Page 2 of 47 E XECUTIVE S UMMARY

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

human health risk assessments fo r the broad-spectrum insecticide fipronil to determine the scope of work necessary to support the registration revi ew process. HED has considered the current use patterns (OPPIN Database and current labels) as we ll as the available t oxicity and exposure information for fipronil. The most recent hum an health risk assessment for fipronil was conducted in conjunction with a petition to supp ort 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 necessita te 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 br oad-spectrum insecticide belonging to the phenylpyrazole cl ass of insecticides.

Fipronil is registered for a vari ety of agricultural and home-use pr oducts, 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/tablette d, wettable powder, emulsifiable concentrate, flowable concentrate, soluble concentrate, re ady-to-use soluble, pressurized liquid, and bait stations. The oldest label (C ombat abf5, EPA Reg. 64240-39), wa s first registered on May 27, 1998 for ant control use on domestic dwellings. Currently there are several EPA registered products including seven Special Lo cal Need (SLN) registrations: four (4) Louisiana, two (2) Mississippi, and one (1) Tennessee. Also ther e is an emergency exemption (Section 18) registration granted to Oregon fo r the control of the cabbage maggot on turnips and rutabagas (D317073). Pending registrations rece ntly assessed include a rea dy–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 registra tions under review include several spoton formulations for pet treatments. 1

Currently, the 40 CFR § 180.517 has permanent tole rances 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, go at, hog, horse and sheep; eggs; milk fat; potato and potato wet peel; poultry fat, meat and m eat byproducts; and rice gr ain and straw. Timelimited tolerances for turnip and rutabaga are in effect until 12/31/13. Finally, tolerances for

indirect or inadvertent residues are establishe d in/on wheat, grain, fora ge, hay, and straw. According to the revised version of Ta ble 1 OPPTS 860.1000 (ChemSAC, 30/June/2008) a tolerance is required pr ocess 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 pro cessed potato waste should be included. The

1 Pending and Active Registrations for Fipronil 129121 / 120068- PRISM Query Results: 01/13/2011Page 3 of 47 tolerance expression in the 40 CFR § 180.517 need s 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 addi tion: 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 fo llicular 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 th e 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 occupa tional inhalation and dermal risks of fipronil. In addition , an immunotoxicity study is required as a part of new data requirements for conventional pesticide regi stration (40 CFR Part 158). Ther e are no data gaps for the assessment of the effects of fipr onil on developing animals following in utero and/or early postnatal exposure based on a two-generati on reproduction study in rats and prenatal developmental toxicity studies in rats and rabbits. The fiproni l 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 (H IARC) concluded that using the acute and chronic reference doses (RfDs) fo r 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 re sidue 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 year s 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 concer n for the general population and all population subgroups.

An updated dietary exposure assessment is rec ommended if: 1) the FQPA safety factor changes, 2) a new Drinking Water Assessmen t (DWA) reflects change s 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 p ercent of crop treated changes significantly by year 2014 a new dietary asse ssment may be needed.

Residential application and post-ap plication exposures from the uses of fipronil on pets and from residential uses of fipronil to c ontrol fire ants and other outdoo r nuisance pests for children and adults, have been previously assessed and are below HED’s level of concern. No additional dataPage 4 of 47 gaps were identified in the residential exposure assessment during the registration review scoping process.

Previously assessed aggregate risk estimates ar e 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, rev isions to the aggregate assessment may be required in Registration Review to incorporat e any changes to the toxicological endpoints and uncertainty factors; this will be determ ined once outstanding toxicology data have been received and reviewed by the Agency.

There is potential for short- and intermediate-term occupatio nal exposure to fipronil during mixing, loading, application, and post-application ac tivities. 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 mainta in 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 interm ediate-term exposure risks are not of concern to the Agency (i.e., and MOE ≥ 100) at baseline level of person al protection for most exposure

scenarios.

An updated occupational assessment may be requi red for any fipronil use site if new data are identified which impact exposure estimates, new points of depa rture, a revised FQPA SF, or revisions to exposure policie s and procedures ar e made. As for the seed treatment use (corn field seed treatment) , the maximum amount of seed treated per day migh t have to be revisited since HED is currently in the process of rev ising 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 ov er 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 illnesse s associated with exposure to fipronil—surveillance data from 11 states in the United States, 2001–2007.”Page 5 of 47 1.0 F IPRONIL F ORMULATIONS AND U SE P ATTERNS

Fipronil formulations include dus t, granules, pelletted/tabletted, wettable powder, emulsifiable concentrate, flowable concentrate, soluble concen trate, ready-to-use soluble, pressurized liquid, and bait stations (solid, liqui d and gel formulations).

HED used the Biological and Economics Analys is Division (BEAD) Label Data System to identify all agricultural and non-ag ricultural 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 re viewed by BEAD. These requests were for outside structures, potatoes, and sweet potatoes. Currently, there is an emergency exemption registration granted to Oregon for th e control of the cabbage maggot on turnips and rutabagas (D317073, Clock-Rust M., 08/17/2005). Time-limited toleranc es for turnip and rutabaga are in effect until 12/31/13.

Maximum rates of application for Food and Non-F ood 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 Re gistration 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, peri meter 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: ag ricultural crops incl uding potatoes, rutabagas, and turnip (infurrow uses); orchards, fruit trees, Christma s tree plantings, fore st lands and pines; outdoor/indoor ornamentals plants and trees; ornamental lawns and turf (golf courses, parks, cemeteries, athletic fields, a nd other recreational and commerci al 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 genera l 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 dw ellings including: apartments, homes, hotels, Food/Feed Handling Establishments (non-food/feed areas only), restaura nts, hospitals, nursing homes (non-patient areas), motels, hobby greenhous es, interiorscapes, office buildings, schools, zoos, pet quarters, sewers and drainage systems, camp sites, parks and re creational areas, rights of way, transportation equipment (buses, boats, car go trucks, trailers, ships, trains), warehouses and other institutional, commerci al, and industrial buildings. Othe r non-agricultural uses include paths and patios and ant mound treatment.Page 6 of 47 Fipronil is registered for a vari ety of home-use products. Reside ntial uses (household/domestic dwellings) include perimeter treatments/outside surfaces, ant mound treatments and ready to use squeeze and spot-on flea and tick treat ments for domestic animals.

Application Equipment for Fipronil Treatments 2

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 broadcas t applications for ant control

4. Slurry type seed treater for field corn seed treatment

5. Low pressure handwand for ant mound trea tment on outdoor ornamentals, greenhouses and perimeter treatment of non-agricultural out door 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 spra y formulations for ant control

8. Injection equipment and syringe applicat or for crack and crevice applications

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

2.0 H AZARD I DENTIFICATION /T OXICOLOGY

Fipronil is a broad-spectrum ins ecticide belonging to the pyrazole class of insecticides. The toxicology database provides evid ence of neurotoxic activity as evidenced by neurologic signs in several studies and species. Fipr onil is also associated with alte rations in the thyroid-pituitary hormonal status, resulting in alte rations in thyroid hormonal leve ls and thyroid follicular cell

tumors.

