UNITED ST A TES ENVIRONMENT AL PROTECTION AGENCY 

MEMORANDUM 

Date: 19-AUG-2015 

WASHINGTON, D.C. 20460 

OFFICE OF 

Cll El\llCAL SAFETY A D 

POLUITION PllEVENTION 

SUBJECT: Teflubenzuron. Human Health Risk Assessment for the Proposed Tolerances 

without a U.S. Registration for Residues of Teflubenzuron in/on the Commodities 

of Orange, Lemon, Apple, Grape, Tomato, Melon, Broccoli, Cauliflower, 

Sunflower, Soybean, Corn, Coffee Bean, Sugarcane, Mango, Papaya, Pineapple, 

and Livestock Commodities. 

PC Code: 129048 DP Barcode: 0426404 

Decision No.: 486593 Registration No.: NA 

Pclilion No.: 4 E8230 Regulatory Action: Tolerances Wilhout U.S. 

RegistTation 

Risk Assessment Type: Single Chemical/Aggregate Case No.: NA 

TXR No.: NA CASNo.: 83121-18-0 

M RID No.: NA 40 CFR: § 180.TBD 

FROM: Anwar Y. Dunbar, Ph.D., Pharmacologist ~ ,,!':_ · }J~ George F. Kramer, Ph.D., Senior Chemist ~ C::::::~~-::::::i~:;...----

Risk Assessment Branch I (RAB I) ~ - .. 

Heallh Effects Division (HED; 7509P) ~ 

THROUGH: Thurston G. Morton, Acting Branch hief $~ ::;--

RAB I, HED (7509P) 

And 

Christine L. Olinger, Designated Reviewer 

PV Shah, Designated Reviewer 

Risk Assessment Review Committee (RARC) 

HED (7509P) 

TO: Carlyn Patrella, Risk Review Manager 

Richard Gebken, Risk Manager 

Registration Division (RD; 7505P) 

HED of the Office of Pesticide Programs (OPP) is charged with estimating the risk to human 

health from exposure to pesticides. RD of OPP has requested that HED evaluate hazard and 

exposure data and conduct a dietary exposure assessment as needed, to estimate the risk to 

human health that wi ll result from the proposed use of the new active ingredient, teflubenzuron, 

[N-[[(3,5-dichloro-2,4-difluorophenyl)arnino]carbonyl]-2,6-difluorobenzamide]. 

Page I of 30 
Tetlubenzuron Human Health Risk Assessment 0426404 

A summary of the findings and an assessment of human risk resulting from the proposed uses are 

provided in this document. The risk assessment and hazard characterization were provided by 

Anwar Dunbar (RAB 1 ), and the dietary risk assessment and residue chemistry review were 

provided by George Kramer (RAB 1 ). 

Table of Contents 

1.0 Executive Summary ... ..................................................... .............. ... .......... .... ... ... .... ...... .... 4 

2.0 HED Recommendations .................. .... ... ..... .... .... .... .... ................. ..................................... 5 

2.1 Data Deficiencies .... ....... ....... ............ ... ......... .................................................................. 5 

2.2 Tolerance Considerations ........................................................... .......... ....... ... ... ....... ..... 6 

2.2.1 Enforcement Analytical Method ........................... .............. .......... .......... ... ... ....... ..... 6 

2.2.2 Recommended Tolerances .. ........ ............ ................................ ....... ...... ...................... 6 

2.2.3 Revisions to Petitioned-For Tolerances .................................................................... 7 

2.2.4 International Harmonization ................................................. ... .... ... ...... .... ...... .......... 7 

2.3 Label Recommendations ....... .... ........ .... ........ ........ ... .................. ... .......... ....... ...... .......... 8 

3.0 Introduction ... .......... .... ... .... .... ... .... ... ......... ............ ............................................................. 8 

3.1 Chemical Identity .......... ............ ....................................................................... ... ........... 8 

3.2 Physical/Chemical Properties ..................................... ....... .......... ....... ... ... ....... ... ... ........ 8 

3.3 Use Pattern .......... .................. .................... .... .... ... .... .......... .... .... ..................................... 8 

3.4 Anticipated Exposure Pathways ................................................................................... 9 

4.0 Hazard Characterization and Dose-Response Assessment ......... ................................... 9 

4.1 Toxicology Studies Available for Analysis ................................................................ ... 9 

4.2 Absorption, Distribution, Metabolism, & Elimination (ADME) ............................. 10 

4.2.1 Dermal Absorption ......................................... ....... ................................................... 11 

4.3 Toxicological Effects .................................................................................................... 11 

4.4 Safety factor for Infants and Children (FQPA Safety Factor) .... ............................ 11 

4.4.1 Completeness of the Toxicology Database .............................................................. 11 

4.4.2 Evidence of Neurotoxicity ........................................................................................ 11 

4.4.3 Evidence of Sensitivity/Susceptibility in the Developing or Young Animal.. ... ... 11 

4.4.4 Residual Uncertainty in the Exposure Database ................................................... 12 

4.5 Toxicity Endpoint and Point of Departure Selections ....... ............. ...... .................... 12 

4.5.1 Dose-Response Assessment ..................................................................................... . 12 

4.5.2 Recommendation for Combining Routes of Exposures for Risk Assessment ..... 12 

4.5.3 Cancer Classification and Risk Assessment Recommendation ............................ 12 

4.5.4 Summary of Points of Departure and Toxicity Endpoints Used in Human Risk 

Assessment .................................................... ............ ................................ .......... ... .......... ... ..... 13 

5.0 Dietary Exposure and Risk Assessment ..... .... ..... ....... .............. ........................ .............. 13 

5.1 Mctabolite/Degradatc Residue Profile ....................................................................... 13 

5.1.1 Summary of Plant and Animal Metabolism Studies ................................ ......... 13 

5.1.2 Summary of Environmental Degradation ............. .......................... .... ... ............ 14 

5.1.3 Comparison of Metabolic Pathways .................................................................... 14 

5.1.4 Residues of Concern Summary and Rationale ............ ....................................... 14 

5.2 Food Residue Profile .................................................................................... ... .......... ... 15 

5.3 Drinking Water Residue Profile ....... .... ........ .... ........ ....... ... ....... ... .... ... ... .......... .......... 16 

5.4 Dietary (Food + Drinking Water) Risk Assessment.. ................................................ 16 

6.0 Residential (Non-Occupational) Exposure/Risk Characterization ............................. 16 

7.0 Aggregate Exposure/Risk Characterization ............... ................................................. .. 17 

8.0 Cumulative Exposure/Risk Characterization ............ ........... ........................................ 17 

9.0 Occupational Exposure/Risk Characterization ............................................................ 17 

Page 2 of30 
Teflubenzuron Human Health Risk Assessment D426404

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Appendix A. Toxicology Profile and Executive Summaries .................................................. 18

A.2 Toxicity Profiles............................................................................................................ 18

A.3 Hazard Identification and Endpoint Selection .......................................................... 24

Appendix B. Metabolism Considerations................................................................................ 27

B.1. Metabolism Summary Table....................................................................................... 27

B.2 Metabolic Pathways ..................................................................................................... 29

Appendix C. Physical/Chemical Properties............................................................................. 30
Teflubenzuron Human Health Risk Assessment D426404

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1.0 Executive Summary

The new active ingredient (ai) teflubenzuron (N-[[(3,5-dichloro-2,4-

difluorophenyl)amino]carbonyl]-2,6-difluorobenzamide) is a benzoylurea growth regulator 

insecticide. It acts by inhibition of chitin synthesis and molting, disrupting chitin deposition in 

the insect cuticle after ingestion, ultimately resulting in insect mortality at molting. The 

registrant (BASF) submitted a petition for establishment of tolerances for residues of 

teflubenzuron in/on oranges, lemons, apples, grapes, tomatoes, melons, broccoli, cauliflower, 

sunflowers, soybean, corn, coffee beans, sugarcane, mangos, papaya, and pineapples. There are 

no domestic uses proposed or established. The proposed tolerances are expressed in terms of the 

parent only.

Exposure Profile: Based on the proposed uses of teflubenzuron, dietary exposure (food only) is 

the only anticipated exposure pathway. As there are no domestic agricultural or residential uses 

registered or proposed for teflubenzuron, there is no potential for drinking water, residential, or 

occupational exposure.

Hazard Assessment: The effects in the teflubenzuron database are indicative of hepatotoxicity. 

In all species tested there were adverse effects in the liver; increased enzyme release and 

numerous microscopic indicators of liver injury (diffuse hypertrophy, disseminated single-cell

necrosis, patchy glycogen storage, Kupffer cell proliferation, phagocytic foci, lipofuscin 

accumulation, and patchy fatty changes). In the mouse, which is the most sensitive species 

compared to the rat and the dog, there were liver adenomas following chronic exposure. There is 

no evidence of neurotoxicity, immunotoxicity, or genotoxicity.

There is evidence of increased quantitative offspring susceptibility for teflubenzuron in the rat 

two-generation reproductive study. While there were no parental effects, adverse offspring 

effects were observed and consisted of decreased F2 litter weights and increased incidence of 

unilateral dilatation of the renal pelvis in F1 offspring. There were no effects in the 

developmental rat study up to the highest dose tested. In the developmental rabbit study, 

maternal effects were observed at the limit dose and were consistent with liver toxicity. No fetal 

effects were observed.

Food Quality Protection Act (FQPA) Safety Factor (SF) Decision: The teflubenzuron risk 

assessment team recommends that the 10X FQPA SF be reduced to 1X for all exposure 

scenarios. The toxicity database is complete and dietary exposure analyses are unlikely to 

underestimate exposure. There is no evidence of neurotoxicity and the chronic dietary endpoint 

is protective of the offspring effects in the 2-generation reproductive study. Lastly, there are no 

residual uncertainties in the exposure database.

