Effect and Mechanism
Hexane, methyl n-butyl ketone
Aromatic solvents Benzene
Drug purification Degreasing, dry cleaning
Degreasing, paint stripping, aerosol propellant Wood glue, plastics manufacturing
Petroleum product, adhesives and coatings Adhesives
Hepatic centrilobular necrosis, likely from reactive metabolites
Sensitizes the myocardium to epinephrine, interferes with alcohol metabolism
Metabolized to CO, resulting in formation of carboxy-hemoglobin
Polyneuropathy from their metabolite, 2,5-hexanedione
Leukemia, aplastic anemia, likely from reactive intermediates
Cerebellar degeneration with repeated high-dose exposure (glue sniffing)
T ABLE 7.7 Toxicity of Selected Pesticides
Class and Examples
Organochlorine insecticides DDT, chlordane, aldrin, heptachlor
Organophosphate insecticides Bromophos, chlorpyrifos, parathion, malathion, diazinon
Carbamate insecticides Carbaryl
Pyrethrin and pyrethroid insecticides Pyrethrin I, II;fenvalerate, permethrin
Chlorophenoxy herbicides 2,4-D;2,4,5-T
Bipyridyl herbicides Paraquat, diquat
Compound 1080, warfarin, strychnine
Neuronal hyperactivity;convulsions;impaired vision, concentration, and memory Altered membrane permeability to Na+, K+ Block repolarization by inhibiting Na+, K+-ATPase Block GABA-stimulated chloride uptake
Bronchoconstriction and secretion, muscular weakness or paralysis,
CNS depression, including respiratory centers Inhibition of acetylcholinesterase (reversible or irreversible) Same as organophosphate insecticides Inhibition of acetylcholinesterase (reversible) Neuronal hyperactivity, incoordination, tremors with hyperthermia, seizures
Delayed inactivation of channels in excitable tissues, causing repetitive firing and at high doses, depolarization Block GABA-stimulated chloride uptake Muscle weakness, aching, and tenderness;hypotonia
Delayed respiratory distress, fibrosis, and atelectasis Gastrointestinal, liver, and kidney toxicity Formation of reactive oxygen species Block tricarboxylic acid cycle (fluoroacetates) Prevent blood clotting Induce seizures
ATPase, adenosine triphosphatase;GABA, ^-aminobutyric acid;2,4-D, 2,4-dichlorophenoxyacetic acid;2,4,5-T, 2,4,5-trichlorophenoxyacetic acid.
yield an oxygenated metabolite that will react with the active site of acetylcholinesterase (AChE), resulting in irreversible enzyme inhibition. Symptoms of poisoning are due to excessive stimulation of cholinergic receptors. In cases of lethal poisoning in humans, death is from respiratory failure. Distal neuropathy of the lower limbs also has been seen.
The carbamate insecticides also inhibit AChE. The mechanism of inhibition is similar, but the reaction is reversible.
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