Page 595 - Veterinary Toxicology, Basic and Clinical Principles, 3rd Edition

560 SECTION | VII Herbicides and Fungicides

VetBooks.ir this can lead to detoxication of EPN and O-demethylation that were exposed to fresh chemical on treated foliage
(Susan, 2003). Glyphosate is not a dermal irritant and
of p-nitro anisole. N-demethylation of aminopyrine
does not induce photosensitization; and formulations can
increases for 1 3 weeks and then returns to normal
(Hodgson and Meyer, 1997). Recovery from diuron intox- cause severe occupational contact dermatitis. Glyphosate
ication is quick (within 72 h), and no signs of skin irrita- is an ocular irritant in the rabbit and human, with minor
tion or dermal sensitization have been reported in guinea to moderate conjunctival irritation and slight iritis that
pigs. Linuron in sheep causes erythrocytosis and leukocy- usually disappears within 48 h after exposure (Acquavella
tosis with hypohemoglobinemia and hypoproteinemia, et al., 1999; JMPR, 2004). Formulations of glyphosate
hematuria and ataxia, enteritis, degeneration of the liver can cause intoxication in humans, which may be due to
and muscular dystrophy (Liu, 2010). In chickens, it leads the presence of surfactants such as polyoxyethyleneamine.
to loss of weight, dyspnea, cyanosis and diarrhea. It is This class of surfactants has been associated with hemoly-
nontoxic to fish (Lorgue et al., 1996). Fluometuron is less sis and with GI tract and central nervous system (CNS)
toxic than diuron. In sheep, depression, salivation, grind- effects (Talbot et al., 1991). There is no evidence of
ing of teeth, chewing movements of the jaws, mydriasis, mutagenic or carcinogenic potential of glyphosate.
dyspnea, incoordination of movements and drowsiness are Several investigations do indicate the teratogenicity and
commonly seen. On histopathology, severe congestion of reproductive toxicity of glyphosate. However, there is fur-
red pulp with corresponding atrophy of the white pulp of ther need to conduct such studies and other parameters
the spleen and depletion of the lymphocyte elements have involving risk assessment of these compounds (Antoniou
been reported (Mehmood et al., 1995). The acute LD 50 of et al., 2012). It does not have adverse effects on reproduc-
isoproturon in rats is similar to that of diuron and does tive performance in animals, except at very high doses
not produce any overt signs of toxicity, except at very maternal toxicity has been reported (JMPR, 2004). The
high doses. A single oral dose of isoproturon in mice may testicular seminiferous tubules of rats treated with glypho-
produce some neurotoxic effects at very high doses and sate indicated decreased epithelium lengths. The commer-
may reduce spontaneous and forced locomotor activity cial formulation of glyphosate (Roundup, Monsanto Co.)
(Sarkar and Gupta, 1993a,b). is a potent endocrine disruptor in vivo and causes distur-
Polyurea herbicides have been suspected to have some bances in the reproductive development of rats (Romano
mutagenic effects but do not have carcinogenic potential et al., 2010) and may lead to human breast cancer cells
(Liu, 2010). In general, the compounds do not cause growth via estrogen receptors (Thongprakaisang et al.,
developmental toxicity; however, buturon, linuron and 2013).
monolinuron are known to cause some teratogenic abnor- The acute oral toxicity of glufosinate is low, and glu-
malities in experimental animals (Table 44.1). Isoproturon fosinate is slightly more hazardous than glyphosate.
has been reported to cause maturational malformation of Common signs of toxicity include CNS excitation and
sperm and decreased spermatogenesis in rats (Liu, 2010). hypothermia in animals (Ebert et al., 1990; Hack et al.,
1994). Glufosinate ammonium formulation has been
involved in a number of poisoning cases (cardiovascular
Phosphonomethyl Amino Acids or Inhibitors and CNS adverse effects) possibly due to surfactant-
induced penetration into the CNS (Watanabe and Sano,
of Aromatic Acid Biosynthesis
1998). The compound is not considered to be mutagenic,
Two organophosphorus compounds, glyphosate (Roundup teratogenic, or carcinogenic, except in whole-embryo cul-
and Vision; N-(phosphonomethyl) glycine) and glufosi- ture. Teratogenic effects in mice have been observed,
nate (Basta; N-(phosphonomethyl)homoalanine), are resulting in apoptosis in the neuroepithelium of the devel-
broad-spectrum, nonselective systemic herbicides. oping embryo (Watanabe, 1997).
Although they exist as free acids, due to their low solubil-
ity, they are marketed as the isopropyl amine or trimethyl- Protoporphyrinogen Oxidase Inhibitors
sulfonium salts of glyphosate and the ammonium salt of
glufosinate. In the past, the Protox-inhibiting herbicides were often
Glyphosate has low acute oral toxicity in mice and termed “DPE-type herbicides,” and almost all of the
rats and is unlikely to pose acute hazard in normal use. Protox inhibitors were DPEs. This nomenclature led to
The LD 50 of trimethylsulfonium salt is 750 mg/kg BW. confusion concerning the classification of these herbicides
The animals most affected are cattle, sheep and dogs. because other DPE herbicides have an entirely different
Dogs and cats show eye, skin and upper respiratory tract molecular site of action (i.e., inhibition of acetyl-CoA car-
signs when exposed during or subsequent to an applica- boxylase). Since then, many other structurally related
tion to weeds or grass. Nausea, vomiting, staggering and Protox inhibitors have been commercialized. In general,
hind leg weakness have been reported in dogs and cats the newer products are more potent Protox inhibitors,