paraquat toxicity

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PARAQUAT TOXICITY Katie Krimetz Western University of Health Sciences CVM DVM 2010 September 8, 2008

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Sept 2008 - My elected 3rd Year Prestation; reviews paraquat toxicity in dogs

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Page 1: Paraquat Toxicity

PARAQUAT TOXICITY

Katie Krimetz

Western University of Health SciencesCVM DVM 2010

September 8, 2008

Page 2: Paraquat Toxicity

Headlines

July 2003 – Laurelhurst Park, Portland, OR(11)

August 2004 – Willamette Park, Portland, OR(11)

Images: http://www.aspca.org/site/DocServer/vetm0904_755-762.pdf?docID=5581&AddInterest=1101

Page 3: Paraquat Toxicity

WHY CAN’T WE FIX THIS?

HOW DO I RECOGNIZE/DIFFERENTIATE CLINICAL SIGNS?

Page 4: Paraquat Toxicity

1,1’-dimethyl-4,4’-bipyridylium Uses

Non-selective contact herbicide Allowed no-till farming

Sources Restricted Use

Pesticide CommercialApplicator License(13)

Today products have <0.44% paraquat(4)

Older products with 50% paraquatcan be found(4)

Protective Measures Emetics, Bitters, Odor, Color

Image: http://agri.astate.edu/weeds/select_images.html

Page 5: Paraquat Toxicity

Toxicity Exposure(4,5)

Ingestion Absorption at brush border Primarily absorbed in the jejunum

Skin – blisters, burns, nail damage Eyes – stinging sensation, inflammation, corneal ulcer Inhalation – nausea, headache, epistaxis

Toxic Levels(4)

Oral LD50 – dogs: unknown

cats: 30-50 mg/kg I.V.

LD50 – dogs: 7.48 mg/kg cats: ??

Image: http://www.broyhill.com/images/interior/safety.gif

Page 6: Paraquat Toxicity

Mechanism of Toxicity

Paraquat is taken up actively and selectively Polyamine transporter(4,15)

Required for maintenance of high metabolic activity levels

Cells depend on them for growth, renewal and metabolism

Type I and II Alveolar cells most commonly affected by toxicity(4)

Damage mostly confined to areas with high accumulations of paraquat

Page 7: Paraquat Toxicity

Mechanism of Toxicity Absorbed portion accumulates in tissues Cyclic oxidation-reduction rxns free

radicals Oxygen and hydroxyl

Free radicals overwhelm cellular defense Cause damage to tissues, esp membrane

lipids

Image: http://www.syngenta.com/pqmedguide/downloads/paraquat_booklet.pdf

Page 8: Paraquat Toxicity

Clinical Signs & Pathophysiology

GI upset and vomiting present at all levels of toxicity Remember: emetics

added to formulation “Early” Signs:

Compromised renal function Mild hypertension Pulmonary alveolar damage

Edema Hemorrhage

Inevitable: Death by respiratory failure

Image: 2007 MS ClipArt

Page 9: Paraquat Toxicity

Clinical Signs & Pathophysiology

“Moderate” dose (>20-30mg/kg but <40-50mg/kg)(5)

Immediately: vomiting Hours: diarrhea, abd pain, throat/mouth ulcerations 1-4 d: renal failure, hepatic fxn impaired,

tachycardia 1-2 wk: cough, hemoptysis, pleural effusion,

pulmonary fibrosis

“High” dose (>40-50 mg/kg) (Systemic poisoning) (5)

Immediately: vomiting Hours-days: Acute pulmonary edema, renal failure,

hepatocellular damage, intra/extrahepatic bile duct and gall bladder necrosis, adrenal failure

Page 10: Paraquat Toxicity

Diagnosis

Histologic examination of tissues (lungs!)(4,5,6)

Spectrophotometry, gas/liquid chromatography(4,5)

HPLC Fluorescense(5)

Radioimmunoassay(4)

Dithionite reaction/dithionite spot test(4,5)

Solid Phase Extraction(5)

Elevated Serum Lipase(4)

Radiographs?(4)Image: http://picasaweb.google.com/aluapa/PathGallery/photo#5102345173274680146

Page 11: Paraquat Toxicity

[Realistic] Diagnosis Histologic examination of tissues Dithionite reaction/dithionite spot

test Elevated Serum Lipase Radiographs

CAUTION – Misdiagnoses/Complications Ingestion of unknown food Vomiting may be only clinical sign Serum lipase – ddx: pancreatitis Radiographs – usually appreciate

abnormalities in late stage of toxicity

Images: http://www.achilles-online.com

Page 12: Paraquat Toxicity

Treatment EARLY! Within hours in order to be effective

Adsorbent(4)

