Nitrate poisoning (toxicosis) in animals, especially ruminants, results from excess consumption of nitrates from plants or water or via ingestion of nitrate-containing fertilizers. The nitrate ion (NO3–) is reduced to a nitrite ion (NO2–), which is rapidly absorbed and leads to the formation of methemoglobin, which inhibits oxygen transport. This results in dyspnea, cyanotic mucous membranes, weakness, and, in severe cases, death due to anoxia. Ruminants are more susceptible than other large animals because rumen microbiota can rapidly reduce nitrates to nitrites. Methylene blue, administered IV, will reverse methemoglobinemia and can be effective as a treatment with supportive care. Ocular fluid specimens are the most appropriate sample for postmortem testing, in conjunction with laboratory testing of suspected sources of nitrate exposure.
Many species are susceptible to nitrate and nitrite poisoning; however, cattle are most frequently affected. Ruminants are especially vulnerable because ruminal microbiota reduce nitrate to ammonia, with nitrite (approximately 10 times more toxic than nitrate) as an intermediate product during digestion. Nitrate reduction (and nitrite production) occurs in the cecum of equids but not to the same extent as in ruminants.
Young pigs also have GI microbiota capable of reducing nitrate to nitrite; however, adult monogastric animals (except equids) are more resistant to nitrate toxicosis because this metabolic pathway is age-limited.
Acute toxicosis is manifested primarily by methemoglobin formation. Nitrite ions combine with RBCs, oxidizing ferrous iron in hemoglobin, forming stable methemoglobin, which is incapable of oxygen transport, and thus resulting in anoxia. Tissue hypoxia stimulates secondary vasodilatory effects in vascular smooth muscle. Ingested nitrates (eg, from fertilizers) can also directly irritate GI mucosa, producing abdominal pain and diarrhea.
Although usually acute, the effects of nitrite or nitrate toxicosis can be subacute or chronic and can include delayed growth, decreased milk production, vitamin A deficiency, minor transitory goitrogenic effects, abortion, fetotoxicity, and increased susceptibility to infection. Chronic nitrate toxicosis remains poorly characterized. Nonetheless, most current evidence does not support decreased milk production in dairy cows due to excessive dietary nitrate exposure alone.
Etiology of Nitrate and Nitrite Poisoning
Nitrates and nitrites are used in pickling and curing brines during meat preservation processes, as well as in certain machine oils, anticorrosion tablets, gunpowders, explosives, and fertilizers. They can also serve as therapeutic agents for certain noninfectious diseases, (eg, cyanide poisoning).
Toxicosis most often occurs in naive domestic species, most commonly due to ingestion of plants containing excess nitrates—particularly by hungry animals engorging themselves, thus ingesting an enormous volume of nitrate. Confounding metabolic interactions with nonprotein nitrogen, monensin, and other feed components can exacerbate the effects of excessive nitrate content in animal diets, especially when coupled with management errors.
Nitrate toxicosis can also result from accidental ingestion of fertilizer or other chemicals. Nitrate concentrations may be hazardous in ponds with extensive feedlot or fertilizer runoff; these types of nitrate sources can also contaminate shallow, poorly cased wells. Although nitrate concentrations are increasing in groundwater in the US, well water is rarely the sole cause of nitrate toxicosis. Water with both high nitrate concentration and considerable coliform contamination has greater potential to adversely affect health and productivity than the presence of either nitrates or bacteria alone.
Crops that readily concentrate nitrate include the following:
cereal grasses, especially oats (Avena spp), millet (Pennisetum spp), and rye (Lolium spp)
corn (maize; Zea spp)
sunflower (Helianthus spp)
sorghums (Sorghum spp)
Weeds that commonly have high nitrate concentrations include the following:
pigweed (Amaranthus spp)
lamb’s-quarter (Chenopodium spp)
thistle (Silybum spp and other genera)
jimsonweed (Datura spp)
fireweed (Kochia spp)
smartweed (Polygonum spp)
Johnson grass (Sorghum halepense)
Anhydrous ammonia, nitrate fertilizers, and soils naturally high in nitrogen tend to increase nitrate content in forage.
