EPA-PMRA-CDPR-Syngenta Meeting 

February 13, 2013

Thiamethoxam and Bee Health
2

EPA-PMRA-CDPR-Syngenta Meeting on Bee Health

● Syngenta recognizes the important role 

that pollinators play in agriculture and the 

serious challenges facing the global health 

of honey bees

● We wish to provide an update on the 

completed, current and planned research 

regarding the safety of thiamethoxam 

(TMX) to honey bees

● We would like to gain a better 

understanding on the future regulatory 

landscape and data requirements in 

support of a science-based regulatory 

process
3

Meeting Agenda

● Introduction

● SAP White Paper and Impact on Thiamethoxam Data Generation

- Toxicological data

- Residue data (pollen, nectar, other)

- Future plans in response to SAP White Paper

● Thiamethoxam Re-evaluation/Registration Review Discussion 

- Impact on current Conditions of Registrations, timelines, next steps

● Sustainability and Stewardship

● Q&A and Discussion
4

Current Data Requirements for Thiamethoxam

Canada:

- Plant fate study for the seed treatment use pattern 

- Plant fate study and a hive study for foliar and soil-applied products

USA:

- EPA: 

- Full field studies (including field residues) for seed treatment, foliar and 

soil uses

- California: 

- Nectar and pollen residue data in specific crops treated by soil or foliar 

application

- Toxicity study on honey bee larvae (completed)

Canada and USA:

- Data gaps identified by the registration review (EPA) and re-evaluation 

(PMRA) processes

● It is our understanding that these Conditions of Registration should be 

addressed in a tiered approach as outlined in the SAP White Paper
5

Global Research on Thiamethoxam

● Completed research available to 

evaluate the short- and long-term 

effects of TMX to honey bees under 

laboratory and field conditions

- Acute and chronic toxicity data

- Residue levels in pollen and nectar 

tested from various crops

- Multi-year (4 year) hive health studies 

with seed treatment exposure (corn, oil 

seed rape); accepted for publication

- Rotational residue study in pollen and 

nectar following seed treatment/soil 

use

- Monitoring programs (e.g. FR)
SAP White Paper and Impact on 

Thiamethoxam Data Generation
7

Toxicity of Thiamethoxam to Honey Bees

Study / Endpoint Value (TMX)

Adult (oral) LD50 0.005 μg ai/bee

Adult (contact) LD50 0.024 μg ai/bee

Adult 10-d chronic NOEC 32 μg ai/L

(0.00898 μg ai/bee)

Larval (oral) LC50 >113 μg ai/g diet
8

Understanding Exposure to Thiamethoxam

● Refinement of the Tier 1 exposure assessment through the use of 

pollen and nectar data from the treated crop (potential surrogate)

● Various residue studies were conducted to meet regulatory needs 

in other jurisdictions

● Future studies will involve crops selected based on the criteria 

below:

- Relevance to the agricultural landscape in North America

- Application rate

- Ability to surrogate to other crops or use patterns

- Attractiveness to honey bees

- Commercially pollinated

- Likelihood of exposure (e.g. timing of application relative to bloom)
9

North American Uses of Thiamethoxam

Bee attractive crops: Crops that 

are commercially pollinated and/or 

documented to consistently attract 

honey bees when flowering due to 

the production of nectar and/or 

preferred pollen

Foliar

• Cucurbit Vegetables

• Fruiting Vegetables

• Citrus

• Berries

• Cotton

• Pome Fruit

• Stone Fruit

• Tropical Fruit

• Tree Nuts

• Mint

• Legumes

• Brassica Vegetables

• Leafy Vegetables

• Root Vegetables

• Tuberous/Corm 

• Globe Artichoke

• Grapes

Soil

• Cucurbit Vegetables

• Fruiting Vegetables

• Citrus

• Berries

• Brassica Vegetables

• Leafy Vegetables

• Root Vegetables

• Tuberous/Corm

Seed Treatment

• Cucurbit Vegetables

• Cotton

• Canola

• Alfalfa

• Sunflower

• Brassica Vegetables

• Leafy Vegetables

• Root Vegetables

• Legumes

• Peanuts

• Cereals

• Corn

• Rice
10

Seed Treatment Uses – North America

Attractive to Bees

(In Scope)

