Mandipropamid Human Health Risk Assessment D 416292

Page **1** of **7** UNITED STATES ENVIRONMENTAL PROTECTION AGENCY

WASHINGTON, D.C. 20460 **OFFICE OF CHEMICA** **L SA FETY**  **AND POLLUTION PREVENTION**  **MEMORANDUM** Date : Nov 2 5 , 2013 **SUBJECT: Mandipropamid**  : Amendment to Revised Human Health Risk Assessment F or New Use s O n Basil, G inseng and Snap Beans, as Well as Crop Group Expansions for Fruiting V egetable ; Small F ruit, V ine C limbing , Except Fuzzy Kiwifruit ; and Bulb O nion and Green O nion Subgroups . PC Code: 036602 DP Number: D 416292 Decision No.: 47274 7 Registration No. : 100 - 1254 Petition No.: 2E8126 Regulatory Action: Section 3 Risk Assessment Type: Single Chemical Aggregate Case No.: 7058 TXR No.: NA CAS No.: 3 7 4726 - 62 - 2 MRID No.: None 40 CFR: **§** 180. 637 **FROM:** Dennis McNeill y, Chemist and Risk Assessor

Jaime D’Agostino, Toxicologist Risk Assessment Branch II Health Effects Division (7509P) **THROUGH:** Christina Swartz, Chief

Risk Assessment Branch II Health Effects Division (7509P) **TO:** Laura Nollen/Barbara Madden, RM 05

Risk Integration, Minor Use, Emergency Response Branch Registration Division (7505P) **This document is the same as D40910**  **1 (D. McNeilly, 10/31/13) , except it was r**  **evised to include a corrected**  **t oxicology**  **d ata**  **r equirements**  **table as**  **an Appendix**  **. This appendix replaces the appendix B1**  **in the Aug 27, 2013**  **amende d risk assessment**  **(D414944, D. McNeilly) . The**  **neurotox icity**  **studies were misrepres ented in the requirement table**  **and are corrected in this table**  **.** Sy ngenta has contacted the Registration Division concerning HED’s Aug 27, 2013 risk assessment for mandipropamid . That risk assessment involved, inter alia, a request b y IR- 4 to expand theMandipropamid Human Health Risk Assessment D 416292

Page **2** of **7** three crop subgroups, i.e., for s mall f ruit, v ine c limbing, e xcept f uzzy kiwifruit; and bulb o nion and green o nion s ubgroups . Sy ngenta request s that the US toleranc e for grapes (subgroup 13 - 07F) and onions (both bulb (subgroup 3 - 07A) and green onions (subgroup 3 - 07B) ) remain at the current level s to maintain the existing harmonization with Canada. Sy ngenta has submitted export information from the USDA with this request for grapes and onions and these data demonstrate that the major export market for US growers of these commodities is Canada. Sy ngenta also states that m aintaining this harmonization with Canada is critical to allowing US growers to continue to export to other key

markets, such as the EU. IR- 4 had requested several crop group conversions that HED had recommended harmonizing with Codex, but that will result in disharmony with Canadian tolerances, as follows: a) The U.S. subgroup 13 - 07F, represented b y grape, is being recommended at 2.0 ppm in order to harmonize with Codex. This will supersede the current U.S. grape tolerance at 1.4 ppm, which will no longer be harmonized with the Canadian tolerance grape MRL at 1.4 mg/kg. b) The U.S. subgroup 3 - 07 A tolerance (translated from bulb onion) will be harmonized with Codex at 0.1 ppm; however, this tolerance will supersede the current bulb onion U.S. tolerance at 0.05 ppm, which was harmonized with Canada. The U.S. 3 - 07A tolerance will no longer be harmonized with Canada. c) Finall y, the U.S. subgroup 3 - 07B tolerance (translated from green onion) will be harmonized with Codex at 7.0 ppm; however, this tolerance will supersede the current green onion U.S. tolerance at 4.0 ppm, which was harmonized with Canada. The U.S. 3 - 07B tolerance will no longer be harmonized with Canada. HED had recommended for harmonization with CODEX in the Aug 27, 2013 risk assessment, rather than harmonization with the existing Canadian MRL s , due to the FQPA directive to harmonize with CODEX. However, in this case it appears that the greatest trade irritant would be created b y not harmonizing the US tolerances with the Canadian MRL s. Therefore HED is revising the tolerance recommendations for these three crop subgroups to harm onize with PMRA as follows (the other tolerance recommendations remain the same) : **Tolerance Revision**  **Summary for Mandipropamid**  **. Comm**  **odity as Proposed by Registrant**  **Proposed Tolerance (ppm)**  **Revised**

