Skip to main content
  • Published:

Neurotoxic Effects of Prenatal Trichlorfon Administration in Pigs

Nevrotoksiske effekter forƄrsaket av prenatal administrasjon av triklorfon til gris

Abstract

Pregnant sows were administered trichlorfon (NeguvonĀ®) during gestation. Examination of the offspring revealed clinical symptoms which included ataxia and tremor. The weights of the cerebrum and the celebellum were significantly reduced (67% and 41% of the control values). There was a clear correlation between the decrease in total brain weight and decrease in cerebellar weight (r = 0.94). Histological examination showed a well preserved lamination of the cerebral and cerebellar cortex. Periodical loss of Purkinje cells was the most notable finding in the cerebellum. The molecular layer in such regions was markedly thinned. Neurochemical investigations of the cerebellum showed a significant decrease in specific activity of the transmitter synthesizing enzymes choline acetyltransferase, glutamate decarboxylase and aromatic amino acid decarboxylase (61.6%, 30.3% and 47.1% of the control values, respectively). No effect in high affinity D-aspartate uptake was observed.

Sammendrag

Drektive purker ble gitt triklorfon (NeguvonĀ®) oralt pĆ„ dag 71, 77, 87 og 98 etter bedekning. Grisungene viste symptomer som ataksi og tremor. Vektene av cerebrum og cerebellum var signifikant redusert og utgjorde henholdsvis 67% og 41% av kontrolldyrene. Det var klar korrelasjon mellom reduksjonen i total hjernevekt og reduksjonen i vekten av cerebellum (r = 0.94). Histologiske undersĆøkelser viste en tydelig laminering av cortex bĆ„de i cerebrum og cerebellum. Stedvis tap av Purkinje celler ble observert i cerebellum.

Nevrokjemiske undersĆøkelser av cerebellum viste signifikant reduksjon i aktiviteten av de transmittor syntetiserende enzymene kolin acetyltransferase, glutamat dekarboksylase og aromatisk aminosyre dekarboksylase (henholdsvis 30,4%, 69,7% og 52,9% av kontrollverdiene). Ingen effekt pĆ„ hĆøy affinitet D-aspartat opptak ble observert.

References

  • Albers R W, Brady R O: The distribution of glutamate decarboxylase in the nervous system of the rhesus monkey. J. Biol. Chem. 1959,234, 926ā€“928.

    ArticleĀ  CASĀ  PubMedĀ  Google ScholarĀ 

  • Baron R L, Johnson H: Neurological disruption produced in hens by two organophosphate esters. Brit. J. Pharmacol. 1964,23, 295ā€“304.

    CASĀ  PubMedĀ  PubMed CentralĀ  Google ScholarĀ 

  • Berge G Ī, Nafstad I: Teratogenicity and embryoto-xicity of orally administered fenchlorphos in blue foxes. Acta vet. scand. 1983,24, 99ā€“112.

    ArticleĀ  CASĀ  PubMedĀ  PubMed CentralĀ  Google ScholarĀ 

  • Black I R: Regulation of autonomic development. Annu. Rev. Neurosci. 1978,1, 183ā€“214.

    ArticleĀ  CASĀ  PubMedĀ  Google ScholarĀ 

  • Broch O J, Fonnum F: The regional and subcellular distribution of catechol-O-methyl-transferase in the rat brain. J. Neurochem. 1972,19, 2049ā€“2055.

    ArticleĀ  CASĀ  PubMedĀ  Google ScholarĀ 

  • Budreau C H, Singh R P: Teratogenicity and em-bryotoxicity of demeton and fenthion in CF # 1 mouse embryos. Toxicol. Appi. Pharmacol. 1973,24, 324ā€“332.

    ArticleĀ  CASĀ  Google ScholarĀ 

  • Bunge R, Johnson M, Ross CD: Nature and narture in development of the autonomic neuron. Science 1978,199, 1409ā€“1416.

    ArticleĀ  CASĀ  PubMedĀ  Google ScholarĀ 

  • Byron J W: Manipulation of the cell cycle of the hemopoietic stem cell. Exp. Hematol. 1975,3, 44ā€“53.

    CASĀ  PubMedĀ  Google ScholarĀ 

  • Belske G, Kronevi T, Lindgren Ī O: Congenital tremor in pigs in Sweden. Nord. Vet. Med. 1978,30, 534ā€“537.

    Google ScholarĀ 

  • Davison A N, Dobbing J: Myelination as a vulnerable period in brain development. Brit. Med. Bull. 1966,22, 40ā€“44.

    ArticleĀ  CASĀ  PubMedĀ  Google ScholarĀ 

  • Dickerson JWT, Dobbing J: Prenatal and postnatal growth and development of the central nervous system of the pig. Proc. Roy. Soc. B. 1967,166, 384ā€“395.

