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UNITED STATES ENVIRONMENTAL PROTECTION AGENCY

WASHINGTON, D.C. 20460

OFFICE OF

CHEMICAL SAFETY AND

POLLUTION PREVENTION

MEMORANDUM

Date: 18-JUN-2015

SUBJECT: Novaluron: Human Health Risk Assessment for the Petition for the 

Establishment of Permanent Tolerances for Residues of Novaluron in/on 

Avocado; Carrot; Succulent Bean; Vegetable, Fruiting, Crop Group 8-10; Fruit, 

Pome, Crop Group 11-10; Cherry Subgroup 12-12A; Peach Subgroup 12-12B; 

and Plum Subgroup 12-12C; and Revisions to the Label to Include Uses on 

Greenhouse-Grown Cucumber. 

PC Code: 124002 DP Barcode: D426068

Decision No.: 487502 Registration No.: 66222-35

Petition No.: 4E8241 Regulatory Action: Section 3

Risk Assessment Type: Single Chemical/Aggregate Case No.: 7615

TXR No.: NA CAS No.: 116714-46-6

MRID No.: NA 40 CFR: §180.598

FROM: Julie L. Van Alstine, MPH, Environmental Health Scientist

Anwar Y. Dunbar, Ph.D., Pharmacologist

Lata Venkateshwara, Environmental Scientist

Risk Assessment Branch 1 (RAB1)

Health Effects Division (HED; 7509P)

THROUGH: Charles W. Smith III, Branch Chief

George F. Kramer, Ph.D., Branch Senior Chemist 

RAB1/HED (7509P)

TO: Barbara Madden (RM 05)/Laura Nollen/Sidney Jackson

Registration Division (RD; 7505P) 

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

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

exposure data and conduct dietary, occupational, residential, and aggregate exposure 

assessments, as needed, to estimate the risk to human health that will result from all registered 

and proposed uses of novaluron (N-[[[3-chloro-4-[1,1,2-trifluoro-2-(trifluoromethoxy)ethoxy] 

phenyl]amino]carbonyl]-2,6-difluorobenzamide). A summary of the findings and an assessment 

of human risk resulting from the registered and proposed uses for novaluron are provided in this 

document. The risk assessment was provided by Julie Van Alstine (RAB1), the occupational and 

residential exposure assessments were provided by Lata Venkateshwara (RAB1), the hazard 

characterization was provided by Anwar Dunbar (RAB1), the drinking water assessment was 
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provided by He Zhong of the Environmental Fate and Effects Division (EFED), and the dietary

assessment was provided by Richard Duncan of the Department of Pesticide Regulation at the 

California Environmental Protection Agency.

The most recent human health risk assessment was conducted in conjunction with a request for 

the use of novaluron to control pests on furniture, in animal quarters, carpets, kennels, livestock 

and poultry houses, food and non-food warehouses, in food-handling establishments, around 

perimeters, and lawns (Memo, J. Van Alstine, et al., 05-FEB-2014; D409210). 
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Table of Contents

1.0 Executive Summary............................................................................................................. 5

2.0 HED Recommendations....................................................................................................... 7

2.1 Data Deficiencies ............................................................................................................. 7

2.2 Tolerance Considerations................................................................................................. 7

2.2.1 Enforcement Analytical Method .................................................................................. 7

2.2.2 Recommended Tolerances............................................................................................ 8

2.2.3 Revisions to Petitioned-For Tolerances........................................................................ 9

2.2.4 International Harmonization......................................................................................... 9

2.3 Label Recommendations................................................................................................ 10

3.0 Introduction........................................................................................................................ 10

3.1 Chemical Identity ........................................................................................................... 10

3.2 Physical/Chemical Characteristics................................................................................. 10

3.3 Pesticide Use Pattern...................................................................................................... 11

3.4 Anticipated Exposure Pathways..................................................................................... 12

3.5 Consideration of Environmental Justice ........................................................................ 12

4.0 Hazard Characterization and Dose-Response Assessment................................................ 13

4.1 Toxicology Studies Available for Analysis ................................................................... 13

4.2 Absorption, Distribution, Metabolism, and Excretion (ADME).................................... 13

4.3 Toxicological Effects ..................................................................................................... 13

4.4 Safety Factor for Infants and Children (FQPA Safety Factor)....................................... 14

4.4.1 Completeness of the Toxicology Database ................................................................ 14

4.4.2 Evidence of Neurotoxicity.......................................................................................... 14

4.4.3 Evidence of Sensitivity/Susceptibility in the Developing or Young Animal............. 14

4.4.4 Residual Uncertainty in the Exposure Database......................................................... 15

4.5 Toxicity Endpoint and Point of Departure Selections.................................................... 15

4.5.1 Dose-Response Assessment ....................................................................................... 15

4.5.2 Recommendation for Combining Routes of Exposures for Risk Assessment ........... 16

4.5.3 Cancer Classification and Risk Assessment Recommendation.................................. 16

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

Assessment................................................................................................................................ 16

5.0 Dietary Exposure and Risk Assessment ............................................................................ 18

5.1 Residues of Concern Summary and Rationale............................................................... 18

5.2 Food Residue Profile...................................................................................................... 19

5.3 Water Residue Profile .................................................................................................... 20

5.4 Dietary Risk Assessment................................................................................................ 21

5.4.1 Description of Residue Data Used in Dietary Assessment......................................... 21

5.4.2 Percent Crop Treated Used in Dietary Assessment.................................................... 22

5.4.3 Acute Dietary Risk Assessment ................................................................................. 22

5.4.4 Chronic Dietary Risk Assessment .............................................................................. 22

5.4.5 Cancer Dietary Risk Assessment................................................................................ 22

5.4.6 Summary Table........................................................................................................... 22

6.0 Residential (Non-Occupational) Exposure/Risk Characterization .................................... 23

6.1 Residential Handler Exposure and Post-Application Exposure..................................... 23

6.2 Combined Residential Risk Estimates........................................................................... 24

6.3 Residential Risk Estimates for Use in Aggregate Assessment ...................................... 24

6.4 Spray Drift...................................................................................................................... 27

6.5 Residential Bystander Post-Application Inhalation Exposure ....................................... 27
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7.0 Aggregate Exposure/Risk Characterization....................................................................... 27

7.1 Short-Term Aggregate Risk ........................................................................................... 28

7.2 Intermediate- and Long-Term Aggregate Risk .............................................................. 28

8.0 Cumulative Exposure/Risk Characterization..................................................................... 29

9.0 Occupational Exposure/Risk Characterization .................................................................. 29

9.1 Short-/Intermediate-Term Handler Risk ........................................................................ 29

9.2 Short-/Intermediate-Term Post-Application Risk .......................................................... 33

9.2.1 Inhalation Post-application Risk................................................................................. 33

9.2.2 Dermal Post-application Risk..................................................................................... 33

10.0 References.......................................................................................................................... 34

Appendix A. Toxicology Profile and Executive Summaries....................................................... 36

A.1 Toxicology Data Requirements...................................................................................... 36

A.2 Toxicity Profiles............................................................................................................. 37

Appendix B. Physical/Chemical Properties................................................................................. 41

Appendix C. Review of Human Research ................................................................................... 41
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1.0 Executive Summary

Background: Novaluron, a benzoylphenyl urea compound, is a pesticide chemical belonging to 

the class of insecticides called insect-growth regulators (IGRs). Tolerances for residues of 

novaluron are established under 40 CFR §180.598 in/on a wide variety of crops at levels ranging 

from 0.01 to 50 ppm. Tolerances for residues of novaluron are also established in/on the 

following livestock commodities: eggs, milk, milk fat, and the meat, fat, kidney, liver, and meat 

byproducts (except kidney and liver) of cattle, goat, horse, sheep, poultry, and hog. 

Additionally, novaluron is registered for use in food and feed handling establishments, and a 

tolerance of 0.01 ppm has been established for residues of novaluron in/on food and feed 

commodities other than those covered by a higher tolerance as a result of use on growing crops.

The Interregional Research Project No. 4 (IR-4) has submitted a Section 3 request for the 

proposed new uses of novaluron on avocado and carrot, to expand the use pattern for succulent 

beans, to update crop group commodity definitions for fruiting vegetable group 8-10, pome fruit 

group 11-10, cherry subgroup 12-12A, peach subgroup 12-12B, and plum subgroup 12-12C, and 

to add greenhouse-grown cucumbers to the label. The end-use product associated with these 

registration requests is Rimon®0.83EC Insecticide (EPA Reg. No. 66222-35) which contains 

9.3% ai by weight [equivalent to 0.83 pound (lb) ai/gallon (gal)]. A tolerance may now be 

established for residues of novaluron in/on bean, succulent based on the newly submitted lima 

bean field trial data and the previously submitted succulent snap bean field trial data. Since the 

proposed application scenarios for the updated croup group commodity definitions of fruiting 

vegetable group 8-10, pome fruit group 11-10, cherry subgroup 12-12A, peach subgroup 12-12B, 

and plum subgroup 12-12C are identical or lower than the rates previously reviewed, no residue 

data were submitted for these commodities and none are required. A tolerance has already been 

established for residues of novaluron in/on cucurbit vegetable group 9; however, use of 

novaluron on greenhouse-grown cucumbers was prohibited. The petitioner has provided field 

trial data for greenhouse-grown cucumbers to expand the use pattern to include greenhousegrown cucumbers. 

Hazard Assessment: In subchronic and chronic toxicity studies, novaluron primarily produced 

hematotoxic effects (toxicity to blood) such as methemoglobinemia, decreased hemoglobin, 

decreased hematocrit, and decreased red blood corpuscles (RBCs or erythrocytes) that were 

associated with compensatory erythropoiesis. No maternal and/or developmental toxicity was 

observed in animals in either the rat or the rabbit developmental toxicity studies. In the twogeneration reproductive toxicity study, increased spleen weights were observed in parents and 

offspring at the same dose, and reproductive toxicity was observed in males only at a higher 

dose. Neurotoxic effects, including clinical signs, changes in functional-observation battery

(FOB) parameters, and neuropathology were observed following a single dose at the limit dose 

only (2000 mg/kg/day) in the acute neurotoxicity study in rats. However, no signs of 

neurotoxicity or neuropathology were observed following repeated dosing in the subchronic 

neurotoxicity study in rats at similar doses and there was no evidence of neuropathology

observed in subchronic and chronic toxicity studies in rats, mice, or dogs. Novaluron has low 

acute toxicity via the oral (Toxicity Category IV), dermal (Toxicity Category III), and inhalation 

routes (Toxicity Category IV). No ocular (Toxicity Category IV) or dermal irritation (Toxicity

Category IV) was noted. Novaluron is not a dermal sensitizer. Potential signs of 

immunotoxicity occurred at twice the limit dose and consisted only of a decreased anti-sheep red 

blood cell (SRBC) response in female rats. There was no evidence of either carcinogenic or 
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genotoxic potential and novaluron has been classified as “not likely to be carcinogenic to 

humans” based on the lack of evidence for carcinogenicity in mice and rats. 

Consistent with previous risk assessments for novaluron, the novaluron risk assessment team 

recommends that the 10X Food Quality Protection Act Safety Factor (FQPA SF) be reduced to 

1X for all exposure scenarios, as discussed in Section 4.4.

Food Residue Profile: The nature of the residue in plants and livestock is adequately 

understood. The Organization for Economic Co-operation and Development (OECD) tolerancecalculation procedures and the submitted residue data sets were used to calculate the HEDrecommended tolerances. There is an adequate residue analytical method for the purposes of 

tolerance enforcement. The submitted field trial residue data are adequate, and provided that the 

data deficiencies identified in Section 2.1 are addressed, there are no residue chemistry issues 

that would preclude establishing permanent tolerances for residues of novaluron in the raw 

agricultural commodities (RACs) outlined in Table 2.2.2. The U.S., Canadian, and Codex 

residue definitions are harmonized. HED has considered harmonization in the tolerance 

recommendations that are presented in Table 2.2.2.

Exposure/Risk Assessment Characterization: An acute dietary assessment was not conducted 

for novaluron because an endpoint of concern attributable to a single dose was not identified. A 

chronic risk assessment was conducted for dietary (food and drinking water) exposure based on 

the existing and proposed uses. The chronic assessment directly incorporated drinking water 

estimates provided by EFED. Assumptions for the chronic dietary assessment included average 

field trial residues for the majority of commodities, anticipated residues (ARs) for meat, milk, 

hog, and poultry commodities, average percent crop treated (PCT) data for apples, blueberries, 

cabbage, cauliflower, cotton, dry beans, pears, peppers, potatoes, strawberries, and tomatoes, and 

percent crop treated for new use (PCTn) data for the recently registered grain sorghum and sweet 

corn uses. For the remaining food commodities, 100% PCT was assumed. The registered foodhandling use was also incorporated into the dietary assessment. Empirical processing factors for 

apple juice (translated to pear and stone fruit juice), cottonseed oil, dried plums, and tomato paste 

and purée, and DEEM (ver. 7.81) default processing factors for the remaining processed 

commodities were also used. All exposure and risk estimates were not of concern. A cancer 

dietary assessment was not conducted because novaluron is classified as “not likely to be 

carcinogenic to humans.”

The currently registered residential uses (indoor spot/crack and crevice, outdoor perimeter, pet 

spot-on, etc.) are expected to result in dermal and inhalation exposures for adults (handlers and 

post-application) and post-application dermal, incidental oral, and inhalation exposures for 

children (1 to <2 years old). The dermal route of exposure was not quantitatively assessed 

because a dermal endpoint was not selected for any exposure duration. These registered uses 

were previously updated in the February 2014 risk assessment to reflect use of the 2012 

Residential Standard Operating Procedures (SOPs). All residential handler (adult) and postapplication (adult and children) scenarios resulted in margins of exposure (MOEs) greater than 

100 and are not of concern to HED. 