• Cucurbit Vegetables

• Cotton

• Canola

• Sunflower

Not Attractive

(or Out of Scope)

• Brassica Vegetables

• Leafy Vegetables

• Root Vegetables

• Sugar Beets*

• Legumes

• Peanuts

• Cereals

• Corn

• Rice

• Alfalfa**

* Sugar beets: harvested prior to flowering

** Alfalfa: exposure to bees is mitigated by requiring the treated crop to be cut prior to 

first bloom
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Residue Data – Seed Treatment

Crop

US/CDN 

Max Rate 

mg ai/seed

Study Rate

mg ai/seed

Pollen Residue 

(ppb)

Nectar Residue 

(ppb) Study

Status

TMX 322704 TMX 322704

Cotton 0.375

0.245 <1 <1 <1 <1

Complete

0.208 <1 <1 <1 <1

Sunflowera 0.25 0.264 <1 – 4.4 <1 <1 <1

Corna 1.25 0.87 <1 – 12 <1 – 7 NA NA

Soybeansb 0.1512

0.1512 1.06 - 21.4b <1 - 4.82b

---

0.076 1.02 - 6.66b <1 - 0.87b

Oilseed rape Not registered 419 – 451 

g ai/100 kgc

<1 – 4

d <1 – 1 <0.5 – 7d <1 – 1

NA : Corn does not produce nectar

a Multiple studies conducted; trial with maximum residue levels reported in the table

b Reproductive structure analyzed as surrogate for nectar and pollen

c Multiple studies 

d Samples collected from foraging bees
12

Residue Data – Carry-Over to Flowering Crops from 

Treated Seed

Study Study Rate

Pollen Residue (ppb) Nectar Residue (ppb)

TMX 322704 TMX 322704

Treated corn planted (Spring 

2008) followed by treated barley 

(Fall 2008) followed by untreated 

alfalfa, OSR and Phacelia (2009)

(collected from forager bees)

Corn:

287 ai/100 kg

(75 g ai/ha)

Barley:

70 g ai/100 kg

(72 g ai/ha)

Alfalfa:

51

OSR:

<1 – 1

Phacelia:

<1 – 39

Alfalfa:

2

OSR:

<1 – 3

Phacelia:

<1 – 2 

Alfalfa:

<0.5 – 0.6

OSR:

<0.5 – 2.2

Phacelia:

<0.5

Alfalfa:

<1

OSR:

<1

Phacelia

<1 – 1
13

Seed Treatment – Residue Summary

● Current nectar and pollen residue 

data cover all bee relevant crops 

identified except for cucurbits

● Syngenta believes that residue data 

from the major crops grown in North 

America supports the use of TMX 

as a seed treatment

● What are the Agency’s position on 

the extrapolation of these data to 

support the use of TMX on cucurbit 

vegetables?

Attractive to Bees

(In Scope)

• Cucurbit 

Vegetables

• Cotton

• Canola

• Sunflower

Not Attractive

(or Out of Scope)

• Brassica 

Vegetables

• Leafy Vegetables

• Root Vegetables

• Sugar Beets*

• Legumes

• Peanuts

• Cereals

• Corn

• Rice

• Alfalfa**

* Sugar beets: harvested 

prior to flowering

** Alfalfa: exposure to bees is 

mitigated by requiring the 

treated crop to be cut prior to 

first bloom
14

Foliar Uses – North America

Attractive to Bees

(In Scope)

• Cucurbit Vegetables

• Fruiting Vegetables

• Citrus

• Berries

• Cotton

• Pome Fruit

• Stone Fruit

• Tropical Fruit

• Tree Nuts

Not Attractive

(or Out of Scope)

• Brassica Vegetables

• Leafy Vegetables

• Root Vegetables

• Tuberous/Corm 

• Legumes

• Globe Artichoke

• Grapes

• Mint*

* Mint is typically harvested prior to bloom for optimal oil production
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Residue Data – Foliar Application