Dose-Response Assessment: The chronic reference dose (cRfD) of 0.021 mg/kg/day was 

determined on the basis of the carcinogenicity study in mice. The lowest-observed adverseeffect level (LOAEL) of 10.5 mg/kg/day is based on increased microscopic lesions in the liver 

(diffuse hypertrophy, centrilobular single-cell necrosis, patchy glycogen storage, Kupffer cell 

proliferation, phagocytic foci, and centrilobular fatty change) associated with increased relative 

liver weights. The no-observed adverse-effect level (NOAEL) of 2.1 mg/kg/day is protective of 

all effects for all durations. This study is appropriate for the duration of exposure and is 

considered protective of the general U.S. population and all population subgroups. A total 

uncertainty factor (UF) of 100X (10X for interspecies extrapolation, 10X for intraspecies 

variability, and a 1X FQPA SF) was applied to this NOAEL generating a chronic population-
Teflubenzuron Human Health Risk Assessment D426404

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adjusted dose (cPAD) of 0.021 mg/kg/day. An acute reference dose (aRfD) for the general U.S. 

population, including infants and children, was not established because no endpoint of concern 

attributable to a single dose was identified in the toxicological database for teflubenzuron.

In accordance with the EPA’s Final Guidelines for Carcinogen Risk Assessment (March, 2005), 

the CARC classified teflubenzuron as “Suggestive Evidence of Carcinogenic Potential” based on 

the presence of rare liver tumors in male mice only. There was no evidence of carcinogenicity in 

female mice or in male or female rats. There is also no concern for mutagenicity. Quantification 

of cancer risk is not required. The CARC recommended using a non-linear approach (i.e., RfD) 

that will adequately account for all chronic toxicity, including carcinogenicity, which could 

result from exposure to teflubenzuron. 

Dietary Risk Estimates (Food Only): A chronic dietary (food only) exposure and risk 

assessment was conducted for the general U.S. population and various population subgroups 

using the Dietary Exposure Evaluation Model software with the Food Commodity Intake 

Database (DEEM-FCID) Version 3.16. This software uses 2003-2008 food consumption data 

from the U.S. Department of Agriculture’s (USDA’s) National Health and Nutrition 

Examination Survey, What We Eat in America, (NHANES/WWEIA). The unrefined chronic 

assessment assumed that teflubenzuron residues are present in all commodities at tolerance levels 

and that 100% of all crops are treated. DEEM Version 7.81 default processing factors were used 

to estimate residues in processed commodities, except for apple and orange juice for which 

empirical processing factors were used since processing studies showed that residues were 

greatly reduced when apples and oranges are processed into juice. Drinking water estimates 

were not incorporated into the chronic dietary assessment, as there are no domestic uses 

proposed or established. Using the DEEM-FCID software, dietary risk is estimated at 17% of 

the cPAD for the general U.S. population and 50% of the cPAD for children 1 to 2 years old, the 

population subgroup with the highest estimated chronic dietary exposure to teflubenzuron. The 

chronic dietary risk assessment shows that for all included commodities, the chronic dietary risk 

estimates are below HED’s level of concern (i.e., <100% cPAD). An endpoint of concern 

attributable to a single dose was not identified; therefore, an acute dietary assessment was not 

performed. 

Aggregate Exposure Assessment: Because this action is for tolerances without U.S. registration 

and there are no proposed or existing uses of teflubenzuron that would result in drinking water or 

residential exposures, the chronic dietary (food only) exposure estimates represent the aggregate 

exposure assessment.

2.0 HED Recommendations

HED is also unable to recommend in favor of the tolerance for residues in/on grape and raisins 

due to the absence of a grape processing study. There are no data gaps that would preclude 

establishing the recommended tolerances for residues of teflubenzuron in/on the remainder of the 

requested crops. The specific tolerance recommendations are discussed in Section 2.2.2.

2.1 Data Deficiencies

With the exception of a processing study for residues of teflubenzuron in/on grape, there are no data 

deficiencies at this time. HED notes that additional plant metabolism, livestock metabolism, 

confined rotational crop, and livestock feeding studies may be necessary to support any future use 

proposed for the U.S. 
Teflubenzuron Human Health Risk Assessment D426404

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2.2 Tolerance Considerations

2.2.1 Enforcement Analytical Method

The petitioner has submitted a high-performance liquid chromatography method with tandem 

mass-spectrometry detection (LC-MS/MS) analytical method, BASF Method L0160/01, for 

analysis of residues of teflubenzuron in/on dry and oily crop commodities. The method has been 

adequately validated by the petitioner as well as by an independent laboratory, and was also 

adequately radiovalidated using weathered samples obtained from metabolism studies. HED has 

determined BASF Method L0160/01 is suitable as an enforcement method for plant 

commodities, as defined in Standard Operating Procedure (SOP) No. ACB-019 (9/15/08). In 

addition, the QuEChERS multiresidue method (MRM) is considered suitable for the analysis of 

teflubenzuron in fruits and vegetables.

2.2.2 Recommended Tolerances 

HED has reviewed the available residue data and has determined the appropriate tolerance levels 

for residues of teflubenzuron (Table 2.2.2.1). The recommended tolerance expression is as 

follows:

(a) General. (1) Tolerances are established for residues of the insecticide teflubenzuron, 

including its metabolites and degradates, in or on the commodities in the table below. 

Compliance with the tolerance levels specified below is to be determined by measuring 

only teflubenzuron (N-[[(3,5-dichloro-2,4-difluorophenyl)amino]carbonyl]-2,6-

difluorobenzamide).

Table 2.2.2.1. Tolerance Summary for Teflubenzuron.

Commodity1 Proposed Tolerance 

(ppm)

HED-Recommended 

Tolerance (ppm)

Comments 

(correct commodity definition)

Apple 0.5 1.0 Harmonization with the Codex 

MRL for pome fruit.

Apple, wet pomace 0.8 - Not required as the commodity is 

not likely to be imported.

Broccoli 0.2 0.20 Significant figures.

Cattle, muscle 0.01 - No expectation of finite residues.

Cattle, meat byproducts 0.01 -

Cauliflower 0.01 0.01 -

Citrus, oil 90 100 Higher value calculated using 

HED policies for processed 

commodities.

Coffee, bean, green 0.6 0.60 Significant figures

Corn, field 0.01 0.01 Corn, field, grain

Corn, field, refined oil 0.02 0.02 -

Egg 0.01 - No expectation of finite residues.

Grape 1 - Tolerances not recommended due 

Grape, raisin 3 - to lack of grape processing study.

Goat, muscle 0.01 - No expectation of finite residues.

Goat, meat byproducts 0.01 -

Horse, muscle 0.01 -

Horse, meat byproducts 0.01 -

Lemon 0.9 0.80 Lower value calculated using 

OECD tolerance calculator.
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Table 2.2.2.1. Tolerance Summary for Teflubenzuron.

Commodity1 Proposed Tolerance 

(ppm)

HED-Recommended 

Tolerance (ppm)

Comments 

(correct commodity definition)

Mango 1.5 1.5 -

Melon 0.3 0.30 Melon, subgroup 9A

Milk 0.01 - No expectation of finite residues.

Orange 0.6 0.60 Significant figures.

Papaya 0.4 0.50 Higher value calculated using 

OECD tolerance calculator.

Pineapple 0.8 0.80 Significant figures.

Pork, muscle 0.01 - No expectation of finite residues.

Pork, meat byproducts 0.01 -

Poultry, muscle 0.01 -

Poultry, meat 

byproducts

0.01 -

Sheep, muscle 0.01 -

Sheep, meat byproducts 0.01 -

Soybean, seed 0.05 0.05 -

Soybean, hulls 0.4 0.15 Lower value calculated using 

HED policies for processed 

commodities.

Sugarcane, cane 0.01 0.01 -

Sunflower, seed 0.3 0.30 Significant figures.

Tomato 1.5 1.5 -

Tomato, paste 5 - Not required; concentration of 

residues is not expected.

1

 No U.S. registration as of [publication date of the tolerances].

2.2.3 Revisions to Petitioned-For Tolerances

For some commodities, the proposed tolerance levels differ slightly from those being 

recommended by HED. Although both the petitioner and HED have used the OECD 

(Organization for Economic Cooperation and Development) calculation procedures to obtain 

tolerance levels, if a higher residue value was observed at a preharvest interval (PHI) longer than 

the minimum PHI, then HED used the highest value, resulting in tolerance recommendations that 

are different from the proposed values. In the case of apple, HED is recommending a higher 

tolerance in order to harmonize with the established Codex maximum residue limit (MRL). 

Based on the results of the livestock feeding studies, there is no expectation of finite residues in 

livestock commodities [§180.6(a)(3)]; therefore, HED is recommending against establishing 

tolerances for residues in livestock commodities. In addition, HED is recommending a number 

of changes in the numerical expression of the tolerance values in order to conform to current 

HED policy on significant figures. HED is also unable to recommend in favor of the tolerance 

for residues in/on grape and raisins due to the absence of a grape processing study.

2.2.4 International Harmonization

There are no established Canadian, Mexican, or Codex MRLs for residues of teflubenzuron, with 

the exception of a Codex MRL of 1 ppm for residues in pome fruit. As the currently established 

Codex MRL is higher than the calculated tolerance value of 0.50 ppm for apple, HED is 

recommending harmonization with the Codex MRL of 1 ppm. 
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2.3 Label Recommendations

None, as no U.S. registrations are requested.

3.0 Introduction

3.1 Chemical Identity

The chemical structure and nomenclature of teflubenzuron is presented in Table 3.1.1. 

Table 3.1.1. Teflubenzuron Nomenclature.