**Recommended Tolerance (ppm)**  **Comments; Correct Commodity**  **Definition** Fruit, small, vine climbing, subgroup 13 - 07F, except fuzzy kiwifruit 2.0 1.4 Fruit, small, vine climbing, except fuzzy kiwifruit, subgroup 13 - 07F . See footnote a below. Onion, bulb, subgroup 3 - 07A 0.1 0.05 See footnote b below. Onion, green, subgroup 3 - 07B 7.0 4.0 See footnote c below. * Notes: a) When the crop subgroup 13 - 07F tolerance is established, then the grape tolerance should be deleted. b) When the crop subgroup 3 - 07A tolerance is established, then the tolerance for onion, dry bulb should be deleted. c) When the crop subgroup 3 - 07B tolerance is established, then the tolerance for Onion, green should be deleted.Mandipropamid Human Health Risk Assessment D 416292

Page **3** of **7** Since the previous dietary assessment was conducted using the high er tolerance/exposure level recommended in the original risk assessment (i.e., subgroups 13 - 07F, 3 - 07A, and 3 - 07B) , and there were no risks of concern, a new dietary assessment is not necessary . **HED Recommendations**  HED recommend s in favor o f establishing tolerance s for residues of mandipropamid as specified in Section 2.2 . 2. **Data Deficiencies** No additional data are required to support HED’s currentl y recommended tolerances ; however , additional data would be needed to support all of the propo sed tolerances associated with the petition. The submitted snap bean data do not support the proposed tolerances in succulent beans and cowpea forage (ChemSAC meeting; 17 July 2013). Additional field trial data on a succulent shelled bean cultivar (such as lima beans) would be necessary in order to establish a tolerance in succulent beans. Because of the possibility of detectable residues occurring in dairy cattle commodities (fat, milk and liver) arising from the feeding of treated cowpea forage, the concurrent establishment of mandipropamid tolerances at the limit of quantitation (LOQ) in those commodities would be necessary . However, with no validated anal ytical method for enforcing tolerances in livestock commodities, it is not possible to establish such tolerances. Therefore, the proposed tolerance in cowpea forage cannot be established until a validated method for determining mandipropamid residues in livestock (cattle) commodities is available. Any such method submitted would need an independent laboratory validation (ILV) . (If tolerances for additional livestock feed items other than cowpea forage are proposed , a livestock feeding study should be submitted.) Since the last risk assessment, an immunotoxicity study was received which fulfills a previously identified data gap . In this study, no evidence of immunotoxicity was observed up to the highest dose tested (649 mg/kg/day). In addition, HED’s Hazard and Science Policy Council ( HASPOC ) determined that a subchronic inhalation study in the rat is not required for mandipropamid ( TXR # 0056 610, J. Alstine, 3/ 14/2013 ). **Tolerance Considerations** HED has examined the toxicology and residue chemistry

database for mandipropamid. There are no issues that would pre clude establishing tolerance s for mandipropamid for the commodities listed in Table 2.2.2. **Note s**  **to RD:** a) When the crop subgroup 13 - 07F tolerance is established , then the grape tolerance should be deleted. b) When the crop subgroup 3 - 07A tolerance is established , then the tolerance for onion, dry

bulb, should be deleted. c) When the crop subgroup 3 - 07B tolerance is established , then the tolerance for o nion, green should be deleted. d) According to HED’s Interim Guidance on Tolerance Expressions (S. Knizner; 27 May 2009), the tolerance expression for mandipropamid cited in 40CFR §180.6 37 [a] should be revised to state: Tolerances are established for residues of mandipropamid, including its metabolites and degradates, in or on the commodities listed in theMandipropamid Human Health Risk Assessment D 416292

