Chlorinated Hydrocarbon Compounds (Toxicity)
Because of persistent tissue residues and chronic toxicity, use of chlorinated hydrocarbon compounds has been drastically curtailed. Only lindane and methoxychlor are approved for use on or around livestock. Detectable residues of some chlorinated hydrocarbon insecticides, including BHC, heptachlor, heptachlor epoxide, lindane, and oxychlordane, can be found in fatty tissue after acute or chronic exposure.
Aldrin is a potent insecticide similar to dieldrin with the same order of toxicity (see Dieldrin). It is no longer registered in the USA but was used for termite control. The oral LD50 in rats is 39 mg/kg, and the dermal LD50 in rabbits is 65 mg/kg. In farm animals, the toxic dose is ~15–30 mg/kg.
Benzene hexachloride (BHC) is composed of 12%–45% γ isomer. BHC was a useful insecticide for large animals and dogs but is highly toxic to cats in the concentrations necessary for parasite control. Only the γ isomer (γ−BHC, lindane) is a useful insecticidal agent; the other isomers are stored for excessively long periods in body tissues. Lindane, which contains >99% of the γ isomer, should be used in preference to the technical grade of BHC, which contains several isomers. The oral LD50 of lindane in rats is 76 mg/kg, and the dermal LD50 in rabbits is 500 mg/kg. Presently, BHC is not sold in the USA.
Cattle in good condition have tolerated 0.2% lindane applications, but stressed, emaciated cattle have been poisoned from spraying or dipping in 0.075% lindane. Horses and pigs appear to tolerate 0.2%–0.5%, and sheep and goats ordinarily tolerate 0.5% applications. Emaciation and lactation increase the susceptibility of animals to poisoning by lindane; such animals should be treated with extreme caution. Young calves are very susceptible to lindane and are poisoned by a single oral dose of 4.4 mg/kg. Mild signs appear in sheep given 22 mg/kg, and death occurs at 100 mg/kg. Adult cattle have tolerated 13 mg/kg without signs. BHC is stored in body fat and excreted in milk.
Chlordane is no longer registered as an insecticide in the USA. Exposure occurs when livestock consume treated plants or when they come in direct contact through carelessness and accidents. The lethal dose of chlordane for most species is in the range of 200–300 mg/kg. Very young calves have been killed by doses of 44 mg/kg, and the minimum toxic dose for cattle is ~88 mg/kg. Cattle fed chlordane at 25 ppm of their diet for 56 days showed 19 ppm in their fat at the end of the feeding. Topical emulsions and suspensions have been used safely on dogs at concentrations up to 0.25%, provided freshly diluted materials were used; dry powders up to 5% have been safe. The no-effect level in dogs in a 2-yr feeding study was 3 mg/kg. Pigeons and Leghorn cockerels and pullets suffered no effects after 1–2 mo exposure to vapors emanating from chlordane-treated surfaces. The oral LD50 in rats is 283 mg/kg, and the dermal LD50 in rabbits is 580 mg/kg.
Dieldrin is not a registered pesticide in the USA. Residues limit its application, and it is one of the most toxic chlorinated hydrocarbon insecticides. The oral LD50 in rats is 40 mg/kg, and the dermal LD50 in rabbits is 65 mg/kg. Young dairy calves are poisoned by 8.8 mg/kg, PO, but tolerate 4.4 mg/kg, whereas adult cattle tolerate 8.8 mg/kg and are poisoned by 22 mg/kg. Pigs tolerate 22 mg/kg and are poisoned by 44 mg/kg. Horses are poisoned by 22 mg/kg. Because of its effectiveness against insect pests on crops and pasture and the low dosage per acre, dieldrin is not likely to poison livestock grazing the treated areas. Diets containing 25 ppm of dieldrin have been fed to cattle and sheep for 16 wk without harmful effects other than residues in fat, which are slow to disappear. Great care must be exercised in marketing animals that have grazed treated areas or consumed products from previously treated areas. There is a zero tolerance level for residues in edible tissues.
Statements pertaining to dieldrin also apply, in general, to endrin, the most toxic of the three chlorinated cyclodiene insecticides.