Fullers Earth, Activated Charcoal (rodent - add Mg citrate!) (4)

ER? Kitty litter Caution with esophageal tubes

Remove it(4)

Emesis – but then control Gastric lavage

Fluids/Forced Diuresis(4,5)

Analgesics – opiates best(5)

NO OXYGEN!(4,5)

Nitrous Oxide improves gas exchange

Page 13: Paraquat Toxicity

Treatment in Research

Taurine @CRI, followed by hemodialysis(8)

Antioxidants(4,5)

N-acetyl cysteine(5)

Desferriozamine(5)

Propanolol(5)

Collagen synthesisinhibitor(4)

Radiotherapy(5)

Lung Transplant(5)

Page 14: Paraquat Toxicity

Prognosis

Prognosis – Grave

Depends on circumstance of poisoning:

Good circumstances: inhalation, skin exposure, dilute formula

Bad circumstances: ingestion

Image: http://www.syngenta.com/pqmedguide/downloads/paraquat_booklet.pdf

Page 15: Paraquat Toxicity

Prognosis

Indicators of a better prognosis:

•Young Age•Recent Last meal/size•Accidental Ingestion

•Lack of lesions

•Lack of:Renal, hepatic, pancreatic,

or respiratory failureImage: http://farm1.static.flickr.com/66/187783004_db3362fd81.jpg?v=0

Page 16: Paraquat Toxicity

But there IS hope!!

Different Formulation Alginate Additive Gramoxone Inteon(7,14)

First used in human medicine for acid reflux Gelling action extends paraquat retention in stomach 0.79% absorbed/hour

Other Possibilities… A higher concentration

(10g/L) would be better(7)

Require mixing prior to use?(2,17)

Image: www.syngentacropprotection-us.com

Image: 2007 MS ClipArt

Page 17: Paraquat Toxicity

Resources1. AG PICoboSCP. Paraquat: Get the Facts at the Paraquat Information Center. 2008; http://www.paraquat.com/, 2008.

2. Betman ND. New Formulation of Paraquat: A Step in the Wrong Direction? Public Library of Science. 2008.

3. Broyhill I. Personal Safety Procedures. 2006; http://www.broyhill.com/images/interior/safety.gif.

4. Cope RB, BCs, BVSc, PhD. Helping animals exposed to the herbicide paraquat. Veterinary Medicine. 2004;September 2004:755-762. http://www.aspca.org/site/DocServer/vetm0904_755-762.pdf?docID=5581&AddInterest=1101.

5. CTL S. Paraquat Poisoning a practical guide to diagnosis, first aid and hospital treatment2008.

6. Hampson EC, Pond SM. Ultrastructure of canine lung during the proliferative phase of paraquat toxicity. Br J Exp Pathol. Feb 1988;69(1):57-68.

7. Heylings JR, Farnworth MJ, Swain CM, Clapp MJ, Elliott BM. Identification of an alginate-based formulation of paraquat to reduce the exposure of the herbicide following oral ingestion. Toxicology. Nov 20 2007;241(1-2):1-10.

8. Izumi K, Nagata R, Motoya T, et al. Preventive effect of taurine against acute paraquat intoxication in beagles. Jpn J Pharmacol. Jun 1989;50(2):229-233.

9. Paula. Path Gallery. In: Paraquat Toxicity l, dog, 20x, ed. Picasa Web Albums. Vol 2007.

10. Prevention CfDCa. Facts about Paraquat. 2006; http://www.bt.cdc.gov/agent/paraquat/basics/facts.asp, 2008.

11. Robben J. Test on dead dog points to paraquat. Portland Tribune. 7/25/2003, 2003.

12. Spradley P. Pesticide Commercial Applicator License for Applying Restricted Use Pesticides. 2006; http://www.aragriculture.org/pesticides/training/commlicense.htm.

13. Syngenta. Gramoxone Inteon Label2008.

14. Wallace HM, Fraser AV, and Hughes A. A Perspective of Polyamine Metabolism. Biochemical Journal. 2003(376):1-14.

15. Wiesbrook M. Recent Happenings with Paraquat. May 2006 Newsletter. 2006. http://web.extension.uiuc.edu/ipr/i4147_829.html#2.

16. Wilks MS, al e. Improvement in Survival After Paraquat Ingestion Following Introduction of a New Formulation in Sri Lanka. PLoS Medicine. 2008;5(2).

Page 18: Paraquat Toxicity

QUESTIONS&

DISCUSSION