 Immunotoxicity yes

no

yes y es

---

no

a Based on the decisions of HASPOC, the requirement for the acute and subchronic neurotoxici ty battery has been waived ( D. Smegal

, 2012, TXR No. 0055275 ).

### Page 16 of 36

Table 4 : Acute Toxicity Studies for Trifluralin, Technical

Guideline

No. Study Type MRID No. Results Toxicity Category

870.1100 Acute Oral (Rat) 00157486 (1985)

Acceptable/Guideline LD50 > 5000 mg/kg

IV

870.1200 Acute Dermal (Rat) 00157482 (1985)

Acceptable/Guideline LD50 > 2000 mg/kg

III

870.1200 Acute Dermal (Rabbit) 00158820 (1985)

Acceptable/guideline LD50 > 2000 mg/kg

III

870.1200 Acute Dermal (Rabbit) 40822202 (1988)

Acceptable/guideline LD50 > 5000 mg/kg

IV

870.1300 Acute Inhalation (Rat) 00155261 (1982)

Acceptable/guideline LC50 > 4660 mg/m 3 , 4.66 mg/L

IV

870.2400 Primary Eye Irritation

(Rabbit) 00157483 (1985)

Accepta ble/Guideline Conjunctival redness at 24hr, cleared by 4 days

III

870.2500 Primary Skin Irritation 00157485 (1985)

Acceptable/Guideline Not an irritant

IV

870.2600 Dermal Sensitization 00157484 (1985)

Acceptable/Guideline Sensitizing a gent

N/A



### Table 5: Toxicity Profile for Trifluralin

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

/Doses Comments

870.3100

2

- Week R

- F Feeding

- Rats (male) 00157154 (1983)

0, 6500 ppm

range

- finding study for 00157156 (1985), 41038301 (1986)

Acceptable/Nonguideline NOAEL = not achieved LOAEL = 6500 ppm based on renal epith damage, urine triple phosphates crystals and urinary

sediment

870.3100

90

- Day Oral toxicity

- Rat 00151906 (1980)

0, 800, 2000, or 5000 ppm M: 0, 59, 154, an d 392 mg/kg/day NOAEL = 2000 ppm (154/168 mg/kg/day, M/F) LOAEL = 5000 (392/421 mg/kg/day, M/F) Based on minor decreases in overall body weight gains and food consumption in males and females,

### Page 17 of 36

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

/Doses Comments

F: 0, 69, 168, and 421 mg/kg/day

Acceptable/Guideline dec reased hemoglobin, alkaline phosphatase, and alanine aminotransferase in the males, and increased absolute and relative (to body) liver weights in males and females.

870.3200

21/28

- Day dermal toxicity

- rabbit 41993810 (1991)

0, 100, 500, or 1000 mg/kg /day,
[ formulation containing 35.8%

trifluralin and 2.6% XRD

- 498]

Acceptable/Guideline Systemic NOAEL =1000 mg/kg/day Systemic LOAEL = Not achieved

Dermal NOAEL = Not achieved Dermal LOAEL = 100 mg/kg/day, edema, and/or scaling and fissuring 100 mg/kg/ day

based skin irritation

870.3200

31

- Day dermal toxicity

rat 00153171 (1982)

0, 40, 200, or 1000 mg/kg/day

Acceptable/Guideline Systemic NOAEL = 1000 mg/kg/day (limit dose) Systemic LOAEL = not achieved

Dermal NOAEL = 40 mg/kg/day.

Dermal LOAEL = 200 mg/kg/day based on sub

epidermal inflammation and ulcerations.

870.3200

21/28

- Day dermal toxicity

- rat 00152888 (1985)

0, 1000 mg/kg/day (limit dose)

Acceptable/Guideline Systemic NOAEL = 1000 mg/kg/day. Systemic LOAEL = Not achieved

Dermal N OAEL= Not achieved Dermal LOAEL = 1000 mg/kg/day (limit dose) based on erythema, edema, and desquamination of the treated skin.

870.3465

30

- Day inhalation toxicity 40392312 (1987) reformat of 00151904 (1982)

0, 100, 301, 1006 mg/m 3
(6 hours/day 5 d ays/week for up to 30 days)

Acceptable/Nonguideline NOAEL = 301 mg/m 3
LOAEL = 1006 mg/m 3 based on increased bilirubin in females and incidences of dyspnea and

ruffled fur in males and females.

870.3700 [83

- 3(a)]

Developmental Toxicity Study

- Rat 00 151899 (1983), 00159620 (1986), 40392310 (1987)

0, 20, 100, 500 mg/kg/day Acceptable/Guideline Systemic Maternal NOAEL = 100 mg/kg/day Systemic Maternal LOAEL = 500 mg/kg/day based on mortality, clinical signs, decreased body weight gains, decreased fo od consumption, and increased liver and spleen weights, Developmental NOAEL =100 mg/kg/day. Developmental LOAEL = 500 mg/kg/day based on

reduced ossification of the vertebrae and ribs and thickened, wavy or bent ribs and increased incidences of resorptio ns

870.3700 [83

- 3(a)] 00152419 (1984) 0, 100, 225, 495, or 1000 Maternal NOAEL = 495 mg/kg/day Maternal LOAEL = 1000 mg/kg/day based

### Page 18 of 36

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

/Doses Comments

Developmental Toxicity Study

- Rat mg/kg/day Acceptable/Guideline decreased body weights and decreased food

consumpt ion.

