Incident Report

Subform I: General Information

1. Report Type.

New incident report

Incident Report Number: 2018-6467

2. Registrant Information.

Registrant Reference Number: USA-BAYERBAH-2018-US0061015 (Report 527711)

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.

16-OCT-18

5. Location of incident.

Country: UNITED STATES

Prov / State: PENNSYLVANIA

6. Date incident was first observed.

04-OCT-18

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. 27585      PMRA Submission No.       EPA Registration No.

Product Name: advantageII 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).

On 04Oct2018, a 3.1 kg, feline, at 18 months of age and having fleas, was administered 1 tube of Advantage II Small Cat (Imidacloprid-Pyriproxyfen) topically by the owner. Immediately post Advantage II application, the feline exhibited mydriasis and hyperactivity. On 05Oct2018, the feline exhibited application site alopecia and application site bleeding. On 06Oct2018, the owner consulted a veterinarian and bathed the feline with a liquid dish soap as instructed. The feline was not examined.

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

Medical Professional

2. Type of animal affected

Cat / Chat

3. Breed

crossbred

4. Number of animals affected

1

5. Sex

Female

6. Age (provide a range if necessary )

1.5

7. Weight (provide a range if necessary )

3.175

kg

8. Route(s) of exposure

Skin

9. What was the length of exposure?

>1 wk <=1 mo / > 1 sem < = 1 mois

10. Time between exposure and onset of symptoms

<=30 min / <=30 min

11. List all symptoms

System

• Eye
  • Symptom - Pupil dilation

• General
  • Symptom - Hyperactivity

• Skin
  • Symptom - Hair loss
  • Symptom - Bleeding
  • Symptom - Other
  • Specify - Necrosis - Post necrospy finding

• Cardiovascular System
  • Symptom - Other
  • Specify - Myocarditis

• Blood
  • Symptom - Other
  • Specify - Abnormal test result

• General
  • Symptom - Death

12. How long did the symptoms last?

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

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 06Oct2018, the owner consulted a veterinarian and bathed the feline with a liquid dish soap as instructed. The feline was not examined. On 09Oct2018, the feline died. A necropsy examination was performed; the results were unknown. On 09Oct2018, the feline died. On 10 Oct 2018, the cat's remains were taken to another veterinary hospital. At that location, blood was removed from the remains 28 hours after death and a Chemistry panel, FeLV/FIV HW Snap test and SDMA tests were performed. Results indicated that the cat was positive for feline leukemia virus. Abnormal blood results included Glucose 338, (74-159 mg/dL), Phosphorus > 16 mg/dL, (3.1-7.6), Albumin 4.7, (2.2-4.0 g/dL), Lipase 4209, (100-1400 U/L), and SDMA 28 (0-14 ug/dL). There was no evidence of kidney disease, BUN and Creatinine were normal, and specific gravity was 1.045. A urinalysis was performed and the results were normal. Radiographs were taken, but results are unknown. A necropsy with tissue histology was performed. At the application site, there was a half inch diameter full thickness coagulative necrosis affecting the epidermis, follicular epithelium and dermal collagen. The heart had mild multifocal chronic lymphoplasmacytic and fibrosing myocarditis. The chronicity of these lesions were felt to be consistent with a potential cause of death in the patient. Other changes noted in the necropsy were thought to be due to autolytic changes associated with death.

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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

Advantage: O - Unclassifiable/unassessable Neurological sign of mydriasis and behavioural disorder of hyperactivity are unspecific and not expected with appropriate topical product use. No oral product exposure witnessed. In individual cases, dermal reaction like alopecia at the application site is possible in animals that are particular sensitive. However reported application site bleeding later of necrosis are not expected. Self-trauma or secondary bacterial infection may have aggravated the signs. Later reported death as well as later revealed severe necropsy signs of cardiovascular disorder of fibrosing myocarditis, elevated levels of glucose, phosphorus, albumin, lipase, and symmetric dimethylarginine are not expected after product application, as inconsistent with pharmaco-toxicological product profile. Product has wide margin of safety. The oral LD50 in rat is 642 mg/kg BW. 24-fold over dosage tolerated by cats without showing any side effect. Time to onset is short for initially reported signs, but long for later reported death and revealed necropsy signs. Other causes must be considered. Overall, a product relation is considered unassessable.