paraquat toxicity
DESCRIPTION
Sept 2008 - My elected 3rd Year Prestation; reviews paraquat toxicity in dogsTRANSCRIPT
PARAQUAT TOXICITY
Katie Krimetz
Western University of Health SciencesCVM DVM 2010
September 8, 2008
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
WHY CAN’T WE FIX THIS?
HOW DO I RECOGNIZE/DIFFERENTIATE CLINICAL SIGNS?
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
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
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
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
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
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
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
[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
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
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)
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
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
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
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).
QUESTIONS&
DISCUSSION