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EXECUTIVE SUMMARY

EPA’s Health Effects Division (HED) has evaluated the available data and the most recent 

human health risk assessments for the broad-spectrum insecticide fipronil to determine the scope 

of work necessary to support the registration review process. HED has considered the current 

use patterns (OPPIN Database and current labels) as well as the available toxicity and exposure 

information for fipronil. The most recent human health risk assessment for fipronil was 

conducted in conjunction with a petition to support and maintain the established rice grain 

tolerance for imported rice (PP# 8E7480, D360652, D. Drew, 09/22/2009). 

The purpose of the scoping process is to determine whether sufficient data are available to assess 

the safety of this pesticide, as well as to determine whether any new data have been submitted 

since the last assessment that would necessitate conducting a new human health risk assessment 

to support registration review. 

Fipronil [5-amino-1-(2,6-dichloro-4-(trifluoromethyl)phenyl)-4-[(1R,S)-

(trifluoromethyl)sulfinyl]-1H-pyrazole-3-carbonitrile] is a broad-spectrum insecticide belonging 

to the phenylpyrazole class of insecticides. 

 

Fipronil is registered for a variety of agricultural and home-use products, including those to treat 

outdoor ant pests, as well as to treat fleas and ticks on pets. EPA registered products are 

formulated as: dust, granules, pelletted/tabletted, wettable powder, emulsifiable concentrate, 

flowable concentrate, soluble concentrate, ready-to-use soluble, pressurized liquid, and bait 

stations. The oldest label (Combat abf5, EPA Reg. 64240-39), was first registered on May 27, 

1998 for ant control use on domestic dwellings. Currently there are several EPA registered 

products including seven Special Local Need (SLN) registrations: four (4) Louisiana, two (2) 

Mississippi, and one (1) Tennessee. Also there is an emergency exemption (Section 18) 

registration granted to Oregon for the control of the cabbage maggot on turnips and rutabagas 

(D317073). Pending registrations recently assessed include a ready–to-use product to be applied 

as a foam from pressurized cans (D380721, M. Dow, 08/11/2010) and a dry aerosol spray 

(D385945, M. Dow, 01/25/2011). Other pending registrations under review include several spoton formulations for pet treatments. 1

Currently, the 40 CFR § 180.517 has permanent tolerances for fipronil (which include its 2 

metabolites and 1 photodegradate) in/on: field corn grain, stover and forage; the fat, liver, meat 

and meat byproducts (except liver) of cattle, goat, hog, horse and sheep; eggs; milk fat; potato 

and potato wet peel; poultry fat, meat and meat byproducts; and rice grain and straw. Timelimited tolerances for turnip and rutabaga are in effect until 12/31/13. Finally, tolerances for 

indirect or inadvertent residues are established in/on wheat, grain, forage, hay, and straw. 

According to the revised version of Table 1 OPPTS 860.1000 (ChemSAC, 30/June/2008) a 

tolerance is required process potato waste. The tolerance for potato wet peel currently 

included in the 40 CFR § 180.517 should be revoked as this is no longer an important feed 

item and a tolerance of 0.10 ppm for processed potato waste should be included. The 

 

1 Pending and Active Registrations for Fipronil 129121 / 120068-PRISM Query Results: 01/13/2011
Page 3 of 47

tolerance expression in the 40 CFR § 180.517 needs to be modified according to the new 

Interim Guidance on Tolerance Expressions (S. Knizner, 27/May/2009). 

In the summary document for the petition for uses in imported rice, HED requested revocation of 

the tolerance for rice straw based on the absence of U.S. registrations and the fact that is not a 

significant import commodity. This needs to be updated in the Code of Federal Regulations 

(CFR) (D360652, W. Donovan, 08/25/2009). In addition: label amendments, additional data 

from Japan, and crop field trials from Brazil were required. 

In acute toxicity studies, fipronil exhibits low to moderate toxicity, depending on the route of 

exposure and species. Fipronil has been classified by the HED CPRC as a Group C - Possible 

Human Carcinogen, based on increases in thyroid follicular cell tumors in both sexes of the rat, 

which were statistically significant by both pair-wise and trend analyses. 

The available toxicity data for fipronil are adequate to assess the chemical’s hazard potential 

although there are several data gaps. A 28/90-day inhalation toxicity and 90-day dermal study 

in the rat have been requested to further characterize the occupational inhalation and dermal risks 

of fipronil. In addition, an immunotoxicity study is required as a part of new data requirements 

for conventional pesticide registration (40 CFR Part 158). There are no data gaps for the 

assessment of the effects of fipronil on developing animals following in utero and/or early 

postnatal exposure based on a two-generation reproduction study in rats and prenatal 

developmental toxicity studies in rats and rabbits. The fipronil photodegradate MB 46513 is not 

an animal metabolite. However, significant quantities are produced in certain crops (e.g., rice). 

Therefore, it was determined that a hazard assessment for MB 46513 was needed. The Hazard 

Identification Assessment Review Committee (HIARC) concluded that using the acute and 

chronic reference doses (RfDs) for fipronil to evaluate the risk due to acute and chronic dietary 

exposure to MB46513 is health protective. 

The most recent acute dietary assessment was unrefined while the chronic dietary assessment 

was refined with anticipated residue levels and percent crop treated information. An FQPA 

safety factor of 1X was used. Exposure from drinking water was incorporated in the acute and 

chronic risk assessments using one in ten years peak and average concentrations, respectively. 

The acute and chronic dietary risk assessments (using DEEM) indicated that dietary risk 

estimates were below HED’s level of concern for the general population and all population 

subgroups. 

An updated dietary exposure assessment is recommended if: 1) the FQPA safety factor 

changes, 2) a new Drinking Water Assessment (DWA) reflects changes in the estimated 

drinking water concentration, or 3) a request for a new use is received. Nevertheless, the 

Screening Level Usage Analysis reports used in the last dietary assessment are dated July 

23, 2009 and August 27, 2009; therefore, if the percent of crop treated changes significantly 

by year 2014 a new dietary assessment may be needed. 

Residential application and post-application exposures from the uses of fipronil on pets and from 

residential uses of fipronil to control fire ants and other outdoor nuisance pests for children and 

adults, have been previously assessed and are below HED’s level of concern. No additional data 
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gaps were identified in the residential exposure assessment during the registration review 

scoping process. 

Previously assessed aggregate risk estimates are below HED’s level of concern for children and 

adults. 

The upcoming policy revisions in the SOPs for Residential Exposure Assessment may 

require revisions to the residential assessment of fipronil, in which case a new aggregate 

assessment may be required. Additionally, revisions to the aggregate assessment may be 

required in Registration Review to incorporate any changes to the toxicological endpoints 

and uncertainty factors; this will be determined once outstanding toxicology data have 

been received and reviewed by the Agency. 

There is potential for short- and intermediate-term occupational exposure to fipronil during 

mixing, loading, application, and post-application activities. Exposure and risks from currently 

registered uses have previously been assessed (ref: D246176, G. Kramer et al., 05/22/1998; 

D269725, M. Dow, 10/18/2000; D244048, M. Dow, 10/24/2000; D331890, B. Hanson, 

06/19/2007). The most recent human health risk assessment for fipronil was conducted in 

conjunction with a petition to support and maintain the established rice grain tolerance for 

imported rice (PP# 8E7480, D360652, D. Drew, 09/22/2009). Results from occupational handler 

scenarios assessed indicate that short- and intermediate-term exposure risks are not of concern to 

the Agency (i.e., and MOE ≥ 100) at baseline level of personal protection for most exposure 

scenarios. 

An updated occupational assessment may be required for any fipronil use site if new data are 

identified which impact exposure estimates, new points of departure, a revised FQPA SF, or 

revisions to exposure policies and procedures are made. As for the seed treatment use (corn 

field seed treatment), the maximum amount of seed treated per day might have to be revisited 

since HED is currently in the process of revising ExpoSAC Policy 15: Amount of Seed 

Treated or Planted per Day (March 2, 2004) in efforts to update the daily amount of seed 

treated in commercial seed treatment facilities. 

A moderately large number of incidents have been reported involving fipronil. Although the 

frequency of incidents appears to be decreasing over time and majority of incidents were of low 

to moderate severity, there were eight incidents classified as major severity and one incident 

resulted in a death due to an allergic reaction. Therefore, based on the number of incidents 

reported, and the effects noted in the incidents, the evaluation warrants further analysis in 

the preliminary risk assessment phase of registration review. This further analysis will 

include reviewing other incident data from other sources (such as, SENSOR and PCC) as well as 

the NIOSH article “Acute illnesses associated with exposure to fipronil—surveillance data from 

11 states in the United States, 2001–2007.” 
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1.0 FIPRONIL FORMULATIONS AND USE PATTERNS 

Fipronil formulations include dust, granules, pelletted/tabletted, wettable powder, emulsifiable 

concentrate, flowable concentrate, soluble concentrate, ready-to-use soluble, pressurized liquid, 

and bait stations (solid, liquid and gel formulations). 

HED used the Biological and Economics Analysis Division (BEAD) Label Data System to 

identify all agricultural and non-agricultural uses of fipronil. See Fipronil HED Master Label 

Report (11/08/2010) for a complete list. There have been multiple emergency exemption 

(Section 18) requests for the use of fipronil that have been reviewed by BEAD. These requests 

were for outside structures, potatoes, and sweet potatoes. Currently, there is an emergency 

exemption registration granted to Oregon for the control of the cabbage maggot on turnips and 

rutabagas (D317073, Clock-Rust M., 08/17/2005). Time-limited tolerances for turnip and 

rutabaga are in effect until 12/31/13. 

Maximum rates of application for Food and Non-Food uses of fipronil vary depending on the site 

and the application method. See Appendix E-Fipronil Products (PRD Appendix A: Food/Feed 

& Non –Food/Non-Feed Uses Considered in Registration Review, 11/08/2010) for a complete 

list. 

Agricultural Uses 

In agricultural settings fipronil may be applied as an outdoor general surface spray, foliar and 

containerized treatment, seed treatments, perimeter and spot treatment, soil sub-surface /slit 

applications, bait applications and ant mound treatments, wood treatment and injection 

applications for termite control. 

Agricultural use sites include: agricultural crops including potatoes, rutabagas, and turnip (infurrow uses); orchards, fruit trees, Christmas tree plantings, forest lands and pines; 

outdoor/indoor ornamentals plants and trees; ornamental lawns and turf (golf courses, parks, 

cemeteries, athletic fields, and other recreational and commercial areas); interior landscapes, 

greenhouses, and nursery uses; ant mounds, potting soil and seed treatment (field corn for export 

only). 

Non-Agricultural and Residential Uses 

The product may be applied as an outdoor general surface spray, perimeter treatment, crack and 

crevice and spot treatment, void treatment, bait application and ready to use sprays for pest 

control in and around commercial and domestic dwellings including: apartments, homes, hotels, 

Food/Feed Handling Establishments (non-food/feed areas only), restaurants, hospitals, nursing 

homes (non-patient areas), motels, hobby greenhouses, interiorscapes, office buildings, schools, 

zoos, pet quarters, sewers and drainage systems, camp sites, parks and recreational areas, rights 

of way, transportation equipment (buses, boats, cargo trucks, trailers, ships, trains), warehouses 

and other institutional, commercial, and industrial buildings. Other non-agricultural uses include 

paths and patios and ant mound treatment. 
Page 6 of 47

Fipronil is registered for a variety of home-use products. Residential uses (household/domestic 

dwellings) include perimeter treatments/outside surfaces, ant mound treatments and ready to use 

squeeze and spot-on flea and tick treatments for domestic animals. 

Application Equipment for Fipronil Treatments2

Application equipment used for fipronil treatments include: 

1. Open-cab ground-boom spray equipment for in-furrow treatment 

2. Aircraft/helicopter for broadcast bait applications for leaf cutter ant control 

3. Granule applicator for broadcast applications for ant control 

4. Slurry type seed treater for field corn seed treatment 

5. Low pressure handwand for ant mound treatment on outdoor ornamentals, greenhouses 

and perimeter treatment of non-agricultural outdoor areas, structures, buildings, etc. 

6. Glove, squeeze applicator, and ready to–use trigger spray formulations for “spot-on” 

products on pets 

7. Bait stations and ready to–use spray formulations for ant control 

8. Injection equipment and syringe applicator for crack and crevice applications 

9. Soil injection equipment for void and sub-surface treatment applications 

2.0 HAZARD IDENTIFICATION/TOXICOLOGY

Fipronil is a broad-spectrum insecticide belonging to the pyrazole class of insecticides. The 

toxicology database provides evidence of neurotoxic activity as evidenced by neurologic signs in 

several studies and species. Fipronil is also associated with alterations in the thyroid-pituitary 

hormonal status, resulting in alterations in thyroid hormonal levels and thyroid follicular cell 

tumors. 

The toxicology database for fipronil is adequate, however, a 28/90-day inhalation toxicity and 

90-day dermal study in the rat has been requested to further characterize the occupational 

inhalation and dermal risks of fipronil. (See Appendix C- Rationales for Toxicology Data 

Requirements). The toxicology database for fipronil does not show any definite evidence of 

treatment-related effects on the immune system, however a new data requirement is the 

immunotoxicity study. Some decreases in the albumin to globulins were noted in the subchronic and/or chronic studies in rats but were not considered evidence for a direct immunotoxic 

effect. There were no alterations in leukocytes or effects on thymus or spleen weight reported. 