For the proposed and registered uses, human health aggregate risk assessments have been 

conducted for short- and intermediate-/long-term aggregate exposure (food + drinking water + 

residential) scenarios. An acute aggregate assessment was not conducted for novaluron because 

an endpoint of concern attributable to a single dose was not identified. A cancer aggregate risk 
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assessment was not performed because novaluron was classified as “not likely to be carcinogenic 

to humans.” All potential exposure pathways were assessed in the aggregate risk assessment as a 

conservative, health-protective measure. No aggregate risk estimates exceed HED’s level of 

concern (LOC) for the scenarios listed above. 

Based on the proposed uses, occupational exposures to novaluron are expected for short- and 

intermediate-term durations during mixing, loading, applying, and other handling activities. 

Short- and intermediate-term inhalation risks do not exceed HED’s LOC (i.e., all MOEs were 

greater than 100 for short- and intermediate-term exposures) at baseline personal-protective 

equipment (PPE). A quantitative occupational post-application inhalation exposure assessment 

was not performed. Handler exposure resulting from application of pesticides outdoors is likely

to result in higher exposure than post-application exposure. Therefore, it is expected that the

handler inhalation exposure estimates would be protective of most occupational post-application 

inhalation exposure scenarios. The dermal route of exposure was not quantitatively assessed for 

handler and post-application exposure because a dermal endpoint was not selected for any 

exposure duration. 

This risk assessment relies in part on data from studies in which adult human subjects were 

intentionally exposed to a pesticide or other chemical. Please refer to Appendix C for a 

discussion of the human study data used in this risk assessment. 

2.0 HED Recommendations

Pending resolution of the deficiencies outlined in Section 2.1, there are no other residue 

chemistry, residential, occupational, or toxicology data deficiencies that would preclude granting 

a registration for the requested uses of Rimon®0.83EC Insecticide and the establishment of 

permanent tolerances under 40 CFR §180.598 (a) as outlined in Table 2.2.2. 

2.1 Data Deficiencies

860.1650 Submittal of Analytical Reference Standards

An analytical standard for novaluron is currently available in the National Pesticide Standards 

Repository (personal communication with Theresa Cole, 29-JAN-2015); however, the standard 

expired on 07-MAR-2015. A new reference standard should be sent to the Analytical Chemistry

Lab, which is located at Fort Meade, to the attention of either Theresa Cole or Thuy Nygen at the 

following address:

USEPA

National Pesticide Standards Repository/Analytical Chemistry Branch/OPP

701 Mapes Road

Fort George G. Meade, MD 20755-5350

(Note that the mail will be returned if the extended zip code is not used.)

2.2 Tolerance Considerations

2.2.1 Enforcement Analytical Method
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Makhteshim-Agan of North America (MANA) previously submitted under PP#2F6430 a gas 

chromatography/electron-capture detection (GC/ECD) residue analytical method for the analysis 

of residues of novaluron in/on pome fruit, cabbage, and potato commodities. A second method, 

high-performance liquid chromatography/ultraviolet (HPLC/UV), was also submitted for the 

analysis of novaluron residues only in/on cotton commodities. Successful independent 

laboratory validations (ILVs) of the GC/ECD and HPLC/UV methods have been completed with 

apples and undelinted cottonseed, respectively. Acceptable radiovalidation data have been 

submitted and reviewed in D325183 for the GC/ECD method. An interference study was 

requested and a specific single-analyte confirmatory method was submitted, reviewed, and 

considered acceptable (Memo, J. Langsdale, 21-OCT-2008; D355574).

The Analytical Chemistry Branch (ACB) of the Biological and Economics Analysis Division 

(BEAD) concluded that based upon review of the submitted method validation data, without 

laboratory validation, that the GC/ECD and HPLC/UV methods appear suitable for food 

tolerance enforcement in plants and cotton. The ACB recommended that the analytical methods 

do not need to be laboratory validated by EPA (Memo, S. Levy, 15-SEP-2004; D306998). Both 

methods have been forwarded to the FDA for inclusion in the Pesticide Analytical Method 

Volume II (PAM II) as a Letter Method (Letter, S. Levy to the FDA, 15-SEP-2004; D307595).

2.2.2 Recommended Tolerances

The proposed uses and the submitted data support the permanent tolerances for residues of the 

insecticide novaluron, including its metabolites and degradates, in or on the commodities listed 

in Table 2.2.2. Compliance with the tolerance levels specified below is to be determined by

measuring only novaluron (N-[[[3-chloro-4-[1,1,2-trifluoro-2-

(trifluoromethoxy)ethoxy]phenyl]amino]carbonyl]-2,6-difluorobenzamide).

A revised Section F is required for PP# 4E8241 which cites the appropriate CAS name for 

novaluron (N-[[[3-chloro-4-[1,1,2-trifluoro-2-(trifluoromethoxy)ethoxy]phenyl]amino]carbonyl]-

2,6-difluorobenzamide) and reflects the recommended tolerances and commodity definitions 

presented in Table 2.2.2.

Table 2.2.2. Tolerance Summary for Novaluron.

Commodity Proposed 

Tolerance (ppm)

HED-Recommended 

Tolerance (ppm)

Comments; 

Correct Commodity Definition

Avocado 0.60 0.60

Carrot 0.05 0.05

Bean 0.60 0.70

Harmonize with Codex MRL 

Bean, succulent1

Vegetable, fruiting, group 8-

102 1.0 1.0

Fruit, pome, group 11-1032.0 3.0 Harmonize with Codex MRL 

Cherry subgroup 12-12A48.0 8.0

Peach subgroup 12-12B51.9 1.9

Plum subgroup 12-12C51.9 1.9

Vegetable, cucurbit, group 9 -- 0.20 Harmonize with Codex MRL 

Plum, prune, dried -- 3.0 Harmonize with Codex MRL 

1

This tolerance will replace the existing tolerance of 0.60 ppm on bean, succulent, snap. The dry bean tolerance 

will not be impacted. 
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2 This tolerance will replace the existing tolerances of 1.0 ppm on vegetable, fruiting, group 8, and also cocona, 

African eggplant, pea eggplant, scarlet eggplant, goji berry, garden huckleberry, martynia, naranjilla, okra, roselle, 

sunberry, bush tomato, currant tomato, and tree tomato. 

3 This tolerance will replace the existing tolerance of 2.0 ppm on fruit, pome, group 11. 

4 This tolerance will replace the existing tolerance of 8.0 ppm on cherry. 

5 These tolerances will replace the existing tolerance of 1.9 ppm on fruit, stone, group 12, except cherry.

2.2.3 Revisions to Petitioned-For Tolerances

The OECD calculator and available data support a tolerance of 0.70 ppm for residues of 

novaluron in/on lima beans. A tolerance is currently established for residues of novaluron in/on 

bean, snap, succulent at 0.60 ppm and the petitioner has requested a crop group tolerance for 

“beans.” Based on the available data, a tolerance should be established for residues of novaluron 

in bean, succulent and HED is recommending for a tolerance value of 0.70 ppm in order to 

harmonize with the established Codex tolerance of 0.7 ppm for residues of novaluron in common 

beans (pods and/or immature seeds). This recommendation will not impact the tolerance 

established for residues in/on dry beans. 

No new pome fruit crop field trial data were submitted. The petitioner has requested that the 

existing tolerance be expanded to fruit, pome, group 11-10. HED recommends that the U.S. 

tolerance be increased from 2.0 to 3.0 ppm in order to harmonize with Codex. 

The OECD tolerance calculator and the submitted greenhouse-grown cucumber data support a 

tolerance of 0.15 ppm for residues of novaluron in greenhouse-grown cucumbers, which is the 

same as the established tolerance for residues of novaluron in/on vegetable, cucurbit, group 9. 

Codex has established a tolerance for residues of novaluron in fruiting vegetable cucurbits at 0.2 

ppm; therefore, HED is recommending that the U.S. tolerance for vegetable, cucurbit, group 9 be 

revised to 0.20 ppm in order to harmonize with Codex. 

The following tolerances for residues of novaluron in/on stone fruit have been established: 

cherry at 8.0 ppm; fruit, stone, group 12, except cherry at 1.9 ppm; and plum, prune, dried at 2.6 

ppm [40 CFR §180.598(a)]. No new plum field trial data were submitted. The petitioner has 

requested that the existing tolerances for residues of novaluron in/on stone fruit be expanded to 

cherry subgroup 12-12A, peach subgroup 12-12B, and plum subgroup 12-12C. The stone fruit 

tolerance levels are harmonized with Canada (8.0 ppm for cherry, 1.9 ppm for fruit, stone, group 

12, except cherry, and 2.6 ppm for plum, prune, dried); however, they are not harmonized with 

Codex (7 ppm for stone fruit and 3 ppm for prunes). HED recommends for harmonization of the 

plum, prune, dried tolerance level with Codex (3.0 ppm). 

2.2.4 International Harmonization

No Canadian, Codex, or Mexican MRLs have been established for residues of novaluron in/on 

avocado and carrot. Codex has established the following MRLs for residues of novaluron: 0.7 

ppm common bean (pods and/or immature seeds); 0.7 ppm on fruiting vegetables other than 

cucurbits; 3 ppm in pome fruit; 3 ppm in prunes; 7 ppm in stone fruits; and 0.2 ppm in fruiting 

vegetables cucurbits. Canada has established the following MRLs for residues of novaluron: 0.6 

ppm in edible-podded snap beans; 0.8 ppm in bell peppers; 0.9 ppm in non-bell peppers; 2 ppm 

in apples, Asian pears, crabapples, loquats, mayhaws, pears, and quinces; 2.6 ppm in plum, 

prune, dried; 8 ppm in sweet and tart cherries; and 1.9 ppm in apricots, fresh prune plums, 
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nectarines, peaches, plumcots, and plums. HED is recommending to harmonize tolerance/MRL

levels with Codex for the following commodities and crop groups: bean, succulent (0.70 ppm);

vegetable, cucurbit, group 9 (0.20 ppm); fruit, pome, group 11-10 (3.0 ppm); and plum, prune, 

dried (3.0 ppm). HED does not recommend to lower the tolerance level for residues of 

novaluron in vegetable, fruiting, group 8-10 to harmonize with Codex and Canada since the 

current U.S. tolerance is based on greenhouse-grown tomato data that support a tolerance value 

of 1.0 ppm (Memo, G. Kramer, 07-FEB-2008; D340137). 

2.3 Label Recommendations

A revised Section B is requested which:

 Updates the pear application-rate information so that the maximum seasonal application 

rate and maximum numbers of applications are concordant. The proposed label implies 

that up to two 32-ounce applications may be made per season, which would result in a 

maximum seasonal rate of 64 ounces (~0.4 lb ai/A/season); however, the label 

specifically indicates that the maximum seasonal application rate is 96 ounces (~0.6 lb 

ai/A/season; equivalent to 3 applications). The field trial data support a maximum 

seasonal application rate of 0.97 lb ai/A.

 Indicates that the product may be used on “beans, succulent” and “beans, dry” instead of 

the proposed “beans.” 

3.0 Introduction

3.1 Chemical Identity

Table 3.1. Novaluron Nomenclature.

Chemical structure

Common name Novaluron

IUPAC name 1-[3-chloro-4-(1,1,2-trifluoro-2-trifluoromethoxyethoxy)phenyl]-3-[2,6-

difluorobenzoyl]urea

CAS name N-[[[3-chloro-4-[1,1,2-trifluoro-2-

(trifluoromethoxy)ethoxy]phenyl]amino]carbonyl]-2,6-difluorobenzamide

CAS registry number 116714-46-6

End-use product (EP) Rimon®

0.83EC Insecticide (EPA Reg. No. 66222-35)

3.2 Physical/Chemical Characteristics

Novaluron acts as an insecticide mainly by ingestion, but has some contact activity. It has a low 

vapor pressure (1.2 x 10-7 mm Hg) and appears to be immobile in soils according to the McCall 

classification (McCall et al., 1980). A table of the physicochemical properties can be found in 

Appendix B. 

O

N

H

N

H

O

F

F

Cl

O

O

CF3

F

F

F
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3.3 Pesticide Use Pattern

IR-4 has submitted a draft label for Rimon®0.83EC Insecticide (EPA Reg. No. 66222-35) to 

include the proposed new uses and updated crop groupings. The proposed label requires 

applicators and other handlers to wear a long-sleeved shirt, long pants, protective eyewear, 

chemical-resistant gloves, and shoes plus socks. There are no proposed application rate changes 

for cucurbits, fruiting vegetables, pome fruit, and stone fruit. The pear maximum seasonal 

application rate on the proposed label is lower than the maximum seasonal application rate that 

was assessed to establish the tolerance for residues of novaluron in pome fruit. A revised 

Section B is required, as discussed in Section 2.3. 

Table 3.3. Summary of Directions for Proposed Use of Novaluron.

Applic. 

Timing, Type, 

and Equip.†

Formulation 

[EPA Reg. 

No.]

Max Applic. 

Rate (lb ai/A)

Max. No. 

Applic. 

per 

Season

Max. 

Seasonal 

Applic. Rate 

(lb ai/A)1

PHI 

(days)

Use Directions and 

Limitations

Proposed Uses

Avocado

Aerial, Airblast

Emulsifiable 

Concentrate

[66222-35]

0.125

3 (at max. 

single 

appl. rate)

0.375 1

Use a minimum spray volume of 

100 GPA

RTI: 14 days

Carrot

Aerial, Ground

Emulsifiable 

Concentrate

[66222-35]

0.080

3 (at max. 

single 

appl. rate)

0.240 3

Use a minimum spray volume of 

20 GPA

RTI: 7 days

Greenhouse Cucumbers 

Ground, or

Handheld spray 

equipment

Emulsifiable 

Concentrate

[66222-35]

0.059 – 0.078

Or 0.0008 lb 

ai/gal

3 (at max. 

single appl. 

rate)

0.234 1

The use of novaluron on crops 

grown for food in greenhouses, 

except tomatoes and cucumbers, is 

prohibited. 

