UNITED STATES ENVIRONMENTAL PROTECTION AGENCY 

WASHINGTON, D.C. 20460 

MEMORANDUM 

DATE: February 25, 2016 

OFFICE OF CHEMICAL SAFETY 

AND POLLUTION PREVENTION 

SUBJECT: Fluazinam. Human Health Risk Assessment to Support Section 3 Registration 

for New Uses on Tuberous and Corm, Subgroup IC, Mayhaw, Squash/Cucumber 

Subgroup 9B; Amended Uses on Cabbage. 

PC Code: 129098 

Decision Nos.: 499960 

Petition Nos.: 5£8349 

DP Barcodes: 0426143 

Registration Nos.: 71512-1 

Regulatory Action: Section 3 Registration 

Risk Assessment Type: Single Chemical Case No.: 7013 

Aggregate 

TXRNo.: NA 

MRIDNo.: NA 

CAS No.: 79622-59-6 

40 CFR: §180.574 

FROM: 

Ger

Elizabeth 

ad Thornton, 

Holman, 

nvironmentalAr

Physical Scienti

~c

st/Risk 

tio~ 

Assessor 

~c alist 

~ rJ--1'11 ' ~ 

Karl yn Middleton, TOX_icologis~;~ J o-rv 

Risk Assessment Branch II J 

Health Effects Division (7509P) 

Sumitra Bose Biswas, Chemist o.Q~ Jrv 

Risk Assessment Branch VI 

Health Effects Division (7509P) 

THROUGH: Chr

Risk 

ist

Assessment 

ina Swartz, 

Branch 

Branch 

II 

Chief ~~ Health Effects Division (7509P) 

TO: Erik Kraft, Risk Manager Reviewer 

Heather Garvie, Review Manager #24 

Fungicide-Herbicide Branch 

A. Willis Ertman, Risk Manager Reviewer 

Barbara Madden, Minor Use Team Leader 

Risk Integration, Minor Use and Emergency Response Branch 

Registration Division (7505P) 

Page 1 of 51 
The Registration Division (RD) requested that the Health Effects Division (HED) conduct an 

exposure and risk assessment for the proposed new uses of fluazinam: (1) adding foliar 

application to the existing use pattern on cabbage; (2) proposed new foliar uses on mayhaw; (3) 

new foliar and banded soil drench uses on squash/cucumber subgroup 9B; and (4) an expansion 

from existing foliar uses on potato to tuberous and corm vegetables subgroup l C. The attached 

human health risk assessment addresses dietary, aggregate and occupational exposure and risk 

associated with the proposed uses of fluazinam. With appropriate mitigation for the identified 

occupational risks, there are no risks of concern associated with these proposed uses. 

Page 2 of 51 
Page 3 of 51

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

2.1 Data Deficiencies/Conditions of Registration .............................................................. 9

2.2 Tolerance Considerations.............................................................................................. 9

2.2.1 Enforcement Analytical Method............................................................................... 9

2.2.2 International Harmonization ................................................................................... 10

2.2.3 Recommended Tolerances...................................................................................... 10

2.2.4 Revisions to Petitioned-For Tolerances.................................................................. 11

2.3 Label Recommendations.............................................................................................. 11

3.0 Introduction...................................................................................................................... 11

3.1 Chemical Identity ......................................................................................................... 12

3.2 Physical/Chemical Characteristics ............................................................................. 12

3.3 Pesticide Use Pattern for Proposed Commodities..................................................... 12

3.4 Anticipated Exposure Pathways................................................................................. 13

3.5 Consideration of Environmental Justice.................................................................... 14

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

5.1 Metabolite/Degradate Residue Profile ....................................................................... 18

5.1.1 Summary of Plant and Animal Metabolism Studies............................................... 18

5.1.2 Summary of Environmental Degradation ............................................................... 19

5.1.3 Comparison of Metabolic Pathways....................................................................... 19

5.1.4 Residues of Concern Summary and Rationale........................................................ 20

5.2 Food Residue Profile .................................................................................................... 21

5.3 Water Residue Profile.................................................................................................. 23

5.4 Dietary Risk Assessment.............................................................................................. 23

5.4.1 Description of Residue Data Used in Dietary Assessment..................................... 23

5.4.2 Percent Crop Treated Used in Dietary Assessment ................................................ 24

5.4.3 Acute Dietary Risk Assessment.............................................................................. 24

5.4.4 Chronic Dietary Risk Assessment .......................................................................... 24

5.4.5 Cancer Dietary Risk Assessment............................................................................ 24

5.4.6 Summary Table....................................................................................................... 25

6.0 Residential (Non-Occupational) Exposure/Risk Characterization ............................. 25

6.1 Residential Handler Exposure and Risk.................................................................... 25

6.2 Residential Post-application Exposure....................................................................... 25

6.3 Combined Residential Risk Estimates........................................................................ 26

6.6 Residential Bystander Post-Application Inhalation Exposure ................................ 28

7.0 Aggregate Exposure/Risk Characterization.................................................................. 28

7.1 Acute Aggregate Risk................................................................................................... 28

7.2 Short-/Intermediate-Term Aggregate Risk Estimates.............................................. 28

7.3 Chronic Aggregate Risk .............................................................................................. 29

7.4 Cancer Aggregate Risk ................................................................................................ 29

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

9.0 Occupational Exposure/Risk Characterization ............................................................ 30

9.1 Occupational Handler Exposure/Risk Estimates...................................................... 30

9.2 Occupational Post-application Exposure/Risk Estimates ........................................ 35

9.2.1 Occupational Post-application Inhalation Exposure/Risk Estimates...................... 35

9.2.2 Occupational Post-application Dermal Exposure/Risk Estimates.......................... 35

10.0 References......................................................................................................................... 38
Page 4 of 51

Appendix A. HEC Inhalation Calculations............................................................................. 39

Appendix B. International Residue Limit Status Sheet ......................................................... 40

Appendix C. Fluazinam Physical/Chemical Properties ......................................................... 41

Appendix D. Review of Human Research................................................................................ 42

Appendix E. Structures of Fluazinam Metabolites and Degradates of Concern.................. 43

Appendix F: Fluazinam Toxicology Profile Tables................................................................ 44
Page 5 of 51

1.0 Executive Summary

The Interregional Research Project No. 4 (IR-4) submitted petitions to establish tolerances 

associated with the following proposed new uses of fluazinam: (1) adding foliar application to 

the existing use pattern on cabbage; (2) proposed new foliar uses on mayhaw; (3) new foliar and 

banded soil drench uses on squash/cucumber subgroup 9B; and (4) an expansion from existing 

foliar uses on potato to tuberous and corm vegetables subgroup 1C. This human health risk 

assessment presents HED’s conclusions with respect to the risk estimates associated with the 

proposed uses for fluazinam. 

Fluazinam (3-chloro-N-[3-chloro-2,6-dinitro-4-(trifluoromethyl)phenyl]-5-(trifluoromethyl)-2-

pyridinamine) is a preventive contact fungicide with a multi-site fungicidal mode of action. It 

disrupts the production of energy at several metabolic sites within the fungal cell. Fluazinam is a 

protectant fungicide. When it is applied to plants, it remains primarily on the plant surface and 

kills any fungal spores that come into contact with it. It is not taken up to any extent by the plant 

and, unlike systemic fungicides, is not translocated within the plant.

HED has assessed exposures and risks from the proposed uses of fluazinam. The petition is for a 

foliar use on mayhaw; a foliar use and a banded soil drench use on squash/cucumber subgroup 

9B; a new foliar use on cabbage (there are existing soil incorporation use and transplant soil 

drench use on cabbage); and an expansion of the foliar use on potato to tuberous and corm 

vegetables 1C. The uses are for the existing end-use product Omega® 500F—an SC containing 

40% fluazinam, 4.17 lbs active ingredient (ai) per gallon of product (EPA Reg. #71512-1). The 

proposed maximum single application rates range from 0.26 to 0.78 lb ai/acre and may be 

applied every 7 to 10 days and up to 10 times per growing season depending on the application 

rate used and the crop. The preharvest interval (PHI) associated with these uses are 7 days on 

cabbage and squash/cucumber, and 28 days on mayhaw. 

Based on the proposed use pattern, the duration of exposure for the proposed uses are expected 

to be short-term (1 to 30 days) and intermediate-term (1 to 6 months). Long-term exposures 

(greater than 6 months) are not anticipated.

Hazard Characterization and Endpoint Selection

The toxicology database for fluazinam is complete. The liver is a primary target organ for 

fluazinam and numerous liver effects were observed in rats, mice, and dogs after oral and dermal 

exposure. After inhalation exposure, portal of entry effects (increased lung/bronchial weights, 

alveolar macrophages and peribronchiolar proliferation) were seen. 

Clinical signs and immune related effects were also observed in toxicity studies; however, clear 

NOAELs have been established for the effects noted and the points of departure (PODs) and 

endpoints selected for risk assessment are protective.

There was no evidence of increased quantitative or qualitative susceptibility in the rabbit 

developmental or rat reproduction studies. However, quantitative susceptibility was seen in rat 

developmental and DNT studies where fetal/offspring effects were observed in the absence of 
Page 6 of 51

maternal toxicity. The concern is low for the increased susceptibility noted in the studies since 

clear NOAELs are established, and the most sensitive endpoints/PODs are used for risk 

assessment. Therefore, the FQPA safety factor has been reduced to 1x. 

Fluazinam is classified as having “Suggestive evidence of carcinogenicity, but not sufficient to 

assess human carcinogenic potential,” based on increases in thyroid gland follicular cell tumors 

in male rats and increases in hepatocellular tumors in male mice. The Cancer Assessment 

Review Committee (CARC) determined that quantification of cancer risk using a non-linear 

approach (i.e., RfD) would adequately account for all chronic toxicity, including carcinogenicity, 

that could result from exposure to fluazinam. There is no mutagenicity concern for fluazinam. 

Since the last risk assessment, the technical ingredient was updated for fluazinam and new acute 

lethality (LD50) studies were submitted. As a result, the Toxicity Category for acute inhalation 

toxicity (II to III) and primary eye irritation (I to III) were revised. For this assessment, the 

toxicological endpoints, points of departure (PODs), and uncertainty factors selected for risk 

assessment remain the same as in the previous assessment. However, the inhalation HECs have 

been updated to incorporate activity specific breathing rates (appendix A). No other substantive 

changes have been made to the hazard characterization/endpoint selection. 

Metabolism/Metabolites and Degradates of Concern

The metabolism of fluazinam in primary crops, rotational crops, and animals has been 

adequately delineated. The residue of concern for risk assessment in bulb vegetables as well as 

in root and tuber vegetables is parent fluazinam. For all other plant commodities, the residues of 

concern in plants for risk assessment are fluazinam and its metabolite AMGT. In drinking water, 

the degradates of concern for risk assessment are parent fluazinam and its transformation 

products. In livestock commodities, the residues of concern for risk assessment are fluazinam,

the metabolites known as AMPA, DAPA, and their sulfamate conjugates.

Food Residue Profile

The food use profiles for the proposed commodities are complete and adequate for tolerance 

setting and risk assessment purposes. The number, geographic representation, and the use 

patterns of the cabbage, cucumber, and squash field trial data are adequate and support the 

requested use patterns. The residue data were generated using a validated data collection 

method, and are supported by adequate storage stability data. No new field trial data were 

submitted to support expansion of the current uses of potato to Vegetables, Tuberous, Corm crop 

subgroup 1C. Since the requested expansion of the crop groups are for the identical formulation 

and use pattern, no new residue chemistry data, including processing studies, are required to 

support these requests. The recommended tolerances for the proposed uses are listed in Table 

2.2.3.

Adequate analytical methods are available for enforcement of tolerances in plant and livestock 

commodities. In addition, the FDA Multiresidue Methods (MRMs) can serve as a confirmatory 

procedure for residues of fluazinam, but not for the metabolites. The necessary analytical 
Page 7 of 51

reference standards for fluazinam are available in the EPA National Pesticide Standards 

Repository.

Dietary Exposure and Risk

Acute and chronic dietary exposure and risk assessments were conducted, including food and 

drinking water contributions from the existing uses as well as the proposed uses. The acute and 

chronic assessments are based on 100% crop treated assumptions and incorporate modeled 

estimated drinking water concentrations (EDWCs) that account for both parent fluazinam and its 

transformation products. Default processing factors were used for all processed commodities for 

which default factors were available. The acute analysis is based on tolerance-level residues for 

all commodities and uses high-end residue estimates for the metabolite AMGT. The chronic 

analysis is based on tolerance-level residues for all commodities except apples. For apples, the 

average field trial value was used. As a result, the acute and chronic exposure and risk estimates 

are considered to be conservative. The acute and chronic dietary risk estimates are below HED’s 

level of concern for all population subgroups, including those comprised of infants and children. 

The acute dietary risk estimate for the general U.S. population is 5.7% of the acute Population 

Adjusted Dose (aPAD). The population subgroup with the highest acute dietary risk estimate is 

Females 13-49, which uses 32% of the aPAD. The chronic dietary risk estimate for the general 

U.S. population is 41% of the chronic PAD (cPAD). The most highly exposed population 

subgroup is All Infants (<1 year old), which uses 92% of the cPAD. As the chronic dietary 

endpoint and dose are protective of potential cancer effects, cancer dietary risk is also not of 

concern. Because such conservative assumptions were made in the assessments, HED is 

confident that the acute and chronic dietary exposure assessments do not underestimate risk to 

the general U.S. population or any population subgroup or life stage.

Residential Exposure and Risk 

The residential exposure database is complete and adequate. There are no proposed residential 

uses; however, there is an existing use of fluazinam on golf course turf. Individuals can be 

exposed when they play golf on treated turf, and therefore a residential dermal post-application 

assessment was previously conducted for golfers. Residential post-application exposure to 

golfers was assessed using the HED Standard Operating Procedures (SOPs) for Residential 

Exposure Assessment (2012), as well as chemical-specific residue data from the turf transferable 

residue (TTR) study. Dermal post-application exposure and risk estimates for golfers resulted in 

MOEs greater than the LOC of 100, and were not of concern (e.g., lowest MOE = 780).

Aggregate Exposure and Risk

The acute aggregate risk estimates are equivalent to the corresponding dietary (food plus water) 

risk estimates, which are not of concern. Chronic dietary exposure is considered to be a 

background exposure level to which the short-term residential exposure is added. The short-term 

aggregate risk assessments resulted in estimated MOEs of 690 to 890. For fluazinam, the LOC 

for short-term risk is an MOE of 100. As the resulting aggregate MOEs exceed the LOC of 100, 

aggregate dietary and residential risk estimates are not of concern.
Page 8 of 51

Occupational

The occupational exposure database is complete and adequate for assessing occupational 

exposure to fluazinam for both the registered and proposed uses.

It is HED policy 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 Version 1.1 (PHED 1.1), and the Agricultural Handler 

Exposure Task Force (AHETF) database. Some of these data are proprietary (e.g., AHETF 

data), and subject to the data protection provisions of FIFRA. Default assumptions established 

by HED’s Science Advisory Council for Exposure were used for parameters such as body 

weight, acres treated, and amount handled.

Occupational handler assessments considered both dermal and inhalation short-term exposures. 

