Chapter 47 Miscellaneous Herbicides, Fungicides, and Nematocides
Public perception of risk is greatly influenced by the voluntary nature of the risk. Thus consumers who purchase pesticide products for their own use often have a different perception of risk from these products compared with products used by others, such as veterinarians, farmers, or pest control or lawn care service operators. With the exception of the anticoagulant rodenticides, inquiries about possible pesticide poisoning in pet animals are more directly proportional to the frequency of use of the pesticide than to the toxicity ranking of the pesticide. The Environmental Protection Agency (EPA) reports on sales and usage of pesticides for the home and garden in 1999 are shown in Table 47-1. Cancellations of the residential uses of chlorpyrifos and diazinon have occurred since 1999, resulting in a significant decrease in the use of organophosphate insecticides in the home and garden sector.
|Pesticide||Millions of Pounds|
(Approximate quantities, 1999.)
Most often a pet owner suspects a pesticide poisoning when the pet shows clinical signs within a short time following a known environmental pesticide application. In virtually all incidents of illness, the pet owner wants a diagnosis of causation. If exposure to a toxic substance is suspected, an effort should be made to identify the substance, the date of application and exposure, and the method of pesticide use and exposure.
The clinical signs should be biologically consistent with the toxicology of the suspected toxicant. Seizures, for example, will not occur from exposure to urea fertilizer at any dose. The Internet is an excellent resource for information on pesticides. The Extoxnet site contains summaries of many pesticides.2 Material safety data sheets (MSDS) are available from suppliers and manufacturer home pages. And, of course, “the dose makes the poison.” Therefore, because the MSDS for a product lists the potential toxic effects, it is important to determine if the exposure was to the undiluted product or to some end-use dilution before concluding that there was a cause-and-effect relationship. For example, many liquid formulations of herbicides that must be diluted before use are severe eye irritants and may even be corrosive to the eye in the undiluted form. Yet when diluted for use (e.g., 1 tsp/gal of water), the end-use dilution can be less irritating to the eye than ordinary hair shampoo.
Vomiting is a common complaint in dogs and cats and is so nonspecific that the sign itself is not sufficient to establish a cause-and-effect relationship to a known pesticide exposure. It is generally well known that dogs and cats vomit after eating grass, whether or not it has been treated with aherbicide. The time course of onset of signs following pesticide exposure is also important. Both environmental degradation and low application rates make it most unlikely that exposure to pesticide application residues several days after the application would be toxicologically significant. Errors that result in overapplication of herbicides to plants most often produce visible damage to the plant. A twofold to threefold error in application of herbicide/fertilizer combinations to lawns will produce obvious signs of phytotoxicity.
Chemically, 2,4-D is 2-chloro-4-phenoxyacetic acid. It is usually formulated as salts, esters, or amine derivatives.2 2,4-D is used for control of broadleaf weeds on residential and commercial properties and in some areas on roadside rights-of-way. Residues on treated turf are in the range of 35 to 75 ppm and dissipate rapidly in the first several days following the application. A residue tolerance of 300 ppm has been established on pasture grasses.
Poisoning is almost always due to accidental ingestion of concentrates or sprays. Technical-grade phenoxy herbicides are irritating to the eye and mucous membranes and somewhat less irritating to skin and are also phytotoxic to most plants. Dogs appear to be somewhat more sensitive to phenoxy herbicides than other species of domestic animals. The approximate oral median lethal dose (LD50) for 2,4-D in the dog has been reported to be 100 mg/kg.3 However, Beasley and colleagues4 orally dosed English pointers with 8.8, 43.7, 86.7, 175, and 200 mg/kg 2,4-D, and all survived. Doses of 175 or 220 mg/kg of body weight produced overt signs of toxicosis characterized by myotonia, vomiting, and weakness. The lower doses did not produce overt clinical signs, but electromyographic abnormalities were detectable at exposures of 8.8 mg/kg. Multiple dosages of 20 mg/kg daily for approximately 3 weeks or 25 mg/kg for 6 days were lethal for dogs.3,5
Even at an exposure of 20 mg/kg of body weight, it is not likely that dogs will be significantly poisoned by exposure to properly treated lawns. The greatest hazard to dogs is ingestion of undiluted product, discarded or excess spray that had been previously mixed, or pools of spray that have collected in low spots or in containers. Arnold and colleagues6 attempted to produce 2,4-D toxicosis by placing English pointers on enclosed turf plots to confine the animals for controlled periods of continuous exposure. One enclosure was sprayed with 2,4-D at a rate of 168 mg/square meter, which is the maximum recommended rate for lawns, and another enclosure was sprayed at four times the maximum recommended rate. The dogs were placed in the enclosures within 30 minutes of spraying and were observed five times each day for a period of 7 days. Detailed clinical examinations included electromyograms, which were performed on days 1 and 7 after exposure. No adverse effects were detected in any of the clinical, hematological, biochemical, electrophysiological, or postmortem examinations. A 2,4-D concentration of 500 ppm (25 mg/kg of body weight) in the diet caused no ill effects in dogs during a 2-year study. In a more recent study, the level of 2,4-D at which no observable effects were noted in chronic toxicity in dogs was determined to be 1.0 mg/kg/day.7
Orally administered 2,4-D is rapidly and extensively absorbed by the gastrointestinal tract. The extent of dermal absorption varies according to the chemical form of the product and the species of animal, varying from about 5% for the acid in humans to 85% for the ester in rats. Absorbed 2,4-D salts and esters are rapidly converted to 2,4-D acid and excreted by the renal anion transport system. The renal anion transport system is saturable and appears to account for the longer half-life and greater sensitivity to toxicity in the dog. 2,4-D concentrations of 718 μg/mL and 1075 μg/mL were present in the serum of dogs dosed with 175 or 220 mg 2,4-D/kg of body weight, respectively. The peak serum concentration was 121 μg/mL following an oral exposure of 8.8 mg/kg of body weight.