No indications of immunotoxicity were indicated in a search of the open literature. The overall 

weight of evidence suggests that fipronil does not directly target the immune system. The other 

studies do not specifically monitor toxicity to the immune system, therefore, an immunotoxicity 

study is required as a part of the new data requirements in the 40 CFR Part 158 for conventional 

pesticide registration. However, the Agency does not believe that conducting a functional 

immunotoxicity study will result in a lower PoD than that currently used for overall risk 

assessment and the current PoDs will be maintained. Therefore, a database uncertainty factor 

UFDB is not needed to account for lack of this study. There is otherwise confidence in the quality 

 

2

 EFED Label Data Report, 11/08/2010 
Page 7 of 47

of the existing studies and the reliability of the toxicity endpoints identified for use in risk 

assessment. 

There are no data gaps for the assessment of the effects of fipronil on developing animals 

following in utero and/or early postnatal exposure based on a two-generation reproduction study 

in rats and prenatal developmental toxicity studies in rats and rabbits. In addition, an acceptable 

developmental neurotoxicity study was conducted with fipronil. Although there is no evidence 

of potential for enhanced pre- or post-natal susceptibility in infants and children in the 

developmental and reproduction studies, the developmental neurotoxicity study identified a 

developmental no-observed-adverse-effect-level (NOAEL) which was less than the maternal 

NOAEL, indicating an apparent susceptibility issue. However, the HIARC concluded that the 

apparent increased susceptibility in the developmental neurotoxicity study was not supported by 

the overall weight-of-the-evidence. (Fipronil HIARC Report, June 9, 1999). Evaluation of the 

database indicated that: 1) the offspring body weight findings in the developmental neurotoxicity 

study are not supported by the results of the two-generation reproduction study in rats at similar 

treatment levels; 2) increased susceptibility to the offspring was not demonstrated in the prenatal 

developmental toxicity study nor the two-generation reproduction study in rats; and 3) no 

increased susceptibility was seen in the prenatal developmental toxicity study in rats following in 

utero exposure to the photodegradate, MB 46513. This evaluation was supported in the 2009 risk 

assessment for fipronil on imported rice (D360652, D. Drew, 09/22/2009). The Food Quality 

Protection Act Safety Factor Committee (FQPA SFC) recommended that the 10X factor for 

enhanced sensitivity to infants and children (as required by FQPA) was reduced to 1X for 

fipronil (Memo, HED Doc. No. 012619, B. Tarplee, 05/12/1998). The other uncertainty factors 

for fipronil are 10X for intra-species and 10X for inter-species variation. 

In acute toxicity studies, fipronil exhibits low to moderate toxicity, depending on the route of 

exposure and species. (See Appendix B - Fipronil Toxicology Table 1.0). Fipronil has moderate 

acute toxicity (toxicity category II) by the oral and inhalation routes in rats. By the dermal route, 

it is of moderate toxicity in rabbits, and low toxicity in rats (III). Fipronil technical is relatively 

non-irritating to the skin (IV) and eye (III) of rabbits and is not a dermal sensitizer. Dermal 

absorption in rats is estimated to be 1% or less based on a dermal absorption study. 

Fipronil showed neuromuscular toxicity in both rats and dogs as evidenced by signs in the acute 

and sub-chronic screening batteries in the rat, in developmental neurotoxicity and chronic 

carcinogenicity studies in the rat, and in two chronic dog studies. Clinical signs of 

neuromuscular toxicity were not observed in the mouse or rat at 28 or 90 days. The rat and 

mouse showed evidence of liver and/or thyroid alterations at all time periods (chronic only for 

the mouse). 

The acute dietary endpoint is based on decreased hind leg splay (a neuromuscular deficit). The 

short- and intermediate-term incidental oral endpoints are based on decreased body weight, food 

consumption, and feed efficiency. Chronic dietary and long-term endpoints are based on 

increased incidence of seizures and death, alterations in clinical chemistry (protein) and changes 

in thyroid hormone levels. 
Page 8 of 47

Fipronil has been classified by the HED Carcinogenicity Peer Review Committee (CPRC) 

document dated July 18, 1997, as a Group C - Possible Human Carcinogen, based on increases in 

thyroid follicular cell tumors in both sexes of the rat, which were statistically significant by both 

pair-wise and trend analyses. There is no apparent concern for mutagenicity (no mutagenic 

activity). The RfD methodology should be used to estimate human risk because the thyroid 

tumors appear to be related to a disruption in the thyroid-pituitary status. Dietary risk concerns 

due to long-term consumption of fipronil residues are adequately addressed by the DEEMTM

chronic exposure analysis using the RfD. 

The fipronil photodegradate MB 46513 is not an animal metabolite. However, significant 

quantities are produced in certain crops (e.g., rice). Therefore, it was determined that a hazard 

assessment for MB 46513 was needed. The HIARC concluded that there were differences as 

well as similarities between the toxicity profiles for fipronil and MB 46513 (MB 46513 HIARC 

memo, December 6, 2000). Differences included the occurrence of thyroid neoplasia in the rats 

treated with fipronil, but not MB 46513. Although, in the rat, both fipronil and MB 46513 result 

in clinical signs of neuromuscular toxicity, these signs do not appear with fipronil until later 

(after 90 days). Chronic exposure to the rat with both compounds results in qualitatively and 

quantitatively similar neurologic effects. Other measured signs of neuromuscular toxicity 

(observed in the acute neurotoxicity study), appear to occur at about the same dose for both 

compounds. Therefore, it appears that, in the rat, the differences between the two compounds 

are qualitative for thyroid effects; but for neuromuscular toxicity, the differences appear to be 

more quantitative, with longer exposure to fipronil needed in the rat to result in the same clinical 

signs as MB 46513. In the dog, the two compounds are similar for neuromuscular toxicity. In 

the mouse, there is no neuromuscular toxicity with fipronil, but there is with MB 46513. The 

HIARC concluded that using the acute and chronic reference doses (RfDs) for fipronil to 

evaluate the risk due to acute and chronic dietary exposure to MB46513 is health protective 

because the acute and chronic RfDs for MB 46513 are based on the same study type with the 

same neuromuscular toxicity endpoints; thus, the RfDs are similar (MB 46513 HIARC memo, 

December 6, 2000). The HIARC also determined that the potential for increased susceptibility 

of infants and children from exposure to MB 46513 would be the same as fipronil; therefore, no 

separate FQPA evaluation is required. The most recent risk assessment for fipronil in 2009 also 

supported this decision (D360652, D. Drew, 09/22/2009). 

The summary of toxicological endpoints for fipronil is listed in Appendix B, Table 3. 

Conclusion 

The toxicology database for fipronil is adequate to assess the chemical’s hazard potential 

although there are several data gaps. A 28/90-day inhalation toxicity and 90-day dermal study in 

the rat have been requested to further characterize the occupational inhalation and dermal risks of 

fipronil. In addition, an immunotoxicity study is required as a part of new data requirements for 

conventional pesticide registration (40 CFR Part 158). 

3.0 RESIDUE CHEMISTRY
Page 9 of 47

The nomenclature, registration numbers, PC Code and chemical structure of fipronil, its two 

metabolites MB 45950 and MB 46136, and it photodegradate MB 46513 are listed in Appendix 

A. 

The nature of the residue in rice, corn, rotational crops and animals (goat and hen) is adequately 

understood based on metabolism studies in which plants were treated or animals were fed with 

radiolabel fipronil (D236164, R. Loranger, 05/28/1997 and D368740, W. Donovan, 08/25/2009). 

The HED Metabolism Committee determined that the fipronil residues of concern for the 

tolerance expression and dietary risk assessment in plant and animal commodities are the parent, 

and the metabolites MB 46136 and MB 45950. The photodegradate MB 46513 is also required 

for crops in which metabolism data indicates that it comprises a significant portion of the TRR 

(i.e. rice, potatoes, and rotational crops). 

Currently, the 40 CFR § 180.517 has permanent tolerances for fipronil (which includes its two 

metabolites and one photodegradate) in/on field corn grain, stover and forage; the fat, liver, meat 

and meat byproducts (except liver) of cattle, goat, hog, horse and sheep; eggs; milk fat; potato 

and potato wet peel; poultry fat, meat and meat byproducts; and rice grain and straw. Timelimited tolerances for turnip and rutabaga are in effect until 12/31/13. Finally, tolerances for 

indirect or inadvertent residues are established in/on wheat, grain, forage, hay, and straw. See 

Appendix D for a complete list of these commodities with the tolerance level. Domestic uses of 

fipronil in rice were canceled but the tolerance was maintained to cover residues in/on imported 

rice treated with fipronil. However, in 2009, HED requested revocation of the tolerance for 

rice straw based on the absence of U.S. registrations and the fact that it is not a significant 

import commodity. This needs to be updated in the 40 CFR § 180.517 (D360652, W. 

Donovan, 08/25/2009). 

Adequate enforcement methods for plant and livestock commodities are available and have been 

successfully approved by Analytical Chemistry Laboratory (ACL) with minor revision 

recommendations which have been adequately addressed by the registrant. In the plant method, 

fipronil and metabolites MB 46136 and MB 45950 plus photodegradate MB 46513 are 

determined using gas chromatography with an electron-capture detector (GC/ECD). Limits of 

quantitation (LOQs) ranging 0.005-0.01 ppm were reported. 

Studies describing multiresidue method testing of fipronil, its metabolites MB 45950 and MB 

46136, and photodegradate MB 46513 have been submitted previously by the petitioner and 

forwarded by EPA to Food and Drug Administration (FDA). Acceptable recoveries of fipronil 

and its metabolites MB 45950 and MB 46136 were obtained in corn forage using Protocol E. 

Acceptable recoveries of MB 46513 were obtained in corn forage using Protocol E and cotton 

seed using Protocol F. 

Label changes to Regent 4SC (EPA Reg No.7969-207) for rotational crops were performed as 

recommended (D331890, B. Madden, 06/19/2007). For the previous petition for uses in 

imported rice (PP#8E7480), several label amendments; more data from Japan and crop field 

trials from Brazil were required. For the Japanese trials, information concerning the field portion 

of the study and the analytical portion of the study must be submitted. To support the proposed 

foliar use in Brazil, data are required which depict magnitude of the residues of fipronil 
Page 10 of 47

and its metabolites MB 45950, MB 46136, and MB 46513 in/on rice grain harvested 30 days 

following postemergence foliar treatment of the proposed formulated product (KLAP) at 

12 g ai/ha. 

According to the revised version of Table 1 OPPTS 860.1000 (ChemSAC, 06/30/2008) several 

processing studies are required to establish a tolerance for feed items that correspond to RACs 

treated with fipronil. Tolerances for corn, milled byproducts; rice, bran; and potato, process 

waste may be needed. However, these will not be required for corn milled byproducts and rice 

bran since previous processing studies show that residues do not concentrate in these 

commodities (D197451, G.F. Kramer, 06/07/1994 and D368740, W. Donovan, 08/25/2009). In 

addition, the tolerance for potato wet peel is used for dietary burden calculations that include 

process potato waste feed commodity (OPPTS 860.1000). Potato wet peel is no longer an 

important feed item. The tolerance for potato, wet peel currently included in the 40 CFR § 

180.517 should be revoked and a tolerance of 0.10 ppm for process potato waste should be 

included. 

In 2009 HED established interim guidance on writing tolerance expressions for enforcement 

purposes (S. Knizner, 05/27/2009). In order to add clarity to the language used to establish the 

coverage of the tolerance expression and measurement of the level of the residue in the raw 

agricultural commodity (RAC), the text in the 40 CFR § 180.517 should read: “(a) General. (1) 

Tolerances are established for residues of fipronil, including its metabolites and degradates, in or 

on the commodities in the table below. Compliance with the tolerance levels specified below is 

to be determined by measuring fipronil (5-amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-

[(1R,S) (trifluoromethyl) sulfinyl]-1H-pyrazole-3-carbonitrile) and its metabolites 5-amino-1-

[2,6-dichloro-4-(trifluoromethyl) phenyl]-4-[(trifluoromethyl) sulfonyl]-1H-pyrazole-3-

carbonitrile and 5-amino-1-[2,6-dichloro-4-(trifluoromethyl) phenyl]-4-[(trifluoromethyl)thio]-

1H-pyrazole-3-carbonitrile and its photodegradate 5-amino-1-(2,6-dichloro-4-

(trifluoromethyl)phenyl]-4-[(1R,S)-(trifluoromethyl)]-1H-pyrazole-3-carbonitrile.” 

Conclusions 

The following residue chemistry deficiencies need to be addressed: 

• Revocation of the tolerance for rice straw 

• Label amendments, additional data from Japan and crop field trials from Brazil are 

required based on deficiencies identified in the petition for uses in imported rice 

• Revocation of the tolerance for potato wet peel and establishment of a tolerance of 0.10 

ppm for potato, process waste 

• Modification of the tolerance expression in the 40 CFR § 180.517 according to the new 

HED guidance 

4.0 DIETARY EXPOSURE

Unrefined acute and refined chronic (with anticipated residue levels and percent Crop Treated 

information) dietary risk assessments were conducted to evaluate exposure from food residues of 

the insecticide fipronil using the version 2.03 Dietary Exposure Evaluation Model (DEEM-
Page 11 of 47

FCIDTM). It uses food consumption data from the U.S. Department of Agriculture’s Continuing 

Surveys of Food Intakes by Individuals (CSFII) from 1994-1996 and 1998 to calculate dietary 

risk. These analyses were performed in support of petition PP#8E7480 submitted to change the 

tolerance for fipronil on rice into that of an import regulatory level. 