The estimates are considered to be protective of intermediate-term exposure and risk. All 

occupational handler scenarios for dermal and inhalation exposure, with the exception of dermal 

exposure for airblast applicator, are not of concern at the label specified PPE or use of an 

enclosed cockpit for aerial applications. For airblast applicators, risks of concern for dermal 

application were identified, but with additional PPE (e.g., chemically resistant hat), the dermal 

exposure MOEs are above the LOC. Risk estimates of concern were also identified for 

mechanically-pressurized handgun for cabbage and squash/cucumber subgroup 9B, even at the 

highest level of appropriate mitigation available (e.g., double layer and gloves). However, based 

on personal communication with RD, the registrant intends to submit a revised label that will 

prohibit the use of mechanically-pressurized handgun. 

There is potential for dermal exposure during occupational post-application activities, such as 

crop maintenance activities, scouting, irrigation, and harvesting. Chemical-specific dislodgeable 

foliar residue (DFR) studies were submitted by the registrant and reviewed by HED, and the 

results of these studies were incorporated into HED’s review of the existing and proposed uses. 

All post-application dermal scenarios resulted in MOEs greater than the LOC of 100 on day 0, 

with the exception of hand weeding cabbage, and are not of concern. At 12 and 24 hours after 

last application, MOEs for hand weeding cabbage increase to 98 and 100 respectively.

Restricted Entry Interval (REI)

Fluazinam is classified as Toxicity Category III via the dermal route, Toxicity Category IV for 

skin irritation potential, and Toxicity Category III for eye irritation potential. It is also a skin 

sensitizer. Under 40 CFR 156.208 (c) (2), ai’s classified as Acute III or IV for acute dermal, eye 

irritation and primary skin irritation are assigned a 12-hour REI. In the case of hand weeding 

activities on cabbage, identified MOEs were 98 at 12 hours and 100 at 24 hours. However, HED 

does not consider an MOE of 98 at 12 hours to be of concern, as it is essentially equivalent to an 

MOE of 100. All other short- and intermediate-term post-application risk estimates were not a 

concern on day 0. Therefore, the [156 subpart K] Worker Protection Statement interim REI of 

12 hours should be adequate to protect agricultural workers from post-application exposure to 

fluazinam.
2.0 HED Recommendations

HED has no objection to registration of the proposed Section 3 use of fluazinam on mayhaw, 

cabbage, squash/cucumber, and tuberous and corm vegetables, subgroup 1C.

Provided a revised section F (as noted in Section 2.2.4) is submitted, there are no residue 

chemistry considerations that would preclude granting the requested use on cabbage, cucumber, 

squash as well as the necessary tolerances, as listed in Section 2.2.3, required to support those 

uses. HED has no objection to the proposed extrapolation from the apple tolerance to mayhaw 

and expansion of the current use of fluazinam on potato to include all commodities of 

Vegetables, Tuberous and Corm subgroup 1C.

In addition, HED notes that risks of concern were identified for airblast applicators, but with 

additional PPE (e.g. chemically resistant hat), the dermal exposure MOEs are above the LOC 

(see Section 9.0 for further details). 

2.1 Data Deficiencies/Conditions of Registration

None. In addition, as part of this petition, IR-4 submitted previously requested storage stability 

on lettuce. This storage stability data was a condition of registration under a previous petition 

(PP#8E7506). The submitted data are adequate and therefore fulfill this previously identified 

condition of registration. 

2.2 Tolerance Considerations

2.2.1 Enforcement Analytical Method

An adequate GC/ECD method (6148-94-0170-MD-001) entitled “Fluazinam: Method for the 

Analysis in Peanut Nutmeat” (MRID 43521016) is available for enforcing fluazinam tolerances 

on plant commodities. The method was adequately radiovalidated and underwent a successful 

independent laboratory validation (ILV) trial. The method was forwarded to Biological and 

Economic Analysis Division’s (BEAD) Analytical Chemistry Branch (ACB) for a TMV trial, 

and was subsequently determined to be suitable as a tolerance-enforcement method (Memo, 

D266802, P. Golden, 6/22/2001). For this method, residues of fluazinam are extracted with 

methanol:acetic acid (100:2, v/v), filtered, diluted with 0.2 N HCl, and partitioned into hexane. 

Residues are then further partitioned into 0.5 N NaOH, the aqueous phase is acidified, and 

residues are partitioned back into hexane. The resulting hexane fraction is concentrated, and 

residues are purified using a Florisil column eluted with hexane:ethyl ether (80:20, v/v). 

Residues are concentrated to dryness, redissolved in hexane, and analyzed by GC/ECD using 

external standards for quantitation. The method LOQ is 0.01 ppm for fluazinam in plant 

commodities. This method is adequate for tolerance enforcement purposes for all the 

commodities that are subject to this petition.

Adequate FDA multiresidue method (MRM) testing data are available for fluazinam and its 

metabolite AMGT. As fluazinam is partially recovered through Sections 302, 303, and 304 of 

PAM Volume I, the MRMs can serve as a confirmatory procedure for residues of fluazinam. 

The FDA MRM methods are not suitable for determining residues of AMGT.
Fluazinam Human Health Risk Assessment DP No. D426143

Page 10 of 51

Conclusion: Acceptable methodology is available for tolerance enforcement purposes for 

residues of concern in/on all the commodities that are the subject of this assessment. 

2.2.2 International Harmonization

There are currently no Codex or Mexican maximum residue limits (MRLs) for residues of 

fluazinam on cabbage, mayhaw, squash/cucumber subgroup 9B, Vegetable, Tuberous and Corm, 

Subgroup 1C, and Vegetable, Brassica leafy, Group 5, except cabbage. The Agency is currently 

harmonized with Canada in respect to the residue definition in plant commodities. There are no 

Canadian MRLs for both mayhaw and squash/cucumber subgroup 9B. The Canadian MRL for 

cabbage is lower (0.01 ppm) than the proposed US tolerance (3.0 ppm) due to the proposed new 

U.S. use pattern for cabbage. For a summary of the international MRLs, please see Appendix B. 

2.2.3 Recommended Tolerances

The recommended tolerances are listed in Table 2.2.3, and should be added to the table in 

40CFR §180.574(a)(1): Tolerances are established for residues of fluazinam, 3-chloro-N-[3-

chloro-2,6-dinitro-4-(trifluoromethyl)phenyl]-5-(trifluoromethyl)-2-pyridinamine), including its 

metabolites and degradates, in or on the commodities in the table. Compliance with the 

tolerance levels is to be determined by measuring only fluazinam.

Table 2.2.3. Tolerance Summary for Fluazinam.

Commodity Proposed/Existing

Tolerance (ppm)

HED-Recommended 

Tolerance (ppm)

Comments

(correct commodity definition)

40 CFR 180.574(a) (1) Tolerance for Residues.

Cabbage 3.0 3.0 None

Mayhaw 2.0 2.0 Extrapolation from current 

apple tolerance.

Squash/cucumber 

subgroup 9B

0.05 0.07

Cucurbit Vegetables Crop 

Group 9

Existing tolerance (0.07 ppm) 

for melon subgroup 9A can be 

removed from 40CFR and 

replaced by this crop group 

tolerance.

Melon subgroup 9A 0.07 Remove

Cucurbit Vegetables Crop 

Group 9

Existing tolerance (0.07 ppm) 

for melon subgroup 9A can be 

removed from 40CFR and 

replaced by this crop group 

tolerance.

Vegetable, Brassica 

leafy, Group 5, Except 

cabbage

0.01 0.01

Established tolerance for 

Vegetable, Brassica leafy, 

Group 5 can be removed from 

40CFR and replaced by this 

crop group tolerance.
Fluazinam Human Health Risk Assessment DP No. D426143

Page 11 of 51

2.2.4 Revisions to Petitioned-For Tolerances

IR-4 is requested to submit a revised Section F to reflect the tolerance expression for mayhaw, 

cabbage and squash/cucumber subgroup 9B under 40 CFR 180.574 (a) (1) category and remove 

the request to establish tolerances for the for these crops and crop sub/groups under 40 CFR 

180.574 (a) (2) category. According to plant metabolism study, for setting tolerances, the 

residues of concern in plants include fluazinam and AMGT for wine grapes, but only parent

fluazinam for all other plant commodities.

IR-4 is requested to submit a revised Section F proposing a single crop group tolerance for crop

group 9 at 0.07 ppm instead of separate tolerances for subgroups 9A and 9B. As part of the 

revised section F, IR-4 is requested to remove the existing tolerance for melon sub group 9A and 

replace it by cucurbit vegetable crop group 9.

2.3 Label Recommendations

As part of the occupational exposure assessment, HED identified risks of concern associated 

with the use of mechanically-pressurized handgun for cabbage and squash/cucumber subgroup 

9B, even at the highest level of appropriate mitigation available (e.g., double layer and gloves). 

For further details on these risks of concern, please see Section 9.0 of this assessment. Based on 

personal communication with RD, the registrant intends to submit a revised label that prohibits 

the use of this application method. HED concurs that with this label revision, the risks of 

concern will no longer be an issue. 

3.0 Introduction

Vegetable, Tuberous 

and Corm, Subgroup 

1C

0.02 0.02

Established tolerance for 

potato can be removed from 

40CFR and replaced by this 

subgroup tolerance.

40 CFR 180.574(a) (2) Tolerance for Residues

Cabbage 3.0

Remove

Remove the request to 

establish tolerances for these 

crops and crop sub/groups 

under 40 CFR 180.574 (a) (2) 

category. And Submit a revised 

Section F to reflect the 

tolerance expression for 

mayhaw, cabbage and 

squash/cucumber subgroup 9B 

under 40 CFR 180.574 (a) (1) 

category.

According to plant metabolism 

study, for setting tolerances, 

the residues of concern in 

plants include fluazinam and 

AMGT for wine grapes, but 

only parent fluazinam for all 

other plant commodities.

Mayhaw 2.0

Squash/Cucumber 

Subgroup 9B

0.05
Fluazinam Human Health Risk Assessment DP No. D426143

Page 12 of 51

3.1 Chemical Identity

Table 3.1. Fluazinam Nomenclature

Compound Chemical Structure

 

Empirical Formula C13H4Cl2F6N4O4

Molecular Weight 465.1

Common Name Fluazinam

Company Experimental Names Fluazinam, IKF-1216

IUPAC Name 3-chloro-N-(3-chloro-5-trifluoromethyl-2-pyridyl)-α,α,α-trifluoro-2,6-dinitrop-toluidine

CAS Name 3-chloro-N-[3-chloro-2,6-dinitro-4-(trifluoromethyl)phenyl]-5-

(trifluoromethyl)-2-pyridinamine

CAS Number 79622-59-6

End-use Product/(EP) Omega® 500F Fungicide (EPA Reg. No. 71512-1)

Fluazinam Turf Fungicide (EPA Reg. No. 71512-20)

3.2 Physical/Chemical Characteristics

Fluazinam has a relatively high octanol/water partition coefficient. The log KOW value is 3.56

(KOW = 3,630). Fluazinam has a vapor pressure of 1.73 x 10-7 mm Hg at 25oC. See Appendix C

for a listing of fluazinam’s physical and chemical properties. 

3.3 Pesticide Use Pattern for Proposed Commodities

There is currently a single end-use product (EP) for fluazinam registered in the U.S. for use on 

several food and feed crops. This product is Omega® 500F (EPA Reg. No. 71512-1), which is a 

4.17 lb/gal soluble-concentrate (SC) formulation. The proposed use directions are summarized 

in Table 3.3.

OMEGA® 500F may be applied as a foliar spray using aerial, chemigation (i.e., sprinkler 

irrigation system), ground and handheld equipment. The proposed Restricted Entry Interval 

(REI) is 12 hours for all crops and is considered adequate. The Personal Protective Equipment 

(PPE) statement on the proposed label requires applicators, flaggers, and other handlers to wear 

long-sleeved shirt and long pants, socks, chemical-resistant gloves and footwear, and protective 

eyewear. When mixing and loading also wear a chemical-resistant apron. 

N

N

H

CF3

Cl

Cl CF3

NO2 O2N
Fluazinam Human Health Risk Assessment DP No. D426143

Page 13 of 51

The proposed use patterns are shown below in Table 3.3. Fluazinam was previously registered 

for a transplant soil drench and soil incorporation on cabbage. This assessment only considers 

the current petition for a foliar use on cabbage. Fluazinam spray volume ranges from 20 to 100 

gallons per acre for dilute sprays, and 5 to 10 gallons per acre for concentrate ground and aerial 

sprays.

Table 3.3. Summary of Directions for New Uses of Fluazinam.

Applic. 

Timing, Type, 

and Equip.

Formulation 

[EPA Reg. 

No. 71512-1]

Max Single 

Applic. Rate

Max. No. 

Applic. per 

Season

Max. Seasonal 

Applic. Rate PHI Use Directions and 

Limitations lb ai/A lb ai/A days

Cabbage

Aerial, 

Chemigation, 

Groundboom, 

Mechanicallypressurized 

Handgun

OMEGA®

500F

40% ai, 

Soluble 

Concentrate

(4.17 lb 

ai/gal)

0.5

(foliar)

6

(foliar)

3.0

(foliar) 7

Use 20 to 60 gallons of 

water per acre for foliar 

applications. May be 

retreated every 7 days.

Mayhaw

Aerial, Airblast, 

Chemigation, 

Mechanicallypressurized 

Handgun

OMEGA®

500F

40% ai, 

Soluble 

Concentrate

(4.17 lb 

ai/gal)

0.45

(foliar)

10

(foliar)

4.5

(foliar) 28

Applications are based on 

tree size requiring a dilute 

spray of 200 gallons per 

acre. May be retreated every 

7 to 10 days.

Squash/Cucumber Subgroup 9B

Aerial, 

Chemigation, 

Groundboom, 

Mechanicallypressurized 

Handgun

OMEGA®

500F

40% ai, 

Soluble 

Concentrate

(4.17 lb 

ai/gal)

0.78

(foliar)

0.78

(banded soil drench)

4

(foliar)

1

(banded soil 

drench)

3.9

(foliar and 

banded soil 

drench)

7

Use 20 to 60 gallons of 

water per acre for foliar 

applications. May be 

retreated every 7 days.

Tuberous and Corm Vegetables Subgroup 1C

Aerial, 

Chemigation, 

Groundboom, 

Mechanicallypressurized 

Handgun

OMEGA®

500F

40% ai, 

Soluble 

Concentrate

(4.17 lb 

ai/gal)

0.26

(foliar) NS 1.8(foliar) 14

Use 20-100 gallons per 

acre. May be retreated every 

7 to 10 days.

3.4 Anticipated Exposure Pathways

Humans might be exposed to fluazinam in food and drinking water because fluazinam may be 

applied directly to row crops and golf course turfgrass. Residential exposure may occur due to 

contact with treated golf course turf. The registered and proposed uses also result in the potential 

for occupational (handler/post-application) exposures. In addition, applicators might be exposed 
Fluazinam Human Health Risk Assessment DP No. D426143

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while handling the pesticide prior to application, mixing/loading the pesticide, and during 

application.

