Anilide, Acetamides, or Amide
These herbicides (propanil, cypromid,
are plant growth regulators, and some members of this group are more toxic than
others. Hemolysis, methemoglobinemia, and immunotoxicity have occurred after
experimental exposure to propanil. (For discussion of bensulide, see Organophosphate Compounds.)
Bipyridyl Compounds or
Quaternary Ammonium Herbicides
The bipyridyl compounds (diquat, paraquat) produce toxic
effects in the tissues of exposed animals by development of free radicals.
Tissues can be irritated after contact. For example, mouth lesions have been
seen after contact with recently sprayed pastures. Skin irritation and corneal
opacity occur on external exposure to these chemicals, and inhalation is
dangerous. Animals, including people, have died as a result of drinking from
Paraquat and diquat have somewhat different mechanisms of
action. Diquat exerts most of its harmful effects in the GI tract. Animals
drinking from an old diquat container showed anorexia, gastritis, GI distension,
and severe loss of water into the lumen of the GI tract. Signs of renal
impairment, CNS excitement, and convulsions occur in severely affected
individuals. Lung lesions are uncommon.
Paraquat has a biphasic toxic action after ingestion.
Immediate effects include excitement, convulsions or depression and
incoordination, gastroenteritis with anorexia, and possibly renal involvement
and respiratory difficulty. Eye, nasal, and skin irritation can be caused by
direct contact, followed within days to 2 wk by pulmonary lesions as a result of
lipid-membrane peroxidation and thus destruction of the type I alveolar
pneumocytes. This is reflected in progressive respiratory distress and is
evident on necropsy as pulmonary edema, hyaline membrane deposition, and
There is no specific treatment. Because these chemicals
are absorbed slowly, intensive oral administration of adsorbents in large
quantities and cathartics is advised. Bentonite or Fuller's earth is preferred,
but activated charcoal will suffice. Toxicity of paraquat is enhanced by
deficiency of vitamin E or selenium, oxygen, and low tissue activity of
glutathione peroxidase. Therefore, vitamin E and selenium with supportive
therapy may be useful in early stages of intoxication. Excretion may be
accelerated by forced diuresis induced by mannitol and furosemide. Oxygen
therapy and fluid therapy are contraindicated.
Carbamate and Thiocarbamate
These herbicides (terbucarb, asulam, carboxazole, EPTC,
pebulate, triallate, vernolate, butylate, thiobencarb) are moderately toxic;
however, they are used at low concentrations, and poisoning problems would not
be expected from normal use. Massive overdosage, as seen with accidental
exposure, produces signs similar to those induced by the insecticide carbamates,
with lack of appetite, depression, respiratory difficulty, mouth watering,
diarrhea, weakness, and seizures. Thiobencarb has induced toxic neuropathies in
neonatal and adult laboratory rats. It appears to increase permeability of the
blood-brain barrier. There is no suitable antidote. Supportive and symptomatic
treatment is recommended.
Aromatic/Benzoic Acid Compounds
The herbicides in this group (chloramben, dicamba, and
naptalam) have a low order of toxicity to domestic animals, and poisoning after
normal use has not been reported. Environmental persistence and toxicity to
wildlife is also low. The signs and lesions are similar to those described for
the phenoxy acid derivatives (see Phenoxy Acid Derivatives). There
is no suitable antidote. Supportive and symptomatic treatment is
These acids and their salts and esters (2,4-D [2-4-dichlorophenoxyacetic acid],
dalapon, dichlorprop [2,4-DP],
[2,4,5-trichlorophenoxyacetic acid], 2,4-DB, MCPA, MCPB, mecoprop, and silvex) are commonly used to control
undesirable plants. As a group, they are essentially nontoxic to animals, except
silvex which is unusually very toxic. When large doses are fed experimentally,
general depression, anorexia, weight loss, tenseness, and muscular weakness
(particularly of the hindquarters) are noted. Large doses in cattle may
interfere with rumen function. Dogs may develop myotonia, ataxia, posterior
weakness, vomiting, diarrhea, and metabolic acidosis. The oral
LD50 for 2,4-D and 2,4,5-T in dogs is 100–800 mg/kg.
