Although nitrate is locally irritant in large doses it is usually nitrite derived from it which is the more toxic ion. Nitrate nitrite poisoning has been reported commonly in grazing ruminants in New Zealand and other countries, it can be very serious, sudden and spectacular in its occurrence.
Sheep, cattle, (particularly dairy cattle) deer, goats, pigs and occasionally cats and dogs are susceptible to nitrite poisoning. Pigs appear to be the most susceptible of the domestic animals and sheep are more resistant than cattle.
Fodder that contains from 1 - 1.5 percent of potassium nitrate on a dry matter basis may cause acute intoxication in ruminants. This level is somewhat arbitrary as the special environmental conditions which prevail at a given time influence considerably the occurrence of poisoning. The highest concentration of nitrate NO3 is found in the stems and stalks of the plants rather than the leaves. Plants that produce nitrate poisoning are usually grown in well manured soils. In some cases of poisoning in New Zealand nitrate levels in pasture as high as 5% on a dry matter basis have been recorded. A survey (1998) conducted in the lower North Island reported over 90% of pasture samples with dangerous nitrate levels higher than 1%.
Active growth of plants after rain following dry or drought conditions often leads to nitrate/nitrite poisoning. Nitrate tends to accumulate in and near the roots of plants during a drought and is taken up rapidly when regrowth follows after rain or irrigation. Also the absence of light tends to favour the storage of NO3 while in bright light e.g. sunlight, plant reductases tend to convert stored NO3 to amino acids and proteins. Hence nitrate/nitrite toxicity is frequently seen after dull overcast weather conditions favourable to growth but not to photosynthetic activity. Other factors that can increase the risk of nitrate poisoning include a high rate of feed consumption, high carbohydrate in the diet, lack of adaption to high nitrate feed, herbicide treatment of plants and soil sulphur and molybdenum deficiency. However climatic factors as mentioned are very important.
Plants are the main source of nitrate for grazing stock and many have been listed as high level storers of nitrate. Some of the more common are:
Other less important sources of nitrate include nitrate whey which contains calcium nitrate added during cheese making to prevent fermentation. This can be converted into nitrite.
Well water may contain excess nitrate. This is likely where a deep well is filled by seepage from highly fertile soils.
Sodium nitrite used as a preservative in pet foods has been associated with deaths in cats and dogs. In one case the pet food contained levels of nitrite at 2900 mg/kg. Nitrite is used in canned and processed rolls pet foods to retain the colour of fresh red meat, concentrations are low ranging from 15 - 30 mg/kg. High levels of nitrite tend to make pet food unpalatable for cats.
Acute nitrate poisoning usually occurs when forages contain greater than 10,000 mg/kg or 1% nitrate on a dry matter basis. Water containing 0.15% nitrate is potentially toxic. Both sources can contribute to nitrate toxicosis and should be evaluated when feed or forage sources have marginal levels of nitrate. Toxic doses are included in Table 21.
Table 21 Lethal doses of nitrate or nitrite in various species
| Source | Species | Lethal Dose mg/kg |
| nitrate | cattle | 330 - 616 |
| sheep | 308 | |
| sodium nitrite | rabbits | 80 - 90 |
| pigs | 90 | |
| sheep | 170 |
Note: Heinz body anaemia. This is due to the presence in all brassicas of S methyl cysteine sulphoxide (SMCO) an amino acid in the NPN fraction. Rumen microflora convert part of the SMCO to an oxidative drug of which the principle component is dimethyl disulphide this reacts with components of red cells when absorbed into the blood producing an abnormal level of Heinz bodies and lowering Hb concentrations. Heinz body anaemia develops after 1 - 3 weeks feeding on brassicas (kale) and recovery will occur if feeding is stopped. Continued feeding may lead to death.
In ruminants nitrate is normally converted to ammonia and hydroxylamine in the rumen. Above a certain concentration of nitrate however the rate of reduction of nitrite to ammonia becomes limited and nitrite accumulates.
The absorbed nitrite oxidises the haemoglobin (Fe+2) of the blood into methaemoglobin (Fe+3) which is unable to act as an oxygen carrier. Animals have a limited capacity to reduce methaemoglobin back to haemoglobin via methaemoglobin reductase but the process is easily overwhelmed by high levels of nitrite. If this change is sufficiently complete, animals may die of tissue anoxia. Clinical signs are usually seen when about 20% of the haemoglobin is converted to methaemoglobin and death occurs when the level reaches about 80%.
Nitrites are also vasodilators and may contribute to tissue anoxia by causing peripheral circulatory failure. A cow can consume a toxic amount of plant material of high nitrate content in one hour. If the NO3 intake is spread over a longer period cattle can tolerate high levels. Also if there is adequate readily available carbohydrate to support optimal rumen microbial activity the risks are less. Young animals (neonates and the foetus) are more susceptible to nitrite toxicity than adults.
Horses and pigs (monogastric animals) can tolerate high levels of nitrate in the food because they have no mechanism for converting NO3 to NO2 before it can be absorbed. Pigs have been poisoned generally from nitrite directly or from fodder in which NO3 has been converted to NO2 by either holding or cooking and holding.
When nitrite is ingested preformed, the effects are rapid. When conversion of nitrate to nitrite occurs in the rumen there is a delay of a few hours before clinical signs are apparent. In cattle maximum methaemoglobinaemia usually occurs about 5 hours after high levels of nitrate begin to accumulate.
In acute poisoning there may be sudden death without affected animals showing any clinical signs. Death usually occurs within 12 to 24 hours of ingestion of the toxic plants. Pregnant animals may abort their foetuses.