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://www.eh.doe.gov/oepa/guidance/justice/eo12898.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’s National Health and Nutrition Examination Survey, What We Eat in America, 

(NHANES/WWEIA), and are used in pesticide risk assessments for all registered food uses of a 

pesticide. These data are analyzed and categorized by subgroups based on age, season of the 

year, ethnic group, and region of the country. Additionally, OPP is able to assess dietary 

exposure to smaller, specialized subgroups, and exposure assessments are performed when 

conditions or circumstances warrant. Whenever appropriate, non-dietary exposures based on 

home use of pesticide products and 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 Characterization

Fluazinam is a preventive contact fungicide with a multi-site mode of action. The fungicidal 

mode of action involves disruption of the production of energy at several metabolic sites within 

the fungal cell. Fluazinam is a protectant fungicide. Unlike systemic fungicides, it is not taken 

up to any extent by the plant, and is not translocated within the plant. When applied to plants it 

remains primarily on the plant surface. The mammalian mode of action is unknown at this time.

With the exception of updated human equivalent concentrations (HECs) for inhalation exposure 

to incorporate activity specific breathing rates (see Appendix A), there have been no changes in 

the fluazinam hazard characterization or toxicology database. Therefore, only a brief summary 

of this hazard characterization is provided below. For a detailed fluazinam hazard 

characterization and dose-response characterization, please see the most recent fluazinam risk 

assessment (D397601, D. Dotson, 09/10/2012). Since the last risk assessment, the technical 

product was updated and new acute lethality studies (Appendix F, Table F.1) were submitted for 

the fluazinam technical. As a result, the acute inhalation toxicity category changed from II to III

and primary eye irritation changed from I to III (D407410, C. Swartz, 02/14/2013). 

The toxicology database for fluazinam is complete. The liver is a primary target organ for 

fluazinam and numerous liver effects were observed in rats, mice, and dogs after oral and dermal 
Fluazinam Human Health Risk Assessment DP No. D426143

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exposure. Treatment-related effects were also noted in other organs; however, these effects were 

not regularly observed in all three species or in all studies in a given species. After inhalation 

exposure, portal of entry effects were observed including increases in lung/bronchial weights and 

increased incidences of alveolar macrophages and peribronchiolar proliferation. 

Decreased motor activity was seen at the limit dose in an acute neurotoxicity study. However, 

no signs of neurotoxicity were observed in two subchronic neurotoxicity studies. A neurotoxic 

lesion was observed in subchronic and chronic studies in mice and dogs, as well as in special 

studies in rats. However, a series of special studies were submitted to address the lesions and 

they were found to be reversible and attributed to an impurity (impurity-5). 

There was no evidence of increased quantitative or qualitative susceptibility in a rabbit 

developmental toxicity study or rat reproduction studies. In a rat developmental toxicity study, 

there was evidence of increased quantitative susceptibility (when endpoints are updated to 

current policy). Skeletal abnormalities/facial/palate clefts were seen in fetuses in the absence of 

treatment related maternal toxicity (decreased body weight gain/food consumption seen). In the 

DNT study, increased quantitative susceptibility was also observed; offspring effects (decreased 

pup weight and delayed preputial separation) were seen in the absence of maternal toxicity. 

However, the concern is low for the increased susceptibility seen in the developmental studies 

since clear NOAELs are established, and the most sensitive endpoints are used for risk 

assessment. Therefore, the FQPA safety factor has been reduced to 1x. 

 

Significant suppressions of anti-sheep red blood cell (anti-SRBC) antibody-forming cell assay 

(AFC) response were demonstrated at the highest dose tested in a mouse immunotoxicity study. 

However, clear NOAELs have been established for the effects and the points of departure 

(PODs) and endpoints selected for risk assessment are protective of potential immunotoxicity. 

Fluazinam is classified as having “Suggestive evidence of carcinogenicity, but not sufficient to 

assess human carcinogenic potential,” based on increases in thyroid gland follicular cell tumors 

in male rats and increases in hepatocellular tumors in male mice. The CARC determined that 

quantification of cancer risk using a non-linear approach (i.e., RfD) would adequately account 

for all chronic toxicity, including carcinogenicity, that could result from exposure to fluazinam. 

There is no mutagenicity concern for fluazinam. 

The dose and endpoint for acute dietary risk assessment (general population) were selected from

an acute neurotoxicity study in which clinical signs including decreased motor activity and soft 

stools were observed at high doses. For acute dietary risk assessment for females 13-49, a 

developmental toxicity study in rabbits was used, and the endpoint selected was total litter 

resorptions and skeletal abnormalities. For the chronic dietary risk assessment, the 

carcinogenicity study in mice and the chronic study in dogs were selected as co-critical studies. 

Route-specific toxicity studies were available for assessing both dermal and inhalation risks. In 

the dermal study, the endpoint consisted of liver effects, while in the inhalation study the effects 

observed were lung histopathology and increased lung and bronchial weights. For the dermal 

risk assessment, the dermal toxicity and dermal absorption studies were used to determine a 

refined dermal equivalent dose (RDD) for assessing short- and intermediate-term dermal 
Fluazinam Human Health Risk Assessment DP No. D426143

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exposure. For inhalation exposure, human equivalent concentrations (HECs) and human 

equivalent doses (HEDs) were calculated for use in the inhalation risk assessments. 

For dietary risk assessments, the conventional 100x uncertainty factor was applied (10x

interspecies factor and 10x intraspecies factor). For the dermal assessment, the level of concern 

(LOC) is a margin of exposure (MOE) of 100 (10x interspecies factor and 10x intraspecies 

factor). For inhalation risk assessments, the LOC is an MOE of 30 based on an interspecies 

factor of 3x and an intraspecies factor of 10x; the interspecies factor was reduced from 10x to 3x, 

since calculation of human equivalent calculations (HECs) accounts for pharmacokinetic (not 

pharmacodynamic) interspecies differences between animals and humans.

Table 4.0.a. Toxicological Doses and Endpoints for Fluazinam for Use in Dietary and Non-Occupational Human 

Health Risk Assessments

Exposure/ 

Scenario

Point of 

Departure

Uncertainty/

FQPA 

Safety 

Factors

RfD, PAD, Level of 

Concern for Risk 

Assessment

Study and Toxicological Effects

Acute Dietary 

(General 

population)

NOAEL=

50 mg/kg/day

UF: 100x

UFA= 10x

UFH=10x

FQPA SF=1x

Acute RfD =0.5 

mg/kg/day

aPAD= 0.5mg/kg/day

Acute Neurotoxicity-Rats.

LOAEL = 1000 mg/kg/day based on 

decreased motor activity and soft stools 

on day of dosing. 

Acute Dietary

(Females 13-

49 years of 

age)

NOAEL 

(developmental) 

= 7 mg/kg/day

UF: 100x

UFA= 10x

UFH=10x

FQPA SF=1x

Acute RfD =0.07 

mg/kg/day

aPAD = 0.07mg/kg/day

Developmental Toxicity- Rabbits.

Developmental LOAEL = 12 mg/kg/day 

based on increased incidence of total litter 

resorptions and possibly increased 

incidence of fetal skeletal abnormalities.

Chronic 

Dietary (All 

Populations)

NOAEL=

1.1 mg/kg/day

(mouse study)

UF: 100x

UFA= 10x

UFH=10x

FQPA SF=1x

Chronic RfD =0.011 

mg/kg/day

cPAD

= 0.011mg/kg/day

Co-critical: Carcinogenicity-Mice.

LOAEL = 10.7 mg/kg/day based on liver 

histopathology and increased liver 

weight. 

Chronic Dog.

LOAEL = 10 mg/kg/day based on 

marginal increases in the incidence of 

nasal dryness in females and the 

incidence/severity of gastric lymphoid 

hyperplasia in both sexes. 

Dermal ShortTerm (1-30 

days) 

Dermal POD=

24.4 mg/kg/day

UF: 100x

UFA=10x

UFH=10x

Residential LOC:

MOE = 100 

21-Day Dermal Toxicity-Rats

LOAEL= 100 mg/kg/day based on liver 

effects (increased AST and cholesterol 

levels). Dermal NOAEL=10 mg/kg/day

A Refined Dermal Equivalent Dose 

(RDD) of 24.4 mg/kg/day was calculated 

using the dermal NOAEL and dermal 

absorption data.
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Table 4.0.a. Toxicological Doses and Endpoints for Fluazinam for Use in Dietary and Non-Occupational Human 

Health Risk Assessments

Exposure/ 

Scenario

Point of 

Departure

Uncertainty/

FQPA 

Safety 

Factors

RfD, PAD, Level of 

Concern for Risk 

Assessment

Study and Toxicological Effects

Inhalation 

Short-Term 

(1-30 days) 

NOAEL=

0.003 mg/L 

(See HEC/HED 

calculations in 

Appendix A)

UF: 30x

UFA=3x

UFH=10x

Residential LOC:

MOE = 30

4 week inhalation study in the rat.

LOAEL = 0.020 mg/L based on a dose 

related increase in absolute and relative 

lung/bronchial weights in both sexes. At 

0.100 mg/L, increased lung/bronchial 

weights were also seen , along with lung 

histopathology (alveolar macrophages, 

peribronchiolar proliferation) in both 

sexes.

Cancer (oral, 

dermal, 

inhalation)

Classification: “Suggestive Evidence of Carcinogenicity, but not sufficient to assess human carcinogenic 

potential.”

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

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

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

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

sensitivity among members of the human population (intraspecies). PAD = population adjusted dose (a = acute, c = 

chronic). RfD = reference dose. MOE = margin of exposure. LOC = level of concern. N/A = not applicable. HEC 

= human equivalent concentration; HED = human equivalent dose. RDD= Dermal NOAEL x (animal in vitro 

human in vitro); RDD = 10 mg/kg/day x (40.17%  16.49%) = 24.4 mg/kg/day. 

Table 4.0.b Summary of Toxicological Doses and Endpoints for Fluazinam for Use in

Occupational Human Health Risk Assessments

Exposure/ 

Scenario Point of Departure

Uncertainty/

FQPA Safety 

Factors

Level of Concern for 

Risk Assessment

Study and Toxicological Effects

Dermal 

Short-Term 

(1-30 days); 

Intermediate

-Term (1-6 

months) 

Dermal POD=

24.4 mg/kg/day

UF=100x

UFA=10x

UFH=10x

Occupational LOC for 

MOE = 100 

21-Day Dermal Toxicity-Rats

LOAEL= 100 mg/kg/day based on liver 

effects (increased AST and cholesterol 

levels). Dermal NOAEL=10 mg/kg/day

A Refined Dermal Equivalent Dose 

(RDD) of 24.4 mg/kg/day was calculated 

using the dermal NOAEL and dermal 

absorption data. 
Fluazinam Human Health Risk Assessment DP No. D426143

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Table 4.0.b Summary of Toxicological Doses and Endpoints for Fluazinam for Use in

Occupational Human Health Risk Assessments

Exposure/ 

Scenario Point of Departure

Uncertainty/

FQPA Safety 

Factors

Level of Concern for 

Risk Assessment

Study and Toxicological Effects

Inhalation 

Short-Term 

(1-30 days); 

Intermediate

-Term (1-6 

months) 

NOAEL=

0.003 mg/L 

(See HEC/HED 

calculations in 

Appendix A)

UF=30X

UFA=3x

UFH=10x

Occupational LOC: 

MOE = 30

4 week inhalation study in the rat.

LOAEL = 0.020 mg/L based on a doserelated increase in absolute and relative 

lung/bronchial weights in both sexes. At 

0.100 mg/L, increased lung/bronchial 

weights were also seen, along with lung 

histopathology (alveolar macrophages, 

peribronchiolar proliferation) in both 

sexes.

Cancer 

(oral, 

dermal, 

inhalation)

Classification: “Suggestive evidence of carcinogenicity, but not sufficient to assess human carcinogenic 

potential”

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

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

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

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

sensitivity among members of the human population (intraspecies). MOE = margin of exposure. LOC = level of 

concern. HEC = human equivalent concentration; HED = human equivalent dose. RDD= Dermal NOAEL x (animal 

in vitro  human in vitro); RDD = 10 mg/kg/day x (40.17%  16.49%) = 24.4 mg/kg/day. 

5.0 Dietary Exposure and Risk Assessment 

5.1 Metabolite/Degradate Residue Profile

5.1.1 Summary of Plant and Animal Metabolism Studies

The nature of fluazinam residues in plants is adequately understood based on metabolism studies 

on potatoes, peanuts, apples, and grapes. The residue of concern in peanuts and root and tuber 

vegetables is parent fluazinam for purposes of both dietary risk assessment and tolerance

enforcement (D272624, W. Cutchin, 4/23/2001). For all other crops, the residues of concern 

include both fluazinam and its metabolite AMGT for purposes of dietary risk assessment. For 

tolerance enforcement, the residues of concern in plants include fluazinam and AMGT for wine 

grapes, but only fluazinam for all other plant commodities.

The nature of fluazinam residues in rotational crops is adequately understood. Based on the 

absence of metabolites containing the intact fluazinam nucleus, HED has determined that the 

residue of concern in rotational crops is the parent compound, and that rotational crop tolerances 

are not required for fluazinam. The available confined field rotational crop study supports the 

30-day plantback interval (PBI) that is currently listed on the label for crops without direct uses 

of fluazinam.
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The nature of the residue in livestock is also understood based on acceptable goat and hen 

metabolism studies. The fluazinam residues of regulatory interest in animal commodities are 

parent plus the metabolites AMPA and DAPA and their sulfamate conjugates.

5.1.2 Summary of Environmental Degradation

The environmental fate studies for fluazinam indicate that the parent compound forms 

transformation compounds that, in most cases, are similar in structure to the parent. Fluazinam 

does not undergo degradation. Instead, it undergoes transformation into a series of products, all 

of which are structurally similar to the parent compound. For modeling drinking water residues, 

the Environmental Fate and Effects Division (EFED) assumed that the physicochemical 

characteristics were similar for both the parent and its products (i.e., the total toxic residue 

approach).

5.1.3 Comparison of Metabolic Pathways

Fluazinam is a secondary amine whose substituents are substituted phenyl and pyridinyl rings. 

The primary metabolic and degradation pathways involve reduction of nitro groups on the 

phenyl ring followed by hydrolysis or conjugation of the various substituents on both rings. Two 

of the primary metabolites and degradates are AMPA and DAPA, and their hydrolysis or 

conjugation products. These compounds are primary metabolites in plants, ruminants, poultry, 

drinking water, and rats.

In plants, fluazinam undergoes reduction of one of the nitro groups to an amine, forming AMPA. 

AMPA can then be conjugated with glutathione, with subsequent degradation of the glutathione 

moiety to cysteine. The AMPA-cysteine conjugate then undergoes transamination, reduction, 

and conjugation with glucose to form AMGT. In addition, both rings of fluazinam appear to be 

labile to ring cleavage, and subsequent degradation of the rings into small fragments occurs. 

These fragments can then be incorporated into a variety of natural plant components.

In ruminants and poultry, the metabolism of [14C]-fluazinam is comparable, and involves 

reduction of one or both nitro groups on the phenyl ring to form AMPA, MAPA, or DAPA. 

Fluazinam also undergoes dehalogenation and hydroxylation of the chlorine on the phenyl ring 

to form HYPA. These compounds can then undergo conjugation with glutathione, and 

subsequent degradation of the glutathione component yields a variety of polar compounds. 

Although the ring structure of the parent molecule remains intact, fluazinam per se was only a 

minor component (≤2.7% TRR) of the [14C]-residues in poultry tissues and eggs, and was not 

detected in ruminant tissues or milk.

In drinking water, the primary degradates include DCPA, CAPA, DAPA, HYPA, and AMPA. 

