Toxicology 2 Course 5: Fertilizers and Nitrogen Compounds

CONTENTS

• FERTILIZERS
• NITROGEN FERTILIZERS
• PHOSPHATE FERTILIZERS
• POTASSIUM FERTILIZERS

Emanuela Badea
assistant professor | DVM | PhD | MSc
Faculty of Veterinary Medicine of Bucharest
UASVMII. FERTILIZERS

A fertilizer is any material of natural or synthetic origin (other than liming materials) that is
applied to soil or plants to provide one or more plant nutrients essential for plant growth. There
are many sources of fertilizers, both natural and industrial products.

In the last half of the twentieth century, the increased use of nitrogen fertilizers (800% increase
between 1961 and 2019) was an essential component of the increased productivity of
conventional food systems (over 30% per capita). According to the Special Report on Climate
Change and Earth, these practices are key factors in global warming.

NITROGEN FERTILIZERS

II. 1. NITROGEN FERTILIZERS
Nitrogen fertilizers are made of ammonia (NH3), which is sometimes injected directly into the
soil. Ammonia is produced by the Haber-Bosch process. In this energy-intensive process,
natural methane gas (CH4) usually supplies hydrogen, while nitrogen (N2) comes from the air.
The ammonia thus obtained is used as a raw material for all other nitrogen fertilizers, such as
anhydrous ammonium nitrate (NH4NO3) and urea (CO(NH2)2). Ammonia can also be produced
through the Ostwald process.

The main nitrogen-based fertilisers are nitrate and nitrite salts, and include:
sodium nitrate (Silitra; Chile saltpeter), calcium nitrate (Norway's saltpeter), ammonium nitrate
(Montana saltpeter; Leuna saltpeter), potassium nitrate, calcium nitrite, ammonium sulphate,
ammonium chloride, calcium cyanamide, ammonia, urea.

• NaNO3- sodium nitrate, Chile saltpeter
• Ca(NO3)2- calcium nitrate
• KNO3- potassium nitrate
• NH4NO3- ammonium nitrate
• Ca(NO2)2- calcium nitrite
  . (NH4)2SO4- ammonium sulphate
• NH4Cl - ammonium chloride
• CaCN2- calcium cyanamide
• NH3- ammonia
• CH2(NH2)2- urea

Causes of Intoxication

Intoxication occurs by eating plants that have a high capacity of accumulating nitrates and
nitrites, mainly oats, barley, rye, corn, clover, sugar beet leaves, potato leaves, rapeseed, and
mustard. These plants accumulate large amounts of nitrates and nitrites during periods of
drought that are followed by precipitations, when the nitrate content of the plants can rise to a
toxic level (10-30%).

2Causes which lead to high nitrogen concentration in plants:

• portion of the plant: it accumulates a lot in the roots, in the leaf mass (spinach, lettuce),
  in seeds and fruits (in grasses in the milk-wax phase)
• vegetation phase - in the milk-wax phase the level is higher and decreases as the seeds
  mature
• feed harvesting and storage technology: in the case of green fodder, if stored in large
  piles, the conversion of nitrates into nitrites takes place and the metabolism is blocked
• fodder plants with luxurious growth

The assimilation of nitrogen by plants is influenced by weather conditions, but also by various
trace elements. Soil pH influences the solubility and assimilability of trace elements that play a
role in achieving high nitrate concentrations in plants. Molybdenum is a cofactor of nitrate-
reductase (which reduces nitrates to the more toxic nitrites), being antagonized by manganese.
Also, successive stages of reduction of nitrates to nitrites also require copper, iron, and
magnesium.

Intoxication can also occur as a result of the consumption of plants from the Brassicaceae
family (syn. Cruciferae), such as cabbage, kale, cauliflower, broccoli, turnip, Chinese cabbage,
rapeseed, etc., treated with some herbicides (e.g., 2,4-D, 2,4,5-T), which alter the protidic
metabolism of these plants in the direction of nitrate production.

Also, a cause of intoxication could be plant storage conditions (humidity and heat or moulding),
which favour the transformation of nitrates into nitrites.

Another possible cause may be animal pica syndrome. For example, piglets consume liquid
manure, while cattle have a real pleasure to directly consume nitrogen fertilizers.

Nitrate and nitrite intoxication also occurs as a result of drinking water polluted with
nitrogenous substances, which can reach water by draining in the groundwater after land
treatment, or as a result of pollution of water sources with liquid manure, dung, ammonia
waters, silage brine, or decomposed organic materials.

The maximum allowable limit (MAL) of NO2 is 0.5 mg/L, and MAL of NO3 is 50 mg/L.

Toxicokinetics

The toxicity depends on the species (ruminants are sensitive), age (young animals are more
sensitive), health status, dose, and water consumption (if the animals are watered immediately
after toxicant ingestion, intoxication occurs more quickly).

Toxic doses are 1g/kg for cattle, sheep, and equines, 0.7 g/kg for pigs, 1.9 g/kg for leporids, but
they can also reach 4 g/kg.

Toxicity depends on the chemical substance, nitrites being 6-12 times more toxic than nitrates.
Also, potassium salts are more toxic than sodium salts.

Normal levels of nitrates in the blood are 3.4±0.2 mg/100 ml in cattle, 5.4±1.2 mg/100 ml in pigs
and 3.5±0.3 mg/100 ml in sheep.