Offspring NOAEL = 495 mg/kg/day Offspring LOAEL = 1000 mg/kg/day based on decreased fetal body weights.

Developmental NOAEL = 1000 mg/kg/day
Developmental LOAEL was not established



### .

870.3700 [83

- 3(b)]

Developmental Toxicity

- Rabbit 00152421 (1984)

0, 100, 225, 500 mg/kg/day

Acceptable/Guideline Maternal NOAEL = 100 mg/kg/day Maternal LOAEL = 225 mg/kg/day based on abortions, macroscopic changes in the liver and lungs, and decreased food consumption.

Developmental NOAEL = 100 mg/kg/day Developmental LOAEL = 225 mg/kg based on

abortions.

870.3800 [83

- 4]

2

- Gen Repro

- Rat 00151901 (1984) 00151902 (1984) Feed analysis 00151903 (1984) Path

0, 200, 650, 2000 ppm 0, 20, 32.5, 200 mg/kg/day (1 ppm = 0.5 mg/kg/day)

Acceptable/Guideline Parental NOAEL = 200 ppm (10 mg/kg/day). Parental LOAEL = 650 ppm (32.5 mg/kg/day) based on mortality due to acute renal failure and increased lesions of the renal proximal tubules in the F1 females; increased relative (to body) weights of the liver, kidne y (males), and testes in both generations.

Offspring NOAEL = 200 ppm (10 mg/kg/day) Offspring LOAEL = 650 ppm (32.5 mg/kg/day) based on decreased pup weights in both generations and increased relative to body liver weights in the F2b females

Repro NOAEL = 2000 ppm (100 mg/kg/day) Repro LOAEL = Not established.

### Page 19 of 36

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

/Doses Comments

870.3800 [83

- 4]

2

- Gen Repro

- Rat 40405007 (1987)

0, 50, 450, 4000 ppm M: 0, 3.9, 35, 295 mg/kg/day F: 0, 4.7, 42, 337 mg/kg/day

Acceptable/Guideline Parental NOAEL = 450 ppm [35/4 2 mg/kg/day M/F] Parental LOAEL = 4000 ppm [295/337 mg/kg/day M/F] based on decreased body weights, body weight gains, food consumption, and food efficiency in males and females of both generations; decreased ovary weights in both generations; colon

dis tension in the F1 males; and uterine atrophy in the females of both generations.

Offspring NOAEL = 450 ppm (35/42 mg/kg/day M/F] Offspring LOAEL = 4000 ppm [295/337mg/kg/day , M/F] based on decreased pup weight

in F1a litters

Repro NOAEL = 450 ppm (3 5/42 mg/kg/day) Repro LOAEL = 4000 ppm [295/337 mg/kg/day , M/F), based on decreased fetal, neonatal, and litter viability and decreased lactation index in the F1a pups; and decreased number of implantation sites, newborn pups, litter size, and pup weigh ts in both generations.

870.4100 [83

- 1(b)]

1

- Year Oral (capsule) Study

- Dog 00151908(1984), 00159618 (1985)

0, 30, 150, or 750 ppm 0.0, 0.8, 3.8, 18.8 mg/kg /day

Acceptable/guideline NOAEL =30 ppm (0.8 mg/kg/day LOAEL = 150 ppm (3.8 mg/kg/day) based on increased absolute liver weights in males

870.4100 [83

- 1(b)] 42447001 (1992) Systemic NOAEL = 2.4 mg/kg/day

### Page 20 of 36

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

/Doses Comments

1

- Year Oral (capsule) Study

- Dog 0, 0.75, 2.4, 40 mg/kg/day

Acceptable/Guideline Systemic LOAEL = 40 mg/kg/day, based on increased frequency of abnormal stool and pigment deposition in the kidney and liver in males and females, decreased body weights and body weight gains, and on decreased erythrocytes and hemoglobin and increased thrombocytes in males.

870.4300 [83

- 5(a)]

24

- Month Chronic Toxicity/ Carcinogenicity Study

- Rat 00162457 (1985), 00162458 (1985)

0, 200, 800, or 3200 ppm M: 0, 10, 40, and 169 mg/kg/day F: 0, 13, 53, and 219 mg/kg/day

Acceptable/guideline NOAEL = 800 ppm (40/53 mg/kg/day M/F). LOAEL = 3200 ppm (169 /219 mg/kg/day M/F) based on decreases in body weight and body weight gains.

At the doses tested, the carcinogenic potential of trifluralin was negative. Dosing was considered adequate based on differences in body weight and body weight gains

870 .4300 [83

- 2(a)]

24

- Month Carcinogenicity Study

- Mouse 00158935 (1986), 40392313 (1987)

0, 50, 200, or 800 ppm M: 0, 7.5, 29, and 118 mg/kg/day F: 0, 10.5, 41, and 165 mg/kg/day

Unacceptable/guideline Systemic NOAEL = 800 ppm (118/165 mg/kg/day i n males/females) Systemic LOAEL = Not achieved

At the doses tested, the carcinogenic potential of trifluralin was negative. Dosing was considered inadequate as a toxic effect was not observed, and the

limit dose was not tested

870.5100

Bacterial reve rse gene mutation assay MRID 00148345 (1984) Acceptable/Guideline Trifluralin was tested up to the limit of solubility (400 μg/plate

- S9; 800 μg/plate +S9). No cytotoxicity was observed in any strain at up to 800 (+S9) or 400 (

- S9) μg/plate. No tr eatment

- related increases in revertant colonies were observed at any dose in any strain (±S9). The positive controls induced the appropriate responses.

