PRINCIPLES OF TOXICOLOGY

360 PROPERTIES AND EFFECTS OF PESTICIDES
Copper Compounds
Exposure to dust and powder formulations of copper-based fungicides has been reported to cause
irritation of the skin, eyes, and respiratory tract. Systemic intoxication in humans by copper fungicides
has been rarely reported. Ingestion of the compound has reportedly caused gastrointestinal irritation,
nausea and vomiting, diarrhea, headache, sweating, weakness, liver enlargement, hemolysis and
methemoglobinemia, albuminuria, hemoglobinurina, and occasionally renal failure. Treatment of
copper intoxication can include an effort to prevent absorption (e.g., lavage) followed by chelation
therapy.
15.6 RODENTICIDES
The rodenticides, as the name indicates, are a class of compounds designed to specifically target
rodents. These compounds have, in some cases, taken advantage of physiological differences between
rodents and other mammals (viz., humans) that make rodents more susceptible to their toxic effects.
The most efficient route of exposure of these compounds is via ingestion.
This class of rodenticides works by depression of the vitamin K synthesis of the blood clotting
factors II (prothrombin), VII, IX, and X. This anti-coagulant property manifests as diffuse internal
hemorrhaging occurring typically after several days of rodenticide bait ingestion. Warfarin (see Figure
15.8) is a commonly used coumarin rodenticide that causes its toxic effects by inhibiting the formation
of prothrombin and the inhibition of vitamin K–dependent factors in the body. Other anticoagulant
rodenticides include coumafuryl, brodifacoum, difenacoum, and prolin. Warfarin is known to be
absorbed both dermally and from ingestion. Signs and symptoms of intoxication with warfarin include
epistaxis, hemoptysis, bleeding gums, gastrointestinal tract and genitourinary tract hemorrhage, and
ecchymoses.
The indandiones, unlike the coumarins, cause nervous system, cardiac, and pulmonary effects in
laboratory animals preceding the death from the anticoagulant effects. These types of adverse effects
have not been reported in cases of human exposure. Examples of indandione rodenticides include
diphacinone, diphacin, and chlorphacinone.
The most prominent clinical laboratory sign from the administration of these classes of compounds
is an increased prothrombin time and a decrease in plasma prothrombin concentration. Treatment of
toxicity from coumarins and indandions consists of the administration of vitamin K 1 .
Thallium Sulfate
Thallium sulfate is readily absorbed via ingestion and dermally, as well as via inhalation. The target
organs of thallium sulfate include the gastrointestinal tract (hemorrhagic gastroenteritis), heart and
blood vessels, kidneys, liver, skin, and the hair. Symptoms such as headache, lethargy, muscle
weakness, numbness, tremor, ataxia, myoclonia, convulsions, delirium, and coma are seen in cases of
O O
OH
CHCH 2COCH 3
C 6H 5
Figure 15.8 Warfarin.