Crop

Max Rate

lbs ai/A

(g ai/ha)

Study Rate

lbs ai/A

(g ai/ha)

Study

Application 

Timing

Pollen Residue 

(ppb)

Nectar Residue 

(ppb) Study

Status

TMX 322704 TMX 322704

Peach 0.172 

(193.3)

0.056 x 1 

(62.9 x 1)

Pre-bloom

(6 days) <5 <5 <5 <5 Complete
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Residue Data – Foliar (Continuously Flowering Crops)

Crop

Study/Max

Rate

lbs ai/A

(g ai/ha)

Pollen Residue 

(ppb)

Nectar Residue 

(ppb) Status

TMX 322704 TMX 322704

Melon (Italy) 0.089 

(100)

39a <5a <1 - 8

a <1a

Complete

- - 8 - 16b <1b

aApplication made 10-d prior to bloom

b Application made 5-d prior to bloom
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Foliar – Residue Summary

- The use of peach (pre-bloom) and stone 

fruit (post-bloom) studies as a surrogate 

for citrus, pome, and tropical fruit

- The use of strawberry data as surrogate 

for other berry crops (e.g. cranberries, 

blueberries, etc.)

- The use of almond data (if conducted) 

as surrogate for all tree nuts

● Syngenta plans to conduct a residue 

study with a cucurbit vegetable to match 

the North American use pattern

- Can data from cucurbit vegetable study

be used as surrogate for fruiting 

vegetables?

Attractive to Bees

(In Scope)

• Cucurbit Vegetables

• Fruiting Vegetables

• Citrus

• Berries

• Cotton

• Pome Fruit

• Stone Fruit

• Tropical Fruit

• Tree Nuts

Not Attractive

(or Out of Scope)

• Brassica Vegetables

• Leafy Vegetables

• Root Vegetables

• Tuberous/Corm 

• Legumes

• Globe Artichoke

• Grapes

• Mint*

● Pollen and nectar residue data will be available for stone fruit, cotton, cucurbit 

vegetables, strawberries and potentially almonds

● What are the Agency’s positions on surrogating residue data among similar 

crops or use patterns? For example:
18

Soil Uses – North America

Attractive to Bees

(In Scope)

• Cucurbit Vegetables

• Fruiting Vegetables

• Citrus

• Berries (e.g. 

strawberries)

Not Attractive

(or Out of Scope)

• Brassica Vegetables

• Leafy Vegetables

• Root Vegetables

• Tuberous/Corm
19

Residue Data – Soil Application

Crop

Max Rate 

lbs ai/A

(g ai/ha)

Study Rate

lbs ai/A

(g ai/ha)

Pollen Residue 

(ppb)

Nectar Residue 

(ppb) Study

Status

TMX 322704 TMX 322704

Cucurbits 

(Cucumber)

0.172 

(192)

0.172 

(192) 1.29 - 8.22 0.23 - 2.58 1.26 -11.48 <1 -1.75

Complete

Tomatoa

0.172 

(192)

0.172 

(192) 2.2 - 45.7a 13.2 - 80.2a

---

a Whole flower analyzed as surrogate for nectar and pollen
20

Soil – Residue Summary

● Pollen and nectar data are available for cucurbit vegetables 

and will be available for citrus in 2013

- Can cucurbit vegetable data be used as surrogate for fruiting 

vegetables and strawberries?