The toxicology database for fipronil is adequa te, however, a 28/90-day in halation toxicity and 90-day dermal study in the rat has been request ed to further characterize the occupational inhalation and dermal risks of fipronil. (See Appendix C - Rationales for Toxicology Data Requirements)

. The toxicology database for fipronil doe s not show any definite evidence of treatment-related effects on the immune syst em, however a new data requirement is the immunotoxicity study. Some decr eases 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 no t directly target the i mmune system. The other studies do not specifically monitor toxicity to the immune system, theref ore, 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

UF DB is not needed to account for lack of this st udy. There is otherwise co nfidence in the quality

2 EFED Label Data Report, 11/08/2010Page 7 of 47 of the existing studies and the re liability of the toxici ty endpoints identified for use in risk

assessment.

There are no data gaps for th e assessment of the effects of fipronil on developing animals following in utero and/or early postnatal exposure base d on a two-generation reproduction study in rats and prenatal developmental toxicity studie s 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 ininfants and children in the developmental and reproduction studies, the developmental ne urotoxicity study identified a developmental no-observed-adve rse-effect-level (NOAEL) whic h was less than the maternal NOAEL, indicating an apparent su sceptibility issue. However, the HIARC concluded that the apparent increased susceptibility in the develo pmental neurotoxicity study was not supported by the overall weight-of-the-eviden ce. (Fipronil HIARC Report, J une 9, 1999). Evaluation of the database indicated that: 1) the offspring body wei ght findings in the developmental neurotoxicity study are not supported by the result s of the two-generation reproduc tion study in rats at similar treatment levels; 2) increased susceptibility to th e offspring was not demons trated in the prenatal developmental toxicity study nor the two-ge neration 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 photodegrad ate, MB 46513. This evaluation was supported in the 2009 risk assessment for fipronil on importe d rice (D360652, D. Drew, 09/22/2009). The Food Quality Protection Act Safety Factor Committee (FQP A 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-spe cies 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). Fipron il technical is relatively non-irritating to the skin (IV) a nd 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 ra ts and dogs as evidenced by signs in the acute and sub-chronic screening batteri es in the rat, in developmen tal neurotoxicity and chronic carcinogenicity studies in the rat, and in two chronic dog st udies. 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 al terations at all time pe riods (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 Carc inogenicity Peer Review Committee (CPRC) document dated July 18, 1997, as a Group C - Possible Human Carcinog en, based on increases in thyroid follicular cell tumors in both sexes of the rat, which we re statistically significant by both pair-wise and trend analyses. There is no apparent concern fo r 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 th e thyroid-pituitary status. Dietary risk concerns due to long-term consumption of fipronil re sidues are adequately addressed by the DEEM TM 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 c oncluded 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 ne oplasia in the rats treated with fipronil, but not MB 46513. Although, in the rat, both fipronil and MB 46513 result in clinical signs of neuromuscu lar toxicity, these signs do not a ppear with fipronil until later (after 90 days). Chronic exposure to the rat with both compounds resu lts in qualitatively and quantitatively similar neurologic effects. Othe r measured signs of ne uromuscular toxicity (observed in the acute neurotoxi city 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 neurom uscular toxicity, the differences appear to be more quantitative, with longer exposure to fipronil n eeded in the rat to resu lt 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 wi th fipronil, but there is with MB 46513. The HIARC concluded that using th e acute and chronic reference doses (RfDs) for fipronil to

evaluate the risk due to acut e 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 ar e similar (MB 46513 HIARC memo, December 6, 2000). The HIARC also determined th at the potential for in creased susceptibility of infants and children from exposure to MB 46513 w ould 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 e ndpoints for fipronil is listed in Appendix B, Table 3.

Conclusion The toxicology database for fipronil is adequa te to assess the chemical’s hazard potential although there are several data ga ps. A 28/90-day inhalation toxici ty and 90-day dermal study in the rat have been requested to fu rther characterize the occupationa l inhalation and dermal risks of fipronil. In addition, an immunotoxi city study is required as a part of new data requirements for conventional pesticide regi stration (40 CFR Part 158).

3.0 R ESIDUE C HEMISTRYPage 9 of 47 The nomenclature, registration numbers, PC Code and chemical structure of fipronil, its two metabolites MB 45950 and MB 46136, and it pho todegradate MB 46513 are listed in Appendix

A

.

The nature of the residue in rice, corn, rotational crops and animal s (goat and hen) is adequately understood based on metabolism studies in which plan ts 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. Th e photodegradate MB 46513 is also required for crops in which metabolism data indicates th at it comprises a significant portion of the TRR (i.e. rice, potatoes, a nd rotational crops).

Currently, the 40 CFR § 180.517 has permanent tolera nces for fipronil (whi ch 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, go at, hog, horse and sheep; eggs; milk fat; potato and potato wet peel; poultry fat, meat and m eat byproducts; and rice gr ain and straw. Timelimited tolerances for turnip and rutabaga are in effect until 12/31/13. Finally, tolerances for

indirect or inadvertent residues are establishe d in/on wheat, grain, fora ge, 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. registratio ns 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 live stock commodities are available and have been successfully approved by Analytical Chemis try Laboratory (ACL) with minor revision recommendations which have been adequately ad dressed 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 el ectron-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 Administrati on (FDA). Acceptable recoveries of fipronil

and its metabolites MB 45950 and MB 46136 were obtai ned 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). Fo r the previous petition for uses in imported rice (PP#8E7480), several label amendmen ts; more data from Japan and crop field trials from Brazil were required. For the Japanese trials, inform ation concerning the field portion of the study and the analytical portio n of the study must be submitted. To support the proposed foliar use in Brazil, data are required which depict magnitude of th e residues of fipronilPage 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 Tabl e 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 cor n, 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 calc ulations that include process potato waste feed commodity (OPPTS 860.1000). Potato wet peel is no longer an important feed item. The tolerance for potat o, wet peel currently included in the 40 CFR §

180.517 should be revoked and a tolerance of 0.1 0 ppm for process potato waste should be

included.