Page **4** of **7** table below. Compliance with the tolerance levels specified below is to be determined b y measuring only mandipropamid (4 - chloro -N - [2 - [3 - methoxy- 4 - (2 -prop ynylox y)phenyl]ethyl] - α - (2 - propy nyloxy)benzeneacetamide ) in or on the commodity . **Recommended Tolerances**  Pending submission of a revised Section F (to propose tolerance levels in accordance with those recommended b y HED , and to correct some of the commodity definitions) , there are no residue chemistry issues that would preclude establishing tolerance s in the requested commodities , except for those in cowpea forage and succulent beans . The recommended tolerances are listed in Table 2.2.2. **Table 2.2.2**  **. Tolerance Summary for**  **Mandipropamid .**  **Comm odity as Proposed by**  **Registrant Proposed**  **Tolerance (ppm)**  **Recommended**

**Tolerance (ppm) Comments;**  **Correct Commodity Definition**  Basil, fresh 30 30 Basil, fresh leaves Basil, dried 200 200 Basil, dried leaves Bean, succulent 0.90 None Field trial data on a succulent shelled bean cultivar is needed. Bean, snap None 0.90 The snap bean field trials support the establishment of this tolerance. Ginseng 0.3 0.30 Cow pea, forage 15 None A validated method (i.e. with an ILV) for residues in cattle commodities is needed . Vegetable, fruiting, group 8 - 10 1.0 1.0 Fruit, small, vine climbing, subgroup 13 - 07F, except fuzzy kiwifruit 2.0 1.4 Fruit, small, vine climbing, except fuzzy kiwifruit, subgroup 13 - 07F . See footnote a below. Onion, bulb, subgroup 3 - 07A 0.1 0.0 5 See foot note b below. Onion, green, subgroup 3 - 07B 7.0 4 .0 See foot note c below. * Notes: a) When the crop subgroup 13 - 07F tolerance is established, then the grape tolerance should be deleted. b) When the crop subgroup 3 - 07A tolerance is established, then the tolerance for onion, dry bulb should be deleted. c) When the crop subgroup 3 - 07B tolerance is established, then the tolerance for Onion, green should be deleted. **Revisions to Petitioned -**  **For Tolerances** Instead of the proposed tolerance in ginseng (0.3 ppm), HED recommends establishing the tolerance at 0.30 ppm, in order to avoid the situation where a field sample containing residues significantl y above the tolerance (0.34 ppm, for example) would be consi dered non - violative. For the same reason, HED recommends that the proposed tolerance of 0.1 ppm in bulb onions ( subgroup 3 - 07A) be revised to 0. 1 0 ppm . The submitted snap bean data do not support the proposed tolerance in succulent bean s . A cowpea forag e tolerance cannot be established due to the lack of a livestock anal ytical enforcement method , and a supporting livestock anal ytical method ILV ( See Section 2.1 ). Therefore, HED is not recommending in favor of the proposed tolerances in succulent bean s and cowpea forage .Mandipropamid Human Health Risk Assessment D 416292