Compound: ai Chemical Structure

Common name Teflubenzuron

Company experimental name BAS 309 I

IUPAC name 1-(3,5-dichloro-2,4-difluorophenyl)-3-(2,6-difluorobenzoyl)urea

CAS name N-[[(3,5-dichloro-2,4-difluorophenyl)amino]carbonyl]-2,6-difluorobenzamide

CAS # 83121-18-0

End-use product/EP Nomolt®, Imunit®

3.2 Physical/Chemical Properties

Technical-grade teflubenzuron is a solid at room temperature and all environmentally relevant 

temperatures. The compound is not volatile (i.e., vapor pressure is 6.87 x 10-9 mm Hg at 20° C); 

thus, there is little likelihood for exposure to teflubenzuron in the vapor phase. The technicalgrade material has a log KOW of 4.98 at pH 5, indicating that the compound is fat-soluble.

3.3 Use Pattern

The petitioner provided copies and English translations of the proposed Nomolt® and Imunit®

labels from several South and Central American countries. Nomolt® is a SC formulation 

containing 13.56% teflubenzuron for ground or aerial applications to oranges, lemons, apples, 

grapes, tomatoes, melons, broccoli, cauliflower, sunflowers, soybean, corn, coffee beans, 

sugarcane, and papaya. Imunit® is a SC formulation containing 7.1% teflubenzuron and 7.1% 

alpha-cypermethrin for ground or aerial applications to oranges, sunflowers, mango, and 

pineapples. The proposed critical good agricultural practices (GAP) use directions, as identified 

by the petitioner, are detailed in Table 3.3.1.
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Table 3.3.1. Summary of Proposed Critical GAP Use Directions.

Crop Country Product Name

Application

Rate (lb ai/A)

Max. No. 

Apps.

RTI

(days)

Application

Rate/Season (lb

ai/A)

PHI 

(days)

Oranges 

and Lemons Brazil Nomolt® 0.107 2 15 0.214 28

Oranges

Costa Rica, 

Honduras

Nomolt® 0.033 2 15 0.066 15

Brazil Imunit

® 0.033 2

10

10

3.11x30

0.066 15

Apple Brazil Nomolt® 0.040 4 10 0.160 7

Grapes Brazil Nomolt® 0.067 3 7 0.201 7

Tomato

Argentina, 

Columbia, 

Costa Rica, 

Guatemala

Nomolt® 0.067 2 7 0.134 14

Melon Brazil Nomolt® 0.067 3 7 0.201 7

Broccoli

Costa Rica, 

Guatemala, 

Honduras

Nomolt® 0.033 2 7 0.066 14

Cauliflower

Costa Rica, 

Guatemala, 

Honduras

Nomolt® 0.020 (1st 

app. 0.023) 3 7 0.063 21

Soybean

Brazil, 

Argentina

Nomolt® 0.030 3 10 0.090 21

Sunflower

Uruguay, 

Argentina

Nomolt® 0.011 2 15 0.022 7

Brazil Imunit

® 0.011 2 15

5.31x40

0.022 7

Corn Brazil Nomolt® 0.020 4 7 0.080 30

Coffee Brazil Nomolt®

0.067 2 30 0.134 30

0.033 2 30 0.066 15

Sugarcane Brazil Nomolt® 0.020 3 30 0.060 40

Mango Brazil Imunit

® 0.268 3 7

2.51x00

0.804 15

Papaya Brazil Nomolt® 0.067 3 7 0.201 7

Pineapple Brazil Imunit

® 0.268 3 7 0.804 15

3.4 Anticipated Exposure Pathways

Based on proposed teflubenzuron application scenarios, dietary exposure (food only) is the only 

anticipated exposure pathway. As there are no domestic agricultural or residential uses 

registered or proposed for teflubenzuron, there is no potential for drinking water, residential, or 

occupational exposure.

4.0 Hazard Characterization and Dose-Response Assessment

4.1 Toxicology Studies Available for Analysis

The hazard database for teflubenzuron is adequate for dose-response and FQPA evaluation. 

Teflubenzuron was evaluated for the following: 

(1) Subchronic and chronic oral toxicity in rats, mice and dogs; 

(2) Developmental toxicity in rats and rabbits; 

(3) Reproductive and postnatal toxicity in rats; 

(4) Carcinogenicity in mice and rats; 

(5) Neurotoxicity in rats; 
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(6) Immunotoxicity in mice; 

(7) Genetic toxicology studies; and

(8) Absorption, Distribution, Metabolism, and Excretion (ADME) studies.

Appendix A includes a summary of the teflubenzuron toxicological database. 

4.2 Absorption, Distribution, Metabolism, & Elimination (ADME)

The ADME for teflubenzuron was well characterized in a series of oral gavage studies using 

low- and high-doses (25 and 750 mg/kg bw). Animals were tested using single and repeated 

dosing regimens. Biliary excretion and tissue accumulation experiments were also carried out. 

Regarding absorption, following a single oral dose of 25 mg/kg bw, the maximum plasma 

concentration (Cmax) was 0.46 μg/mL and the time to peak plasma levels (Tmax) was 8 hours for 

males. For females, the Cmax was 0.25 μg/mL and the Tmax ranged from 2 to 8 hours. From 1 to 

8 hours post dosing, nearly constant plasma levels were found and started to decline at 24 hours. 

Plasma concentrations declined to less than 0.01 μg equivalents/mL in both sexes at the end of 

the experimental period (7 days). 

Following single oral dosing at 750 mg/kg bw, the Cmax was 3.27 μg/mL and the Tmax was 24 

hours. For females, the Cmax was 1.43 μg/mL and the Tmax was 0.67 hours. The second day after 

treatment, the plasma levels declined to 1.05 μg/mL in males while levels were consistent in 

females. By the end of the 7-day testing period, plasma levels decreased to 0.06 and 0.08 μg 

equivalents/mL in male and female rats, respectively. 

Tissue accumulation and distribution was negligible for both sexes treated with radiolabeled test 

material for 7 consecutive days; being less than 1% of the administered dose at all intervals. The 

highest detectable levels of the radiolabel were in the liver (~0.23-0.33% for both sexes) which 

peaked from 1 to 6 hours post dosing and then gradually decreased. All other tissues were less 

than 0.1%.

The majority of the radiolabel was recovered in the feces (>90%), and was identified as the 

parent compound. Three metabolites were isolated. Two products were structural isomers 

formed by hydroxylation of the benzoyl ring at positions 3 and 4, while the remaining metabolite 

was formed by substitution of one fluorine atom by hydroxide, likely on the aniline ring. Biliary 

extracts showed meta-hydroxylation of the benzoyl ring followed by conjugation was the 

predominant pathway. Only very small amounts of radioactivity co-eluted with the 

hydroxylated-aniline derivatives of parent teflubenzuron while hydrolytic treatments of bile 

indicated that phenyl urea may also be present as a sulfate conjugate.

Regarding excretion, following single low-dosing, radiolabel detected in the 0- to 48-hour 

interval yielded 45.43-46.60% of the administered dose in the feces, 15.28-17.04% in the bile, 

and 1.26-1.54% in the urine in both sexes. For this interval and dose, the amount of radiolabel 

remaining in the tissues and carcass accounted for an average of 23% of the administered dose. 

Following single high-dosing, radiolabel detected in the 0- to 48-hour interval, yielded 57.91-

71.77% of the administered dose in the feces, 1.64-2.12% in the bile, and 0.29-0.40% in the 

urine in both sexes. For this interval and dose, the amount of radiolabel remaining in the tissues 

and carcass accounted for an average of 19% of the administered dose.
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4.2.1 Dermal Absorption

As only tolerances without U.S. registration are proposed, there are no dermal absorption or

dermal toxicity studies available for teflubenzuron. 

4.3 Toxicological Effects

The effects in the teflubenzuron database are indicative of hepatotoxicity. In all species tested 

there were adverse effects in the liver; increased enzyme release and numerous microscopic 

indicators of liver injury (diffuse hypertrophy, disseminated single-cell necrosis, patchy glycogen 

storage, Kupffer cell proliferation, phagocytic foci, lipofuscin accumulation, and patchy fatty 

changes). In the mouse, which is the most sensitive species compared to the rat and the dog, 

there were liver adenomas following chronic exposure. There is no evidence of neurotoxicity, 

immunotoxicity, or genotoxicity.

There is evidence of a quantitative increase in offspring susceptibility for teflubenzuron in the rat 

two-generation reproductive study. While there were no parental effects, offspring effects were 

observed and consisted of decreased F2 litter weights and increased incidence of unilateral 

dilatation of the renal pelvis in F1 offspring. However, there were no effects in the 

developmental rat study up to the highest dose tested. In the developmental rabbit study, no fetal 

effects were observed, but maternal effects consistent with liver toxicity were observed at the 

limit dose.

Teflubenzuron is categorized as having low acute lethality by the oral, dermal or inhalation 

routes (Toxicity Categories III and IV). It is not a dermal sensitizer or an eye irritant.

4.4 Safety factor for Infants and Children (FQPA Safety Factor)

The teflubenzuron risk assessment team recommends that the 10X FQPA SF be reduced to 1X 

for all exposure scenarios. The toxicity database is complete and dietary exposure analyses are 

unlikely to underestimate exposure. There is no evidence of neurotoxicity and the selected 

endpoints are protective of increased offspring susceptibility. Lastly, there are no residual 

uncertainties in the exposure database.

4.4.1 Completeness of the Toxicology Database

The existing toxicology database for teflubenzuron is adequate for FQPA evaluation. 

Developmental toxicity studies in rats and rabbits, a two-generation reproduction study in rats, 

and neurotoxicity studies in rats are available for FQPA consideration.