In 2009 HED established interim guidance on writ ing 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 expres sion and measurement of the le vel of the residue in the raw agricultural commodity (R AC), 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-ami no-1-[2,6-dichloro-4-(tr ifluoromethyl)phenyl]-4- [(1R,S) (trifluoromethyl) sulfi nyl]-1H-pyrazole-3-carbonitrile) and its metabolites 5-amino-1- [2,6-dichloro-4-(trifluoromet hyl) phenyl]-4-[(trifluoromet hyl) sulfonyl]-1H-pyrazole-3- carbonitrile and 5-amino-1-[2,6-di chloro-4-(trifluoromethyl) phenyl ]-4-[(trifluoromethyl)thio]- 1H-pyrazole-3-carbonitrile and its phot odegradate 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 tolera nce for rice straw

• Label amendments, additional data from Japa n and crop field trials from Brazil are required based on deficiencies identified in the petition for uses in imported rice

• Revocation of the tolerance fo r potato wet peel and establis hment 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 D IETARY E XPOSURE

Unrefined acute and refined chr onic (with anticipated residue le vels and percent Crop Treated information) dietary risk assessments were conduc ted to evaluate exposur e 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 th e U.S. Department of Agriculture’s Continuing Surveys of Food Intakes by Individuals (C SFII) from 1994-1996 and 1998 to calculate dietary risk. These analyses were performed in s upport 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 pr oducts were estimated and incorporated in the acute and chronic dietary assessment, respectively.

An unrefined acute and refined chronic dietary risk analyses were c onducted using the DEEMFCIDTM model to estimate the exposure to fipron il. The acute dietary analysis at the 95 th

percentile of exposure gives risk estimates be low the 100% of the aPAD threshold level of concern for each population subgroup. For th e 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. Fo r children 1-2 years of age, the resulting chronic dietary risk was reported at 95% cP AD with an exposure of 0.000190 mg/kg/day. A critical commodity contribution analysis made fo r children 1-2 years of age, the most highly exposed population subgroup, has shown dairy pr oducts, meat, and cereal grains to be the chronic dietary risk drivers of fipronil compri sing 43%, 14% and 11% of the total exposure respectively (D368732, P. Savoia, 9/17/2009).

Conclusion

An updated dietary exposure assessment is recomme nded if the FQPA safety factor changes, if a new DWA reflect changes in the estimated drinki ng water concentration, or if a request for a new use is received. Nevertheless, the Screening Le vel Usage Analysis reports used in the last dietary assessment are dated July 23, 2009 and Augus t 27, 2009; therefore, if the percent of crop treated changes significantly by year 2014 a new dietary asse ssment may be needed.

5.0 T OLERANCE A SSESSMENT AND I NTERNATIONAL H ARMONIZATION

Where possible, EPA encourages the harmoni zation 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 fipr onil 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 wast e should be established. A Codex MRL has been established for fipronil residues in sev eral RACs. The proposed import tolerance is

not harmonized with the establis hed MRL, a fact attributable to the difference in tolerancePage 12 of 47 expression between Codex and the U.S. There are currently no established Canadian and Mexican MRLs for fipronil.

6.0 R ESIDENTIAL E XPOSURE

Residential Handler and Post-application Exposure

Residential exposure to fipronil is anticipated for individual s 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 pote ntial. However, for fi pronil the toxicity routespecific endpoint effects and point s of departure are the same fo r both short- and intermediateterm exposure durations.

Residential uses include perimeter treatments/out side 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-appli cation exposures from currently re gistered 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. Margin s of exposure (MOE) for dermal contact and inhalation resulting from assessment of granular formulations we re 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 re sidential lawns are 0.0011 lb ai/ acre (bait stations ) and 0.025 lb ai/ acre (g ranular formulations).

Pet Treatment Use

HED has determined that there is the potential for exposure in residential settings during the application process for homeowners (adults onl y) 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 prod ucts. HED previously assessed the application of fipronil shampoo, spot-on and spray-on products and no risks of concer n were identified.

Adult dermal and child (3 to < 6 years old) derm al 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 aggregat e assessment, the pet spot-on use has been

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

Residential Bystander Post A pplication Inhalation ExposurePage 13 of 47 The need for a bystander inhala tion risk assessment for fipron il should be examined during registration review. Based on the Agency's curr ent practices, a quantitative post-application inhalation exposure assessment has not been perfor med 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 pos t-application inhalation e xposure to individuals nearby to pesticide applications. The Agency s ought expert advice and input on issues related to volatilization of pesticid es 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/scipol y/SAP/meetings/2009/120109meeting.html ). The Agency is in the process of ev aluating the SAP report and may, as appropriate, develop policies and procedures to identify the need for a nd, subsequently, the wa y to incorporate postapplication inhalation expos ure into the Agency's risk assessment s. If new policies or procedures are put into place, the Agency ma y revisit the need for a quantit ative post-application inhalation exposure assessment for fipronil.

Conclusions

The residential exposure database is adequate to support the registra tion review process for fipronil. An updated residential exposure assess ment may be required u nder registration review based upon revisions to HED’s Resi dential 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 FQ PA 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 revi ew 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 volatilizat ion). The Agency will consider the need for a bystander inhalation risk assessment fo r fipronil during re gistration review.

7.0 A GGREGATE E XPOSURE AND R ISK A SSESSMENT

In accordance with FQPA, HED considers and aggr egates pesticide exposures and risks from three major sources: food, drinking water, a nd residential exposures . In an aggregate assessment, exposures from dietary and residentia l 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 va rious sources, HED considers both the route and duration of exposure.

Fipronil is currently registered for the following residential non-di etary 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 resident ial 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 applica tion per year, and repeated applic ations, if necessary, may only be made once every one to three months during flea or tick season). Therefor e, since pet and turfPage 14 of 47 treatment applications are infrequent, for aggr egate risk assessment, exposures from these

treatments have not been combined.

Based on fipronil’s existing uses, the worst case a ggregate 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 estim ates to determine short-and intermediate aggregate risks. Previously assessed aggregate ri sk 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 fo r Residential Exposure Assessment may require

revisions to the residential asse ssment 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 toxico logical endpoints and uncer tainty factors; this will be determined once outstanding toxicology da ta have been received and reviewed by the Agency.

8.0 O CCUPATIONAL E XPOSURE

Occupational Handler

Occupational exposure to fipronil is anticipat ed 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 Divisi on (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, gra nules, pelletted/tabletted, wett able powder, emulsifiable concentrate, flowable concentrate, solubl e concentrate formulations for broadcast applications.

3. Mixer/Loader in support of bait st ation aerial applic ation operations

4. Applicator of subsurface/slit application treatment

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

6. Mixer/loader/applicator perfor ming broadcast application fo r leaf cutter ant control

7. Mixer/Loader and Appli cator exposure for soil in jection applications

8. Mix/load/application for greenhous es (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 (MLA P) 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 handle r 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 tr eatment), the maximum amount of seed treated per day might have to be revisited since HED is cu rrently 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 comme rcial seed treatment facilities. With the increasing demand for hybridized treated seeds, there have been m odifications not only in the seed treatment equipment, but in the market shares of new a nd 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 s eed which is treated in the commercial seed

treatment facilities.

Furthermore, recommended unit exposures for o ccupational handler assessments have generally been derived only from PHED. However, recently both the Out door Residential Exposure Task Force (ORETF) and Agricultural Handler E xposure Task Force (AHETF) have produced pesticide handler exposure monitoring data th at the Agency is using in place of PHED (http://www.epa.gov/pesticides/sci ence/handler-exposure-data.html). As more reliable data become available (such as that from the AH ETF and ORETF), the Agency will continue to replace existing data. Reviewers should in corporate new exposure monitoring data, as necessary, during Registration Review.

