Source: Landcare Research (1964). Control of poisons. Royal ...

1080 Reassessment Application October 2006
Appendix C
Brownsey, R. W., Bridges, B. J., and Denton, R. M. (1977). Effects of fluoroacetate and (-)-hydroxycitrate
on fatty acid synthesis in rat epididymal adipose tissue. Biochemical Society transactions 5, 1286-1288.
Keywords: fluoroacetate/citrate/metabolism/testes
Abstract: Regualtion of the conversion of pyruvate (derived from glucose) into fatty acids in rat adipose
tissue appears to be largely brought about by parallel changes in the proportions of pyruvate dehydrogenase
and acetyl-CoA carboxylase in their respective active forms. We conclude form this study as we have
previously on other evidence that the concentration of citrate is probably not of great importance in the
regulation of fatty acid synthesis.
Buckley, N. A., Whyte, I. M., O'Connell, D. L., and Dawson, A. H. (1999). Activated charcoal reduces the
need for N-Acetylcysteine treatment after Acetaminophen (Paracetamol) overdose. Clinical Toxicology 37,
753-757.
Keywords: antidote/treatment/poisoning/humans
Abstract: Background: The evidence for efficacy of gastric lavage and activated charcoal for
gastrointestinal decontamination in poisoning has relied entirely on volunteer studies and/or
pharmacokinetic studies and evidence for any clinical benefits or resource savings is lacking. Aim of study:
To investigate the value of gastrointestinal decontamination using gastric lavage and/or activated charcoal
in acetaminophen (paracetamol) poisoning. Patients and Methods: We analyzed a series of 981 consecutive
acetaminophen poisonings. These patients were treated with gastric lavage and activated charcoal, activated
charcoal alone, or no gastrointestinal decontamination. The decision as to which treatment was received
was determined by patient cooperation, the treating physician, coingested drugs, and time to presentation
after overdose. Results: Ot 981 patients admitted over 10 years, 10% (100) had serum concentrations of
acetaminophen that indicated a probable or high risk of hepatotoxicity. The risk of toxic concentrations for
patients ingesting less than 10g of acetaminophen was very low. In patients presenting within 24 hours,
who had ingested 10g or more, those who had been given activated charcoal were significantly less likely
to have probable or high tisk concentrations (Odds ratio 0.36, 95% CI 0.23-0.58, p < 0.0001). Gastric
lavage, in addition to activated charcoal, did not further decrease the risk (Odds ratio 1.12, 95% CI 0.57-
2.20, p = 0.86). Conclusions: Toxic concentrations of serum acetaminophen (paracetamol) are uncommon
in patients ingesting less than 10 g. In those ingesting more, activated charcoal appears to reduce the
number of patients who achieve toxic acetaminophen concentrations and thus may reduce the need for
treatmernt and hospital stay.
Buffa, P. and Peters, R. A. (1950). The in vivo formation of citrate induced by fluoroacetate and its
significance. Journal of physiology 110, 488-500.
Keywords: metabolism/mode of action/persistence in
animals/citrate/fluoroacetate/enzyme/biochemistry/aconitase
Buffa, P., Guarriero-Bobyleva, V, and Pasquali-Rochetti, I. (1971). Biochemical effects of fluoroacetate
poisoning in rat liver. CIBA Foundation Symposia 2, 303-326.
Keywords: fluoroacetate/poisoning/liver/metabolism/mode of action/lethal dose/citrate/fluorocitrate/rats
Abstract: The mode of action of fluoroacetate in the liver of the rat has been studied. The response of liver
tissue to fluoroacetate posioning depends in a decisive manner on the nutritional state of the animal. In the
fed rat a lethal dose of fluoroacetate causes marked accumulation of citrate, rapid fall in the amount of
glycogen and decrease of tissue ATP. In the rat starved for 24 hours, the concentration of liver glycogen is
very low, the amount of ATP is reduced by about 40% and fluoroacetate poisoning causes only a slight
increase in liver citrate. In teh fed rat the tricarboxylic acid cycle runs mostly on pyruvate, and
fluoroacetate is converted to fluorocitrate; when the tricarboxylic acid cycle runs mostly on fatty acids, as is
the case in the starved rat, very little fluoroacetate is converted to fluorocitrate in the liver. In the liver
slices obtained for fluoroacetate-poisoned fed rats the endogenous respiration is not inhibited and the citrate
previously accumulated is metabolized. The mirochondria isolated from the poisoned liver are inhibited in
their ability to oxidize added citrate (by over 50%), cis-aconitate (by about 15%) and oxaloacetate (by
about 30%), whereas they oxidize other intermediates of the cycle and pyruvate and glutamate at normal
rates. Oxidative phosphorylation is not affected. Extramitochondrial aconitate hydratase is virtually
unaffected in the liver cell poisoned with fluoroacetate and in conjunction with extramitochondrial NADPlinked
isocitrate dehydrogenase, it provides an alternative metabolic pathway for the citrate which has
diffused out of the mitochondria into the cytosol.
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