The last Drinking Water Assessment (DWA) of fipronil used for the most recent dietary 

assessment for import uses on rice was performed in 2007 (D 322415, J. Hetrick, 06/19/2007). 

The one in ten year peak (0.002654 ppm) and average (0.000318 ppm) drinking water 

concentrations of fipronil and its degradation products were estimated and incorporated in the 

acute and chronic dietary assessment, respectively. 

An unrefined acute and refined chronic dietary risk analyses were conducted using the DEEMFCIDTM model to estimate the exposure to fipronil. The acute dietary analysis at the 95th

percentile of exposure gives risk estimates below the 100% of the aPAD threshold level of 

concern for each population subgroup. For the most highly exposed population subgroup, 

children 1-2 years of age, acute dietary risk was estimated to be only 25% of the aPAD with an 

exposure of 0.006209 mg/kg/day. The refined chronic analysis also yielded risk estimates below 

100% of the cPAD for each population subgroup. For children 1-2 years of age, the resulting 

chronic dietary risk was reported at 95% cPAD with an exposure of 0.000190 mg/kg/day. A 

critical commodity contribution analysis made for children 1-2 years of age, the most highly 

exposed population subgroup, has shown dairy products, meat, and cereal grains to be the 

chronic dietary risk drivers of fipronil comprising 43%, 14% and 11% of the total exposure 

respectively (D368732, P. Savoia, 9/17/2009). 

Conclusion 

An updated dietary exposure assessment is recommended if the FQPA safety factor changes, if a 

new DWA reflect changes in the estimated drinking water concentration, or if a request for a 

new use is received. Nevertheless, the Screening Level Usage Analysis reports used in the last 

dietary assessment are dated July 23, 2009 and August 27, 2009; therefore, if the percent of crop 

treated changes significantly by year 2014 a new dietary assessment may be needed. 

5.0 TOLERANCE ASSESSMENT AND INTERNATIONAL HARMONIZATION

Where possible, EPA encourages the harmonization of the US Tolerances and Maximum 

Residue Limits (MRLs) in key export markets. A table with the US tolerances, the Canada 

MRLs, Mexico MRLs and Codex MRLs for fipronil in registered RACs is provided in 

Appendix D- International Residue Limits. 

The established tolerance for rice straw at 0.10 ppm should be revoked from the 40 CFR 

180.517 since there are no U.S. registrations for fipronil, and rice straw is not a significant 

import commodity. In addition, the tolerance for potato wet peel should be revoked and a 

tolerance of 0.10 ppm for potato processed waste should be established. A Codex MRL has 

been established for fipronil residues in several RACs. The proposed import tolerance is 

not harmonized with the established MRL, a fact attributable to the difference in tolerance 
Page 12 of 47

expression between Codex and the U.S. There are currently no established Canadian and 

Mexican MRLs for fipronil. 

6.0 RESIDENTIAL EXPOSURE

Residential Handler and Post-application Exposure

Residential exposure to fipronil is anticipated for individuals who apply fipronil-containing 

products and from post-application exposure, or re-entry into previously treated areas. While 

residential exposures are considered to be at least short-term in duration, others are also 

considered to have intermediate-term duration potential. However, for fipronil the toxicity routespecific endpoint effects and points of departure are the same for both short- and intermediateterm exposure durations. 

Residential uses include perimeter treatments/outside surfaces, ant mound treatments and ready 

to use squeeze and spot-on flea and tick treatments for domestic animals. HED has previously 

assessed application and post-application exposures from currently registered residential uses of 

fipronil (ref: D246176, G. Kramer et al., 05/22/1998; D269725, M. Dow, 10/18/2000; D244048, 

M. Dow, 10/24/2000; D331890, B. Hanson, 06/19/2007; D360652, D. Drew et al., 09/22/2009). 

Ant Treatment Use

The 2000 assessment (D244048, M. Dow, 10/24/2000) evaluated homeowner exposure from the 

registered fipronil products used to control fire ants. Margins of exposure (MOE) for dermal 

contact and inhalation resulting from assessment of granular formulations were not of concern to 

HED. Since then, several of these registrations have been withdrawn or are no longer active, 

while others are conditionally active. Maximum application rates for residential lawns are 0.0011 

lb ai/ acre (bait stations) and 0.025 lb ai/ acre (granular formulations). 

Pet Treatment Use

HED has determined that there is the potential for exposure in residential settings during the 

application process for homeowners (adults only) who purchase and use pet products containing 

fipronil. There is also potential for post-application exposure (adults and children) from 

contacting pets previously treated with these products. HED previously assessed the application 

of fipronil shampoo, spot-on and spray-on products and no risks of concern were identified. 

Adult dermal and child (3 to < 6 years old) dermal and incidental oral post-application exposure 

(combined) was previously assessed and these were not of concern to the Agency (i.e., an MOE 

≥ 100). For the purpose of the fipronil aggregate assessment, the pet spot-on use has been 

identified as the worst case estimate for exposures to children <6 years old. 

Residential Bystander Post Application Inhalation Exposure
Page 13 of 47

The need for a bystander inhalation risk assessment for fipronil should be examined during 

registration review. Based on the Agency's current practices, a quantitative post-application 

inhalation exposure assessment has not been performed for fipronil at this time primarily because 

it has very low vapor pressure (vapor pressure of 3.75 x 10 -9 mm Hg). However, volatilization 

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

nearby to 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. The Agency received the SAP’s final report 

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

Agency is in the process of evaluating the SAP report and may, as appropriate, develop policies 

and procedures to identify the need for and, subsequently, the way to incorporate postapplication inhalation exposure into the Agency's risk assessments. If new policies or procedures 

are put into place, the Agency may revisit the need for a quantitative post-application inhalation 

exposure assessment for fipronil. 

Conclusions 

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

fipronil. An updated residential exposure assessment may be required under registration review 

based upon revisions to HED’s Residential SOPs which was reviewed by the Scientific Advisory 

Panel (SAP) in October 2009. Furthermore, if new data are identified which impact exposure 

estimates, new points of departure, a revised FQPA SF, or revisions to exposure policies and 

procedures are made a new residential assessment will be conducted. An updated assessment of 

fipronil pet products will be required under registration review based upon the updates to the 

SOPs for Residential Exposure Assessment. 

Furthermore, residential bystander exposures might occur as a result of spray applications and 

off-site transport (e.g., spray drift or volatilization). The Agency will consider the need for a 

bystander inhalation risk assessment for fipronil during registration review. 

7.0 AGGREGATE EXPOSURE AND RISK ASSESSMENT 

In accordance with FQPA, HED considers and aggregates pesticide exposures and risks from 

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

assessment, exposures from dietary and residential sources are added together and compared to 

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

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

duration of exposure. 

Fipronil is currently registered for the following residential non-dietary sites: 1) For use on cats 

and dogs for flea control and 2) for use on turf to control fire ants. These products may be 

applied by homeowners. EPA assessed residential exposure using the following assumptions: 

The probability of applying fipronil to dogs and cats to control fleas and ticks and applying 

fipronil to control turf pests on the same day is considered to be negligible (e.g. application on 

turf is limited to one application per year, and repeated applications, if necessary, may only be 

made once every one to three months during flea or tick season). Therefore, since pet and turf 
Page 14 of 47

treatment applications are infrequent, for aggregate risk assessment, exposures from these 

treatments have not been combined. 

Based on fipronil’s existing uses, the worst case aggregate exposure for adults is represented by 

their combined estimated handler dermal and inhalation exposures resulting from applying a 

fipronil product to control fire ants. The worst case aggregate exposure for children <6 years old 

is represented by their combined estimated post-application dermal and incidental oral exposures 

resulting from contact with fipronil-treated pets. These combined exposures/risks are used with 

average food and drinking water exposure estimates to determine short-and intermediate 

aggregate risks. Previously assessed aggregate risk estimates were below HED's level of concern 

for children and adults (D360652, D. Drew et al., 09/22/2009). 

Conclusions 

The upcoming policy revisions in the SOPs for Residential Exposure Assessment may require 

revisions to the residential assessment of fipronil, in which case a new aggregate assessment may 

be required. Additionally, revisions to the aggregate assessment may be required in Registration 

Review to incorporate any changes to the toxicological endpoints and uncertainty factors; this 

will be determined once outstanding toxicology data have been received and reviewed by the 

Agency. 

8.0 OCCUPATIONAL EXPOSURE 

Occupational Handler 

Occupational exposure to fipronil is anticipated for adults who apply fipronil -containing 

products and from post-application exposure, or re-entry into previously treated areas. HED 

used the Biological and Economics Analysis Division (BEAD) Label Data System to identify all 

occupational uses of fipronil. 

Based upon the current use patterns, potential occupational exposure scenarios include: 

1. Seed treatment workers (loader/applicators, sewers, baggers) 

2. Mixer/loader using dust, granules, pelletted/tabletted, wettable powder, emulsifiable 

concentrate, flowable concentrate, soluble concentrate formulations for broadcast 

applications. 

3. Mixer/Loader in support of bait station aerial application operations 

4. Applicator of subsurface/slit application treatment 

5. Applicator using open-cab ground-boom spray equipment for in-furrow treatment 

6. Mixer/loader/applicator performing broadcast application for leaf cutter ant control 

7. Mixer/Loader and Applicator exposure for soil injection applications 

8. Mix/load/application for greenhouses (low pressure handwand); 

9. Mix/load/application (MLAP) on non-agricultural outdoor areas, structures, buildings etc. 

(low pressure handwand); 

10. Mix/load/application (MLAP) for outdoor ornamentals (low pressure handwand); 

11. Mix/load/application (MLAP) for ant mounds (low pressure handwand); 
Page 15 of 47

12. Applicator of ready-to-use and “spot-on” products on pets 

13. Applicator of bait stations and ready- to-use spray formulations 

14. Syringe applicator for crack and crevice applications 

15. Foam application for void and soil treatment applications 

Results from assessments of occupational handler scenarios previously evaluated indicate that 

short- and intermediate-term exposure/risks are not of concern to the Agency (i.e., and MOE ≥

100) at either baseline or minimum level of personal protection (gloves, coveralls). 

Quantitative handler exposure/risk assessments have not been performed for application of spoton products since handler contact is expected to be negligible. 

As for the seed treatment use (corn field seed treatment), the maximum amount of seed treated per 

day might have to be revisited since HED is currently in the process of revising ExpoSAC Policy 

15: Amount of Seed Treated or Planted per Day (March 2, 2004) in efforts to update the daily 

amount of seed treated in commercial seed treatment facilities. With the increasing demand for 

hybridized treated seeds, there have been modifications not only in the seed treatment 

equipment, but in the market shares of new and currently registered pesticide products. HED 

understands that due to the high cost of producing hybrid seeds, direct seeding is done in a 

precision manner which requires lower volumes of seed per acre. However, this does not 

provide a direct correlation to the amount of seed which is treated in the commercial seed 

treatment facilities. 

Furthermore, recommended unit exposures for occupational handler assessments have generally 

been derived only from PHED. However, recently both the Outdoor Residential Exposure Task 

Force (ORETF) and Agricultural Handler Exposure Task Force (AHETF) have produced 

pesticide handler exposure monitoring data that the Agency is using in place of PHED 

(http://www.epa.gov/pesticides/science/handler-exposure-data.html). As more reliable data 

become available (such as that from the AHETF and ORETF), the Agency will continue to 

replace existing data. Reviewers should incorporate new exposure monitoring data, as 

necessary, during Registration Review. 

Conclusions 

An updated occupational assessment may be required for any fipronil use site if new data are 

identified which impact exposure estimates, new points of departure, a revised FQPA SF, or 

revisions to exposure policies and procedures are made. 

Occupational Post-application Exposures and Risks 

Occupational post-application exposure to fipronil is anticipated to occur based on the use 

pattern of the chemical. 

In-Furrow Uses (Potatoes, Turnips and Rutabagas)

Dermal post-application occupational exposure based on the in-furrow uses of fipronil are 

expected to be negligible as the soil is normally not contacted after incorporation. 
Page 16 of 47

Seed Treatment Use

Occupational handler exposure is expected for individuals involved in commercial seed 

treatment (primary handlers) and planting treated seeds (secondary handlers). However, the seed 

treatment use is for field corn seed to be exported only, and secondary handlers are not involved; 

therefore post-application exposure to fipronil treated seeds is not expected to occur. 

Pet Treatment Use

Domestic pets are expected to be treated and immediately returned to their owners such that 

post-application contact will be negligible. EPA believes that the residential post-application 

exposure/risk assessment is a worst case surrogate for any potential occupational postapplication exposures. Therefore an occupational post-application dermal exposure assessment 

was not performed. 

Leaf-Cutter Ant Use 

For the leaf-cutter ant (dry broadcast use), post-application exposure is expected to be negligible. 

Fipronil is applied as a dry granule. Relative to other uses, the rates of application are very low 

for the 0.003% medium granular formulation. 

Conclusions 

An updated occupational post- application assessment may be required for any fipronil use site if 

new data are identified which impact exposure estimates, new points of departure, a revised FQPA 

SF, or revisions to exposure policies and procedures are made. 

9.0 PUBLIC HEALTH AND PESTICIDE EPIDEMIOLOGY DATA 

A moderately large number of incidents have been reported involving fipronil (D387320, S. 

