Toxicology of heavy metals and radioactive pollution

TOXICOLOGY 2

COURSE 7

CONTENTS

POLLUTION

• HEAVY METALS
• CADMIUM
• FLUORIDE
• MOLYBDENUM
• SELENIUM
• ZINC
• RADIOACTIVE POLLUTION

Emanuela Badea assistant professor | DVM | PhD | MSc Faculty of Veterinary Medicine of Bucharest UASVM

III. POLLUTION

III. 2. HEAVY METALS

III. 2. 3. CADMIUM

Cadmium (Cd) is considered to be one of the most toxic elements in the environment (alongside mercury, lead, or arsenic), its industrial-scale use triggering a serious ecotoxicological problem. Starting in 1910 and continuing through 1945, cadmium was released in significant quantities by mining operations in Japan. This triggered the appearance of a mass cadmium intoxication, which was named itai-itai disease, causing osteoporosis, osteomalacia, muscle pain, and the death of many people. The disease first appeared around 1912, but it was only in 1955 that cadmium was established to be the cause of the disease.

Cadmium is an element used in zinc, lead, and copper production technology (zinc mines and refineries, metallurgical plants, copper and lead processing plants, etc.). Cadmium is part of Ni- Cd batteries, and is also necessary for metal plating technology. Cadmium is a metal byproduct of mining, being toxic to most organisms.

Causes of intoxication

Cadmium poisoning may occur as a result of grazing on contaminated areas, such as:

• areas irrigated with Cd-polluted water from industrial waste
• areas fertilized with sludge from urban wastewater treatment plants containing large amounts of cadmium
• land situated in the vicinity of industrial sites that pollute the atmosphere with Cd
• land bordering heavily circulated road arteries, Cd being present in motor oils and tires

In addition, drinking from contaminated waters can also lead to Cd intoxication.

Feed low in calcium, zinc, iron, protein, and vitamin D worsens the intoxication.

Toxicokinetics

Cadmium enters the body, usually by the respiratory route, but also by the digestive (with increased absorption in iron deficient patients) and transcutaneous route.

Gastrointestinal absorption is done at the level of the duodenum, the absorption coefficient being higher in the acidic medium or when animals receive a dairy diet. After systemic absorption, Cd binds to metallothionein, a cysteine-rich protein, plays a role in the protection against metal toxicity and oxidative stress. Metallothionein can also chelate mercury, lead, arsenic, zinc, copper, and selenium.

Cadmium is distributed mainly to the liver and kidneys. Excretion is done through faeces, urine, saliva, and perspiration. It does not cross the placenta; however, low concentrations were found in breast milk.

2The half-life of Cd is between 7 and 30 years.

Toxicodynamics

Cadmium interferes with the homeostasis and function of different macrominerals and trace elements, such as Ca, Zn, Se or Fe, because of chemical similarities and competition for binding sites.

Cadmium displaces Zn in proteins and enzymes, such as erythrocyte and testicular carbonic anhydrase, alcohol dehydrogenase, alkaline phosphatase, DNA and RNA polymerases, renal carboxypeptidase, and superoxide dismutase, altering their structure and function. For example, by replacing enzymatic Zn in testicular tissue and destroying the structure of this tissue, Cd alters the qualities of sperm, which causes the reproduction to be compromised.

Cadmium decreases Fe levels in tissues and impairs erythropoiesis, thus leading to anaemia. Cd also decreases Se levels and compromises antioxidant defences, causing oxidative stress.

Cd antagonizes Ca at different levels. It decreases Ca absorption from the gastrointestinal tract, and it replaces Ca in hydroxyapatite crystals, causing skeletal damage and decreased bone density. In addition, Cd accumulates in renal tubular cells and interferes with Ca homeostasis, increasing renal elimination of Ca, and also leading to kidney dysfunction.

Cadmium also inhibits thiol-dependent enzymes, such as glutathione peroxidase, and other types of enzymes, like ATP-ase and aldolase.

Cd inhibits oxidative phosphorylation in the mitochondria, reducing DNA synthesis. It also inhibits pancreatic insulin.

Cadmium increases the activity of tyrosine hydroxylase, in this way stimulating the synthesis of precursors for adrenaline and noradrenaline.

Finally, cadmium is also embryotoxic, teratogenic, and carcinogenic.

Clinical signs

The acute form of cadmium intoxication, in case of oral exposure, is associated with anorexia, haematemesis, severe colic, diarrhoea, hypotension, myoclonia, convulsions, and polyuria. In case of respiratory exposure, progressive chemical pneumonia, pulmonary edema (coughing, foamy nasal discharge, dyspnoea), and respiratory arrest can appear.

The chronic form evolves with anaemia, balance disorders, skeletal issues, growth stagnation, compromised sperm quality, and infecundity.

