Monochloroacetic acid toxicity in the mouse associated with blood-brain barrier damage

Thesis/Dissertation · Wed Jan 01 00:00:00 EST 1986

OSTI ID:5503751

Berardi, M R

Monochloroacetic acid (MCA) damages the blood-brain barrier (BBB) of mice when administered orally at lethal doses. Damage was characterized by the finding of RBC's in the brain parenchyma of mice exhibiting neurologic dysfunction after MCA treatment, and by the entry of (/sup 14/C)inulin and (/sup 3/H)dopamine into the brain following a lethal dose of MCA. Results of acute toxicity studies, pharmacological antidote studies, and toxicokinetics studies in mice and rats are also presented. Acute toxicity of MCA in rats and mice by several routes of administration was determined. Toxicity of molten MCA by the dermal route was characterized by a small amount of surface area exposure and short application time necessary to produce death in both species. Some mice surviving an acute lethal oral dose of MCA exhibited a rigid clasping of the front paws (myotonia) with impairment of walking. Oral administration of (/sup 14/C)MCA to both mice and rats was followed by a rapid elimination of radioactivity from non-cerebral tissues and rapid appearance in the urine. As the dose was increased from a trace dose to a toxic dose, the percent of the administrated dose which was found in the tissues, including brain regions, was greatly increased. Two hours after oral administration of an LD80 of MCA to mice, and coinciding with the onset of toxic signs, entry of (/sup 14/C)inulin into brain regions was significantly increased compared to controls. Both MCA lethality and front paw dysfunction in mice appear to be associated with damage to the BBB.

• Research Organization: Rutgers-the State Univ., New Brunswick, NJ (USA)
• OSTI ID: 5503751
• Resource Relation: Other Information: Thesis (Ph. D.)
• Country of Publication: United States
• Language: English

Related Subjects

63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
BRAIN
HISTOLOGY
CHLORINATED ALIPHATIC HYDROCARBONS
PHARMACOLOGY
TOXICITY
BLOOD-BRAIN BARRIER
CARBON 14 COMPOUNDS
DOPAMINE
ERYTHROCYTES
INULIN
MICE
RATS
TRITIUM COMPOUNDS
AMINES
ANIMALS
AROMATICS
AUTONOMIC NERVOUS SYSTEM AGENTS
BIOLOGICAL MATERIALS
BLOOD
BLOOD CELLS
BODY
BODY FLUIDS
CARBOHYDRATES
CARDIOTONICS
CARDIOVASCULAR AGENTS
CENTRAL NERVOUS SYSTEM
DRUGS
HALOGENATED ALIPHATIC HYDROCARBONS
HYDROXY COMPOUNDS
LABELLED COMPOUNDS
MAMMALS
MATERIALS
NERVOUS SYSTEM
NEUROREGULATORS
ORGANIC CHLORINE COMPOUNDS
ORGANIC COMPOUNDS
ORGANIC HALOGEN COMPOUNDS
ORGANS
PHENOLS
POLYPHENOLS
POLYSACCHARIDES
RODENTS
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SYMPATHOMIMETICS
VERTEBRATES
560300* - Chemicals Metabolism & Toxicology