Even large doses, up to 2 g/kg, have not been shown to leave residues in the fat
of animals. These compounds are plant growth regulators, and treatment may
result in increased palatability of some poisonous plants as well as increased
nitrate and cyanide content.
The use of 2,4,5-T was curtailed because extremely toxic
contaminants, collectively called dioxins (TCDD and HCDD), were found in
technical grade material (see Persistent Halogenated Aromatic Poisoning). TCDD is
considered carcinogenic, mutagenic, teratogenic, and fetotoxic, and is able to
cause reproductive damage and other toxic effects. Although manufacturing
methods have reduced the level of the contaminants, use of this herbicide is
very limited worldwide.
Treatment is usually symptomatic and supportive. IV fluids
should be given to promote diuresis. Adsorbents and drugs that aid in
restoration of liver function are recommended.
Several substituted dinitrophenols alone or as salts such
as dinitrophenol, dinitrocresol, dinoseb, and binapacryl are highly toxic to all
classes of animals (LD50 20–100 mg/kg body wt). Poisoning
can occur if animals are sprayed accidentally or have immediate access to forage
that has been sprayed, because these compounds are readily absorbed through skin
or lungs. Dinitrophenolic herbicides markedly increase oxygen consumption and
deplete glycogen reserves. Clinical signs include fever, dyspnea, acidosis,
tachycardia, and convulsions, followed by coma and death with a rapid onset of
rigor mortis. Cataracts can occur in animals with chronic dinitrophenol
intoxication. In cattle and other ruminants, methemoglobinemia, intravascular
hemolysis, and hemoproteinemia have been seen. Exposure to these compounds may
cause yellow staining of the skin, conjunctiva, or hair.
An effective antidote for dinitrophenol compounds is not
known. Affected animals should be cooled and sedated to help control
hyperthermia. Use of physical cooling measures (eg, cool baths or sponging and
keeping the animal in a shaded area) are recommended. Atropine sulfate, aspirin,
and antipyretics should not be used. Dextrose-saline infusions in combination
with diuretics and tranquilizers such as diazepam (not barbiturates) are very
useful. Phenothiazine tranquilizers are contraindicated. IV administration of
large doses of sodium bicarbonate (in carnivores), parenteral vitamin A, and
oxygen therapy may be useful. If the toxin was ingested and the animal is alert,
emetics should be administered; if the animal is depressed, gastric lavage and
treatment with activated charcoal should be performed.
In ruminants with methemoglobinemia, methylene blue
solution (2%–4%, 10 mg/kg, IV, tid, during the first 24–48 hr) and ascorbic acid
(5–10 mg/kg, IV) are useful.
Organophosphate compounds such as glyphosate,
are broad-spectrum, nonselective systemic herbicides. Glyphosate and glufosinate
exist as free acids, but because of their slow solubility they are marketed as
the isopropyl amine or trimethylsulfonium salts of glyphosate and the ammonium
salt of glufosinate. These are widely used herbicides with low toxicity.
However, they are toxic to fish. Sprayed forage appears to be preferred by
cattle for 5–7 days after application, but this causes little or no
Dogs and cats show eye, skin, and upper respiratory tract
signs when exposed during or subsequent to an application to weeds or grass.
Nausea, vomiting, staggering, and hindleg weakness have been seen in dogs and
cats exposed to fresh chemical on treated foliage. The signs usually disappear
when exposure ceases, and minimal symptomatic treatment is needed. However,
formulations of these compounds may lead to hemolysis and GI, cardiovascular,
and CNS effects due to presence of the surfactant polyoxyethyleneamine.
Treatment should include washing the chemical off the skin, evacuating the
stomach, and tranquilizing the animal. Massive exposure with acute signs due to
accidental poisoning should be handled as an organophosphate poisoning (see Organophosphates (Toxicity)).