4.4.2 Evidence of Neurotoxicity

There is no evidence of neurotoxicity in the teflubenzuron hazard database, which includes acute 

and subchronic neurotoxicity studies.

4.4.3 Evidence of Sensitivity/Susceptibility in the Developing or Young Animal

There is no evidence for increased fetal susceptibility. There is an observed increased offspring 

susceptibility in the two-generation reproductive study, but the concern is low since; 1) the 

effects in pups are well characterized with a clear NOAEL; and 2) the effects are protected for by 
Teflubenzuron Human Health Risk Assessment D426404

Page 12 of 30

the selected chronic dietary endpoint. Therefore, there are no residual uncertainties for pre-/postnatal toxicity. 

4.4.4 Residual Uncertainty in the Exposure Database

There are no residual uncertainties in the exposure database. The exposure databases are sufficient 

to determine the nature/magnitude of the residue in food and dietary analyses are unlikely to 

underestimate risk of exposure from teflubenzuron. In addition, there are no currently proposed 

residential uses.

4.5 Toxicity Endpoint and Point of Departure Selections

4.5.1 Dose-Response Assessment

Acute Dietary Endpoint: An acute population-adjusted dose (aPAD) for the general U.S. 

population, including infants and children, was not established because no endpoint of concern 

attributable to a single dose was identified in the toxicological database for teflubenzuron. 

Therefore, an acute dietary assessment was not performed. 

Chronic Dietary Endpoint: The cPAD of 0.021 mg/kg/day was determined on the basis of the 

carcinogenicity study in mice. The LOAEL of 10.5 mg/kg/day is based on increased 

microscopic lesions in the liver (diffuse hypertrophy, centrilobular single-cell necrosis, patchy 

glycogen storage, Kupffer cell proliferation, phagocytic foci, and centrilobular fatty changes) 

associated with increased relative liver weights. The NOAEL of 2.1 mg/kg/day is protective of 

all effects seen following chronic exposure, including the two-generation reproduction toxicity 

study. This study is appropriate for the duration of exposure and is considered protective of the 

general U.S. population and all population subgroups. This study provides the most protective 

point of departure in the hazard database with a NOAEL of 2.1 mg/kg/day. A total UF of 100X 

(10X for interspecies extrapolation, 10X for intraspecies variability, and a 1X FQPA SF) was 

applied to this NOAEL, generating a cPAD of 0.021 mg/kg/day.

4.5.2 Recommendation for Combining Routes of Exposures for Risk Assessment

As there are no domestic agricultural or residential uses registered or proposed for teflubenzuron, 

there is no potential for residential/occupational exposure.

4.5.3 Cancer Classification and Risk Assessment Recommendation

In accordance with the EPA’s Final Guidelines for Carcinogen Risk Assessment (March, 2005), 

the CARC classified teflubenzuron as “Suggestive Evidence of Carcinogenic Potential” based on 

the presence of rare liver tumors in male mice only. There was no evidence of carcinogenicity in 

female mice or in male or female rats. There is also no concern for mutagenicity. 

Quantification of teflubenzuron’s carcinogenic potential is not required. The CARC 

recommended using a non-linear approach (i.e., RfD) that will adequately account for all chronic 

toxicity, including carcinogenicity, that could result from exposure to teflubenzuron. 
Teflubenzuron Human Health Risk Assessment D426404

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4.5.4 Summary of Points of Departure and Toxicity Endpoints Used in Human Risk 

Assessment

Table 4.5.4.1. Summary of Toxicological Doses and Endpoints for teflubenzuron for Use in Dietary and 

Non-Occupational Human Health Risk Assessments.

Exposure/ 

Scenario

Point of 

Departure

Uncertainty/FQPA 

SFs

RfD, PAD, 

LOC for Risk 

Assessment

Study and Toxicological Effects

Acute Dietary 

(General 

Population, 

including 

Infants and 

Children)

An endpoint of concern attributable to a single dose was not identified. An acute RfD was not 

established.

Chronic 

Dietary (All 

Populations)

NOAEL = 

2.1 

mg/kg/day

UFA = 10X

UFH = 10X

FQPA SF = 1X

Chronic RfD 

= 0.021

mg/kg/day

cPAD = 

0.021 

mg/kg/day

Carcinogenicity (mouse)

LOAEL = 10.5 mg/kg bw/day (M), based 

on increased microscopic lesions in the 

liver (diffuse hypertrophy, centrilobular 

single-cell necrosis, patchy glycogen 

storage, Kupffer cell proliferation, 

phagocytic foci, and centrilobular fatty 

change) associated with increased 

relative liver weight.

Cancer (oral, 

dermal, 

inhalation)

Classification: “Suggestive Evidence of Carcinogenic Potential” based on the presence of rare 

liver tumors in male mice only. Quantification of teflubenzuron’s carcinogenic potential is not 

required. The CARC recommended using a non-linear approach (i.e., RfD)) that will 

adequately account for all chronic toxicity, including carcinogenicity that could result from 

exposure to teflubenzuron. 

Point of departure (POD) = A data point or an estimated point that is derived from observed dose-response data and 

used to mark the beginning of extrapolation to determine risk associated with lower environmentally relevant human 

exposures. NOAEL = no-observed adverse-effect level. LOAEL = lowest-observed adverse-effect level. UF = 

uncertainty factor. UFA = extrapolation from animal to human (interspecies). UFH = potential variation in 

sensitivity among members of the human population (intraspecies). FQPA SF = FQPA Safety Factor. PAD = 

population-adjusted dose (a = acute, c = chronic). RfD = reference dose. LOC = level of concern. 

5.0 Dietary Exposure and Risk Assessment 

D418271, G. Kramer, 18-AUG-2015 (residue chemistry chapter for the current action)

D426403, G. Kramer, 18-AUG-2015 (dietary exposure analysis for the current action)

5.1 Metabolite/Degradate Residue Profile

5.1.1 Summary of Plant and Animal Metabolism Studies

The petitioner has provided plant metabolism studies in diverse crops (spinach, cotton, potato, 

and apple); however, only one study (spinach; MRID 49168727) was determined to be 

scientifically acceptable. The other studies were determined to be tentatively acceptable pending 

submission of supporting data. However, as the parent teflubenzuron generally accounted for 

>95% of TRR, submission of these data would be unlikely to change the results. Using a 

weight-of-evidence approach, HED thus concludes that the translocation and metabolism of 

teflubenzuron in plants is minimal. Parent teflubenzuron is the only residue of concern for risk 

assessment and tolerance enforcement. HED notes that this conclusion pertains only to imported 

commodities, and that additional plant metabolism studies (and/or supporting data for the 

submitted studies) may be necessary to support any future use proposed for the U.S.
Teflubenzuron Human Health Risk Assessment D426404

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The petitioner has provided ruminant and poultry metabolism studies; however, neither study 

was determined to be scientifically acceptable. The potential for actual residues in livestock 

tissues is minimal (the maximum TRR values extrapolated to a 1X dose are 0.008 ppm in 

ruminants and 0.0006 ppm in poultry). Minor metabolites resulting from hydroxylation 

(Metabolite 3381 in ruminants) and ring cleavage (3,5-dichloro-2,4-difluorophenyl urea in 

poultry) were also seen in rats (see Figure B.2.1 in Appendix B). Metabolite 3381 was 

monitored in the livestock feeding studies, but residues were found to be non-quantifiable. HED 

notes that conclusions on the nature of the residue in livestock pertain only to this petition, and 

that additional livestock metabolism studies may be necessary to support any future uses that 

result in higher dietary burdens.

5.1.2 Summary of Environmental Degradation

As there are no domestic agricultural or residential uses registered or proposed for teflubenzuron, 

environmental degradation is not relevant for this petition.

5.1.3 Comparison of Metabolic Pathways

Translocation and metabolism of teflubenzuron in plants is minimal. No metabolites were 

identified. The absorption of teflubenzuron in livestock is minimal. Minor metabolites resulting 

from hydroxylation (Metabolite 3381 in ruminants) and ring cleavage (3,5-dichloro-2,4-

difluorophenyl urea in poultry) were also seen in rats (see Figure B.2.1). 

5.1.4 Residues of Concern Summary and Rationale

Upon examination of the available data, the HED Residues of Concern Knowledgebase 

Subcommittee (ROCKS) determined that the parent compound, teflubenzuron, is a suitable 

residue definition for purposes of both tolerance enforcement and risk assessment in plants and 

livestock commodities (Memo, E. Holman, 22-MAY-2015, D426402). 

Table 5.1.4.1. Summary of Metabolites and Degradates to be Included in the Risk Assessment 

and Tolerance Expression.

Matrix Residues Included in Risk 

Assessment

Residues Included in 

Tolerance Expression

Plants Primary Crop Teflubenzuron Teflubenzuron

Rotational Crop Not Applicable Not Applicable

Livestock Ruminant Teflubenzuron Teflubenzuron Poultry

Primary Plants. The petitioner has provided plant metabolism studies in diverse crops (spinach, 

cotton, potato, and apple); however, only one study (spinach) was determined to be scientifically 

acceptable. The other studies were determined to be tentatively acceptable pending submission 

of supporting data. However, as the parent teflubenzuron generally accounted for >95% of the 

TRR, submission of these data would be unlikely to change the results. Using a weight-ofevidence approach, HED concludes that the translocation and metabolism of teflubenzuron in 

plants is minimal. No metabolites were identified. Parent teflubenzuron is thus adequate as the 

only residue of concern for risk assessment and tolerance enforcement. HED notes that this 

conclusion pertains only to imported commodities, and that additional plant metabolism studies 

may be necessary to support any future use proposed for the U.S.
Teflubenzuron Human Health Risk Assessment D426404

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Livestock. The petitioner has provided ruminant and poultry metabolism studies; however, 

neither study was determined to be scientifically acceptable. The potential for actual residues in 

livestock tissues is minimal (the maximum TRR values extrapolated to a 1X dose are 0.008 ppm 

in ruminants and 0.0006 ppm in poultry) and imported livestock commodities are not likely to be 

significant contributors to chronic dietary exposure (an aRfD was not established.). Using a 

weight-of-evidence approach, HED concludes that the absorption of teflubenzuron in livestock is 

minimal. Minor metabolites resulting from hydroxylation (Metabolite 3381 in ruminants) and 

ring cleavage (3,5-dichloro-2,4-difluorophenyl urea in poultry) were also seen in rats (see 

Appendix B). Metabolite 3381 was determined in the livestock feeding studies, but residues 

were found to be non-quantifiable. Parent teflubenzuron is thus adequate as the only residue of 

concern for risk assessment and tolerance enforcement. HED notes that this conclusion pertains 

only to the current action, and that additional livestock metabolism studies may be necessary to 

support any future uses that result in higher dietary burdens.

