Page 594 - Veterinary Toxicology, Basic and Clinical Principles, 3rd Edition

Toxicity of Herbicides Chapter | 44 559

VetBooks.ir doses (Table 44.1) and reproductive problems in humans nary fibrosis and increased respiratory distress. The mor-
Upon long-term exposure, there is progressive pulmo-
(Gupta, 2017). The group of compounds neither induces
adverse effects in the nervous and immune systems nor
phological changes seen in animals include degeneration
has any potential to induce cancer or mutagenicity in lab- and vacuolization of pneumocytes, damage to type I and
oratory animals. 2,4-D was found to be noncarcinogenic type II alveolar epithelial cells, destruction of the epithe-
to rats, mice and dogs. Dogs are the most sensitive ani- lial membranes and proliferation of fibrotic cells. The ani-
mals, whereas sheep, cattle and poultry are less sensitive mals die as a consequence of reduced gas exchange and
(Yano et al., 1991a,b; Munro et al., 1992; Kennepohl the development of severe hypoxia.
et al., 2010). Gross lesions include pulmonary congestion, edema
In dogs and pigs, GI signs of toxicity include anorexia, and hemorrhages. Lingual ulcers may be seen. Other find-
rumen atony, diarrhea, ulceration of oral mucosa, bloat ings include failure of lungs to collapse when chest is
and rumen stasis in cattle and vomiting, diarrhea, saliva- opened and areas of hemorrhages, fibrosis and atelectasis.
tion, etc. Neuromuscular signs include depression and Microscopic lesions include necrosis of type I alveolar
muscular weakness in cattle and ataxia, posterior weak- epithelial cells followed by progressive alveolar and intes-
ness (particularly the pelvic limbs) and periodic clonic tinal fibrosis and alveolar emphysema. Renal proximal
spasms (at high doses) in dogs. Silvex is unusual for tubular degeneration and moderate centrilobular hepatic
this group because it is very toxic and small doses degeneration may also be seen (Smith, 1997). In mice,
(2 6 mg/kg BW) may cause ill effects in dogs (Sandhu paraquat did not readily cross the placenta, whereas in
and Brar, 2000). rats it readily crossed the placenta, being detected in
fetuses within 30 min of an intravenous injection to preg-
nant rats (Lock and Wilks, 2010). It has neither carcino-
Bipyridyl Derivatives genic nor mutagenic potential; however, high doses
injected into pregnant rats and mice on various days of
This chemical class of herbicides includes paraquat gestation may cause significant maternal toxicity but do
0
0
(1,1 -dimethyl-4,4 -bipyridylium dichloride) and diquat not produce teratogenic effects (Bus and Gibson, 1975).
0
0
(1,1 -ethylene-2,2 -bipyridylium dibromide). Paraquat is Diquat is formulated as dibromide salt and is slightly
usually formulated as dichloride salt (also known as less toxic to dogs than is paraquat. After chronic expo-
methyl viologen). The bis(methyl sulfate) salt is no longer sure, the major target organs are the GI tract, the liver and
commercialized. Paraquat is nonselective and is a fast- the kidneys; however, lungs are not affected (Hayes,
acting contact herbicide. This compound is one of the 1982). The presence of cataracts in both dogs and rats has
most toxic of the commonly used herbicides, and the tox- been observed. Similar signs of toxicity have been seen in
icity varies in different animals depending on the formula- mice, guinea pigs, rabbits, dogs, and monkeys. Diquat has
tion and species used. The toxic doses (oral LD 50 )of no effect on fertility, is not teratogenic and produces feto-
paraquat and diquat in rats are 150 and 231 mg/kg BW, toxicity only at doses that are maternally toxic. In a multi-
respectively, and this class of herbicides is classified as generation study, at high doses, cataracts were observed
moderately hazardous. Paraquat is a skin and eye irritant in rats (FAO/WHO, 1993).
but not a skin sensitizer in animals. Mice are less sensitive
than rats to orally administered paraquat, whereas guinea Ureas and Thioureas
pigs, cats, monkeys and rabbits are more sensitive (Murray
and Gibson, 1972; Bus et al., 1976a,b; Nagata et al., 1992; The ureas and thioureas (polyureas) are available under
Lorgue et al., 1996; JMPR, 2003; Lock and Wilks, 2010). different names, such as diuron, fluometuron, isoproturon,
Cattle and sheep are more sensitive than other species. linuron, buturon, chlorbromuron, chlortoluron, chloroxur-
As indicated previously, paraquat and diquat have on, difenoxuron, fenuron, methiuron, metobromuron,
somewhat different mechanisms of action. Diquat exerts metoxuron, monuron, neburon, parafluron, siduron,
most of its harmful effects in the GI tract. The major tebuthiuron, tetrafluron and thidiazuron.
cause of death after exposure to paraquat is lung damage. In general, polyureas have low acute toxicity and
However, rabbits do not show signs of respiratory dis- are unlikely to present any hazard in normal use, with
tress. Immediate toxic effects include convulsions or the exception of tebuthiuron, which may be slightly
depression and incoordination, gastroenteritis and, finally, hazardous.
difficult respiration due to pulmonary edema and alveolar Diuron and monuron are potent inducers of hepatic
fibrosis (2 7 days). Animals that survive the first few metabolizing enzymes compared to those polyurea herbi-
days develop dehydration, pallor or cyanosis, tachycardia, cides with one or no halogen substitutions (chlortoluron
tachypnea, harsh respiratory sounds and emphysema or and isoproturon). Male rats are more sensitive than
pneumomediastinum. females to the enzyme-inducing activity of diuron, and