Toxicology 2 Course 4: Pesticides, Fungicides, and Herbicides

CONTENTS

PESTICIDES

• FUNGICIDES
• DITHIOCARBAMATES
• PENTACHLOROPHENOLS
• DINITROPHENOLS AND DINITROORTHOCRESOLS
• COPPER-BASED FUNGICIDES
• HERBICIDES
• CHLORATES
• CHLOROPHENOXY ACID DERIVATIVES
• TRIAZINES

Emanuela Badea assistant professor | DVM | PhD | MSc Faculty of Veterinary Medicine of Bucharest UASVMI. PESTICIDES

I. 3. FUNGICIDES

I. 3. 3. DITHIOCARBAMATES

Dithiocarbamates are derivatives of dithiocarbamic acid. From a toxicological point of view, two classes of dithiocarbamic compounds with fungicidal effect are of interest:

• thiuram disulfides, represented by tetramethylthiuram disulfide (TMTD) . metal dithiocarbamates

Tetramethylthiuram disulfide - TMTD

TMTD (trade names: Tiuram, etc.) is used in agriculture as a fungicide, in the antifungal treatment of seeds, but also during vegetation (foliar fungicide). The intoxication is mainly found in intensively farmed birds and pigs. In birds, feeding on TMDT-treated seeds at 15 mg/kg feed causes the egg shells to deform. Prolonged administration (2 months) of feed containing 30-60 ppm TMDT causes embryonic death, decreased growth after hatching, hypovitaminosis A, and muscle asthenia. Poults are more resilient, withstanding doses of over 200 ppm in feed without producing clinically visible disorders.

Clinical signs and anatomopathological changes

In high doses, TMTD causes acute intoxication that manifests itself dramatically, but nonspecific, with nervous depression, ataxia, polyuria, diarrhoea (sometimes haemorrhagic), with nonspecific congestive-hemorrhagic lesions in the parenchymal organs. In pigs, in the acute and subacute forms of intoxication there is cortical nervous depression that alternates with short-term excitation crises, photophobia, dyspnoea, paresis, and paraclinical neutrophilia, with corresponding lymphopenia. The chronic form occurs after consuming feed treated with TMDT for 45 days, with more than 1 g/day. Clinically, physical asthenia and growth stagnation can be observed, and, paraclinically, leukopenia. The main lesion, in addition to hepatic and renal dystrophy, is thyroid hyperplasia. In dogs, intoxication results exclusively in thyroid disorders (TMTD blocks the enzymatic synthesis of organic compounds with iodine).

Diagnosis of TMTD Intoxication

The diagnosis is made on the basis of laboratory analyses of feed (chromatographic methods of TMTD identification), corelated with the anamnesis and clinical signs.

Metal dithiocarbamates

Metal dithiocarbamates are mainly represented by Zineb, Maneb, Urbazid, Nabam, which contain in their molecule zinc, manganese, arsenic, and sodium respectively. The mixture of Zineb and Maneb is called Mancozeb. These compounds are used to treat vegetables, fruits, ornamental plants, but also field crops. In sheep, chronic intoxication occurs as a result of consuming 500 mg/kg of feed for 15 days.

Clinical signs and anatomopathological changes in Metal Dithiocarbamates

The clinical signs are represented by anorexia, nervous depression, diarrhoea, and the anatomopathological changes observed are haemorrhages, liver degeneration, pulmonary congestion and oedema. In cattle, the same signs are found as in TMDT poisoning, with the addition of alopecia. In dogs, thyroid disorders with glandular hyperplasia and decreased amount of organic iodine are found.

Treatment for Dithiocarbamates

There is no suitable antidote. Supportive and symptomatic treatment is recommended.

I. 3. 4. PENTACHLOROPHENOLS

Pentachlorophenols are used in agriculture for their fungicide, bactericide, insecticide, molluscicide action, and they are also used for the protection of wood used in construction. The most important compound is pentachlorophenol - PCP (trade names: Pentachlorol, Santophen, Dowicide 7, etc.).

Toxicodynamics of PCP

PCP inhibits glycolytic oxidative phosphorylation, inactivates respiratory enzymes, destroys mitochondrial structure, chemically binds to actin and myosin, shortening muscle fibres, decreases tactile sensitivity, coagulates tissue proteins, causes hypotension, and causes painful anaesthesia.

Clinical signs of Pentachlorophenol Exposure

The overacute and acute forms appear a few minutes, maximum a few hours after the toxicant enters the body and is manifested with severe dyspnoea with a tendency to asphyxia, accompanied by cold sweats, hypersalivation, vomiting, diarrhoea and nervous depression. The subacute and chronic forms are more common, causing respiratory failure (noticeable even at very low effort), sweating, hyperthermia, sialorrhea, nervous depression, bradycardia, kidney pain (in the lumbar region), oliguria, haematuria, albuminuria.

Anatomopathological changes from PCP

There is a rapid onset of postmortem rigidity (in the order of minutes), the skin is hyperaemic, with lesions visible at the site of contact with the toxicant, stomatitis, esophagitis, gastroenteritis (in case of oral exposure), fatty liver degeneration, renal degeneration, subepicardial haemorrhage, and pulmonary congestion. The blood is brown, the gastric and intestinal contents smell of phenol, and the bladder is full of olive-green or brown urine.

Diagnosis of Pentachlorophenol Poisoning

The diagnosis is based on the anamnesis and clinical signs, but mainly on the phenol odour of the gastrointestinal contents.