Conclusions

An updated occupational assessment may be requir ed 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 expo sure to fipronil is anticipa ted 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 c ontacted after in corporation.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 expor ted only, and secondary hand lers are not involved; therefore post-applicatio n exposure to fipronil treated seed s is not expected to occur.

Pet Treatment Use Domestic pets are expected to be treated and i mmediately 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 occupationa l post-application dermal exposure assessment was not performed.

Leaf-Cutter Ant Use For the leaf-cutter ant (dry broadc ast use), post-application exposure is expected to be negligible. Fipronil is applied as a dry granul e. Relative to other uses, the ra tes 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 es timates, new points of departure, a revised FQPA SF, or revisions to exposure po licies and procedures are made.

9.0 P UBLIC H EALTH AND P ESTICIDE E PIDEMIOLOGY D ATA

A moderately large number of incidents have been reported involving fipronil (D387320, S. Recore, 03/01/2011). Although the frequency of inci dents appears to be decreasing over time and majority of incidents were low to moderate seve rity, there were eight in cidents classified as major severity and one incident resulted in a death due to an allergic reaction.

The OPP Incident Data System (IDS) was utiliz ed 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 Ro denticide Act (FIFRA) Section 6 (a) (2) reports from registrants, other federal and state hea lth and environmental agencies and individual consumers. Since 1992, OPP compiles these reports in IDS. IDS contain re ports from across the U.S. and most incidents have all relevant produc t information recorded. Reports submitted to the IDS represent anecdotal reports or allegations only, unless otherw ise 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 incide nt data for death, major and moderate incidents,

and it includes more details a bout the location, date and nature of the incident. Main IDS incidents involving only one pesticide are consider ed to provide more certain information about the potential effects of exposure from the pesticid e, and therefore these incidents are listed inPage 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 cate gories 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 distinguish ed 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: neurologi cal, 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 app licators and their spouse s. If there are AHS findings relevant to a particular pesticide going through registration review, the Agency will ensure they are considered in the problem fo rmulation/scoping phase of the process and, if appropriate, fully reviewed in the risk asse ssment phase of the process. The AHS includes information on use of 50 different pesticide activ e ingredients commonly us ed in agriculture.

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

Conclusions

Based on the number of incidents reported invol ving fipronil, and the effects noted in the incidents, the evaluation warrants further analysis in the prelim inary risk assessment phase of registration review. This further anal ysis 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 E NVIRONMENTAL J USTICE

There do not appear to be any particular soci oeconomic 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 h ealth risk assessments for fipronil, in accordance with U.S. Executive Order 12898, "Federal Acti ons to Address Environmental Justice in Minority Populations and Lo w-Income Populations," http://www.epa.gov/compliance/resour ces/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 ri sk assessments, including, but not limited to, people who obtain drinking water fro m sources near agricultural ar eas, the variability of diets within the U.S., and people who may be exposed when harvesting crops. Should these highestPage 18 of 47 exposures indicate potential risks of concern, OPP further refine s the risk assessments to ensure

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

11.0 C UMULATIVE R ISK A SSESSMENT

EPA does not have, at this time, available da ta 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 cu mulative risk assessment is not anticipated at this time.

12.0 E NDOCRINE D ISRUPTOR S CREENING P ROGRAM

As required by FIFRA and FFDCA, EPA reviews num erous studies to asse ss potential adverse outcomes from exposure to chemicals. Collectiv ely, these studies includ e acute, subchronic and chronic toxicity, including asse ssments of carcinogenicity, ne urotoxicity, developmental, reproductive, and general or systemic toxicity. These studies include e ndpoints which may be susceptible to endocrine influe nce, including effects on endocri ne target organ histopathology, organ weights, estrus cyclicity, sexual maturatio n, fertility, pregnancy rates, reproductive loss, and sex ratios in offspring. For ecological hazard assessments, EPA evaluates acute tests and chronic studies that assess gr owth, developmental and reprod uctive 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 fr om the existing hazard database. However, as required by FFDCA section 408(p), fi pronil is subject to the endoc rine screening part of the Endocrine Disruptor Screening Program (EDSP).

EPA has developed the EDSP to determine whet her 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 ot her such endocrine effect s as the Administrator may designate.” The EDSP employs a two-tiered approach to making th e 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 estrog en, androgen, or thyroid (E, A, or T) hormonal systems. Chemicals that go th rough Tier 1 screening and are found to have the potential to interact with E, A, or T hormonal systems will proceed to the next stag e of the EDSP where EPA will determine which, if any, of th e Tier 2 tests are necessary base d on the available data. Tier 2 testing is designed to identify a ny adverse endocrine-related eff ects 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 pest icide 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 issu e future EDSP orders/data callins, requiring the submission of EDSP screening assays for fipron il. For further information onPage 19 of 47 the status of the EDSP, the policie s and procedures, the lis t 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 H UMAN S TUDIES

Past fipronil risk assessments rely in part on data in generic database s from studies in which adult human subjects were intent ionally exposed to a pesticide to determine their dermal and inhalation exposure. Many such studies, invo lving exposure to many different pesticides, comprise generic pesticide exposure databases su ch 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-pe sticide generic exposure databases, and has found no clear and convincing evidence that the conduct of any of them was either fundamentally unethical or signifi cantly deficient relativ e to the ethical sta ndards prevailing at

the time the research was conducted. There is no regulatory barrier to continued reliance on these studies, and all applicab le requirements of EPA’s Rule for the Protection of Human Subjects of Research (40 CFR Pa rt 26) have been satisfied.

14.0 D ATA R EQUIREMENTS

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 R EFERENCES

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 Da ta Report, 11/08/2010Page 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 Pr ofile 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 Comb ination 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 Ri ce Grain Tolerance for Imported Rice.

Savoia, P., D368732, 9/17/2009. Fiproni l. 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 Ectoparasiticid e for Dogs that Contains Fipronil, (S)- Methoprene and Amitra z.

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 Iden tification Assessment Review Committee.

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

and Risk Assessment/ Charact erization 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 Iden tification 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-dich loro-4-(trifluor omethyl)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: C 12 H 4 Cl 2 F 6 N 4 Molecular Weight: 437.15

1.2 Structural Formula of Fipronil, Metabolites, and Photodegradate

N N N H 2 CN S O

F 3 C

Cl Cl

CF 3

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

carbonitrile N N N H 2 CN

Cl Cl

CF 3 F 3 C

5-amino-1-(2,6-dichloro-4- (trifluoromethyl)phenyl]-4-[(1R,S)- (trifluoromethyl)]-1H-py razole-3-carbonitrilePage 23 of 47 5-amino-1-(2,6-dichloro-4- (trifluoromethyl)phenyl)-4- [(trifluoromethyl)sul fonyl]-1H-pyrazole-3-

carbonitrile N N N H 2 CN S F 3 C

Cl Cl

CF 3

5-amino-1-(2,6-dichloro-4- (trifluoromethyl)phenyl)-4- [(trifluoromethyl)t hio]-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 P

ow = 4.01 N N N H 2 CN S O

F 3 C

Cl Cl

CF 3 OPage 24 of 47 Appendix B: Fipronil Toxicology

Table 1. Acute Toxicity Data on Fipronil Technical.

