The carbamates are esters of carbamic acid. Unlike organophosphates (OPs), carbamates are not structurally complex. The volume of carbamates used now exceeds that of OPs because carbamates are considered safer than OPs.
The oral LD50 in rats is 0.9 mg/kg, and the dermal LD50 in rabbits is 5 mg/kg. Dogs are frequently poisoned with malicious intent, and cattle and deer are poisoned accidentally.
The oral LD50 in rats is 307 mg/kg, and the dermal LD50 in rabbits is 2,000 mg/kg. Carbaryl appears to be a safe insecticide as a 2% spray is nontoxic to calves, and 4% is nontoxic to mature cattle when applied dermally.
The oral LD50 in rats, dogs, chickens, ducks, pheasants, quails, and wild birds is 8, 19, 6.3, 0.415, 4.2, 5, and 0.42 mg/kg, respectively. Dogs are commonly poisoned with malicious intent by the tainting of food. The minimum toxic dose in cattle and sheep is 4.5 mg/kg, becoming lethal at 18 and 9 mg/kg, respectively. Cattle and other domestic animals are often poisoned by accidental exposure. Pigs have been poisoned after drinking water contaminated by this pesticide. In Africa, wildlife populations (including deer, lions, and birds) are declining because of the malicious use of carbofuran. The dermal LD50 in rabbits is 2,550 mg/kg.
The oral LD50 in rats is 17 mg/kg, and the dermal LD50 in rabbits is 5,000 mg/kg. Dogs have been commonly poisoned with malicious intent by the tainting of food. Cattle have been poisoned after consumption of forage inadvertently sprayed with methomyl.
The oral LD50 is 95 mg/kg in rats and >800 mg/kg in goats. The dermal LD50 in rabbits is >1,000 mg/kg.
Mechanism of Action of Organophosphate and Carbamate Toxicosis in Animals
The toxicity of OP and carbamate insecticides is due to inhibition of the AChE enzyme within the nervous tissue and at the neuromuscular junction. The OPs inhibit AChE irreversibly by phosphorylation, and carbamates inhibit AChE reversibly by carbamylation. As a result of AChE inhibition, accumulation of acetylcholine (ACh) occurs, which overstimulates muscarinic ACh receptors (mAChRs) and nicotinic ACh receptors (nAChRs). Overstimulation of these receptors leads to signs of hypercholinergic preponderance, such as hypersecretions (salivation, lacrimation, urination, and diarrhea), convulsions, and muscle fasciculations. Seizures and death ensue due to noncholinergic mechanisms involving hyperstimulation of N-methyl-D-aspartate (NMDA) receptors, adenosinergic, gamma-aminobutyric acid (GABA-ergic), monoaminergic systems, and others. The persistence of excitotoxicity for more than an hour can lead to oxidative and nitrosative stress, neuroinflammation and neurodegeneration in the cortex, amygdala, and hippocampus, which are areas of the brain primarily involved in initiation and propagation of convulsions and seizures. Finally, death occurs due to respiratory failure.
Clinical Findings for Carbamate Toxicosis in Animals
The carbamate insecticides act similarly to the OPs Organophosphate Toxicosis in Animals The organophosphates (OPs) are derivatives of phosphoric or phosphonic acid. Currently, there are hundreds of OP compounds in use, and they have replaced the banned organochlorine compounds... read more in that they inhibit AChE at nerve synapses and neuromuscular junctions. This inhibition is reversible because the inhibiting bond is much less durable; thus, the inhibition of blood AChE activity frequently is not evident in the laboratory. Signs include hypersalivation, GI hypermotility, abdominal cramping, vomiting, diarrhea, sweating, dyspnea, cyanosis, miosis, muscle fasciculations (in extreme cases, tetany followed by weakness and paralysis), and convulsions. The acronym SLUD (salivation, lacrimation, urination, and diarrhea) describes the overall clinical features of carbamate poisoning (ie, the cholinergic toxidrome). Death usually results from respiratory failure and hypoxia due to bronchoconstriction leading to tracheobronchial secretion and pulmonary edema.
Diagnosis of Carbamate Toxicosis in Animals
Diagnosis of carbamate poisoning usually depends on history of exposure to a particular carbamate and response to treatment with atropine. However, when a history of carbamate poisoning is not provided, but cholinergic signs and a clear positive response to atropine suggest carbamate or OP poisoning, AChE activity should be determined in RBCs or whole blood (live animals), or in brain cortex (dead animals). Enzyme activity that is substantially inhibited (>50%) is confirmatory. Signs of hypercholinergic activity are usually seen with AChE inhibition >70%. Screening GI contents for carbamate insecticides by gas chromatography–mass spectrometry (GC-MS) is helpful in identification, confirmation, and quantitation of a particular carbamate and aids in differential diagnosis if an OP insecticide is also involved.
Treatment of Carbamate Toxicosis in Animals
Treatment of carbamate poisoning is similar to that of OP poisoning in that atropine sulfate injections readily reverse the effects. Recommended dosages for atropine are as follows:
dogs and cats—dosed to effect (repeated as needed), usually 0.2–2 mg/kg, parenterally, one-fourth of the dose given IV and the remainder given SC (cats should be dosed at the lower end of this range)
cattle and sheep—0.6–1 mg/kg, one-fourth of the dose IV and the remainder SC, repeated as needed
horses and pigs—0.1–0.2 mg/kg, IV, repeated as needed
Pralidoxime (2-PAM) should not be used to treat carbamate poisoning but can be beneficial if poisoning is caused by a mixture of OPs and carbamates. Signs of excessive cholinergic activity may warrant its use, if the cause is OP exposure. Because 2-PAM can be fatal if given too rapidly, it must be administered slowly (ie, in 5% dextrose over a 10-minute period). Also, 2-PAM solution should be prepared fresh. Old solutions are known to produce cyanide.
The use of morphine or barbiturates is contraindicated.