There was no evidence of induced mutant colonies over background

### Page 21 of 36

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

/Doses Comments

870.5100 Bacterial reverse gene

mu tation assay MRID 40334707 (1987) Acceptable/Guideline In a reverse gene mutation assay in bacteria (MRID 40334707), Salmonella typhimurium strains TA98, TA100, TA1535, TA1537, and TA1538 were exposed to trifluralin (96.8% a.i., Lot/Batch #: 335/336) in dimethyl sulfoxide (DMSO) at concentrations of 30, 100, 300, 1000, 3000, or 10,000 μg/plate in the presence and absence of mammalian metabolic activation (S9). The standard plate incorporation method was used.

Standard strain

- specific mutagens served as positive

controls.

Trifluralin was tested up to the limit of solubility (3000 μg/plate, +/

- S9). No cytotoxicity was observed in any strain at up to 3000 μg/plate (+/

- S9). No treatment

related increases in revertant colonies were observed at any dose in any strain (+/

- S9). The positive controls induced the appropriate responses. There was no

evidence of induced mutant colonies over background.

870.5100 Bacterial reverse gene mutation assay MRID 00153173 (1979)

Acceptable/Guideline In a revers e gene mutation assay in bacteria (MRID 00153173), Salmonella typhimurium strains TA98, TA100, TA1535, TA1537, and TA1538 were exposed to HOE 38474 (trifluralin; purity not reported; Lot/Batch #: OH AT204) in DMSO at concentrations of 0, 4, 20, 100, 500, 2 500, or 10,000 μg/plate (+/

- S9).

Standard strain

- specific positive controls were used.

HOE 38474 was tested up to the limit dose (10,000 μg/plate, +/

- S9). No treatment

- related increases in revertant colonies were observed at any dose in any strain (±S9) . The positive controls induced the appropriate responses. There was no evidence of induced mutant colonies over background

.

870.5250 Gene Mutation Assay

- Yeast MRID 00151898 ((1982) Acceptable/Guideline The test material was tested up to the l imit of solubility (1000 mg/L); however, no solubility data were provided. No treatment

- related increases in mutation frequency were observed at any dose with or without

S9

- activation. The positive controls induced the appropriate response . There was no concentration

related positive response of induced mutant colonies over background

.

### Page 22 of 36

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

/Doses Comments

870.5300

In vitro mammalian cell gene mutation assay MRID 00126661 Acceptable/Guideline In a mammalian cell gene mutation assay at the thymidine kinase (TK) locus, m ouse lymphoma L5178Y cells cultured in vitro were exposed to trifluralin (95.0% a.i.; Lot/Batch #: 00554AP2) in DMSO for 4 hours at 8 concentrations ranging from 0.5 to 20 μg/mL (individual doses not reported) both in the presence and absence of S9

- activat ion.

Trifluralin was tested up to cytotoxic concentrations (20 μg/mL, +/

- S9). No treatment

- related increases in mutation frequency were observed at any dose compared to controls. The positive controls induced the appropriate response. There was no con centration

related positive

response of induced mutant colonies over background.

870.5300

Mammalian Cell Forward Gene Mutation Assay MRID 40765601 (1988) Acceptable/Guideline In a mammalian cell gene mutation assay at the HGPRT locus (MRID 40765601) , Chinese hamster ovary (CHO) cells cultured in vitro were exposed to trifluralin (97.6% a.i.; Lot/Batch #: 39) in dimethyl sulfoxide for 4 hours at concentrations of 50, 100, 150, 200, 300, 400, or 500 μg/mL (Trial 1,

- S9); 50, 100, 200, 300, 500, 600, or 700 μg/mL (Trial 2,

- S9); 50, 100, 200, 250, 300, 400, or 500 μg/mL (Trial 1, +S9); and 50, 100, 200, 300, 400, 500, or 600 μg/mL (Trial 2, +S9).

Trifluralin was tested up to cytotoxic concentrations (>=200 μg/mL, +/

- S9) and the limit of solubility (>=10 0 μg/mL, +/

- S9). No treatment

- related increases in mutant frequency were observed in either trial in the presence or absence of S9. The positive controls induced the appropriate response. There was no

evidence of induced mutant colonies over background in the presence or absence of S9

- activation.

### Page 23 of 36

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

/Doses Comments

870.5300

Mammalian Cell Forward Gene Mutation Assay MRID 00148318 (1984) Acceptable/Guideline In a mammalian cell gene mutation assay at the HGPRT locus (MRID 00148318), Chinese hamster ovary ( CHO) cells cultured in vitro were exposed to triflurex technical (trifluralin; purity not reported; Lot/Batch #: not reported) in ethanol for 4 hours at concentrations of 10, 50, 100, 200, 300, 400, or 500 μg/mL (

- S9) and 50, 100, 200, 300, 400, 500, or 60 0 μg/mL (+S9).