Although there are metabolites and degradates in plants, livestock, and drinking water that were 

not found in the rat, these compounds are structurally similar to the parent compound. The 

toxicity of these compounds is considered to be comparable to that of the parent. The 

toxicological endpoints that were selected for fluazinam are expected to be protective for the 

metabolites and degradates.
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5.1.4 Residues of Concern Summary and Rationale

HED has concluded that the residue of concern in peanuts and root and tuber vegetables is parent 

fluazinam for purposes of both dietary risk assessment and tolerance enforcement (D272624, W. 

Cutchin, 4/23/2001). For all other crops, the residues of concern include both fluazinam and its 

metabolite AMGT for purposes of dietary risk assessment. For tolerance enforcement, the 

residues of concern in plants include fluazinam and AMGT for wine grapes, but only fluazinam 

for all other plant commodities. AMGT is included in the tolerance for wine grapes because it is 

the only adequate measure of misuse for residues in wine. The parent does not serve as a misuse 

measure in wine because it degrades during the fermentation process. Based on structural 

similarity, AMGT is assumed to have comparable toxicity as the parent and, therefore, is 

included for dietary risk assessment in those crops where it is present at significant levels.

Based on the absence of metabolites containing the intact fluazinam nucleus in rotational crop 

studies, HED has determined that the residue of concern in rotational crops is the parent 

compound, and that rotational crop tolerances are not required for fluazinam. The available 

confined field rotational crop study supports the 30-day plant-back interval (PBI) that is 

currently listed on the label for crops without direct uses of fluazinam.

The fluazinam residues of regulatory interest in animal commodities are parent plus the 

metabolites AMPA and DAPA and their sulfamate conjugates. These metabolites were the 

primary metabolites in the ruminant and poultry metabolism studies. AMPA and DAPA are 

structurally similar to fluazinam. They are the products formed by reduction of one or both nitro 

groups on the phenyl ring to form the mono- and di-amino metabolites. Their toxicity is 

assumed to be comparable to that of the parent compound (D272624, W. Cutchin, 4/23/2001). 

Table 5.1.4. Summary of Metabolites and Degradates to be included in the

Risk Assessment and Tolerance Expression

Matrix Residues included in Risk 

Assessment

Residues included in 

Tolerance Expression

Plants Primary Crop: grapes Parent fluazinam and AMGT Parent fluazinam and AMGT

Primary Crop: peanuts, 

root/tuber vegetables, 

bulb vegetables 

Parent fluazinam Parent fluazinam

Primary Crop: all 

others

Parent fluazinam and AMGT Parent fluazinam

Rotational Crop N/A Note: Tolerances are not 

required based on the absence 

of residues in rotational crops 

at the requested plant back 

interval.

Livestock Ruminant Parent fluazinam, AMPA, and 

DAPA, and their sulfate 

conjugates

Parent fluazinam, AMPA, and 

DAPA, and their sulfate 

conjugates
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Table 5.1.4. Summary of Metabolites and Degradates to be included in the

Risk Assessment and Tolerance Expression

Matrix Residues included in Risk 

Assessment

Residues included in 

Tolerance Expression

Poultry Parent fluazinam, AMPA, and 

DAPA, and their sulfate 

conjugates

Parent fluazinam, AMPA, and 

DAPA, and their sulfate 

conjugates

Drinking Water Fluazinam, CAPA, DAPA, 

DCPA, HYPA, and AMPA

Not Applicable

Under 40 CFR §180.574(a)(1), tolerances are established for residues of fluazinam, 3-chloro-N-

[3-chloro-2,6-dinitro-4-(trifluoromethyl)phenyl]-5-(trifluoromethyl)-2-pyridinamine), including 

its metabolites and degradates, in or on the commodities in the table. Compliance with the 

tolerance levels is to be determined by measuring only fluazinam. The existing tolerances for 

residues in grapes and livestock commodities are listed Under 40 CFR §180.574(a)(2) and (a)(3),

respectively, including the relevant coverage and compliance statements. No changes to these 

tolerance expressions are needed in conjunction with the proposed uses.

5.2 Food Residue Profile

The food use profile for the proposed commodities is adequate and complete for tolerance setting 

and risk assessment purposes (D426241, S. Biswas, 09/18/2015). The submitted field trial data 

for fluazinam on cabbage, cucumber, and summer squash are acceptable and support the 

proposed uses. Adequate numbers of trials were conducted in the appropriate geographic regions 

at approximately 1x the maximum proposed rate, and the appropriate samples were collected 

from each test at, or close to, the proposed PHI. Adequate storage stability data were submitted 

for cabbage, cucumber, and summer squash. The data indicated that residues were stable over 

the storage durations used in the field trial and processing studies. 

In addition, as part of this petition, IR-4 submitted previously requested storage stability on 

lettuce. This storage stability data was a condition of registration under a previous petition 

(PP#8E7506). The submitted data are adequate and therefore fulfill this previously identified 

condition of registration. 

Quantifiable residues of fluazinam were found in cucumber, summer squash, and cabbage. The 

ranges of residues in the samples of these commodities can be found in Table 5.2. No 

quantifiable residues of AMGT were found in any samples of any commodities tested. 

No new field trial were submitted for mayhaw, an existing member of pome fruit group 11-10. 

The tolerance for residues on mayhaw was requested based on the June 20th, 2013 ChemSAC 

decision that provides an allowance for extrapolating apple residue data to mayhaw. The 

proposed label and the available field trial data for fluazinam residues in/on apple are adequate 

for the proposed translation of apple data to mayhaw.
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Similarly, no new field trial data were submitted to support the requested expansion of the 

current use on potatoes to the Vegetable, tuberous and corm, subgroup 1C. The representative 

commodity for crop subgroup 1C is potato. Since a potato use is already on the label (Omega® 

500F) for which expansion to crop subgroup 1C is requested, and since the expansion to crop 

subgroup 1C is for the identical use pattern currently registered for potato, no new data are 

required to support the requested use on the crop subgroup 1C. The newly requested use on crop 

subgroup 1C commodities is considered adequately supported by the residue data previously 

submitted to establish the potato use.

There are no processed food or feed commodities associated with the requested use on cabbage, 

cucumber and summer squash; therefore, a discussion of processed foods or feeds is not 

appropriate to this petition. Although there are processed commodities associated with potatoes, 

processing studies were not required since the petitioner has requested a crop group expansion 

which is supported with previously submitted data, including processing studies.

There are no livestock feedstuffs associated with the proposed new use on cabbage, cucumber and 

summer squash. Therefore, the proposed new uses have no impact on the existing tolerances for 

livestock commodities (0.05 ppm for the fat and meat byproducts of cattle, goats, horses, and 

sheep) and these existing livestock tolerances are adequate.

Table 5.2 provides a summary of the cabbage, summer squash, and cucumber field trial data.

Table 5.2. Summary of Fluazinam Field Trial Residue Data.

Crop 

Matrix

Analyte Total 

Application Rate

(lb ai/A)

PHI 

(days)

n

1 Residues (ppm)

Min.2 Max.2 LAFT3 HAFT3 Median3 Mean3 SD3

Cucumbers Fluazinam 3.90-3.96

5.68 (1 trial)

6-7 6 <0.01 0.0316 <0.01 0.0267 0.01 0.0128 0.0068

AMGT <0.01 <0.01 <0.01 <0.01 0.01 0.01 N/A

Combined4 <0.02 <0.0416 <0.02 <0.0367 0.020 0.0228 0.0068

Summer 

squash

Fluazinam 3.62-3.95 6-7 6 <0.01 0.0165 <0.01 <0.0132 0.010 0.0109 0.0014

AMGT <0.01 <0.01 <0.01 <0.01 0.01 0.01 N/A

Combined4 <0.02 <0.0265 <0.02 <0.0232 0.020 0.0209 0.0014

Cabbage Fluazinam 2.964-3.583 6-7 8 0.124 1.67 0.129 1.45 0.457 0.635 0.521

AMGT <0.01 <0.01 <0.01 <0.01 0.01 0.01 N/A

Combined4 <0.134 <1.68 <0.139 <1.46 0.467 0.645 0.521

1 n = number of field trials.

2 Values based on total number of samples.

3 Values based on per-trial averages. LAFT = lowest average field trial, HAFT = highest average field trial, SD = standard 

deviation. N/A = Not applicable.

4 Combined residues of fluazinam and AMGT.

The Organization for Economic Cooperation and Development (OECD) MRL calculator was 

used to determine appropriate tolerance levels for the residues of fluazinam (parent only) for 

cabbage, cucumber, squash, and mayhaw. Both cucumber and squash are representative crops of 

crop subgroup 9B. Based on the results from the OECD calculator, the tolerance level for 

cucumber (0.04 ppm) is higher than that of squash (0.02 ppm). Based on HED’s policy, since 

the differences between the recommended tolerances is <5x, then it is appropriate to recommend 

for a tolerance for the crop subgroup 9B based on the highest calculated value. However, both 

squash and cucumber are also representative crops for cucurbit vegetables crop group 9 and a 
Fluazinam Human Health Risk Assessment DP No. D426143

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tolerance is currently established for melon subgroup 9A at 0.07 ppm which is higher than the 

proposed tolerance (0.05 ppm) for subgroup 9B. Based on the residue data review and HED’s 

policy, it is appropriate to recommend a tolerance for a crop group based on highest tolerance 

value. Therefore, HED is recommending a single crop group tolerance for crop group 9 at 0.07 

ppm instead of separate tolerances for subgroups 9A and 9B. The recommended tolerances for 

proposed new uses are listed in Table 2.2.3.

5.3 Water Residue Profile

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

Environmental Fate and Effects Division (EFED; D426144, J. Meléndez, 10/6/2015) and 

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

sources” and “water, indirect, all sources.” The residues of concern in drinking water for risk 

assessment are parent fluazinam and its transformation products, including DCPA, CAPA, 

DAPA, HYPA, and AMPA.

The estimated acute and chronic EDWCs are based on ground application of fluazinam to turf. 

The values are provided in Table 5.3, below. The groundwater value was generated using the 

Pesticide Root Zone Model for Groundwater (PRZM-GW) Model and the surface water values 

were generated using the FQPA Index Reservoir Screening Tool (FIRST) Model. The surface 

water estimate was used for the acute assessment because this estimate was higher than the 

groundwater value. In contrast, the groundwater estimate was used for the chronic assessment, 

because this estimate was higher than the surface water value. Both acute and chronic estimates 

included parent and degradates. For the acute assessment, a value of 226 ppb was used, and for 

the chronic assessment, a value of 119 ppb was used. This value also includes both parent and 

degradates. For more information about EFED’s drinking water models, see 

http://www.epa.gov/oppefed1/models/ water.

Table 5.3. Maximum Tier 1 Estimated Drinking Water Concentrations Based on Ground

Application of Fluazinam to Turf at a Seasonal Rate of 8.4 lb a.i./A

Source/Model

Fluazinam Total Residues of Fluazinam1

Acute/ppb Chronic/ppb Acute/ppb Chronic/ppb

Surface Waters/FIRST 217 2 1.47 2262 37.8

Groundwater/PRZM-GW 0.538 0.319 1372 1192

1. Including the following transformation products: DCPA, HYPA, CAPA, DAPA and AMPA.

2. Exceeds the solubility of fluazinam at pH 7 (71 ppb), but not the solubility at pH 11 (350 ppm).

5.4 Dietary Risk Assessment

D429506, E. Holman, 02/25/2016

5.4.1 Description of Residue Data Used in Dietary Assessment

Acute and chronic dietary (food and drinking water) exposure and risk assessments were 

conducted using the Dietary Exposure Evaluation Model DEEM-FCIDTM, Version 3.16 which 

uses food consumption data from the U.S. Department of Agriculture’s National Health and 
Fluazinam Human Health Risk Assessment DP No. D426143

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Nutrition Examination Survey, What We Eat in America, (NHANES/WWEIA). This dietary 

survey was conducted from 2003 to 2008.

The acute analysis is based on tolerance-level residues for all commodities and uses high-end 

residue estimates for the metabolite AMGT. In addition, the acute assessment assumes 100% 

crop treated and incorporates modeled EDWCs that account for both parent fluazinam and its 

transformation products. Default processing factors were used for all relevant processed 

commodities without separate tolerances. Therefore, the resulting exposure and risk estimates 

are considered to be very conservative.

The chronic analysis is based on tolerance-level residues for all commodities except apples. For 

apples, the average field trial value was used. As with the acute assessment, it incorporates highend estimates for AMGT, 100% crop treated assumptions, default processing factors for all

relevant processed commodities without a separate tolerance, and modeled EDWCs that account 

for both parent and transformation products. Again, the resulting exposure and risk estimates are 

considered to be conservative.

Because such conservative assumptions were made in the assessments, the resulting exposure 

and risk estimates are considered to be conservative as well. HED is confident that the acute and 

chronic dietary exposure assessments significantly overestimate risk to the general U.S. 

population and its various population subgroups.

5.4.2 Percent Crop Treated Used in Dietary Assessment

The acute and chronic assessments were both based on the assumption that 100% of all 

commodities with fluazinam tolerances will be treated.

5.4.3 Acute Dietary Risk Assessment

The acute risk estimates at the 95th percentile of exposure are below HED’s level of concern for 

all population subgroups, including those comprised of infants and children. Generally, HED is 

concerned when risk estimates exceed 100% of the population-adjusted dose (PAD). The acute 

risk estimate for the general U.S. population is 5.7% of the acute PAD (aPAD). The aPAD is 

lower for females 13 to 49 years old. Although Children 1-2 years old have the highest exposure 

estimate (0.112064 mg/kg/day; 22% aPAD), the population subgroup with the highest risk 

estimate is females 13 to 49 years old, with 32% of the aPAD (0.022220 mg/kg/day). Since the 

assessment used an assumption of 100% CT, the risk estimates are being reported at the 95th

percentile of exposure. The acute dietary risk estimates are given in Table 5.4.6.

5.4.4 Chronic Dietary Risk Assessment

Chronic risk estimates are also below HED’s level of concern for all population subgroups. The 

risk estimate for the general U.S. population is 41% of the chronic PAD (cPAD). The most 

highly exposed population subgroup is All Infants (<1 year old), which uses 92% of the cPAD.

The chronic dietary risk estimates are given in Table 5.4.6.

5.4.5 Cancer Dietary Risk Assessment
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Fluazinam is classified as having “suggestive evidence of carcinogenicity, but not sufficient to 

assess human carcinogenic potential.” The CARC determined that quantification of risk using a 

non-linear approach (i.e., RfD) will adequately account for all chronic toxicity, including 

carcinogenicity, that could result from exposure to fluazinam. As a result, a separate dietary 

exposure assessment for cancer risk was not performed.