Endosulfan is widely used to control insect and mite pests on a variety of crops and orchards. It is heavily used on tobacco. Endosulfan is very toxic to mammalian species. The oral LD50 in rats is 18 mg/kg, and the dermal LD50 in rabbits is 74 mg/kg. The LD50 of endosulfan in dogs is 77 mg/kg. Its lethal dose in cattle is 8 g. Generally, cattle are poisoned by accidental exposure, and dogs are poisoned by malicious intent. Exposure of cattle to endosulfan produces residues in the liver, kidneys, muscle, and milk.
Heptachlor is not currently registered in the USA and is not recommended for use on livestock in the USA. Among its few agricultural applications, heptachlor is used for residual control of subterranean termites. The oral LD50 in rats is 40 mg/kg, and the dermal LD50 in rabbits is 119 mg/kg. Because it is very effective against certain plant-feeding insects, it is encountered from time to time in some geographic areas grazed by livestock. Young dairy calves tolerate dosages as high as 13 mg/kg but are poisoned by 22 mg/kg. Sheep tolerate 22 mg/kg but are poisoned by 40 mg/kg. Diets containing 60 ppm of heptachlor have been fed to cattle for 16 wk without harmful effects other than residues in fat. Heptachlor is converted to heptachlor epoxide by animals and stored in body fat. For this reason, a specific analysis performed for heptachlor usually yields negative results, while that for epoxide is positive.
Methoxychlor is one of the safest chlorinated hydrocarbon insecticides and one of the few with active registration in the USA. The oral LD50 in rats is 5,000 mg/kg, and the dermal LD50 in rabbits is 2,820 mg/kg. Young dairy calves tolerate 265 mg/kg; 500 mg/kg is mildly toxic. While 1 g/kg produces rather severe poisoning in young calves, sheep are not affected. One dog was given 990 mg/kg/day for 30 days without showing signs. Six applications to cattle of a 0.5% spray at 3-wk intervals produced fat residues of 2.4 ppm; ~0.4 ppm of methoxychlor is found in milk 1 day after spraying a cow with a 0.5% concentration. Methoxychlor sprays are not approved for use on animals producing milk for human consumption. Cattle and sheep store essentially no methoxychlor when fed 25 ppm in the total diet for 112 days. If methoxychlor is used as recommended, the established tolerance in fat will not be exceeded. Commercial products are available for garden, orchard, and field crops, and for horses and ponies.
Numerous reports suggest that methoxychlor has negative reproductive effects in laboratory animal experiments, but this has not been seen in the field.
Toxaphene is no longer under active registration in the USA. It has been used with reasonable safety if recommendations were followed, but it can cause poisoning when applied or ingested in excessive quantities. The oral LD50 in rats is 40 mg/kg, and the dermal LD50 in rabbits is 600 mg/kg. Dogs and cats are particularly susceptible. Young calves have been poisoned by 1% toxaphene sprays, while all other farm animals except poultry can withstand 1% or more as sprays or dips. Chickens have been poisoned by dipping in 0.1% emulsions, and turkeys have been poisoned by spraying with 0.5% material. Toxaphene is primarily an acute toxicant and does not persist long in the tissues. Adult cattle have been mildly intoxicated by 4% sprays and severely affected by 8%. Adult cattle have been poisoned from being dipped in emulsions that contained only 0.5% toxaphene (an amount ordinarily safe) because the emulsions had begun to break down, allowing the fine droplets to coalesce into larger droplets that readily adhere to the hair of cattle. The resultant dosage becomes equivalent to that obtained by spray treatments of much higher concentrations. Toxaphene is lethal to young calves at 8.8 mg/kg but not at 4.4 mg/kg. The minimum toxic dose for cattle is ~33 mg/kg, and for sheep between 22 and 33 mg/kg. Spraying Hereford cattle 12 times at 2-wk intervals with 0.5% toxaphene produced a maximum residue of 8 ppm in fat. Cattle fed 10 ppm of toxaphene in the diet for 30 days had no detectable toxaphene tissue residues, whereas steers fed 100 ppm for 112 days stored only 40 ppm in their fat (this amount was eliminated 2 mo after the toxaphene was discontinued).
