Bovis ISSN 2398-2993

Nitrate poisoning

Contributor(s): Nicola Bates , Alan Murphy

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Introduction

  • Cause: ingestion of nitrate or nitrite, usually in nitrate-accumulating plants.
  • Signs: dyspnea, methemoglobinemia and sudden death, abortion.
  • Diagnosis: history and clinical signs, confirmation of nitrate or nitrate in suspect feed, water, tissue samples and/or rumen content.
  • Treatment: supportive.
  • Prognosis: depends on severity of methemoglobinemia and response to treatment.

Pathogenesis

Etiology

  • Nitrate or nitrite poisoning can occur in several circumstances. Including the following.
    • Ingestion of plants which have accumulated excess nitrates. Plants take up nitrogen in the form of nitrate but normally little accumulates because it is rapidly converted to plant amino acids and proteins. Under stress conditions photosynthesis is reduced and impairs the efficiency of nitrate incorporation and results in accumulation. These stresses include:
      • Drought
      • Frost
      • Herbicide application.
    • Ingestion of plant material spoiled by bacteria or fungi, which can result in nitrate formation.
    • Ingestion of nitrate-based fertilizer by hungry animals.
    • Ingestion of lush pasture rich in nitrates in hungry animals.
    • Nitrates and nitrites are water soluble. Ingestion of water, including well water contaminated with nitrate-based fertilizer or organic waste. Water contamination may occur after a period of drought followed by rain which washes nitrate in top soil into water sources.
    • Ingestion of contaminated feed-stuff.
    • Most nitrate in plants accumulates in the lower stalks and stems rather than the leaves, grains or seeds. The plants listed in this table Plants associated with nitrate poisoning have been associated with nitrate poisoning (not an exhaustive list).

Predisposing factors

General

  • Susceptibility of animals depends on a variety of factors including amount and rate of intake, environment (eat more food in cold weather) and metabolic state (pregnancy, age, pre-existing disease).

Specific

  • Feeding of plants that have been subject to environmental stress.
  • Hunger.

Pathophysiology

  • Ruminants, particularly cattle, are susceptible.
  • Nitrates are irritant to the gastrointestinal tract but toxic effects usually occur when nitrates are converted to nitrite in vivo by rumen bacteria.
  • Nitrate (NO3) → Nitrite (NO2) → Ammonia (NH3) → Amino acid → protein
         [bacterial proteins]
  • Rumen conversion of nitrates is an adaptive process, however, in excessive intake the nitrate is converted to nitrite faster than the nitrite is converted to ammonia and as a result, when high doses of nitrate are consumed, nitrite accumulates.
  • Methemoglobinemia occurs as nitrite enters the bloodstream and oxidizes ferrous iron (Fe2+) to ferric iron (Fe3+) in hemoglobin. Both nitrates and nitrites also reduce vascular tone decreasing oxygen supply to tissues.
  • Reproductive effects are a result of complex effects on fetal and maternal homeostasis.
    • Early effects include reduced fertility probably due to hormonal imbalance that interferes with embryo implantation. Depressed progesterone concentrations have been demonstrated in cattle fed nitrate. Hypovitaminosis A or E may also affect fertility.
    • Abortion is often seen in the 3rd trimester, and may be due to a sudden decrease in transplacental oxygen transfer. Nitrite has been shown to cross the placenta and induce methemoglobinemia in the fetus.
  • The No-Observed Adverse Effect Level (NOAEL) for nitrate in cattle is estimated to be:
    • 3.3 mg/kg/day in adults.
    • 11 mg/kg/day in calves.
  • The lethal dose of nitrate is 500 mg/kg in cattle or approximately 2% of their diet.

Timecourse

  • Sudden onset of signs.
  • Usually after 1-6 hours of feeding.
  • Death can occur 1-24 hours.
  • Abortion usually occurs 3-7 days after exposure but can occur up to 2 weeks later.