5.2 Food Residue Profile

The residue chemistry database includes submissions addressing analytical methods; metabolism 

in target crops, rotational crops, and livestock; storage stability; residues from field trials; 

residues from ruminant and poultry feeding studies; and residues in processed commodities. 

During the 90-day screen of the data, the lack of a processing study for residues of teflubenzuron 

in/on grape was identified as a data gap (Memo, A. Dunbar et al., 30-APR-2014; D419593). 

ChemSAC determined that raisin-processing data are required (Minutes of 18-JUN-2014 

ChemSAC meeting). As HED would be unable to recommend in favor of a tolerance for 

residues in/on grape in the absence of the requisite processing study, the grape field trial data 

have not been reviewed at this time. 

With the exception of a processing study for residues of teflubenzuron in/on grape, the submitted 

residue data are adequate to fulfill data requirements. Based on the North American Free Trade 

Agreement (NAFTA) guidance (NAFTA Guidance Document on Data Requirements for 

Tolerances on Imported Commodities in the United States and Canada, 12/05), an adequate 

number of trials were performed for each crop in the countries where use is proposed or which 

represent the critical GAP. Teflubenzuron residues were limited to the surface of crops and 

dissipated slowly under field conditions. The recommended tolerance levels for residues of 

teflubenzuron in/on imported oranges, lemons, apples, tomatoes, melons, broccoli, sunflowers, 

soybean, coffee beans, mangos, papaya, and pineapples were obtained using the OECD 

tolerance-calculation procedures. As all residues in sugarcane, cauliflower, and field corn grain 

were below the LOQ, HED recommended the method LOQ (0.01 ppm) as the tolerance level for 

these commodities. Based on the results of the livestock feeding studies, there is no expectation 

of finite residues in livestock commodities [§180.6(a)(3)].

The submitted processing data are adequate to fulfill data requirements. Significant 

concentration of teflubenzuron residues was seen in the following commodities: apple, wet 

pomace and dry pomace; citrus, oil; corn, aspirated grain fractions (AGF) and refined oil; 

pineapple, process residue; soybean, AGF and hulls; and tomato, wet pomace and peel. 

Tolerances for residues in apple, dry pomace; and tomato, wet pomace and peel are not required 

as the Agency does not generally establish tolerances for residues in these commodities. 

Tolerances for residues in apple, wet pomace; AGFs; and pineapple, process residue are not 

required as these commodities are not likely to be imported. Significant reduction of 

teflubenzuron residues was seen in the following commodities: applesauce, apple juice, orange 

juice, roasted coffee beans, instant coffee, corn grits, corn meal, cornstarch, soybean meal, 
Teflubenzuron Human Health Risk Assessment D426404

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soybean oil, molasses, refined sugar, sunflower meal, sunflower oil, tomato purée, and tomato 

juice. The appropriate tolerance levels for citrus, oil; corn, refined oil; and soybean, hulls are 

shown in Table 2.2.2.1.

5.3 Drinking Water Residue Profile

As there are no domestic agricultural or residential uses registered or proposed for teflubenzuron, 

a drinking water assessment is not relevant for this petition. 

5.4 Dietary (Food + Drinking Water) Risk Assessment

A chronic (food only) analysis was performed using DEEM-FCID, ver. 3.16, which incorporates 

consumption data from the USDA NHANES/WWEIA; 2003-2008, to estimate the dietary 

exposure of the U.S. population and various population subgroups. The unrefined chronic 

assessment assumed that teflubenzuron residues are present in all commodities at tolerance levels 

and that 100% of all crops are treated. DEEM Version 7.81 default processing factors were used 

to estimate residues in processed commodities, except for apple and orange juice for which 

empirical processing factors of 0.08 and 0.04, respectively, were used. Drinking water estimates 

were not incorporated into the chronic dietary assessment, as there are no domestic uses 

proposed or established. The results are summarized in Table 5.4.1. The resulting chronic food 

estimates are not of concern to HED (<100% cPAD) for U.S. general population and all 

population subgroups (≤50% cPAD); the most highly exposed population subgroup is children 1-

2 years old. The chronic dietary exposure and risk estimates are highly conservative since they 

assume that all subject crops consumed in this country have been treated (but use is not 

registered not in the U.S.) and that residues are present at tolerance levels. Dietary exposure 

estimates could be refined using anticipated residues and percent crop imported data. However, 

since estimated exposures and risks using conservative assumptions are below HED’s level of 

concern, such refinement is not warranted.

Table 5.4.1. Summary of Dietary (Food and Drinking Water) Exposure and Risk for Teflubenzuron.*

Population Subgroup

Acute Dietary Chronic Dietary Cancer

Dietary 

Exposure 

(mg/kg/day)

% aPAD*

Dietary 

Exposure

(mg/kg/day)

% cPAD*

Dietary 

Exposure

(mg/kg/day)

Risk

General U.S. Population

N/A N/A

0.003505 17

N/A N/A

All Infants (<1 year old) 0.004994 24

Children 1-2 years old 0.010548 50

Children 3-5 years old 0.009182 44

Children 6-12 years old 0.005347 26

Youth 13-19 years old 0.003075 15

Adults 20-49 years old 0.002822 13

Adults 50-99 years old 0.002525 12

Females 13-49 years old 0.002709 13

*Population subgroup with the highest exposure and risk is in bold type. 

6.0 Residential (Non-Occupational) Exposure/Risk Characterization

As there are no domestic agricultural or residential uses registered or proposed for teflubenzuron, 

a residential exposure assessment was not performed.
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7.0 Aggregate Exposure/Risk Characterization

In accordance with the FQPA, HED must consider and aggregate (add) pesticide exposures and 

risks from three major sources: food, drinking water, and residential exposures. In an aggregate 

assessment, exposures from relevant sources are added together and compared to quantitative 

estimates of hazard (e.g., a NOAEL or PAD), or the risks themselves can be aggregated. When 

aggregating exposures and risks from various sources, HED considers both the route and 

duration of exposure. Because this action is for tolerances without a U.S. registration and there 

are no proposed or existing uses of teflubenzuron which would result in drinking water or 

residential exposures, the dietary (food only) exposure estimates provided in Table 5.4.1 

represent the aggregate exposure assessment.

8.0 Cumulative Exposure/Risk Characterization

Unlike other pesticides for which EPA has followed a cumulative risk approach based on a 

common mechanism of toxicity, EPA has not made a common mechanism of toxicity finding as 

to teflubenzuron and any other substances and teflubenzuron does not appear to produce a toxic 

metabolite produced by other substances. For the purposes of this tolerance action, therefore,

EPA has not assumed that teflubenzuron has a common mechanism of toxicity with other 

substances. For information regarding EPA’s efforts to determine which chemicals have a 

common mechanism of toxicity and to evaluate the cumulative effects of such chemicals, see 

the policy statements released by EPA’s Office of Pesticide Programs concerning common 

mechanism determinations and procedures for cumulating effects from substances found to 

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

9.0 Occupational Exposure/Risk Characterization

Since the proposed use is for a tolerance without an U.S. registration, an occupational exposure 

assessment is unnecessary. 

Appendix A. Toxicology Profile and Executive Summaries

Appendix B. Metabolism Considerations

Appendix C. Physical/Chemical Properties of Teflubenzuron

RDI: RAB1 (17-JUN-2015)

Anwar Dunbar:S10952:Potomac Yard 1:703-603-0611:7509P:RAB1
Teflubenzuron Human Health Risk Assessment D426404

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Appendix A. Toxicology Profile and Executive Summaries

The requirements (40 CFR 158.340) for an import tolerance for teflubenzuron are in Table 1. Use of the new 

guideline numbers does not imply that the new (1998) guideline protocols were used.

Study Technical

Required Satisfied

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 (nonrodent).........................................

870.3200 21-Day Dermal..............................................................

870.3250 90-Day Dermal..............................................................

870.3465 90-Day Inhalation..........................................................

Yes

Yes

No1

No1

No1

Yes

Yes

-

-

-

870.3700a Developmental Toxicity (rodent) ..................................

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

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

Yes

Yes

Yes

No

Yes

No

870.4100a Chronic Toxicity (rodent)..............................................

870.4100b Chronic Toxicity (nonrodent)........................................

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

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

870.4300 Chronic/Oncogenicity ...................................................

Yes

Yes

-

Yes

Yes

Yes

Yes

-

Yes

Yes

870.5100 Mutagenicity—Gene Mutation - bacterial.....................

870.5300 Mutagenicity—Gene Mutation - mammalian ...............

870.5xxx Mutagenicity—Structural Chromosomal Aberrations...

870.5xxx Mutagenicity—Other Genotoxic Effects.......................

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 Develop. Neurotoxicity .................................................