Triflurex technical was tested up to cytotoxic concentrations (>=200 μg/mL,

- S9 and >=300 μg/mL, +S9) and the limit of solubility (>=100 μg/mL, +/

- S9).

No treatment

- related increases in mutant frequency

were observed in either trial in the presence or absence of S9. The positive controls induced the appropriate

response. There was no evidence of induced mutant colonies over background in the presence or absence

of S9

- activation.

870.5385

In Vivo Mammalian Cytogenetics [Bone Marrow/Sperm atogonial Aberration Test] MRID 40765603 (1988) Acceptable/Guideline In a bone marrow/spermatogonial chromosome aberration assay (MRID 40765603), ICR mice (10 males/dose, spermatogonial tissue; and 5/sex/dose, bone marrow) were dosed once daily via gav age (10 mL/kg) with trifluralin (97.6% a.i., Lot/Batch No 39) in corn oil at doses of 0, 62.5, 208, or 625 mg/kg for 5 consecutive days. Bone marrow and spermatogonial cells were

harvested at 4.5 hours after the last treatment.

Mortalities were observed in the 625 mg/kg females (2/5 treated vs. 1/5 controls), and at 62.5 mg/kg in the males (2/10 treated vs. 1/10 controls) and females (2/5

treated vs. 1/5 controls). Clinical signs of toxicity (lethargy, swollen neck, and yellow stains around the

mouth and perianal area) were also observed at >=62.5 mg/kg. No statistically significant increases in the percent of aberrant cells were observed at any dose in either sex in the bone marrow assay or in the males in the spermatogonial assay. Trifluralin was t ested at an adequate dose based on mortalities observed at >=62.5 mg/kg. The positive control induced the appropriate

response. There was no evidence of chromosome aberration induced over background

### Page 24 of 36

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

/Doses Comments

870.5385

In Vivo Mammalian Cytogenetics [Bone

Marrow Chromosome Aberration Test] MRID 00148320 Acceptable/Guideline In a bone marrow chromosome aberration assay (MRID 00148320), 5 Sprague

- Dawley (HSD:([SD] BR)

rats/sex/dose/sacrifice time were treated once via oral gavage with Triflurex technical (triflur alin; 97.3% a.i.; Batch #: 5320), in corn oil at doses of 0, 500, 1650, or 5000 mg/kg. Bone marrow cells were harvested at 6, 24, or 48 hours after treatment.

Mortality was observed at 1650 (3/15 males and 5/15 females) and 5000 (2/15 males and 1/15 fema les) mg/kg upon initial dosing; however, these animals were replaced and only one replacement 1650 mg/kg female in the 48 hour group died after

dosing. Triflurex technical induced minimal bone marrow toxicity (as indicated by decreased mitotic
index) at 500 mg/kg in males and 1650 mg/kg in females. Dosing was considered adequate based on bone marrow toxicity and that the animals were dosed above the limit dose (2000 mg/kg). No statistically significant increases in the percent of aberrant cells

were o bserved at any dose or sampling time compared to concurrent controls. The positive control induced the appropriate response. There was no evidence of chromosome aberration induced over background

.

870.5395

In vivo Mouse Erythrocyte Micronucleus

assay MRID 00151895 (1981) Acceptable/Guideline In a bone marrow micronucleus assay, 5 NMRI mice/sex/dose were treated via oral gavage with HOE 38474 (Trifluralin; 98.3% a.i., Lot/Batch #: OH AT208), in sesame oil at doses of 0, 25, 250, or 2500 mg/kg on two consecutive days (24 hours apart). Bone

marrow cells were harvested at 6 hours after the last

treatment.

No unscheduled deaths occurred during the study. No clinical signs of toxicity were observed. No statistically significant differences in the numb er of micronucleated polychromatic erythrocytes (MPCE) or normocytes and no decrease in polychromatic erythrocyte to normocyte (PCE:NCE) ratios were noted in the treated animals compared to controls; however, only individual data were provided. Additional ly, although no evidence of cytotoxicity (decreased PCE: NCE) was noted in the bone marrow, the animals were sufficiently dosed (the limit dose was given twice). The test material was

### Page 25 of 36

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

/Doses Comments

absorbed as indicated by the presence of orange urine in the 2500 mg/kg animals. The positive control induced the appropriate response. There was no significant increase in the frequency of micronucleated polychromatic erythrocytes in bone marrow compared to controls.

### Page 26 of 36

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

/Doses Comments

870.5450

Dominant Lethal

- Rat MRID 00148319 (198 4) Acceptable/Guideline In a dominant lethal assay (MRID 00148319), groups of 20 male Sprague

- Dawley (CD) rats/dose were treated once daily via gavage (1.0 mL/dose) with Triflurex technical (trifluralin; 97.3% a.i.; Batch #: 5320), in corn

oil for 5 cons ecutive days at doses of 0, 100, 333, or 1000 mg/kg/day (total doses of 0, 500, 1665, or 5000 mg/kg). Beginning two days after the last exposure, each male was mated sequentially to two untreated female rats per week for seven weeks. At 14 days after

the midpoint of each mating week, the females were killed, determined to be pregnant or not pregnant, and the number of corpora lutea, living, dead, and total implantations was determined. On the fifth day of dosing, the positive control males were given a s ingle dose of triethylenemelamine (TEM; 0.3 mg/kg, i.p. in 0.9% saline).