Recore, 03/01/2011). Although the frequency of incidents appears to be decreasing over time and 

majority of incidents were low to moderate severity, there were eight incidents classified as 

major severity and one incident resulted in a death due to an allergic reaction. 

The OPP Incident Data System (IDS) was utilized for pesticide incident data on the active 

ingredient fipronil (PC Code 129121). The purpose of the database search is to identify potential 

patterns on the frequency and severity of the health effects attributed to fipronil exposure. The 

IDS includes reports of alleged human health incidents from various sources, including 

mandatory Federal Insecticide, Fungicide and Rodenticide Act (FIFRA) Section 6 (a) (2) reports 

from registrants, other federal and state health and environmental agencies and individual 

consumers. Since 1992, OPP compiles these reports in IDS. IDS contain reports from across the 

U.S. and most incidents have all relevant product information recorded. Reports submitted to the 

IDS represent anecdotal reports or allegations only, unless otherwise stated in the report. 

IDS records incidents, resulting in higher severity outcomes in more detail, in a module called 

the Main IDS module. This system stores incident data for death, major and moderate incidents, 

and it includes more details about the location, date and nature of the incident. Main IDS 

incidents involving only one pesticide are considered to provide more certain information about 

the potential effects of exposure from the pesticide, and therefore these incidents are listed in 
Page 17 of 47

Appendix 1 of the Review of Human Incidents memo for Fipronil (D387320, S. Recore, 

03/01/2011). The less severe human incidents (minor, unknown, or no effects outcomes) are 

reported by registrants as counts called aggregate summaries and are recorded in a separate 

module called Aggregate IDS. 

Aggregate IDS, from January 1, 2002 to May 27, 2010, include 3855 incidents involving 

fipronil. Because it falls within the categories reported as counts (which includes minor, 

unknown or no effects), there is no unique report that provides details about the incident and 

single chemical incidents are not distinguished from multiple chemical incidents. 

For the Main IDS, from January 1, 2002 to November 30, 2010, 1164 cases were reported 

involving the active ingredient Fipronil. Of these 1164 cases, 453 cases were reported for single 

chemical fipronil only in the database. Reported cases include: neurological, respiratory, ocular, 

and renal health effects. 

The Agricultural Health Study (AHS) is a high quality, prospective epidemiology study 

evaluating the link between pesticide use and various health outcomes including cancer. The 

AHS includes private and commercial pesticide applicators and their spouses. If there are AHS 

findings relevant to a particular pesticide going through registration review, the Agency will 

ensure they are considered in the problem formulation/scoping phase of the process and, if 

appropriate, fully reviewed in the risk assessment phase of the process. The AHS includes 

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

Fipronil is not included in the AHS, and therefore does not provide information for this report. 

Conclusions 

Based on the number of incidents reported involving fipronil, and the effects noted in the 

incidents, the evaluation warrants further analysis in the preliminary risk assessment phase of 

registration review. This further analysis will include reviewing other incident data from other 

sources (such as, SENSOR and PCC) as well as the NIOSH article “Acute illnesses associated with 

exposure to fipronil—surveillance data from 11 states in the United States, 2001–2007.” 

10.0 ENVIRONMENTAL JUSTICE

There do not appear to be any particular socioeconomic subgroups that may experience a higher 

degree of exposure to fipronil. Potential areas of environmental justice concerns, to the extent 

possible, will be considered in future human health risk assessments for fipronil, in accordance 

with U.S. Executive Order 12898, "Federal Actions to Address Environmental Justice in 

Minority Populations and Low-Income Populations," 

http://www.epa.gov/compliance/resources/policies/ej/exec_order_12898.pdf. The Office of 

Pesticide Programs (OPP) typically considers the highest potential exposures from the legal use 

of a pesticide when conducting human health risk assessments, including, but not limited to, 

people who obtain drinking water from sources near agricultural areas, the variability of diets 

within the U.S., and people who may be exposed when harvesting crops. Should these highest 
Page 18 of 47

exposures indicate potential risks of concern, OPP further refines the risk assessments to ensure 

that the risk estimates are based on the best available information. 

11.0 CUMULATIVE RISK ASSESSMENT 

EPA does not have, at this time, available data to determine whether fipronil has a common 

mechanism of toxicity with other substances or how to include this pesticide in a cumulative risk 

assessment. Therefore, EPA has not assumed that fipronil has a common mechanism of toxicity 

with other substances and a cumulative risk assessment is not anticipated at this time. 

12.0 ENDOCRINE DISRUPTOR SCREENING PROGRAM

As required by FIFRA and FFDCA, EPA reviews numerous studies to assess potential adverse 

outcomes from exposure to chemicals. Collectively, these studies include acute, subchronic and 

chronic toxicity, including assessments of carcinogenicity, neurotoxicity, developmental, 

reproductive, and general or systemic toxicity. These studies include endpoints which may be 

susceptible to endocrine influence, including effects on endocrine target organ histopathology, 

organ weights, estrus cyclicity, sexual maturation, fertility, pregnancy rates, reproductive loss, 

and sex ratios in offspring. For ecological hazard assessments, EPA evaluates acute tests and 

chronic studies that assess growth, developmental and reproductive effects in different 

taxonomic groups. As part of fipronil’s most recent registration decision (PP# 8E7480, 

D360652, D. Drew, 09/22/2009), EPA reviewed these data and selected the most sensitive 

endpoints for relevant risk assessment scenarios from the existing hazard database. However, as 

required by FFDCA section 408(p), fipronil is subject to the endocrine screening part of the 

Endocrine Disruptor Screening Program (EDSP). 

EPA has developed the EDSP to determine whether certain substances (including pesticide 

active and other ingredients) may have an effect in humans or wildlife similar to an effect 

produced by a “naturally occurring estrogen, or other such endocrine effects as the Administrator 

may designate.” The EDSP employs a two-tiered approach to making the statutorily required 

determinations. Tier 1 consists of a battery of 11 screening assays to identify the potential of a 

chemical substance to interact with the estrogen, androgen, or thyroid (E, A, or T) hormonal 

systems. Chemicals that go through Tier 1 screening and are found to have the potential to 

interact with E, A, or T hormonal systems will proceed to the next stage of the EDSP where EPA 

will determine which, if any, of the Tier 2 tests are necessary based on the available data. Tier 2 

testing is designed to identify any adverse endocrine-related effects caused by the substance, and 

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

Under FFDCA section 408(p), the Agency must screen all pesticide chemicals. Between 

October 2009 and February 2010, EPA issued test orders/data call-ins for the first group of 67 

chemicals, which contains 58 pesticide active ingredients and 9 inert ingredients. Fipronil is not 

among the group of 58 pesticide active ingredients on the initial list to be screened under the 

EDSP. Accordingly, as part of registration review, EPA will issue future EDSP orders/data callins, requiring the submission of EDSP screening assays for fipronil. For further information on 
Page 19 of 47

the status of the EDSP, the policies and procedures, the list of 67 chemicals, future lists, the test 

guidelines and the Tier 1 screening battery, please visit our website: http://www.epa.gov/endo/. 

13.0 HUMAN STUDIES

Past fipronil risk assessments rely in part on data in generic databases from studies in which 

adult human subjects were intentionally exposed to a pesticide to determine their dermal and 

inhalation exposure. Many such studies, involving exposure to many different pesticides, 

comprise generic pesticide exposure databases such as the Outdoor Residential Exposure Task 

Force (ORETF) Database and the Pesticide Handler Exposure Database (PHED). EPA has 

reviewed all the studies supporting these multi-pesticide generic exposure databases, and has 

found no clear and convincing evidence that the conduct of any of them was either 

fundamentally unethical or significantly deficient relative to the ethical standards prevailing at 

the time the research was conducted. There is no regulatory barrier to continued reliance on 

these studies, and all applicable requirements of EPA’s Rule for the Protection of Human 

Subjects of Research (40 CFR Part 26) have been satisfied. 

14.0 DATA REQUIREMENTS

Toxicology

(See Appendix C for Data Requirement Rationales.) 

• Guideline 870.3250 90-Day Dermal Study 

• Guideline 870.3465 - 90-Day/28-Day Inhalation Study 

• Guideline 870.7800 - Immunotoxicity 

Residue Chemistry

(See Appendix D for International Residue Limits) 

Occupational and Residential

No data gaps currently identified. 

15.0 REFERENCES

Recore, S., D387320. 03/01/2011. Fipronil: Review of Human Incidents. 

Irwin, W., 03/21/2011. Fipronil Scoping Document for Regulatory Review: Hazard Section 

Encarnación, I., 03/2011. Fipronil Scoping Document for Regulatory Review: Residue 

Chemistry, Dietary Assessment, Aggregate Risk and Harmonization. 

Fipronil 129121: EFED Label Data Report, 11/08/2010 
Page 20 of 47

Fipronil 129121: HED Master Label Report - 11/08/2010. 

PRD Appendix A: Food/Feed & Non –Food/Non-Feed Uses Considered in Registration Review

(11/08/2010). 

Brassard D., Transmittal of BEAD Chemical Profile for Registration Review: Fipronil (PC 

Code: 129121), 10/26/2010. 

Rivera-Lupiáñez A., D372054, 10/13/2010. HED Review of “A Study to Determine the 

Haircoat Distribution of a Single Topical Treatment with a Combination of ML-2 ,095,988 

509T and ML-3,948,906 in Dogs” (MRID 47914240). 

Drew D. et al., D360652, 09/22/2009. Fipronil: Human Health Risk Assessment Petition to 

Support and Maintain the Established Rice Grain Tolerance for Imported Rice. 

Savoia, P., D368732, 9/17/2009. Fipronil. Acute and Chronic Aggregate Dietary Exposure 

Assessment for the Consumption of Imported Rice Commodities. 

Britton, W., D, D367277, 08/26/2009. HED Review of, Residential Hazard, Exposure and Risk 

Assessment for a New, Topical Ectoparasiticide for Dogs that Contains Fipronil, (S)-

Methoprene and Amitraz. 

Donovan, W.H., D368740, 08/25/2009. Fipronil. Petition to Support and Maintain the 

Established Rice Grain Tolerance as an Import Tolerance. Summary of Analytical Chemistry 

and Residue Data. 

Clock-Rust M., D317073, 08/17/2005. Exposure/Risk Assessment for the Proposed Section 3 

Uses on Onion Seed, Shallot Seed, Potatoes, Sweet Potatoes, and on Turf for Control of Leaf 

Cutter Ants, and Section 18 Uses on Turnips and Rutabagas in Oregon. 

Sibold, A., D317073, 08/17/2005. Fipronil - Exposure/Risk Assessment for the Proposed Section 3 Uses 

 on Onion Seed, Shallot Seed Potatoes, Sweet Potatoes, and on Turf for Control of Leaf Cutter Ants, and 

 Section 18 Uses on Turnips and Rutabagas in Oregon. 

Copley, M., HED DOC. NO. 014399, 12/06/2000, MB 46513, Photodegradate of Fipronil: REEVALUATION - Report of the Hazard Identification Assessment Review Committee. 

Dow M. and Vogel D., D244048, 10/24/2000. Occupational & Residential Human Exposure 

and Risk Assessment/ Characterization for Eight Fipronil Products Used Against Fire 

Ants and Other Pests. 

Copley, M., HED Document No. 013426, 06/09/1999, FIPRONIL: SECOND REEVALUATION - Report of the Hazard Identification Assessment Review Committee. 
Page 21 of 47

Kramer, G.F., D197451, 06/07/1994. New Chemical – Fipronil in/on Corn RACs. Evaluation 

of residue data and analytical methods. 

 
Page 22 of 47

Appendix A: Chemistry 

 

1.0 PHYSICAL/CHEMICAL PROPERTIES CHARACTERIZATION

1.1 Identification of Active Ingredient 

Chemical Name: (5-amino-1-(2,6-dichloro-4-(trifluoromethyl)phenyl)-4-

[(1R,S)-(trifluoromethyl)sulfinyl]-1H-pyrazole-3-carbonitrile) 

Common Name: Fipronil 

Trade Name: Regent®

Chemical Type: Insecticide 

PC Code Number: 129121 

CAS Registry No.: 120068-37-3 

Empirical Formula: C12H4Cl2F6N4

Molecular Weight: 437.15 

1.2 Structural Formula of Fipronil, Metabolites, and Photodegradate 

N

N

H2N

S CN

O

F3C

Cl Cl

CF3

5-amino-1-(2,6-dichloro-4-

(trifluoromethyl)phenyl)-4-[(1R,S)-

(trifluoromethyl)sulfinyl]-1H-pyrazole-3-

carbonitrile 

N

N

H2N

CN

Cl Cl

CF3

F3C

5-amino-1-(2,6-dichloro-4-

(trifluoromethyl)phenyl]-4-[(1R,S)-

(trifluoromethyl)]-1H-pyrazole-3-carbonitrile 
Page 23 of 47

5-amino-1-(2,6-dichloro-4-

(trifluoromethyl)phenyl)-4-

[(trifluoromethyl)sulfonyl]-1H-pyrazole-3-

carbonitrile 

N

N

H2N

S CN

F3C

Cl Cl

CF3

5-amino-1-(2,6-dichloro-4-

(trifluoromethyl)phenyl)-4-

[(trifluoromethyl)thio]-1H-pyrazole-3-

carbonitrile 

1.3 Physical and Chemical Properties 

Vapor Pressure: 2.8 x 10-9 mm Hg at 20°C 

Water Solubility: deionized water: 1.9 mg/L; water, pH 5: 0.0024 g/L; water, 

pH 9: 0.0022 g/L 

Octanol/Water Partition Coefficient: log Pow = 4.01 

 

N

N

H2N

S CN

O

F3C

Cl Cl

CF3

O
Page 24 of 47

Appendix B: Fipronil Toxicology 

Table 1. Acute Toxicity Data on Fipronil Technical. 