No

No

Yes

Yes

No

-

-

Yes

Yes

-

870.7485 General Metabolism......................................................

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

870.7800 Immunotoxicity .............................................................

Yes

No

Yes

Yes

-

Yes

1- Not required for tolerances without U.S. registration.

A.2 Toxicity Profiles

Table A.2.1. Acute Toxicity Profile - Test Substance.

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

870.1100 Acute oral [rat] 42727305 LD50 ≥ 5000 

mg/kg

IV

870.1100 Acute oral [mouse] 42727306 LD50 ≥ 5000 

mg/kg

IV

870.1200 Acute dermal [rat] 42727307 LD50 > 2000 

mg/kg

III

870.1300 Acute inhalation [inhalation] 42727308 LC50 = 5.038 

mg/L

IV

870.2400 Acute eye irritation [rabbit] 42727309 Teflubenzuron is 

minimally 

irritating.

IV
Teflubenzuron Human Health Risk Assessment D426404

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Table A.2.1. Acute Toxicity Profile - Test Substance.

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

870.2500 Acute dermal irritation [rabbit] 42727310, 

42727311

Non-irritating to

rabbits under 

these study 

conditions

IV

870.2600 Skin sensitization [guinea pig] 42727312 No evidence of 

irritation

Negative

Table A.2.2. Subchronic, Chronic, and Other Toxicity Profile.

Guideline 

No. 

Study Type MRID No. (year)/ 

Classification/Doses

Results

870.3100 28-Day oral 

toxicity (rat)

49168793 (1986)

Acceptable/Non-guideline

0, 500, 1000, 2000, 4000, 

8000, 16,000, or 32,000 

ppm 

(0, 39, 77, 154, 305, 624, 

1259, and 2160 mg/kg 

bw/day [M])

(0, 38, 78, 158, 320, 607, 

1313, and 2544 mg/kg 

bw/day [F])

The NOAEL for male and female rats treated 

with teflubenzuron for 28 days was 32,000 ppm 

(equivalent to 2520 mg/kg bw/day for males 

and 2544 mg/kg bw/day for females). 

A LOAEL was not established. 

The data also indicated that test material 

absorption became saturated at dietary 

concentrations of 1000 and 2000 ppm in male 

and female rats, respectively. 

870.3100 28-Day oral 

toxicity (rat)

49168791, 49168792 

(1983 and 1989)

Acceptable/Non-guideline

0, 100, 1000, or 10,000 

ppm 

(0, 12.8/11.7, 134/114, 

and 1254/1219 mg/kg 

bw/day [M/F]) 

NOAEL = 10,000 ppm (1254/1219 mg/kg 

bw/day [M/F]). 

A LOAEL was not established. 

870.3100 90-Day oral 

toxicity (mouse)

49168795 (1979)

Acceptable/guideline

0, 100, 1000, or 10,000 

ppm (0, 11.85/13.7, 

115.3/143.1, and 

1,213/1,450 mg/kg 

bw/day [M/F])

NOAEL = 100 ppm (11.9/13.7 mg/kg bw/day 

[M/F]).

LOAEL = 1,000 ppm (115/143.1 mg/kg bw/day 

[M/F]) based upon increased liver enzyme 

release, and changes in liver histopathology 

(hepatocellular swelling/fatty changes). 

870.3100 90-Day oral 

toxicity (rat)

49168794, 49168796 

(1983,1984)

Acceptable/guideline

0, 100, 1000, or 10,000 

ppm (0, 8/9, 82/94, and 

809/942 mg/kg bw/day 

[M/F])

NOAEL = 10,000 ppm (809/942 mg/kg bw/day 

[M/F]). 

A LOAEL was not identified.

870.3150 90-Day oral 

toxicity (dog)

49168798 (1985)

Acceptable/guideline

0, 30, or 100 ppm 

(0, 1.0, and 3.6 mg/kg 

bw/day [M] 

0, 1.2, and 4.1 mg/kg 

bw/day [F])

NOAEL was 100 ppm (3.6/4.1 mg/kg bw/day 

[M/F]).

A LOAEL was not identified.
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Table A.2.2. Subchronic, Chronic, and Other Toxicity Profile.

Guideline 

No. 

Study Type MRID No. (year)/ 

Classification/Doses

Results

870.3150 90-Day oral 

toxicity (dog)

49168797 (1985)

Acceptable/guideline

0, 100, 1000, and 10,000 

ppm 

(0, 2.7, 29.0, and 251.8 

mg/kg bw/day [M]

0, 3.1, 36.7, and 327.0 

mg/kg bw/day [F])

NOAEL = 1000 ppm (29.0/36.7 mg/kg bw/day 

[M/F]).

LOAEL = 10,000 ppm (251.8/327.0 mg/kg 

bw/day [M/F]) based on (1) macroscopically 

apparent nodular foci accompanied by 

follicular hyperplasia in the stomachs and (2) 

liver damage described as hepatopathy that 

morphologically resembles chronic active 

hepatitis accompanied by elevated activities for 

several hepatic enzymes (AST, ALT, ALP, 

GGT, and OCT) seen after 4 and/or 8 (but not 

13) weeks of continuous treatment. 

870.3200 21/28-Day dermal 

toxicity (species)

NA NA

870.3465 90-Day inhalation 

toxicity (species)

NA NA

870.3700a Prenatal 

developmental in 

(rat)

49168806, 49168805 

(1987, 1984)

Acceptable/non-guideline

0, 100, 300, or 1000 

mg/kg bw/day

Maternal NOAEL = 1000 mg/kg/day.

The maternal LOAEL was not established.

Developmental NOAEL = 1000 mg/kg/day.

The developmental LOAEL was not 

established.

870.3700b Prenatal 

developmental in 

(rabbit)

49168807, 49168808 

(1984, 1985)

Acceptable/guideline

0, 10, 50, or 250 mg/kg 

bw/day

Maternal NOAEL = 250 mg/kg/day.

The maternal LOAEL was not established.

Developmental NOAEL = 250 mg/kg/day

The developmental LOAEL was not 

established.

870.3700b Prenatal 

developmental in 

(rabbit)

49168809 

(1987)

Acceptable/non-guideline

0, 1000 mg/kg bw/day

Maternal NOAEL is 0 mg/kg/day.

LOAEL is 1000 mg/kg bw/day on increased 

incidence of gross liver findings (granulated cut 

surface).

Developmental NOAEL is 1000 mg/kg/day.

LOAEL was not established.

870.3800 Reproduction and 

fertility effects

(rat)

49168810 (1989)

Acceptable/non-guideline

0, 20, 100, or 500 ppm 

(0, 1.5-1.9, 7.4-9.6, and 

39.6-48.2 mg/kg bw/day 

[M] 

0, 2.2-2.5, 10.8-12.4, and 

54.9-61.5 mg/kg bw/day 

[F])

Parental/Systemic NOAEL = 39.6/54.9 

mg/kg/day (M/F).

A LOAEL was not established. 

Reproductive NOAEL = 39.6/54.9 mg/kg/day 

(M/F).

A LOAEL was not established. 

Offspring NOAEL = 12.4 mg/kg/day.

LOAEL = 61.5 mg/kg/day based on decreased 

F2 litter weights and increased incidence of 

unilateral dilatation of the renal pelvis in F1

offspring.

870.4100b Chronic toxicity 

(dog)

49168801 (1986)

Acceptable /guideline

0, 30, 100, or 500 ppm. 

(0, 0.98, 3.15, and 17.30 

mg/kg bw/day [M] 

0, 1.16, 4.02, and 17.98 

mg/kg bw/day for males 

[F])

NOAEL = 500 ppm (17.30/17.98 mg/kg 

bw/day [M/F]).

A LOAEL was not identified.
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Table A.2.2. Subchronic, Chronic, and Other Toxicity Profile.

Guideline 

No. 

Study Type MRID No. (year)/ 

Classification/Doses

Results

870.4200 Carcinogenicity

(rat)

49168811, 49168812 

(1987, 1989)

Acceptable /guideline

0, 20, 100, 500, 2500, 

10000

0, 1.0, 4.8, 24.8, 122.5, 

and 487.3 mg/kg bw/day 

[M] 

0, 1.2, 5.9, 29.9, 154.0, 

and 615.2 mg/kg bw/day 

[F]

NOAEL = 2500 ppm (25.6/30.5 mg/kg bw/day 

[M/F]).

LOAEL = 10000 ppm (122.5/154.0 mg/kg/day 

[M/F]) based on microscopic effects in the liver 

(fatty change and basophilic and mixed cell 

foci).

No evidence of carcinogenicity.

870.4300 Carcinogenicity

(mouse)

49168813 (1987)

Acceptable/non-guideline

0, 15, 75, or 375 ppm (0, 

2.1, 10.5, and 53.6 mg/kg 

bw/day [M] 

0, 3.1, 15.4, and 71.7 

mg/kg bw/day [F])

NOAEL = 15 ppm (2.1 mg/kg bw/day [M]) and 

75 ppm (15.4 mg/kg bw/day [F]).

LOAEL = 75 ppm (10.5 mg/kg bw/day [M]), 

based on increased microscopic lesions in the 

liver (diffuse hypertrophy, centrilobular singlecell necrosis, patchy glycogen storage, Kupffer 

cell proliferation, phagocytic foci, and 

centrilobular fatty change) associated with 

increased relative liver weight.

LOAEL = 375 ppm (71.7 mg/kg bw/day[F]), 

based on increased microscopic lesions in the 

liver (diffuse hypertrophy, disseminated singlecell necrosis, patchy glycogen storage, Kupffer 

cell proliferation, phagocytic foci, lipofuscin 

accumulation, and patchy fatty change) with 

associated increased absolute and relative liver 

weights and increased alanine aminotransferase 

and lactate dehydrogenase activities.