Anatomopathological changes

The lesions observed more frequently are represented by fatty hepatic degeneration, lipid and vacuolar degeneration in the convoluted tubules, proliferative or fibrous interstitial pneumonia (perivascular or peribronchial), pulmonary oedema, pulmonary emphysema, and bone rarefaction. In addition, testicular swelling is observed, in the initial phase, followed by atrophy and, finally, sclerosis.

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Diagnosis

The diagnosis is established based on the anamnesis (epidemiological investigation), symptomatology, but also based on paraclinical exams which show hypochromic anaemia, hypokalemia, glycosuria, and proteinuria.

Treatment

Symptomatic therapy and decontamination measures should be done as soon as possible after exposure. Gastrointestinal decontamination will include emesis or gastric lavage, activated charcoal, albumin water, and alkaline carbonates (in monogastric animals).

Administration of zinc acetate is used as a specific antidote before absorption, because it competes with Cd for absorption in the gastrointestinal tract and reduces its absorption.

Symptomatic therapy should treat pulmonary oedema (antibiotics, antitussives - e.g., codeine), combat liver failure, and provide adequate fluids.

Chelating agents can be used to bind systemically distributed cadmium and promote its excretion. For this purpose, DMSA (dimercaptosuccinic acid) is recommended to be administered in a dose of 150 mg, 3 times/day, for 5 days, followed by 2 times/day, for 14 days. DMP / BAL and CaNa2EDTA are not recommended as they can increase Cd levels in the kidneys and potentially cause severe kidney injury.

III. 2. 4. FLUORIDE

Fluoride is found in appreciable quantities in various rocks (fluorite, apatite, cryolite, topaz, tourmaline, mica, combinations with silicates, fluorapatite, superphosphates, etc.).

Fluoride is also found in appreciable quantities in the dust and smoke of industrial plants (thermal power plants, foundries, pottery, ceramics, phosphate fertilizers, iron ore calcining furnaces, steel mills, glass factories, aluminium factories, etc.).

In the form of liquid and vapours, fluoride can mainly be emitted by aluminium and hydrofluoric acid factories.

Plants with 1 ppm fluoride can be dangerous to animals in certain circumstances.

Toxicokinetics

All animals are sensitive to fluoride, the order of sensitivity being: calves, dairy cows, other categories of cattle, sheep, goats, horses, pigs, and birds.

Additionally, the following categories are more sensitive:

• cattle breeds with high milk production
• animals with preexisting comorbidities
• animals receiving feed deficient in Ca, P, vitamins, proteins

4. animals that sit directly on the ground (breeders say that "evil comes from the ground"; in this way, the animals are more exposed to inhaling fluoride particles)

• animals going through high-temperature oscillations (from day to night or between seasons)

There is no danger of calf poisoning by blood route or by milk if the cow ingests less than 9 mg fluoride/kg body weight, the danger to the calf appearing only when it begins to consume the contaminated feed. The maximum concentration that adult bovine animals can tolerate in feed is estimated at 30-50 ppm F. Sheep and swine can tolerate 100 ppm F in feed, and domestic gallinaceous birds can tolerate 300 ppm F in feed.

Dental disorders can occur even at 0.2-0.5 mg/m3 air, the maximum allowed being 0.01 mg/m3/day.

Fluoride is easily absorbed from the digestive tract. It accumulates particularly in bone tissue (approximately 95-98% of the fluoride retained over time in the body) and is slowly eliminated through urine, milk, faeces, etc. (approximately 50% in two years, 50% of the remaining F after another two years, and so on).

Toxicodynamics

In toxic quantities, fluoride acts as an enzyme inhibitor, but more importantly it will exert its toxic effects on bone tissue, due to the affinity of fluoride for calcium and tricalcium phosphate, with which it forms complex fluorapatite molecules.

Fluoride in excess causes osteoporosis and moderate levels of osteosclerosis. At the same time, fluoride can also be fixed in structures that are richer in connective tissue, i.e., tendons, fascia, cartilage, etc., in the form of insoluble compounds, causing the animals to become cachectic.

Additionally, fluoride also produces kidney and thyroid disorders.

Clinical signs

Acute fluoride intoxication is associated with anorexia, decreased milk production, weight loss, the presence of a large amount of fluoride in the urine, and rapid death.

Fluorosis, the chronic form of fluoride intoxication, is expressed by limping, in one or more legs, anterior, posterior or diagonally. The limping leg is kept up, showing pain and tremors of the muscle groups, symptoms which are more pronounced in cattle. Therefore, the gait is rigid, with reduced flexion of the limbs. The limps are remitted in 2-3 weeks if the affected animal is removed from the contaminated area, or if the contaminated food and fluorinated water are removed. When the limping comes from grazing on contaminated pastures (after at least two grazing seasons), during winter it will not be manifested (if the feed is not contaminated).

Fractures occur especially at the level of the 3rd phalanx.

Other bone deformities are related to the increased size of the sternum, lower jaw, metacarpal, metatarsal, and phalangeal bones. At palpation, bone deformities are painful. Exostoses are located on the surface of long bones, but also in the ribs, a phenomenon called "beading of the 5