Guideline No./ Study Type MRID No. Results Toxicity 

Category 

870.1100 Acute oral toxicity 

- rat 

42918628 LD50 = male 92/female 

103 mg/kg; male + 

female 97 mg/kg 

II 

870.1200 Acute dermal toxicity 

- rat 

42918629 LD50 = >2000 mg/kg III 

870.1200 Acute dermal toxicity 

- rabbit 

42918630 LD50 = 354 mg/kg II 

870.1300 Acute inhalation toxicity 

- rat 

43544401 LC50 = male 0.36/female 

0.42 mg/L; male + 

female 0.39 mg/L 

II 

870.2400 Acute eye irritation 

- rabbit 

42918632 mild transient ocular 

irritant 

III 

870.2500 Acute dermal irritation 

- rabbit 

42918633 slight dermal irritant IV 

870.2600 Skin sensitization 

- Guinea pig 

42918634 non sensitizing 

Table 2. Toxicity Profile of Fipronil Technical. 

Guideline No./ 

Study Type 

MRID No. (year)/ 

Classification /Doses

Results 

FIPRONIL

870.3100 

28-Day oral 

toxicity range 

finding 

- rat 

44028301 (1996) 

Acceptable/guideline 

 0, 25, 50, 100, 200, 

400 ppm 

_ 0, 3.4, 6.9, 13, 24, 

45 mg/kg/day 

_ 0, 3.5, 6.7, 13, 25, 

55 mg/kg/day 

NOAEL = male <3.4 mg/kg/day 

LOAEL = 3.4 mg/kg/day based on: (male/female) 

thyroid follicular hypertrophy, change in protein, 

and (female) increased liver weight. 
Page 25 of 47

Table 2. Toxicity Profile of Fipronil Technical. 

Guideline No./ 

Study Type 

MRID No. (year)/ 

Classification /Doses

Results 

870.3100 

90-Day oral 

toxicity 

- rat 

42918643, 43501701 

(1991) 

minimum 

0, 1, 5, 30, 300 ppm 

M 0, 0.70, 0.33, 1.9, 

20 mg/kg/day 

F 0, 0.070, 0.37, 2.3, 

24 mg/kg/day 

NOAEL = 0.33 mg/kg/day 

LOAEL = 1.9 mg/kg/day based on: altered serum 

protein, increased liver, and thyroid weight. 

870.3100 

90-Day oral 

toxicity 

- mouse 

44262804 (1991) 

Acceptable/nonguide

line 

0, 1, 3, 10, 25 ppm 

M 0, 0.13, 0.38, 1.3, 

3.2 mg/kg/day 

F 0, 0.17, 0.57, 1.7, 

4.5 mg/kg/day 

NOAEL = 1.3 mg/kg/day 

LOAEL = 3.2 mg/kg/day based on: increased 

body weight gain (BWG). 

870.3150 

90-Day oral 

toxicity 

- dog 

42918642 (1991) 

guideline 

capsule 

0, 0.5, 2.0, 10 

mg/kg/day 

NOAEL = male 2.0 mg/kg/day, female 0.5 

mg/kg/day 

LOAEL = male 10 mg/kg/day, female 2.0 

mg/kg/day based on: clinical signs of toxicity 

(male/female), and increased BWG (female). 

870.3200 

21-Day dermal 

toxicity 

- rabbit 

42918644 (1993) 

guideline 

0, 0.5, 1.0, 5.0, 10 

mg/kg/day 

systemic NOAEL = 5.0 mg/kg/day 

LOAEL = 10 mg/kg/day based on: decreased 

BWG, decreased food consumption (FC), and 

hyperactivity. 

dermal NOAEL = 10 mg/kg/day 

LOAEL = >10 mg/kg/day. 

870.3700a 

Prenatal 

developmental 

- rat 

42977903 (1991) 

minimum 

0, 1.0, 4.0, 20 

mg/kg/day 

Maternal NOAEL = 4.0 mg/kg/day 

LOAEL = 20 mg/kg/day based on: decreased 

BWG, increased water consumption (WC), 

decreased FC, and decreased food efficiency (FE). 

Developmental NOAEL = 20 mg/kg/day 

LOAEL =>20 mg/kg/day. 

870.3700b 

Prenatal 

developmental 

42918646 (1990) 

minimum 

0, 0.10, 0.20, 0.50, 

Maternal NOAEL = <0.10 mg/kg/day 

LOAEL = 0.10 mg/kg/day based on: decreased 

BWG, decreased FC, and decreased FE. 

Developmental NOAEL = 1.0 mg/kg/day 
Page 26 of 47

Table 2. Toxicity Profile of Fipronil Technical. 

Guideline No./ 

Study Type 

MRID No. (year)/ 

Classification /Doses

Results 

- rabbit 1.0 mg/kg/day LOAEL = >1.0 mg/kg/day. 

870.3800 

Reproduction 

and fertility 

effects 

- rat 

42918647 (1992) 

minimum 

0, 3.0, 30, 300 ppm 

M 0, 0.25, 2.5, 26 

mg/kg/day 

F 0, 0.27, 2.7, 28 

mg/kg/day 

Parental/Systemic NOAEL = 0.25 mg/kg/day 

LOAEL = 2.5 mg/kg/day based on: (male/female) 

increased thyroid, and liver weight, (female) 

decreased pituitary weight, and increased 

follicular epithelial hypertrophy. 

Reproductive NOAEL = 2.5 mg/kg/day 

LOAEL = 26 mg/kg/day based on: clinical signs, 

decreased litter size, decreased BW, decreased 

mating, decreased fertility index, decreased postimplant survival and offspring postnatal survival, 

and delayed physical development. 

Offspring NOAEL = 26 mg/kg/day 

LOAEL = >26 mg/kg/day. 

870.4100a 

Chronic toxicity 

- rodent 

42918648 (1993) 

Acceptable/guideline 

0, 0.5, 1.5, 300 ppm 

M 0, 0.019, 0.059, 

1.3, 13 mg/kg/d 

F 0, 0.025, 0.078, 

1.6, 17 mg/kg/d 

NOAEL = 0.019 mg/kg/day 

LOAEL = 0.059 mg/kg/day based on: clinical 

signs, alterations in clinical chemistry, and thyroid 

parameters. 

870.4100b 

Chronic toxicity 

– dog 

42918645 (1993) 

Acceptable 

dietary 

0, 0.075, 0.30, 1.0, 

3.0/2.0 mg/kg/day 

(constant conc.) 

NOAEL = M 1.0 mg/kg/day; F 0.30mg/kg/day 

LOAEL = M 2.0 mg/kg/day; F 1.0 mg/kg/day 

based on: clinical signs of neurotoxicity. 

870.4100b 

Chronic toxicity 

– dog 

42918645 (1992) 

guideline 

capsule 

0, 0.2, 2.0, 5.0 

mg/kg/day 

NOAEL = 0.2 mg/kg/day 

LOAEL = 2.0 mg/kg/day based on: (male/female) 

decreased BWG, increased liver weight, liver 

histopath, and (male) decreased FE and clinical 

signs of neurotoxicity. 

870.4200 

Carcinogenicity 

- rat 

42918648 (1993) 

Acceptable/guideline 

0, 0.5, 1.5, 300 ppm 

M 0, 0.019, 0.059, 

1.3, 13 mg/kg/d 

NOAEL = M 0.019 mg/kg/day, F 0.025 

mg/kg/day 

LOAEL = M 0.059 mg/kg/day based on clinical 

signs, alterations in clinical chemistry, and thyroid 

parameters. 
Page 27 of 47

Table 2. Toxicity Profile of Fipronil Technical. 

Guideline No./ 

Study Type 

MRID No. (year)/ 

Classification /Doses

Results 

F 0, 0.025, 0.078, 

1.6, 17 mg/kg/d 

F 0.078 mg/kg/day based on clinical signs, 

alterations in clinical chemistry, and thyroid 

parameters. 

Evidence of thyroid carcinogenicity.

870.4300 

Carcinogenicity 

mouse 

42918649, 43501702 

(1993) 

minimum 

0, 0.10, 0.50, 10, 30, 

60 ppm 

M 0, 0.011, 0.055, 

1.2, 3.4 mg/kg/day 

F 0, 0.012, 0.063, 

1.2, 3.6 mg/kg/day 

NOAEL = 0.055 mg/kg/day 

LOAEL = 1.2 mg/kg/day based on decreased 

BWG, decreased FE, increased liver weight, and 

liver histopath. 

No evidence of carcinogenicity.

Gene Mutation 

870.5100 

Salmonella 

typhimurium and 

Escherichia coli

42918652 (1988) 

Acceptable 

In two independent experiments, fipronil (90.6% 

a.i.) was not mutagenic in 4 strains of S. 

typhimurium at concentrations up to 500 μg/plate 

in the presence or absence of S9 activation. 

Gene Mutation 

870.5300 

In vitro assay in 

mammalian 

cells/Chinese 

hamster V79 

cells 

42918651 (1993) 

Acceptable 

In two independent experiments, fipronil (97.2% 

a.i.) was negative for inducing forward gene 

mutations at the HGPRT locus in cultured Chinese 

hamster V79 cells at concentrations up to 385.65 

μg/ml both with and without S9 activation. 

Cytogenetics 

870.5375 

in vitro/human 

lymphocytes 

42918653 (1988) 

Acceptable 

There was no evidence of a clastogenic effect 

when human lymphocytes were exposed in vitro

to fipronil (90.6% a.i.) at doses of 75, 150 or 300 

μg/ml with and without S9 activation. 

Cytogenetics 

870.5395 

In vivo mouse 

micronucleus 

assay 

43680801 (1995) 

Acceptable 

There was no evidence of a clastogenic or 

aneugenic effect at any MB46030 dose or at any 

harvest time. 

870.6200a 

- rat 

42918635 (1993) 

minimum 

NOAEL = 0.5 mg/kg 

LOAEL = 5.0 mg/kg based on: decreased 
Page 28 of 47

Table 2. Toxicity Profile of Fipronil Technical. 

Guideline No./ 

Study Type 

MRID No. (year)/ 

Classification /Doses

Results 

Acute 

neuromuscular 

toxicity 

screening battery 

0, 0.5, 5.0, 50 mg/kg hindlimb splay. 

870.6200a 

- rat 

Acute 

neuromuscular 

toxicity 

screening battery 

44431801 (1997) 

Acceptable(guideline

) 

NOAEL = 2.5 mg/kg 

LOAEL = 7.5 mg/kg based on: (male) decreased 

hindlimb splay; (female) decreased BW, FC, FE, 

and grooming. 

870.6200b 

- rat 

Subchronic 

neuromuscular 

toxicity 

screening battery 

43291703 (1993) 

Acceptable 

0, 0.5, 5.0, 150 ppm 

M 0, 0.030, 0.30, 8.9 

mg/kg/day 

F 0, 0.035, 0.35, 11 

mg/kg/day 

NOAEL = 0.30 mg/kg/day 

LOAEL = 8.9 mg/kg/day based on: FOB 

findings. 

870.6300 

Developmental 

neuromuscular 

toxicity 

- rat 

44039002, 44501102, 

44501103 (1995) 

Acceptable/guideline 

0, 0.5, 10, 200 ppm 

0, 0.05, 0.90, 15 

mg/kg/day 

Maternal NOAEL = 0.9 mg/kg/day 

LOAEL = 15 mg/kg/day based on: decreased 

BW, decreased BWG, and decreased FC. 

Developmental NOAEL = 0.05 mg/kg/day 

LOAEL = 0.9 mg/kg/day based on decreased pup 

wt, increased preputial separation time.

Neurotox NOAEL = 0.9 mg/kg/day 

LOAEL = 15 mg/kg/day based on decreased 

auditory startle response, decreased swimming 

direction scores, group mean angle measurements 

and water “Y” maze times trails, and decreased 

absolute brain weight. 

870.7485 

Metabolism and 

pharmacokinetic 

– rat 

42918655, 43253701 

(1992) 

minimum 

4, 150 mg/kg-single 

dose 4 mg/kg x 14 

days- repeated dose 

The rate and extent of absorption appeared similar 

among all dose groups (4 and 150 mg/kg (single 

dose) and 4 mg/kg x 14 days (repeated dose)), but 

may have been decreased at the high dose. 

Distribution data showed significant amounts of 

residual radioactivity in carcass, G.I. tract, liver, 

adrenals, and abdominal fat at 168 hours post-dose 

for all rats in all dose groups. Repeated low oral 

dosing or a single high oral dose resulted in an 
Page 29 of 47

Table 2. Toxicity Profile of Fipronil Technical. 