There was a treatment-related increase in tumor 

incidence of hepatocellular adenomas in males 

of the 375-ppm (10.5 mg/kg/day) group when 

compared to controls. The incidence of 

hepatocellular adenomas was 6/50, 5/50, 11/50, 

and 16/50 at 0, 15, 75, and 375 ppm, 

respectively. 

Evidence of carcinogenicity (an increased 

occurrence of liver adenomas and 

carcinomas at 75 and 375 ppm).

870.5100 Bacterial Mutation 

Assay In S. 

typhimurium And 

E .coli

49168814 (1982)

Acceptable /guideline

Non-activated conditions: 

0, 125, 250, 500, 1250, 

2500 and 5000 μg/plate

Activated conditions: 

0, 125, 250, 500, 1250, 

2500 and 5000 μg/plate

There was no evidence of induced mutant 

colonies over background.
Teflubenzuron Human Health Risk Assessment D426404

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Table A.2.2. Subchronic, Chronic, and Other Toxicity Profile.

Guideline 

No. 

Study Type MRID No. (year)/ 

Classification/Doses

Results

870.5100 Bacterial Mutation 

Assay In S. 

typhimurium And 

E .coli

49168815 (1982)

Acceptable /guideline

Non-activated conditions: 

0, 25, 50, 125, 250, 500 

and 1000 μg/plate

Activated conditions: 

0, 25, 50, 125, 250, 500

Third test: 0, 25, 50, 75, 

100, 125, 150, 200, 250, 

300, 350, 400, 450 and 

500 μg/plate

There was no evidence of induced mutant 

colonies over background.

870.5100 In vitro Bacterial 

Gene Mutation In 

Salmonella 

typhimurium and 

E. coli

49168817 (2003)

Acceptable /guideline

0, 5, 17, 50, 167, 500 and 

1667 μg/plate ± S9

There was no evidence of induced mutant 

colonies over background.

870.5300 In Vitro

Mammalian Cell 

Gene Mutation 

Test

49168816 (1986)

Acceptable /guideline

0, 5, 10, 25 and 50 μg/mL 

± S9 

Either without or with S9 activation, the test 

article did not induce a mutagenic response in 

Chinese hamster V79 cells at any concentration 

level. There was no evidence of induced 

mutant colonies over background.

870.5735 In Vitro

Cytogenetics

49168817 (1985)

Acceptable /guideline

0 and 50 μg/mL (7-hour 

preparation time) 

0, 4, 25 and 50 μg/mL 

(18-hour preparation time) 

0 and 50 μg/mL (28-hour 

preparation time)

Without or with S9 activation, there was no 

increase in the percent of aberrant cells, 

including or excluding gaps, or in the percent 

of cells with exchanges, among the cells that 

were treated with the test article using a 7, 18,

or 28-hour preparation interval. All of the 

positive controls gave appropriate responses. 

There was no evidence of chromosome 

aberrations induced over background.

870.5395 In vivo

Mammalian 

Cytogenetics -

Erythrocyte 

Micronucleus 

assay

49168818 (1983)

Acceptable /guideline

5000 mg/kg bw (M/F)

There was not a significant increase in the 

frequency of micronucleated polychromatic 

erythrocytes in bone marrow after any 

treatment condition in either sex.

870.5550 Unscheduled 

DNA Synthesis in 

Primary Rat 

Hepatocytes/Mam

malian Cell 

Culture

49168818 (1986)

Acceptable /guideline

0, 0.4, 1.0, 4.0, 10.0, 40.0 

and 100.0 μg/mL for 3 h 

(preliminary cytotoxicity 

assay)

0, 1.0, 3.3, 10.0, 33.0 and 

100.0 μg/mL, for 3 hours 

(main assay)

There was no evidence that unscheduled DNA 

synthesis, as determined by unscheduled 

incorporation of (3H)-Tdr into hepatocyte DNA 

[(3H)-Tdr dpm/μg DNA], was induced.

870.6200a Acute 

neurotoxicity 

screening battery

49168820 (2010)

Acceptable /guideline

0, 125, 500, or 2000 

mg/kg

Systemic NOAEL = 2000 mg/kg/day.

Systemic LOAEL was not established.

Neurotoxicity NOAEL = 2000 mg/kg/day.

Neurotoxicity LOAEL was not established.

870.6200b Subchronic 

neurotoxicity 

screening battery

49168821 (2011)

Acceptable /guideline

0, 100, 300 or 1000 mg/kg 

bw/day

Systemic NOAEL = 1000 mg/kg/day.

Systemic LOAEL was not established.

Neurotoxicity NOAEL = 1000 mg/kg/day.

Neurotoxicity LOAEL was not established.

870.7485 Metabolism and 

pharmacokinetics

(rats)

46198823, 49168824, 

49168825, 49168826 

(1984, 1986, 1985 and 

Regarding absorption, following a single oral 

dose of 25 mg/kg bw, the Cmax was 0.46 μg/mL

and the Tmax was 8 hours for males. For 
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Table A.2.2. Subchronic, Chronic, and Other Toxicity Profile.

Guideline 

No. 

Study Type MRID No. (year)/ 

Classification/Doses

Results

1987)

Acceptable /guideline

25 (single and repeated) 

and 750 mg/kg bw 

(single)

females, the Cmax was 0.25 μg/mL and the Tmax

ranged from 2 to 8 hours. From the 1 to the 8 

hours post dosing, nearly constant plasma 

levels were found and started to decline at 

twenty-four hours. Plasma concentrations 

declined to less than 0.01 μg equivalents/mL in 

both sexes at the end of the experimental period 

(7 days). 

Following single oral dosing at 750 mg/kg bw, 

the Cmax was 3.27 μg/mL and the Tmax was 24 

hours. For females, the Cmax was 1.43 μg/mL

and the Tmax was 0.67 hours. The second day 

after treatment, the plasma levels declined to 

0.06 and 0.08 μg equivalents/mL in male and 

female rats by the end of the 7 days, 

respectively. 

Individual average biliary excretion values for 

the single low-dose for males and females were 

17.04 ± 0.04 % and 15.28 ± 5.18 % of the total 

absorbed dose. For the high-dose of 750 mg/kg 

bw, the values for males and females were 1.64 

± 0.94 % and 2.12 ± 0.21 % respectively 

suggesting saturation of absorption from the GI 

tract.

Tissue accumulation and distribution was 

negligible for both sexes treated with 

radiolabeled test material for 7 consecutive 

days, being less than 1% of the administered 

dose at all intervals. The highest detectable 

levels of the radiolabel were in the liver (~0.23-

0.33% for both sexes) which peaked from 1 to 

6 hours and then gradually decreased. All other 

tissues were less than 0.1%.

The majority of the radiolabel was recovered in 

the feces (>90%), and was identified as the 

parent compound. Three metabolites were 

isolated. Two products were structural isomers 

formed by hydroxylation of the benzoyl ring at 

positions 3 and 4, while the remaining 

metabolite was formed by substitution of one 

fluorine atom by hydroxide, likely on the 

aniline ring. Biliary extracts showed metahydroxylation of the benzoyl ring followed by 

conjugation was the predominant pathway. 

Only very small amounts of radioactivity coeluted with the hydroxylated-aniline derivatives 

of teflubenzuron while hydrolytic treatments of 

bile indicated that phenyl urea may also be 

present as a sulfate conjugate.

Regarding excretion, following single low

dosing of bile-duct cannulated rats, for both 

sexes radioactivity excreted in the 0- to 48-hour 

interval yielded 45.43-46.60% excretion of the 

administered dose in the feces, 15.28-17.04% 

in the bile, and 1.26-1.54% in the urine. 

Following a single high dosing of bile ductcannulated rats, radiolabel excreted in the 0- to 
Teflubenzuron Human Health Risk Assessment D426404

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Table A.2.2. Subchronic, Chronic, and Other Toxicity Profile.

Guideline 

No. 

Study Type MRID No. (year)/ 

Classification/Doses

Results

48-hour interval, in both sexes, feces accounted 

for 57.91-71.77% of the administered dose, 

1.64-2.12% in the bile, and 0.29-0.40% in the 

urine.

870.7800 Immunotoxicity 

(mouse)

49168822 (2011)

Acceptable /guideline

0, 200, 1000, or 5000 ppm

(0, 44, 218, or 1059 

mg/kg bw/day [M])

Systemic NOAEL was ≥ 5000 ppm (equivalent 

to 1059 mg/kg bw/day).

The systemic LOAEL for dietary 

administration not identified.

Immunotoxicity NOAEL was ≥ 5000 ppm 

(equivalent to 1059 mg/kg bw/day).

The immunotoxicity LOAEL was not 

identified.

A.3 Hazard Identification and Endpoint Selection

A.3.1 Chronic Reference Dose (cRfD) `

Study Selected: Carcinogenicity - mice, feeding

MRID No.: 49168813

Executive Summary: In a carcinogenicity study (MRID 49168813), teflubenzuron (92.4±0.9% 

ai, batch no. DW 44/83) was administered to 60 NMRI mice/sex/dose in the diet at dose levels of 

0, 15, 75, or 375 ppm (equivalent to 0, 2.1, 10.5, and 53.6 mg/kg bw/day for males and 0, 3.1, 

15.4, and 71.7 mg/kg bw/day for females) for 78 weeks. Ten mice/sex/dose were sacrificed at 52 

weeks for interim evaluations. Evaluated parameters included mortality, clinical signs, body 

weight, body weight gain, food consumption, ophthalmoscopic examination, hematology, 

clinical chemistry, organ weights, and gross and histopathological examination. 

In all three dose groups, no treatment-related effects were observed on the following parameters: 

mortality, clinical signs, body weight, body weight gain, food consumption, ophthalmoscopic 

examination, and hematology parameters. 