One 1000 mg/kg male (#8476) was found dead 72 hours

after the last treatment. Triflurex technical was tested at the limit dose (5000 mg/kg = 1000 mg/kg/day X 5 days). There were no treatment

- related effects on fertility, number of implants, pre

- implantation losses, number of dead implants, number of females with 1 or 2 dead implants, or ratio of dead implants to total implants at any dose in the study. The positive control

induce d the appropriate response. There was no time

related positive response of increased pre

- or post

implantation loss compared to controls.

### Page 27 of 36

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

/Doses Comments

870.5450

Dominant Lethal

- Mouse MRID 00151896 (1984) Acceptable/Guideline In a dominant lethal assay (MRID 00151896), 30 male NMRI mice were dosed once daily for 5 consecutive days via oral gavage (5 mL/kg) with HOE 38474 (trifluralin; 98.3% a.i.; Lot/Batch #: OHZD99002), in sesame oil at concentrations of 0, 10, 100, or 1000 mg/kg. After th e final treatment, each male was mated with 13 untreated females during separate 4

- day intervals over a 52 day period.

No treatment

- related mortalities were noted during the study. No treatment

- related effects on clinical signs, body weight, fertilizatio n rate, and pre

- or post

implantation loss were observed; however, no data were provided. The positive control

(cyclophosphamide) increased the number of post

implantation fetal losses . There was no time

- related positive response of increased pre

- or p ost

implantation loss compared to controls.

870.5550

Unscheduled DNA synthesis in mammalian

cell culture MRID 40765602 (1988) Acceptable/Guideline In an unscheduled DNA synthesis assay (MRID), primary rat hepatocyte cultures were exposed to

triflural in (97.6% a.i.; Lot/Batch #: 39) in DMSO for

18

- 19 hours at concentrations of 0, 0.032, 0.214, 0.404, 0.917, 2.22, 4.36, 8.52, 21.3, 42.9, 88.0, 448, or 898 μg/mL. Fifteen doses ranging from 0.032

- 898 μg/mL were used in each assay; however, the three dose s between 0.032 and 0.214 μg/mL were not reported.

Trifluralin was tested up to cytotoxic levels (determined by trypan blue exclusion), 88.0 μg/mL in rat #1 and 42.9 μg/mL in rat #2. There were no marked increases observed in the mean NNG or percent cell s in repair at any dose in either trial. The positive controls induced marked increases in mean NNG and the percent of cells in repair. There was no evidence that unscheduled DNA synthesis, as determined by radioactive tracer procedures (nuclear silver g rain counts), was

induced

.

### Page 28 of 36

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

/Doses Comments

870.5550

Unscheduled DNA synthesis in mammalian

cell culture MRID 00151894 (1982) Acceptable/Guideline In an unscheduled DNA synthesis assay (MRID 00151894), HeLa cell cultures were exposed to HOE 38474 (trifluralin, 98.3% a.i.; Lot/Batch #: OH AT 208) in DMSO for 1 hour at concentrations of 0, 50, 100 or 500 μg/mL both in the presence and absence of S9

- activation.

HOE 38474 was tested up to cytotoxic concentrations (>= 50 μg/mL, +/

- S9). No statistically significant

increa ses in mean counts per minute of the test material with hydroxyurea were noted compared to concurrent solvent controls at any dose level, either in the presence

or absence of S9

- activation. The positive controls induced the appropriate response. There wa s no evidence that unscheduled DNA synthesis, as determined by liquid scintillation counting procedures, was induced

.

870.5900

In vivo Sister Chromatid Exchange (SCE) Assay MRID 00133426 (1983) Acceptable/Guideline In a mammalian cell cytogenetics assay [SCE induction] using the BrdU tablet method , groups of 3 female Chinese hamsters/dose were exposed once via gavage (10 mL/kg) to trifluralin (95.0% a.i., Lot/batch No 00554AP2) in DMSO and 10% acacia at concentrations of 200, 300, 400, or 500 mg/kg at 5 hours following BrdU tablet implantation. Bone marrow was collected

at 21 hours after treatment.

