Page 1 of 8 SUPPLEMENTAL PETITION REQUESTING A PERMANENT EXEMPTION FROM THE

REQUIREMENT OF TOLERANCE FOR RESIDUES OF JOINT INERTS TASK FORCE , CLUSTER SU PPORT TEAM 9 NONYL PHENOL ETHOXYLATE PHOSPHATE AND SULFAT E DERIVATIVES IN OR ON RAW AGRICULTURAL COMMODITIES AND APPLIED TO ANIMALS SUBMITTED BY JOINT INERTS TASK FO RCE CLUSTER SUPPORT TEAM 9 ADDRESS 1156 15 TH STREET, NW, SUITE 400 WASHINGTON, DC 200 05 DATE April 8 , 2011Page 2 of 8 Background As mandated by the Food Quality Protection Act (FQPA) of 1996, EPA conducted a reassessment of tolerances and exemptions from the requirement of tolerances for inert ingredients used in pesticide products to determine i f they met Federal Food, Drug, and Cosmetic Act’s (FFDCA) revised standard of safety. As a result of that reassessment, the Agency published a Final Rule in the Federal Register (FR) Notice Volume 71, No. 153, p. 45422, August 9, 2006, “Inert Ingredients; Revocation of Tolerance Exemptions with Insufficient Data for Reassessment”, that proposed revocation of specific exemptions from the requirement of a tolerance due to insufficient data. The f ollowing is a brief chronology of the Joint Inerts Task For ce (JITF) Cluster Support Team 9 ( CST 9 , EPA Company Number 84943 ) responses and data generation to comply with the August 9, 2006 revocation.