Attractive to Bees

(In Scope)

• Cucurbit Vegetables

• Fruiting Vegetables

• Citrus

• Berries

Not Attractive

(or Out of Scope)

• Brassica Vegetables

• Leafy Vegetables

• Root Vegetables

• Tuberous/Corm
21

Risk Assessment – Soil Use (Cucumber)

● Tier I – Use of measured residues

Assessment

Nectar 

Residue

(μg ai/L)

Feeding Rate

(mg food/bee)

Dose-based 

EEC 

(μg ai/bee)

Toxicity

Endpoint 

(μg ai/bee)

RQ

Adult Acute

TMX 10.58a 292 0.0034 0.005 0.62

TMX+322704 12.55a,b 292 0.0037 0.005 0.73

Adult Chronic

TMX 10.58a 292 0.0034 0.00898 0.34

TMX+322704 12.55a,b 292 0.0037 0.00898 0.41

Larval Acute

TMX 10.58a 120 0.0014 13.56c <0.01

TMX+322704 12.55a,b 120 0.0015 13.56c <0.01

Acute LOC = 0.4; Chronic LOC = 1.0

a 95th percentile value (n=9)

b TMX + 322704 = TMX (ppb) + 322704 (ppb) x 1.165; 1.165 = TMX MW (291.02) / 322704 MW (249.8)

c Conversion of LC50 (113 mg/kg) to a dose estimate per bee by multiply by the larval feeding rate (120 mg 

food/bee)
22

Risk Assessment – Tier II Refinement

● Exceeding the acute LOC of 0.4 would trigger a Tier II study for 

further refinement of the risk assessment

● If a semi-field study (tunnel study) is conducted with cucumber, 

can this study be used to support all soil uses?

● If multiple crops are identified as needing Tier II studies to refine 

the risk assessment, can a hive feeding study be used to 

establish a hive-level NOEC that could be used to compare with 

pollen and nectar residues for all crops and uses?
Thiamethoxam Re-evaluation/

Re-registration 
24

Q&A – Open Discussion

● Will the current conditions of registration change to reflect the 

SAP White Paper process? 

- Example: A hive health study has been required before the 

completion of tier 1 residue data

● We understand the DCI will be issued by the end of February 

2013. What are the other milestones for the EPA/PMRA joint 

thiamethoxam registration review / re-evaluation?

- How will the Agencies collaborate?

- When will Syngenta Canada receive the PMRA request for submitted, 

underway and planned studies?
25

Q&A – Open Discussion

● Syngenta is committed to addressing the conditions of 

registration; however, higher tiered data may not be completed 

within the 24 month timeline outlined in the EPA work plan. What 

recommendations do the Agencies have based on the following 

timeline proposal:

- 2013 – 2014: Pollen and nectar residue

- 2013 – 2015: Tier II studies (as required)

- 2016 – 2017: Full field study (if triggered)

● What regulatory implications do the Agencies see from the recent 

EFSA report?
Sustainability and 

Stewardship
27

Syngenta Activities Related to Pollinator Health

● Syngenta is actively promoting the link 

between pollinator health and sustainable 

agriculture

● Increasing the awareness of bee health 

issues

- www.plightofthebees.com

● Encouraging biodiversity at the farm level

- Operation Pollinator

- 3

rd year of academic research on the benefit 

(yield) to crops adjacent to pollinator habitats

- Scoping additional opportunities with third 

parties

- Fondation de la Faune (trial project underway)

- Others
28

Pollinator Health Activities (cont’d)

● Ongoing varroacide evaluation projects

● Epidemiological review of bee health in 

Europe 

- Lead: J. Cresswell, Exeter University (UK)

● Bee health model in development that 

integrates internal hive factors (e.g. Varroa, 

disease) with external stressors (e.g. forage 

availability)

- In collaboration with: Rothamsted Research 

(J. Osborne, M. Belcher), Warwick Univ. (D. 

Chandler), Helmholtz UFZ (V. Grimm)

- Several publications in various stage of 

preparation (in review or draft)
29

Stewardship – Initial Focus on Seed Treatment

● Internal activities and collaborative projects 

underway:

- Seed treatment quality, formulation design and 

application technology

- Promotion of “best practices”

- Syngenta and CLC ST Certification Programs 

- ASTA/CLA collaborations

- Communication of Best Management Practices 

(e.g. CLC/CLA, ASTA, GFO, grower meetings, 

etc.)

- Corn Dust Research Consortium through 

Pollinator Partnerships

- A multi-stakeholder initiative to investigate ways to 

reduce honey bee exposure to dust during planting 

of treated corn seeds
30