Bensulide, listed as a plant growth regulator, has an oral
LD50 in rats of 271–770 mg/kg; in dogs, the lethal
dose is >200 mg/kg. The most prominent clinical sign is anorexia, but other
signs are similar to those caused by 2,4-D poisoning.
Triazolopyrimidine herbicides includecloransulam-methyl,
metosulam. The acute oral
toxicity is very low. There is no suitable antidote. Supportive and symptomatic
treatment is recommended.
The ureas and thioureas (polyureas) are available under
different names such as diuron, fluometuron,
linuron, buturon, chlorbromuron,
metoxuron, monuron, neburon, parafluron,
thidiazuron. Of these, diuron
and fluometuron are the most commonly used in the USA, whereas isoproturon is
mostly used in other countries. In general, these compounds have low acute
toxicity and are unlikely to present any hazard in normal use, except
tebuthiuron, which may be slightly hazardous. Cattle are more sensitive to
polyurea herbicides than sheep, cats, and dogs.
Signs and lesions are similar to those described for the
phenoxyacetic herbicides (see Phenoxy Acid Derivatives). The
substituted urea herbicides induce hepatic microsomal enzymes and may alter
metabolism of other xenobiotic agents. Altered calcium metabolism and bone
morphology have been seen in laboratory animals. Recovery from diuron
intoxication is quick (within 72 hr), and no signs of skin irritation or dermal
sensitization have been reported in guinea pigs. After repeated administration,
hemoglobin levels and RBC counts are significantly reduced, while methemoglobin
concentration and WBC counts are increased. Increased pigmentation (hemosiderin)
in the spleen is seen histopathologically. Linuron in sheep causes
erythrocytosis and leukocytosis with hypohemoglobinemia and hypoproteinemia,
hematuria, ataxia, enteritis, degeneration of the liver, and muscular dystrophy.
In chickens, it leads to weight loss, dyspnea, cyanosis, and diarrhea. It is
nontoxic to fish. Fluometuron is less toxic than diuron. In sheep, depression,
salivation, grinding of teeth, chewing movements of the jaws, mydriasis,
dyspnea, incoordination of movements, and drowsiness are commonly seen. On
histopathology, severe congestion of the red pulp with corresponding atrophy
of the white pulp of the spleen and depletion of the lymphocyte elements have
been reported. The acute LD50 of isoproturon in rats is
similar to that of diuron.
Polyurea herbicides have been suspected to have some
mutagenic effects but do not have carcinogenic potential. In general, these
compounds do not cause developmental and reproductive toxicity, except for
monolinuron, linuron, and buturon, which are known to cause some teratogenic
abnormalities in experimental animals. There is no suitable antidote. Supportive
and symptomatic treatment is recommended.
Alkanoic Acids or Aryloxyphenoxypropionic Compounds
Members of this group (diclofop, fenoxaprop,
fluazifop, haloxyfop) have moderately low
toxicity (acute oral LD50 in rats 950 mg/kg to >4,000
mg/kg), except for haloxyfop-methyl (LD50 ~400 mg/kg).
These compounds are more toxic if exposure is dermal. The dermal
LD50 of diclofop in rabbits is only 180 mg/kg. There
is no suitable antidote. Supportive and symptomatic treatment is
Toxicity of this group of herbicides
chloremuron) appears to be
quite low. The oral acute LD50 in rats is in the range of
4,000–5,000 mg/kg. The dermal acute LD50 in rabbits is
~2,000 mg/kg. There is no suitable antidote. Supportive and symptomatic
treatment is recommended.
Triazines and triazoles have been used extensively as
selective herbicides. These herbicides are inhibitors of photosynthesis and
include both the asymmetric and symmetric triazines. Examples of symmetric
triazines are chlorostriazines (simazine, atrazine, propazine, and
thiomethyl-s-triazines (ametryn, prometryn, terbutryn), and
methoxy-s-triazine (prometon). The commonly used
asymmetric triazine is metribuzin.