Tomato RTI: 7 days 

Cucumber RTI: 14 days. 

Proposed Crop Group Expansion (Same Application Scenario that is Currently Registered)

Bean, Succulent2

Aerial, Ground

Emulsifiable 

Concentrate

[66222-35]

0.039 - 0.078

3 (at max. 

single appl. 

rate)

0.234 1 RTI: 7 days

Proposed Crop Group Commodity Updates (Same Application Scenarios that are Currently Registered)

Pears (Group 11-10 pear; Asian pear)

Aerial, Ground

Emulsifiable 

Concentrate

[66222-35]

0.13 – 0.21

2 or 3 (at 

max. single 

appl. rate)

0.42 or 0.63314

For use only in Colorado, 

Michigan, New York, 

Pennsylvania, Washington and 

Oregon.

Not registered in California

RTI: 10 days

Fruit, Pome, Group 11-10 Except Pears (Apple; azarole; crabapple; loquat; mayhaw; medlar; quince; Chinese quince; 

Japanese quince; tejocote; cultivars, varieties, and/or hybrids of these )

Aerial, Ground

Emulsifiable 

Concentrate

[66222-35]

0.097 – 0.32

3 (at max. 

single appl. 

rate)

0.97 14 Not registered in California.

RTI: 10 days

Stone Fruit (capulin; black cherry; Nanking cherry; sweet cherry; tart cherry; cultivars, varieties, and/or hybrids of 

these; nectarine; peach; cultivars, varieties, and/or hybrids of these: apricot; Japanese apricot; Chinese jujube; plum; 

American plum; beach plum; Canada plum; cherry plum; Chickasaw plum; Damson plum; Japanese plum; Klamath 

plum; prune plum; plumcot; sloe; cultivars, varieties, and/or hybrids of these)

Aerial, Ground

Emulsifiable 

Concentrate

[66222-35]

0.129 – 0.32

3 (at max. 

single appl. 

rate)1

0.97 8

Not registered in California.

RTI: 7 days
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Table 3.3. Summary of Directions for Proposed Use of Novaluron.

Applic. 

Timing, Type, 

and Equip.†

Formulation 

[EPA Reg. 

No.]

Max Applic. 

Rate (lb ai/A)

Max. No. 

Applic. 

per 

Season

Max. 

Seasonal 

Applic. Rate 

(lb ai/A)1

PHI 

(days)

Use Directions and 

Limitations

Vegetable, Fruiting, Group 8-10 [tomatoes (including bush, currant, and tree tomatoes), peppers, eggplants (including 

African, pea, and scarlet eggplants), tomatillo, groundcherry, pepino, okra, cocona, goji berry, garden huckleberry, 

martynia, naranjilla, roselle, and sunberry]

Ground, or

Handheld spray 

equipment

Emulsifiable 

Concentrate

[66222-35]

0.059 – 0.078

Or 0.0008 lb 

ai/gal

3 (at max. 

single 

appl. rate)

0.233 1

The use of novaluron on crops 

grown for food in greenhouses, 

except tomatoes and cucumbers, 

is prohibited. 

RTI: 7 days 

1 Maximum seasonal rates may not match the maximum application rate times the maximum number of applications 

due to rounding.

2 Novaluron is already registered for use on succulent snap beans and dry beans. Based on the submitted lima bean 

data, HED is recommending for a tolerance to be established in beans, succulent. This will replace the succulent 

snap bean tolerance, but will not impact dry beans. The use pattern is the same as what was previously registered. 

2

It is not clear from the current label whether two applications or three applications may be made per season. The 

label implies that two applications may be made; however the maximum seasonal application rate is for three 

applications. A revised label is required. 

3.4 Anticipated Exposure Pathways

RD has requested an assessment of human health risk to support the IR-4-proposed new uses of 

novaluron on avocado and carrot, to expand the use pattern for succulent beans, to update croup 

group commodity definitions for fruiting vegetable group 8-10, pome fruit group 11-10, cherry

subgroup 12-12A, peach subgroup 12-12B, and plum subgroup 12-12C, and to add greenhousegrown cucumbers to the label. Humans may be exposed to novaluron in food and drinking 

water, since novaluron may be applied directly to growing crops and application may result in 

novaluron reaching surface and ground water sources of drinking water. Adults and children 

may be exposed to novaluron in residential settings due to the currently registered uses. In an 

occupational setting, applicators may be exposed while handling the pesticide prior to 

application, as well as during application and post-application. 

This risk assessment considers all of the aforementioned exposure pathways based on the 

proposed new uses of novaluron, but also considers the existing registered uses for the dietary

and residential exposure assessments. 

3.5 Consideration of 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://epa.gov/compliance/ej/resources/policy/exec_order_12898.pdf). As a part of every

pesticide risk assessment, OPP considers a large variety of consumer subgroups according to 

well-established procedures. In line with OPP policy, HED estimates risks to population 

subgroups from pesticide exposures that are based on patterns of that subgroup’s food and water 

consumption, and activities in and around the home that involve pesticide use in a residential 

setting. Extensive data on food consumption patterns are compiled by the U.S. Department of 

Agriculture (USDA) under the National Health and Nutrition Examination Survey, What We Eat 

in America, (NHANES/WWEIA; 2003-2008) and are used in pesticide risk assessments for all 

registered food uses of a pesticide. These data are analyzed and categorized by subgroups based 
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on age and ethnic group. Additionally, OPP is able to assess dietary exposure to smaller, 

specialized subgroups and exposure assessments are performed when conditions or 

circumstances warrant. Whenever appropriate, non-dietary exposures based on home use of 

pesticide products and associated risks for adult applicators and for toddlers, youths, and adults 

entering or playing on treated areas post-application are evaluated. Further considerations are 

currently in development as OPP has committed resources and expertise to the development of 

specialized software and models that consider exposure to bystanders and farm workers as well 

as lifestyle and traditional dietary patterns among specific subgroups.

4.0 Hazard Characterization and Dose-Response Assessment

4.1 Toxicology Studies Available for Analysis

The hazard database for novaluron is complete and adequate for risk assessment of the proposed 

uses. On March 15, 2012, the Hazard and Science Policy Council (HASPOC) concluded, based 

on a weight-of-evidence (WOE) approach, that a subchronic inhalation toxicity study was not 

required (TXR# 0052351). This approach considered all of the available hazard and exposure 

information for novaluron. However, this study may be necessary to support future uses. 

Additionally, a guideline immunotoxicity study has been submitted and reviewed by the Agency 

(MRID 48690105).

4.2 Absorption, Distribution, Metabolism, and Excretion (ADME)

Novaluron exhibited marginal oral absorption (16-18%), and absorption appeared to be saturated 

for the high dose. Peak plasma concentrations occurred at 2-5 hours. The most prevalent urinary

metabolite was 2, 6-difluorobenzoic acid. Other components individually represented no more 

than 5.9% of the dose and most represented considerably less than 1%. Quantitatively, fecal 

metabolites accounted for <2% of the dose. In the repeated-dose group, some tissues such as fat 

contained measurable radioactivity at 168 hours post dose, but did not appear to suggest 

significant potential for bioaccumulation or sequestration at the doses tested. Biliary

contribution for fecal excretion appears to be insignificant. Excretion was relatively rapid and 

was complete within 48 hours primarily via the feces and to a lesser extent via urine in rat.

4.3 Toxicological Effects

In subchronic and chronic toxicity studies, novaluron’s primary and most sensitive effects were 

on the hematopoietic system. These effects do not appear to worsen with time, and included 

methemoglobinemia, decreased hemoglobin, decreased hematocrit, decreased RBCs (or 

erythrocytes), and increased reticulocyte counts that were associated with compensatory

erythropoiesis. Increased spleen weights and/or hemosiderosis in the spleen were considered to 

be due to enhanced removal of damaged erythrocytes and not to a direct immunotoxic effect (at 

doses ≥27 mg/kg/day). 

There was no maternal or developmental toxicity seen in the rat and rabbit developmental 

toxicity studies up to the limit doses (1000 mg/kg/day). In the two-generation reproductive 

toxicity study in rats, both parental and offspring toxicity (increased spleen weights) were 

observed at the same dose (74.2 mg/kg/day). Reproductive toxicity (decreases in epididymal 

sperm counts and increased age at preputial separation in the F1 generation) was observed at a 
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higher dose than the increased spleen weights and were consistent with the primary effects in the 

database. 

Clinical signs of neurotoxicity (piloerection, irregular breathing), changes in FOB parameters 

(increased head swaying, abnormal gait), and neuropathology (sciatic and tibial nerve 

degeneration) were seen in the rat acute neurotoxicity study at the limit dose (2000 mg/kg/day). 

However, no signs of neurotoxicity or neuropathology were observed in the subchronic 

neurotoxicity study in rats at similar doses or in any other subchronic or chronic toxicity study in 

rats, mice, or dogs.

In the submitted immunotoxicity study, the only sign of potential immunotoxicity for novaluron 

was a decreased anti-SRBC response at twice the limit dose in female rats. 

Novaluron was categorized as having low acute toxicity via the oral (Toxicity Category IV), 

dermal (Toxicity Category III), and inhalation routes (Toxicity Category IV). No ocular 

(Toxicity Category IV) or dermal irritation (Toxicity Category IV) was noted. Novaluron is not 

a dermal sensitizer and no adverse effects were observed in the 28-day dermal study in rats up to 

the limit dose (1000 mg/kg/day).

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

The RAB1 risk assessment team concluded that the FQPA SF could be reduced to 1X based on 

the following considerations outlined in more detail in the sections below: 1) the toxicology

database for novaluron is complete and adequate for risk assessment of the proposed and 

registered uses; 2) novaluron is not considered neurotoxic; 3) there is no evidence of increased 

susceptibility to offspring; and 4) the exposure databases are sufficient and are unlikely to 

underestimate exposure.

4.4.1 Completeness of the Toxicology Database

The toxicology database for novaluron is adequate for quantification of risk for dietary, 

residential, and occupational uses and FQPA SF evaluation. The following acceptable studies 

are available for evaluation of neurotoxicity and offspring sensitivity: developmental toxicity

studies in rats and rabbits, a two-generation reproduction study in rats, and acute and subchronic 

neurotoxicity studies in rats. 

4.4.2 Evidence of Neurotoxicity

Acute and subchronic neurotoxicity screening batteries were performed with novaluron in rats. 

Novaluron is not considered neurotoxic, since effects observed in the acute neurotoxicity study

were observed at the limit dose only and were not reproduced at similar, repeated doses in the 

subchronic neurotoxicity study. In addition, no evidence of neuropathology was observed in 

subchronic and chronic toxicity studies in rats, mice, or dogs. 

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

There is no evidence of increased susceptibility in the rat or rabbit developmental toxicity studies 

up to the limit dose or in the two-generation reproduction study in rats. 
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4.4.4 Residual Uncertainty in the Exposure Database

There are no residual uncertainties with regard to dietary and residential exposure assessments. 

The chronic dietary food exposure assessment utilized average field trial residues, ARs for 

livestock commodities, average PCT and PCTn data, and empirical and default processing 

factors. The registered food-handling use was also incorporated into the dietary assessment. The 

dietary drinking water assessment utilized water concentration values generated by the Pesticide 

Root Zone Model for Ground Water (PRZM-GW). The resulting screening-level estimated 

drinking water concentrations (EDWCs) provide conservative, health-protective, high-end 

estimates of water concentrations that will not likely be exceeded. Although data were used to 

refine the dietary exposure assessments, the assessments are not expected to underestimate 

dietary (food and water) exposures. 

The residential handler and post-application exposure assessments are based upon the 2012 

Residential SOPs. The residential SOPs are based upon reasonable worst-case assumptions and 

are not expected to underestimate risk. These assessments of exposure are not likely to 

underestimate the resulting estimates of risk from exposure to novaluron.

4.5 Toxicity Endpoint and Point of Departure Selections

4.5.1 Dose-Response Assessment

Acute Dietary Endpoint: An acute reference dose (aRfD) for the general U.S. population, 

including infants and children, was not established since an endpoint of concern attributable to a 

single dose was not identified. In the acute neurotoxicity study, neurotoxic signs and 

neuropathology were seen only at the lowest-observed adverse-effect level (LOAEL) of 2000 

mg/kg (limit dose). The no-observed adverse-effect level (NOAEL) is 650 mg/kg. These effects 

are not of concern for acute dietary risk assessment based upon the magnitude of the dose and 

also in relation to the most sensitive effects and target organs in novaluron’s hazard database.

No developmental toxicity was seen at the limit dose in either rat or rabbit prenatal 

developmental toxicity studies.

Chronic Dietary Endpoint: The chronic reference dose (cRfD) of 0.011 mg/kg/day was 

determined on the basis of the chronic/carcinogenicity study in rats. The LOAEL of 30.6 

mg/kg/day is based on evidence of erythrocyte damage and turnover resulting in a regenerative 

anemia. This study provides the most protective point of departure (POD) in the hazard database 

with a NOAEL of 1.1 mg/kg/day. A total uncertainty factor (UF) of 100X (10X for interspecies 

extrapolation, 10X for intraspecies variability, and a 1X FQPA SF) was applied to the NOAEL 

of 1.1 mg/kg/day. Therefore, the chronic population-adjusted dose (cPAD) is 0.011 mg/kg/day. 

This study is appropriate for the duration of exposure and is protective of the general U.S. 

population.

