Nitrate toxicosis

By Steve Ensley, DVM, PhD, Veterinary Toxicologist and Mike Carlson, PhD, Analytical Chemist

Nitrate (NO3) toxicosis is actually caused by nitrite (NO2). Nitrate itself is not toxic, only when it is converted to nitrite. Many species of animals are susceptible to nitrate poisoning, but ruminants are the most commonly affected. Ruminants are especially vulnerable to poisoning by nitrate because of the nitrate-reducing potential of rumen bacteria. Rumen microorganisms reduce nitrate to nitrite. The rumen microflora's capability to form nitrites allows ruminants to be poisoned by ingested nitrate as well as preformed nitrite. Monogastric animals and horses are less susceptible to nitrate poisoning. Young pigs and human infants also have gastrointestinal microflora capable of reducing nitrate to nitrite because the pH of the stomach is not as low as mature swine or adults.

Acute intoxication from nitrite/nitrate in cattle is manifested primarily by methemoglobinemia and resultant anoxia. Clinical signs of concentrations reach 20 - 30% of total hemoglobin, and death may occur when methemoglobinemia exceeds 75%.

Clinical problems associated with low level chronic nitrate exposure include abortion and infertility, poor growth rates or retarded growth, lowered milk production, vitamin A deficiency, weak goitrogenic effects and increased susceptibility to infection.

Excessive nitrate exposure in livestock may be determined through laboratory analysis for nitrate and nitrite in both antemortem and postmortem specimens. Plasma is the preferred antemortem specimen instead of serum, because some plasma protein-bound nitrate or nitrite could be lost in the clot if only serum was collected. Appropriate postmortem specimens include ocular fluids from fetus or dam. The presence or absence of nitrate in rumen content is not a reliable indicator of ingested dietary nitrate concentrations; submission of rumen contents is not recommended.

Methemoglobinemia alone is not a reliable biological indicator of nitrite exposure. Nitrate and nitrite concentrations >20 µg NO3/ml and >0.5 µg NO2/ml, respectively, in maternal and perinatal serum, plasma, ocular fluids and other similar biological fluids, are indicative of excessive nitrate/nitrite exposure. Normal NO3 and NO2 concentrations in similar diagnostic specimens are usually <10 µg NO3/ml and <0.2 µg NO2/ml, respectively. Elevated dietary nitrite concentrations are usually found along with high nitrate concentrations in diagnostic specimens. Acute exposures are characterized, in general, by significant nitrite and nitrate concentrations. Elevated nitrite concentrations alone may reflect postmortem decomposition or bacterial contamination with subsequent in vitro NO3 reduction to NO2. Another possibility is the endogenous production of nitrite (or nitrate) by activated macrophages.

A latent period may exist between maternal nitrate exposure and equilibrium in perinatal ocular fluids. Aqueous humor is actively secreted into the anterior chamber at a rate of about 0.1 ml/hr, and nitrate is thought to enter the aqueous humor of the eye by this mechanism. Equilibrium between aqueous and vitreous humor is by passive diffusion rather than active secretion, so nitrate or nitrite may be present in comparatively lesser concentrations in vitreous humor after acute or sub-chronic exposure.

Feed/forage with nitrate concentrations of 10,000 ppm NO3 have significant risk of causing acute nitrate toxicosis in ruminants. Hay with excessive nitrate is more hazardous than green chop or pasture with similar nitrate content. Large round bales with excessive nitrate are potentially dangerous if stored outside; precipitation can leach and subsequently concentrate most of the total nitrate present into the lower third of the bales. Diets of pregnant beef cows should not exceed 5,000 ppm NO3. High nitrate feed may be diluted or mixed with low nitrate feed sources to achieve appropriate concentrations. Fattening animals may be acclimated to higher nitrate content in feeds to reduce risk, especially in pasturing summer annuals such as sorghum-sudan hybrids. Feeding grain with high nitrate forages provides additional energy to apparently assist the conversion of nitrate to bacterial protein in the rumen and minimizes the intermediate nitrite production that would more likely occur with roughage alone. Most producers could supplement grain while adapting cattle to high nitrate forages.

Several units of concentration for nitrite and nitrate are used in scientific literature and laboratory reports. This practice has caused confusion at times. Certain scientific disciplines prefer reporting nitrate concentrations as % KNO3; others as ppm NO3-N or ppm NO3. A table of conversion factors is provided to expedite conversion between various units of concentration. To use, multiply the current unit of concentration by the appropriate factor to find the desired unit of concentration, i.e. ppm NO3-N x 4.426 = ppm NO3. This laboratory routinely uses NO3 and NO2 as the reported units.

Nitrate and nitrite values in submitted postmortem specimens can be used to evaluate exposure to nitrate/nitrite, but should not be used as the only diagnostic criteria to diagnose whether an abortion is caused by elevated dietary nitrate. Nitrate/nitrite exposure may be a contributing factor or an incidental finding associated with infectious and other etiologies of abortion, subclinical disease or death.

Table: Find current unit of concentration on top row. Find desired unit of concentration at left column. Obtain conversion factor at intersection of row and column. Desired concentration - current concentration x conversion factor.

FROM NO3-N   NO3   KNO3   NO2-N   NO2
NO3-N   1.000   0.226   0.139   1.000   0.305
NO3   4.426   1.000   0.613   4.426   1.348
KNO3   7.217   1.631   1.000   7.217   2.198
NO2-N   1.000   0.226   0.139   1.000   0.305
NO2   3.284   0.742   0.455   3.284   1.000