5.4.6 Summary Table

Table 5.4.6 Summary of Acute and Chronic Exposure and Risk Estimates for Fluazinam

Population Subgroup Acute Assessment (95th Percentile) Chronic Assessment

aPAD, 

mg/kg/day

Exposure 

Estimate, 

mg/kg/day

% aPAD cPAD, 

mg/kg/day

Exposure Estimate, 

mg/kg/day

% 

cPAD

U.S Population 0.5 0.028533 5.7 0.011 0.004521 41

All infants* 0.5 0.085186 17 0.011 0.010122 92

Children 1-2 yrs 0.5 0.112064 22 0.011 0.009750 89

Children 3-5 yrs 0.5 0.065310 13 0.011 0.006614 60

Children 6-12 yrs 0.5 0.034218 6.8 0.011 0.004161 38

Youth 13-19 yrs 0.5 0.019517 3.9 0.011 0.002981 27

Adults 20-49 yrs 0.5 0.021791 4.4 0.011 0.004243 39

Adults 50-99 yrs 0.5 0.019444 3.9 0.011 0.004490 41

Females 13-49 yrs* 0.07 0.022220 32 0.011 0.004338 39

*The subpopulation with the highest acute or chronic risk estimate

6.0 Residential (Non-Occupational) Exposure/Risk Characterization

6.1 Residential Handler Exposure and Risk

The Agency uses the term “Handlers” to describe those individuals who are involved in the 

pesticide application process. A residential handler assessment has not been conducted for 

fluazinam, since the end-use product, Fluazinam Turf Fungicide, limits the application site to 

golf courses only. The proposed label also includes the following statement in the use 

restrictions section: “Do not apply product to home lawns (turf) or any other residential turf.”

6.2 Residential Post-application Exposure

Fluazinam residential post-application scenarios include individuals playing golf on treated turf. 

Children 6 to <11 years old, youths 11 to <16 years old, and adults can potentially be exposed 

when they play golf on treated turf. Post-application residential exposure was assessed using 

default assumptions and transfer coefficients from the HED SOPs for Residential Exposure 

Assessments, (2012), as well as chemical-specific residue data from a turf transferable residue 

(TTR) study (MRID No. 48361527). Although HED typically assesses oral (hand-to-mouth) 

post-application exposure and risk for toddlers playing on treated turf, these exposures are not 

expected for golf course turf, and were therefore not assessed.

6.2.1 Dermal Post-application Exposure
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Short-term residential post-application dermal exposures resulting in MOEs greater than or equal 

to 100 are not of concern. Short-term dermal post-application exposure and risk analyses for 

golfers resulted in MOEs greater than the LOC and are not of concern. The highest risk estimate 

(lowest MOE) was for youth golfers aged 6 to <11 years old, with an MOE of 780. A summary 

of the residential short-term dermal exposure and risk estimates is shown in Table 6.2.1.

Table 6.2.1. Residential Post-application Short-term Dermal Exposure and Risk Estimates for Fluazinam

Scenario Application 

Rate

(lb ai/A)

TTR 1

(μg/cm2)

CF TC

(cm2/hr)

ET 

(hrs)

BW 

(kg)

Dose 2 

(mg/kg/day)

Dermal

MOE 3

Golfer

6 to < 11 yrs old 0.7 0.0865 0.001 2,900 4 32 0.031356 780

11 to < 16 yrs old 0.7 0.0865 0.001 4,400 4 57 0.026709 910

Adult 0.7 0.0865 0.001 5,300 4 80 0.022923 1,100

1. Turf Transferable Residues (TTR) = 0.0865 ug/cm2is based on predicted day 0 residue value calculated from chemicalspecific data (MRID No. 48361527).

2. Dermal Dose (mg/kg/day) = [TTR (μg/cm2) x 0.001 (mg/μg) x TC (cm2/hr) x ET (hr/day)]/ BW (kg).

3. Dermal MOE = (POD (24.4 mg/kg/day)) ÷ (Dermal Dose (mg/kg/day)).

6.2.2 Inhalation Post-application 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 

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 

fluazinam.

6.3 Combined Residential Risk Estimates

HED combines risk values resulting from separate exposure scenarios when it is likely they can 

occur simultaneously based on the use pattern and when the toxicological effects are the same 

across different routes of exposure. Since the application of fluazinam is only directed for golf 

courses, incidental oral post-application exposure for children is also expected to be negligible. 

The only route of exposure is through the dermal route (i.e., dermal post-application exposure). 

Therefore, combined residential exposure assessment for golfers is not required. 

6.4.2 Residential Risk Estimates for Use in Aggregate Assessment

The residential scenarios and risk estimates identified for use in performing an aggregate 

exposure assessment as part of the fluazinam human health risk assessment are: dermal postapplication exposure resulting from treated golf courses for adults (MOE = 1,100) and for 

children 6 to < 11yrs old (MOE = 780).
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6.5 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 fluazinam. 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 is currently quantitatively evaluated for each pesticide 

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

considered concurrently. However, fluazinam recently completed a registration review 

assessment (D397601, D. Dotson, 09/10/2012) prior to the finalization of this spray drift policy. 

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. 

Therefore, given that this was not assessed during registration review, as part of this assessment, 

HED has used the procedures described in this document to assess the potential for spray drift 

exposure. Fluazinam products have existing labels for use on golf course turf, thus it was 

considered whether the risk assessment for that use may be considered protective of any type of 

exposure that would be associated with spray drift. It should be noted that the registered 

residential uses on turf result in exposure greater than potential exposure from spray drift; 

therefore, no new residential assessment needs to be completed. If the maximum application rate 

on crops adjusted by the amount of drift expected is less than or equal to existing turf application 

rates, the existing turf assessment is considered protective of spray drift exposure. The currently 

registered maximum single application rate of fluazinam for Brassica vegetables is 1.3 lb ai/A. 

The highest degree of spray drift noted for any application method immediately adjacent to a 

treated field (Tier 1 output from the aerial application using fine to medium spray quality) results 

in an deposition fraction of 0.26 of the application rate. A quantitative spray drift assessment for 

fluazinam is not required because the maximum application rate to a crop/target site multiplied 

by the adjustment factor for drift of 0.26 is less than the maximum direct spray residential turf 

application rate [(0.70 lb ai/A)]2for any fluazinam products. The turf post-application MOEs 

have been previously assessed and are based on the revised SOPs for Residential Exposure 

Assessment (i.e., see above in Section 6.2). 

It is noted that the use rates proposed for this petition are 0.26-0.78 lb ai/A/application; therefore, 

the spray drift assessment associated with the registered use rates is protective of the anticipated 

exposure from this new use action. 

 

1 Available: http://www.epa.gov/opp00001/factsheets/spraydrift.htm 

2 1.3 lb ai/A x 0.26 ≤ 0.70 lb ai/A
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6.6 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 

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 

fluazinam.

7.0 Aggregate Exposure/Risk Characterization

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

risk estimates 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 risk estimates themselves can 

be aggregated. When aggregating exposures and risks from various sources, HED considers 

both the route and duration of exposure.

7.1 Acute Aggregate Risk

Acute aggregate risk results from exposure to residues in food and drinking water. The acute 

dietary exposure analysis included both food and drinking water. Therefore, acute aggregate risk

estimates are equivalent to the acute dietary risk estimates, as discussed in Section 5.4.3, above. 

All risk estimates are not of concern.

7.2 Short-/Intermediate-Term Aggregate Risk Estimates

For the short-term aggregate risk assessment, the only relevant residential exposure scenario, 

dermal post-application, was combined with background exposure from food and water.

The chronic dietary exposure estimates are the background exposure levels that were added 

directly to the residential dermal post-application exposure estimates. Of the population 

subgroups comprised of adults, the subgroup Adults 50-99 had the highest dietary exposure 

estimate. For the child and youth population subgroups, the dietary groups did not directly 

overlap with the representative residential life stages. Specifically, the closest dietary subgroup 

to the residential life stage children 6-<11 was children 6-12, and the closest dietary subgroup to 

the residential life stage youth 12-<16 was youth 13-19. 

The short-term aggregate risk assessments resulted in estimated MOEs of 690 to 890. For 

fluazinam, the LOC for short-term risk is an MOE of 100. As the resulting aggregate MOEs

exceed the LOC of 100, aggregate dietary and residential risk estimates are not of concern. 

Because the background exposure from food and water is so low relative to the dermal exposure 
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estimates, the short-term aggregate MOEs are the similar to those estimated for the dermal route 

alone. The aggregate risk estimates are given in Table 7.2.

Table 7.2. Residential Short-/Intermediate-Term Aggregate Risk Calculations

Population

Short- or Intermediate-Term Scenario

POD

mg/kg/day LOC1

Max 

Allowable 

Exposure2

mg/kg/day

Average 

Food and 

Water 

Exposure 

mg/kg/day

Residential Postapplication 

Dermal Exposure 

mg/kg/day3

Total 

Exposure4

mg/kg/day

Aggregate 

MOE (food, 

water, and 

residential)

5

Children 6-<11 24.4 100 0.244 0.004161 0.031356 0.035517 690

Youth 11-<16 24.4 100 0.244 0.002981 0.026709 0.029690 820

Adults 24.4 100 0.244 0.004490 0.022923 0.027413 890

1. An UF of 100x was applied to account for interspecies extrapolation (10x) and intraspecies variation (10x). No 

additional uncertainty factors/safety factors are required.

2. Maximum Allowable Exposure (mg/kg/day) = POD/LOC

3. Residential Exposure = Dermal exposure from treated turf (see table 6.2.1). 

4. Total Exposure = Avg Food & Water Exposure + Residential Exposure

5. Aggregate MOE = [POD (24.4 mg/kg/day) ÷ (Avg Food & Water Exposure + Residential Exposure 

(mg/kg/day))]

7.3 Chronic Aggregate Risk

There are no residential scenarios that result in long-term exposure. As a result, the chronic 

aggregate risk assessment results from long-term exposure to residues in food and drinking water

only. The chronic dietary exposure analysis included both food and drinking water and, 

therefore, the chronic aggregate risk assessment is equivalent to the chronic dietary assessment

discussed in Section 5.4.4, above. All risk estimates are below HED’s level of concern.

7.4 Cancer Aggregate Risk

Fluazinam is classified as having “suggestive evidence of carcinogenicity, but not sufficient to 

assess human carcinogenic potential.” The CARC determined that quantification of risk using a 

non-linear approach (i.e., RfD) will adequately account for all chronic toxicity, including 

carcinogenicity, that could result from exposure to fluazinam. As a result, a separate dietary 

exposure assessment for cancer risk was not performed.

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 fluazinam and any other substances, and fluazinam does not appear to produce a toxic 

metabolite produced by other substances. For the purposes of this risk assessment, therefore, 

EPA has not assumed that fluazinam 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/.
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9.0 Occupational Exposure/Risk Characterization

9.1 Occupational Handler Exposure/Risk Estimates

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 the 

following scenarios:

 Mixing and loading liquids for aerial, airblast, chemigation, and groundboom

applications;

 Applying sprays with aerial, airblast, and groundboom equipment;

 Flagging for aerial applications; and

 Mixing, loading, and applying liquids via mechanically-pressurized handgun for foliar 

applications.

As per the label instructions, fluazinam may be applied every 7 days multiple times throughout 

the growing season. Using the maximum application rates for all new uses, the maximum 

number of times fluazinam may be applied ranges from 4 for cabbage, to 10 times for mayhaw. 

Based on these proposed new uses, short- and intermediate-term exposures are expected. Longterm exposures are not expected.

Estimates of dermal and inhalation exposure were calculated for various levels of personal 

protective equipment (PPE). Results are presented for “baseline,” defined as a single layer of 

clothing consisting of a long sleeved shirt, long pants, shoes plus socks, no protective gloves, and 

no respirator, as well as baseline with various levels of PPE as necessary (e.g., gloves, respirator, 

etc). The fluazinam product label directs mixers, loaders, applicators and other handlers to wear:

baseline clothing (i.e., long-sleeved shirt and long pants, socks), chemical-resistant gloves and 

footwear, and protective eyewear. Those who are mixing, loading, or cleaning equipment must 

also wear a chemical resistant apron. 

Detailed descriptions of the occupational handler assessment are available in G. Thornton

(D430208, 02/25/2016). 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 chemicalspecific data, include PHED 1.1, the 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 Table3”, 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 website4. 

 

3 Available: http://www2.epa.gov/sites/production/files/2015-09/documents/handler-exposure-table-2015.pdf

4 Available: http://www2.epa.gov/pesticide-science-and-assessing-pesticide-risks/occupational-pesticide-handlerexposure-data
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In addition to the generic exposure data to assess occupational exposure and risk, HED used 

standard assumptions with respect to the area treated, the hours worked in a day, and the average 

adult body weight (80 kg).

Occupational Handler Non-Cancer Exposure and Risk Estimates

Table 9.1 presents the short-term dermal and inhalation risk estimates for handlers. Since the 

endpoints selected for risk assessment are different for dermal (liver effects) and inhalation (lung 

effects) routes of exposure, the exposure and risk cannot be combined. Therefore, dermal and 

inhalation risks were calculated and presented separately. 

The occupational handler exposure and risk estimates indicate that the short- and intermediateterm dermal (LOC < 100) and inhalation (LOC < 30) MOEs are not of concern at or below the 

level of personal protection specified on the label (double layer and gloves), with the exception 

of dermal exposure during the use of airblast applicator and mechanically-pressurized handgun. 

Based on personal email communication with RD, the registrant intends to submit a revised label 

that prohibits the use of mechanically-pressurized handgun, thus mitigating the risks of concern 

associated with this application method. For airblast applicators, risks of concern for dermal 

application were identified, but with additional PPE (e.g., chemically resistant hat), the dermal 

exposure MOEs are above the LOC. All inhalation exposure and risk estimates pass at baseline 

protection. All scenarios resulting in aerial applicator exposure are assumed to occur using 

engineering controls for this assessment. Risk estimates, dermal exposure, and mitigation levels 

are included below in Table 9.1.

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 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 GPS for swath guidance in agricultural aviation has grown steadily 

from the mid 1990’s. Over the same time period, the use of human flaggers for aerial pesticide 

applications has decreased steadily from ~15% in the late 1990’s 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.
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Table 9.1. Occupational Handler Non-Cancer Exposure and Risk Estimates for Fluazinam.

Exposure 

Scenario Crop or Target

Dermal Unit 

Exposure

(μg/lb ai)1

Inhalation Unit 

Exposure (μg/lb 

ai)1 Maximum 

Application 

Rate3

Area Treated 

or Amount 

Handled 

Daily4

Dermal

LOC = 100

Inhalation

LOC = 30

[Level of PPE or 

Engineering 

Control]

2

[Level of PPE or 

Engineering 

Control]

2

Dose 

(mg/kg/day)5 MOE6 Dose (mg/kg/day)7 MOE8

Mixer/Loader

Aerial

Tuberous and Corm 

Subgroup 1C

37.6

[SL/G]

0.219

[Baseline]

0.26 

lb ai/acre 1200 Acres 0.146 170 0.000854 150

Cabbage 37.6

[SL/G]

0.219

[Baseline]

0.5 

lb ai/acre 350 Acres 0.0823 300 0.000479 260

Squash/Cucumber

Subgroup 9B

37.6

[SL/G]

0.219

[Baseline]

0.78

lb ai/acre 350 Acres 0.129 190 0.000748 170

Mayhaw 37.6

[SL/G]

0.219

[Baseline]

0.45

lb ai/acre 350 Acres 0.074 330 0.000431 290

Airblast Mayhaw 220

[Baseline]

0.219

[Baseline]

0.45

lb ai/acre 40 Acres 0.0495 490 0.0000493 2500

Chemigation

Tuberous and Corm 

Subgroup 1C

37.6

[SL/G]

0.219

[Baseline]

0.26 

lb ai/acre 350 Acres 0.0428 570 0.000249 500

Cabbage 37.6

[SL/G]

0.219

[Baseline]

0.5 

lb ai/acre 350 Acres 0.0823 300 0.000479 260

Squash/Cucumber 

Subgroup 9B

37.6

[SL/G]

0.219

[Baseline]

0.78

lb ai/acre 350 Acres 0.129 190 0.000748 170

Mayhaw 37.6

[SL/G]

0.219

[Baseline]

0.45

lb ai/acre 350 Acres 0.074 330 0.000431 290

Groundboom

Tuberous and Corm 

Subgroup 1C

220

[Baseline]

0.219

[Baseline]

0.26 

lb ai/acre 200 Acres 0.143 170 0.000143 870

Cabbage 220

[Baseline]

0.219

[Baseline]

0.5

lb ai/acre 80 Acres 0.11 220 0.00011 1100

Squash/Cucumber 

Subgroup 9B

220

[Baseline]

0.219

[Baseline]

0.78

lb ai/acre 80 Acres 0.171 140 0.000171 730

Applicator
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Table 9.1. Occupational Handler Non-Cancer Exposure and Risk Estimates for Fluazinam.