Incidental Oral Endpoints for All Durations: The POD chosen for all incidental oral scenario 

durations is based on the NOAEL of 4.38 mg/kg/day from the 90-day feeding study in rats. The 

LOAEL is 8.64 mg/kg/day based upon clinical chemical effects (decreased hemoglobin, 

hematocrit, and RBC counts) and changes in histopathology (increased hematopoiesis and 

hemosiderosis in spleen and liver). The LOC is 100 (10X for interspecies extrapolation and 10X 

for intraspecies variability and an FQPA SF of 1X). This study is protective of the offspring 
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effects observed in the two-generation reproductive study and is thus protective of infants and 

children in residential settings. 

Dermal Endpoint for All Durations: No adverse dermal or systemic effects were observed in the 

28-day dermal study in rats; therefore, a short-term dermal endpoint was not selected. The 

dermal study specifically looked for blood effects, the target for novaluron, and there were no 

treatment related effects up to the limit dose. Although dermal endpoints were previously 

selected for the intermediate- and long-term scenarios, the toxicity profile for novaluron does not 

show progression of toxicity with increased duration. Furthermore, there is no concern for 

susceptibility since no effects were observed in the developmental or reproduction toxicity

studies in rats or rabbits. Therefore, there is no concern for any duration of dermal exposure and

a quantitative dermal assessment is not required.

Inhalation Endpoints for All Durations: Similar to the incidental oral endpoint, the POD chosen 

for all inhalation scenario durations is based on the NOAEL of 4.38 mg/kg/day from the 90-day

feeding study in rats. The LOAEL is 8.64 mg/kg/day based upon clinical chemical effects 

(decreased hemoglobin, hematocrit, and RBC counts) and changes in histopathology (increased 

hematopoiesis and hemosiderosis in spleen and liver). The LOC for residential and occupational 

exposures are for MOEs <100 (similar to the intermediate-term dermal endpoint). This study is 

protective of children and adults in residential settings, as well as workers in occupational 

settings.

4.5.2 Recommendation for Combining Routes of Exposures for Risk Assessment

Based upon common effects and the use of an oral 90-day study in rats for the incidental oral and 

inhalation routes, these exposures can be combined for all residential scenarios for all durations. 

Since there are no dermal endpoints for novaluron, dermal exposures do not need to be combined 

with inhalation exposures for residential and occupational assessments. 

4.5.3 Cancer Classification and Risk Assessment Recommendation

In accordance with the EPA Draft Guidelines for Carcinogen Risk Assessment (July 1999), 

novaluron is classified as “not likely to be carcinogenic to humans” based on the lack of 

evidence for carcinogenicity in mice and rats (TXR# 0052361).

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 Novaluron for Use in Dietary and NonOccupational 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)

None None None

An endpoint of concern attributable to a 

single dose was not identified. An acute 

RfD was not established.
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Table 4.5.4.1. Summary of Toxicological Doses and Endpoints for Novaluron for Use in Dietary and NonOccupational Human health Risk Assessments.

Exposure/ 

Scenario

Point of 

Departure

Uncertainty/

FQPA SFs

RfD, PAD, 

LOC for 

Risk 

Assessment

Study and Toxicological Effects

Chronic 

Dietary (All 

Populations)

NOAEL = 

1.1 

mg/kg/day

UFA = 10X

UFH = 10X

FQPA SF = 1X

Chronic RfD 

= 0.011 

mg/kg/day

cPAD = 0.011 

mg/kg/day

Combined chronic 

toxicity/carcinogenicity feeding in rat

LOAEL = 30.6 mg/kg/day based on 

erythrocyte damage resulting in a 

compensatory regenerative anemia.

Incidental 

Oral, All 

Durations 

NOAEL = 

4.38

mg/kg/day

UFA = 10X

UFH = 10X

FQPA SF = 1X

Residential 

LOC for 

MOE <100

90-day feeding study in rat

LOAEL = 8.64 mg/kg/day based on 

clinical chemistry (decreased hemoglobin, 

hematocrit, and RBC counts) and 

histopathology (increased hematopoiesis 

and hemosiderosis in spleen and liver).

Dermal, All 

Durations

A short-term dermal endpoint was not selected since there were no adverse dermal or systemic 

effects observed in the 28-day dermal study in rats and no concern for increased offspring 

susceptibility. Therefore, there is no concern for any duration of dermal exposure and no dermal 

endpoints are required.

Inhalation, All 

Durations 

NOAEL = 

4.38

mg/kg/day 

(inhalationabsorption 

rate = 100%)

UFA = 10X

UFH =10X

FQPA SF = 1X

Residential 

LOC for 

MOE <100

90-day feeding study in rat

LOAEL = 8.64 mg/kg/day based on 

clinical chemistry (decreased hemoglobin, 

hematocrit, and RBC counts) and 

histopathology (increased hematopoiesis 

and hemosiderosis in spleen and liver).

Cancer (oral, 

dermal, 

inhalation)

Classification: Not likely to be carcinogenic to humans.

Point of departure = 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 (c = chronic). RfD = reference dose. LOC = level of concern. MOE = margin of 

exposure. 

Table 4.5.4.2. Summary of Toxicological Doses and Endpoints for Novaluron for Use in Occupational 

Human health Risk Assessments.

Exposure/ 

Scenario

Point of 

Departure

Uncertainty/

FQPA SFs

RfD, PAD, 

LOC for 

Risk 

Assessment

Study and Toxicological Effects

Dermal, All 

Durations

A short-term dermal endpoint was not selected since there were no adverse dermal or systemic 

effects observed in the 28-day dermal study in rats. Therefore, there is no concern for any duration 

of dermal exposure and no dermal endpoints are required.

Inhalation, 

All 

Durations 

NOAEL = 

4.38

mg/kg/day 

(inhalationabsorption 

rate = 100%)

UFA = 10X

UFH =10X

Occupational 

LOC for 

MOE <100

90-day feeding study in rat

LOAEL = 8.64 mg/kg/day based on 

clinical chemistry (decreased hemoglobin, 

hematocrit, and RBC counts) and 

histopathology (increased hematopoiesis 

and hemosiderosis in spleen and liver).

Cancer (oral, 

dermal, 

inhalation)

Classification: Not likely to be carcinogenic to humans.

Point of departure = 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 
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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). MOE = margin of exposure. LOC = level of 

concern. 

5.0 Dietary Exposure and Risk Assessment 

5.1 Residues of Concern Summary and Rationale

HED previously concluded that the nature of the residue in plants is adequately understood based 

on acceptable metabolism studies conducted on apples, cabbage, cotton, and potatoes using 

[difluorophenyl-U14C]novaluron and [chlorophenyl-U14C]novaluron as the test substances 

(Memo, G. Kramer, 22-MAR-2004; D285474). These studies indicate that novaluron is not 

extensively metabolized in these crops. The parent compound, novaluron, either was the only 

residue component identified or was the predominant residue component in all analyzed plant 

matrices. The reviewed studies also indicate that novaluron, when foliarly applied during the 

vegetative growth stage, is not readily translocated to mature apple fruit, potato tubers, or 

cottonseed (Memo, G. Kramer, 22-MAR-2004; D285474). Based on these studies, the 

Metabolism Assessment and Review Committee (MARC) determined that the residue of concern 

in crops for purposes of tolerance enforcement and risk assessment is novaluron only (Memo, G. 

Kramer et al., 03-FEB-2004; D297646). Additionally, the HED MARC determined that for 

tolerance assessment and risk assessment, parent only is the residue of concern in rotational 

crops (Memo, G. Kramer et al., 03-FEB-2004; D297646).

HED also previously concluded that the nature of the residue in livestock is adequately 

understood based on the submitted goat and hen metabolism studies (Memo, G. Kramer, 22-

MAR-2004; D285474). The HED MARC determined that the residue of concern in livestock for 

purposes of tolerance enforcement and risk assessment is novaluron only (Memo, G. Kramer et 

al., 03-FEB-2004; D297646).

The HED MARC concluded that parent and the chlorophenyl urea and chloroaniline degradates 

are residues of potential concern to be included in the drinking water assessment. Monitoring 

data are not available for novaluron or its chlorophenyl urea and chloroaniline degradates in 

surface water or ground water. Concentrations in surface water and ground water were estimated 

using standard EFED drinking water models.

Table 5.1. Summary of Metabolites and Degradates to be included in the Risk Assessment and Tolerance 

Expression.1

Matrix Residues Included in Risk 

Assessment

Residues Included in Tolerance 

Expression

Plants

Primary Crop Novaluron Novaluron

Rotational Crop Novaluron Novaluron

Livestock

Ruminant Novaluron Novaluron

Poultry Novaluron Novaluron

Drinking Water Novaluron and chlorophenyl urea and 

chloroaniline degradates Not Applicable

1 Memo, G. Kramer et al., 03-FEB-2004; D297646.
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5.2 Food Residue Profile

No new data were submitted to support tolerances for residues of novaluron in/on fruiting 

vegetable group 8-10, pome fruit group 11-10, cherry subgroup 12-12A, peach subgroup 12-12B, 

and plum subgroup 12-12C. The petitioner has requested that existing tolerances be expanded to 

their updated croup group commodity definitions. A tolerance has already been established for 

residues of novaluron in/on cucurbit vegetable group 9; however, the use of novaluron on 

greenhouse-grown cucumbers was excluded in the label. The petitioner has provided field trial 

data for greenhouse-grown cucumbers to expand the use pattern to include greenhouse-grown 

cucumbers. Field trial data were previously submitted and reviewed for succulent snap beans. 

The current petition includes field trial data for lima bean. There are adequate field trial data 

available to establish a tolerance for residues of novaluron in/on bean, succulent based on the 

available lima bean and succulent snap bean field trial data. 

The submitted field trial residue data for avocado, carrot, cucumber, and lima bean are adequate 

to support the establishment of the requested tolerances. GC/ECD methods that are similar to the 

enforcement method were used for data collection and the methods were adequately validated in 

conjunction with the avocado, carrot, greenhouse cucumber, and lima bean field trials. The field 

trial data reflect the proposed use pattern and an adequate number of trials were conducted in the 

appropriate geographic regions. Although only five independent lima bean field trials were 

submitted, an additional field trial is not required since HED does not expect that the submission 

of an additional lima bean field trial would result in a higher recommended tolerance for residues 

of novaluron in/on succulent beans. The remaining proposed tolerances pertain to updates to the 

crop group/subgroup commodity definitions. Since the proposed application scenarios are 

identical or lower than the application scenarios previously reviewed, no residue data were 

submitted and none are required. 

Concurrent storage stability data were submitted for avocado, carrot, cucumber, and lima bean. 

These data demonstrate that residues of novaluron were stable for the durations that the field trial 

samples were frozen. HED previously requested storage stability data on dried plums and on 

grain sorghum forage, grain, aspirated grain fractions (AGF), and stover. Acceptable dried plum 

and sorghum grain and forage storage stability have been submitted; therefore, these deficiencies 

are now resolved.

There are no processed commodities associated with avocado, carrot, cucumber, and lima bean. 

There are processed commodities associated with fruiting vegetables, pome fruit, and stone fruit; 

however, processing studies were not required for the submission since the petitioner has 

requested updates to the crop group commodity definitions that are supported with previously

submitted data, including processing studies. 

The field trial data for avocado, greenhouse-grown cucumber, and lima bean were entered into 

the OECD tolerance calculator to determine the appropriate tolerance level. The OECD 

tolerance calculation procedures were not used for carrot because all of the residues were less 

than the lowest level of method validation (LLMV; 0.05 ppm). The output from the tolerance 

calculator and the submitted field trial data support the HED-recommended tolerances outlined 

in Table 2.2.2. When possible, the recommended tolerances have been harmonized with Codex.

Carrot culls are the only livestock feed item associated with the current petition. The 

incorporation of carrot culls into the reasonably balanced dietary burdens (RBDBs) calculations 
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did not result in increased livestock dietary burdens. As a result, revised RBDBs and livestock 

tolerances were not required. 

The carrot, cucumber, and bean commodities associated with the current petitions may be 

rotated. Avocados, pome fruit, and stone fruit are not rotated. Based on the results of the 

submitted confined rotational crop study, the appropriate PBI for all non-labeled crops is 30 

days. The current and proposed labels include a restriction that only registered crops may be 

rotated to a treated field within 30 days of the final application, which is appropriate for this 

petition. Future uses that have significantly higher application rates will require confined 

rotational crop studies at higher rates using chlorophenyl-labeled novaluron. 

5.3 Water Residue Profile

The residues of concern in drinking water for purposes of risk assessment are novaluron, the 

chlorophenyl urea degradate (1-[3-chloro-4-(1,1,2-trifluoro-2-

trifluoromethoxyethoxy)phenyl]urea), and the chloroaniline degradate (3-chloro-4-(1,1,2-

trifluoro-2-trifluoromethoxyethoxy)aniline) (Memo, G. Kramer et al., 03-FEB-04; D297646). 

The drinking water concentrations used in the dietary risk assessment were provided by EFED in 

the following memorandum: “Drinking Water Assessment in Support of the New Indoor and 

Outdoor non-food Use of Novaluron for Pest Control” (H. Zhong, 07-AUG-2013; D412441) and 

were incorporated directly into this dietary assessment under the food categories “water, direct, 

all sources” and “water, indirect, all sources.” Surface and ground water EDWCs were 

calculated using the Pesticide Root Zone Model/Exposure Analysis Modeling System 

(PRZM/EXAMS), the Screening Concentration in Ground Water (SCI-GROW), and Pesticide 

Root Zone Model for Ground Water (PRZM-GW) models. A summary of the modeled scenarios 

can be found in the drinking water memo (H. Zhong, 07-AUG-2013; D412441). EFED has 

indicated that revised drinking water estimates are not required based on the proposed uses 

(Memo, H. Zhong, 2-SEP-2014; D418740).

