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The effect of trichlorfon and other organophosphates on prenatal brain development in the guinea pig

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Abstract

The organophosphates trichlorfon, dichlorvos, dimethoate, soman, triortho-cresyl phosphate (TOCP), and the diethoxy-analogue of trichlorfon (O,O-diethyl 2,2,2-trichloro-1-hydroxyethylphosphonate, ethyl-trichlorfon), were administrated to guinea pigs between day 42 and 46 of gestation. When the offsprings were examined at birth, there was a severe reduction in brain weight in the case of trichlorfon and dichlorvos, but not after treatment with the other organophosphates. The reduction in weight was most pronounced for cerebellum, medulla oblongata, thalamus/hypothalamus and quadrigemina. The effect was less marked for cerebral cortex and hippocampus. Since soman, a potent anticholinesterase, and TOCP, an inhibitor of neuropathy target esterase, did not show any effects, this excludes that the brain hypoplasia can be caused by inhibition of these two enzymes. Further, the lack of effect with ethyl-trichlorfon has shed some light on the part of the trichlorfon molecule which could be involved in the formation of the hypoplasia. It is suggested that alkylation of DNA may be involved in the development of the lesion. The possible consequences for a teratogenic effect of trichlorfon and dichlorvos on humans are discussed.

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Authors and Affiliations

  1. Institute of Biology, Dept. of Molecular Cell Biology, University of Oslo, P.O. Box 1050 Blindern, N-0316, Oslo, Norway

    Anna Mehl & Tore M. Schanke

  2. Division for Environmental Toxicology, Norwegian Defense Research Establishment, P.O. Box 25, N-2007, Kjeller, Norway

    Bjørn A. Johnsen & Frode Fonnum

Authors
  1. Anna Mehl
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  2. Tore M. Schanke
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  3. Bjørn A. Johnsen
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  4. Frode Fonnum
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Special issue dedicated to Dr. Bernard W. Agranoff.

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Mehl, A., Schanke, T.M., Johnsen, B.A. et al. The effect of trichlorfon and other organophosphates on prenatal brain development in the guinea pig. Neurochem Res 19, 569–574 (1994). https://doi.org/10.1007/BF00971332

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