Trifluralin was tested up to cytotoxic

concentrations (>=400 mg/kg). Cytotoxicity (as

indicated by an increase in the number of first division

metap hase figures) was observed in all animals at >=400 mg/kg. No statistically significant increases in SCE frequency were observed at any dose compared to controls. The positive control induced the appropriate

response. There was no evidence of SCE induced over background

870.7845 (85

- 1)

Metabolism

- Rat Urinary metabolites 41218901 (1989) Acceptable/Guideline There was no sex

- dependent effect on metabolic profiles. A minimum of 20

- 30 non

- conjugated

metabolites and an additional 10

- 20 conjugated

met abolites were present in the urine, but no parent compound was detected. Information on the percentage

of the administered dose excreted in the urine was not

### Page 29 of 36

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

/Doses Comments

provided. However, no single metabolite accounted for

more than 8

- 10% of the total urinary radio activity, and the majority of the metabolites were present at 1

- 2% of the total urinary radioactivity. Thus, almost all of the metabolites were minor (<5% of the total radioactive dose). Metabolite F1B was found at 8.2

- 8.9% of the total urinary radioacti vity in both sexes, and Metabolite F2, N

- [(3

- (acetylamino)

- 2

- amino

- 5

- (trifluoromethyl)phenyl] acetamide, was found at 4.0

- 5.2%. Metabolite F1B was partially characterized as retaining the trifluoromethyl groups, the two equivalent aromatic protons, and th e two nitro groups, but the propyl groups were lost. Ten other metabolites were identified (<0.1

- 3.7% of total urinary radioactivity, each compound in each sex). Two additional metabolites were partially characterized (0.1

- 2.6% of total urinary

radioacti vity, each compound in each sex).

Four metabolic pathways were identified as follows: (i)

oxidative N

- dealkylation of one or both propyl groups and metabolites which were hydroxylated on the propyl side chain; (ii) reduction of one or both nitro groups t o the corresponding amine; (iii) cyclization reactions to give a variety of substituted and unsubstituted benzimidazole metabolites; and (iv) conjugation reactions, including acetylation of the reduced nitro groups, sulfate, and glucuronic acid conjugates.

Special study

3

- Mo Feeding

- Rat with Urinalysis study 00157156 (1985), 40138301(1986) 41086101 (1989)

0, 50, 200, 800, 3200, and 6400

ppm 0, 2.6, 10.7, 42.2, 170.2, and 342.1 mg/kg/day

Acceptable/Nonguideline NOAEL = 200 ppm (10.7 mg/kg/day)

LOAEL for nephrotoxicity = 800 ppm (42.2 mg/kg/day), based on the presence of cortical tubular cytoplasmic hyaline droplets; increased total protein, AST, and LDH in the urine; and increased urinary volume upon protein electrophoresis and urinalysis.

### Page 30 of 36 Table 6 .1: Summary of Toxicological Points of Departure and Endpoints for Trifluralin for Used in Dietary and Non

dietary Human Health Risk Assessments

Exposure/

Scenario Point of

Departure Uncertainty

Factors Level of Concern for

Risk Assessment Study and T oxicological Effects

Acute Dietary (Females 13

- 50 years of age) NOAEL = 100

mg/kg/day UF A =10x

UF H =10x FQPA SF

=1 100 mg/kg/day NOAEL

100 (UF)

aRfD = 1.0 mg/kg/day Developmental Toxicity Study

– Rat LOAEL = 500 mg/kg/day, based

on increased total litter resorptions Acute Dietary

(General population, including infants and children) No endpoints identified from the available developments toxicity studies (rat and rabbit) appropriate for

an acute dietary assessment for trifluralin.

Chronic Dietary (All populations) NOAEL =

2.4 mg/kg/day UF A =10x

UF H =10x FQPA SF

=1 2 .4mg/kg/day NOAEL

100 (UF)

cRfD = 0.024 mg/kg/day Chronic (cap sule) Toxicity

– Dog

LOAEL = 40 mg/kg/day, based on increased frequency o f abnormal stool, decreased body weights and body weight gains, and decreased erythrocytes and hemoglobin and increased thrombocytes (males)

Incidental Oral

Short

- Term (1

- 30 days) NOAEL =

10 mg/kg/day UF A =10x

UF H =10x FQPA SF

=1 Residential LOC for MOE

= 100 Two

- generation Reproduction Study

in Rats LOAEL = 32.5 mg/kg/day, based on decreased pup weights in both generations

Incidental Oral

Intermediate

- Term (1

- 6 months ) NOAEL =

10 mg/kg/day UF A =10x

UF H =10x FQPA SF

=1 Residential LOC for MOE

= 100 Special Urinalysis Study in Rats

LOAEL = 40 mg/kg/day, based on the presence of tubular cytoplasmic hyaline droplets; increased total protein, AST, and LDH in the urine; albumin α1

- globulin and α 2

- globulin observed by urine electrophoresis; and increased urinary volume

Dermal

Short

- Term (1

- 30 days) No quantification required since there was no systemic toxicity at the limit dose in the dermal toxicity

study. There are no develo pmental toxicity concerns. The HIARC also recommends that the products containing trifluralin should be labeled as SENSITIZER

### Page 31 of 36 Table 6 .1: Summary of Toxicological Points of Departure and Endpoints for Trifluralin for Used in Dietary and Non

dietary Human Health Risk Assessments

Dermal

Intermediate

- term (1

- 6 months) NOAEL = 10

mg/kg/day

(Dermal Absorption rate = 3 %) UF A =10x

UF H =10x FQPA SF

=1 Resi dential LOC for MOE

= 100 Special Urinalysis Study in Rats

LOAEL = 40 mg/kg/day, based on the presence of tubular cytoplasmic hyaline droplets; increased total protein, AST, and LDH in the urine; albumin α 1

- globulin and α 2

- globulin observed by urine electrophoresis; and increased urinary volume

Dermal Long

- term (>6 months) NOAEL =

2.4 mg/kg/day

(Dermal Absorption rate =

3 % when appropriate) UF A =10x

UF H =10x FQPA SF

=1 Residential LOC for MOE

= 100 Ch ronic (capsule) Toxicity

– Dog

LOAEL = 40 mg/kg/day, based on increased frequency of abnormal stool, decreased body weights and body weight gains, and decreased erythrocytes and hemoglobin and increased thrombocytes (males)

Dermal Long

- term (>6 months) Lo ng

- term dermal exposure is not expected based on the use pattern for paclobutrazol.