Excess nitrate in plants is generally associated with damp weather conditions and cool temperatures (eg, approximately 13°C [55°F]), although high concentrations are also likely to develop when growth is rapid during hot, humid weather. Drought conditions, particularly if they occur when plants are immature, can result in vegetation with high nitrate content. Decreased light, cloudy weather, and shading associated with crowded planting can also cause increased concentrations of nitrates in plants.
Well-aerated soil with a low pH and low or deficient amounts of molybdenum, sulfur, or phosphorus in soil tend to enhance nitrate uptake, whereas soil deficiencies of copper, cobalt, or manganese tend to decrease nitrate uptake. Anything that stunts growth increases nitrate accumulation in the roots and lower stalks of plants.
Phenoxy acid derivative herbicides (eg, 2,4-D) applied to nitrate-accumulating plants during early stages of growth cause increased growth and a high nitrate residual (10–30%) in surviving plants, which can become lush and attractive to animals that previously avoided them.
Nitrate does not selectively accumulate in fruits or grain and is found chiefly in the lower stalk, with lesser amounts in the upper stalk and leaves. Nitrate in plants can be converted to nitrite under favorable conditions of moisture, heat, and microbial activity after harvesting.
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Clinical Findings of Nitrate and Nitrite Poisoning
Clinical signs of nitrite poisoning usually appear acutely because of tissue hypoxia and hypotension resulting from vasodilation. Rapid, weak heartbeat with decreased body temperature, muscle tremors, weakness, and ataxia are early clinical signs of toxicosis at methemoglobinemia concentrations of 30–40%. Brown, cyanotic mucous membranes develop rapidly as methemoglobinemia exceeds 50%. Dyspnea, tachypnea, anxiety, and frequent urination are common. Some monogastric animals, usually because of excess nitrate exposure from nonplant sources, exhibit salivation, vomiting, diarrhea, abdominal pain, and gastric hemorrhage.
Affected animals can die suddenly without appearing ill, with terminal anoxic seizures within 1 hour, or after a clinical course of 12–24 hours or longer. Acute, lethal toxicoses almost always result from development of ≥ 80% methemoglobinemia (1).
In certain conditions, adverse effects might not be apparent until animals have been eating nitrate-containing forages for days to weeks. Some animals that develop marked dyspnea recover but then develop interstitial pulmonary emphysema and have continued clinical signs of respiratory distress; most of these animals recover fully within 10–14 days. Abortion and stillbirths occur in some cattle 5–14 days after excessive nitrate/nitrite exposure; however, this is likely only in cows that have survived an initial acute ≥ 50% methemoglobinemia for 6–12 hours or longer.
Lesions in Nitrate and Nitrite Poisoning
Blood that contains methemoglobin usually has a chocolate-brown color; however, dark red hues may also be evident. Pinpoint or larger hemorrhages (petechiae, ecchymoses) can appear on serosal surfaces. Ascites has been reported in stillborn calves, as have pulmonary and GI edema and hemorrhage in neonatal calves with excessive maternal nitrate exposure. However, dark brown discoloration of blood and/or tissues in moribund or recently dead animals is not pathognomonic, and other causes of methemoglobin must be considered. If necropsy is postponed too long, the brown discoloration can disappear, with conversion of methemoglobin back to Hgb.
Diagnosis of Nitrate and Nitrite Poisoning
Laboratory analysis for nitrate concentration in both ante- and postmortem specimens, including plasma, ocular fluid, fetal fluids, or maternal uterine fluid
Laboratory testing of suspected sources of nitrate exposure
Field tests to measure nitrate using diphenylamine blue for forage and nitrate test strips for water and body fluids
Nitrate toxicosis can be assessed by means of laboratory analysis for nitrate concentration in both ante- and postmortem specimens. Plasma is the preferred antemortem specimen, because some plasma protein–bound nitrite could be lost because of clotting if serum is collected. Ocular fluid is the preferred postmortem sample for nitrate testing. Additional postmortem specimens in cases of abortion include fetal pleural or thoracic fluids, fetal gastric contents, and maternal uterine fluid.
All specimens should be frozen in clean plastic or glass containers before submission, except when whole blood is collected for methemoglobin analysis. Because the amount of nitrate in rumen contents is not representative of dietary concentrations, evaluation of rumen contents is not indicated.