Guideline No./ 

Study Type 

MRID No. (year)/ 

Classification /Doses

Results 

overall decrease in the amount of residual 

radioactivity found, but an increase in the amount 

in abdominal fat, carcass, and adrenals. Feces 

appeared to be the major route of excretion for 

fipronil derived radioactivity (45-75%). Excretion 

in urine was between 5-25%. Increases in the % 

excreted in urine and feces were observed with 

repeated low or a single high doses, while the % 

found in all tissues combined decreased. There 

were no significant sex-related differences in 

excretion. Major metabolites in urine included 

two ring-opened products of the metabolite MB 

45,897, two oxidation products, and the parent 

chemical. In feces, parent was detected as a 

significant fraction of the sample radioactivity as 

well as the oxidation products. Whole blood halflife ranged from 149-200 hours in male and 

female rats at 4 mg/kg, with 0-168 hours. Area 

under curves (AUCs) approximately equal 

between sexes. At 150 mg/kg, whole blood half 

life was noticeably decreased to 54.4 hours in 

male rats and 51.2 hours in female rats. Blood 

AUCs at this dose were approximately 

proportional to the increase in dose. 

870.7600 

Dermal 

penetration 

- rat 

43737308 (1995) 

Acceptable 

<1% at 24 hours. 

 

Table 3. Summary of Toxicological Dose and Endpoints for Fipronil for Use in Human 

Risk Assessment 1. 

Exposure 

Scenario 

(Fipronil) 

Dose Used in 

Risk 

Assessment, 

UF 

FQPA SF and 

Endpoint for Risk 

Assessment 

Study and Toxicological Effects 
Page 30 of 47

Table 3. Summary of Toxicological Dose and Endpoints for Fipronil for Use in Human 

Risk Assessment 1. 

Exposure 

Scenario 

(Fipronil) 

Dose Used in 

Risk 

Assessment, 

UF 

FQPA SF and 

Endpoint for Risk 

Assessment 

Study and Toxicological Effects 

Acute Dietary 

all populations

including 

infants and 

children 

NOAEL= 2.5 

mg/kg 

UF = 100 

Acute RfD = 

0.025 mg/kg 

FQPA SF = 1 

aPAD = acute RfD

 FQPA SF 

= 0.025 mg/kg 

Acute neuromuscular toxicity - rat 

LOAEL = 7.0 mg/kg based on: 

decreased hind leg splay in males at 

7 hours. 

Chronic Dietary 

all populations

NOAEL= 

0.019 

mg/kg/day 

UF = 100 

Chronic RfD

= 0.0002 

mg/kg/day 

FQPA SF = 1 

cPAD = chr RfD

 FQPA SF 

= 0.0002 mg/kg/d 

Chronic/carcinogenicity study - rat 

LOAEL = 0.059 mg/kg/day based 

on: increased incidence of seizures 

and death, alterations in clinical 

chemistry (protein), increased TSH, 

and decreased T4. 

Short-Term 

Incidental Oral 

(1-7 days) 

oral study 

LOAEL <0.1 

mg/kg/day 

UF of 3 for 

no NOAEL, 

100 for 

interspecies 

extrapolation 

and 

intraspecies 

variation 

LOC for MOE = 

300 (Residential, 

includes the FQPA 

SF) 

Developmental toxicity Study - 

rabbit 

LOAEL = ≤ 0.1 mg/kg/day based 

on: maternal toxicity of decreased 

body weight gain, decreased food 

consumption, and decreased food 

efficiency. 

IntermediateTerm Incidental 

Oral (1 week - 

several months) 

oral study 

LOAEL <0.1 

mg/kg/day 

UF of 3 for 

no NOAEL, 

100 for 

interspecies 

extrapolation 

and 

intraspecies 

variation 

LOC for MOE = 

300 (includes the 

FQPA SF) 

Developmental Toxicity Study - 

rabbit 

LOAEL = ≤ 0.1 mg/kg/day based 

on: maternal toxicity of decreased 

body weight gain, decreased food 

consumption, and decreased food 

efficiency. 

Short-Term 

Dermal (1-7 

dermal study 

NOAEL= 5 

LOC for MOE = 

100 (includes 

21-Day dermal toxicity study - 

rabbit 
Page 31 of 47

Table 3. Summary of Toxicological Dose and Endpoints for Fipronil for Use in Human 

Risk Assessment 1. 

Exposure 

Scenario 

(Fipronil) 

Dose Used in 

Risk 

Assessment, 

UF 

FQPA SF and 

Endpoint for Risk 

Assessment 

Study and Toxicological Effects 

days) mg/kg/day FQPA SF) LOAEL = 10.0 mg/kg/day based on: 

decreased body weight gain, and 

food consumption in both sexes. 

IntermediateTerm Dermal (1 

week - several 

months) 

dermal study 

NOAEL= 5 

mg/kg/day 

LOC for MOE = 

100 (includes 

FQPA SF) 

21-Day dermal toxicity study - 

rabbit 

LOAEL = 10.0 mg/kg/day based on: 

decreased body weight gain, and 

food consumption in both sexes. 

Long-Term 

Dermal (several 

months - 

lifetime) 

oral study 

NOAEL= 

0.019 

mg/kg/day 

(dermal 

absorption 

rate = 1%) 

LOC for MOE = 

100 (includes 

FQPA SF) 

Chronic/carcinogenicity study - rat 

LOAEL = 0.059 mg/kg/day based 

on: increased incidence of seizures 

and death, alterations in clinical 

chemistry (protein), increased TSH, 

and decreased T4. 

Short-Term 

Inhalation (1-7 

days) 

oral study 

NOAEL= 

0.05 

mg/kg/day 

(inhalation 

absorption 

rate = 100%) 

LOC for MOE = 

100 (includes 

FQPA SF) 

Developmental neurotoxicity - rat 

LOAEL = 0.90 mg/kg/day based on: 

decrease in group mean pup weights 

during lactation, and significant 

increase in time of preputial 

separation in males (dietary). 

IntermediateTerm Inhalation 

(1 week - 

several months) 

oral study 

NOAEL= 

0.05 

mg/kg/day 

(inhalation 

absorption 

rate = 100%) 

LOC for MOE = 

100 (includes 

FQPA SF) 

Developmental neurotoxicity - rat 

LOAEL = 0.90 mg/kg/day based on: 

decrease in group mean pup weights 

during lactation, and significant 

increase in time of preputial 

separation in males (dietary). 

Long-Term 

Inhalation 

(several months 

- lifetime) 

oral study 

NOAEL= 

0.019 

mg/kg/day 

(inhalation 

absorption 

LOC for MOE = 

100 (includes 

FQPA SF) 

Chronic/carcinogenicity rat study 

LOAEL = 0.059 mg/kg/day based 

on: increased incidence of seizures 

and death, alterations in clinical 

chemistry (protein), increased TSH, 

and decreased T4. 
Page 32 of 47

Table 3. Summary of Toxicological Dose and Endpoints for Fipronil for Use in Human 

Risk Assessment 1. 

Exposure 

Scenario 

(Fipronil) 

Dose Used in 

Risk 

Assessment, 

UF 

FQPA SF and 

Endpoint for Risk 

Assessment 

Study and Toxicological Effects 

rate = 100%) 

Cancer (oral, 

dermal, 

inhalation) 

Group C - 

possible 

human 

carcinogen 

Use chronic RfD to 

estimate human 

risk 

Increases in thyroid follicular cell 

tumors with fipronil (male/female) 

1 UF = uncertainty factor, FQPA SF = FQPA Safety Factor, NOAEL = no observed 

adverse effect level, LOAEL = lowest observed adverse effect level, PAD = population 

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

MOE = margin of exposure. 

 
Page 33 of 47

Appendix C: Rationales for Toxicology Data Requirements 

Toxicology

870.3250 90-Day Dermal Study 

 The Agency needs a 90-day dermal toxicity study for pesticides because the 

dermal route will be the primary route of exposures for chemicals designated with 

this use pattern. A 21/28 day dermal toxicity test is insufficient to identify 

potential hazards for non-food use pesticides because of the concern for the longer 

duration exposure associated with this use pattern. For example, professional 

applicators may be subjected to repeated exposure during the 3 month period of 

peak summer usage. For this type of increased exposure, professional applicators 

may not be adequately protected using data from a 21/28-day study. Additionally, 

the 21-day dermal study revealed adverse responses such as decreased body 

weight gain and decreased food consumption at the study LOAEL, suggesting that 

further dermal testing is required to determine whether longer exposure may 

decrease the dermal LOAEL and NOAEL values. 

870.3465 90-Day/28-Day Inhalation Study 

This requirement is based on the potential inhalation exposure to workers from all 

registered spray application uses. This study is required if there is the likelihood 

of significant repeated inhalation exposure to the pesticide as a gas, vapor or 

aerosol. The exposure time may be reduced from 90 days to 28 days pending 

exposure patterns, plateauing of effects and considering overall toxicity potential 

of fipronil. 

870.7800 Immunotoxicity 

There is a new requirement for a series 870.7800 immunotoxicity study. 

Immunotoxicity study is required as a part of the new data requirements in the 40 

CFR Part 158 for conventional pesticide registration. Because the immune 

system is highly complex, studies not specifically conducted to assess 

immunotoxic endpoints are inadequate to characterize a pesticide’s potential 

immunotoxicity. While data from hematology, lymphoid organ weights, and 

histopathology in routine chronic or sub-chronic toxicity studies may offer useful 

information on potential immunotoxic effects, these endpoints alone are 

insufficient to predict immunotoxicity. In the absence of required studies, EPA 

may use a database uncertainty factor of up to 10X. Once all data have been 

received and reviewed, the Fipronil Registration Review Team recommends that 

the points of departure and uncertainty factors used for risk assessment purposes 

be re-examined and a new risk assessment done, if necessary. 
Page 34 of 47

Guideline Number: 870.7800

Study Title: Immunotoxicity

Rationale for Requiring the Data

This study is a new data requirement under 40 CFR Part 158 as a part of the data 

requirements for registration of a pesticide (food and non-food uses). 

The Immunotoxicity Test Guideline (OPPTS 870.7800) prescribes functional 

immunotoxicity testing and is designed to evaluate the potential of repeated fipronil 

exposure to produce adverse effects (i.e. suppression) on the immune system. 

Immunosuppression is a deficit in the ability of the immune system to respond to a 

challenge of bacterial or viral infections such as tuberculosis (TB), Severe Acquired 

Respiratory Syndrome (SARS), or neoplasia. Because the immune system is highly 

complex, studies assessing functional immunotoxic endpoints are helpful in fully 

characterizing a pesticide’s potential immunotoxicity. These data will be used in 

combination with data from hematology, lymphoid organ weights, and histopathology in 

routine chronic or sub-chronic toxicity studies to characterize potential immunotoxic 

effects. 

Practical Utility of the Data

How will the data be used?

These animal studies can be used to select endpoints and doses for use in risk assessment 

of all exposure scenarios and are considered a primary data source for reliable reference 

dose calculation. For example, animal studies have demonstrated that immunotoxicity in 

rodents is one of the more sensitive manifestations of TCDD (2,3,7,8-tetrachlorodibenzop-dioxin) among developmental, reproductive, and endocrinologic toxicities. 

Additionally, the EPA has established an oral reference dose (RfD) for tributyltin oxide 

(TBTO) based on observed immunotoxicity in animal studies (IRIS, 1997). 

How could the data impact the Agency's future decision-making?

If the immunotoxicity study shows that fipronil poses either a greater or a diminished risk 

than that given in the interim decision’s conclusion, the risk assessments for fipronil may 

need to be revised to reflect the magnitude of potential risk derived from the new data. 

 

If the Agency does not have this data, then a 10X database uncertainty factor may be 

applied for conducting a risk assessment from the available studies. 

 
Page 35 of 47

Appendix D: International Residue Limits 

International Residue Limits 

Fipronil (129121; 02/02/2011) 

Summary of US and International Tolerances and Maximum Residue Limits 

Residue Definition:

US Canada Mexico2 Codex3

40 CFR 180.517 

Plant/Livestock: Fipronil (5-amino-1-[2,6-

dichloro-4-(trifluoromethyl)phenyl]-4-[(1R,S)-

(trifluoromethyl)sulfinyl]-1H-pyrazole-3-

carbonitrile) and its metabolites 5-amino-1-

[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-

[(trifluoromethyl) sulfonyl]-1H-pyrazole-3-

carbonitrile and 5-amino-1-[2,6-dichloro-4-

(trifluoromethyl) phenyl]-4-

[(trifluoromethyl)thio]-1H-pyrazole-3-

carbonitrile and its photodegradate 5-amino-1-

(2,6-dichloro-4-(trifluoromethyl)phenyl]-4-

[(1R,S)-(trifluoromethyl)]-1H-pyrazole-3-

carbonitrile. 

None Plant commodities: 

fipronil (fatsoluble). 

Animal 

commodities: sum 

of fipronil and 5-

amino-3-cyano-1-

(2,6-dichloro-4-

trifluoromethylphe

nyl)-4-

trifluoromethylsulp

honylpyrazole (MB 

46136), expressed 

as fipronil (fatsoluble).

