Info

Uses

Effect and Mechanism

Aliphatic solvents

Chloroform

Trichloroethylene

Methylene chloride

Hexane, methyl n-butyl ketone

Aromatic solvents Benzene

Toluene

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

Rodenticides

Compound 1080, warfarin, strychnine

Effect and Mechanism

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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