Exposure 

Scenario Crop or Target

Dermal Unit 

Exposure

(μg/lb ai)1

Inhalation Unit 

Exposure (μg/lb 

ai)1 Maximum 

Application 

Rate3

Area Treated 

or Amount 

Handled 

Daily4

Dermal

LOC = 100

Inhalation

LOC = 30

[Level of PPE or 

Engineering 

Control]

2

[Level of PPE or 

Engineering 

Control]

2

Dose 

(mg/kg/day)5 MOE6 Dose (mg/kg/day)7 MOE8

Aerial

Tuberous and Corm 

Subgroup 1C

2.08

[EC]

0.0049

[EC]

0.26 

lb ai/acre 1200 Acres 0.00811 3000 0.0000191 3200

Cabbage 2.08

[EC]

0.0049

[EC]

0.5 

lb ai/acre 350 Acres 0.00455 5400 0.0000107 5800

Squash/Cucumber 

Subgroup 9B

2.08

[EC]

0.0049

[EC]

0.78

lb ai/acre 350 Acres 0.0071 3400 0.0000168 3700

Mayhaw 2.08

[EC]

0.0049

[EC]

0.45

lb ai/acre 350 Acres 0.0041 6000 0.00000965 6400

Airblast Mayhaw

1480

[DL/G] 4.71

[Baseline]

0.45

lb ai/acre 40 Acres

0.333 73

0.00106 58 215

[SL/G/CRH] 0.0484 500

Groundboom

Tuberous and Corm 

Subgroup 1C

78.6

[Baseline]

0.34

[Baseline] 0.26 lb ai/acre 200 Acres 0.0511 480 0.000221 280

Cabbage 78.6

[Baseline]

0.34

[Baseline]

0.5

lb ai/acre 80 Acres 0.0393 620 0.00017 360

Squash/Cucumber 

Subgroup 9B

78.6

[Baseline]

0.34

[Baseline]

0.78

lb ai/acre 80 Acres 0.0613 400 0.000265 230

Flagger

Aerial

Tuberous and Corm 

Subgroup 1C

11

[Baseline]

0.35

[Baseline]

0.26 

lb ai/acre 1200 Acres 0.0125 200 0.000399 540

Cabbage 11

[Baseline]

0.35

[Baseline]

0.5 

lb ai/acre 350 Acres 0.0241 1000 0.000766 280

Squash/Cucumber 

Subgroup 9B

11

[Baseline]

0.35

[Baseline]

0.78

lb ai/acre 350 Acres 0.0375 650 0.0012 180

Mayhaw 11

[Baseline]

0.35

[Baseline]

0.45

lb ai/acre 350 Acres 0.0216 1100 0.000689 310

Mixer/Loader/Applicator
Fluazinam Human Health Risk Assessment DP No. D426143

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Table 9.1. Occupational Handler Non-Cancer Exposure and Risk Estimates for Fluazinam.

Exposure 

Scenario Crop or Target

Dermal Unit 

Exposure

(μg/lb ai)1

Inhalation Unit 

Exposure (μg/lb 

ai)1 Maximum 

Application 

Rate3

Area Treated 

or Amount 

Handled 

Daily4

Dermal

LOC = 100

Inhalation

LOC = 30

[Level of PPE or 

Engineering 

Control]

2

[Level of PPE or 

Engineering 

Control]

2

Dose 

(mg/kg/day)5 MOE6 Dose (mg/kg/day)7 MOE8

Mechanicallypressurized 

Handgun

Tuberous and Corm 

Subgroup 1C

6050

[Baseline] 8.68

[Baseline]

0.013

lb ai/gal 1000 Gallons

0.984 25

0.00141 150 1360

[DL/G] 0.221 110

Cabbage

6050

[Baseline] 8.68

[Baseline]

0.025

lb ai/gal 1000 Gallons

1.89 13

0.00271 80 1360

[DL/G] 0.425 57

Squash/Cucumber 

Subgroup 9B

6050

[Baseline] 8.68

[Baseline]

0.039

lb ai/gal 1000 Gallons

2.95 8.3

0.00424 51 1360

[DL/G] 0.663 37

Mayhaw 6050

[Baseline]

8.68

[Baseline]

0.00225

lb ai/gal 1000 Gallons 0.17 140 0.000244 890

1. Unit exposures and description of mitigation levels are found in the “Occupational Pesticide Handler Unit Exposure Surrogate Reference Table” (September 2015)

2. Level of PPE or Engineering controls: Baseline is considered single layer, no gloves, and no respirator; SL/G is single layer and gloves; DL/G is double layer and gloves; PF5 R is "Protection 

Factor 5" respirator assuming an 80% reduction in exposure; SL/G/CRH is single layer, gloves, and chemical resistant hat. The label PPE is considered to be DL/G.

3. Based on registered or proposed label (Reg. No. 71512-1).

4. Exposure Science Advisory Council Policy #9.1.

5. Dermal Dose = Dermal Unit Exposure (μg/lb ai) × Conversion Factor (0.001 mg/μg) × Application Rate (lb ai/acre or gal) × Area Treated or Amount Handled Daily (A or gal/day) 

÷ BW (80 kg).

6. Dermal MOE = Dermal POD (mg/kg/day) ÷ Dermal Dose (mg/kg/day).

7. Inhalation Dose = Inhalation Unit Exposure (μg/lb ai) × Conversion Factor (0.001 mg/μg) × Application Rate (lb ai/acre or gal) × Area Treated or Amount Handled Daily (A or gal/day) ÷ BW 

(kg).

8. Inhalation MOE = Inhalation NOAEL (mg/kg/day) ÷ Inhalation Dose (mg/kg/day).
Fluazinam Human Health Risk Assessment DP No. D426143

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9.2 Occupational Post-application Exposure/Risk Estimates

9.2.1 Occupational Post-application Inhalation Exposure/Risk Estimates

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 Federal Insecticide, Fungicide, and Rodenticide Act 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-HQOPP-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 fluazinam.

In addition, the Agency is continuing to evaluate the available post-application inhalation 

exposure data generated by the Agricultural Reentry Task Force. 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.

9.2.2 Occupational Post-application Dermal Exposure/Risk Estimates

Occupational workers who enter treated fields to perform post-application activities such as hand 

weeding and scouting might be exposed to fluazinam residues. Based on the use pattern, 

workers might be exposed to short- and intermediate-term exposure durations. Detailed 

descriptions of the occupational post-application dermal assessment are available in G. Thornton, 

(D430208, 02/25/2016). 

Transfer Coefficients: It is the policy of HED to use the best available data to assess postapplication exposure. Sources of generic post-application data, used as surrogate data in the 

absence of chemical-specific data, are derived from ARTF exposure monitoring studies, and, as 

proprietary data, are subject to the data protection provisions of FIFRA. The standard values 

recommended for use in predicting post-application exposure that are used in this assessment, 

known as “transfer coefficients”, are presented in the ExpoSAC Policy 3” 

(http://www.epa.gov/pesticides/science/exposac_policy3.pdf), which, along with additional 
Fluazinam Human Health Risk Assessment DP No. D426143

Page 36 of 51

information about the ARTF data, can be found at: http://www.epa.gov/pesticides/science/postapp-exposure-data.html. 

Dislodgeable Foliar Residues: Chemical-specific dislodgeable foliar residue (DFR) studies on 

apples (MRID#: 45584203), potatoes (MRID #: 45584202), and peanuts (MRID#: 45584201) 

were submitted and reviewed by HED. The studies demonstrated that dislodgeable foliar residue 

values declined over time. 

The peanut DFR study was used to assess post-application exposure and risk estimates from 

contact with cabbage and crops in the squash/cucumber subgroup 9B because it was the most 

conservative DFR value. As apple and potato are the representative commodities for the 

proposed crops, mayhaw and tuberous and corm vegetables subgroup 1C respectively, the apple 

DFR and potato DFR studies were used to assess post-application exposure and risk estimates 

from contact with mayhaw and tuberous and corm vegetables subgroup 1C.

Dermal exposures during post-application activities were estimated using: 1) the maximum 

single application rate on the proposed label for each crop (0.26-0.78 lb ai/acre), 2) a standard 

body weight for the general population (80 kg), and 3) an average occupational workday of 8 

hours per day.

Occupational Post-application Non-Cancer Dermal Risk Estimates

A summary of the post-application exposure and risk estimates for the proposed uses is provided 

in Table 9.2.2. Only risk estimates for the highest contact activity are shown below. All 

scenarios resulted in MOEs greater than the LOC of 100 on day 0, with the exception of hand 

weeding cabbage, and are not of concern. At 12 and 24 hours after last application, MOEs for 

hand weeding cabbage increase to 98 and 100 respectively.

Table 9.2.2. Occupational Post-application Non-Cancer Exposure and Risk Estimates for Fluazinam.

Crop/Site Activities

Transfer 

Coefficient 

(cm2/hr)

DAT1 DFR/TTR

(μg/cm2)

Dermal Dose2

MOE3

(mg/kg/day)

Short- and Intermediate-term

Cabbage Hand Weeding 4200

0.5 0.594 0.249 98

1 0.564 0.236 100

Mayhaw Thinning Fruit 3600 0 0.055 0.017 1400

Squash/Cucumber 

Subgroup 9B

Irrigation 

(hand set) 1900 0 0.984 0.186 130

Tuberous and 

Corm Vegetables 

Subgroup 1C

Irrigation 

(hand set) 1900 0 0.236 0.044 550

1 DAT = Day(s) after treatment

2 Daily Dermal Dose = [DFR (μg/cm2) × Transfer Coefficient × 0.001 mg/μg × 8 hrs/day]  BW (80 kg).

3 MOE = POD (POD = 24.4 mg/kg/day) / Daily Dermal Dose.

4 Fluazinam Peanut DFR data used (MRID# 45584201)

5 Fluazinam Apple DFR data used (MRID# 45584203)
Fluazinam Human Health Risk Assessment DP No. D426143

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6 Fluazinam Potato DFR data used (MRID# 45584202)

Restricted Entry Interval

Fluazinam is classified as Toxicity Category III via the dermal route and Toxicity Category IV 

for skin irritation potential. It is a skin sensitizer. Under 40 CFR 156.208 (c) (2), ai’s classified 

as Acute III or IV for acute dermal, eye irritation and primary skin irritation are assigned a 12-

hour REI. In the case of hand weeding activities on cabbage, identified MOEs were 98 at 12 

hours and 100 at 24 hours. However, HED does not consider an MOE of 98 at 12 hours to be of 

concern, as it is essentially equivalent to an MOE of 100. All other short- and intermediate-term 

post-application risk estimates were not a concern on day 0. Therefore, the [156 subpart K] 

Worker Protection Statement interim REI of 12 hours should be adequate to protect agricultural 

workers from post-application exposure to fluazinam. 
Fluazinam Human Health Risk Assessment DP No. D397601

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10.0 References

D. Dotson, K. Middleton, Z. Figueroa, 9/10/2012, D397601, Fluazinam. Human Health Risk 

Assessment to Support New Uses on Soybeans, the Melon Subgroup (9-A), and the 

Pepper/Eggplant Subgroup (8-10B), and to Support Registration Review

C Swartz, M Doherty, 2/14/2013, D407410. Fluazinam. Addendum to the Human Health Risk 

Assessment for New Uses and Registration Review: Incorporation of New Acute Toxicity Data 

and Updated Restricted Entry Interval (REI).

S. Biswas, 09/18/2015, D426241. Fluazinam. Petition for the Establishment of Permanent 

Tolerances and Registration for New Uses on Tuberous and Corm, Subgroup 1C, Mayhaw, 

Squash/Cucumber Subgroup 9B; Amended Uses on Cabbage; and Removal of Cabbage from 

Vegetable, Brassica leafy, group 5. Summary of Analytical Chemistry and Residue Data.

E. Holman, 02/25/2016, D429506, Fluazinam. Acute and Chronic Aggregate Dietary (Food and 

Drinking Water) Exposure and Risk Assessments for the Section 3 Registration Action for New 

Uses on Tuberous and Corm, Subgroup 1C, Mayhaw, Squash/Cucumber Subgroup 9B; 

Amended Uses on Cabbage; and Removal of Cabbage from Vegetable, Brassica leafy, group 5.

G. Thornton, 02/25/2016, D430208, Fluazinam. Occupational and Residential Exposure 

Assessment for Proposed Uses on Cabbage (foliar), Mayhaw, Squash/Cucumber Subgroup 9B 

and to Expand the Existing use on Potatoes to Tuberous and Corm Vegetables Subgroup 1C.

J. Melendez, 10/6/2015, D426144, Tier I Estimated Drinking Waters Concentrations of 

Fluazinam and its Transformation Products for Use in the Human Health Risk Assessment for 

the Registration of the New Uses on Mayhaw, Cabbage and Chinese cabbage, Cucurbit 

Vegetables, Squash/Cucumber Subgroup 9B, and Root and Tuber Vegetables, Tuberous and 

Corm Subgroup 1C

W. Cutchin, 4/23/2001, D272624, Fluazinam. Decision by Metabolism Assessment Review 

Committee (MARC)

List of Appendices

Appendix A. HEC Inhalation Calculations

Appendix B. International Residue Limit Status Sheet

Appendix C. Fluazinam Physical/Chemical Properties

Appendix D. Review of Human Research

Appendix E. Structures of Fluazinam Metabolites and Degradates of Concern

Appendix F. Toxicity Profile Tables
Fluazinam Human Health Risk Assessment DP No. D397601

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Appendix A. HEC Inhalation Calculations

In response to the data requirements for registration review, a 4 week repeated dose rat inhalation

toxicity study (MRID 48571410) was conducted to assess the effects of fluazinam via the 

inhalation route. Fluazinam was administered to 10/sex CD rats (nose only) for a total of 6 

hours/day (two 3 hr exposures), 5 days/week, as an aerosol with an average mass medium 

aerodynamic diameter (MMAD) of 4.7 and a geometric standard deviation (σ) of 2.7. The 

LOAEL of 0.020 mg/L is based on a dose related increase in absolute and relative lung/bronchial 

weights in both sexes. The NOAEL is 0.003 mg/L.

Fluazinam: HECs and HEDs: 4 Week Subchronic Inhalation Study in Rats (MRID 48571410)

Short and 

intermediate

-term 

Inhalation

Inhalation NOAEL = 

0.003 mg/L (See 

HEC/HED calculations 

below)

UFA= 3X

UFH =10X

Residential 

and 

Occupational 

LOC for MOE 

= 30

Inhalation LOAEL = 

0.020 mg/L is based on a 

dose related increase in 

absolute and relative 

lung/bronchial weights in 

both sexes. 