Guideline No./ Study Ty pe MRID No. Results Toxicity Category

870.1100 Acute oral toxicity

- rat 42918628 LD 50 = male 92/female 103 mg/kg; male + female 97 mg/kg II

870.1200 Acute dermal toxicity

- rat 42918629 LD 50 = >2000 mg/kg III

870.1200 Acute dermal toxicity

- rabbit 42918630 LD 50 = 354 mg/kg II

870.1300 Acute inhalation toxicity

- rat 43544401 LC 50 = 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 ba sed on: (male/female) thyroid follicular hypertr ophy, 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 ba sed 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: clin ical 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, Materna l NOAEL = <0.10 mg/kg/day LOAEL = 0.10 mg/kg/day based on: decreased BWG, decreased FC, and decreased FE. Developmenta l NOAEL = 1.0 mg/kg/dayPage 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 ba sed 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 base d on: clinical signs, decreased litter size, decreased BW, decreasedmating, 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 clinic al 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 si gns 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 ba sed on: (male/female) decreased BWG, increased liver weight, liver histopath, and (male) decr eased 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/da y based on clinical signs, alterations in clinic al 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, incr eased 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 μ g/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

μ g/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

μ g/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 a ny 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: decreasedPage 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/da y 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 respons e, 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 fa t at 168 hours post-dose for all rats in all dose groups. Repeated low oral dosing or a single high oral dose resulted in anPage 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 radioactiv ity (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 metabolit es 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 aswell 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 EffectsPage 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 -

rabbitPage 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 thyroi d follicular cell tumors with fipronil (male/female)

1 UF = uncertainty factor, FQPA SF = FQ PA Safety Factor, NOAEL = no observed adverse effect level, LOAEL = lowest obser ved adverse effect level, PAD = population adjusted dose (a = acute, c = chronic) Rf D = 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 toxi city 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 toxi city test is insufficient to identify potential hazards for non-food use pesticid es because of the concern for the longer duration exposure associated with this use pattern. For example, professional applicators may be subjected to repeat ed 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 consump tion 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 th ere is the likelihood of significant repeated inhalation exposure to the pe sticide as a gas, vapor or aerosol. The exposure time may be redu ced from 90 days to 28 days pending exposure patterns, plateauing of effects a nd considering overall toxicity potential of fipronil.

870.7800 Immunotoxicity There is a new requirement for a series 870.7800 immunotoxicity study. Immunotoxicity study is require d as a part of the new data requirements in the 40 CFR Part 158 for conventional pesticid e registration. Because the immune system is highly complex, studies no t specifically conducted to assess immunotoxic endpoints are inadequate to characterize a pest icide’s potential immunotoxicity. While data from he matology, lymphoid organ weights, and histopathology in routine chronic or sub-ch ronic 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 Regi stration Review Team recommends that the points of departure and uncertainty f actors 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 ev aluate 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 vira l infections such as tuberc ulosis (TB), Severe Acquired Respiratory Syndrome (SARS), or neoplasia . Because the immune system is highly complex, studies assessing functional i mmunotoxic endpoints are helpful in fully characterizing a pesticide’s pot ential immunotoxicity. These data will be used in combination with data from hematology, lym phoid organ weights, and histopathology in routine chronic or sub-chronic toxicity st udies 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, reproduc tive, and endocrinol ogic toxicities. Additionally, the EPA has established an oral reference dose (RfD) for tributyltin oxide (TBTO) based on observed immunotoxici ty 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 gr eater or a diminished risk than that given in the interim decision’s c onclusion, 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 assessm ent 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 Mexico 2 Codex 3

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)-(trifluoromet hyl)]-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), expressedas fipronil (fatsoluble).

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

US Canada Mexico 2 Codex 3

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 RicePage 36 of 47 Summary of US and International Tolerances and Maximum Residue Limits Residue Definition :

US Canada Mexico 2 Codex 3

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 co mmodity, 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-(trifluoro methyl) 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-carbonitr ile) 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-[(1 R,S)-(trifluoromethy l)]-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 12/31/13Page 37 of 47 Tolerances with regio nal registrations. [Reserved]

Indirect or inadvertent residues

. Tolerances are established for combined in direct 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 liste d 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 0.03Page38of47Appendix E: Fipronil ProductsPRD Appendix A:Food/Feed & Non –Food/Non-Feed Uses Considered in Registration Review(11/08/2010) Partial Report

Food (F) / Non-food (N)Use SiteFormulationDescriptionA. I. Max AppRate/AppMax # Apps /CCA. I. Max AppRate/CCMax # Apps /YearA. I. Max AppRate/YearFDAIRY FARM MILK HANDLINGFACILITIES/EQUIPMENTBAIT/SOLIDNDCNSNSNSNSFFOOD/GROCERY/MARKETING/STORAGE/DISTRIBUTIONFACILITY PREMISEBAIT/SOLID.00000002 lb /spotNSNSNSNSFHOUSEHOLD/DOMESTICDWELLINGS INDOOR FOODHANDLING AREASBAIT/SOLID.0041 lb / aNSNSNSNSFORCHARDS (UNSPECIFIED)BAIT/SOLIDNDCNSNSNSNSFPOTATO, WHITE/IRISHFLOWABLECONCENTRATE.1 lb / aNSNSNSNSNBATHROOM PREMISES/HARDSURFACESBAIT/SOLID.00000055 lb /placementNSNSNSNSNBATHROOM PREMISES/HARDSURFACESBAIT/SOLIDNDCNSNSNSNSNCATS (ADULTS/KITTENS)LIQUIDNDCNSNSNSNSNCHRISTMAS TREEPLANTATIONSGRANULAR.0006 lb / cu ftNSNSNSNSNCOMMERCIAL/INDUSTRIALLAWNSBAIT/SOLIDNDCNSNS4/yrNSNCOMMERCIAL/INDUSTRIALLAWNSBAIT/SOLID.000025 lb / aNSNS4/yrNSNCOMMERCIAL/INDUSTRIALLAWNSGRANULAR.025 lb / aNSNSNS.05lb / aNCOMMERCIAL/INSTITUTIONAL/INDUSTRIAL PREMISES/EQUIP.(INDOOR)BAIT/LIQUID.00001196 lb /placementNSNSNSNSNCOMMERCIAL/INSTITUTIONAL/INDUSTRIAL PREMISES/EQUIP.(INDOOR)BAIT/SOLID.00000002 lb /spotNSNSNSNSPage39of47