Predisposing factors intervene in inducing the intoxication, such as starvation, which increase
the sensitivity to nitrate-nitrite intoxication, while feeding with adequate rations may increase
3the tolerance of bovines, which will be able to tolerate amounts of nitrate-nitrites high enough
to convert 50% of haemoglobin into methaemoglobin, without any harmful effects.

The change in ruminal pH, the existence of anaemias or other diseases that decrease the level
of haemoglobin, as well as the previous conversion of nitrates into nitrites, are other
predisposing factors that may hasten the onset of the symptoms of intoxication.

Toxicodynamics

Nitrates have a local irritant action, leading to congestion and bleeding in the digestive tract and
renal congestion.

Nitrates, in the presence of nitrate reductase, from the rumen, blood, or feed, are reduced to
nitrites. Nitrites then decompose into ammonia and hydroxylamine.

A nitrite molecule interacts with two oxyhaemoglobin molecules. This interaction is actually an
oxidation of Fe2+ (ferrous iron) to Fe3+ (ferric iron), thus converting haemoglobin to
methaemoglobin, which is not able to carry oxygen, leading to tissue anoxia.

Nitrites also have a strong vasodilating action, effect for which they are therapeutically used,
but which, in the case of intoxication, produce peripheral vascular collapse.

Nitrites also reduce vitamin A and E, mainly inhibiting the conversion of carotenoids into vitamin
A in the liver, possibly as a result of the inhibitory action of nitrites on the thyroid.

Nitrites reduce the activity of acetylcholinesterase, which makes the mechanism of action and
some of the clinical manifestations very similar to those observed in the acute form of the
organophosphate intoxication.

Clinical Signs

The effect of nitrates is maximum on the digestive system (vomiturition, vomiting, colic,
diarrhoea) and on the kidneys (pollakiuria, polyuria following renal congestion, with loss of Ca
and Mg ions).

Nitrites induce the formation of methaemoglobin. Normal methemoglobinemia is 2-4%.
Respiratory failure occurs at 13-15%, at 50% respiratory failure being severe. At levels of over
60%, there is severe tissue asphyxia.

The main signs are the consequence of hypoxia, represented by restlessness, tachypnoea,
dyspnoea, oral breathing, cyanosis, tachycardia, and venous pulse. The onset of vertigo,
astasia, and muscle cramps indicate the onset of peripheral collapse following the vasodilating
effect of nitrites. Abortion is seen in gestating females. Surviving cattle often have interstitial
pulmonary emphysema.

In chronic evolutions, in case of prolonged consumption of subtoxic doses of nitrates, there is
an increase in signs of avitaminosis A, with growth delays in youth, decreased milk production,
recurrent indigestion, reproduction disorders (infecundity, abortions, mortality in newborns),
following the depletion of the liver reserves of vitamin A in mothers.

Anatomopathological Changes

4Characteristic anatomopathological changes are represented by the chocolate colour of the
blood. Less often, blood can also be bright red, due to the formation of nitrosyl-haemoglobin
(requiring differential diagnosis to cyanide intoxication).

When opening the body, sometimes the pungent smell of nitrogen gases, congestion and severe
bleeding in the forestomaches, stomach, intestines, renal congestion, submucous and
subserous haemorrhages (congestion is due to the vasodilating effect of nitrites) can be
observed.

The apparent mucous membranes are cyanotic. Aborted foetuses are mummified, or have
asphyxia-related changes (hydrothorax, ascites, perirenal and subepicardial haemorrhages,
splenic and hepatic necrotic foci, calcified and circumscribed cotyledons).

Diagnosis

The diagnosis is relatively easy to put in the acute evolution form, but slightly harder in subacute
and especially subclinical intoxications.

Differential diagnosis is required to rule out intoxications with silage gases, hydrocyanic acid,
cyanogenic glycosides and cyanides (bright red blood), cardiotoxic plants (e.g., common
foxglove, oleander), digoxin, hydrogen sulphide (dark red blood), carbon monoxide
(carboxyhaemoglobin), MgSO4, and calcium gluconate.

In ruminants, differential diagnosis also includes grass tetany and interstitial atypical
pneumonia.

In pigs, differential diagnosis also includes salmonellosis, swine erysipelas, swine fever, heart
or respiratory diseases.

Therapeutic Diagnosis

Diagnosis
Therapeutic diagnosis can be established by administering methylene blue. To confirm the
diagnosis, it is necessary to evaluate the methemoglobinemia and dose nitrates and nitrites in
feed, water, and biological fluids (serum, urine, ruminal juice). Levels considered harmful are
300 mg nitrate/L of drinking water and 700-1500 mg nitrate/kg feed. A level of 1% nitrate in feed
causes abortion.

Prophylaxis

As prophylaxis, the following measures are recommended:

• periodic checks of drinking water and feed
• obligation to comply with the waiting period of several weeks from the time of treatment
  of a field until the allowance for consumption of plants
• judicious application of herbicides (e.g., 2,4-D)
• supervising the storage and handling of nitrogen fertilisers
• prohibition of the storage of feed alongside fertilisers
• administration of satisfactory rations, abundant in carbohydrates, that increase
  tolerance to nitrates
• preventive administration of vitamin A
• treatment of allotriophagia (in pigs)

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