Page 610 - Veterinary Toxicology, Basic and Clinical Principles, 3rd Edition

Toxicity of Fungicides Chapter | 45 575

VetBooks.ir Metallic Fungicides LD 50 of 2047 mg/kg BW in the rat and is a mild irritant
in the rabbit eye. The compound has the potential to pro-
Inorganic metallic fungicides were first used in agriculture.
duce pulmonary adenoma, but it is neither embryotoxic
They are protective and preventive. Mercuric and mercu-
nor teratogenic in mice (Ballantyne, 2003). Chloroneb,
rous compounds have been withdrawn because of their tox-
quintozene, and dicloran have low toxicity, and dinocap
icity. Ethylmercury phosphate, 2-methoxyethylmercury
is a moderate eye irritant and has a human skin sensitizing
chloride, phenylmercury chloride and phenylmercury ace-
potential. HCB, like other organochlorine compounds,
tate are used as seed treatments for cereals and fodder beet
possesses all the properties of chemical stability, slow
(Lorgue et al., 1996). Cattle, sheep, and pigs are the most
degradation, and biotransformation with potential to accu-
affected species. Oral LD 50 ranges from 10 to 500 mg/kg
mulate in adipose tissues and organs containing a high
BW, depending on the species and the particular compound
content of lipid membranes, and it has the ability to
involved. The organic metallic fungicides are both aliphatic
induce a range of tissue cytochrome P450 as well as con-
and aromatic. Many are of moderate to high mammalian
jugate enzymes. Repeated exposure in animals results in
toxicity, with several being immunotoxic and neurotoxic.
hepatomegaly and porphyria as well as focal alopecia
Livestock exposed to mercurials may develop central ner-
with itching and eruptions, followed by pigmented scars,
vous system (CNS) and skin changes. The CNS signs
anorexia and neurotoxicity expressed as irritability, ataxia
include incoordination and ataxia, body swaying followed
and tremors. The compound can increase hepatic and thy-
by prostration, convulsions and death. CNS stimulation is
roid tumors in hamsters and is teratogenic in mice (renal
seen in calves, dogs, cats, rats, and humans. However, other
and palate malformations) and in rats (increased incidence
species (adult cattle, swine, and fowl) manifest CNS depres-
of 14th rib). HCB is also toxic to developing perinatal
sion. Other signs associated with organomercurials are
animals (Table 45.1) and causes adverse effects on the
bronchopneumonia, hyperpyrexia, epistasis, mucous mem-
immune system (Costa, 2008). PCP has oral LD 50 of
brane hemorrhages, hematuria and bloody feces. Skin
150 210 mg/kg BW in the rat. Common signs of toxicity
lesions include eczema, pustules, ulceration, keratinization,
are increased respiration, increased body temperature, tre-
dehydration, weakness, and death (Sandhu and Brar, 2009).
mors, convulsions, loss in righting reflex, and asphyxial
Typical organotins are di- and trialkyl and triphenyltins. In
spasms. Corneal injury may result from splashes or vapor
general, they are severely irritating to the skin, eyes and
overexposure. Toxicity is more often due to contamina-
mucosa, and several are hepatorenotoxic and immunotoxic.
tion of commercial-grade PCP. Technical-grade PCP
They have been shown to increase susceptibility to infec-
causes hepatic porphyria, increased microsomal monooxy-
tion, decrease lymphopoiesis and decrease T lymphocyte
genase activity and increased liver weight. Lethal dose in
production. Trialkyl tins cross the BBB and are centrally
cattle and sheep is in the range of 120 140 mg/kg BW.
neurotoxic (WHO, 1990).
Chronic toxicity leads to emaciation, weight loss, reduced
productivity (milk, eggs, meat, etc.), and increased mor-
Halogenated Substituted Monocyclic tality in poultry (ATSDR, 1994; Lorgue et al., 1996).
Aromatics
This class of chemicals includes chlorothalonil, dicloran, Chloroalkylthiodicarboximides
HCB, quintozene, PCP, dichlorophen, dinocap, tecnazene
(Phthalimides)
and chloroneb. Chlorothalonil is a nontoxic halogenated
benzonitrile fungicide. Dermal irritation has been This class of chemicals contains broad-spectrum fungi-
observed following repeated exposure in the rat and rab- cides (captan, folpet, captafol, etc.) used as surface pro-
bit. Chlorothalonil causes irreversible and severe ocular tectants on many crops. They are usually nontoxic to
lesions in rabbits. Signs of toxicity include decreased BW mammals. The oral LD 50 in rats is as follows: captan,
and decreased hematological parameters, increased abso- .9000 mg/kg BW; folpet, .10,000 mg/kg BW; and cap-
lute kidney weight, vacuolar degeneration in the proximal tafol, .5000 mg/kg BW. However, a low-protein diet
tubular epithelium, and hyperplasia of the forestomach. makes the animal more sensitive. Of this class of chemi-
Chlorothalonil is not genotoxic in vivo. Treatment-related cals, folpet and captafol, which are true phthalimides,
increase in renal tubular adenoma and carcinoma, squa- have been deregistered; only captan, being structurally
mous cell adenoma, and carcinomas of the forestomach of different with a cyclohexene ring, is being used. The com-
both species have been reported. Chlorothalonil is not a pound is a severe eye irritant because of its high reactiv-
developmental or reproductive toxicant when tested up to ity. Folpet induces incidences of diarrhea, vomiting,
doses that cause significant maternal toxicity and mater- salivation, reduced food intake, and reduced BW gain.
nal death; however, a significant increase in the incidence Testes weights are reduced in dogs. A single dose applied
of postimplantation loss due to early embryonic death has to the skin results in mild to low irritation. Long-term
been observed (Parsons, 2010). Tecnazene has an oral exposure to rats causes hyperkeratosis and acanthosis of