Suspected sources of nitrate exposure should also be submitted for laboratory testing.
Methemoglobin analysis alone is not a reliable indicator of nitrate toxicosis or nitrite exposure except in acute toxicosis because 50% of methemoglobin is converted back to Hgb in approximately 2 hours, and alternative forms of nonoxygenated Hgb formed by reaction with nitrite are not detected via methemoglobin testing.
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Nitrate and nitrite concentrations > 20 ppm and > 0.5 ppm, respectively, in maternal and perinatal serum, plasma, ocular fluid, and other similar biological fluids are usually indicative of excessive nitrate or nitrite exposure in most domestic animal species (2). In acutely poisoned ruminant livestock, nitrate and nitrite concentrations as high as 300 ppm and 25–50 ppm, respectively, can be found in plasma or serum, with approximately one-third less in postmortem ocular fluid because of delayed equilibrium via diffusion. However, postmortem ocular fluid nitrate concentrations are relatively stable and remain diagnostically relevant for up to 60 hours after death. Once collected for testing, plasma, serum, and ocular fluid specimens maintain stable nitrate concentration for testing for at least 1 week if refrigerated and 1 month at –20°C (−4°F).
Normally expected nitrate and nitrite concentrations in similar diagnostic specimens are usually < 10 ppm and < 0.2 ppm, respectively.Nitrate and nitrite concentrations > 10 but < 20 ppm and > 0.2 but < 0.5 ppm, respectively, are suspect and indicate nitrate or nitrite exposure of unknown duration, extent, or origin (2). It has been reported that the half-lives of nitrate in beef cattle, sheep, and ponies are 7.7, 4.2, and 4.8 hours, respectively (3, 4). Therefore, it would be at least five biological half-lives (24–36 hours) before increased nitrate concentrations from excessive nitrate exposure diminish to normally expected values, allowing additional time for appropriate antemortem specimen collection.
A latent period may exist between excessive maternal dietary nitrate exposure and equilibrium in perinatal ocular fluid. Aqueous humor is actively secreted into the anterior chamber at a rate of approximately 0.1 mL/hour, and nitrate and nitrite are thought to enter the globe of the eye via this mechanism. Equilibrium between aqueous and vitreous humor is by passive diffusion rather than by active secretion, so nitrate or nitrite can be present in comparatively lesser concentrations in vitreous humor after acute exposure.
Field tests for nitrate are presumptive and should be confirmed by means of standard analytical methods at a qualified laboratory. The diphenylamine blue test (1% in concentrated sulfuric acid) is more suitable to determine the presence or absence of nitrate in suspected forages. Nitrate test strips (dipsticks) are effective in determining nitrate values in water supplies and can be used to evaluate nitrate and nitrite concentrations in serum, plasma, ocular fluid, and urine.
Differential diagnoses include the following:
other toxicoses, eg, cyanide, urea, pesticides, toxic gases (eg, carbon monoxide, hydrogen sulfide), chlorates, aniline dyes, aminophenols, or drugs (eg, sulfonamides, phenacetin, and acetaminophen)
various infectious or noninfectious diseases (eg, grain overload, hypocalcemia, hypomagnesemia, pulmonary adenomatosis, or emphysema)
any other cause of sudden, unexplained deaths
Treatment of Nitrate and Nitrite Poisoning
Injection IV of methylene blue one or more times to treat methemoglobinemia
Low stress handling of affected animals
Removal of any sources of continued exposure to excess nitrates
Slow IV injection of 1–2% methylene blue in distilled water or isotonic (0.9% NaCl) saline solution should be administered at 4–15 mg/kg or more (5, 6), depending on severity of exposure. Lower dosages may be repeated in 20–30 minutes if the initial response is not satisfactory. Lower dosages of methylene blue can be used in all species; only ruminants can safely tolerate higher dosages. If additional exposure or absorption occurs during therapy, retreatment with methylene blue every 6–8 hours should be considered.
Affected animals should be handled to minimize stress, which can exacerbate effects of hypoxia. Animals should be removed from the source of excess nitrates and given other supportive care as needed.
