Page 596 - Veterinary Toxicology, Basic and Clinical Principles, 3rd Edition

Toxicity of Herbicides Chapter | 44 561

VetBooks.ir resulting in lower application rates than those of the older a public health concern (Susan, 2003). Atrazine is more
toxic to rats but comparatively less toxic to sheep and cat-
herbicides of this class. Some of them appear to be ana-
tle than is simazine. These herbicides are classified as
logs of the substrate or a substrate/product transition state
of the enzyme (Reddy et al., 1998; Dayan and Duke, liver microsomal enzyme inducers and are converted to
2010). N-dealkylated derivatives. In contrast to simazine, it is
After the first generation of Protox inhibitors (with the not excreted in milk. Triazines seem to have no potential
exception of oxadiazon), which were based on the DPE, to be mutagenic or to produce carcinogenicity in animals.
numerous other nonoxygen-bridged compounds (non-DPE However, feeding of very high levels of some triazines
Protox inhibitors) with the same site of action (carfentra- resulted in mammary tumors in rats. Terbutryn also
zone, JV 485 and oxadiargyl) were commercialized caused thyroid and liver tumors in female rats
(Dayan and Duke, 2010). Protox inhibitors have little (Breckenridge et al., 2010). The exception is cyanazine,
acute toxicity and are unlikely to pose any acute hazard in which is more acutely toxic, weak mutagenic, and results
normal use. These compounds increase the porphyrin in developmental toxicity, presumably because of the
levels in animals when administered orally, and the por- presence of cyano moiety (Hodgson and Meyer, 1997).
phyrin levels return to normal within a few days. Rats and
mice are sensitive and variegate porphyria-like symptoms Substituted Anilines
can be generated in mice with high doses of Protox inhi-
bitors. The majority of these compounds are neither muta- Substituted anilines are used as systemic herbicides.
genic nor carcinogenic in nature, and the developmental The commonly used herbicides are alachlor, acetochlor,
toxicity correlates with Protox accumulation. Most Protox butachlor, metolachlor and propachlor.
inhibitors, except bifenox and oxyfluorfen, are non- to This class of herbicides is slightly hazardous, except
moderately toxic to aquatic wildlife (Dayan and Duke, butachlor, which is not likely to pose any hazard. The
2010). It has been reported in rats that prenatal exposure compounds are nonirritant to eyes, slight to moderate skin
to sulfentrazone leads to neurodevelopmental effects (de irritant, and produce skin sensitization in guinea pigs.
Castro et al., 2007). Lower doses in rats and dogs do not produce any adverse
effects; however, long-term exposure in dogs causes hepa-
totoxicity and splenic effects. The ocular lesions (progres-
Triazines and Triazoles
sive uveal degenerative syndrome) produced by alachlor
These herbicides are inhibitors of photosynthesis and are considered to be unique to the Long Evans rat
include both the asymmetrical and the symmetrical tria- because the response has not been observed in other
zines. Examples of symmetrical triazines are chloro-S- strains of rats, mice, or dogs. At high oral doses, it may
triazines (atrazine, simazine, propazine, terbuthylazine lead to maternal and fetal toxicity but may not cause any
and cyanazine); the thiomethyl-S-triazines (ametryn, adverse effect on reproduction. It is neither teratogenic
prometryn and terbutryn), and the methoxy-S-triazine nor produces any microbial genotoxicity. Alachlor has the
(prometon) (Breckenridge et al., 2010). The commonly potential to produce thyroid tumors and adenocarcinomas
used asymmetrical triazine is metribuzin. of the stomach and nasal turbinates of Long Evans rats
These herbicides have low oral toxicity and are and in the lungs (bronchoalveolar) of CD-1 mice at high
unlikely to pose acute hazards in normal use, except for doses. It is considered to be a human carcinogen (Ahrens,
ametryn and metribuzin, which may be slightly to moder- 1994; Monsanto, 1997a,b; Heydens et al., 2010).
ately hazardous. They are generally neither irritants to the Long-term exposure of acetochlor to rats has no
skin or eye nor skin sensitizers. The exceptions are atra- adverse effects on reproductive performance. Acetochlor
zine, which is a skin sensitizer in guinea pigs, and cyana- is converted into a rat-specific metabolite that may be
zine, which is toxic by the oral route. However, related to the nasal and thyroid tumors, thus posing no
sensitivity of sheep and cattle to these herbicides is appre- genetic or carcinogenic hazard to humans (Ashby et al.,
ciably high. The main symptoms are anorexia, hemotoxia, 1996). Butachlor does not adversely affect reproductive
hypothermia, locomotor disturbances, irritability, tachyp- performance or pup survival. It is nongenotoxic. Butachlor
nea and hypersensitivity (Sandhu and Brar, 2000). Doses induced multiple tumors in SD rats but not in F344 rats or
of 500 mg/kg of simazine or 30 mg/kg atrazine for 30 60 CD-1 mice (Heydens et al., 2010). Metolachlor can
days are lethal to sheep. Deaths have been reported in increase the incidence of liver tumors in rats and has been
sheep and horses grazing triazine-treated pasture 1 7 classified as a possible human carcinogen (Monsanto,
days after spraying. Cumulative effects are not seen. 1991; Wilson and Takei, 1999; Heydens et al., 2010).
Metribuzin is slightly more toxic than simazine, but it Compared to other substituted anilines, propachlor is
does not produce any harmful effects in dogs fed at severely irritating to the eye and slightly irritating to the
100 ppm in the diet. Simazine is excreted in milk, so it is skin. Propachlor produces skin sensitization in guinea