The EDWC values are meant to represent upper-bound estimates of the concentrations that might 

be found in surface water and groundwater based upon existing and proposed uses. Since the 

residues of concern in drinking water for risk assessment purposes are novaluron, the 

chlorophenyl urea degradate, and the chloroaniline degradate, these EDWCs were calculated 

using a molecular weight conversion and then combined for each modeled scenario. The 

degradates are assumed to have equal toxicity to the parent. The chronic dietary exposure and 

risk assessment incorporated the highest total EDWC of 77.8 μg/L (0.0778 ppm) that was 

simulated using the PRZM-GW model with the proposed poultry operation use and WI corn 

scenario (Table 5.2). 

Table 5.2. Summary of Novaluron EDWCs from Ground Water Using PRZM-GW Modeling for Poultry 

Operations.1

Crop/Scenario Highest Daily 

Value (μg/L)

Post Breakthrough 

Average (μg/L)

Average Simulation 

Breakthrough Time (Days)

Novaluron

Wisconsin Corn - WI Central Sands

Met File (14920.dvf) 2.58E-18 Incomplete Incomplete

Chlorophenyl Urea Degradate

Wisconsin Corn - WI Central Sands

Met File (14920.dvf) 0.00815 Incomplete Incomplete

Chloroaniline Degradate

Wisconsin Corn - WI Central Sands 84.2 77.8 15,661
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Met File (14920.dvf)

Total of Novaluron and Chlorophenyl Urea and Chloroaniline Degradates

Wisconsin Corn - WI Central Sands

Met File (14920.dvf) 84.21 77.8 15,661

1 EFED simulated ground water EDWCs using a newer PRZM-GW model for six vulnerable sites in VA, FL, GA, 

NC, and WI. This table summarizes the highest EDWCs for novaluron and its degradates that resulted from the 

proposed poultry operation uses combined with the Wisconsin Corn - WI Central Sands site. The WI site provides 

the highest total EDWC, and was used in the dietary exposure assessment. A value of 0 was used for novaluron and 

chlorophenyl urea in the total calculation since the post-breakthrough averages are incomplete for these EDWCs. 

5.4 Dietary Risk Assessment

5.4.1 Description of Residue Data Used in Dietary Assessment

A partially refined chronic dietary-exposure (food plus water) and risk assessment was 

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

Intake Database (DEEM-FCID) Version 3.16, which uses food consumption data from the 

USDA’s NHANES/WWEIA from 2003 through 2008. The assessment was performed for the 

general U.S. population and all population subgroups. The chronic analysis incorporated 

recently updated average PCT and PCTn data. ARs for meat, milk, hog, and poultry 

commodities were calculated using average field trial residues, PCTn and PCT data, and 100 

PCT for some commodities. The chronic analysis also incorporated average field trial residues 

for the majority of commodities, average greenhouse trial residues for tomatoes and cucumbers, 

and half-LOQ residues for food commodities other than those covered by a higher tolerance as a 

result of use on growing crops from the registered use in food and feed handling establishments. 

Additionally, empirical processing factors for apple juice (translated to pear and stone fruit 

juice), cottonseed oil, dried plums, and tomato paste and purée, and DEEM (ver. 7.81) default 

processing factors for the remaining processed commodities, where provided were incorporated. 

The chronic dietary exposure and risk assessment incorporated the highest total EDWC of 77.8 

μg/L (0.0778 ppm) that was simulated using the PRZM-GW model with the proposed poultry

operation use and WI corn scenario. 
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5.4.2 Percent Crop Treated Used in Dietary Assessment

A Screening Level Usage Analysis (SLUA) memorandum entitled, “Usage Report Package in 

Support of Novaluron (124002), BEAN DP# 421177” (C. Doucoure, 30-JUN-2014) and a PCTn 

memorandum entitled, “Update of Percent Crop Treated for New Use (PCTn): Novaluron 

(124002) Use on Sorghum and Sweet Corn” (C. Doucoure, et al., 01-FEB-2013) were provided 

by BEAD. The market leader approach was used by BEAD to determine the PCTn values for 

sorghum and sweet corn. 

The chronic dietary analysis incorporated average PCT data for apples (10%), blueberries (<1%), 

(cabbage (5%), cauliflower (<2.5%), cotton (<2.5%), dry beans (<1%), pears (15%), peppers 

(<2.5%), potatoes (<2.5%), strawberries (35%), and tomatoes (<2.5%) and average PCTn data 

for grain sorghum (2%) and sweet corn (36%). 100 PCT was assumed for the remaining food 

commodities. Livestock dietary burdens of novaluron were calculated based on the registered 

uses, and incorporated average field trial residues, PCTn data for grain sorghum (2%) and sweet 

corn (36%), average PCT data for apple (10%) and cotton (<2.5%), and an assumption of 100 

PCT for sugarcane, AGF, and cowpea seed. These livestock dietary burdens were used, along 

with average transfer coefficients, to calculate anticipated secondary residues for meat, milk, 

hog, and poultry commodities, which were incorporated into the chronic dietary assessment. 

5.4.3 Acute Dietary Risk Assessment

An acute dietary assessment was not conducted for novaluron because an endpoint of concern 

attributable to a single dose was not identified. 

5.4.4 Chronic Dietary Risk Assessment

Chronic dietary risk estimates (food and drinking water) are not of concern for the general 

population or any other population subgroup. The assessment was partially refined and the 

highest exposure and risk estimates were for the population subgroup children 1-2 years old, 

which utilized 73% of the cPAD for novaluron. The chronic exposure estimate for the general 

U.S. population utilized 28% of the cPAD. A summary table of dietary exposure and risk for 

novaluron can be found in Section 5.4.6. Although further refinement to the analysis is not 

required at this time, future assessments could be refined using additional average field trial 

values, additional PCT data, cooking factors, and/or monitoring data. 

5.4.5 Cancer Dietary Risk Assessment

A cancer dietary assessment was not conducted because novaluron is classified as “not likely to 

be carcinogenic to humans.”

5.4.6 Summary Table

Table 5.4.6. Summary of Chronic Dietary Exposure (Food and Drinking Water) and Risk for Novaluron.1

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 0.003071 28

N/A N/A All Infants (<1 year old) 0.006289 57
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Table 5.4.6. Summary of Chronic Dietary Exposure (Food and Drinking Water) and Risk for Novaluron.1

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

Children 1-2 years old 0.008014 73

Children 3-5 years old 0.005711 52

Children 6-12 years old 0.003746 34

Youth 13-19 years old 0.002424 22

Adults 20-49 years old 0.002659 24

Adults 50-99 years old 0.002671 24

Females 13-49 years old 0.002640 24

1

Population with the greatest exposure is in bold. 

6.0 Residential (Non-Occupational) Exposure/Risk Characterization

There are no new proposed residential uses for the current action; however there are currently 

registered use of novaluron for indoor (spot/crack and crevice) and outdoor (perimeter) 

applications for the control of roaches and crickets, as well as on pets as a spot-on product for the 

control of fleas and ticks. Novaluron is also registered to control fleas, cockroaches, flies, 

mosquitoes, gnats, crickets, litter beetles and ants on furniture, animal quarters, carpets, kennels, 

poultry houses and lawns. The risks are presented here for the recommentadion of scenarios to

be in the aggregate assessment. Details of the exposure and risk estimate are provided in a 

previous occupational and residentail exposure assessments (L. Venkateshwara, 05-FEB-2014; 

D412298).

6.1 Residential Handler Exposure and Post-Application Exposure

Table 6.1 provides a summary of the residential handler and post-application exposures and risk 

estimates for the currently registered uses of novaluron. All residential handler and postapplication scenarios resulted in MOEs greater than 100 and, therefore, are not of concern to 

HED.

Table 6.1. Summary of Residential Exposure/Risk Estimates for Registered Uses of Novaluron.

Use Exposure Scenario Dose 

(mg/kg/day) MOE Source

Indoor crack and 

crevice / spot 

treatment

Residential 

Handler

Inhalation

Mixing/loading/applying wettable 

powders with manuallypressurized handwand0.00014 ST: 3,200

D401261

Applying ready-to-use 

formulations with trigger-pump 

sprayer

0.0000076 ST: 

570,000

Postapplication 

Inhalation

Adults 0.000049 ST: 89,000

Children 

(1 to <2 years old) 0.00021 ST: 21,000

Postapplication 

Incidental 

Oral1

Crack 

and 

Crevice

Carpet

Children 

(1 to <2 

years old)

0.00059 ST: 7,400

Hard 

surfaces 0.000196 ST: 22,000

Spot

Carpet 0.00288 ST: 1,500

Hard 

surfaces 0.00096 ST: 4,600

Pet Spot-on

Postapplication 

Incidental 

Children 

(1 to <2 years old) 0.00022 ST/IT/LT: 20,000 D410803
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Table 6.1. Summary of Residential Exposure/Risk Estimates for Registered Uses of Novaluron.

Use Exposure Scenario Dose 

(mg/kg/day) MOE Source

Oral

Indoor 

broadcast/spot/crack 

and crevice treatment

Residential 

Handler

Inhalation

Mixing/Loading/Applying Liquids 

with Manually-Pressurized Handwand 0.000011 410,000

D412298

Postapplication 

Inhalation

Adults 0.0000038 1,100,000

Children 

(1 to <2 years old) 0.000016 270,000

Postapplication 

Incidental 

Oral1

Broadcast

Carpet

Children 

(1 to <2 

years old)

0.0045 980

Hard 

Surfaces 0.0015 2,900

Spot

Carpet 0.0022 2,000

Hard 

Surfaces 0.000757 5,900

Crack and 

Crevice

Carpet 0.000472 9,300

Hard 

Surfaces 0.000157 28,000

Liquid Application 

to Turf

Residential 

Handler

Inhalation

Mixing/Loading/Applying Liquids 

with Hose End Sprayer 0.0000047 940,000

Mixing/Loading/Applying Liquids 

with Manually-Pressurized Handwand 0.00000018 24,000,000

Mixing/Loading/Applying Liquids 

with Sprinkler Can

0.0000021 2,000,000

Mixing/Loading/Applying Liquids 

with Backpack 0.0000014 3,100,000

Postapplication 

Incidental 

Oral

ST Hand-to-Mouth 0.0005 8,500

ST Object-to-mouth 0.00002 280,000

ST/IT Soil Ingestion 1.2E-06 3,800,000

6.2 Combined Residential Risk Estimates 

Table 6.2 provides a summary of the combined (i.e., dermal, incidental oral, and inhalation) 

residential exposure and risk estimates for children 1 to <2 years old for the registered indoor use 

of novaluron. The combined exposure estimates resulted in MOEs greater than 100 and, 

therefore, are not of concern to HED. 

Table 6.2. Residential Combined Exposure and Risk Estimates for Registered Uses of Novaluron.

Combined 

Exposure 

Scenario

Lifestage Exposure Scenario Route of 

Exposure Dose

Combined 

Short-term

Total Dose1

Combined 

Short-term

Total MOEs2

Indoor 

Application 

Scenario

Child

Post-application: Indoor Carpet

Crack and Crevice

Dermal N/A

Inhalation 0.00021 0.0008 5,500

Hand to Mouth 0.00059

Post-application: Indoor Carpet 

– Spot Treatment

Dermal N/A

Inhalation 0.00021 0.0031 1,400

Hand to Mouth 0.00288

Post-application –Indoor Carpet 

Broadcast

Dermal N/A

Inhalation 0.00016 0.0046 940

Hand to Mouth 0.00448

1 Combined Dose = see Table 6.2 for residential exposures.

2 Combined MOE = NOAEL (mg/kg/day) / Combined Dose (mg/kg/day); where the short-term NOAEL = 4.38 mg/kg/day.

6.3 Residential Risk Estimates for Use in Aggregate Assessment
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Table 6.3 reflects the residential risk estimates that are recommended for use in the aggregate 

assessment for novaluron.

 The recommended residential exposure for use in the short-term adult aggregate 

assessment reflects handler inhalation exposure from crack and crevice applications to 

both indoor use sites via manually-pressurized handwand (see D401261).

 The recommended residential exposure for use in the short-term children 1 to <2 years 

old aggregate assessment reflects post-application inhalation and hand-to-mouth 

exposures from the registered indoor carpet broadcast applications (see D412298).

 The recommended residential exposure for use in the intermediate- and long-term 

children 1 to <2 years old aggregate assessment reflects post-application hand-to-mouth 

exposures from the dog spot-on use (see D410803).
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Table 6.3. Recommendations for the Residential Exposures for the Novaluron Aggregate Assessment.1

Lifestage

Residential Handler Residential Post-application

Dose (mg/kg/day)2 MOE3 Dose (mg/kg/day)4 MOE5

Dermal Inhalation Total Dermal Inhalation Total Dermal Inhalation Oral Total Dermal Inhalation Oral Total

Short-Term

Adult NA 0.00014 0.00014 NA 3,200 3,200 NA 0.000049 N/A 0.000049 NA 89,000 N/A 89,000

Child N/A NA 0.00016 0.00448 0.00464 NA 270,000 980 940

Intermediate- and Long-Term

Child N/A N/A N/A 0.00022 0.00022 N/A N/A 20,000 20,000

1 Bolded risk estimates should contribute to the residential exposure portion of the aggregate assessment. 

2 Residential Handler Dose = the highest handler dose for each applicable lifestage of all scenarios assessed. Total = inhalation only.

3 Residential Handler MOE = the MOEs associated with the highest doses identified. Total = Inhalation MOE only.

4 Residential Post-application Dose = the highest post-application dose for each applicable lifestage of all scenarios assessed. Total = inhalation + incidental oral, where applicable.