Control of Nitrate and Nitrite Poisoning
Animals may adapt to higher nitrate content in feeds, especially when grazing summer annuals such as sorghum-Sudan grass hybrids. Multiple small feedings help animals adapt. Trace mineral supplements and a balanced diet can help prevent nutritional or metabolic disorders associated with long-term excess dietary nitrate consumption. Feeding grain with high-nitrate forages may decrease nitrite production. However, caution is advised when combining other feed additives and components, including nonprotein nitrogen, ionophores (such as monensin), and other growth and performance enhancers, with high-nitrate diets in ruminants.
Appropriate management practices, especially regarding acclimation, are critical. Forage nitrate concentrations > 1% nitrate (10,000 ppm) on a dry-weight basis can cause acute toxicosis in unacclimated animals, and forage nitrate concentrations ≤ 5,000 ppm (dry-weight basis) are recommended for pregnant beef cows. However, even forage concentrations of 1,000 ppm dry-weight basis have been lethal to hungry cows engorging themselves in a single feeding within an hour, so the total dose of nitrate ingested is a key factor (7).
High-nitrate-concentration forages can also be harvested and stored as silage rather than as dried hay or green chop; this can decrease the nitrate content in forages by up to 50%. Raising cutter heads of machinery during harvesting operations selectively leaves the more hazardous stalk bases in the field.
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Hay appears to be more hazardous than fresh green chop or pasture with similar nitrate content. Heating can encourage bacterial conversion of nitrate to nitrite; therefore, feeding hay, straw, or fodder that has been damp or wet for several days and stockpiled green-chopped forage should be avoided. Large, round bales with excess nitrates are especially dangerous if stored uncovered outside; rain and snow can leach and subsequently concentrate most of the total nitrate present into the lower third of these bales.
Water transported in improperly cleaned liquid fertilizer tanks may have an extremely high nitrate concentration. Young, unweaned livestock, especially neonatal pigs, can be more sensitive to nitrate in water.
Key Points
Nitrate poisoning, more common in ruminants, is caused by ingestion of excess nitrates from plant sources (including feed and forage), water sources, or nitrate-containing fertilizers.
Nitrate ions are reduced to nitrite ions in the rumen and rapidly absorbed, forming methemoglobin, which results in hypoxia. Treatment with methylene blue can be effective to reverse this.
Laboratory analysis of ocular fluid and suspected sources of nitrates aids diagnosis.
For More Information
Hall JO. Nitrate and nitrite accumulating plants. In: Gupta RC, ed. Veterinary Toxicology: Basic and Clinical Principles. 4th ed. Academic Press; 2025:943-948.
References
Chen RJ, Nappe TM. Methemoglobinemia. StatPearls. Updated December 14, 2025. Accessed March 31, 2026. https://www.ncbi.nlm.nih.gov/books/NBK537317/
Ensley S, Carlson M. Nitrate toxicosis. University of Nebraska–Lincoln School of Veterinary Medicine and Biomedical Sciences. Accessed March 31, 2026. https://vbms.unl.edu/nitrate-toxicosis/
Nitrate (serum or ocular fluid). North Dakota State University Veterinary Diagnostic Laboratory. Accessed March 31, 2026. https://www.vdl.ndsu.edu/tests/nitrate/
Schneider NR, Yeary RA. Nitrite and nitrate pharmacokinetics in the dog, sheep, and pony. Am J Vet Res. 1974;36(7):941-948. doi:10.2460/ajvr.1975.36.07.941
Burrows GE. Nitrate intoxication. J Am Vet Med Assoc. 1980;177(1):82-83. doi:10.2460/javma.1980.177.01.82
Ford EG IV, Sheela FF, Yeatts J, Baynes RE. Pharmacokinetics and withdrawal interval calculations for meat and milk of intravenously administered compounded methylene blue in healthy cattle. Am J Vet Res. 2025;87(2). doi:10.2460/ajvr.25.08.0303
Arnold M, Romano M, Lehmkuhler J, Smith R. Forage-related disorders in cattle: nitrate poisoning. University of Kentucky Cooperative Extension; 2022. Accessed March 31, 2026. https://publications.mgcafe.uky.edu/sites/publications.ca.uky.edu/files/ID217.pdf