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

US Canada Mexico2 Codex3 

Cattle, fat 0.40 

Cattle, liver 0.10 0.1 

Cattle, meat 0.04 0.5 (fat) 

Cattle, meat byproducts, except liver 0.04 0.02 Cattle kidney 

Corn, field, grain 0.02 0.01 Maize 

Corn, field, stover 0.30 0.1 Maize fodder 

(dry) 

Corn, field, forage 0.15 

Egg 0.03 0.02 

Goat, fat 0.40 

Goat, liver 0.10 

Goat, meat 0.04 

Goat, meat byproducts, except liver 0.04 

Hog, fat 0.04 

Hog, liver 0.02 

Hog, meat 0.01 

Hog, meat byproducts, except liver 0.01 

Horse, fat 0.40 

Horse, liver 0.10 

Horse, meat 0.04 

Horse, meat byproducts, except liver 0.04 

Milk, fat (reflecting 0.05 ppm in 

whole milk) 

1.50 

Potato 0.03 0.02 

Potato, wet peel 0.10 

Poultry, fat 0.05 

Poultry, meat 0.02 0.01 

Poultry, meat byproducts 0.02 0.02 

Rice, grain 0.04 0.01 Rice 
Page 36 of 47

Summary of US and International Tolerances and Maximum Residue Limits 

Residue Definition:

US Canada Mexico2 Codex3

Rice, straw 0.10 0.2 Rice straw 

fodder, dry 

Sheep, fat 0.40 

Sheep, liver 0.10 

Sheep, meat 0.04 

Sheep, meat byproducts, except 

liver 

0.04 

MRLs with no US equivalent 

Banana 0.005 

Barley 0.002 (*) 

Cabbages, Head 0.02 

Cattle milk 0.02 

Flowerhead brassicas (includes 

Brococoli: Brocolli, Chinese and 

Cauliflower) 

 0.02 

Oats 0.002 (*) 

Rye 0.002 (*) 

Sugar beet 0.2 

Sunflower seed 0.002 (*) 

Triticale 0.002 (*) 

Wheat 0.002 (*) 

 

Completed: M. Negussie; 02/03/2011 

1

 Includes commodities listed in the CFR as of today. 

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

3 * = absent at the limit of quantitation; Po = postharvest treatment, such as treatment of stored grains. PoP = 

processed postharvest treated commodity, such as processing of treated stored wheat. (fat) = to be measured on the 

fat portion of the sample. MRLs indicated as proposed have not been finalized by the CCPR and the CAC. 

Section 18 emergency exemptions. Time-limited tolerances are established for combined residues of the 

insecticide, fipronil, 5-amino-1-(2,6-dichloro-4-(trifluoromethyl) phenyl)-4-((1,R,S)-trifluoromethyl)sulfinyl)-1-Hpyrazole-3-carbonitrile and its 2 metabolites MB45950 (5-amino-1-(2,6-dichloro-4-(trifluoromethyl)phenyl)-4-

[(trifluoromethyl)thio]-1H-pyrazole-3-carbonitrile) and MB46136 (5-amino-1-(2,6-dichloro-4-

(trifluoromethyl)phenyl)-4-[(trifluoromethyl)sulfonyl]-1H-pyrazole-3-carbonitrile) and its photodegradate MB46513 

(5-amino-1-(2,6-dichloro-4-(trifluoromethyl)phenyl]-4-[(1R,S)-(trifluoromethyl)]-1H-pyrazole-3-carbonitrile), in 

connection with use of the pesticide under Section 18 emergency exemptions granted by EPA. The tolerances expire 

and are revoked on the dates specified in the table for this paragraph. 

Commodity Parts per million Expiration/revocation date 

Rutabaga 1.0 12/31/13

Turnip 1.0 12/31/13
Page 37 of 47

Tolerances with regional registrations. [Reserved] 

Indirect or inadvertent residues. Tolerances are established for combined indirect or inadvertent residues of the 

insecticide fipronil and its metabolites and photodegradate in or on food commodities when present therein as a 

result of the application of fipronil to growing crops listed in paragraphs (a) and (b) of this section and other 

nonfood crops to read as follows: 

Commodity Parts per million 

Wheat, forage 0.02

Wheat, grain 0.005

Wheat, hay 0.03

Wheat, straw 0.03
Page 38 of 47

Appendix E: Fipronil Products PRD Appendix A: Food/Feed & Non –Food/Non-Feed Uses Considered in Registration Review (11/08/2010) P

Food (F) / 

Non-food (N) Use Site Formulation Description A. I. Max App Rate/App Max # Apps / CC A. I. Max App Rate/CC Max # Apps / Year 

F 

DAIRY FARM MILK HANDLING FACILITIES/EQUIPMENT BAIT/SOLID NDC NS NS NS 

F 

FOOD/GROCERY/MARKETING/ STORAGE/DISTRIBUTION FACILITY PREMISE BAIT/SOLID 

.00000002 lb / 

spot NS NS NS 

F 

HOUSEHOLD/DOMESTIC DWELLINGS INDOOR FOOD HANDLING AREAS BAIT/SOLID .0041 lb / a NS NS NS 

F ORCHARDS (UNSPECIFIED) BAIT/SOLID NDC NS NS NS F POTATO, WHITE/IRISH 

FLOWABLE CONCENTRATE .1 lb / a NS NS NS 

N 

BATHROOM PREMISES/HARD SURFACES BAIT/SOLID 

.00000055 lb / 

placement NS NS NS 

N 

BATHROOM PREMISES/HARD SURFACES BAIT/SOLID NDC NS NS NS 

N CATS (ADULTS/KITTENS) LIQUID NDC NS NS NS N 

CHRISTMAS TREE PLANTATIONS GRANULAR .0006 lb / cu ft NS NS NS 

N 

COMMERCIAL/INDUSTRIAL LAWNS BAIT/SOLID NDC NS NS 4/yr 

N 

COMMERCIAL/INDUSTRIAL LAWNS BAIT/SOLID .000025 lb / a NS NS 4/yr 

N 

COMMERCIAL/INDUSTRIAL LAWNS GRANULAR .025 lb / a NS NS NS 

N 

COMMERCIAL/INSTITUTIONAL/ INDUSTRIAL PREMISES/EQUIP. (INDOOR) BAIT/LIQUID 

.00001196 lb / 

placement NS NS NS 

N 

COMMERCIAL/INSTITUTIONAL /INDUSTRIAL PREMISES/EQUIP. (INDOOR) BAIT/SOLID 

.00000002 lb / 

spot NS NS NS 
Page 39 of 47

Food (F) / 

Non-food (N) Use Site Formulation Description A. I. Max App Rate/App Max # Apps / CC A. I. Max App Rate/CC Max # Apps / Year 

N 

COMMERCIAL/INSTITUTIONAL /INDUSTRIAL PREMISES/EQUIP. (INDOOR) BAIT/SOLID 

.00000055 lb / 

placement NS NS NS 

N 

COMMERCIAL/INSTITUTIONAL/ INDUSTRIAL PREMISES/EQUIP. (INDOOR) BAIT/SOLID 

.00000099 lb / 

room NS NS NS 

N 

COMMERCIAL/INSTITUTIONAL/ INDUSTRIAL PREMISES/EQUIP. (INDOOR) BAIT/SOLID .0041 lb / a NS NS NS 

N 

COMMERCIAL/INSTITUTIONAL/ INDUSTRIAL PREMISES/EQUIP. (INDOOR) BAIT/SOLID NDC NS NS NS 

N 

COMMERCIAL/INSTITUTIONAL /INDUSTRIAL PREMISES/EQUIPMENT (OUTDOOR) BAIT/LIQUID 

.00001196 lb / 

placement NS NS NS 

N 

COMMERCIAL/INSTITUTIONAL /INDUSTRIAL PREMISES/EQUIPMENT (OUTDOOR) BAIT/SOLID 

.00000002 lb / 

spot NS NS NS 

N 

COMMERCIAL/INSTITUTIONAL/ INDUSTRIAL PREMISES/EQUIPMENT (OUTDOOR) BAIT/SOLID NDC NS NS NS 

N 

COMMERCIAL/INSTITUTIONAL/ INDUSTRIAL PREMISES/EQUIPMENT (OUTDOOR) BAIT/SOLID .0041 lb / a NS NS NS 

N 

COMMERCIAL/INSTITUTIONAL /INDUSTRIAL PREMISES/EQUIPMENT (OUTDOOR) BAIT/SOLID NDC NS NS NS 

N 

COMMERCIAL/INSTITUTIONAL/ INDUSTRIAL PREMISES/EQUIPMENT (OUTDOOR) 

EMULSIFIABLE CONCENTRATE 

.00001554 lb / 

linear ft NS NS 2/yr 

N 

COMMERCIAL/INSTITUTIONAL /INDUSTRIAL PREMISES/EQUIPMENT (OUTDOOR) 

EMULSIFIABLE CONCENTRATE .005 lb / 1 gal NS NS 2/yr 
Page 40 of 47

Food (F) / 

Non-food (N) Use Site Formulation Description A. I. Max App Rate/App Max # Apps / CC A. I. Max App Rate/CC Max # Apps / Year 

N 

COMMERCIAL/INSTITUTIONAL/ INDUSTRIAL PREMISES/EQUIPMENT (OUTDOOR) GRANULAR .025 lb / a NS NS NS 

N 

COMMERCIAL/INSTITUTIONAL/ INDUSTRIAL PREMISES/EQUIPMENT (OUTDOOR) 

WETTABLE POWDER 

.00001631 lb / 

linear ft NS NS 2/yr 

N 

COMMERCIAL/INSTITUTIONAL /INDUSTRIAL PREMISES/EQUIPMENT (OUTDOOR) 

WETTABLE POWDER 

.1305 lb / 25 

gal NS NS 2/yr 

N 

COMMERCIAL STORAGES/WAREHOUSES PREMISES BAIT/LIQUID 

.00001196 lb / 

placement NS NS NS 

N 

COMMERCIAL STORAGES/WAREHOUSES PREMISES BAIT/SOLID 

.00000055 lb / 

placement NS NS NS 

N 

COMMERCIAL STORAGES/WAREHOUSES PREMISES BAIT/SOLID 

.00000099 lb / 

room NS NS NS 

N 

COMMERCIAL STORAGES/WAREHOUSES PREMISES BAIT/SOLID .0041 lb / a NS NS NS 

N 

COMMERCIAL STORAGES/WAREHOUSES PREMISES BAIT/SOLID NDC NS NS NS 

N 

COMMERCIAL TRANSPORTATION FACILITIESNONFEED/NONFOOD BAIT/LIQUID .00001196 lb / placement NS NS NS 

N 

COMMERCIAL TRANSPORTATION FACILITIESNONFEED/NONFOOD BAIT/SOLID .00000055 lb / placement NS NS NS 

N 

COMMERCIAL TRANSPORTATION FACILITIESNONFEED/NONFOOD BAIT/SOLID .00000099 lb / room NS NS NS 

N 

COMMERCIAL TRANSPORTATION FACILITIESNONFEED/NONFOOD BAIT/SOLID .0041 lb / a NS NS NS 
Page 41 of 47

Food (F) / 

Non-food (N) Use Site Formulation Description A. I. Max App Rate/App Max # Apps / CC A. I. Max App Rate/CC Max # Apps / Year 

N 

COMMERCIAL TRANSPORTATION FACILITIESNONFEED/NONFOOD BAIT/SOLID NDC NS NS NS 

N CORN, FIELD 

FLOWABLE CONCENTRATE 

.0992 lb / lb 

seed NS NS NS 

N 

DAIRIES/CHEESE PROCESSING PLANT PREMISES (NONFOOD CONTACT) BAIT/SOLID 

.00000002 lb / 

spot NS NS NS 

N 

DOGS/CANINES (ADULTS/PUPPIES) LIQUID NDC NS NS NS 

N 

DOGS/CANINES (ADULTS/PUPPIES) 

LIQUID-READY TO USE 

.0009 lb / lb 

animal NS NS NS 

N DRAINAGE SYSTEMS BAIT/SOLID .0024 lb / a NS NS NS N DRAINAGE SYSTEMS 

EMULSIFIABLE CONCENTRATE .0393 lb / drain NS NS NS 

N DRAINAGE SYSTEMS 

EMULSIFIABLE CONCENTRATE 1713.7 lb / a NS NS NS 

N DRAINAGE SYSTEMS 

WETTABLE POWDER .0418 lb / drain NS NS NS 

N DRAINAGE SYSTEMS 

WETTABLE POWDER 1818.8 lb / a NS NS NS 

N EATING ESTABLISHMENTS BAIT/SOLID 

.00000099 lb / 

room NS NS NS 

N EATING ESTABLISHMENTS BAIT/SOLID NDC NS NS NS N 

EATING ESTABLISHMENTS FOOD HANDLING AREAS (NONFOOD CONTACT) BAIT/SOLID 

.00000002 lb / 

spot NS NS NS 

N 

EATING ESTABLISHMENTS FOOD HANDLING AREAS (NONFOOD CONTACT) BAIT/SOLID NDC NS NS NS 

N 

EATING ESTABLISHMENTS FOOD SERVING AREAS (NONFOOD CONTACT) BAIT/LIQUID 

.00001196 lb / 

placement NS NS NS 

N 

EATING ESTABLISHMENTS FOOD SERVING AREAS (NONFOOD CONTACT) BAIT/SOLID 

.00000002 lb / 

spot NS NS NS 

N 

EATING ESTABLISHMENTS FOOD SERVING AREAS (NONFOOD CONTACT) BAIT/SOLID .0041 lb / a NS NS NS 

N 

EATING ESTABLISHMENTS NONFOOD AREAS (NONFOOD CONTACT) BAIT/SOLID NDC NS NS NS 
Page 42 of 47

Food (F) / 

Non-food (N) Use Site Formulation Description A. I. Max App Rate/App Max # Apps / CC A. I. Max App Rate/CC Max # Apps / Year 