2,4-D is widely distributed in tissues with little accumulation in fat. Plasma or serum appears to be the best specimen to use for laboratory confirmations of 2,4-D poisoning. Kidney tissue is an alternative sample. Pharmacokinetic data suggest that kidney to plasma ratios approach unity as the renal organic anion system becomes saturated. Data also suggest that plasma and kidney concentrations of up to 100 ppm may be present in animals that do not show signs of intoxication.
The clinical signs in dogs are characteristic and include vomiting and an initial disinclination to move and a passivity that gradually becomes worse as a pattern of myotonia develops. This rigidity of skeletal muscles is combined with ataxia, progressive apathy, depression, and muscular weakness, particularly of the posterior limbs. Myotonia has been produced by exposure to 2,4-D and 2,4,5-T in dogs. At high doses, the condition can be induced in less than 1 hour after administration. Spontaneous movement ceases, and when startled, animals make sudden spastic movements and sometimes lose the ability to stand or rise. Opisthotonos may also occur. A potential biochemical lesion associated with myotonia is an increase in basic paranitrophenyl phosphatase related to increased passive flux of potassium. This may lead to myotonia through a compensatory decrease in chloride conductance. Periodic clonic spasms and finally coma are the typical sequelae of phenoxy herbicide poisoning in dogs. During the clinical course of poisoning there is marked anorexia; there may be vomiting and occasionally passage of blood-tinged feces. Postmortem examination often reveals necrotic ulcers of the oral mucosa, signs of irritation in the gastrointestinal tract, and sometimes necrosis of the small intestine, and focal necrosis in the liver and degeneration of renal tubules. However, there are no reports of renal failure in dogs from any exposure to 2,4-D.
There are no specific antidotes. Since 2,4-D is excreted almost quantitatively in urine as the free acid, forced alkaline diuresis should enhance excretion. Unless there is severe central nervous system (CNS) depression (rare), recovery should be rapid.
An association between 2,4-D and canine malignant lymphoma in dogs was reported in the Journal of the National Cancer Institute (NCI) in 1991.8 This report not only raised concern by homeowners and veterinarians, but also in some instances was used to indict lawn care in a generic sense. The NCI reported a twofold increase in risk of canine malignant lymphoma associated with four or more yearly homeowner applications of 2,4-D. It is unusual for any homeowner (or commercial lawn care companies) to apply 2,4-D four or more times per year; thus the validity of pet owners’ responses to the NCI questionnaire or interviews concerning the application of lawn care products is questionable.
Two critiques of the NCI report have been published. A panel of experts concluded that because of numerous limitations in the design of the study an association was not established between 2,4-D and canine malignant lymphoma.9
Kaneene and Miller did not confirm a dose-response relationship between 2,4-D use and canine malignant lymphoma and concluded that the occurrence of canine malignant lymphoma was not significantly associated with the use of 2,4-D.10
An increased risk of transitional cell carcinoma of the urinary bladder of Scottish Terriers exposed to lawns or gardens treated with phenoxy herbicides was reported by Glickman et al.11 The authors proposed a gene-environment interaction to the development of the bladder tumors. The cause-effect relationship was based on information obtained by questionnaires completed by owners of dogs in the case and control groups. Additional studies are needed to replicate the results and to more specifically confirm exposures.