Treatment for Pentachlorophenol Intoxication

Treatment consists of gastric lavage with saline solution, administration of charcoal suspension, olive oil (inactivates or reduces the absorption of the toxicant from the stomach), albumin water, and mucilage. Cutaneous decontamination is done by washing the animal with lightly bicarbonate water and detergent. Decontamination procedures are followed by respiratory support, oxygen therapy, fluid therapy, and symptomatic treatment.

I. 3. 5. DINITROPHENOLS AND DINITROORTHOCRESOLS

Dinitrophenols and dinitroorthocresols are by-products from the dye industry and are used in agriculture as fungicides, insecticides, herbicides, but also as wood protectors. The main products are dinitrophenol (DNP) and dinitroorthocresol (DNOC). The active substance is solid, yellow, odorless, tasteless, insoluble in water, soluble in organic solvents.

Toxicokinetics of DNP and DNOC

DNP and DNOC enter the body and are eliminated through any route (faeces, urine, milk, sputum, sweating, etc.). Elimination is slow. Oily preparations are absorbed rapidly through the transcutaneous route. In ruminants, part of the DNOC is metabolized by rumen microorganisms, and another part is metabolized in tissues, often the metabolites being less toxic.

Toxicodynamics of Dinitrophenols

DNP and DNOC stimulate oxidative metabolism, increasing the metabolic rate, which explains the state of liveliness observed at the onset of symptoms in intoxicated animals. DNP and DNOC uncouple oxidative phosphorylation and the energy generated from the electron transport chain is dissipated as heat rather than being used to produce ATP, decreasing the body's thermal efficiency. In conclusion, the energy provided by the oxidation of carbohydrates can no longer be useful to the cell and is lost in the form of heat, causing an increase in body temperature. There is an increased food consumption because of the increased metabolic rate and appetite. The animals that are fed normally, without increasing the feed ration, lose weight in a short time, the disappearance of fat deposits being visible.

Clinical signs of Dinitrophenol Intoxication

Intoxication is generally enzootic in nature and can have overacute, acute and chronic evolutions. The overacute form is characterized by manifestations of severe nervous excitation, with accelerated breathing and pulse. An important clinical sign is hyperthermia, followed by 1-2 hours of coma, and death shortly after. The higher the ambient temperature, the faster the evolution will be. In the acute form, initially, the general condition is good (for 10-15 minutes), the animal being very lively, and then, suddenly, there are nervous disorders associated with depression, tremors of the muscles of the hind limbs, then generalized convulsions, sweating, paresis of the forestomaches, colic, paresis and then paralysis of the limbs due to muscle atony, polyuria followed by oliguria, with brown or reddish-brown urine, severe dyspnoea that eventually progresses to asphyxia, seizures and death. The postmortem rigidity is installed immediately. In the chronic form, the skin, mucous membranes, hair, appendages appear jaundiced, progressive weight loss to cachexia, nervous depression, paresis of the forestomach, diarrhoea. If no measures are taken to remove the toxicant, the clinical manifestations worsen, leading to severe nervous disorders, dominated by cerebral ataxia syndrome. In humans, pigs and ducklings there is an opacification of the lens. In pigs, the initial state of exaggerated liveliness is followed by sudden death. Sows abort, and, in male pigs, spermatogenesis is affected.

Anatomopathological changes from Dinitrophenols

The installation of postmortem rigidity appears shortly, due to the increased lactic acid level in the striated muscles and the low level of ATP. Apparent mucous membranes, skin, hair, wool, feathers, lips, perioral region, penis, and vulva have a jaundiced appearance, due to the yellow colour of DNP compounds. The skin around the wattles in birds is bright yellow. The digestive mucosa is brown (from the mucosa of the oral cavity to the anus), and the mucosa of the fundic region of the stomach is wrinkled and has ulcers. The intestinal contents are yellow or brown. The mucosa and contents of the bladder are yellow. The muscles have yellow tendons, aponeuroses and interfascicular connective tissue, and the liver is enlarged, friable, and yellow. The kidneys have interstitial nephritis with subcapsular haemorrhage.

Diagnosis of Dinitrophenol Poisoning

The diagnosis is based on clinical signs, feed control (which is usually yellow) and laboratory tests.

Treatment for Dinitrophenol Intoxication

Gastrointestinal decontamination should include a gastric lavage with 5% sodium bicarbonate solution, administration of activated charcoal and saline purgatives. Oily purgatives and atropine (which suppresses perspiration) are contraindicated. Therapy is symptomatic. The aim is to lower the patients' body temperature, for which animals should be isolated in cool, outdoor places and should have water at their disposal. Barbiturates should be used to control seizures. Therapy should also include glucose IV.

I. 3. 6. COPPER-BASED FUNGICIDES

The most important copper-based fungicides are:

• bordeaux mixture (Bordo Mix): copper sulfate and calcium hydroxide/slaked lime
• burgundy mixture: copper sulfate and sodium carbonate . copper oxychloride
• copper sulphate (blue vitriol, bluestone)
• basic copper acetate (verdigris)
• copper acetoarsenite (Paris green)

Causes of Intoxication from Copper-Based Fungicides

Poisoning can occur through the consumption of plants recently sprayed with copper-based solutions, by accidental ingestion of copper-based solutions or nibbling of copper sulphate crystals from places accessible to birds.