Food (F) / Non-food (N)Use SiteFormulationDescriptionA. I. Max AppRate/AppMax # Apps /CCA. I. Max AppRate/CCMax # Apps /YearA. I. Max AppRate/YearNCOMMERCIAL/INSTITUTIONAL/INDUSTRIAL PREMISES/EQUIP.(INDOOR)BAIT/SOLID.00000055 lb /placementNSNSNSNSNCOMMERCIAL/INSTITUTIONAL/INDUSTRIAL PREMISES/EQUIP.(INDOOR)BAIT/SOLID.00000099 lb /roomNSNSNSNSNCOMMERCIAL/INSTITUTIONAL/INDUSTRIAL PREMISES/EQUIP.(INDOOR)BAIT/SOLID.0041 lb / aNSNSNSNSNCOMMERCIAL/INSTITUTIONAL/INDUSTRIAL PREMISES/EQUIP.(INDOOR)BAIT/SOLIDNDCNSNSNSNSNCOMMERCIAL/INSTITUTIONAL/INDUSTRIALPREMISES/EQUIPMENT(OUTDOOR)BAIT/LIQUID.00001196 lb /placementNSNSNSNSNCOMMERCIAL/INSTITUTIONAL/INDUSTRIALPREMISES/EQUIPMENT(OUTDOOR)BAIT/SOLID.00000002 lb /spotNSNSNSNSNCOMMERCIAL/INSTITUTIONAL/INDUSTRIALPREMISES/EQUIPMENT(OUTDOOR)BAIT/SOLIDNDCNSNSNSNSNCOMMERCIAL/INSTITUTIONAL/INDUSTRIALPREMISES/EQUIPMENT(OUTDOOR)BAIT/SOLID.0041 lb / aNSNSNSNSNCOMMERCIAL/INSTITUTIONAL/INDUSTRIALPREMISES/EQUIPMENT(OUTDOOR)BAIT/SOLIDNDCNSNSNSNSNCOMMERCIAL/INSTITUTIONAL/INDUSTRIALPREMISES/EQUIPMENT(OUTDOOR)EMULSIFIABLECONCENTRATE.00001554 lb /linear ftNSNS2/yrNSNCOMMERCIAL/INSTITUTIONAL/INDUSTRIALPREMISES/EQUIPMENT(OUTDOOR)EMULSIFIABLECONCENTRATE.005 lb / 1 galNSNS2/yrNSPage40of47

Food (F) / Non-food (N)Use SiteFormulationDescriptionA. I. Max AppRate/AppMax # Apps /CCA. I. Max AppRate/CCMax # Apps /YearA. I. Max AppRate/YearNCOMMERCIAL/INSTITUTIONAL/INDUSTRIALPREMISES/EQUIPMENT(OUTDOOR)GRANULAR.025 lb / aNSNSNS.05lb / aNCOMMERCIAL/INSTITUTIONAL/INDUSTRIALPREMISES/EQUIPMENT(OUTDOOR)WETTABLEPOWDER.00001631 lb /linear ftNSNS2/yrNSNCOMMERCIAL/INSTITUTIONAL/INDUSTRIALPREMISES/EQUIPMENT(OUTDOOR)WETTABLEPOWDER.1305 lb / 25galNSNS2/yrNSNCOMMERCIALSTORAGES/WAREHOUSESPREMISESBAIT/LIQUID.00001196 lb /placementNSNSNSNSNCOMMERCIALSTORAGES/WAREHOUSESPREMISESBAIT/SOLID.00000055 lb /placementNSNSNSNSNCOMMERCIALSTORAGES/WAREHOUSESPREMISESBAIT/SOLID.00000099 lb /roomNSNSNSNSNCOMMERCIALSTORAGES/WAREHOUSESPREMISESBAIT/SOLID.0041 lb / aNSNSNSNSNCOMMERCIALSTORAGES/WAREHOUSESPREMISESBAIT/SOLIDNDCNSNSNSNSNCOMMERCIALTRANSPORTATION FACILITIESNONFEED/NONFOODBAIT/LIQUID.00001196 lb /placementNSNSNSNSNCOMMERCIALTRANSPORTATION FACILITIESNONFEED/NONFOODBAIT/SOLID.00000055 lb /placementNSNSNSNSNCOMMERCIALTRANSPORTATION FACILITIESNONFEED/NONFOODBAIT/SOLID.00000099 lb /roomNSNSNSNSNCOMMERCIALTRANSPORTATION FACILITIESNONFEED/NONFOODBAIT/SOLID.0041 lb / aNSNSNSNSPage41of47

Food (F) / Non-food (N)Use SiteFormulationDescriptionA. I. Max AppRate/AppMax # Apps /CCA. I. Max AppRate/CCMax # Apps /YearA. I. Max AppRate/YearNCOMMERCIALTRANSPORTATION FACILITIESNONFEED/NONFOODBAIT/SOLIDNDCNSNSNSNSNCORN, FIELDFLOWABLECONCENTRATE.0992 lb / lbseedNSNSNSNSNDAIRIES/CHEESE PROCESSINGPLANT PREMISES (NONFOODCONTACT)BAIT/SOLID.00000002 lb /spotNSNSNSNSNDOGS/CANINES(ADULTS/PUPPIES)LIQUIDNDCNSNSNSNSNDOGS/CANINES(ADULTS/PUPPIES)LIQUID-READYTO USE.0009 lb / lbanimalNSNSNSNSNDRAINAGE SYSTEMSBAIT/SOLID.0024 lb / aNSNSNSNSNDRAINAGE SYSTEMSEMULSIFIABLECONCENTRATE.0393 lb / drainNSNSNSNSNDRAINAGE SYSTEMSEMULSIFIABLECONCENTRATE1713.7 lb / aNSNSNSNSNDRAINAGE SYSTEMSWETTABLEPOWDER.0418 lb / drainNSNSNSNSNDRAINAGE SYSTEMSWETTABLEPOWDER1818.8 lb / aNSNSNSNSNEATING ESTABLISHMENTSBAIT/SOLID.00000099 lb /roomNSNSNSNSNEATING ESTABLISHMENTSBAIT/SOLIDNDCNSNSNSNSNEATING ESTABLISHMENTSFOOD HANDLING AREAS(NONFOOD CONTACT)BAIT/SOLID.00000002 lb /spotNSNSNSNSNEATING ESTABLISHMENTSFOOD HANDLING AREAS(NONFOOD CONTACT)BAIT/SOLIDNDCNSNSNSNSNEATING ESTABLISHMENTSFOOD SERVING AREAS(NONFOOD CONTACT)BAIT/LIQUID.00001196 lb /placementNSNSNSNSNEATING ESTABLISHMENTSFOOD SERVING AREAS(NONFOOD CONTACT)BAIT/SOLID.00000002 lb /spotNSNSNSNSNEATING ESTABLISHMENTSFOOD SERVING AREAS(NONFOOD CONTACT)BAIT/SOLID.0041 lb / aNSNSNSNSNEATING ESTABLISHMENTS NONFOOD AREAS (NONFOODCONTACT)BAIT/SOLIDNDCNSNSNSNSPage42of47

