Document ID: EPA-HQ-OPP-2012-0980-0012
Agency: epa
Document Type: Supporting & Related Material
Title: 
Posted Date: 2013-12-20T05:00Z

UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
                            WASHINGTON, D.C.  20460
                                                                      OFFICE OF
                                                            CHEMICAL SAFETY AND
\* MERGEFORMAT
                                                           POLLUTION PREVENTION

MEMORANDUM

Date:  Nov 25, 2013

SUBJECT:  Mandipropamid:  Amendment to Revised Human Health Risk Assessment For New Uses On Basil, Ginseng and Snap Beans, as Well as Crop Group Expansions for Fruiting Vegetable; Small Fruit, Vine Climbing, Except Fuzzy Kiwifruit; and Bulb Onion and Green Onion Subgroups.  

PC Code:  036602
DP Number:  D416292
Decision No.:  472747
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.:  374726-62-2
MRID No.:   None
40 CFR:  §180.637

FROM:	Dennis McNeilly, 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 D409101 (D. McNeilly, 10/31/13), except it was revised 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.

Syngenta has contacted the Registration Division concerning HED's Aug 27, 2013 risk assessment for mandipropamid.  That risk assessment involved, inter alia, a request by IR-4 to expand the three crop subgroups, i.e., for small fruit, vine climbing, except fuzzy kiwifruit; and bulb onion and green onion subgroups.  Syngenta requests that the US tolerance for grapes (subgroup 13-07F) and onions (both bulb (subgroup 3-07A) and green onions (subgroup 3-07B)) remain at the current levels to maintain the existing harmonization with Canada.  Syngenta 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.  Syngenta also states that maintaining 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 by 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 3-07A 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)  Finally, 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 MRLs, due to the FQPA directive to harmonize with CODEX.  However, in this case it appears that the greatest trade irritant would be created by not harmonizing the US tolerances with the Canadian MRLs.  Therefore HED is revising the tolerance recommendations for these three crop subgroups to harmonize with PMRA as follows (the other tolerance recommendations remain the same):

Tolerance Revision Summary for Mandipropamid.

                      Commodity 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.

Since the previous dietary assessment was conducted using the higher 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 recommends in favor of establishing tolerances for residues of mandipropamid as specified in Section 2.2.2.

Data Deficiencies

No additional data are required to support HED's currently recommended tolerances; however, additional data would be needed to support all of the proposed 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 analytical 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 #0056610, J. Alstine, 3/14/2013).

Tolerance Considerations

HED has examined the toxicology and residue chemistry database for mandipropamid.  There are no issues that would preclude establishing tolerances for mandipropamid for the commodities listed in Table 2.2.2.

Notes 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 onion, 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 §180.637[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 the table below.  Compliance with the tolerance levels specified below is to be determined by measuring only mandipropamid (4-chloro-N-[2-[3-methoxy-4-(2-propynyloxy)phenyl]ethyl]-α-(2-propynyloxy)benzeneacetamide) in or on the commodity.

Recommended Tolerances

Pending submission of a revised Section F (to propose tolerance levels in accordance with those recommended by HED, and to correct some of the commodity definitions), there are no residue chemistry issues that would preclude establishing tolerances 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.

                      Commodity 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

Cowpea, 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
                                     0.05
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.

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 significantly above the tolerance (0.34 ppm, for example) would be considered 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 0.10 ppm.

The submitted snap bean data do not support the proposed tolerance in succulent beans.  A cowpea forage tolerance cannot be established due to the lack of a livestock analytical enforcement method, and a supporting livestock analytical method ILV (See Section 2.1).  Therefore, HED is not recommending in favor of the proposed tolerances in succulent beans and cowpea forage.

HED had originally 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 harmonized with CODEX, rather than harmonization with the existing Canadian MRLs, due to the FQPA directive to harmonize with CODEX.  However, in this case it appears that the greatest trade irritant would be created by not harmonizing the US tolerances with the Canadian MRLs.  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 MRLs, even though this will result in discrepancies between US tolerances and CODEX MRLs.  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 MRL of 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 MRL of 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 MRL of 7.0 ppm in spring onions.

Label Recommendations

None

Pesticide Use Pattern
IR-4 HAS REQUESTED 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.

Table 3.2.  Summary 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 Beans (Cowpea Forage)
                    Foliar; any ground or aerial equipment.
                                  0.09 - 0.13
                                       4
                                     0.52
                                       1
RTI of 7-10 days.  

                              Greenhouse Tomatoes
                    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 aerial application, use only on crops where aerial applications are indicated.  Apply in a minimum of 5 GPA, unless specified otherwise on this label.  Do not apply through any ULV spray system.  For chemigation, use only on crops where chemigation is specified on the label.  Apply no more than 2 sequential applications unless otherwise 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 early entry to treated areas include: coveralls, chemical-resistant gloves 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, snap"), 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 analytical enforcement method, and supporting livestock analytical method ILV. 

No other revisions are made to HED's Aug 27, 2013 risk assessment for mandipropamid.

Appendix .  Toxicology Profile

Toxicology Data Requirements

Note:  This document is the same as D409101, (D. McNeilly, 10/31/13) except it was revised 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