Epidemiology

  • Nitrate poisoning can occur in a variety of circumstances depending on environmental conditions (causing plant stress leading to accumulation of nitrates or run off of fertilizer), local environment and farming practices (eg use of fertilizer, well water), animal factors (health, age, hunger, pregnancy), crop plants and weeds available, etc.

Diagnosis

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Treatment

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Prevention

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Outcomes

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Further Reading

Publications

Refereed Papers

  • Recent references from PubMed and VetMedResource.
  • Ozmen O, Mor F, Sahinduran S, Ayhan U (2015) Pathological and toxicological investigations of chronic nitrate poisoning in cattle. Toxicol Environ Chem 87 (1), 99-106.
  • Cockburn A, Brambilla G, Fernández M L, Arcella D, Bordajandi L R, Cottrill B, van Peteghem C, Dorne J L (2013) Nitrite in feed: from animal health to human health. Toxicol Appl Pharmacol 270(3), 209-217.
  • Binta M G, Mushi E Z (2012) Environmental factors associated with nitrate poisoning in livestock in Botswana. J Pet Environ Technol 3(6), 3-6.
  • Sezer K, Albay M K, Ozmen O, Haligur M, Sahinduran S, Mor F, Köker A (2011) Haematological, biochemical and thyroid gland investigations in pregnant cows and in calves chronically intoxicated with nitrate. Revue Méd Vét 162 (5), 223-228.
  • EFSA (2009) European Food Safety Authority. Nitrite as undesirable substances in animal feed - Scientific Opinion of the Panel on Contaminants in the Food Chain. EFSA J 1017:1-47.
  • Al-Qudah K M, Rousan L M, Ereifej K I (2009) Nitrate/nitrite poisoning in dairy cattle associated with consumption of forages irrigated with municipally treated wastewater. Toxicol Environ Chem 91(1), 163-170.
  • Yeruham I, Shlosberg A, Hanji V, Bellaiche M, Marcus M, Liberboim M (1997) Nitrate toxicosis in beef and dairy cattle herds due to contamination of drinking water and whey. Vet Hum Toxicol 39(5), 296-8.
  • Murphy S A, Power E P (1995) Poisoning of dairy cows by a high nitrate concentration in Italian ryegrass. Irish Vet J 48, 395-397.
  • Bruning-Fann C S, Kaneene J B (1993) The effects of nitrate, nitrite, and N-nitroso compounds on animal health. Vet Hum Toxicol 35(3), 237-253.
  • Smith RA, Suleiman A (1991) Nitrite intoxication from large round bales. Vet Hum Toxicol 33(4), 349-350.
  • Van t’Klooster A T, Taverne M A M, Malestein A, Akkersdijk E M (1990) On the pathogenesis of abortion in acute nitrite toxicosis of pregnant dairy cows. Theriogenology 33(5), 1075-1089.
  • Page R D, Gilson W D, Guthrie L D, Mertens D R, Hatch R C (1990) Serum progesterone and milk production and composition in dairy cows fed two concentrations of nitrate. Vet Hum Toxicol 32(1). 27-31.
  • Ridder W E, Oeheme F W (1974) Nitrates as an environmental, animal, and human hazard. Clin Toxicol 7(2),145-159.

Other sources of information

  • Burrows G E, Tyrl R J (2013) Toxic Plants of North America. 2nd edition. Wiley Blackwell, Ames, Iowa. pp 282-307.
  • Rathje JA, Osweiler G, Ensley S, Janke B, Vosburg Z (2009) Nitrate toxicity in a cow-calf herd. AAVLD Ann Conf Proceedings San Diego, CA, p 61.
  • Vough L R, Castel E K, Barao S M (2006) Causes and prevention: nitrate poisoning of livestock. South Dakota State University Cooperative Extension Service ExEx 4015.
  • Casteel S W, Evans T J (2004) Nitrate. In: Clinical Veterinary Toxicology. KH Plumlee (ed). Mosby, Missouri, pp 127-130.
  • Bolan N S, Kemp P D (2003) A review of factors affecting and prevention of pasture-induced nitrate toxicity in grazing animals. Proceedings of the New Zealand Grassland Association 65, 171-178.

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