The chlorinated hydrocarbon insecticides are general CNS stimulants. They produce a great variety of signs—the most obvious are neuromuscular tremors and convulsions—and there may be obvious behavioral changes common to other poisonings and CNS infections. Body temperature may be very high. Affected animals are generally first noted to be more alert or apprehensive. Muscle fasciculation occurs, becoming visible in the facial region and extending backward until the whole body is involved. Large doses of DDT, DDD, endosulfan, lindane, and methoxychlor cause progressive involvement leading to trembling or shivering, followed by convulsions and death. With the other chlorinated hydrocarbons, muscular twitching is followed by convulsions, usually without the intermediate trembling. Convulsions may be clonic or tonic lasting from a few minutes to several hours, or intermittent and leading to the animal becoming comatose. High fever may accompany convulsions, particularly in warm environments.
Behavioral changes such as abnormal postures (eg, resting the sternum on the ground while remaining upright in the rear, keeping the head down between the forelegs, “head pressing” against a wall or fence, or continual chewing movements) may be seen. Occasionally, an affected animal becomes belligerent and attacks other animals, people, or moving objects. Vocalization is common. Some animals are depressed, almost oblivious to their surroundings, and do not eat or drink; they may last longer than those showing more violent symptoms. Usually, there is a copious flow of thick saliva and urinary incontinence. In certain cases, the clinical signs alternate, with the animal first being extremely excited, then severely depressed.
The severity of the signs seen at a given time is not a sure prognostic index. Some animals have only a single convulsion and die, whereas others suffer innumerable convulsions but subsequently recover. Animals showing acute excitability often have a fever >106°F (41°C). The signs of poisoning by these insecticides are highly suggestive but not diagnostic; other poisons and encephalitis or meningitis must be considered.
Signs of acute intoxication by chlordane in birds are nervous chirping, excitability, collapse on hocks or side, and mucous exudates in the nasal passages. Signs of subacute and chronic intoxication are molting, dehydration and cyanosis of the comb, weight loss, and cessation of egg production.
If death has occurred suddenly, there may be nothing more than cyanosis. More definite lesions occur as the duration of intoxication increases. Usually, there is congestion of various organs (particularly the lungs, liver, and kidneys) and a blanched appearance of all organs if the body temperature was high before death. The heart generally stops in systole, and there may be many hemorrhages of varying size on the epicardium. The appearance of the heart and lungs may suggest a peracute pneumonia and, if the animal was affected for more than a few hours, there may be pulmonary edema. The trachea and bronchi may contain a blood-tinged froth. In many cases, the CSF volume is excessive, and the brain and spinal cord frequently are congested and edematous.
Chemical analysis of brain, liver, kidney, fat, and stomach or rumen contents is necessary to confirm chlorinated hydrocarbon compound poisoning. The suspected source, if identified, should also be analyzed. Brain levels of the insecticide are the most useful. Whole blood, serum, and urine from live animals may be analyzed to evaluate exposure in the rest of the herd or flock. In food animal poisoning, if exposure is more than just the animals visibly affected, fat biopsies from survivors may be necessary to estimate the potential residue. Identification, confirmation, and quantitation of organochlorine insecticides are usually done by gas chromatography coupled with mass spectrometry.
There are no known specific antidotes to chlorinated hydrocarbon compound poisoning. When exposure is by spraying, dipping, or dusting, a thorough bathing without irritating the skin (no brushes), using detergents and copious quantities of cool water, is recommended. If exposure is by ingestion, gastric lavage and saline purgatives are indicated. The use of digestible oils such as corn oil is contraindicated; however, heavy-grade mineral oil plus a purgative hastens the removal of the chemical from the intestine. Activated charcoal appears to be useful in preventing absorption from the GI tract. When signs are excitatory, a sedative anticonvulsant such as a barbiturate or diazepam is indicated. Anything in the environment that stresses the animal (eg, noise, handling) should be reduced or removed if possible. If the animal shows marked depression, anorexia, and dehydration, therapy should be directed toward rehydration and nourishment either IV or by stomach tube. Residues in exposed animals may be reduced by giving a slurry of activated charcoal or providing charcoal in feed. Feeding phenobarbital, 5 g/day, may hasten residue removal.