Mandipropamid Human Health Risk Assessment D416292

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UNITED STATES ENVIRONMENTAL PROTECTION AGENCY

WASHINGTON, D.C. 20460

OFFICE OF

CHEMICAL SAFETY AND

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 
Mandipropamid Human Health Risk Assessment D416292

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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.
Mandipropamid Human Health Risk Assessment D416292

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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 
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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.
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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.
Mandipropamid Human Health Risk Assessment D416292

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Table 3.2. Summary of Proposed Directions for Use of Mandipropamid. 

Application Type; 

Equipment1

Use 

Rate

(lb ai/A)

Max. Uses 

Per Season

Max. Seasonal 

Use Rate

(lb ai/A)

PHI2

(Days)

Use Directions, Application Timing, 

and Limitations3

Basil

Foliar; any ground 

or aerial equipment.

0.09 -

0.13

4 0.52 1 RTI4of 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, chemicalresistant 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.
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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