Incident Report

Subform I: General Information

1. Report Type.

New incident report

Incident Report Number: 2017-5041

2. Registrant Information.

Registrant Reference Number: USA-BAYERBAH-2017-US0038606

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

Address: 2920 Matheson Blvd

City: Mississaugua

Prov / State: ON

Country: Canada

Postal Code: L4W 5R6

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

Domestic Animal

4. Date registrant was first informed of the incident.

11-JUL-17

5. Location of incident.

Country: UNITED STATES

Prov / State: KENTUCKY

6. Date incident was first observed.

Unknown

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. 11556-127

Product Name: advantage II large dog

• Active Ingredient(s)
  • IMIDACLOPRID
    • Guarantee/concentration 9.1 %
  • PYRIPROXYFEN
    • Guarantee/concentration .46 %

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7. b) Type of formulation.

Application Information

8. Product was applied?

Yes

9. Application Rate.

2.5

Units: mL

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).

1 tube of Advantage II Large Dog (Imidacloprid-Pyriproxyfen) topically

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

Labrador Retriever

4. Number of animals affected

1

5. Sex

Female

6. Age (provide a range if necessary )

16

7. Weight (provide a range if necessary )

28.123

kg

8. Route(s) of exposure

Skin

9. What was the length of exposure?

Unknown / Inconnu

10. Time between exposure and onset of symptoms

>2 hrs <=8 hrs / > 2 h < = 8 h

11. List all symptoms

System

• Nervous and Muscular Systems
  • Symptom - Seizure

• Blood
  • Symptom - Other
  • Specify - Splenic neoplasm

• General
  • Symptom - Death
  • Symptom - Other
  • Specify - Abnormal radiograph finding
  • Symptom - Other
  • Specify - Abnormal ultrasound finding

12. How long did the symptoms last?

Persisted until death

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

Yes

14. a) Was the animal hospitalized?

Unknown

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 approximately 2013, a 16 year old, 62 pound, neutered, female, Retriever (Labrador, Black) canine, in unknown condition, with the concomitant medical condition of a history of seizures, was administered 1 tube of Advantage II Large Dog (Imidacloprid-Pyriproxyfen) topically by the owner. Approximately 2 hours post application, the dog had a seizure for 1 minute and resolved. On an unknown date in 2013, the dog was examined by a veterinarian and an ultrasound and radiographs were performed with abnormal findings. The dog was diagnosed with splenic neoplasm. On an unknown date in 2013, the dog was examined by a holistic veterinarian and was administered an unspecified chinese herbal medication by mouth daily. On an unknown date in 2013, the dog died. No necropsy was performed. Due to the sensitive nature of the communication, specific relevant event details were not obtained, nor will such be sought. The reason for the initial call was to discuss use of the product not to report the death in this event. No more information is expected. This case is closed. Note: Previous exposure was well tolerated.

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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

N - Unlikely Reported seizure is not anticipated with topical administration of Advantage II. From a toxicological point of view, neither imidacloprid nor pyriproxyfen does have the potential to provoke seizures in vertebrates. In case of oral ingestion of a considerable amount of product or after administration of an overdose shortly after product application, neurological symptoms such as tremor, ataxia, depression, miosis or mydriasis may occur. The animal in this case had concomitant condition of seizures which may have contributed to the sign. Later revealed abnormal radiograph finding, abnormal ultrasound findings, diagnosed splenic neoplasm and reported death is not expected after topical product application and is inconsistent with the pharmaco-toxicological product profile. Product has wide margin of safety. The oral LD50 in rat is 642 mg/kg BW. 20-fold overdosage tolerated by dogs without showing any side effect. The product has no carcinogen potential. The cause of death may be diagnosed splenic neoplasia and old age of the animal. In case of suspected product involvement, adverse event would have been reported in close proximity and not long time after (approximately 4 years). Moreover, the information regarding the death of the dog was casually provided during an inquiry. Time to onset is short for seizure and unknown for later reported signs. Also the previous exposure was well tolerated. Although no necropsy performed, product involvement is considered unlikely.