Monochloroacetic acid lethality in the rat in relation to lactic acid accumulation in the cerebrospinal fluid
Potential antidotes for human exposure to monochloroacetic acid (MCA) were evaluated using a rodent model. Dichloroacetic acid (DCA) and phenobarbital (PB) but not ethanol or phenytoin, were found to be effective antidotes to monochloroacetic acid (MCA) in rats. DCA (110 mg/kg, ip), administered to rats 15 minutes after a LD-80 of MCA (80 mg/kg, iv), consistently reduced mortality to 0%, while PB reduced mortality to less than 20%. Both DCA and PB were found to be similarly effective in mice. The hypothesis that PB reduces mortality in MCA treated rats by altering the metabolic disposition of MCA was evaluated and rejected. Administration of PB to rats treated with a lethal dose of ({sup 14}C)MCA did not alter the concentrations of MCA or its metabolites in plasma or cerebrospinal fluid (CSF), or the extent of covalent binding between radioactivity equivalent to ({sup 14}C)MCA and brain proteins. The relationship between altered blood-brain barrier permeability and death in MCA treated rats was investigated. Treatment with MCA (80 mg/kg, iv) was associated with a significant (50%) increase in the permeability of the rat blood-brain barrier to ({sup 125}I)BSA. The effect was not altered by treatment with PB, however, suggesting that altered blood-brain barrier permeability does not have an important role in the lethal effect of MCA in rats. The effect of MCA on brain carbohydrate metabolism in vivo was investigated. CSF and blood lactic acid concentrations increased in MCA treated rats, and the increase in CSF levels was dose related. In individual MCA treated rats, CSF lactate concentrations paralleled the time course of ataxia and a discrete threshold for death (18 mmol/L) was observed. The relationship between excess brain lactate levels and death in MCA treated rats was investigated further.
- Research Organization:
- Rutgers-the State Univ., New Brunswick, NJ (USA)
- OSTI ID:
- 5613746
- Resource Relation:
- Other Information: Thesis (Ph. D.)
- Country of Publication:
- United States
- Language:
- English
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ACETIC ACID
TOXICITY
BLOOD-BRAIN BARRIER
PERMEABILITY
LACTIC ACID
BIOLOGICAL ACCUMULATION
PHENOBARBITAL
BIOLOGICAL EFFECTS
CARBON 14 COMPOUNDS
CEREBROSPINAL FLUID
ETHANOL
IODINE 125
MAN
METABOLISM
RATS
TRACER TECHNIQUES
ALCOHOLS
ANESTHETICS
ANIMALS
ANTICONVULSANTS
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BARBITURATES
BETA DECAY RADIOISOTOPES
BIOLOGICAL MATERIALS
BODY FLUIDS
CARBOXYLIC ACIDS
CENTRAL NERVOUS SYSTEM DEPRESSANTS
DAYS LIVING RADIOISOTOPES
DRUGS
ELECTRON CAPTURE RADIOISOTOPES
HETEROCYCLIC COMPOUNDS
HYDROXY ACIDS
HYDROXY COMPOUNDS
HYPNOTICS AND SEDATIVES
INTERMEDIATE MASS NUCLEI
INTERNAL CONVERSION RADIOISOTOPES
IODINE ISOTOPES
ISOTOPE APPLICATIONS
ISOTOPES
LABELLED COMPOUNDS
MAMMALS
MATERIALS
MONOCARBOXYLIC ACIDS
NUCLEI
ODD-EVEN NUCLEI
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANIC OXYGEN COMPOUNDS
PRIMATES
PYRIMIDINES
RADIOISOTOPES
RODENTS
VERTEBRATES
550501* - Metabolism- Tracer Techniques