Organochlorine Pesticides

Chapter 65 Organochlorine Pesticides



Merl F. Raisbeck, DVM, MS, PhD





• The most likely source of acute organochlorine poisoning in small animals is improperly stored stockpiles of outdated pesticides. With the exception of a very few, very limited applications, such as lindane for lice, many organochlorine insecticides have not been used in more than 25 years.

• Clinical signs of organochlorine poisoning are best summarized as neurological. Poisoned animals become hyperesthetic and exhibit motor tremors and convulsions.

• Most pesticides of this class are extremely persistent in body fat. Poisoned animals should be monitored for several weeks for recurrences.

• Most of the modern environmental guidelines (“toxic levels”) are based on theoretical human cancer considerations or upon endocrine effects in nonmammals. Clinicians should be aware when evaluating possible sources of exposure that such guidelines are very low compared with the exposure required for clinical poisoning.


SOURCES


After the introduction of dichlorodiphenyltrichloroethane (DDT) in 1940, a number of halogenated organic compounds were created for use as pesticides. Although there are many toxic chlorinated organic compounds, the term “chlorinated hydrocarbons” or “organochlorine(s)” (OC) usually refers to this group of pesticides. The OC may be classified according to either their intended use (e.g., insecticides, nematocides, and fungicides) or their chemical structure (e.g., chlorinated aryl hydrocarbons, cyclodiene, diphenyl aliphatics, and so on). The latter scheme is most useful from the standpoint of mammalian metabolism and toxicology. With only a few exceptions, the OC are refractory to metabolism and are lipophilic. As such, they tend to be readily absorbed, but only slowly eliminated and thus accumulate in humans, domestic animals, and wildlife, and bioconcentrate in the food chain. Many are suspect or proven carcinogens. As a result, the class has been largely replaced by less persistent agents, such as the organophosphates and pyrethroids. Some examples of OC include aldrin, dieldrin, lindane, chlordane, endosulfan, heptachlor, toxaphene, and methoxychlor.


The OC were heavily used for pest control from the 1950s through the 1970s. Thus contaminated soils or leakage from old dump sites are possible sources of exposure for wildlife and domestic carnivores, especially given the propensity of the class to bioconcentrate in the food chain. Because one of the few remaining legal applications of the OC is ectoparasite control in dogs, accidental overdose is also a possible source of acute toxicosis. The most likely source of poisoning in companion animals, however, is old stockpiles of insecticides and improper waste disposal.



TOXIC DOSE


The acutely toxic dose varies considerably with the specific OC. In general the OC are less acutely toxic than organophosphates or carbamates used for similar purposes. For example, the most potent OC have a mammalian median lethal dose (LD50) of approximately 50 mg/kg bw, tenfold to 100-fold larger than the LD50 of the carbamate, aldicarb. Within the class, the cyclodienes (e.g., heptachlor, chlordane, and dieldrin) are generally most toxic, followed by the aryl hydrocarbons (e.g., lindane and methoxychlor), and finally by the diphenyl aliphatics (DDT, etc.). Because of their lipophilicity, both topical and dermal exposures may result in a notable dose. Their low volatility usually precludes significant respiratory exposure unless aerosolized. Most of the OC have an offensive odor.



TOXICOKINETICS


After exposure the OC are rapidly redistributed via plasma lipoproteins to liver, brain, and other lipid-rich tissue. Adipose tissue serves as a “sink” for the OC, competing with critical organs, such as the brain, for circulating OC in a fashion similar to the short-acting barbiturates. Thus after acute oral exposure to OC, the blood concentration peaks and then declines relatively quickly as redistribution and elimination at first equal and then exceed absorption. Later, as the OC concentrations in fat exceed those in blood, stored pesticide is slowly released back into the systemic circulation, and the rate of decline in blood concentration slows dramatically. The initial period, in which both elimination and redistribution serve to decrease blood concentration, is referred to as the alpha phase. During the later, or beta phase, redistribution from adipose tissue tends to sustain circulating levels and greatly prolongs the half-life. The beta phase half-life of most OC is usually measured in months.


Body fat may also serve as a source of OC poisoning. During prolonged exposure, the adipose OC concentration increases in a logarithmic manner, eventually approaching a plateau in which the relationship between tissue concentrations, blood levels, and excretion rates is in equilibrium with uptake. At this point, the total amount of OC in the body may be several times greater than a toxic dose, but because it is sequestered in fat, poisoning does not occur. However, if the animal is forced to lose weight rapidly, the potentially toxic dose stored in adipose tissue becomes available to the general circulation and may result in acute intoxication.


Lipophilic compounds, such as the OC, are readily passed from blood to mammary cell lipid, which are subsequently secreted as milk fat. Transfer of the OC body burden to milk fat is ensured by the large perfusion of the mammary gland and the favorable concentration gradient created by constant synthesis and secretion of milk. Because milk is the major elimination route of persistent OC, it is a potential source of exposure for neonates. In practice the likelihood of acute poisoning from milk of an asymptomatic dam is relatively low, but the possibility should be considered if a lactating animal has been exposed to an OC.


Metabolism of most OC contributes little to elimination and may actually produce more toxic metabolites. For example, the cyclodienes (e.g., heptachlor) are rapidly converted to their epoxides, and the diphenyl aliphatics are partially dechlorinated, but in both cases the end product is stable, lipophilic, and at least as toxic as its parent. Metabolites are released slowly from the lipid storage depot and transported through the blood to liver, where they are excreted in the bile. However, after excretion into the intestine, many OC are reabsorbed. This enterohepatic recycling also serves to prolong the persistence of the OC in the body.

Related posts:

  1. Miscellaneous Indoor Toxicants
  2. Adverse Drug Reactions
  3. Arsenic
  4. Diethylene Glycol

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Sep 11, 2016 | Posted by in SMALL ANIMAL | Comments Off on Organochlorine Pesticides

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