Exposure Scenario HECs HEDs

Occupationa

l Handler 

HECs and 

HEDs

Ventilation rate=8.3 

L/min

0.00109 mg/L

0.062mg/kg/day

Ventilation rate=16.7 

L/min 0.125 mg/kg/day

Ventilation rate=29 L/min 0.217 mg/kg/day
Fluazinam Human Health Risk Assessment DP No. D397601

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Appendix B. International Residue Limit Status Sheet

Fluazinam (PC Code 129098; Date of Request 8/10/2015)

Summary of US and International Tolerances and Maximum Residue Limits 

Residue Definition:

US Canada Mexico2 Codex

40 CFR 180.574

Plants: Fluazinam, 3-chloro-N-[3-

chloro-2,6-dinitro-4-

(trifluoromethyl)phenyl]-5-

(trifluoromethyl)-2-pyridinamine

3-chloro-N-[3-chloro2,6-dinitro-4-

(trifluoromethyl)phen

yl]-5-

(trifluoromethyl)-2-

pyridinamine

None

Commodity1 Tolerance (ppm) /Maximum Residue Limit (mg/kg)

US Canada Mexico2 Codex

Mayhaw 2.0

Cabbage 3.0 0.01

Squash/cucumber subgroup 

9B

0.05

Vegetable, Brassica leafy, 

group 5, except cabbage

0.01 0.01 bok choy Chinese 

cabbages, broccoli, 

broccoli raab, Brussels 

sprouts, cabbages, 

cauliflower, Chinese 

broccoli, chinese 

mustard cabbages, 

collards, kale, kohlrabi, 

mustard greens, 

mustard spinach, napa 

Chinese cabbages, rape 

leaves

Vegetable, Tuberous and 

corm, Subgroup 1C

0.02 0.02 potatoes

Completed by: M. Negussie; 08/14/15

1

Includes only commodities of interest for this action. Tolerance values should be the HED recommendations and 

not those proposed by the applicant.2 Mexico adopts US tolerances and/or Codex MRLs for its export purposes.
Fluazinam Human Health Risk Assessment DP No. D397601

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Appendix C. Fluazinam Physical/Chemical Properties

Table C.1. Physicochemical Properties of Fluazinam

Parameter Value Reference

Melting Point/Range 115.5°C MRID 42208401

pH 5.85 MRID 43521001

Density (20°C) 1.74 g/cm3 MRID 42208401

Water Solubility (25°C) (pH 5.5): 25 ppb

(pH 7): 71 ppb

(pH 11): 350 ppm

MRID 42208401

Solvent Solubility (25°C) Solvent Solubility (g/L) MRID 42208401

acetone

dichloroethane

ethyl acetate

ethyl ether

hexane

methanol

toluene

645

485

624

168

6.7

162

512

Vapor Pressure (25°C) 1.73 x 10-7 mm Hg

(2.3 x 10-5 Pa)

LSS 2000_1973_2LS_rev

Dissociation Constant (pKa) Average pKa = 7.22 in 50% 

ethanol/water (v/v)

MRID 42208401

Octanol/Water Partition Coefficient 

(KOW)

3,630

(Log Kow = 3.56)

MRID 42208401

UV/Visible Absorption Spectrum pH λmax (nm) PMRA Regulatory Note REG2003-

12 5

7

>10

238

239, 342

260, 343, 482

 
Fluazinam Human Health Risk Assessment DP No. D397601

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Appendix D. 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 Pesticide Handlers Exposure Database Version 1.1 (PHED 1.1); the Agricultural Handler 

Exposure Task Force (AHETF) database; the Outdoor Residential Exposure Task Force 

(ORETF) database; the Agricultural Re-entry Task Force (ARTF) database; and other registrantsubmitted studies (MRID Nos. 46991302, 45584203, 45584202, and 48361527); are subject to 

ethics review pursuant to 40 CFR 26, have received that review, and are compliant with 

applicable ethics requirements. For certain studies, that review might have included review by 

the Human Studies Review Board. Descriptions of data sources as well as guidance on their use 

can be found at http://www.epa.gov/pesticides/science/handler-exposure-data.html and 

http://www.epa.gov/pesticides/science/post-app-exposure-data.html.
Fluazinam Human Health Risk Assessment DP No. D397601

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Appendix E. Structures of Fluazinam Metabolites and Degradates of Concern

Table E.1. Structures of Fluazinam Metabolites and Degradates of Concern

Compound Common Name Structure

Fluazinam

AMGT

Plant Metabolite

AMPA

Livestock Metabolite

Drinking Water Degradate

DAPA

Livestock Metabolite

Drinking Water Degradate

Cl

N

H

CF3

NO2

O2N

N

Cl

F3C

O

OH

OH

OH

HO

O

NH

CF3

O2N

N

F Cl 3C

NH2

S

HOOC

Cl

N

H

CF3

O2N

N

Cl

F3C NH2

Cl

N

H

CF3

N

Cl

F3C NH2

H2N
Fluazinam Human Health Risk Assessment DP No. D397601

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Table E.1. Structures of Fluazinam Metabolites and Degradates of Concern

Compound Common Name Structure

CAPA

Drinking Water Degradate

DCPA

Drinking Water Degradate

HYPA

Drinking Water Degradate

Appendix F: Fluazinam Toxicology Profile Tables

Table F.1. Acute Toxicity Data on Fluazinam-Updated Technical Ingredient

Guideline No./ 

Study Type

Test Substance MRID No. Results Toxicity 

Category

870.1000

Acute oral toxicity 

rats

Technical grade fluazinam

(Batch No. 080204; 96.53% a.i)

48361502 F: LD50 > 5000 mg/kg IV

870.1200

Acute dermal 

toxicity rats

Technical grade fluazinam

(Batch No. 080204; 96.53% a.i)

48361503 M: LD50 > 2000 mg/kg

F: LD50 > 2000 mg/kg

Combined LD50> 2000 

mg/kg 

III

870.1300

Acute inhalation 

toxicity: rats

Technical grade fluazinam (Lot 

No.: A629/1995; 97.3% a.i.) 

48361504 M: LC50 > 1.1 mg/L

F: LC50 > 1.1 mg/L

Combined LC50> 1.1 

mg/L

III

870.1300

Acute inhalation 

toxicity: rats

Technical grade fluazinam

(Batch No. 080204; 96.53% a.i)

48361505 M: LC50 > 1.08 mg/L

F: LC50 > 1.08 mg/L

III

N

H

N

O2N

O2N

Cl

CF3

Cl

HOOC

N

H

N

O2N

COOH

Cl

O2N

Cl

HOOC

DCPA

N

H

N

O2N

CF3

HO

O2N

Cl

F3C
Fluazinam Human Health Risk Assessment DP No. D397601

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Table F.1. Acute Toxicity Data on Fluazinam-Updated Technical Ingredient

Guideline No./ 

Study Type

Test Substance MRID No. Results Toxicity 

Category

Combined LC50> 1.08

mg/L

870.2400

Acute eye irritation

rabbits

Technical grade fluazinam

(Batch No. 080204; 96.53% a.i)

48361506 Moderately irritating III

870.2500 Acute 

dermal irritation

rabbits

Technical grade fluazinam

(Batch No. 080204; 96.53% a.i)

48361507 Non irritating IV

870.2600 Dermal 

sensitization

guinea pigs

Technical grade fluazinam

(Batch No. 080204; 96.53% a.i)

48361508 Positive NA

Table F.2. Acute Toxicity Data on Fluazinam Technical

Guideline No./ 

Study Type

Test Substance MRID No. Results Toxicity 

Category

870.1100 

Acute oral toxicity 

rats

Technical grade fluazinam 

(lot #109; 95.3%)

42248603 M: LD50 = 4500 mg/kg

F: LD50 = 4100 mg/kg

III

Technical grade fluazinam 

(lot #8412-20; 95.3%)

42248602 M: LD50 >5000 mg/kg

F: LD50 >5000 mg/kg

IV

Technical grade fluazinam 

(lot #1/87; 97.9%)

42248604 M: LD50 >5000 mg/kg

F: LD50 >5000 mg/kg

IV

870.1200/Acute 

dermal toxicity: rats

Technical grade fluazinam 

(lot #8303-2; 98.5%)

42248605 M: LD50 >2000 mg/kg

F: LD50 >2000 mg/kg

III

870.1300

Acute inhalation 

toxicity: rats

Technical grade fluazinam 

(lot #109; 95.3%)

42270601 M: LC50 = 0.463 mg/L

F: LD50 = 0.476 mg/L

II

870.2400

Acute eye irritation

rabbits

Technical grade fluazinam 

(lot # SNPE B-1216, No. 

1006; 97.9%)

42248606 Extremely irritating. 

Corneal opacity did NOT 

reverse in 21 days.

I

870.2500 Acute

dermal irritation

rabbits

Technical grade fluazinam 

(lot # SNPE B-1216, No. 

1006; 97.9%)

42248607 Slightly irritating IV

870.2600 Dermal 

sensitization

guinea pigs

Technical grade fluazinam 

(lot # 1030/91; 96.7%)

42274401 Positive NA

Ultra-purified fluazinam 

(lot #Y910401; 100%)

42248608 Negative NA

Table F.3 Acute Toxicity Data on Fluazinam Formulations

Guideline No./ 

Study Type

Test Substance MRID No. Results Toxicity 

Category

870.1100 

Acute oral toxicity 

rats

Omega 500F 

(40% fluazinam)

42974907 M: LD50 >5000 mg/kg

F: LD50 >5000 mg/kg

IV

870.1200 

Acute dermal toxicity

rabbits

Omega 500F

(40% fluazinam)

42974908 M: LD50 >2000 mg/kg

F: LD50 >2000 mg/kg

III

870.1300 Fluazinam 50% WP a 42311001 M: LC50 = 3.0 mg/L IV
Fluazinam Human Health Risk Assessment DP No. D397601

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Table F.3 Acute Toxicity Data on Fluazinam Formulations

Acute inhalation 

toxicity: rats

(51.3% fluazinam) F: LD50 = 3.4 mg/L

870.2400

Acute eye irritation

rabbits

Omega 500F

(40% fluazinam)

42974910 Slightly irritating III

870.2500 Acute 

dermal irritation

rabbits

Omega 500F

(40% fluazinam)

42974911 Moderately irritating II

870.2600 Dermal 

sensitization

guinea pigs

Omega 500F

(40% fluazinam)

42974912 Positive NA

a Study satisfies requirement for testing on Omega 500F.

Table F.4. Subchronic, Chronic and Other Toxicity Studies for Fluazinam Technical

Guideline/

Type of Study

Study Title/

Classification /Doses MRID Results

870.3100

90-Day oral toxicity 

rats

M : 0, 0.15, 0.77, 3.8, 38 

mg/kg/day;

F: 0, 0.17, 0.86, 4.3, 44 

mg/kg/day

Acceptable/guideline

42248610 (1984); 

44807214 (1998) NOAEL: Males: 3.8 mg/kg/day; 

Females: 4.3 mg/kg/day

LOAEL Males = 38 mg/kg/day; 

Females = 44 mg/kg/day based on 

increased liver weights and liver 

histopathology in males, and increased 

lung and uterus weights in females.

870.3150

90-Day oral toxicity 

dogs

M & F: 0, 1, 10, 100 

mg/kg/day 

Acceptable/guideline

42248611 (1991); 

44807215 (1998)

NOAEL = 10 mg/kg/day

LOAEL = 100 mg/kg/day based on 

retinal effects, increased relative liver 

weight, liver histopathology and 

possible increased serum alkaline 

phosphatase in females and possible 

marginal vacuolization of the cerebral 

white matter (equivocal)

870.3200

21-Day dermal 

toxicity

rats

M & F: 0, 10, 100, 1000 

mg/kg/day

Acceptable/guideline

42270602 (1985) Systemic NOAEL = 10 mg/kg/day

LOAEL = 100 mg/kg/day based on 

increased AST and cholesterol levels in 

clinical chemistry determinations 

(males)

Dermal NOAEL = not identified

LOAEL = 10 mg/kg/day based on 

erythema, acanthosis, and dermatitis

870.3465

4 week inhalation 

toxicity

Concentrations of 0, 

0.003, 0.020, or 0.100 

mg/L

Acceptable/guideline

48571410 NOAEL = 0.003 mg/L 

LOAEL = 0.020 mg/L based on a dose 

related increase in absolute and relative 

lung/bronchial weights in both sexes. 

At 0.100 mg/L, increased lung/bronchial 

weights were also seen, along with lung 

histopathology (alveolar macrophages, 

peribronchiolar proliferation) in both 

sexes.

870.3700a F: 0,10, 50, 250 

mg/kg/day

42248613 (1985) Maternal NOAEL = 50 mg/kg/day

LOAEL = 250 mg/kg/day based on 

decreased body weight gain and food 
Fluazinam Human Health Risk Assessment DP No. D397601

Page 47 of 51

Table F.4. Subchronic, Chronic and Other Toxicity Studies for Fluazinam Technical

Guideline/

Type of Study

Study Title/

Classification /Doses MRID Results

Prenatal 

developmental 

toxicity 

rats

Acceptable/guideline consumption and increased water 

consumption and urogenital staining

Developmental NOAEL = 50 

mg/kg/day

LOAEL = 250 mg/kg/day based on 

decreased fetal body weights and 

placental weights, increased facial/cleft 

palates, diaphragmatic hernia, and 

delayed ossification in several bone 

types, greenish amniotic fluid and 

possible increased late resorptions and 

postimplantation loss

870.3700b

Prenatal 

developmental 

toxicity

rabbits

F: 0, 2, 4, 7, 12 

mg/kg/day 

Acceptable/guideline

42248616 (1988) Maternal NOAEL = 4 mg/kg/day

LOAEL = 7 mg/kg/day based on 

decreased food consumption and 

increased liver histopathology.

Developmental NOAEL = 7 mg/kg/day

LOAEL = 12 mg/kg/day based on an 

increase in total litter resorptions and 

possible fetal skeletal abnormalities

870.3700b

Prenatal 

developmental 

toxicity 

rabbits

F: 0, 0.3, 1, 3 mg/kg/day 

Unacceptable/guideline

42248615 (1985); 

42248614 (1984); 

42248617 (1984)

Maternal NOAEL = 3 mg/kg/day

LOAEL = not identified (>3 mg/kg/day)

Developmental NOAEL = 3 mg/kg/day

LOAEL = not identified (>3 mg/kg/day)

870.3800

Reproduction and 

fertility effects

rats

F0 males: 0, 1.5, 7.3, 

36.6 mg/kg/day

F0 females: 0, 1.7, 8.4, 

42.1 mg/kg/day

F1 males: 0, 1.9, 9.7, 

47.3 mg/kg/day

F1 females: 0, 2.2, 10.6, 

53.6 mg/kg/day

Acceptable/guideline

42248619 (1987); 

42208406 (1985); 

42248618 (1986)

Parental/Systemic NOAEL = 1.9 

mg/kg/day

LOAEL = 9.7 mg/kg/day based on liver 

pathology in F1 males

Reproductive NOAEL = 10.6 

mg/kg/day

LOAEL = 53.6 mg/kg/day based on 

decreased number of implantation sites 

and decreased litter sizes to day 4 postpartum for F1 females (F2 litters).

Offspring NOAEL = 8.4 mg/kg/day

LOAEL = 42.1 mg/kg/day based on 

reduced F1 and F2 pup body weight 

gains during lactation.