5 Residential Post-application MOE = the MOEs associated with the highest doses identified. Total = 1/(1/Inhalation MOE) + (1/Incidental oral MOE), where applicable. 
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6.4 Spray Drift

Spray drift is a potential source of exposure to those nearby pesticide applications. This is 

particularly the case with aerial application, but, to a lesser extent, spray drift can also be a 

potential source of exposure from the ground application methods (e.g., groundboom and 

airblast) employed for novaluron. The Agency has been working with the Spray Drift Task 

Force (a task force composed of various registrants which was developed as a result of a Data 

Call-In issued by EPA), EPA Regional Offices and State Lead Agencies for pesticide regulation 

and other parties to develop the best spray drift management practices (see the agency’s Spray

Drift website for more information).1 The agency has also developed a policy on how to 

appropriately consider spray drift as a potential source of exposure in risk assessments for 

pesticides. The potential for spray drift will be quantitatively evaluated for each pesticide during 

the Registration Review process which ensures that all uses for that pesticide will be considered 

concurrently. The approach is outlined in the revised (2012) Standard Operating Procedures 

For Residential Risk Assessment (SOPs) - Residential Exposure Assessment Standard Operating 

Procedures Addenda 1: Consideration of Spray Drift. This document outlines the quantification 

of indirect non-occupational exposure to drift. 

6.5 Residential Bystander Post-Application Inhalation Exposure

Volatilization of pesticides may be a source of post-application inhalation exposure to 

individuals nearby pesticide applications. The Agency sought expert advice and input on issues 

related to volatilization of pesticides from its Federal Insecticide, Fungicide, and Rodenticide Act

(FIFRA) Scientific Advisory Panel (SAP) in December 2009, and received the SAP’s final report 

on March 2, 2010 (http://www.epa.gov/scipoly/SAP/meetings/2009/120109meeting.html). The 

Agency has evaluated the SAP report and has developed a Volatilization Screening Tool and a 

subsequent Volatilization Screening Analysis 

(http://www.regulations.gov/#!docketDetail;D=EPA-HQ-OPP-2014-0219). 

During Registration Review, the Agency will utilize this analysis to determine if data (i.e., flux 

studies, route-specific inhalation toxicological studies) or further analysis is required for 

novaluron.

7.0 Aggregate Exposure/Risk Characterization

In accordance with the FQPA, HED must consider and aggregate 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. In the case of novaluron, aggregate risk assessments were performed for 

short- and intermediate-/long-term aggregate exposures (food + drinking water + residential). 

An acute aggregate assessment was not conducted for novaluron because an endpoint of concern 

attributable to a single dose was not identified. Additionally, a cancer aggregate assessment was 

not conducted because novaluron was classified as “not likely to be carcinogenic to humans.” 

All potential exposure pathways were assessed in the aggregate risk assessment. 

 

1 Available: http://www.epa.gov/opp00001/factsheets/spraydrift.htm 
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7.1 Short-Term Aggregate Risk

Short-term (1- to 30-day) aggregate risk assessments are necessary for both adults and children 

since there is potential for both short-term handler exposure and short-term post-application 

exposure from the residential uses of novaluron. 

For the short-term aggregate risk assessment, potential residential exposures were combined with 

dietary (food and drinking water) exposures. A dermal endpoint has not been selected for 

novaluron; therefore, the short-term adult and child aggregate risk estimates do not include 

dermal exposures. Specifically, the short-term aggregate assessment for adults combines dietary

exposures with handler inhalation exposures resulting from the registered indoor crack and 

crevice uses. For young children, the short-term aggregate assessment combines dietary

exposure with potential post-application inhalation and incidental oral exposure (from hand-tomouth contact with treated surfaces) resulting from the registered indoor uses. See Table 6.3 for 

more information on the residential risk estimates that are recommended for use in the aggregate 

assessment for novaluron. 

The short-term residential exposure estimates were aggregated with the chronic dietary (food + 

drinking water) to provide a worst-case estimate of short-term aggregate risk for the U.S. 

population and children 1-2 years old (the child population subgroup with the highest estimated 

chronic dietary food + drinking water exposure). As the short-term aggregate MOEs are greater 

than 100, risk estimates do not exceed HED’s LOC. 

Table 7.1. Short-Term Aggregate Risk Calculations for Novaluron.

Population

Subgroups

Short-Term Scenario1

NOAEL

(mg/kg/day) LOC2

Max 

Exposure3

(mg/kg/day)

Average 

Dietary 

Exposure

(mg/kg/day)

Residential 

Exposure4

(mg/kg/day)

Aggregate 

MOE

(dietary and 

residential)5

Adult 4.38 100 0.0438 0.002671 0.00014 1560

Children 1-2 

years old 4.38 100 0.0438 0.008014 0.00464 350

1 A dermal endpoint has not been selected for novaluron; therefore, dermal exposure was not included in the short-term aggregate 

assessment. 

2 The LOC (target MOE) includes 10X for interspecies extrapolation and 10X for intraspecies variation.

3 Maximum Exposure (mg/kg/day) = NOAEL/Target MOE.

4 Residential Exposure = Handler Inhalation Exposure for Adults and Post-application Oral Exposure + Post-application 

Inhalation Exposure for Children.

5 Aggregate MOE = [NOAEL ÷ (Avg. Dietary Exposure + Residential Exposure)].

7.2 Intermediate- and Long-Term Aggregate Risk 

Intermediate-term (1- to 6-months) and long-term (>6 months) aggregate risk assessments are 

necessary since there is the potential for intermediate- and long-term post-application exposure 

from the registered pet spot-on use of novaluron. For the intermediate- and long-term aggregate 

risk assessment, potential residential exposures were combined with dietary (food and drinking 

water) exposures. A dermal endpoint has not been selected for novaluron, and inhalation 

exposure is considered negligible for the application of spot-on products; therefore, the 

intermediate- and long-term aggregate risk estimates do not include dermal and inhalation 

exposures. For young children, the intermediate- and long-term aggregate assessment combines 

dietary exposure with potential post-application incidental oral exposure (from hand-to-mouth 

contact with treated pets) resulting from the dog spot-on use. For adults, since there is no 

dermal endpoint and inhalation exposure is expected to be negligible, the average dietary
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consumption (food + drinking water) exposure estimate is representative of intermediate- and 

long-term aggregate risk. See Table 6.3 for more information on the residential risk estimates 

that are recommended for use in the aggregate assessment for novaluron. 

The intermediate- and long-term indoor residential exposure estimates were aggregated with the 

chronic dietary (food+ drinking water) to provide a worst-case estimate of intermediate- and 

long-term aggregate risk for adults and children 1-2 years old (the child population subgroup 

with the highest estimated chronic dietary food + drinking water exposure). As the intermediateand long-term aggregate MOEs are greater than 100, risk estimates do not exceed HED’s LOC. 

Table 7.2. Intermediate- and Long-Term Aggregate Risk Calculations for Novaluron.

Population

Subgroups

Intermediate/Long-Term Scenarios

1

NOAEL

(mg/kg/day) LOC2

Max 

Exposure3

(mg/kg/day)

Average 

Dietary 

Exposure

(mg/kg/day)

Residential 

Exposure4

(mg/kg/day)

Aggregate 

MOE

(dietary and 

residential)5

Adult 4.38 100 0.0438 0.002671 N/A 1640

Children 1-2 

years old 4.38 100 0.0438 0.008014 0.00022 530

1 A dermal endpoint has not been selected for novaluron, and inhalation exposure is considered negligible for the application of 

spot-on products; therefore, the intermediate- and long-term aggregate risk estimates do not include dermal and inhalation 

exposures. 

2 The LOC (target MOE) includes 10X for interspecies extrapolation and 10X for intraspecies variation.

3 Maximum Exposure (mg/kg/day) = NOAEL/Target MOE.

4

For adults, since there is no dermal endpoint and inhalation exposure is expected to be negligible, there is no residential 

exposure estimate to combine with dietary exposures. For children, Residential Exposure = Incidental Oral Exposure. 

5 Aggregate MOE = [NOAEL ÷ (Avg. Dietary Exposure + Residential Exposure)].

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 novaluron and any other substances and novaluron 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 novaluron 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

Occupational exposure assessments of the proposed uses were provided in HED memorandum 

dated 20-MAR-2015 (L. Venkateshwara; D423666). 

9.1 Short-/Intermediate-Term Handler Risk

HED uses the term handlers to describe those individuals who are involved in the pesticide 

application process. HED believes that there are distinct job functions or tasks related to 

applications and exposures can vary depending on the specifics of each task. Job requirements 

(amount of chemical used in each application), the kinds of equipment used, the target being 
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treated, and the level of protection used by a handler can cause exposure levels to differ in a 

manner specific to each application event. 

Based on the anticipated use patterns and current labeling, types of equipment and techniques 

that can potentially be used, occupational handler exposure is expected from the proposed uses. 

The quantitative exposure/risk assessment developed for occupational handlers is based on 

mixing, loading, and applying liquids via aerial, groundboom, and airblast equipment, mixing, 

loading, and applying liquids by backpack sprayers, manually-pressurized handwands, and

mechanically-pressured handguns, and flagging to support aerial applications. 

In addition, the petitioner has requested to expand the use pattern for succulent beans and to 

update crop groupings for fruiting vegetables (group 8-10), pome fruit (group 11-10), cherry

(subgroup 12-12A), peach (subgroup 12-12B), and plum (subgroup 12-12C). No amendments to 

the use patterns (i.e., maximum use rates, RTIs, PHIs, use of adjuvants, etc.) on the subject crops 

have been proposed, including the proposed expanded use on succulent beans. Since there is no 

difference between the occupational scenarios and the agronomics/practices already assessed for 

the revised crop group definitions, the additional crops are already covered by an existing risk 

assessment within its crop group (D364236, L. Venkateshwara, 11/5/2009). 

It is the policy of HED to use the best available data to assess handler exposure. Sources of 

generic handler data, used as surrogate data in the absence of chemical-specific data, include the 

Pesticide Handlers Exposure Database (PHED 1.1), the Agricultural Handlers Exposure Task 

Force (AHETF) database, the Outdoor Residential Exposure Task Force (ORETF) database, or 

other registrant-submitted occupational exposure studies. Some of these data are proprietary

(e.g., AHETF data), and subject to the data protection provisions of FIFRA. The standard values 

recommended for use in predicting handler exposure that are used in this assessment, known as 

“unit exposures,” are outlined in the “Occupational Pesticide Handler Unit Exposure Surrogate 

Reference Table2,” which, along with additional information on HED policy on use of surrogate 

data, including descriptions of the various sources, can be found at the Agency website3. 

Based on HED Science Advisory Council for Exposure (ExpoSAC) SOP No. 9.1, the amount 

treated in a day was assumed to be:

 80 acres for groundboom applications for typical acreage crops (carrot), 

 40 acres for airblast applications for orchard crops (avocado), 

 350 acres for aerial applications for typical acreage crops (carrot) and orchard crops 

(avocado), 

 350 acres for flagging to support aerial treatment,

 40 gals for mixing/loading and applying to support backpack and manually-pressurized 

handwand, and

 1000 gals for mixing/loading and applying to support mechanically-pressurized handgun.

HED classifies exposures from 1 to 30 days as short-term and exposures and 30 days to 6 months 

as intermediate-term. Exposure duration is determined by many things, including the exposed 

population, the use site, the pest pressure triggering the use of the pesticide, and the cultural 

practices surrounding that use site. For most commercial pest control, it is reasonable to believe 

that occupational handlers will not apply the same chemical every day for more than a one-

 

2 Available: http://www.epa.gov/opp00001/science/handler-exposure-table.pdf

3 Available: http://www.epa.gov/pesticides/science/handler-exposure-data.html
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month time frame; however, commercial applicators may apply a product over a period of 

weeks.

The Rimon® 0.83EC Insecticide (EPA Reg. No. 66222-35) label requires applicators and other 

handlers to wear a long-sleeved shirt, long pants, protective eyewear, chemical-resistant gloves, 

and shoes plus socks.

The Agency matches quantitative occupational exposure assessment with appropriate 

characterization of exposure potential. While HED presents quantitative risk estimates for 

human flaggers where appropriate, agricultural aviation has changed dramatically over the past 

two decades. According the 2012 National Agricultural Aviation Association (NAAA) survey of 

their membership, the use of the Global Positioning System (GPS) for swath guidance in 

agricultural aviation has grown steadily from the mid-1990s. Over the same time period, the use 

of human flaggers for aerial pesticide applications has decreased steadily from ~15% in the late 

1990s to only 1% in the most recent (2012) NAAA survey. The Agency will continue to monitor 

all available information sources to best assess and characterize the exposure potential for human 

flaggers in agricultural aerial applications.

HED has no data to assess exposures to pilots using open cockpits. The only data available is for 

exposure to pilots in enclosed cockpits. Therefore, risks to pilots are assessed using the 

engineering control (enclosed cockpits) and baseline attire (long-sleeve shirt, long pants, shoes, 

and socks); per the Agency’s Worker Protection Standard stipulations for engineering controls, 

pilots are not required to wear protective gloves for the duration of the application. With this 

level of protection, there are no risk estimates of concern for applicators.

The dermal route of exposure was not quantitatively assessed for handler exposure because a 

dermal endpoint was not selected for any exposure duration. Table 9.1 presents the 

exposures/risks for short and intermediate-term inhalation exposures at baseline. The inhalation 

risk estimates are not of concern (i.e., MOEs >100) at all baseline scenarios. There is no 

respirator on the label.
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1 Based on “Occupational Pesticide Handler Unit Exposure Surrogate Reference Table” (March 2013); includes data from PHED/ORETF/AHETF (level of mitigation: Baseline, PPE, Eng. Controls). 