N 

FEED MILLS/FEED PROCESSING PLANTS BAIT/SOLID 

.00000002 lb / 

spot NS NS NS 

N FENCEROWS/HEDGEROWS BAIT/LIQUID 

.00001196 lb / 

placement NS NS NS 

N FENCEROWS/HEDGEROWS BAIT/SOLID 

.00000002 lb / 

spot NS NS NS 

N FENCEROWS/HEDGEROWS BAIT/SOLID NDC NS NS NS N 

FOOD PROCESSING PLANT NON-FOOD HANDLING AREAS BAIT/SOLID 

.00000099 lb / 

room NS NS NS 

N 

FOOD PROCESSING PLANT PREMISES (NONFOOD CONTACT) BAIT/LIQUID 

.00001196 lb / 

placement NS NS NS 

N 

FOOD PROCESSING PLANT PREMISES (NONFOOD CONTACT) BAIT/SOLID .0041 lb / a NS NS NS 

N 

FOOD PROCESSING PLANT PREMISES (NONFOOD CONTACT) BAIT/SOLID NDC NS NS NS 

N 

FOOD STORES/MARKETS/SUPERMARKETS PREMISES BAIT/SOLID NDC NS NS NS 

N 

FOREST TREE MANAGEMENT/FOREST PEST MANAGEMENT BAIT/SOLID NDC NS NS NS 

N 

FOREST TREES (SOFTWOODS, CONIFERS) GRANULAR .0006 lb / cu ft NS NS NS 

N GOLF COURSE TURF BAIT/SOLID NDC NS NS 4/yr N GOLF COURSE TURF BAIT/SOLID .000025 lb / a NS NS 4/yr N GOLF COURSE TURF GRANULAR .025 lb / a NS NS NS N 

HOSPITALS/MEDICAL INSTITUTIONS PREMISES (HUMAN/VETERINARY) BAIT/LIQUID 

.00001196 lb / 

placement NS NS NS 

N 

HOSPITALS/MEDICAL INSTITUTIONS PREMISES (HUMAN/VETERINARY) BAIT/SOLID 

.00000055 lb / 

placement NS NS NS 
Page 43 of 47

Food (F) / 

Non-food (N) Use Site Formulation Description A. I. Max App Rate/App Max # Apps / CC A. I. Max App Rate/CC Max # Apps / Year 

N 

HOSPITALS/MEDICAL INSTITUTIONS PREMISES (HUMAN/VETERINARY) BAIT/SOLID 

.00000099 lb / 

room NS NS NS 

N 

HOSPITALS/MEDICAL INSTITUTIONS PREMISES (HUMAN/VETERINARY) BAIT/SOLID .0041 lb / a NS NS NS 

N 

HOSPITALS/MEDICAL INSTITUTIONS PREMISES (HUMAN/VETERINARY) BAIT/SOLID NDC NS NS NS 

N 

HOUSEHOLD/DOMESTIC DWELLINGS CONTENTS BAIT/SOLID 

.00000099 lb / 

room NS NS NS 

N 

HOUSEHOLD/DOMESTIC DWELLINGS INDOOR PREMISES BAIT/LIQUID 

.00001196 lb / 

placement NS NS NS 

N 

HOUSEHOLD/DOMESTIC DWELLINGS INDOOR PREMISES BAIT/SOLID 

.00000002 lb / 

spot NS NS NS 

N 

HOUSEHOLD/DOMESTIC DWELLINGS INDOOR PREMISES BAIT/SOLID 

.00000055 lb / 

placement NS NS NS 

N 

HOUSEHOLD/DOMESTIC DWELLINGS INDOOR PREMISES BAIT/SOLID 

.00000099 lb / 

room NS NS NS 

N 

HOUSEHOLD/DOMESTIC DWELLINGS INDOOR PREMISES BAIT/SOLID .0041 lb / a NS NS NS 

N 

HOUSEHOLD/DOMESTIC DWELLINGS INDOOR PREMISES BAIT/SOLID NDC NS NS NS 

N 

HOUSEHOLD/DOMESTIC DWELLINGS OUTDOOR PREMISES BAIT/LIQUID 

.00001196 lb / 

placement NS NS NS 

N 

HOUSEHOLD/DOMESTIC DWELLINGS OUTDOOR PREMISES BAIT/SOLID 

.00000002 lb / 

spot NS NS NS 

N 

HOUSEHOLD/DOMESTIC DWELLINGS OUTDOOR PREMISES BAIT/SOLID NDC NS NS NS 

N 

HOUSEHOLD/DOMESTIC DWELLINGS OUTDOOR PREMISES BAIT/SOLID .0041 lb / a NS NS NS 

N 

HOUSEHOLD/DOMESTIC DWELLINGS OUTDOOR PREMISES BAIT/SOLID NDC NS NS NS 

N 

HOUSEHOLD/DOMESTIC DWELLINGS OUTDOOR PREMISES 

EMULSIFIABLE CONCENTRATE 

.00001554 lb / 

linear ft NS NS 2/yr 
Page 44 of 47

Food (F) / 

Non-food (N) Use Site Formulation Description A. I. Max App Rate/App Max # Apps / CC A. I. Max App Rate/CC Max # Apps / Year 

N 

HOUSEHOLD/DOMESTIC DWELLINGS OUTDOOR PREMISES 

EMULSIFIABLE CONCENTRATE .005 lb / 1 gal NS NS 2/yr 

N 

HOUSEHOLD/DOMESTIC DWELLINGS OUTDOOR PREMISES 

LIQUID-READY TO USE 

.00000259 lb / 

linear ft NS NS 1/yr 

N 

HOUSEHOLD/DOMESTIC DWELLINGS OUTDOOR PREMISES 

WETTABLE POWDER 

.00001631 lb / 

linear ft NS NS 2/yr 

N 

HOUSEHOLD/DOMESTIC DWELLINGS OUTDOOR PREMISES 

WETTABLE POWDER 

.1305 lb / 25 

gal NS NS 2/yr 

N 

INDUSTRIAL / CONSTRUCTION AREAS (OUTDOOR) 

EMULSIFIABLE CONCENTRATE 

.0039 lb / linear 

ft NS NS NS 

N 

INDUSTRIAL / CONSTRUCTION AREAS (OUTDOOR) 

EMULSIFIABLE CONCENTRATE 64.3 lb / a NS NS NS 

N 

INDUSTRIAL / CONSTRUCTION AREAS (OUTDOOR) 

EMULSIFIABLE CONCENTRATE .976 lb / 98 gal NS NS NS 

N 

INDUSTRIAL / CONSTRUCTION AREAS (OUTDOOR) 

WETTABLE POWDER 

.0042 lb / linear 

ft NS NS NS 

N 

INDUSTRIAL / CONSTRUCTION AREAS (OUTDOOR) 

WETTABLE POWDER 1 lb / 100 gal NS NS NS 

N 

INDUSTRIAL / CONSTRUCTION AREAS (OUTDOOR) 

WETTABLE POWDER 68.2 lb / a NS NS NS 

N 

MEAT PROCESSING PLANT PREMISES (NONFOOD CONTACT) BAIT/SOLID NDC NS NS NS 

N 

NONAGRICULTURAL OUTDOOR BUILDINGS/STRUCTURES BAIT/SOLID NDC NS NS NS 

N 

NONAGRICULTURAL OUTDOOR BUILDINGS/STRUCTURES BAIT/SOLID NDC NS NS NS 

N 

NONAGRICULTURAL UNCULTIVATED AREAS/SOILS BAIT/SOLID NDC NS NS NS 
Page 45 of 47

Food (F) / 

Non-food (N) Use Site Formulation Description A. I. Max App Rate/App Max # Apps / CC A. I. Max App Rate/CC Max # Apps / Year 

N NURSERY STOCK GRANULAR .025 lb / a NS NS NS N 

ORNAMENTAL AND/OR SHADE TREES BAIT/SOLID NDC NS NS NS 

N 

ORNAMENTAL AND/OR SHADE TREES 

EMULSIFIABLE CONCENTRATE .976 lb / 98 gal NS NS NS 

N 

ORNAMENTAL AND/OR SHADE TREES GRANULAR .0006 lb / cu ft NS NS NS 

N 

ORNAMENTAL AND/OR SHADE TREES GRANULAR .025 lb / a NS NS NS 

N 

ORNAMENTAL AND/OR SHADE TREES 

WETTABLE POWDER 1 lb / 100 gal NS NS NS 

N 

ORNAMENTAL HERBACEOUS PLANTS GRANULAR .0006 lb / cu ft NS NS NS 

N 

ORNAMENTAL HERBACEOUS PLANTS GRANULAR .025 lb / a NS NS NS 

N 

ORNAMENTAL LAWNS AND TURF BAIT/SOLID NDC NS NS 4/yr 

N 

ORNAMENTAL LAWNS AND TURF BAIT/SOLID .000025 lb / a NS NS 4/yr 

N 

ORNAMENTAL LAWNS AND TURF GRANULAR .025 lb / a NS NS NS 

N 

ORNAMENTAL NONFLOWERING PLANTS GRANULAR .0006 lb / cu ft NS NS NS 

N 

ORNAMENTAL NONFLOWERING PLANTS GRANULAR .025 lb / a NS NS NS 

N 

ORNAMENTAL SOD FARM (TURF) BAIT/SOLID NDC NS NS 4/yr 

N 

ORNAMENTAL SOD FARM (TURF) BAIT/SOLID .000025 lb / a NS NS 4/yr 
Page 46 of 47

Food (F) / 

Non-food (N) Use Site Formulation Description A. I. Max App Rate/App Max # Apps / CC A. I. Max App Rate/CC Max # Apps / Year 

N 

ORNAMENTAL SOD FARM (TURF) GRANULAR .025 lb / a NS NS NS 

N 

ORNAMENTAL WOODY SHRUBS AND VINES BAIT/SOLID NDC NS NS NS 

N 

ORNAMENTAL WOODY SHRUBS AND VINES GRANULAR .0006 lb / cu ft NS NS NS 

N 

ORNAMENTAL WOODY SHRUBS AND VINES GRANULAR .025 lb / a NS NS NS 

N PATHS/PATIOS BAIT/SOLID .0024 lb / a NS NS NS N 

PAVED AREAS (PRIVATE ROADS/SIDEWALKS) BAIT/SOLID NDC NS NS NS 

N PINE (FOREST/SHELTERBELT) 

FLOWABLE CONCENTRATE .1314 lb / a NS NS 1/yr 

N POTTING SOIL/TOPSOIL GRANULAR .0006 lb / cu ft NS NS NS N RECREATIONAL AREAS GRANULAR .025 lb / a NS NS NS N RECREATION AREA LAWNS BAIT/SOLID NDC NS NS 4/yr N RECREATION AREA LAWNS BAIT/SOLID .000025 lb / a NS NS 4/yr N RECREATION AREA LAWNS GRANULAR .025 lb / a NS NS NS N 

REFUSE/SOLID WASTE CONTAINERS (GARBAGE CANS) BAIT/SOLID NDC NS NS NS 

N 

REFUSE/SOLID WASTE SITES (INDOOR) BAIT/SOLID 

.00000055 lb / 

placement NS NS NS 

N 

REFUSE/SOLID WASTE SITES (INDOOR) BAIT/SOLID NDC NS NS NS 

N 

REFUSE/SOLID WASTE SITES (OUTDOOR) BAIT/SOLID NDC NS NS NS 
Page 47 of 47

Food (F) / 

Non-food (N) Use Site Formulation Description A. I. Max App Rate/App Max # Apps / CC A. I. Max App Rate/CC Max # Apps / Year 

N 

REFUSE/SOLID WASTE SITES (OUTDOOR) BAIT/SOLID NDC NS NS NS 

N RESIDENTIAL LAWNS BAIT/SOLID NDC NS NS 4/yr N RESIDENTIAL LAWNS BAIT/SOLID .0011 lb / a NS NS NS N RESIDENTIAL LAWNS GRANULAR .025 lb / a NS NS NS N SEWAGE SYSTEMS BAIT/SOLID NDC NS NS NS N SEWAGE SYSTEMS BAIT/SOLID .0024 lb / a NS NS NS N SEWAGE SYSTEMS BAIT/SOLID NDC NS NS NS N SHIPS AND BOATS BAIT/LIQUID 

.00001196 lb / 

placement NS NS NS 

N SHIPS AND BOATS BAIT/SOLID 

.00000099 lb / 

room NS NS NS 

N SHIPS AND BOATS BAIT/SOLID .0041 lb / a NS NS NS N UTILITY POLES / RIGHT-OF-WAY 

EMULSIFIABLE CONCENTRATE 

.0039 lb / linear 

ft NS NS NS 

N UTILITY POLES / RIGHT-OF-WAY 

WETTABLE POWDER 

.0042 lb / linear 

ft NS NS NS 

N 

WOOD PROTECTION TREATMENT TO BUILDINGS/PRODUCTS OUTDOOR 

EMULSIFIABLE CONCENTRATE .976 lb / 98 gal NS NS NS 

N 

WOOD PROTECTION TREATMENT TO BUILDINGS/PRODUCTS OUTDOOR 

WETTABLE POWDER 1 lb / 100 gal NS NS NS 

N ZOOS BAIT/LIQUID 

.00001196 lb / 

placement NS NS NS 

N ZOOS BAIT/SOLID 

.00000055 lb / 

placement NS NS NS 

N ZOOS BAIT/SOLID 

.00000099 lb / 

room NS NS NS 

N ZOOS BAIT/SOLID .0041 lb / a NS NS NS N ZOOS BAIT/SOLID NDC NS NS NS 

NDC = No Dosage Conversion NS = Not Specified