Incident Report

Subform I: General Information

1. Report Type.

New incident report

Incident Report Number: 2016-0708

2. Registrant Information.

Registrant Reference Number: 2015KP343

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.

06-JAN-16

5. Location of incident.

Country: UNITED STATES

Prov / State: UNKNOWN

6. Date incident was first observed.

15-NOV-09

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)

---

PMRA Registration No.       PMRA Submission No.       EPA Registration No. 11556-125

Product Name: advantage II medium dog

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

---

7. b) Type of formulation.

Liquid

Application Information

8. Product was applied?

Yes

9. Application Rate.

1

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 approximately 01-Nov-2009, a 6 year old, 20 pound,neutered female, Schnauzer (Miniature) canine, in good condition, with no known concomitant medical conditions, was administered 1 tube of Advantage 20 Topical Solution(Imidacloprid) 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

Other

2. Type of animal affected

Dog / Chien

3. Breed

Miniature Schnauzer

4. Number of animals affected

1

5. Sex

Female

6. Age (provide a range if necessary )

6

7. Weight (provide a range if necessary )

20

lbs

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

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

11. List all symptoms

System

• General
  • Symptom - Death
  • Symptom - Other
  • Specify - Abnormal Test Results

• Renal System
  • Symptom - Other
  • Specify - Urinary Tract Disorder - Urolithiasis

• Nervous and Muscular Systems
  • Symptom - Convulsions
  • Symptom - Seizure

• Renal System
  • Symptom - Inappropriate urination

• General
  • Symptom - Abnormal behaviour

• Gastrointestinal System
  • Symptom - Inappropriate defecation

• Cardiovascular System
  • Symptom - Heart murmur

• Gastrointestinal System
  • Symptom - Diarrhea
  • Symptom - Other
  • Specify - Pancreatitis
  • Symptom - Bloody diarrhea

12. How long did the symptoms last?

Unknown / Inconnu

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 15 Nov 2009 the dog developed bloody diarrhea. The attending veterinarian stated the dog had pancreatitis from a recent food change. It is not known if any treatments were performed. The diarrhea resolved within 2 days. On approximately 01 Feb 2010 the dog had a subsequent product application of Advantage 20. On approximately 20 Feb 2010 the dog was seen by the attending veterinarian and diagnosed with uroliths. The dog was anesthetized with an unspecified anesthetic and the uroliths were surgically removed. On an unknown date in 2012, the dog had another surgery to remove more uroliths. On 01 Oct 2013, the dog had 1 tube of Advantage II Medium Dog (imidacloprid-pyriproxyfen)applied topically by the owner. In Aug 2014 the dog began having seizures. In Sept 2014, the dog developed a behavioral change. In Nov 2014, the dog began to inappropriately urinate and defecate. The dog was seen by the attending veterinarian. Bloodwork was performed and revealed elevated triglycerides. The dog was also diagnosed with a heart murmur. An unspecified dewormer, probiotic, and heart medication were prescribed. In April 2015, the dog developed watery diarrhea. In May 2015, the dog was found deceased. No necropsy was performed. The purpose of the call to Bayer Animal Health was not to report the death of this dog but to inquire about the use of Advantage II Medium Dog on another dog in the home. No more information is expected. Case is closed.

---

To be determined by Registrant

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

Death

19. Provide supplemental information here

Reported signs bloody diarrhea, pancreatitis and later diagnosed uroliths are not related with product as signs occurred before product application. Seizures and heart murmur are also not anticipated with topical use of product as not consistent with its pharmacological/toxicological product profile. Other reported signs, abnormal blood parameter, behavioural signs and watery diarrhea are unspecific and may have various other causes. Death not expected after product application, as inconsistent with pharmaco-toxicological product profile. Product has wide margin of safety. Oral LD50 in rat 642 mg/kg BW. 20-fold over dosage tolerated by dogs without showing any side effect. Dog involved in this case was geriatric, which may have caused death of the animal. Time to onset is exceptionally long (10 months after last application). The purpose of the call to Bayer Animal Health was not to report the death of this dog but to inquire about the use of Advantage II Medium Dog on another dog in the home. Although no necropsy was performed, overall, a product relation considered as unlikely.