870.4100a

Chronic toxicity 

rats

M: 0, 1.0, 1.9, 3.9 

mg/kg/day

F: 0, 1.2, 2.4, 4.9 

mg/kg/day

Acceptable/guideline

44839901 (1993); 

44807213

NOAEL = Males: 1.9 mg/kg/day; 

Females: 4.9 mg/kg/day

LOAEL = Males: 3.9 mg/kg/day; 

Females: not identified (>4.9 

mg/kg/day) based on increased 

testicular atrophy in males and no 

effects in females

870.4100b

Chronic toxicity 

dogs

M & F: 0, 1, 10, 50 

mg/kg/day

Acceptable/guideline

42270603 (1987); 

44807219 (1998)

NOAEL = 1 mg/kg/day

LOAEL = 10 mg/kg/day based on 

gastric lymphoid hyperplasia in both 

sexes and nasal dryness in females
Fluazinam Human Health Risk Assessment DP No. D397601

Page 48 of 51

Table F.4. Subchronic, Chronic and Other Toxicity Studies for Fluazinam Technical

Guideline/

Type of Study

Study Title/

Classification /Doses MRID Results

870.4300

Combined chronic 

toxicity/carcinogenicity

rats

M: 0, 0.04, 0.38, 3.8, 40 

mg/kg/day

F: 0, 0.05, 0.47, 4.9, 53 

mg/kg/day 

Acceptable/guideline

42248620 (1988); 

44807223 (1999); 

45150201 (2000)

NOAEL = Males: 0.38 mg/kg/day; 

Females: 0.47 mg/kg/day

LOAEL = Males: 3.8 mg/kg/day; 

Females: 4.9 mg/kg/day based on liver 

toxicity in both sexes, pancreatic 

exocrine atrophy in females and 

testicular atrophy in males.

Some evidence of carcinogenicity 

(thyroid gland follicular cell tumors) 

in male rats, but not in females.

870.4200b

Carcinogenicity 

mice

M: 0, 0.12, 1.1, 10.7, 

107 mg/kg/day

F: 0, 0.11, 1.2, 11.7, 117 

mg/kg/day

Acceptable/guideline

42208405 (1988); 

44807220 (1996)

NOAEL = Males:1.1 mg/kg/day; 

Females: 1.2 mg/kg/day

LOAEL = Males: 10.7 mg/kg/day; 

Females: 11.7 mg/kg/day based on 

increased incidences of brown 

macrophages in the liver of both sexes, 

eosinophilic vacuolated hepatocytes in 

males, and increased liver weight in 

females

Clear evidence of carcinogenicity

(hepatocellular tumors) in male mice, 

but not in females

870.4200b

Carcinogenicity 

mice

M: 0, 126, 377, 964 

mg/kg/day

F: 0, 162, 453, 1185 

mg/kg/day 

Acceptable/guideline

44807222 (1996); 

44807221 (1998); 

45201301 (2000)

NOAEL = Males:<126 mg/kg/day, 

Females: <162 mg/kg/day

LOAEL = Males: 126 mg/kg/day; 

Females: 162 mg/kg/day based on 

increased liver weights and liver and 

brain histopathology in both sexes

Equivocal/some evidence of 

carcinogenicity (hepatocellular 

tumors) in male mice, but not in 

females

870.5100

Bacterial reverse 

mutation assay 

(Ames test)

Up to 2 μg/plate for S. 

typhimurium strains and 

up to 250 μg/plate for E. 

coli (-S9). Up to 100 

μg/plate for S. 

typhimurium strains and 

Up to 500 μg/plate for E. 

coli (+ S9)

Acceptable/Guideline

42270605 (1988) Negative with and without S9 up to 

cytotoxic concentrations. 

870.5100

Bacterial reverse 

mutation assay 

(Ames test)

Up to 1μg/plate for S. 

typhimurium strains and 

up to 250 μg/plate for E. 

coli (-S9) and up to 100 

μg/plate for S. 

typhimurium strains and 

up to 500 μg/plate for E. 

coli (+S9) 

42270604 (1989) Negative with and without S9 up to 

cytotoxic concentrations. 
Fluazinam Human Health Risk Assessment DP No. D397601

Page 49 of 51

Table F.4. Subchronic, Chronic and Other Toxicity Studies for Fluazinam Technical

Guideline/

Type of Study

Study Title/

Classification /Doses MRID Results

Acceptable/Guideline

870.5300

In vitro mammalian 

gene mutation assay 

Up to 9 μg/mL (+S9), up 

to 0.3 μg/mL (-S9)

Acceptable/guideline

45261801 (2000) Negative with S9 activation up to 9 

μg/mL. Negative without S9 activation 

up to 0.3 μg/mL.

Compound tested to cytotoxic 

concentrations.

870.5300

In vitro mammalian 

gene mutation assay 

Up to 5 μg/mL (+/-S9) 

Acceptable/guideline

45156902 (1986) Negative with and without S9 activation 

up to 5 μg/mL. 

Compound tested to cytotoxic 

concentrations.

870.5375

In vitro mammalian 

chromosome 

aberration (CHL 

cells)

Up to 9.5 μg/mL (+S9) 

up to 4 μg/mL (-S9) 

Acceptable/guideline

42270606 (1988) Negative with and without S9 up to 

cytotoxic concentrations. Cells 

harvested at 24 and 48 hours in 

nonactivated studies and at 24 hours in 

activated studies.

870.5395

Mammalian 

erythrocyte 

micronucleus test

500, 1000, 2000 mg/kg 

(oral gavage) 

Acceptable/guideline

44807224 (1999) Negative at 24 hour sacrifice (500, 

1000, 2000 mg/kg).

Negative at 24, 48, and 72 hour 

sacrifices (2000 mg/kg).

870.5550

UDS in primary rat 

hepatocytes

Unacceptable/guideline

0.05 to 6.25 μg/mL

45156901 (1984) Negative; however there were several 

serious study deficiencies: treatment 

time shorter than recommended, no data 

supporting the claim of cytotoxicity, 

data variability for major endpoints.

870.5550

Differential 

killing/growth 

inhibition in B. 

subtilis

0.003 to 0.3 μg/disk

(-S9)

0.3 to 30 μg/disk (+S9) 

Unacceptable/guideline

42270607 (1988) Negative, however only one replicate 

plate/dose was used. 

870.6200a

Acute neurotoxicity 

screening battery 

rats

M & F: 0, 50, 1000, 

2000 mg/kg 

Acceptable/guideline

44807210 (1995) Systemic NOAEL = 50 mg/kg

LOAEL = 1000 mg/kg based on soft 

stools and decreased motor activity on 

day of dosing.

Neurotoxicity NOAEL = 2000 mg/kg

LOAEL = not identified (>2000 mg/kg)

870.6200b

Subchronic 

neurotoxicity 

screening battery 

rats

M :0, 21, 69, 74, 149, 

233 mg/kg/day;

F: 0, 23, 81, 89, 175, 

280 mg/kg/day 

Acceptable/guideline

44807217 (1998); 

44807218 (1998)

Neurotoxicity NOAEL = Males: 233 

mg/kg/day; Females: 280 mg/kg/day

LOAEL = not identified (Males: >233 

mg/kg/day; Females: > 280 mg/kg/day) 

870.6300

Developmental 

neurotoxicity

0, 2, 10 or 50 mg/kg/day 

Acceptable/NonGuideline

46534401, 

47018301 and 

47037001. 

Maternal:

NOAEL not established. No toxicity at 

highest dose tested. 

Developmental:

NOAEL = 2 mg/kg/day.

LOAEL = 10 mg/kg/day based on 

decreased pup weight and gain and 

delayed balano-preputial separation. 
Fluazinam Human Health Risk Assessment DP No. D397601

Page 50 of 51

Table F.4. Subchronic, Chronic and Other Toxicity Studies for Fluazinam Technical

Guideline/

Type of Study

Study Title/

Classification /Doses MRID Results

870.7485

Metabolism and 

pharmacokinetics

rats

0.5, 50 mg/kg 

Acceptable/guideline

44807233 (1995); 

43521004 thru 

43521008, 

43553001 (1993-

1995)

Only 33-40% of the administered dose 

was absorbed. Most of the administered 

dose was recovered in the feces (>89%). 

Excretion via the urine was minor 

(<4%). Total biliary radioactivity, 

however, represented 25-34% of the 

administered dose, indicating 

considerable enterohepatic circulation. 

870.7600

Dermal AbsorptionRat

500 g/L (Fluazinam SC) 

and 0.5 g/L (diluted 

Fluazinam SC) for 6 

hours

Acceptable/Guideline

48361513 (2001) The mean absorbed dose for Fluazinam 

SC at 24 hours was 0.38% (18.67 μg 

equiv.cm-2). The dermal delivery was 

0.52% (25.72 μg equiv.cm-2). The mean 

absorbed dose for diluted Fluazinam SC 

at 24 hours was 4.08% (0.153 μg

equiv.cm-2). The dermal delivery dose 

was 4.47% (0.169 μg equiv.cm-2).

870.7800

ImmunotoxicityMouse

Acceptable/Guideline

0, 1000, 3000 or 7000 

ppm (0, 217.7, 679.0 or 

1684.6 mg/kg/day)

MRID 48708702 

and 48708703 

(2011)

Under conditions of the combined 

studies, the immunotoxicity NOAEL is 

50 ppm (equivalent to 11 mg/kg/day); 

the LOAEL is 1000 ppm (equivalent to 

231 mg/kg/day) based on decreased 

anti-SRBC AFC response. 

The systemic toxicity NOAEL is 7000 

ppm (1684.6 mg/kg/day); the LOAEL 

was not established.

Non-guideline

In Vitro

Percutaneous 

Absorption of 

Radiolabeled 

Fluazinam in Two 

Formulations

Through Rat Skin

Fluazinam applied to 13 

rat dermatomed skin 

membranes in vitro in 2 

test formulations; 

Fluazinam SC and 

Diluted Fluazinam SC 

(Fluazinam Suspension 

using in vitro flow 

through diffusion cell 

system. The 

formulations were 

applied to skin for 24 

hours at 10 uL/cm2

giving the nominal dose 

levels of 5000 μg/cm2

and 5 μg/cm.2

48361514 (2000) Dermal delivery of Fluazinam from the 

Fluazinam SC (5000 μg/cm2) was 119 

μg equiv/cm2or 2.36% of the applied 

dose. Of this, only 58 μg equiv/cm2 or 

1.16% of the applied dose was absorbed. 

Dermal delivery of Fluazinam from the 

Diluted Fluazinam SC (5 μg/cm2) was 

1.88 μg equiv/cm2 or 40.17% of the 

applied dose. Of this, only 0.75 μg 

equiv/cm2 or 15.95% of the applied dose 

was absorbed. For risk assessment 

purposes the dermal delivery dose at 24 

hours will be used since it includes the 

absorbed dose as well as any material 

potentially absorbed (absorbable dose). 

Non-guideline

In Vitro

Percutaneous 

Absorption of 

Radiolabeled 

Fluazinam in Two 

Formulation 

Through Human 

Skin

Fluazinam applied to 

human dermatomed skin 

membranes in vitro

using a flow through 

diffusion cell system. A 

Suspension Concentrate 

and a Diluted 

Suspension Concentrate 

were used and the 

formulations were 

48361515 (2000) Dermal delivery of Fluazinam from the 

Fluazinam SC was 81 ug equiv.cm2 or 

1.61% of the applied dose. Of this, only 

8 ug equiv. cm2 or 0.15% of the applied 

dose was absorbed. Dermal delivery of 

Fluazinam from the Diluted Fluazinam 

SC was 0.83 ug equiv. cm-2 or 16.49% 

of the applied dose. Of this, only 0.10 

ug equiv. cm2 or 2.08% of the applied 

dose was absorbed. For risk assessment 
Fluazinam Human Health Risk Assessment DP No. D397601

Page 51 of 51

Table F.4. Subchronic, Chronic and Other Toxicity Studies for Fluazinam Technical

Guideline/

Type of Study

Study Title/

Classification /Doses MRID Results

applied to the skin at 10 

μL.cm-2 giving the 

nominal dose levels of 

5000 μg.cm-2 and 5 

μg.cm,-2respectively.

purposes the dermal delivery dose at 24 

hours will be used since it includes the 

absorbed dose as well as any material

potentially absorbed (absorbable dose). 

Non-guideline

Mechanistic Study 

on Thyroid 

Function in Rats

0 50, 1000 and 3000 

ppm for 7 days (0, 3.58, 

71.1, and 212 

mg/kg/day)

Acceptable/Non-guideline

48361509 (2004) Decrease in T4 and an increase or 

increasing trend in TSH at 1000 and 

3000 ppm groups. Increase in UDPGT 

activity toward 4-nitrophenol in all 

treated groups. Thyroid hypertrophy and 

proliferation at 1000 and 3000 ppm.

Non-guideline

Mechanistic Study 

on Thyroid 

Function and its 

Reversibility in Rats

Main: 0 and 3000 ppm 

for 7 days and sacrificed 

(0 and 222 mg/kg/day)

Recovery: 0 and 

3000ppm then 

reversibility for 7 days

Acceptable/Non-guideline 

48361510 (2005) Decreases in T3 and T4 and an 

increasing trend in TSH in the main 

group after treatment at 3000 ppm. In 

the 3000 ppm recovery group after 7 

days, decrease in T3 noted at almost the 

same level, but no changes in T4 or 

TSH. Increase in UDPGT activity 

toward 4-nitrophenol in main group, 

similar changes in recovery group. 

Thyroid proliferation in main group @ 

HDT, no proliferation in recovery group

Non-guideline

Effects on Hepatic 

Drug-Metabolizing 

Enzyme induction, 

Cell Proliferation 

and Oxidative 

Stress in Mice

0 10, 100 and 1000 ppm 

for 3, 7, and 14 days (0, 

1.38, 13.9, and 140 

mg/kg/day)

Acceptable/Non-guideline

48361511 (2001) Increases in cytochrome P-450 content, 

ECOD and PROD in the 1000 ppm 

group. The 100 ppm group showed an 

increase in ECOD and an increasing 

trend in PROD. Increases in CYP1A 

were seen in the 1000 ppm group. The 

100 ppm group also exhibited an 

increase in CYP2B and an increasing 

trend in CYP1A. Hepatic proliferation 

in1000 ppm group after 7 and 14 days. 

No effect on oxidative stress markers. 

Non-guideline

Additional 

Mechanistic Study 

on Hepatic DrugMetabolizing 

Enzyme induction, 

Cell Proliferation 

and the 

Reversibility of its 

Toxic Effects in 

Mice 

Main: 0 and 1000 ppm 

for 14 days and 

sacrificed (0 and 137 

mg/kg/day)

Recovery: 0 and 

1000ppm (0 and 139 

mg/kg/day) then 

reversibility for 14 days

Acceptable/Non-guideline

48361512 (2005) Increases in P-450 PROD, ECOD after 

14 days at 1000 ppm. Returned to 

normal in the satellite group after 14 

days of recovery at 1000ppm. Increase 

in CYP1A and an increasing trend in 

CYP2B in the main group after 14 days 

at 1000 ppm. In the satellite group after 

14 days at 1000 ppm, still a significant 

increase (but lower) in CYP1A. CYP2B 

returned to normal. No changes in 

hepatic proliferation observed in any 

group.