2 Based on registered or proposed label (Reg. No. # 66222-35).

3 Exposure Science Advisory Council Policy #9.1.

4

Inhalation Dose =Inhalation Unit Exposure (μg/lb ai) x Conversion Factor (0.001 mg/ug) x Application Rate (lb ai/gallon) x Amount Handled Daily (gallons/day) /BW (80 kg).

5

Inhalation MOE = Inhalation NOAEL (4.38 mg/kg/day)/ Inhalation Dose (mg/kg/day).

Table 9.1. Short-and Intermediate-Term Occupational Exposure and Risk Estimates for Novaluron. All Estimates are at Baseline Mitigation (i.e., Without Respirator, 

Unless Specified). 

Exposure Scenario Crop or 

Target

Inhalation Unit Exposure (ug/lb 

ai)1 Maximum Application 

Rate2

Area Treated or 

Amount Handled 

Daily3

Inhalation

Mitigation Level Dose (mg/kg/day)4 MOE5

Mixer/Loader

M/L,

EC, Groundboom Applications

Carrot 0.219 0.079 lb ai/A 80 0.0000173 250,000

M/L, 

EC, Aerial Applications

Avocado 0.219 0.125 lb ai/A

350

0.00012 37,000

Carrot 0.079 lb ai/A 0.0000758 58,000

M/L, 

EC, Airblast Applications Avocado 0.219 0.125 lb ai/A 40 0.0000138 320,000

Applicator

Applicator, Spray, Groundboom Open Cab Carrot 0.34 0.079 lb ai/A 80 0.0000034 160,000

Applicator, Spray, Aerial, Broadcast

Avocado 0.068 

(Engineering Control) 0.125 lb ai/A 350 0.00000268 1,600,000

Carrot 0.068 

(Engineering Control) 0.079 lb ai/A 350 0.00000169 2,600,000

Applicator, Spray, Airblast, Broadcast Avocado 4.71 0.125 lb ai/A 40 0.000295 15,000

Flagger

Flagger, Liquids

Avocado

0.035

0.125 lb ai/A 350 0.000191 23,000

Carrot 0.079 lb ai/A 350 0.000121 36,000

Mixer/Loader/Applicator

Mixer/Loader/Applicator, Backpack Sprayer Greenhouse 

grown 

vegetable 

(tomato and 

cucumber)

0.140 0.0008 lb ai/gal 40 gallons 0.000056 78,000

Mixer/Loader/Applicator, Manuallypressurized Handwand 0.03 0.0008 lb ai/gal 40 gallons 0.000012 370,000

Mixer/Loader/Applicator, Mechanicallypressurized Handgun Sprayer 0.120 0.0008 lb ai/gal 1000 gallons 0.0012 3,700
Novaluron Human-Health Risk Assessment DP No. 426068

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9.2 Short-/Intermediate-Term Post-Application Risk

HED uses the term post-application to describe exposures that occur when individuals are 

present in an environment that has been previously treated with a pesticide (also referred to as reentry exposure). Such exposures may occur when workers enter previously treated areas to 

perform job functions, including activities related to crop production, such as scouting for pests 

or harvesting. Post-application exposure levels vary over time and depend on such things as the 

type of activity, the nature of the crop or target that was treated, the type of pesticide application, 

and the chemical’s degradation properties. In addition, the timing of pesticide applications, 

relative to harvest activities, can greatly reduce the potential for post-application exposure. Also 

post-application exposures are anticipated based on the proposed new uses of novaluron.

9.2.1 Inhalation Post-application Risk

There are multiple potential sources of post-application inhalation exposure to individuals 

performing post-application activities in previously treated fields. These potential sources 

include volatilization of pesticides and resuspension of dusts and/or particulates that contain 

pesticides. The Agency sought expert advice and input on issues related to volatilization of 

pesticides from its FIFRA SAP in December 2009, and received the SAP’s final report on March 

2, 2010 (http://www.epa.gov/scipoly/SAP/meetings/2009/120109meeting.html). The Agency

has evaluated the SAP report and has developed a Volatilization Screening Tool and a 

subsequent Volatilization Screening Analysis 

(http://www.regulations.gov/#!docketDetail;D=EPA-HQ-OPP-2014-0219). During Registration 

Review, the Agency will utilize this analysis to determine if data (i.e., flux studies, route-specific 

inhalation toxicological studies) or further analysis is required for novaluron.

In addition, the Agency is continuing to evaluate the available post-application inhalation 

exposure data generated by the Agricultural Reentry Task Force (ARTF). Given these two 

efforts, the Agency will continue to identify the need for and, subsequently, the way to 

incorporate occupational post-application inhalation exposure into the agency's risk assessments.

Although a quantitative occupational post-application inhalation exposure assessment was not 

performed, an inhalation exposure assessment was performed for occupational/commercial 

handlers. Handler exposure resulting from application of pesticides outdoors is likely to result in 

higher exposure than post-application exposure. Therefore, it is expected that these handler 

inhalation exposure estimates would be protective of most occupational post-application 

inhalation exposure scenarios.

The Worker Protection Standard for Agricultural Pesticides contains requirements for protecting 

workers from inhalation exposures during and after greenhouse applications through the use of 

ventilation requirements [40 CFR 170.110, (3) (Restrictions associated with pesticide 

applications)].

9.2.2 Dermal Post-application Risk

Although there is potential for dermal post-application exposure, a quantitative dermal postapplication risk assessment was not conducted because no dermal hazard was identified. 
Novaluron Human-Health Risk Assessment DP No. 426068

Page 34 of 41

Novaluron is classified as acute Toxicity Category III for acute dermal toxicity. It is classified as 

Toxicity Category IV for primary eye irritation and primary skin irritation. Therefore, the 

interim Worker Protection Standard (WPS) REI of 12 hours is adequate to protect agricultural 

workers from post-application exposures to novaluron.

10.0 References

Previous Risk Assessments

 Van Alstine, J., et al., 05-FEB-2014, D409210. Novaluron: Human health Risk 

Assessment for Proposed Section 3 Uses to Control Fleas, Cockroaches, Crickets, Litter 

Beetles, Ants, and Flying Insect Pests on Furniture, Animal Quarters, Carpets, Kennels, 

Livestock and Poultry Houses, Food and Non-Food Warehouses, in Food-Handling 

Establishments, Around Perimeters, and Lawns.

 Van Alstine, J., et al., 21-MAY-2013, D404422. Novaluron: Human health Risk 

Assessment for Proposed Section 3 Uses as a Dog Spot-On and in Cattle and Poultry

Operations and Horse Barns. 

 Van Alstine, J., et al., 15-MAY-2013, D400705. Novaluron: Human health Risk 

Assessment for Proposed Section 3 Uses on Peanut and Soybean. 

 Venkateshwara, L. et al., 15-SEP-2011, D377471. Novaluron: Human health Risk 

Assessment for Proposed Section 3 Uses on Sweet Corn and in Food- or Feed-Handling 

Establishments. 

HASPOC Memo

 Van Alstine, J., 17-APR-2012, TXR # 0052351. Novaluron: Summary of Hazard and 

Science Policy Council (HASPOC) Meeting of March 15, 2012: Recommendations on 

the requirement of a subchronic inhalation study for novaluron.

Dietary Memo

 R. Duncan, et al., 20-APR-2015, D426069. Novaluron. Chronic Dietary (Food and 

Drinking Water) Exposure and Risk Assessment for the Proposed Uses on Avocado; 

Carrot; Succulent Bean; Updated Crop Groupings for Vegetable, Fruiting, Crop Group 8-

10; Fruit, Pome, Crop Group 11-10; Cherry Subgroup 12-12A; Peach Subgroup 12-12B; 

and Plum Subgroup 12-12C; and Revisions to the Label to Include Uses on GreenhouseGrown Cucumber.

Drinking Water Memos

 Zhong, H., 07-AUG-2013, D412441. Drinking Water Assessment in Support of the New 

Indoor and Outdoor non-food Use of Novaluron for Pest Control.

 Zhong, H., 02-SEP-2014; D418740. Drinking Water Assessment in Support of IR-4 New 

and Revised Uses of Novaluron (RIMON®0.83 EC) on Avocado; Beans, Berries (LowGrowing), Bushberries, Carrot; Cotton, Cucurbit Vegetables, Fruiting Vegetables, Head 

and Stem Brassica, Leafy Brassica Greens, Ornamentals (Container Grown Ornamentals 

in Greenhouses, Shadehouses, Outdoor Nurseries), Peanuts, Pears, Pome Fruits, Potatoes 

/ Sweet Potatoes, Sorghum, Soybeans, Stonefruits, Sweet Corn, Sugarcane, Swiss Chard, 

and Turnip Greens.
Novaluron Human-Health Risk Assessment DP No. 426068

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Chemistry Memo

 Van Alstine, J. 16-JUN-2015; D418739. Novaluron. Petition for the Establishment of 

Permanent Tolerances for Residues of Novaluron in/on Avocado; Carrot; Bean, 

Succulent; Vegetable, Fruiting, Crop Group 8-10; Fruit, Pome, Crop Group 11-10; 

Cherry Subgroup 12-12A; Peach Subgroup 12-12B; and Plum Subgroup 12-12C; and 

Revisions to the Label to Include Uses on Greenhouse-Grown Cucumber. Summary of 

Analytical Chemistry and Residue Data.

Occupational and Residential Exposure Memos

 Venkateshwara, L. 20-MAR-2015, D423666. Novaluron. Occupational and Residential 

Exposure Assessment for a Proposed Use on Avocado, Carrot, Greenhouse Tomatoes and 

Greenhouse Cucumbers, and the Expansion of Various Crop Groups Including: Beans, 

Fruiting Vegetable Group 8-10, Pome Fruit Group 11-10, Cherry Subgroup 12-12A, 

Peach Subgroup 12-12B, Plum Subgroup 12-12C.

 Venkateshwara, L., 06-NOV-2013, D412298. Novaluron. Occupational and Residential 

Exposure Assessment for a Proposed Use to Control Fleas, Cockroaches, Crickets, Litter 

Beetles, Ants and Flying Insect Pests on Furniture, Animal Quarters, Carpets, Kennels, 

Poultry Houses, and Lawns.

 Venkateshwara, L., 21-MAY-2013, D410803. Novaluron: Occupational and Residential 

Exposure and Risk Assessment for Proposed Pet Spot-On Use.

 Venkateshwara, L., 30-APR-2013, D401261, Novaluron. Occupational and Residential 

Exposure Assessment for a Proposed Use on Peanuts and Soybeans and a Reevaluation 

of Existing Residential Uses with the Updated Residential SOPs.

 Venkateshwara, L., 25-JAN-2011, DP 378634, Novaluron Occupational and Residential 

Exposure/Risk Assessment for a Crack and Crevice Use. 

cc: J. Van Alstine, A. Dunbar, L. Venkateshwara

RDI: RAB1 (04-MAR-2015); G. Kramer (03-MAR-2015); B. Smith (04-MAR-2015)

J. Van Alstine: S-10951: Potomac Yard 1 (PY1): (703)603-8866: 7509P: RAB1
Novaluron Human-Health Risk Assessment DP No. 426068

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Appendix A. Toxicology Profile and Executive Summaries

A.1 Toxicology Data Requirements

The requirements (40 CFR 158.340) for novaluron are in Table A.1. Use of the new guideline numbers does not 

imply that the new (1998) guideline protocols were used.

Table A.1. Toxicology Data Requirements.

Study

Technical

Required Satisfied

870.1100 Acute Oral Toxicity.......................................................

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

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

870.2400 Acute Eye Irritation .......................................................

870.2500 Acute Dermal Irritation .................................................

870.2600 Skin Sensitization ..........................................................

Yes

Yes

Yes

Yes

Yes

Yes

Yes

Yes

Yes

Yes

Yes

Yes

870.3100 90-Day Oral Toxicity in Rodents ..................................

870.3150 90-Day Oral Toxicity in Nonrodents.............................

870.3200 21/28-Day Dermal Toxicity...........................................

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

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

Yes

No

Yes

No

No1

Yes

--

Yes

--

--

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

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

870.3800 Reproduction and Fertility Effects.................................

Yes

Yes

Yes

Yes

Yes

Yes

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

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

870.4200a Carcinogenicity (rat)......................................................

870.4200b Carcinogenicity (mouse)................................................

870.4300 Combined Chronic Toxicity/Carcinogenicity (mice 

and rats)............................................................................................

No

Yes

No

No

Yes

--

Yes

--

--

Yes

870.5100 Mutagenicity—Bacterial Reverse Mutation Test ..........

870.5300 Mutagenicity—Mammalian Cell Gene Mutation Test ..

870.5375 In vitro Mammalian Chromosomal Aberrations............

870.5395 Mammalian Erythrocyte Micronucleus.........................

870.5550 Unscheduled DNA Synthesis

870.5550 Mutagenicity–Rec assay with Bacillus subtilis

Yes

Yes

Yes

Yes

Yes

Yes

Yes

Yes

Yes

Yes

Yes

Yes

870.6200a Acute Neurotoxicity Screening Battery (rat) .................

870.6200b 90-Day Neurotoxicity Screening Battery (rat)...............

870.6300 Developmental Neurotoxicity........................................

Yes

Yes

No

Yes

Yes

--

870.7485 Metabolism and Pharmacokinetics................................

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

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

Yes

Yes

Yes

Yes

Yes

Yes

1 The HASPOC concluded that a subchronic inhalation toxicity study is not required at this time (Memo, J. Van 

Alstine, 17-APR-2012; TXR # 0052351). 
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A.2 Toxicity Profiles

Table A.2.1. Acute Toxicity of Novaluron.

