Page 611 - Veterinary Toxicology, Basic and Clinical Principles, 3rd Edition

576 SECTION | VII Herbicides and Fungicides

VetBooks.ir the esophagus and stomach, particularly after folpet expo- Enhancement of hepatic thyroid hormone metabolism and
excretion are considered to be the mode of action of thy-
sure. Among ruminants, cattle are the most affected, and
roid tumorigenesis (Hurlety, 1998; Waechter et al., 2010).
captan produces toxicity (oral TD, 250 500 mg/kg BW)
with labored respiration, anorexia, depression, hydrotho- Cyprodinil induced microsomal protein and cytochrome
rax, ascites and gastroenteritis (Sandhu and Brar, 2009). P450 contents along with ethoxyresorufin O-deethylase,
Mutagenicity may be associated with these agents in vitro pentoxyresorufin O-depentylase and lauric acid 11- and
at exceptionally high doses required to elicit biological 12-hydroxylase, as well as cytosolic glutathione S-trans-
effects. These compounds degrade extremely rapidly in ferase activities in rats (Waechter et al., 2010). Cyrodinil
the presence of thiols, with a plasma half-life of only a and mepanipyrim induce the opposite effects on liver and
few seconds. However, duodenal tumors in mice have blood lipid parameters in rats. In general, anilinopyrimi-
been reported, which were considered to be due to the dines do not have adverse effects on developmental toxic-
irritation potential of compounds to the GI tract of rats ity, they are neither genotoxic nor have any carcinogenic
(Gordon, 2010). Some compounds of this class cause potential (Waechter et al., 2010).
developmental effects (Table 45.1), whereas others are
not proven because of, and/or masked by, maternal toxic- Carbamic Acid Derivatives
ity and possible nutritional deficits (Costa, 2008). Captan
induces hyperplasia of the crypt cells. Following treat- The carbamic acid class of fungicides includes dithiocar-
ment with folpet, immune function is reduced, villi length bamates (ferbam, thiram, ziram, propamocarb, etc.) and
is reduced and crypt compartments are expanded, thereby EDBCs (maneb, mancozeb, zineb, nabam, metiram, etc.).
reducing the villi-to-crypt ratio in mice (JMPR, 1990; In general, carbamic acid derivatives, except nabam, have
Tinston, 1995; Waterson, 1995; Gordon, 2010). The most low or moderate acute toxicity via the oral, dermal and
characteristic pathologic finding consists of necrotizing respiratory routes. The main features of toxicity include
and proliferative changes in the nonglandular portion of anorexia, diarrhea, and flatulence followed by neurologi-
the stomach, dilation of the small intestine and focal epi- cal effects, ataxia, muscular contractions and prostration.
thelial hyperplasia in the proximal part of the small intes- With repeated ingestion, there is a possibility of cutane-
tine in mice following treatment with captan (Gordon, ous effects, alopecia and a risk of antithyroid effects,
2010). Captafol differs from captan and folpet in a num- especially with maneb. Certain compounds inhibit ovula-
ber of ways, including structure and chemical activity. tion and egg laying (thiram and ziram). On histopathol-
Both of them have low acute toxicity. They are not carci- ogy, hepatic, renal and pulmonary congestion is common.
nogenic, mutagenic, or teratogenic. They are neither Occasionally, hepatic degeneration, ascites, enteritis, and
selective developmental toxins nor reproductive toxins. hydrothorax have been observed (Lorgue et al., 1996).
They are an irritant of mucus membranes, especially after Propamocarb is nonirritating to the eyes or skin. It
repeated exposures (Gordon, 2010). induces sensitization in a Magnusson Kligman maximi-
zation test. The signs of toxicity include hypokinesia,
lethargy, hunched posture, body tremors, clonic convul-
Anilinopyrimidines
sions, nasal hemorrhages, piloerection, staggering gait,
The anilinopyrimidine class of fungicides includes cypro- and ataxia. Vacuolar changes in various tissues including
dinil, mepanipyrim and pyrimethanil. The compounds choroid plexus in the brain and reduction in organ weights
have low toxicity and are unlikely to present acute have been observed in rats and dogs. Common develop-
hazards in normal use. Cyprodinil produces hepatomegaly ment and reproductive abnormalities include reduction in
with hepatocellular hypertrophy and increased thyroid copulation index (female rats) and BW, retardation in
weights associated with follicular cell hypertrophy and ossification (rat), and increased postimplantation loss
hypochromasia in rats. Subchronic exposure results in (rabbit) (JMPR, 2005). The principal target organ upon
kidney lesions in rats. The compound also causes single repeated exposure to EBDCs is the thyroid. These fungi-
cell necrosis in male mice and depletion of glycogen in cides alter thyroid hormone levels and/or weights. The
female mice, whereas in dogs, increased blood platelets developmental toxicity includes malformations and
have been observed at high doses. Mepanipyrim causes embryo fetotoxic effects at maternally toxic dose levels
hepatocellular fatty vacuolation and lipofuscin deposition with EBDCs in rats (Table 45.1)(Ollinger et al., 2010).
in Kupffer cells and hepatocytes of dogs, whereas such
changes are not observed in cyprodinil-treated rats Benzimidazoles
(Terada et al., 1998). Pyrimethanil produces thyroid fol-
licular cell tumors in rats and enhancement of hepatic thy- The major benzimidazole fungicides include benomyl, car-
roid hormone metabolism, which may be responsible for bendazim, and fuberidazole. Benomyl and carbendazim
thyroid tumorigenesis (Hurlety, 1998). The findings in the have low toxicity, whereas fuberidazole has moderate toxic-
thyroid were considered to be secondary to liver changes. ity. Both benomyl and carbendazim produce reproductive