Page **5** of **7** HED had originall y recommended (Aug 27, 2013) tolerances for: Fruit, small, vine climbing, subgroup 13 - 07F, except fuzzy kiwifruit; Onion, bulb, subgroup 3 - 07A; and Onion, green, subgroup 3 - 07B that were harmoniz ed with CODEX , rather than harmonization with the existing Canadian MRL s , due to the FQPA directive to harmonize with CODEX. However, in this case it appears that the greatest trade irritant would be created b y not harmonizing the US tolerances with the Canadian MRL s. Therefore HED is revising the tolerance recommendations for these three crop subgroups to recommend harmonize with PMRA as described in Table 2.2.2 . **International Harmonization** Neither Codex nor PMRA have established MRLs for mandipropamid in/on fresh basil, dried basil, ginseng, or succulent beans. As such, there is no harmonization issue associated with Codex for these specific proposed new uses in the current action. PMRA and EPA are jointly reviewing the basil, ginseng and snap bean data in the current action, and EPA and PMRA are harmonized for fresh basil, dried basil, and ginseng. PMRA is establishing an MRL in edible -podded beans at 0.9 ppm, while HED is recommending for a tolerance in snap beans at 0.90 ppm. Although the tolerance/MRL level is harmonized, HED cannot harmonize with PMRA on the commodity definition, as the submitted snap bean data do not support use on all succulent beans. Both the current tolerance in crop group 8 (1.0 ppm) and the proposed tolerance in crop group 8 - 10 (1.0 ppm) are harmonized with the Codex (bell and non -bell peppers) and PMRA’s (tomatoes, okras and peppers) MRLs. For the other crop group expansions, EPA is harmonizing with Canadian MRL s, even though this will result in discrepancies between US tolerances an d CODEX MRL s. The HED - recommended tolerance of 1.4 ppm in subgroup 13 - 07F, translated from grape data, will be harmonized with the Canadian MRL in grapes, but will not be harmonized with the CODEX MRLof 2.0 mg/kg in grapes. The HED - recommended tolerance of 0.05 ppm in subgroup 3 - 07A, translated from dry bulb onion data, will be harmonized with PMRA’s MRLof 0.05 ppm in various bulb onions, but will not be harmonized with the Codex MRL 0f 0.1 ppm in bulb onions. The HED - recommended tolerance of 4.0 ppm in subgroup 3 - 07B, translated from green onion data, will be harmonized with PMRA’s MRL in various green onions, but will not be harmonized with the CODEX MRLof 7.0 ppm in spring onions. **L abel Recommendations**  None **Pesticide Use Pattern** IR- 4 has reques ted that new Section 3 uses of the fungicide mandipropamid be added to the label for Revus 2.08SC (EPA Reg . No. 100 - 1254 ). The proposed new uses would be on basil, cowpea forage, ginseng, succulent beans, and greenhouse tomatoes . The proposed use directions are summarized in Table 3. 2 .Mandipropamid Human Health Risk Assessment D 416292

Page **6** of **7 Table**  **3. 2**  **. Summ**  **ary of Proposed**  **Directions for Use of Mandipropamid**  **. Application Type;**  **Equipment 1**  **Use**

**Rate (lb ai/A)**  **Max. Uses**

**Per Season Max. Seasonal** 

**Use Rate (lb ai/A)**  **PHI 2** 

**(Days) Use Directions,**  **Application Timing,**

**and Limitations 3**  **Basil** Foliar; any ground or aerial equipment . 0.09 -

0.13 4 0.52 1 RTI **4** of 7 - 10 days. **Ginseng** Foliar; any ground or aerial equipment. 0.09 -

0.13 4 0.52 2 RTI of 7 - 10 days.

**Succulent B eans**  **(Cowpea Forage)** Foliar; any ground or aerial equipment. 0.09 -

0.13 4 0.52 1 RTI of 7 - 10 days.

