Incident Report

Subform I: General Information

1. Report Type.

New incident report

Incident Report Number: 2019-3164

2. Registrant Information.

Registrant Reference Number: USA-BAYERBAH-2019-US0025811 (Report 567453)

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.

28-MAY-19

5. Location of incident.

Country: UNITED STATES

Prov / State: GEORGIA

6. Date incident was first observed.

27-MAY-19

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. 11556-152

Product Name: Advantage II Large Cat (Imidacloprid-Pyriproxyfen)

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

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7. b) Type of formulation.

Other (specify)

spot on

Application Information

8. Product was applied?

Yes

9. Application Rate.

.8

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).

On 27-May-2019, a 2 year old, 10 pound, neutered, male, Domestic Shorthair cat, in unknown condition, with the concomitant medical condition of lethargy, was bathed with a flea shampoo and then was administered 1 tube of Advantage II Large Cat (Imidacloprid-Pyriproxyfen) via the topical route 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

Cat / Chat

3. Breed

Domestic Shorthair

4. Number of animals affected

1

5. Sex

Male

6. Age (provide a range if necessary )

2

7. Weight (provide a range if necessary )

4.536

kg

8. Route(s) of exposure

Skin

9. What was the length of exposure?

>8 hrs <= 24 hrs / >8 h <= 24 h

10. Time between exposure and onset of symptoms

<=30 min / <=30 min

11. List all symptoms

System

• Nervous and Muscular Systems
  • Symptom - Other
  • Specify - Mental impairment NOS

• General
  • Symptom - Hypothermia

• Nervous and Muscular Systems
  • Symptom - Other
  • Specify - Depressed reflexes]

• Respiratory System
  • Symptom - Tachypnea

• General
  • Symptom - Pale mucous membrane colour

• Eye
  • Symptom - Miosis

• Nervous and Muscular Systems
  • Symptom - Seizure

• Respiratory System
  • Symptom - Dyspnea

• Gastrointestinal System
  • Symptom - Salivating excessively

• General
  • Symptom - Vocalizing

• Gastrointestinal System
  • Symptom - Vomiting
  • Symptom - Diarrhea
  • Symptom - Inappropriate defecation
  • Symptom - Weight loss

• General
  • Symptom - Death

• Respiratory System
  • Symptom - Shortness of breath

• General
  • Symptom - Hesitancy to move
  • Specify - Reluctant to move]

• Nervous and Muscular Systems
  • Symptom - Muscle trembling

• Skin
  • Symptom - Erythema

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?

Yes

14. b) How long was the animal hospitalized?

Unknown

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

Approximately 10 minutes post application, the cat developed hypersalivation. Approximately 12 hours post product application, the cat developed vocalization, intermittent vomiting, diarrhea and inappropriate defecation. The owner bathed the cat with liquid dish soap. On 28-May-2019, the cat was examined by a veterinarian and exhibited weight loss to 9 pounds, shallow breathing, relunctance to move, was mentally obtunded and was vocalizing. The cat was hypothermic with a temperature of 92 degrees Fahrenheit, and reflexes were absent. The cat had a an increased respiratory rate 50 breaths per minute, pale mucous membranes and the pupils were miotic but responsive. Feline leukemia virus and feline immunodeficiency virus tests were performed and were negative. Additional unspecified bloodwork was performed with unknown results. The cat was treated with lactated ringers solution at a rate of 20 ml per hour intravenously, buprenorphine 0.01 ml intramuscularly, cefovecin sodium 0.25 ml subcutaneously, and lactated ringers solution 150 ml subcutaneously. The respiratory rate increased to 56 breaths per minute, the fluid rate was decreased to 15 ml per hour and the cat was administered oxygen therapy. The cat exhibited seizures and agonal breathing (abnormal breathing). The cat was treated with diazepam 0.15 ml intravenously and epinephrine 0.3 ml via the intravenous route by the veterinarian. Cardiopulmonary resuscitation was performed but was unsuccessful and the cat died. No necropsy was performed. Follow up received on 31st May 2019: Approximately 12 hours post product application, the cat developed vocalization, intermittent vomiting, diarrhea and inappropriate defecation. Tremors occurred an unspecified time post application. The owner bathed the cat with liquid dish soap. On 28-May-2019, the cat was examined by a veterinarian and exhibited weight loss to 9 pounds, shallow breathing, relunctance to move, application site erythema, was mentally obtunded and was vocalizing.

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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 - Unclassifiable/unassessable Reported digestive disorders are unspecific and may have many potential causes. Signs are not expected after topical product use and oral product uptake was not witnessed. Vocalisation and reluctant to move are unspecific and may have various other causes. Animal had concomitant condition of lethargy. Reported tremor is not expected with appropriate topical product use. No oral product exposure witnessed. Further reported weight loss, pale mucous membrane, hypothermia, tachypnea, shallow breathing are not expected either. Weight loss is rather suggestive of a more chronic underlying pathology. In individual cases, dermal reaction such as erythema at the application site is possible in animals that are particular sensitive. Constricted pupils, depressed reflexes and mental impairment are not expected and may be associated with seizures. Serious nervous system disorder such as 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. But seizures are not expected. Abnormal breathing is likely associated with seizure. Death is inconsistent with pharmaco-toxicological product profile and experience. Product has wide margin of safety. Oral LD50 in rat is 642 mg/kg BW. 24-fold overdosage tolerated by cats without showing any side effect. Though time to onset is consistent, considering overall aspects, a product relation for the case is unassessable.