**•** On August 30 , 2007 the JITF CST 9 submitted a data development plan to the EPA, Office of Pesticides Program (O PP), Registration Division (RD), Inert Ingredient Assessment Branch (IIAB) , proposing to test the representative Nonylphenol Ethoxylate (NPE) phosphate (CAS RN 68412 - 53 - 3) and sulfate (CAS RN 9014 - 80 - 8) derivatives using the OECD 422, Combined Repeated Dos e Toxicity Study with the Reproduction/Developmental Toxicity in Rats Screening Test. The data development plan was accepted by the Agency on September 19, 2007 . **•** On November 12 , 2008, CST 9 submitted a petition (PP 8E7478) to IIAB proposing to establish an exemption from the requirement of a tolerance to support the NPE phosphate and sulfate d erivatives (NPEPSD) under the Code of Federal Regulations (CFR) Title 40, Section 180.910 and Section 180.930 NPE Phosphate Derivatives (NPEPD) Supported by the JIT F CST 9 α - (p - Nonylphenyl) - ω - hydroxypoly(oxyethylene) mixture of dihydrogen phosphate and mono hydrogen phosphate esters and the corresponding ammonium, calcium, magnesium, monoethanolamine, potassium, sodium, and zinc salts of the phosphate esters; the no nyl group is a propylene trimer isomer and the poly(oxyethylene) content averages 4 - 14 moles or 30 moles CAS RN Chemical Name 51811 - 79 - 1 Poly (oxy - 1, 2 - ethanediyl), α - (nonylphenyl) - ω - hydroxy - , phosphatePage 3 of 8 CAS RN Chemical Name 59139 - 23 - 0 Ethanol, 2 - amino - , compd. with α - (nony lphenyl) - ω hydroxypoly(oxy - 1,2 - ethanediyl) phosphate 67922 - 57 - 0 Poly(oxy - 1,2 - ethanediyl), α - (nonylphenyl) - ω - hydroxy - , phosphate, magnesium salt Poly(oxy - 1,2 - ethanediyl), α - (nonylphnyl) - ω - hydroxy - , phosphate, magnesium salt 68412 - 53 - 3 Poly(oxy - 1,2 - ethaned iyl), α - (4 - nonylphenyl) - ω - hydroxy - , phosphate, sodium salt 68553 - 97 - 9 Poly(oxy - 1,2 - ethanediyl), α - (4 - nonylphenyl) - ω - hydroxy - , phosphate, sodium salt 68954 - 84 - 7 Poly(oxy - 1,2 - ethanediyl), α - (nonylphenyl) - ω - hydroxy - , branched, phosphate, sodium salt 998 21 - 14 - 4 Poly(oxy - 1,2 - ethanediyl), α - (nonylphenyl) - ω - hydroxy - , phosphate, calcium salt 152143 - 22 - 1 Poly(oxy - 1,2 - ethanediyl), α - (4 - nonylphenyl) - ω - hydroxy - , branched, phosphates 51609 - 41 - 7 Poly(oxy - 1,2 - ethanediyl), α - (4 - nonylphenyl) - ω - hydroxy - , phosphate 37340 - 60 - 6 Poly(oxy - 1,2 - ethanediyl), α - (nonylphenyl) - ω - hydroxy - , phosphate, sodium salt 106151 - 63 - 7 Poly(oxy - 1,2 - ethanediyl), α - phosphono - ω - (4 - nonylphenoxy) - , dipotassium salt 68584 - 47 - 4 Poly(oxy - 1,2 - ethanediyl), α - (nonylphenyl) - ω - hydroxy - , branched, ph osphates, potassium salts 52503 - 15 - 8 Poly(oxy - 1,2 - ethanediyl), α - (nonylphenyl) - ω - hydroxy - , phosphate - , potassium salt 68458 - 49 - 1 Polyphosphoric acids, esters with polyethylene glycol nonylphenyl ether NPE Sulfate Derivatives (NPESD) Supported by the J ITF CST 9 α - (p - nonylphenol) - ω - hydroxypoly(oxyethylene) sulfate, ammonium, calcium, magnesium, potassium, sodium, and zinc salts the nonyl group is propylene trimer isomer and the poly(oxyethylene) content averages 4 moles CAS RN Chemical Name 9014 - 90 - 8 Poly (oxy - 1, 2 - ethanediyl), α - sulfo - ω - (nonylphenoxy), sodium salt 9051 - 57 - 4 Poly (oxy - 1, 2 - ethanediyl), α - sulfo - ω(nonylphenoxy), ammonium salt 9081 - 17 - 8 Poly (oxy - 1, 2 - ethanediyl), α - sulfo - ω - (nonylphenoxy), acidPage 4 of 8 CAS RN Chemical Name 68649 - 55 - 8 Poly (oxy - 1, 2 - ethanediyl), α - sulfo - ω - (nonylphenoxy), branched, ammonium salt 68891 - 33 - 8 Poly (oxy - 1, 2 - ethanediyl), α - sulfo - ω - (nonylphenoxy), branched **•** The OECD 422 study conducted on a representati ve NPE phosphate derivative (NPEPD) , Poly(oxy - 1,2 - ethanediyl), α - (4 - nonylphenyl) - ω - hydroxy - , phosphate, sodium salt , CAS RN 68412 - 53 - 3 (MRID # 47603701 ) , indicated no adverse reproductive or developmental toxicity findings in the offspring. The NOAEL, for FQPA risk assessment purposes, was established at 396 mg/kg bw/day which was cons idered to be acceptable according to the criteria specified in the EPA Inerts - Dietary Exposure Evaluation Exposure Model (I DEEM) . **•** The OECD 422 study conducted on representative NPE sulfate derivative (NPESD), Poly (oxy - 1, 2 - ethanediyl), α - sulfo - ω - (no nylphenoxy), sodium salt , CAS RN 9014 - 90 - 8 (MRID # 47603702 ) , indicated no adverse reproductive or developmental toxicity findings in the offspring. The NOAEL, for FQPA risk assessment purposes, was established at 300 mg/kg bw/day which was considered to b e acceptable according to the criteria specified in the EPA Inerts - Dietary Exposure Evaluation Exposure Model (I - DEEM) . **•** O n June 2, 2009, CST 9 provided supplemental information to the petition including chemical identity, metabolism and safety assessme nt data that included drinking water exposure monitoring (MRID # 47766401).

**•** On July 15 , 2009, OPP Health Effects Division (HED) provided a draft risk assessment “ Nonyl phenol Ethoxylates and Their Phosphate and Sulfate ( NPEs

– JITF CST 9 Inert Ingredients ) Human Health Risk Assessment to Support the Proposed Exemption from the Requirement of a Tolerance When Used as Inert Ingredients in Pesticide Formulations ” (PC Code 911703 , DP Barcode D36601 3 ), which requested additional toxicity studies, and residue ch emistry data for both the parent compounds and nonylphenol metabolites. On August 7, 2009, EPA issued a FR N otice which delayed the effective date for the tolerance exemptions.