At 75 ppm, the incidences of centrilobular cell necrosis and Kupffer cell proliferation were 

significantly increased (80% and 50% vs. 0% in the controls) at 52 weeks. At the terminal 

sacrifice, the incidences of diffuse hypertrophy (44% vs. 0% in the control), centrilobular singlecell necrosis (52% vs. 16% in the control), patchy glycogen storage (34% vs. 2% in the control), 

Kupffer cell proliferation (50% vs. 4% in the control) and phagocytic foci (70% vs. 26% in the 

control) were significantly increased in the males. A trend for increasing incidence of 

phagocytic foci was also observed in females (50 vs. 40% in the control). 

At 375 ppm, statistically significant increases were observed in the activities of aspartate 

aminotransferase (↑130-168%), alanine aminotransferase (329-583%), and ornithine carbamyl 

transferase (↑398-549%) in males at 52 and 78 weeks. Alkaline phosphatase activity was 

increased 100% and lactate dehydrogenase was increased 125% in males at 52 weeks. In 

females, alanine aminotransferase activity was significantly increased 124-196% at 52 and 78 

weeks and lactate dehydrogenase activity was significantly increased 66% at 78 weeks. At the 

interim sacrifice at 52 weeks, absolute and relative (to body and brain weights) liver weights 
Teflubenzuron Human Health Risk Assessment D426404

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were increased 30-40% in both sexes, compared to controls. By the terminal sacrifice at 78 

weeks, absolute and relative (to body and brain weights) liver weights in males were increased 

65-70% and 27-28% in females. 

At 52 weeks, several liver lesions were found including diffuse hypertrophy (60% vs. 10% in the 

control), single-cell necrosis (80% vs. 0% in the control), patchy glycogen storage (70% vs. 0% 

in the control), Kupffer cell necrosis (80% vs. 0% in the control), and phagocytic foci. There 

was a trend for increasing incidence of phagocytic foci (80% vs. 40% in the control). In females 

sacrificed at 52 weeks, a significantly increased incidence of patchy fatty changed was observed 

(90% vs. 0% in the control). A trend for increasing incidence of phagocytic foci was also 

observed for females in the mid- and/or high-dose groups (80% vs. 40% in the control). At the 

terminal sacrifice, the incidences of diffuse hypertrophy (84% vs. 0% in the control), 

centrilobular single-cell necrosis (80% vs. 16% in the control), patchy glycogen storage (76% vs. 

2% in the control), Kupffer cell proliferation (70% vs. 4% in the control) and phagocytic foci 

(92% vs. 26% in the control) were significantly increased in the males. Furthermore in males, 

the incidences of nodular hyperplasia (20% vs. 6% in the control), disseminated single-cell

necrosis (40% vs. 8% in the control), lipofuscin accumulation (50% vs. 16% in the control) and

bile duct proliferation (20% vs. 0% in the control) were also significantly increased. In females, 

there was a significant increase in the incidences and severity of diffuse hypertrophy (30% vs. 

2% in the control), disseminated single-cell necrosis (48% vs. 4% in the control), patchy 

glycogen storage (10% vs. 0% in the control), Kupffer cell proliferation (24% vs. 4% in the 

control), phagocytic foci (64% vs. 32% in the control), lipofuscin accumulation (20% vs. 0% in 

the control), and patchy fatty change (42% vs. 2% in the control). 

At the doses tested, there was a treatment-related increase in tumor incidence of hepatocellular 

adenomas in males of the high-dose group when compared to controls. The incidence of 

hepatocellular adenomas was 6/50, 5/50, 11/50, and 16/50 at 0, 15, 75, and 375 ppm, 

respectively. There was no treatment-related effect on the time to appearance of liver tumors. 

Dosing was considered adequate based on microscopic liver lesions in both sexes. Lastly the 

concurrent control was consistent with the historical control.

The LOAEL in male mice is 75 ppm (10.5 mg/kg bw/day), based on increased microscopic 

lesions in the liver (diffuse hypertrophy, centrilobular single-cell necrosis, patchy glycogen 

storage, Kupffer cell proliferation, phagocytic foci, and centrilobular fatty change) 

associated with increased relative liver weight. The NOAEL is 15 ppm (2.1 mg/kg bw/day). 

The LOAEL in female mice is 375 ppm (71.7 mg/kg bw/day), based on increased 

microscopic lesions in the liver (diffuse hypertrophy, disseminated single-cell necrosis, 

patchy glycogen storage, Kupffer cell proliferation, phagocytic foci, lipofuscin 

accumulation, and patchy fatty change) with associated increased absolute and relative 

liver weights and increased alanine aminotransferase and lactate dehydrogenase activities. 

The NOAEL is 75 ppm (15.4 mg/kg bw/day).

Dose and Endpoint for Risk Assessment: NOAEL = 2.1 mg/kg/day based on increased 

microscopic lesions in the liver (diffuse hypertrophy, centrilobular single-cell necrosis, patchy 

glycogen storage, Kupffer cell proliferation, phagocytic foci, and centrilobular fatty change) 

associated with increased relative liver weight at the LOAEL = 10.5 mg/kg/day.

Comments about Study/Endpoint/UFs: This study provides the most protective point of 

departure in the hazard database with a NOAEL of 2.1 mg/kg/day. A total UF of 100X (10X for 

interspecies extrapolation, 10X for intraspecies variability, and a 1X FQPA SF) was applied to 
Teflubenzuron Human Health Risk Assessment D426404

Page 26 of 30

this NOAEL generating a cPAD of 0.021 mg/kg/day. This study is appropriate for the duration 

of exposure. It protects for the offspring effects in the two-generation reproductive study and it 

is protective of the general U.S. population.
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Appendix B. Metabolism Considerations

B.1. Metabolism Summary Table

Table B.1.1. Tabular Summary of Metabolites and Degradates.

Chemical Name (Other Names in 

Parenthesis) and Structure Matrix

Percent TRR (ppm)

Matrices - Major Residue 

(>10% TRR)

Matrices - Minor Residue 

(<10% TRR)

Teflubenzuron Spinach 77-99 (0.083-13.5)

Apple Fruit: 97.3 (1.23)

Leaves: 99.9 (81.5)

Potato Tops: 99.2 (6.07)

Cotton Leaves: 96 (24.1)

Rotational Crops Identified in soil

Ruminant Milk: 4.2 (<0.001)

Poultry Egg Yolk: 80.1 (0.684)

Liver: 26.8 (0.090)

Fat: 94.0 (1.025)

Kidney: 27.1 (0.047)

Rat Feces: 60-90% AD

Water N/A N/A

Metabolite 3381 Ruminant Liver: 0.5 (0.002)

Poultry

Rat Trace amounts in the urine

Water N/A N/A

Metabolite E15

3,5-dichloro-2,4-difluorophenyl urea

Rotational Crops Identified in soil

Ruminant

Poultry Kidney: 11.5 (0.020)

Rat Trace amounts in the feces

Water N/A N/A

3,5-dichloro-2,4-difluoroaniline Rotational Crops Identified in soil

Ruminant

Poultry

Rat

Water N/A N/A

Ruminant

Poultry

Rat Trace amounts in the urine

Water

Ruminant
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Table B.1.1. Tabular Summary of Metabolites and Degradates.

Chemical Name (Other Names in 

Parenthesis) and Structure Matrix

Percent TRR (ppm)

Matrices - Major Residue 

(>10% TRR)

Matrices - Minor Residue 

(<10% TRR)

Poultry

Rat Trace amounts in the urine

Water

Spinach; 49168727; 0.0892 lb ai/A; 1.4X the proposed rate for broccoli; immature & mature leaves; 18-hour, 15-day, and 

30-day PHI.

Apple; 42727332; 0.0019 lb ai/gal/application; fruit & leaves; 30-day PHI.

Potato; 42727333; 0.324 lb ai/A; tubers & leaves; 25-day PHI.

Cotton; 42727334; 0.24 lb ai/A; lint, seeds, & leaves; 14-day PHI.

Goats; 42727336 & MRID 42727337; 25 ppm; 64X MTDB; 8 days.

Laying Hen; 42727338 & MRID 42727339; 25 ppm; 1800X MTDB; 8 days.

Rotational Crops; 49168780 & 49168781; 2.2X, applied to bare soil; lettuce, carrot, and wheat; 28/30, 120/121, and 

365/374 days PBI.

Rat Metabolism; 49168823-26; 25 mg/kg bw/day; Chbb:THOM, 24-192 hr. depuration.
Teflubenzuron Human Health Risk Assessment D426404

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B.2 Metabolic Pathways

Figure B.2.1. Proposed Metabolic Pathway for Animals (copied from Section D of the Tolerance Petition).
Teflubenzuron Human Health Risk Assessment D426404

Page 30 of 30

Appendix C. Physical/Chemical Properties

Table C. Physicochemical Properties of the Teflubenzuron TGAI.

Parameter Value Reference

Molecular weight (g/mole) 381.1 EFSA Scientific Report 

(2008) 184, 50-51

Conclusion on the peer 

review of teflubenzuron

Melting point/range (°C) 225-229°C

Water solubility (mg/L 20°C) <0.01 (pH 5)

<0.01 (pH 7)

0.11 (pH 9)

Solvent solubility (g/L at 20°C) n-Heptane: 0.01

Toluene: 0.74

1,2-Dichloromethane: 1.51

Methanol: 1.06

Acetone: 8.85

Ethyl acetate: 6.28

Vapor pressure at 20°C 6.87 x 10-9 mm Hg

Dissociation constant (pKa) 9.7

Octanol/water partition coefficient at 20°C 

Log(KOW)

4.98 (pH 5)