Inhalation Short

term (1

- 30 days) NOAEL = 81 mg/kg/day) UF A =10x

UF H =10x FQPA SF

=1 Residential LOC for MOE

= 100 30

- Day Inhalation Study

- Rat

LOAEL = 270 mg/kg/day, based on increased methemoglobin and

bilirubin in females and the incidence of dyspenea and ruffled

fur in males and females

Inhalation

Intermediate

- term (1

- 6 months) NOAEL = 100

mg/kg/day (Inhalation absorption rate = 100%) UF A =10x

UF H =10x FQPA SF

=1 Residential for MOE =

100 Special Urinalysis Study in Rats

NOAEL = 40 mg/kg/day, based on the presence of tubular cytoplasmic hyaline droplets; increased total protein, AST, and LDH in the urine; albumin α1

- globulin and α 2

- globulin observed by urine electrophoresis; and increased urinary volume

Inhalation Long

term (1

- 6 months) NOAEL = 100 mg/kg/day (Inhalation absorption rate = 100%) UF A =10x

UF H =10x FQPA SF

=1 Residential LOC for MOE

= 100 Chronic (cap sule) Toxicity

– Dog

LOAEL = 40 mg/kg/day, based on increased frequency of abnormal stool, decreased body weights and body weight gains, and decreased erythrocytes and hemoglobin and increased thrombocytes (males)

Cancer (oral, dermal, inhalation) Classif ication: Group C (“Possible” Human Carcinogen) Q 1 * = 2.96 X 10 - 3 (mg/kg/day) - 1 (TXR No. 00052534)

### Page 32 of 36

1 Explanation of Abbreviations: 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. UF A = extrapolatio n from animal to human (interspecies). UF A = extrapolation from animal to human (interspecies). UF H = potential variation in sensitivity among members of the human population (intraspecies). UF DB = database uncertainty, lack of neurotoxicity (acute and subchronic) and immunotoxicity studies, FQPA SF = FQPA safety factor. MOE = margin of exposure. LOC = level of concern.

### Page 33 of 36 Table 6 .2: Summary of Toxicological Points of Departure and Endpoints for Trifluralin for Used in Residential/ Occupational H uman Health Risk Assessments

Exposure/

Scenario Point of

Departure Uncertainty

Factors Level of Concern for

Risk Assessment Study and Toxicological Effects

Dermal

Short

- Term (1

- 30 days) No quantification required since there was no systemic toxicity at t he limit dose in the dermal toxicity

study. There are no developmental toxicity concerns. The HIARC also recommends that the products containing trifluralin should be labeled as SENSITIZER

Dermal

Intermediate

- term (1

- 6 months) NOAEL = 10

mg/kg/day

(D ermal Absorption rate = 3 %) UF A =10x

UF H =10x FQPA SF

=1 Residential LOC for MOE

= 100 Special Urinalysis Study in Rats

LOAEL = 40 mg/kg/day, based on the presence of tubular cytoplasmic hyaline droplets; increased total protein, AST, and

LDH in the uri ne; albumin α 1

- globulin and α 2

- globulin observed by urine electrophoresis; and increased urinary volume

Dermal Long

- term (>6 months) NOAEL =

2.4 mg/kg/day

(Dermal Absorption rate =

3 % when appropriate) UF A =10x

UF H =10x FQPA SF

=1 Residential LOC for MOE

= 100 Chronic (capsule) Toxicity

– Dog

LOAEL = 40 mg/kg/day, based on increased frequency of abnormal stool, decreased body weights and body weight gains, and decreased erythrocytes and hemoglobin and increased thrombocytes (males)

Dermal Long

- term (> 6 months) Long

- term dermal exposure is not expected based on the use pattern for paclobutrazol.

Inhalation Short

term (1

- 30 days) NOAEL = 81 mg/kg/day) UF A =10x

UF H =10x FQPA SF

=1 Residential LOC for MOE

= 100 30

- Day Inhalation Study

- Rat

LOAEL = 27 0 mg/kg/day, based on increased methemoglobin and

bilirubin in females and the incidence of dyspenea and ruffled

fur in males and females

### Page 34 of 36 Table 6 .2: Summary of Toxicological Points of Departure and Endpoints for Trifluralin for Used in Residential/ Occupational H uman Health Risk Assessments

Inhalation

Intermediate

- term (1

- 6 months) NOAEL = 100

mg/kg/day (Inhalation absorption rate = 100%) UF A =10x

UF H =10x FQPA SF

=1 Residential for MOE =

100 Special Urinalysis Study in Rats

NOAEL = 40 mg/kg/day, based on the presence of tubular cytoplasmic hyaline droplets; increased total protein, AST, and LDH in the urine; albumin α1