Clinical signs of acute poisoning include three syndromes:
Gastrointestinal disturbancesThe only specific feature at post mortem is the brown or coffee coloured blood that has a watery appearance. After death there is a gradual return of the colour of the blood from brown to red due to the formation of the reddish pigment nitric oxide haemoglobin and also the reduction of methaemoglobin back to oxyhaemoglobin, so that the absence of brown blood at post mortem does not exclude a diagnosis of nitrate/ nitrite poisoning. Further the blood from a methaemoglobinaemic animal may contain little or no methaemoglobin by the time it reaches the laboratory due to reduction to oxyhaemoglobin.
Serum nitrate greater than 20µg/mL is diagnostic.
Samples to consider for examination include:
Ante mortem
Post mortem
Plant samples for nitrate estimation should be dried in the oven at about 150ºC overnight and forwarded in a paper bag. Plastic bags may cause sweating, fermentation and loss of nitrate.
The interpretation and successful attainment of helpful diagnostic results depends on several factors and the following points should be noted:
i) For the demonstration of methaemoglobin and/or nitrite in blood. Samples must be taken when symptoms are occurring or within 2 hours of death, kept cool at 4ºC and dispatched promptly to the laboratory. Methaemoglobin disappears from the blood of living animals within 24 hours of a toxic dose.
ii) Anticoagulant blood is usually recommended but the methaemoglobin content may be stabilized for 48 hours by dilution of blood 1:20 in 0.07M phosphate buffer pH 6.6. Tablets can be purchased.
iii) The identification of nitrate and nitrite in blood can be made by use of the diphenylamine test. The latter test is extremely sensitive and can give a positive test in the absence of methaemoglobinaemia.
iv) A sample of aqueous humour can also be used to give a positive diagnosis of nitrate poisoning for up to 60 hours after death.
v) Plant nitrate concentrations of over 50g/kg DMB are toxic. To be safe, plants should contain less than 1.0% potassium nitrate on a dry matter basis.
Nitrate nitrite poisoning is unlikely to be confused with other problems. Copper poisoning is a possibility but this is rare in cattle. Cyanide poisoning from plant origin is also possible but the blood is a bright red colour.
In an outbreak of nitrate nitrite poisoning, have stock (dairy cattle) moved away from dangerous pasture as soon as possible. Animals which are able to be driven from the paddock will usually recover spontaneously, those which are left behind and won't move, because of advanced methaemoglobinaemia are the ones on which to concentrate treatment.
The treatment aims at converting methaemoglobin into oxyhaemoglobin. The specific antidote is methylene blue which is given iv at 1 - 2 (-15)mg/kg as a 1 - 2% solution (1 - 2 g/100 mL) in water for injections. This may need to be repeated in severe cases. It should be injected through a syringe filter.
Methylene blue is rapidly converted to leucomethylene blue and this quickly reduces the methaemoglobin to oxyhaemoglobin. Methylene blue is readily excreted in the urine and if nitrite continues to be absorbed from the alimentary tract, relapses can occur, hence the necessity for repeat dosing in some cases. Note that cases of nitrite poisoning in dogs and cats have also been treated successfully with methylene blue. For cats a single dose of 1.5 mg/kg has been found to be safe and effective in reversing methaemoglobinaemia.
N.B. There is no withholding information for livestock.Feed hay to remainder of herd to increase carbohydrate availability.
Limit access to high nitrate feed by grazing for a restricted period only. One hour at a time would be a safe recommendation.
Look for danger periods e.g. dull warm weather and around crops which may be at risk or else graze cautiously.
This is one toxicosis that veterinarians can help farmers to anticipate and prevent through sound advice about the conditions that are likely to lead to the growth of dangerous pasture.
Table 22 Recommendations for feeding pasture, crops or plants containing nitrates
| Feed Concentration as Nitrate Ion (Dry Matter Basis) | Estimated Toxicological Significance for Cattle |
| 0 - 0.44% | Considered to be safe to feed under all conditions |
| 0.44 - 0.66% | Safe for non-pregnant animals under all conditions. Limit pregnant animals to 50% of the total dry matter in the diet. |
| 0.66 - 0.88% | Limit to 50% of the total dry matter in the diet. |
| 0.88 - 1.54% | Limit to 35 - 40% of the total dry matter in the diet. Feeds with over 0.88% nitrate ion should not be used for pregnant animals. |
| 1.54 - 1.76% | Limit to 25% of the total dry matter in the diet. Do not use for pregnant animals. |
| Over 1.76% | Feeds over 1.76% nitrate ion may be toxic. Do not feed. |
(Source: Pennsylvania State University)
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Surveillance (1974) 1(3): 3 Nitrate poisoning in cattle grazing crops.
Surveillance (1975) 2(2): 18 Nitrate poisoning.
Surveillance (1978) 5(4): Nitrate/nitrite poisoning
Surveillance (1983) 10(3): 21 Nitrate poisoning on brassicas.
Surveillance (1989) 16(3):23 Nitrate poisoning in cattle and sheep.
Surveillance (1990) 17(2): 3 Nitrate poisoning in cattle.
Surveillance (1990) 17(3):29 Nitrate poisoning in dairy cattle on green oats.
Surveillance (1990) 17(4): 3 Nitrate poisoning in sheep on Italian ryegrass.
Surveillance (1993) 20(2): 3 Review of Ruakura cases of nitrate poisoning and plants involved.
Surveillance (1993) 20(3):28 Nitrate poisoning green oats and tama ryegrass.
Surveillance (1995) 22(3):36 Nitrate poisoning cattle.
Surveillance (1996) 23(3):39 Nitrate nitrite poisoning and pet food.
Surveillance (1998) 25(3):15 Nitrate poisoning in cattle.
Surveillance (1998) 25(4):14 Nitrate poisoning in cattle on Italian ryegrass.