Food (F) / Non-food (N)Use SiteFormulationDescriptionA. I. Max AppRate/AppMax # Apps /CCA. I. Max AppRate/CCMax # Apps /YearA. I. Max AppRate/YearNFEED MILLS/FEED PROCESSINGPLANTSBAIT/SOLID.00000002 lb /spotNSNSNSNSNFENCEROWS/HEDGEROWSBAIT/LIQUID.00001196 lb /placementNSNSNSNSNFENCEROWS/HEDGEROWSBAIT/SOLID.00000002 lb /spotNSNSNSNSNFENCEROWS/HEDGEROWSBAIT/SOLIDNDCNSNSNSNSNFOOD PROCESSING PLANTNON-FOOD HANDLING AREASBAIT/SOLID.00000099 lb /roomNSNSNSNSNFOOD PROCESSING PLANTPREMISES (NONFOODCONTACT)BAIT/LIQUID.00001196 lb /placementNSNSNSNSNFOOD PROCESSING PLANTPREMISES (NONFOODCONTACT)BAIT/SOLID.0041 lb / aNSNSNSNSNFOOD PROCESSING PLANTPREMISES (NONFOODCONTACT)BAIT/SOLIDNDCNSNSNSNSNFOODSTORES/MARKETS/SUPERMARKETS PREMISESBAIT/SOLIDNDCNSNSNSNSNFOREST TREEMANAGEMENT/FOREST PESTMANAGEMENTBAIT/SOLIDNDCNSNSNSNSNFOREST TREES (SOFTWOODS,CONIFERS)GRANULAR.0006 lb / cu ftNSNSNSNSNGOLF COURSE TURFBAIT/SOLIDNDCNSNS4/yrNSNGOLF COURSE TURFBAIT/SOLID.000025 lb / aNSNS4/yrNSNGOLF COURSE TURFGRANULAR.025 lb / aNSNSNS.05lb / aNHOSPITALS/MEDICALINSTITUTIONS PREMISES(HUMAN/VETERINARY)BAIT/LIQUID.00001196 lb /placementNSNSNSNSNHOSPITALS/MEDICALINSTITUTIONS PREMISES(HUMAN/VETERINARY)BAIT/SOLID.00000055 lb /placementNSNSNSNSPage43of47

Food (F) / Non-food (N)Use SiteFormulationDescriptionA. I. Max AppRate/AppMax # Apps /CCA. I. Max AppRate/CCMax # Apps /YearA. I. Max AppRate/YearNHOSPITALS/MEDICALINSTITUTIONS PREMISES(HUMAN/VETERINARY)BAIT/SOLID.00000099 lb /roomNSNSNSNSNHOSPITALS/MEDICALINSTITUTIONS PREMISES(HUMAN/VETERINARY)BAIT/SOLID.0041 lb / aNSNSNSNSNHOSPITALS/MEDICALINSTITUTIONS PREMISES(HUMAN/VETERINARY)BAIT/SOLIDNDCNSNSNSNSNHOUSEHOLD/DOMESTICDWELLINGS CONTENTSBAIT/SOLID.00000099 lb /roomNSNSNSNSNHOUSEHOLD/DOMESTICDWELLINGS INDOOR PREMISESBAIT/LIQUID.00001196 lb /placementNSNSNSNSNHOUSEHOLD/DOMESTICDWELLINGS INDOOR PREMISESBAIT/SOLID.00000002 lb /spotNSNSNSNSNHOUSEHOLD/DOMESTICDWELLINGS INDOOR PREMISESBAIT/SOLID.00000055 lb /placementNSNSNSNSNHOUSEHOLD/DOMESTICDWELLINGS INDOOR PREMISESBAIT/SOLID.00000099 lb /roomNSNSNSNSNHOUSEHOLD/DOMESTICDWELLINGS INDOOR PREMISESBAIT/SOLID.0041 lb / aNSNSNSNSNHOUSEHOLD/DOMESTICDWELLINGS INDOOR PREMISESBAIT/SOLIDNDCNSNSNSNSNHOUSEHOLD/DOMESTICDWELLINGS OUTDOORPREMISESBAIT/LIQUID.00001196 lb /placementNSNSNSNSNHOUSEHOLD/DOMESTICDWELLINGS OUTDOORPREMISESBAIT/SOLID.00000002 lb /spotNSNSNSNSNHOUSEHOLD/DOMESTICDWELLINGS OUTDOORPREMISESBAIT/SOLIDNDCNSNSNSNSNHOUSEHOLD/DOMESTICDWELLINGS OUTDOORPREMISESBAIT/SOLID.0041 lb / aNSNSNSNSNHOUSEHOLD/DOMESTICDWELLINGS OUTDOORPREMISESBAIT/SOLIDNDCNSNSNSNSNHOUSEHOLD/DOMESTICDWELLINGS OUTDOORPREMISESEMULSIFIABLECONCENTRATE.00001554 lb /linear ftNSNS2/yrNSPage44of47

Food (F) / Non-food (N)Use SiteFormulationDescriptionA. I. Max AppRate/AppMax # Apps /CCA. I. Max AppRate/CCMax # Apps /YearA. I. Max AppRate/YearNHOUSEHOLD/DOMESTICDWELLINGS OUTDOORPREMISESEMULSIFIABLECONCENTRATE.005 lb / 1 galNSNS2/yrNSNHOUSEHOLD/DOMESTICDWELLINGS OUTDOORPREMISESLIQUID-READYTO USE.00000259 lb /linear ftNSNS1/yrNSNHOUSEHOLD/DOMESTICDWELLINGS OUTDOORPREMISESWETTABLEPOWDER.00001631 lb /linear ftNSNS2/yrNSNHOUSEHOLD/DOMESTICDWELLINGS OUTDOORPREMISESWETTABLEPOWDER.1305 lb / 25galNSNS2/yrNSNINDUSTRIAL / CONSTRUCTIONAREAS (OUTDOOR)EMULSIFIABLECONCENTRATE.0039 lb / linearftNSNSNSNSNINDUSTRIAL / CONSTRUCTIONAREAS (OUTDOOR)EMULSIFIABLECONCENTRATE64.3 lb / aNSNSNSNSNINDUSTRIAL / CONSTRUCTIONAREAS (OUTDOOR)EMULSIFIABLECONCENTRATE.976 lb / 98 galNSNSNSNSNINDUSTRIAL / CONSTRUCTIONAREAS (OUTDOOR)WETTABLEPOWDER.0042 lb / linearftNSNSNSNSNINDUSTRIAL / CONSTRUCTIONAREAS (OUTDOOR)WETTABLEPOWDER1 lb / 100 galNSNSNSNSNINDUSTRIAL / CONSTRUCTIONAREAS (OUTDOOR)WETTABLEPOWDER68.2 lb / aNSNSNSNSNMEAT PROCESSING PLANTPREMISES (NONFOODCONTACT)BAIT/SOLIDNDCNSNSNSNSNNONAGRICULTURAL OUTDOORBUILDINGS/STRUCTURESBAIT/SOLIDNDCNSNSNSNSNNONAGRICULTURAL OUTDOORBUILDINGS/STRUCTURESBAIT/SOLIDNDCNSNSNSNSNNONAGRICULTURALUNCULTIVATED AREAS/SOILSBAIT/SOLIDNDCNSNSNSNSPage45of47