These herbicides have low oral toxicity and are unlikely
to pose acute hazards in normal use, except ametryn and metribuzin, which may be
slightly to moderately hazardous. They do not irritate the skin or eyes and are
not skin sensitizers. The exceptions are atrazine, which is a skin sensitizer,
and cyanazine, which is toxic by the oral route. Sensitivity of sheep and cattle
to these herbicides is appreciably high. The main signs are anorexia, hemotoxia,
hypothermia, locomotor disturbances, irritability, tachypnea, and
hypersensitivity. Simazine is excreted in milk, so it is of public health
concern. Atrazine is more toxic to rats but comparatively less toxic to sheep
and cattle than simazine. When cultured human cells are exposed to atrazine,
splenocytes are damaged; bone marrow cells are not affected. Atrazine induces
liver microsomal enzymes and is converted to N-dealkylated
derivatives. In contrast to simazine, it is not excreted in milk. There is no
suitable antidote. Supportive and symptomatic treatment is recommended.
Protoporphyrinogen Oxidase Inhibitors
Protox inhibitors may be diphenyl ether (DPE) or
non-diphenyl ether (non-DPE) such as nitrofen and oxadiazon. In the past few
years, numerous other non-oxygen-bridged compounds (non-DPE protox inhibitors)
with the same site of action (carfentrazone, JV 485, and oxadiargyl) have been
marketed. Protox inhibitors have little acute toxicity and are unlikely to pose
an acute hazard in normal use. These compounds increase porphyrin levels in
animals when administered orally; the porphyrin levels return to normal within a
few days. There is no suitable antidote. Supportive and symptomatic treatment is
The most commonly used herbicides of this group are
butachlor, metolachlor, and
propachlor. Low doses in rats
and dogs do not produce any adverse effects, but longterm exposure in dogs
causes liver toxicity and affects the spleen. Ocular lesions produced by
alachlor are considered to be unique to the Long-Evans rat, because the response
has not been seen in other strains of rats or in mice or dogs.
Compared with other substituted anilines, propachlor is
severely irritating to the eye and slightly irritating to the skin. Propachlor
produces skin sensitization in guinea pigs. High doses of propachlor produce
erosion, ulceration, and hyperplasia of the mucosa and herniated mucosal glands
in the pyloric region of stomach and hypertrophy and necrosis of the liver in
rats. In dogs, there is poor diet palatability, which results in poor food
consumption and weight loss. There is no suitable antidote. Supportive and
symptomatic treatment is recommended.
Imidazolinone herbicides include imazapyr,
imazaquin. These are selective
broad-spectrum herbicides. Imidazolinone herbicides caused slight to moderate
skeletal myopathy and/or slight anemia in dogs during 1-yr dietary toxicity
studies with three structurally similar imidazolinones (imazapic, imazaquin, and
imazethapyr). There is no evidence of any adverse effect on reproductive
performance or of fetal abnormalities in rats or rabbits. There is no suitable
antidote. Supportive and symptomatic treatment is recommended.
terbacil are commonly used
methyluracil compounds. Toxic doses of bromacil can be hazardous, especially for
sheep, but no field case of toxicity has been reported. The nitrile herbicides,
ioxynil and bromoxynil, may uncouple and/or
inhibit oxidative phosphorylation. Ioxynil, presumably because of its iodine
content, causes enlargement of the thyroid gland in the rat.
A number of substances are used as defoliants in
agriculture. For example, sulfuric acid is used to destroy potato haulms and two
closely related trialkylphosphorothioates (DEF and merphos) to defoliate cotton. A
notable feature of the latter is that it produces organophosphate-induced
delayed neuropathy in hens. Chlomequat is used as a growth
regulator on fruit trees. The signs of toxicity in experimental animals indicate
that it is a partial cholinergic agonist.
Last full review/revision May 2014 by P. K. Gupta, PhD, Post Doc (USA), PGDCA, MSc VM & AH BVSc, FNA VSc,
FASc, AW, FST, FAEB, FACVT (USA), Gold Medalist