**•** In response to the Risk Assessment, CST 9 provided additional regulatory and t echnical information to support the establishment of NPEPD and NPESD tolerance exemptions . On August 14, 2009, CST 9 submitted copies of previously cited publically available data, andPage 5 of 8 copies of data and public literature that CST 9 identified as relevant to the uncertainties identified in the risk assessment. On August 19, 2009, CST 9 submitted a Position Paper regarding the FQPA safety factor.

**•** On the basis of the risk assessment and the information submitted by CST 9 , EPA published the Final Rule (FR Not ice Volume 75, No. 94, pages 27434 - 27443 , May 17, 2010) to establish a time - limited exemption from the requirement of a tolerance for NPEPSDs when used as inert ingredients, not to exceed 7% in pesticide formulations applied to growing crops and raw agricu ltural commodities after harvest ( 40 CFR 180.910 ) and applied to animals (40 CFR 180.930) . This time - limited exemption for the NPEPSD inert ingredients supported by CST 9 will expire May 17, 2012 .

**−** EPA concluded that there is a “reasonable certainty that no harm” will result to the general population or to infants.

**−** The Agency also carefully considered the weight of the evidence with respect to carcinogenicity for both the parent compounds, and concluded that the cancer risks would be negligible.

**−** However, to resolve uncertainty in the mutagenicity database, the Agency requested confirmatory data and requested that CST 9 provide additional mutagenicity testing.

**•** In response to the May 17, 2010 FR Notice, CST 9 conducted two in vivo Mouse Bone Marrow Erythro cyte Micronucleus Test ( OCSPP 870.5395; OECD 474) Following Oral Administration of the representative NPE PD CAS RN 68412 - 53 - 3 (MRID # 47603701) , and of the NPE SD CAS RN 9014 - 90 - 8 (MRID # 47603702) . In accordance with the deadline established by EPA, these data were submitted to the Agency on November 12, 2010. Mouse Bone Marrow Erythrocyte Micronucleus Test (OCSPP 870.5395 ) Following Oral Administration of the NPEPD, CAS RN 68412 - 53 - 3 (MRID # 47603701) Summary

Under the conditions of the assay described in the final report (MRID # 47603701 ) , a single oral administration of the test substance at doses up to and including a dose of 2000 mg/kg did not induce a significant increase in the incidence of micronucleated polychromatic erythrocytes in bone marrow of male or female ICR mice. Therefore, Poly(oxy - 1,2 - ethanediyl),α - (nonylphenyl) - ω - hydroxy - ,branched,phosphates (CAS RN 68412 - 53 - 3), was concluded to be negative in the mouse micronucleus assay.Page 6 of 8 **•** Dose formulation analysis indicated that all formulations were within the acceptance criteria (± 15% of the nominal concentration). Therefore, animals were exposed to the intended doses.

**•** No mortality was observed in any of the treatment groups. All mice in the control groups (vehicle or positive) and all female mice in the test substance treatment group s (500, 1000 and 2000 mg/kg) and all male mice in 500 or 1000 mg/kg treatment groups appeared normal during the course of the study. Lethargy, piloerection and/or hunched position were observed in some of the male mice at 2000 mg/kg.

**•** In the bone marrow, d ose dependent reductions in the ratio of polychromatic erythrocytes to total erythrocytes from 13 % to 18% in male mice and from 3 % to 8% in the female mice in the 24 hour test substance treatment groups were observed. Reductions of 10 % and 1% were also see n in male and female groups at 48 hour post - dose, respectively, relative to the vehicle controls. These reductions suggest bioavailabilty of the test substance.

**•** No statistically significant increase in the incidence of micronucleated polychromatic erythro cytes in test substance groups relative to the respective vehicle control substance groups was observed in male or female mice at 24 or 48 hours after dose administration (p > 0.05, Kastenbaum - Bowman Tables).