    CASĀ  Google ScholarĀ 

  • Dobbing J: Vulnerable periods of brain development. In: CIBA Foundation Symposia. Lipids, Malnutrition & the Developing Brain. Elsevier, Amsterdam 1972, p. 9ā€“20.

    Google ScholarĀ 

  • Done J T, Hebert N: The growth of the cerebellum in the foetal pig. Res. Vet. Sci. 1968,9, 143ā€“148.

    ArticleĀ  CASĀ  PubMedĀ  Google ScholarĀ 

  • Fatzer R, Hani H, Scholl E: Ko.igenitaler Tremor und zerebellƤre Hypoplasie bei Ferkeln nach Be-handlung der Mutterschweine mit NeguvonĀ® wĆ”hrend der TrƤchtigkeit. (Congenital tremor and cerebellar hypoplasia in piglets following trichlorfon treatment of pregnant sows). Schweiz. Arc. Tierheil. 1981 12, 29ā€“36.

    Google ScholarĀ 

  • Fonnum F: Localization of cholinergic and y-amino-butyric acid containing pathways in brain. In: Metabolic Compartmentation in the Brain, ed. R. BalĆ”zs and J. E. Cremer. The Macmillan Press Ltd. 1972, p. 245ā€“257.

    Google ScholarĀ 

  • Fonnum F: A rapid radiochemical method for the determination of choline acetyltransferase. J. Neurochem. 1975, 25, 407ā€“409.

    ArticleĀ  Google ScholarĀ 

  • Fonnum F, Walaas I, Iversen E: Localization of GA-BAergic, cholinergic and aminergic structures on the mesolimbic system. J. Neurochem. 1977,29, 221ā€“230.

    ArticleĀ  CASĀ  PubMedĀ  Google ScholarĀ 

  • Fonnum F, Storm-Mathisen J, Divac I: Biochemical evidence for glutamate as neurotransmitter in corticostriatal and corticothalamic fibres in rat brain. Neuroscience 1981,6, 863ā€“873.

    ArticleĀ  CASĀ  PubMedĀ  Google ScholarĀ 

  • Gamlem HN, Lund A, Moen J H, Berge G Ī: Kongenital tremor og cerebellum-hypoplasi hos sped-griser som en mulig folge av NeguvonĀ®-behand-ling av drektige purker. (Congenital tremor and cerebellar hypoplasia in piglets associated with trichlorfon-treatment of pregnant sows). II. En kasuistisk meddelelse. Norsk Vet. tidssk. 1983,6, 385ā€“387.

    Google ScholarĀ 

  • Greenberg J, La Ham Q N: Malathion induced tera-tism in the developing chick. Can. J. Zool. 1969,47, 539ā€“542.

    ArticleĀ  CASĀ  PubMedĀ  Google ScholarĀ 

  • Harbison R D, Olubadewo J, Dmvedi C, Sastry Ī’ V R: Proposed role of the placental cholinergic system in the regulation of fetal growth and development. In: Basic and Therapeutic Aspects of Perinatal Pharmacology, ed. P. L. Morselli, S. Garattini and F. Sereni, Raven Press, New York, 1975, p. 107ā€“120.

    Google ScholarĀ 

  • Harding JDJ, Done J T, Darbyshire J H: Congeni-tal tremor in piglets and their relation to swine fever. Vet. Ree. 1966,79, 388ā€“389.

    ArticleĀ  CASĀ  Google ScholarĀ 

  • KĆ sa Ī”, Silver A: The correlation between choline acetyltransferase and acetylcholinesterase activity in different areas of the cerebellum of rat and guinea pig. J. Neurochem. 1969,16, 389ā€“396.

    ArticleĀ  Google ScholarĀ 

  • Khera Īš S: Toxic and teratogenic effects of insecticides in duck and chick embryos. Toxicol. Appi. Pharmacol. 1966, 8, 345.

    ArticleĀ  Google ScholarĀ 

  • Khera Īš S, La Ham Q Ī, Ellis C F, Zawidzka Ī– Ī–, Grice C H: Foot deformity in duck from injection of EPN during embryogenesis. Toxicol. Appi. Pharmacol. 1967,8, 540ā€“549.

    ArticleĀ  Google ScholarĀ 

  • Kimbrough R D, Gaines Ī¤ Ī’: Effect on organic phosphorus compounds and alkylating agents on the rat fetus. Arch. Environ. Health 1968,16, 805ā€“808.

    ArticleĀ  CASĀ  PubMedĀ  Google ScholarĀ 

  • Knox B, Askaa J, Basse A, Bitsch V, Eskildsen M, Mandrup M, Ottosen Ī—E, Overby E, Pedersen K B, Rasmussen F: Congenital ataxia and tremor with cerebellar hypoplasia in piglets born by sows treated with NeguvonĀ® vet. during pregnancy. Nord. Vet. Med. 1978,30, 538ā€“545.

