Page 612 - Veterinary Toxicology, Basic and Clinical Principles, 3rd Edition

Toxicity of Fungicides Chapter | 45 577

VetBooks.ir and developmental toxic effects in laboratory animals at fenpropimorph lead to developmental toxicity (Table 45.1),
with an increase in the total number of malformations
high oral doses (Table 45.1). Reproductive toxic effects
(JMPR, 2004).
include decreased sperm count, decreased testicular weights
and histopathological changes, whereas developmental tox-
icity effects include reduced fetal weight and anomalies of
Amides
the eyes (microphthalmia or anophthalmia), skull, and head
(hydrocephaly). The effects observed on the oocytes and Commonly used amide fungicides are fenhexamid, bena-
uterine weight in female rats is direct and is not mediated laxyl, metalaxyl, flutolanil, tolylfluanid, and dichlofluanid.
by endocrine changes (Jeffay et al., 1996; Spencer et al., These compounds are of low toxicity, except for metalaxyl,
1996). A high dose of carbendazim causes an increased which is slightly hazardous. With long-term exposure, bena-
incidence of diffuse proliferation of parafollicular cells of laxyl causes liver steatosis and hematological changes in
the thyroid in female rats. Both of these compounds are not rats and atrophy of seminiferous tubules in dogs. In mice,
carcinogenic in rats; however, lifetime exposure in mice increased mortality associated with amyloidosis has been
shows benign (not malignant), hepatocellular neoplasms observed. Reproductive abnormalities in rats include
and adenomas. Carbendazim is a developmental toxicant decreased BW gain, increased liver weight of pups and
and teratogen (JMPR, 2005). delayed ossification of cranial bones. Minor skeletal
deviations at maternally toxic levels have been reported
in rabbits (JMPR, 2005). Metalaxyl is a 1:1 mixture of
Conazoles
the R-enantiomer and S-enantiomer. Technical-grade
The conazole class of fungicides includes cyproconazole, metalaxyl-M consists of a minimum of 97% of the R-
diniconazole, triadimefon, triadimenol, propiconazole, enantiomer and 3% of the S-enantiomer. The two
and imazalil and has low to moderate acute toxicity. compounds are used as fungicides and are severe irritants to
Triadimenol is triazole, and triadimefon is closely related rabbits. The dog is the most sensitive species, with the liver
chemically to triadimenol, with increasing toxicity for as the target organ. Both substances cause hepatocellular
increasing isomer A ratios (isomer B is less toxic). enlargement in rats, whereas dogs show changes in blood
Triadimenol is nonirritating, whereas technical-grade tria- biochemical parameters indicative of hepatocellular damage
dimefon is sensitizing. The other symptoms of toxicity (JMPR, 2002). Dichlofluanid and tolylfluanid have a fluo-
include liver toxicity and CNS effects (general restless- rine atom substituted for one of the three chlorine atoms on
ness, alternating phases of increased and reduced motility, the trichloromethylthio moiety of captan and folpet. These
and aggressive behavior). Liver adenomas have been two compounds do not share a common mechanism of
observed in female mice. Developmental toxicity indi- action with captan and folpet with regard to mouse duode-
cates increased ovary and testes weights, increased super- nal tumors, principally because they do not induce these
numerary lumbar ribs with triadimenol, and increased tumors. Flutolanil is slightly irritating to the eye. Following
scapula malformations at maternal toxic doses in rabbits long-term exposure, it leads to enlargement of the liver,
after triadimefon exposure (JMPR, 2004). Propiconazole decreased BW and mild hematological disturbances, with
is not an eye irritant in rabbits, but it is irritating to rabbit evidence of increased thyroid weight in rats and dogs. On
skin and a skin sensitizer in guinea pigs. The compound long-term exposure to fenhexamid, the major target organ is
causes reduction in BW, liver toxicity, and adverse the kidney in rats and mice and the hematopoietic system
changes in erythrocytes (rat) and the stomach (dog). (increase in Heinz bodies) and adrenal gland in dogs. At
Following long-term exposure, liver hypertrophy and higher doses, delayed ossification has been observed in rab-
tumors (mice), uterine lumen dilation (rats), and develop- bits but is not teratogenic (JMPR, 2005). Tolylfluanid is a
mental toxicity indicative of reduced pup weight at paren- skin sensitizer and can lead to sedation, decreased motility,
terally toxic dose and skeletal variations in laboratory disturbed behavior and dyspnea. After intraperitoneal injec-
animals have been observed (JMPR, 2004). tion, signs consistent with local irritation, altered liver
enzyme activity, increased liver weight, and histopatholog-
ical changes that are indicative of liver toxicity in mice, rats
Morpholines
and dogs have been reported. At higher doses, signs of renal
The class of morpholine fungicides includes dodemorph, toxicity and discoloration of bones and teeth, particularly
fenpropimorph, and tridemorph. Dodemorph and fenpropi- the skull cap and incisors, have been observed. Alterations
morph are unlikely to cause acute hazards, whereas tride- in thyroid hormone levels have also been observed
morph is moderately hazardous. Dodemorph acetate is in a number of studies in rats. The compound causes
moderately irritating to rabbit skin and a severe irritant to decreased pup viability at maternally toxic doses but is not
rabbit eye. Fenpropimorph is a mild irritant to rabbit skin, teratogenic. These amides are neither genotoxic nor do they
whereas tridemorph is a nonirritant. Tridemorph and have any carcinogenic potential in animals (JMPR, 2002).