- globulin and α 2

- globulin observed by urine electrophoresis; and increased urinary volume

Inhalation Long

term (1

- 6 months) NOAEL = 100 mg/kg/day (Inhalation absorption rate = 100%) UF A =10x

UF H =10x FQPA SF

=1 Residential LOC for MOE

= 100 Chronic (cap sule) Toxicity

– Dog

LOAEL = 40 mg/kg/day, based on increased frequency of abnormal stool, decreased body weights and body weight gains, and decreased erythrocytes and hemoglobin and increased thrombocytes (males)

Cancer (oral, dermal, inhalation) Classif ication: Group C (“Possible” Human Carcinogen) Q 1 * = 2.96 X 10 - 3 (mg/kg/day) - 1 (TXR No. 00052534)



### 1 Explanation of Abbreviations: 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. UF A = extrapolation from animal to human (interspecies). UF A = extrapolation from animal to human (interspecies). UF H = potential variation in sensitivity among members of the human population (intraspecies). UF DB = database uncertainty, lack of neurotoxicity (acute and su bchronic) and immunotoxicity studies, FQPA SF = FQPA safety factor. MOE = margin of exposure. LOC = level of concern.



### Table 7

. Trifluralin International Residue Limits
Summary of US and International Tolerances and Maximum Residue Limits

Residue D efinition :
US Canada Mexico 2 Code x
40 CFR 180. 207 :

Plant: α,α,α

- trifluroro

- 2,6

- dinitro

- N,N

dipropyl

- p

- toluidine

Commodity 1 Tolerance (ppm) /Maximum Residue Limit (mg/kg)

US Canada Mexico 2 Codex Alfalfa, forage 3.0 Alfalfa, hay 2.0
Almond, hulls 0.05 Asparagus 0.05 Barley, grain 0.05

Bar ley, hay 0.05 Barley, straw 0.05

### Page 35 of 36

Table 7

. Trifluralin International Residue Limits
Summary of US and International Tolerances and Maximum Residue Limits

Residue D efinition :
US Canada Mexico 2 Code x

Bean, mung, sprouts 2.0
Carrot, roots 1.0 Celery 0.05 Corn, field, forage 0.05 Corn, field, grain 0.05
Corn, field, stover 0.05 Cotton, gin byproducts 0.05
Cotton, undelinted seed 0.05

Endive 0.05
Flax, seed 0.05 Fruit, citrus, group 10 0.05 Fruit, stone, group 12 0.05 Grape 0.05 Hop, dried cones 0.05
Mustard, seed 0.05 Nut, tree, group 14 0.05

Okra 0.05

Peanut 0.05 Peanut, hay 0.05 Peppermin t, oil 2.0 Peppermint, tops 0.05 Rapeseed, seed 0.05
Safflower, seed 0.05 Sorghum, grain forage 0.05 Sorghum, grain, grain 0.05 Sorghum, grain, stover 0.05 Spearmint, oil 0.05 Spearmint, tops 2.0 Sugarcane, cane 0.05
Sunflower, seed 0.05 Vegetable, brassica, leafy group 5 0.05 Vegetable, bulb, group 3 0.05 Vegetable, cucurbit, group 9 0.05 Vegetable, fruting, group 8 0.05 Vegetable, leaves of root and tuber, group 2 0.05 Vegetable, legume, grou p 6 0.05 Vegetable, root and tuber, group 1 except

carrot 0.05

Wheat, grain 0.05
Wheat, straw 0.05

1 Includes only commoditie s of interest for this action.

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

### Page 36 of 36

Table 8: HED Memoranda Relevant to Registration Review

Author Barcode/TXR # Date Title

R. Griffin D296628 05/07/2004 Trifluralin Human Health Risk

Assessment

R. Griffin D296627 03/04 /2004 Residue Chemistry Chapter for the

TRED Document

D. Smegal D397497 03/06/ 2012 Summary of Hazard and Science Policy Council (HASPOC) R.B. Jaeger TXR No. 0005578 04/11/1986 Peer Review of Trifluralin

R. Griffin TXR No. 0052534 05/11/2004 Revised Trifluralin Quantitative Risk Assessment (Q 1 *) Based on Fisher 344 Rat Dietary Stud ies With 3⁄4 Interspecies Scaling Factor

S. Piper D296628 0 8 / 10 /2004 Anticipated Residues, Acute, Probabilistic, Chronic and Cancer Dietary Exposure Assessment for the

RED S.Piper D399348 02/29/2012 Response to DowAgroSciences’

Comments on the Human Healt h

Risk Assessment and TRED S.Piper D300064 03/09/2004 HED Metabolism Assessment

Review Committee Decision

Document

S. Recore D296625 0 5/ 0 6/2004 Residential Exposure Assessment and

Recommendations for the Tolerance

Reassessment Evaluation Decision (TRED) Document for Trifluralin

S. Recore D300239 0 5/12/2004 Review of “Dissipation of

Transferable Residues of Benefin and

Trifluralin on Turf Treated with a

Formulation of the Pesticides”

S. Recore D397847 0 3/14/2012 Trifluralin Review of Human

Incident

B. P hillips

-- 12/01/2011 BEAD Chemical Profile for Registration Review