    CASĀ  PubMedĀ  Google ScholarĀ 

  • Kronevi T: Kan NeguvonĀ®-behandling av drĆ ktiga suggor orsaka cerebellar hypoplasi hos gris? (Can NeguvonĀ®-treatment of pregnant sows cause cerebellar hypoplasia in piglets?). Svensk Vet. tid. 1977,29, 931ā€“932.

    Google ScholarĀ 

  • Kronevi T, BƤckstrƶm L: Kongenital tremor (skak-sjuke) hos gris (Congenital tremor in piglets). Svensk Vet. tid. 1977,29, 837ā€“841.

    Google ScholarĀ 

  • Kronevi T, Hansen Ī— J, Jonsson O J: Cerebellar hypoplasia of unknown etiology in pigs. Vet. Ree. 1975,96, 403ā€“404.

    ArticleĀ  CASĀ  Google ScholarĀ 

  • Kronevi T, Lindquist J O: Mera om kongenital tremor (skaksjuke) hos gris. (More about congenital tremor in pigs. Case report). Svensk Vet. tid. 1978,50, 415ā€“416.

    Google ScholarĀ 

  • Marx J L: New information about the development of the autonomic nervous system. Science 1979,206, 434ā€“437.

    ArticleĀ  CASĀ  PubMedĀ  Google ScholarĀ 

  • Nafstad I, Berge G, Sannes E, Lyngset A: Teratogenic effects of the organophophorus compound fenchlorphos in rabbits. Acta vet. scand. 1983,24, 295ā€“304.

    ArticleĀ  CASĀ  PubMedĀ  PubMed CentralĀ  Google ScholarĀ 

  • Robinson R J, Tigard JPM: Central nervous system in the new born. Brit. Med. Bull. 1966,22, 49ā€“55.

    ArticleĀ  CASĀ  PubMedĀ  Google ScholarĀ 

  • Rodier Ī” M: Chronology of neuron development: Animal studies and their clinical implications. Develop, med. Child Neurol. 1980,22, 525ā€“545.

    ArticleĀ  CASĀ  Google ScholarĀ 

  • Saito Īš, Barber R, Wu J, Matsuda T, Roberts E, Vaughn J E: Immunohistochemical localization of glutamate decarboxylase in rat cerebellum. Proc. Natl. Acad. Sci. 1974,71, 269ā€“273.

    ArticleĀ  CASĀ  PubMedĀ  PubMed CentralĀ  Google ScholarĀ 

  • Sastry Ī’ VR, Henderson G I: Kinetic mechanisms of human placental choline acetyltransferase. Bio-chem. Pharmacol. 1972,27, 787ā€“802.

    ArticleĀ  Google ScholarĀ 

  • Sastry Ī’ V R, Olubadewo J, Smidt D E: Placental cholinergic system and occurrence of acetylcholine in placenta. Fed. Proc. 1973, 32, 742.

    Google ScholarĀ 

  • Schardein JL: Drugs as teratogens. CRC Press, Inc., Ohio, USA 1976, 77.

    Google ScholarĀ 

  • Scheufler H: Der Einfluss relativ hoher Dosen von Dimethoat and Trichlorphon auf die Keimesent-wicklung der Labormaus. (Influence of relatively high dosis of dimethoat and trichlorfon on the embryonal development of the mouse). Biologis-che Rundschau 1975,13, 238ā€“240.

    CASĀ  Google ScholarĀ 

  • Schulman J A: Chemical neuroanatomy of the cerebellar cortex. In: Chemical Neuroanatomy, ed. P. C. Emson, Raven Press, New York 1983, p. 209ā€“228.

    Google ScholarĀ 

  • Staples R E, Goulding Ī• H: Dipterex teratogenicity in the rat, hamster and mouse when given by gavage. Environm. Health Perspec. 1979, 30, 105ā€“113.

    CASĀ  Google ScholarĀ 

  • Sterri S H, Fonnum F: Isolation of organic anions by extraction with liquid anion exchangers and its application to micromethods for acetylcholinesterase and 4-aminobutyrate aminotransferase. Eur. J. Biochem. 1978,91, 215ā€“222.

    ArticleĀ  CASĀ  PubMedĀ  Google ScholarĀ 

Download references

Acknowledgment

The authors wish to express their sincere thanks to professor Erling Sognen and professor Inger Nafstad for useful help, valuable advice and comments. The technical assistance of Mrs. E. Iversen, Mrs. Sidsel Sohlberg and Mr. T. Myrvold is greatly appreciated. This work was supported by grants from the Norwegian Agricultural Research Council.

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Berge, G.N., Fonnum, F. & Brodai, P. Neurotoxic Effects of Prenatal Trichlorfon Administration in Pigs. Acta Vet Scand 28, 321ā€“332 (1987). https://doi.org/10.1186/BF03548600

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1186/BF03548600

Keywords