**•** Cyclophosamide (CP) , the positive control subs tance, induced a statistically significant increase in the incidence of mic ronucleated PCEs (p ≤ 0.05, Kastenbaum - Bowman Tables) in both male and female mice relative to the respective vehicle control groups. The number of micronucleated PCEs in the vehicle control groups did not exceed the historical vehicle control range. Based upon these, all criteria for a valid test were met as specified in the protocol. Mouse Bone Marrow Erythrocyte Micronucleus Test (OCSPP 870.5395 ) Following Oral Administration of the NPESD CAS RN 9014 - 90 - 8 (MRID # 47603702 ) Under the conditions of the a ssay described in the final report (MRID # 47603702 ) , “ a single oral administration of the test substance at doses up to and including a dose of 2000 mg/kg did not induce a significant increase in the incidence of micronucleated polychromatic erythrocytes in bone marrow of male or female ICR mice. Therefore, Poly (oxy - 1, 2 - ethanediyl), α - sulfo - ω - (nonylphenoxy), sodium salt (CAS RN 9014 - 90 - 8) was concluded to be negative in the mouse micronucleus assay. ”Page 7 of 8 **•** The dose formulation analysis indicated that the mean concentrations for nominal concentrations of 25, 50, and 100 mg/mL were 24.7, 47.7, and 98.5 mg/mL, respectively. The percent recovery of the target concentrations were 98.8%, 95.4%, and 98.5%, respectively. These results were within the acceptance criter ia (± 15% of the nominal concentration). Therefore, animals were exposed to the intended doses.

**•** No mortality was observed in any of the treatment groups. All mice in the control groups (vehicle or positive) and all mice in the 500 mg/kg treatment group ap peared normal during the course of the study. Lethargy and/or piloerection were observed in some of the mice in 1000 and 2000 mg/kg dose groups immediately after dose administration. However, these mice appeared normal during the remaining period of the st udy.

**•** No appreciable reductions in the ratio of polychromatic erythrocytes to total erythrocytes in the test substance groups relative to the respective vehicle control groups were observed in the bone marrow suggesting that the test substance did not inhi bit erythropoiesis markedly.

**•** No statistically significant increase in the incidence of micronucleated polychromatic erythrocytes in test substance groups relative to the respective vehicle control substance groups was observed in male or female mice at 24 or 48 hours after dose administration (p > 0.05, Kastenbaum - Bowman Tables).

**•** Cyclophosamide (CP) , the positive control substance, induced a statistically significant increase in the incidence of micronucleated PCEs (p ≤ 0.05, Kastenbaum - Bowman Tables) in b oth male and female mice relative to the respective vehicle control groups. The number of micronucleated PCEs in the vehicle control groups did not exceed the historical vehicle control range. Based upon these, all criteria for a valid test were met as spe cified in the protocol. Summary Conclusion To summarize, CST 9 believes it has duly fulfilled the testing requirements that were published in the FR Notices of August 9, 2006 and May 17, 2010, respectively. The results of testing, summarized below, prov ided definitive information for EPA to conclude that the use of NPE PSD inert ingredients in pesticide formulations comply with the FQPA mandate of “ reasonable certainty of no harm ” .Page 8 of 8 **•** EPA previously concluded that based on the weight of evidence there is n o evidence of increased susceptibility, neurotoxicity, developmental toxicity, or reproductive toxicity f or the NPE PSD inert ingredients supported by CST 9 . **•** CST 9 conducted two bone marrow assay s (Harmonized Guideline 870.5395

— Mammalian erythrocyte mic ronucleus test) to address any uncertainty in the mutagenicity database. The results of th ese assay s were negative and therefore confir m the Agency’s conclusion that c ancer risks would be negligible . Thus, based on the weight of evidence and body of data that has been submitted, and reviewed by EPA in support of the tolerance exemption s of NPE PSD inert ingredients , CST 9 requests that the Agency establish a permanent exemption for the requirement of a tolerance under the Code of Federal Regulat ions Title 4 0, Section 180.910 , and Section 180.930 for : α - (p - Nonylphenyl) - ω - hydroxypoly(oxyethylene) mixture of dihydrogen phosphate and mono hydrogen phosphate esters and the corresponding ammonium, calcium, magnesium, monoethanolamine, potassium, sodium, and zinc salts of the phosphate esters; the nonyl group is a propylene trimer isomer and the poly(oxyethylene) content averages 4 - 14 moles or 30 moles not to excee d 7% in pesticide formulations. α - (p - nonylphenol) - ω - hydroxypoly(oxyethylene) sulfate, ammonium, calc ium, magnesium, potassium, sodium, and zinc salts the nonyl group is propylene trimer isomer and the poly(oxyethylene) content averages 4 moles (CAS RNs 9014 - 90 - 8, 9051 - 57 - 4, 9081 - 17 - 8, 68649 - 55 - 8, 68891 - 33 - 8) , not to excee d 7% in pesticide formulations.