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

870.1100

(81-1) Acute Oral (rat) 44961001 LD50 >5000 mg/kg IV

870.1200

(81-2) Acute Dermal (rat) 45003201 LD50 >2000 mg/kg III

870.1300

(81-3) Acute Inhalation (rat) 45003202 LC50 >5.15 mg/L IV

870.2400

(81-4) Primary Eye Irritation (rabbit) 45003203 Not an eye irritant IV

870.2500

(81-5 ) Primary Skin Irritation (rabbit) 45003204 Not a dermal irritant IV

87.2600

(81-6) Dermal Sensitization (guinea pig) 45084001 Not a dermal sensitizer N/A

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

Guideline 

No. 

Study Type MRID No. (year)/ 

Classification/Doses

Results

870.3100 90-Day oral 

toxicity (rat)

45651504/45651503 

(1993/1990);

Acceptable/guideline

Study I: 0, 50, 100, 200, 

or 400 ppm (equivalent to 

0, 3.52, 6.93, 13.03, and

27.77 mg/kg bw/day, 

respectively in males and 

0, 4.38, 8.64, 17.54, and 

34.39 mg/kg bw/day, 

respectively in females)

Study II: 0, 10, 320, or 

10,000

ppm (equivalent to 0, 0.7, 

22.2, and 713 mg/kg 

bw/day, respectively in 

males and 0, 0.8, 24.3, 

and 754 mg/kg bw/day, 

respectively in females)

NOAEL = 320 ppm (22.2 mg/kg/day) in males 

and 50 ppm (4.38 mg/kg/day) in females.

LOAEL = 400 ppm (27.77 mg/kg/day) in males 

based on increased occurrence of 

extramedullary hematopoiesis and 

hemosiderosis in spleen; and 100 ppm (8.64 

mg/kg/day) in females based on reduction in 

hemoglobin, hematocrit, and RBC count; 

increased occurrence of extramedullary 

hematopoiesis in the spleen and hemosiderosis 

in the spleen and liver.

870.3200 28-Day dermal 

toxicity (rat)

45288501 (1998);

0, 75, 400, 1000 

mg/kg/day 

Acceptable/Guideline

Systemic NOAEL = 1000 mg/kg/day. 

LOAEL = not established.

Dermal NOAEL = 1000 mg/kg/day.

LOAEL = not established.

870.3700a Prenatal 

developmental in 

(rat)

45082602 (1997); 

0, 250, 500, 1000 

mg/kg/day

Acceptable/Guideline

Maternal NOAEL = 1000 mg/kg/day. 

LOAEL = not established. 

Developmental NOAEL = 1000 mg/kg/day. 

LOAEL = not established.

870.3700b Prenatal 

developmental in 

(rabbit)

45638316, 45638318, 

45638317

(1997,1998);

0, 100, 300, 1000 

mg/kg/day 

Acceptable/Guideline

Maternal NOAEL = 1000 mg/kg/day.

LOAEL = not established.

Developmental NOAEL = 1000 mg/kg/day. 

LOAEL = not established.
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Table A.2.2. Subchronic, Chronic, and Other Toxicity Profile.

Guideline 

No. 

Study Type MRID No. (year)/ 

Classification/Doses

Results

870.3800 Reproduction and 

fertility effects

(rat)

45651505 (Main Study, 

1999), 45638319 

(Preliminary Study, 

1998); 

0, 1000, 4000, or 12,000 

ppm ;

M: 0, 74.2, 297.5, or 

894.9 mg/kg/day 

F: 0, 84.0, 336.7, or 

1009.8 mg/kg/day

Acceptable/Guideline

Parental NOAEL = not established. 

LOAEL (M/F) = 74.2/84.0 mg/kg/day based on 

increased absolute and relative spleen weights.

Offspring NOAEL = not established. 

LOAEL (M/F) = 74.2/84.0 mg/kg/day based on 

increased absolute and relative spleen weights.

Reproductive NOAEL (M/F) = 74.2/1009.8 

mg/kg/day. 

LOAEL (M) = 297.5 mg/kg/day based on 

decreased epididymal sperm counts and 

increased age of preputial separation in the F1

generation. 

Reproductive LOAEL for females was not 

established.

870.4100a Chronic toxicity

(dog)

45638320 (1999);

0, 10, 100, 1000 

mg/kg/day 

Acceptable/Guideline

NOAEL = 10 mg/kg/day.

LOAEL = 100 mg/kg/day based on 

hematologic changes associated with 

histopathological changes in liver and spleen.

870.4200 Chronic/ 

Carcinogenicity

(rat)

45651506 (1995);

0, 25, 700, or 20,000 ppm 

test material;

M: 0, 1.1, 30.6, and 884.2 

mg/kg/day 

F: 0, 1.4, 39.5, and 

1113.5 mg/kg/day

Acceptable/Guideline

NOAEL (M/F) = 1.1/1.4 mg/kg/day.

LOAEL (M/F) = 30.6/39.5 mg/kg/day based on 

erythrocyte damage and turnover resulting in a 

regenerative mild anemia.

No Evidence of Carcinogenicity

870.4300 Chronic/ 

Carcinogenicity

(mouse)

45651507/45877901 

(2000/2003);

0, 30, 450, or 7000 ppm 

test material;

M: 0, 3.6, 53.4, or 800.0 

mg/kg/day 

F: 0, 4.3, 63.3, or 913.4 

mg/kg/day

Acceptable/Guideline

NOAEL (M/F) = 3.6/4.3 mg/kg/day.

LOAEL (M/F) = 53.4/63.3 mg/kg/day based on 

increased erythrocyte turnover due to 

hemoglobin oxidation and resulting in a mild 

anemia.

No Evidence of Carcinogenicity

870.5100 Salmonella 

typhimurium and 

Escherichia coli

Reverse Mutation 

Assay

44961013 (1997);

0, 312.5, 625, 1250, 2500, 

or 5000 μg/plate in the 

presence and absence of 

metabolic activation (±S9)

Acceptable/Guideline

Novaluron, tested up to the limit of solubility 

(2500 μg/plate) and the limit dose (5000 

μg/plate), was not cytotoxic with or without S9 

activation in four S. typhimurium strains and 

one strain of E. coli, and did not induce a 

genotoxic response in any strain.

870.5100 Salmonella 

typhimuriumbacterial reverse 

gene mutation 

assay

45030003 (1986);

0, 10, 33, 100, 333, 1000, 

or 3333 μg/plate in the 

presence and absence of 

mammalian metabolic 

activation (±S9)

Acceptable/Guideline

Novaluron, tested up to the limit of solubility 

(3333 μg/plate), was not cytotoxic with or 

without S9 activation in five S. typhimurium

strains, and did not induce a genotoxic response 

in any strain.

870.5300 Gene Mutation 45638321(1989);

0, 50, 100, 125, 150, 175, 

or 200 μg/mL with and 

without metabolic 

activation (S9-mix) in two 

independent assays.

Acceptable/Guideline

There was no evidence of biologically 

significant induction of mutant colonies over 

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

Guideline 

No. 

Study Type MRID No. (year)/ 

Classification/Doses

Results

870.5375 In vitro

mammalian 

chromosome 

aberration test

44961015 (1992);

40, 200, and 1000 μg/mL, 

with and without 

metabolic activation (±S9)

Acceptable/Guideline

Novaluron produced no evidence of clastogenic 

activity in primary human lymphocytes, in the 

presence or absence of S9 activation.

870.5395 Mammalian 

erythrocyte 

micronucleus test 

in mice

45638322(1989);

0, 1250, 2500, or 5000 

mg/kg body weight

Acceptable/Guideline

There was no statistically significant increase in 

the frequency of micronucleated polychromatic 

erythrocytes in mouse bone marrow at any dose 

or harvest time.

870.5500 Mutagenicity–Rec 

assay with 

Bacillus subtilis

44961014 (1998);

50, 150, 500, 1,500, or 

5,000 μg/plate, with and 

without mammalian 

metabolic activation (±S9)

Acceptable/Guideline

Novaluron was equivocal for bacterial DNA 

damage in the absence of S9 activation, and 

negative for bacterial DNA damage in the 

presence of S9 activation.

870.5550 Unscheduled 

DNA Synthesis in

HeLa S3 Human 

Epitheliod cells

45030002 (1988);

0.125, 0.25, 0.5, 1, 2, 4, 8, 

16, 32, 64, 128, or 256 

μg/mL (±S9)

Acceptable/Guideline

Novaluron was considered not to show any

evidence of causing DNA damage to HeLa S3 

epithelioid cells in this unscheduled DNA 

synthesis test for mutagenic potential.

870.6200a Acute 

neurotoxicity 

screening battery

45082601 (1999);

0, 200, 650, 2000 mg 

novaluron/kg

Acceptable/Guideline

NOAEL = 650 mg/kg/day.

LOAEL = 2000 mg/kg/day based on clinical 

signs (piloerection, irregular breathing), FOB 

parameters (increased head swaying, abnormal 

gait) and neuropathology (sciatic and tibial 

nerve degeneration).

870.6200b Subchronic 

neurotoxicity 

screening battery

46086204 (2002);

0, 17.5/20.5, 174/207, 

1752/2000 mg/kg/day

(M/F)

Acceptable/Guideline

NOAEL (M/F) = 1752/2000 mg/kg/day. 

LOAEL = not established.
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Table A.2.2. Subchronic, Chronic, and Other Toxicity Profile.

Guideline 

No. 

Study Type MRID No. (year)/ 

Classification/Doses

Results

870.7485 Metabolism and 

pharmacokinetics

(rat)

45638401 (2000),

45638323 (1998);

single dose of 2 mg/kg or 

1000 mg/kg, or 14 

multiple 2 mg/kg/day 

doses of unlabeled 

novaluron (Lot no. 

970211/4, 99.3% 

chemical purity) followed 

by a single dose of 

radiolabeled novaluron.

Acceptable/Guideline

Novaluron exhibited marginal absorption (16-

18%), relatively rapid and complete excretion 

within 48 hours primarily via the feces and to a 

lesser extent via urine in rat. Biliary 

contribution for fecal excretion appears to be 

insignificant. Absorption appeared to be 

approaching saturation at high doses. Peak 

plasma concentration occurred at 2-5 hours. 

Urinary metabolite profiles revealed 15 

components and 8 components following 

administration of [chlorophenyl14C]novaluron 

or [difluorophenyl14C]novaluron, respectively. 

The most prevalent urinary metabolite was 2,6-

difluorobenzoic acid represented the majority 

of the urinary radioactivity. Other components 

individually represented no more than 5.9% of 

the dose and most represented considerably less 

than 1%. Parent compound was the most 

prevalent contributor in the feces. The fecal 

metabolite profile revealed two metabolites; 3-

chloro-4-(1,1,2-trifluoro-2-

trifluoromethoxyethoxy)aniline and 1-[3-

chloro-4-(1,1,2-trifluoro-2-

trifluoromethoxyethoxy)phenyl]urea. 

Quantitatively, these were minor components 

accounting for <2% of the dose. In the 

repeated-dose group, some tissues such as fat 

contained measurable radioactivity at 168 hours 

post dose but did not appear to suggest 

significant potential for bioaccumulation or 

sequestration at the doses tested.

870.7600 Dermal 

penetration (rat)

45638415 (2000);

1.0, 0.067, 0.0048, or 

0.0003 mg/cm2

Acceptable/Guideline 

Recovery of administered radioactivity was an 

acceptable 90.19-105.26%. The maximum 

total absorbed dose (expressed as percent of 

administered dose and determined as the sum 

of radioactivity in excreta, cage wash, untreated 

skin, fat, blood, and residual carcass) ranged 

from about 0.5% to 10% of that administered.

870.7600 Immunotoxicity 

(mouse)

48690105 (2011);

0, 100, 1,000, and 10,000 

ppm

(0, 21, 200, 2,115 

mg/kg/day [F])

Acceptable/Guideline

Systemic NOAEL (F) = 2,155 mg/kg/day.

Systemic LOAEL was no observed when tested 

above the limit dose.

Immunotoxicity NOAEL (F) = 200 mg/kg/day. 

Immunotoxicity LOAEL = 2,155 mg/kg/day 

based on decreased anti-SRBC response.
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Appendix B. Physical/Chemical Properties

Table B.1. Physicochemical Properties of Technical Grade Novaluron.

Parameter Value Reference

Melting range 176.5-178.0C

DP# 315780, 3-NOV-2005, 

S. Levy

pH 6.5

Density 1.56 g/cm3

at 22C

Water solubility 3 μg/L at 20C

Solvent solubility (at 25C)

0.00839 g/L in n-heptane

1.88 g/L in xylene

14.5 g/L in methanol

198 g/L in acetone

113 g/L in ethyl acetate

0.98 g/L in n-octanol

Vapor pressure (mm Hg) 1.2 x 10-7

Dissociation constant, pKa Not determined due to low water solubility.

Octanol/water partition coefficient, 

Log(KOW)

4.3 at 25C

UV/visible absorption spectrum

Molar absorption coefficients of at three 

maximum absorbances:

15,400 L/mol  cm at 253 nm (neutral)

9,780 L/mol  cm at 253 nm (acidic)

20,500 L/mol  cm at 263 nm (basic)

Henry’s Constant at 25C 2 x 10-5

atm•m3/mol Product Chemistry, MRID 

44961006

Appendix C. Review of Human Research

This risk assessment relies in part on data from studies in which adult human subjects were 

intentionally exposed to a pesticide or other chemical. These data, which include studies from 

the PHED 1.1, the AHETF database, and the ARTF database are (1) subject to ethics review 

pursuant to 40 CFR 26, (2) have received that review, and (3) are compliant with applicable 

ethics requirements. For certain studies, the ethics review may have included review by the 

Human Studies Review Board. Descriptions of data sources, as well as guidance on their use, 

can be found at the Agency website4. 

 

4

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

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