Incident Report

Subform I: General Information

1. Report Type.

New incident report

Incident Report Number: 2017-3268

2. Registrant Information.

Registrant Reference Number: USA-BAYERBAH-2015-US0061956

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.

01-JUN-17

5. Location of incident.

Country: UNITED STATES

Prov / State: GEORGIA

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. 11556-151

Product Name: Advantage II small cat

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

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7. b) Type of formulation.

Liquid

Application Information

8. Product was applied?

Yes

9. Application Rate.

.4

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/Pipette 1 Days 1 Dose 1 tube of Advantage II Small Cat (Imidacloprid-Pyriproxyfen) was administered topically 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

Female

6. Age (provide a range if necessary )

9

7. Weight (provide a range if necessary )

3.18

kg

8. Route(s) of exposure

Skin

9. What was the length of exposure?

Unknown / Inconnu

10. Time between exposure and onset of symptoms

Unknown / Inconnu

11. List all symptoms

System

• General
  • Symptom - Vocalizing

• Gastrointestinal System
  • Symptom - Salivating excessively

• General
  • Symptom - Other
  • Specify - Behavioural disorder NOS
  • Symptom - Other
  • Specify - Inappropriate urination

• Blood
  • Symptom - Anemia
  • Symptom - Hypocalcemia

• Nervous and Muscular Systems
  • Symptom - Seizure
  • Specify - Tonic seizure

• General
  • Symptom - Death

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?

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 approximately 4-Nov-2015, a 9 year old, 7 pound, neutered, female, Domestic Shorthair feline, in fair condition with a concomitant medical condition of fleas, was administered 1 tube of Advantage II Small Cat (Imidacloprid-Pyriproxyfen) topically by the owner. On an unspecified date post application, in approximately Nov 2015, the cat exhibited a behavior change. The cat was examined by a veterinarian and a blood profile showed low calcium level and anemia. On 4-Dec-2015, the product was reapplied. On 4-Dec-2015, approximately 6 hours post application, the cat was vocalizing, hypersalivating, kicking her hind legs (behavioral disorder NOS), and urinated on the couch (inappropriate urination). The cat was bathed in an unspecified type of liquid dish soap. On 6-Dec-2015 the cat started having seizures and died at home. A necropsy was not performed. Follow up received on 3rd Dec 2015: No further information is expected. 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

N - Unlikely Reported behavioural change is unspecific and may have various other causes. Low calcium level and anemia are not expcted after product application as signs are not in line with pharmaco toxicological product profile. Time to onset is unknown in this case. Later observed behavioural signs may have occurred due to product sensation or smell. Time to onset is short. Hypersalivation after suspected ingestion of product. Sign is consistent with distaste reaction. Serious nervous system disorders such as seizures are 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. Death is also not expected after product application, as inconsistent with pharmacotoxicological product profile. Product has wide margin of safety. Oral LD50 in rat 642 mg/kg BW. 24-fold overdosage tolerated by cats without showing any side effect. Animal involved in this case was in fair condition. Though later reported behavioural signs are deemed to be product related, the more severe signs seizure and death are considered not product related, a product relation deemed to be unlikely.