**G reenhouse**  **T om**  **atoes** Foliar; any ground or aerial equipment. 0.09 -

0.13 4 0.52 1 RTI of 7 - 10 days. May be applied via chemigation . 1. For ground application, apply in a minimum of 10 gallons of water per acre (GPA) , unless specified otherwise on the label. Do not apply through any ultra - low volume (ULV) spray system. For a erial application, u se only on crops w here aerial applications are indicate d. Apply in a minimum of 5 GPA, unless specified otherwise on this label. Do not apply through any ULV spray system. For c hemigation, u se only on crops where chemigation is specified on the label. Apply no more than 2 sequential applications unless oth erwise stated in the crop - specific section. Do not use in transplant production. 2. PHI = Pre - Harvest Interval. 3. Begin applications prior to disease development. Use the shorter interval and/or higher rates under high pressure, or when conditions are conducive to disease. The addition of a spreading/penetrating type adjuvant such as a non - ionic based surfactant (NIS) or crop oil concentrate (COC) or blend is recommended. 4. RTI = Re - Treatment Interval. The Personal Protective Equipment (PPE) statement on the proposed label requires applicators, flaggers and other handlers to wear: long - sleeved shirt and long pants, shoes plus socks. PPE recommended on the proposed label for earl y entry to treated areas include: coveralls, chemical resistant glov es made of any waterproof material, shoes plus socks. Conclusions : The use directions are adequate to allow for evaluation of the residue data. However, as the submitted snap bean data do not support the proposed use on succulent beans, the label section containing directions for use on succulent beans ( “ Bean, succulent”) should instead refer to snap beans (“Bean, sn ap ”) , and the listing of all other succulent bean commodities should be deleted . A cowpea forage tolerance cannot be established due to the lack of a livestock anal ytical enforcement method, and supporting livestock anal ytical method ILV. No other revisions are made to HED’s Aug 27, 2013 risk assessment for mandipropamid .Mandipropamid Human Health Risk Assessment D 416292

Page **7** of **7 A** **ppendix . Toxicology Profile Toxicology Data Requirements**  **Note: This document is the same as**  **D40910 1**  **, (D. McNeilly, 10/31/13)**  **except it was r evised to**  **include a corrected toxicology data requirements table as an Appendix. This appendix replaces the appendix B1 in the Aug 27, 2013 amended risk assessment**  **(D414944, D. McNeilly). The neurotoxicity studies were misrepresented in the requirement table and are**  **corrected in this table.** The requirements (40 CFR 158.340) for food uses of mandipropamid are in the table below . Use of the new guideline numbers does not imply that the new (1998 ) guideline protocols were used . **Study Technical**  **Required Satisfied**  870.1100 Acute Oral Toxicity ................................ ....................... 870.1200 Acute Dermal Toxicity ................................ .................. 870.1300 Acute Inhalation Toxicity ................................ .............. 870.2400 Acute Eye Irritation ................................ ....................... 870.2500 Acute Dermal Irritation ................................ ................. 870.2600 Skin Sensitization ................................ .......................... yes yes yes yes yes yes yes

yes yes yes yes yes 870.3100 90 - Day

Oral Toxicity in Rodents ................................ .. 870.3150 90 - Day

Oral Toxicity in Nonrodents ............................. 870.3200 21/28 - Day Dermal Toxicity ................................ ........... 870.3250 90 - Day Dermal Toxicity ................................ ................ 870.3465 28/90 - Day Inhalation Toxicity ................................ ...... yes yes yes no no yes

yes yes

-

- 870.3700a Prenatal Developmental Toxicity (rodent) ..................... 870.3700b Prenatal Developmental Toxicity (nonrodent) ............... 870.3800 Reproduction and Fertility Effects ................................ . yes yes yes yes

yes yes 870.4100a Chronic Toxicity (rodent) ................................ .............. 870.4100b Chronic Toxicity (nonrodent) ................................ ........ 870.4200a Carcinogenicity (rat) ................................ ...................... 870.4200b Carcinogenicity (mouse) ................................ ................ 870.4300 Combined Chronic Toxicity/Carcinogenicity ................ yes yes yes yes yes yes

yes yes yes yes 870.5100 Mutagenicity

—Bacterial Reverse Mutation Test .......... 870.5300 Mutagenicity

—Mammalian Cell Gene Mutation Test .. 870.5385 Mutagenicity

— Structural Chromosomal Aberrations ... 870.5550 Mutagenicity

—Other Genotoxic Effects ....................... yes yes yes yes yes

yes yes yes 870.6200a Acute Neurotoxicity Screening Battery (rat) ................. 870.6200b 90 - Day

Neurotoxicity Screening Battery (rat) ............... 870.6300 Developmental Neurotoxicity ................................ ........ yes yes no yes

yes

- 870.7485 Metabolism and Pharmacokinetics ................................ 870.7600 Dermal Penetration ................................ ........................ 870.7800 Immunotoxicity ................................ ............................. yes no yes yes

yes yes