Food (F) / Non-food (N)Use SiteFormulationDescriptionA. I. Max AppRate/AppMax # Apps /CCA. I. Max AppRate/CCMax # Apps /YearA. I. Max AppRate/YearNNURSERY STOCKGRANULAR.025 lb / aNSNSNS.025lb / aNORNAMENTAL AND/OR SHADETREESBAIT/SOLIDNDCNSNSNSNSNORNAMENTAL AND/OR SHADETREESEMULSIFIABLECONCENTRATE.976 lb / 98 galNSNSNSNSNORNAMENTAL AND/OR SHADETREESGRANULAR.0006 lb / cu ftNSNSNSNSNORNAMENTAL AND/OR SHADETREESGRANULAR.025 lb / aNSNSNS.025lb / aNORNAMENTAL AND/OR SHADETREESWETTABLEPOWDER1 lb / 100 galNSNSNSNSNORNAMENTAL HERBACEOUSPLANTSGRANULAR.0006 lb / cu ftNSNSNSNSNORNAMENTAL HERBACEOUSPLANTSGRANULAR.025 lb / aNSNSNS.025lb / aNORNAMENTAL LAWNS ANDTURFBAIT/SOLIDNDCNSNS4/yrNSNORNAMENTAL LAWNS ANDTURFBAIT/SOLID.000025 lb / aNSNS4/yrNSNORNAMENTAL LAWNS ANDTURFGRANULAR.025 lb / aNSNSNS.05lb / aNORNAMENTAL NONFLOWERINGPLANTSGRANULAR.0006 lb / cu ftNSNSNSNSNORNAMENTAL NONFLOWERINGPLANTSGRANULAR.025 lb / aNSNSNS.025lb / aNORNAMENTAL SOD FARM(TURF)BAIT/SOLIDNDCNSNS4/yrNSNORNAMENTAL SOD FARM(TURF)BAIT/SOLID.000025 lb / aNSNS4/yrNSPage46of47

Food (F) / Non-food (N)Use SiteFormulationDescriptionA. I. Max AppRate/AppMax # Apps /CCA. I. Max AppRate/CCMax # Apps /YearA. I. Max AppRate/YearNORNAMENTAL SOD FARM(TURF)GRANULAR.025 lb / aNSNSNS.05lb / aNORNAMENTAL WOODY SHRUBSAND VINESBAIT/SOLIDNDCNSNSNSNSNORNAMENTAL WOODY SHRUBSAND VINESGRANULAR.0006 lb / cu ftNSNSNSNSNORNAMENTAL WOODY SHRUBSAND VINESGRANULAR.025 lb / aNSNSNS.025lb / aNPATHS/PATIOSBAIT/SOLID.0024 lb / aNSNSNSNSNPAVED AREAS (PRIVATEROADS/SIDEWALKS)BAIT/SOLIDNDCNSNSNSNSNPINE (FOREST/SHELTERBELT)FLOWABLECONCENTRATE.1314 lb / aNSNS1/yr.1314lb / aNPOTTING SOIL/TOPSOILGRANULAR.0006 lb / cu ftNSNSNSNSNRECREATIONAL AREASGRANULAR.025 lb / aNSNSNS.05lb / aNRECREATION AREA LAWNSBAIT/SOLIDNDCNSNS4/yrNSNRECREATION AREA LAWNSBAIT/SOLID.000025 lb / aNSNS4/yrNSNRECREATION AREA LAWNSGRANULAR.025 lb / aNSNSNS.05lb / aNREFUSE/SOLID WASTECONTAINERS (GARBAGE CANS)BAIT/SOLIDNDCNSNSNSNSNREFUSE/SOLID WASTE SITES(INDOOR)BAIT/SOLID.00000055 lb /placementNSNSNSNSNREFUSE/SOLID WASTE SITES(INDOOR)BAIT/SOLIDNDCNSNSNSNSNREFUSE/SOLID WASTE SITES(OUTDOOR)BAIT/SOLIDNDCNSNSNSNSPage47of47

Food (F) / Non-food (N)Use SiteFormulationDescriptionA. I. Max AppRate/AppMax # Apps /CCA. I. Max AppRate/CCMax # Apps /YearA. I. Max AppRate/YearNREFUSE/SOLID WASTE SITES(OUTDOOR)BAIT/SOLIDNDCNSNSNSNSNRESIDENTIAL LAWNSBAIT/SOLIDNDCNSNS4/yrNSNRESIDENTIAL LAWNSBAIT/SOLID.0011 lb / aNSNSNSNSNRESIDENTIAL LAWNSGRANULAR.025 lb / aNSNSNS.05lb / aNSEWAGE SYSTEMSBAIT/SOLIDNDCNSNSNSNSNSEWAGE SYSTEMSBAIT/SOLID.0024 lb / aNSNSNSNSNSEWAGE SYSTEMSBAIT/SOLIDNDCNSNSNSNSNSHIPS AND BOATSBAIT/LIQUID.00001196 lb /placementNSNSNSNSNSHIPS AND BOATSBAIT/SOLID.00000099 lb /roomNSNSNSNSNSHIPS AND BOATSBAIT/SOLID.0041 lb / aNSNSNSNSNUTILITY POLES / RIGHT-OF-WAYEMULSIFIABLECONCENTRATE.0039 lb / linearftNSNSNSNSNUTILITY POLES / RIGHT-OF-WAYWETTABLEPOWDER.0042 lb / linearftNSNSNSNSNWOOD PROTECTIONTREATMENT TOBUILDINGS/PRODUCTSOUTDOOREMULSIFIABLECONCENTRATE.976 lb / 98 galNSNSNSNSNWOOD PROTECTIONTREATMENT TOBUILDINGS/PRODUCTSOUTDOORWETTABLEPOWDER1 lb / 100 galNSNSNSNSNZOOSBAIT/LIQUID.00001196 lb /placementNSNSNSNSNZOOSBAIT/SOLID.00000055 lb /placementNSNSNSNSNZOOSBAIT/SOLID.00000099 lb /roomNSNSNSNSNZOOSBAIT/SOLID.0041 lb / aNSNSNSNSNZOOSBAIT/SOLIDNDCNSNSNSNSNDC = No Dosage ConversionNS = Not Specified