Incident Report

Subform I: General Information

1. Report Type.

New incident report

Incident Report Number: 2018-0453

2. Registrant Information.

Registrant Reference Number: USA-BAYERBAH-2017-US0077186 (Report 463264)

Registrant Name (Full Legal Name no abbreviations): Bayer inc

Address: 2920 Matheson BLVD

City: Mississaugua

Prov / State: ON

Country: Canada

Postal Code: L5W5R6

3. Select the appropriate subform(s) for the incident.

Domestic Animal

4. Date registrant was first informed of the incident.

11-DEC-17

5. Location of incident.

Country: UNITED STATES

Prov / State: PENNSYLVANIA

6. Date incident was first observed.

09-DEC-17

Product Description

7. a) Provide the active ingredient and, if available, the registration number and product name (include all tank mixes). If the product is not registered provide a submission number.

Active(s)

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PMRA Registration No.       PMRA Submission No.       EPA Registration No. 11556-155

Product Name: Seresto Large Dog

• Active Ingredient(s)
  • FLUMETHRIN
  • IMIDACLOPRID
    • Guarantee/concentration 10 %

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7. b) Type of formulation.

Other (specify)

COLLAR

Application Information

8. Product was applied?

Yes

9. Application Rate.

1

Other Units: Collar

10. Site pesticide was applied to (select all that apply).

Site: Animal / Usage sur un animal domestique

11. Provide any additional information regarding application (how it was applied, amount applied, the size of the area treated etc).

On 07-Dec-2017, a 3 year old, 57.4 pound, intact, female, German Shepherd Dog canine, in unknown condition, with no known concomitant medical conditions, had 1 Seresto Large Dog (Flumethrin-Imidacloprid) collar placed around the neck by the owner.

To be determined by Registrant

12. In your opinion, was the product used according to the label instructions?

Yes

Subform III: Domestic Animal Incident Report

1. Source of Report

Animal's Owner

2. Type of animal affected

Dog / Chien

3. Breed

German Shepherd Dog

4. Number of animals affected

1

5. Sex

Female

6. Age (provide a range if necessary )

3

7. Weight (provide a range if necessary )

26.036

kg

8. Route(s) of exposure

Skin

9. What was the length of exposure?

>3 days <=1 wk / >3 jours <=1 sem

10. Time between exposure and onset of symptoms

>24 hrs <=3 days / >24 h <=3 jours

11. List all symptoms

System

• General
  • Symptom - Death

• Nervous and Muscular Systems
  • Symptom - Seizure

• Respiratory System
  • Symptom - Coughing

• Gastrointestinal System
  • Symptom - Foaming at mouth

• Nervous and Muscular Systems
  • Symptom - Other
  • Specify - Involuntary movement

• General
  • Symptom - Other
  • Specify - Abnormal necropsy finding

12. How long did the symptoms last?

>24 hrs <=3 days / >24 h <=3 jours

13. Was medical treatment provided? Provide details in question 17.

No

14. a) Was the animal hospitalized?

No

14. b) How long was the animal hospitalized?

15. Outcome of the incident

Died

16. How was the animal exposed?

Treatment / Traitement

17. Provide any additional details about the incident

(eg. description of the frequency and severity of the symptoms

On 09 Dec 2017, the dog's rear leg was observed to be moving abnormally and had a seizure, which resolved in approximately 5 minutes. On 10 Dec 2017, the dog was foaming at the mouth and coughing. On 11 Dec 2017, the dog was found deceased in the morning. A gross necropsy did not reveal any abnormalities, however the brain was not visualized and the heart was not evaluated. Follow up received on 28th Dec 2017: On 28-Dec-2017, the results of the histopathology report did not reveal any abnormalities or cause of death. A toxicology screen was negative as well and the heart was still being evaluated. Comments from pathologist: There are no significant changes, the congestion in various organs is likely related to agonal changes. The interlobular and periarterioloar hemorrhage are also likely agonal changes. A cause of death cannot be determined from the tissues submitted. The tissues did not include brain (history of seizures) or myocardium (acute, unexpected death). Follow up received on 09th Jan 2018: Comments from pathologist: There are no significant changes, the congestion in various organs is likely related to agonal changes. The interlobular and periarterioloar hemorrhage are also likely agonal changes. No pathologic diagnosis can be assigned to the myocardium. A cause of death cannot be determined from the tissues submitted. The tissues did not include the brain (history of seizures). No more information is expected; this case is closed.

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To be determined by Registrant

18. Severity classification (if there is more than 1 possible classification

Death

19. Provide supplemental information here

O-Unassessable: The product is not anticipated to cause serious neurological disorders such as seizures after appropriate topical product administration as the controlled release mechanism assures release of only low doses of active ingredient at a time. But seizures were reported in connection with product use in dogs and were requested by authorities to be content of the EU SPC. However, it is known that overdose of 5 collars around the neck of adult dogs for an 8 months period and in 7 week old puppies for a 6 months period did not cause serious signs. This is supported by the extremely low systemic exposure with imidacloprid and flumethrin, particularly during the first week after application. Even with oral product exposure, seizures are not seen. Merely gastrointestinal signs may occur. Any action or treatment may trigger seizures in an animal with a respective disposition. Various etiologies exist for seizure events or paroxysmal signs, e.g. heart disorder, development disorder, metabolic disorder, infection, intoxication, idiopathic epilepsy, trauma, neoplasms. Involuntary movement may be associated with reported seizures. Foaming at mouth and coughing are unspecific signs and may have numerous other causes. Further death is not expected following appropriate topical product application as inconsistent with products pharmacological profile. Product has wide margin of safety. No signs of anaphylaxis reported which would have occurred in close proximity to the collar application. Necropsy findings later revealed congestion in various organs, interlobular and periarterioloar hemorrhage which are likely agonal changes related to death. Cause of death could not be detected, unfortunately brain tissue was not evaluated. Time to onset is short for initial reported signs. Overall considering all aspects, a product involvement is remains unassessable.