Acute toxicity and mutagenicity of the copper complex of pyruvaldehyde-bis (N-4-methylthiosemicarbazone), Cu-PTSM

P. J. Kostyniak, S. M. Nakeeb, E. M. Schopp, A. E. Maccubbin, E. K. John, Mark Green, H. F. Kung

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

Cu-PTSM is a potential imaging agent for the heart and brain when labeled with either 64Cu or 62Cu. Unlabeled Cu-PTSM was evaluated for its acute toxicity and mutagenicity. Cu-PTSM had an i.v. LD50 of 26 mg kg-1 in the rat and 2 mg kg-1 in the rabbit. At necropsy, rats exhibited severely hemorrhagic lungs, histological findings of acute pulmonary congestion, hemorrhage and edema, and mild congestion in kidney, liver and brain. The rabbit displayed marked polymorphonuclear infiltration in alveoli, peribronchial and periarterial areas with marked macrophage hyperplasia, congestion and mild hemorrhage into alveolar spaces. No effects were found in kidney, liver, testes or brain. Administration of 2.16 μg kg-1 day-1 for 5 days per week for 2 weeks resulted in no changes in histopathology, hematology or clinical chemistry parameters. This daily dose is at least 300 times the diagnostic dose intended for use in man. Cu-PTSM was not mutagenic when tested in the absence of S9 supernatant, but elicited a weakly mutagenic response in the presence of S9. Since acute effects in the lung occur at doses approaching 300000 times the diagnostic dose, it is highly unlikely that the clinical use of Cu-PTSM would result in any acute adverse effects.

Original languageEnglish (US)
Pages (from-to)417-421
Number of pages5
JournalJournal of Applied Toxicology
Volume10
Issue number6
StatePublished - 1990
Externally publishedYes

Fingerprint

Toxicity
Brain
Liver
Lung
Rats
Hemorrhage
Rabbits
Kidney
Clinical Chemistry
Macrophages
Lethal Dose 50
Hematology
Infiltration
Hyperplasia
Testis
Edema
copper pyruvaldehyde bis(N(4)-methylthiosemicarbazone) complex
Imaging techniques

Keywords

  • acute toxicity
  • brain
  • Cu-PTSM
  • heart
  • LD
  • mutagenicity
  • pyruvaldehyde-bis- (N-4-methylthiosemicarbazone)
  • rabbit
  • radioimaging agent
  • rat

ASJC Scopus subject areas

  • Toxicology
  • Health, Toxicology and Mutagenesis

Cite this

Kostyniak, P. J., Nakeeb, S. M., Schopp, E. M., Maccubbin, A. E., John, E. K., Green, M., & Kung, H. F. (1990). Acute toxicity and mutagenicity of the copper complex of pyruvaldehyde-bis (N-4-methylthiosemicarbazone), Cu-PTSM. Journal of Applied Toxicology, 10(6), 417-421.

Acute toxicity and mutagenicity of the copper complex of pyruvaldehyde-bis (N-4-methylthiosemicarbazone), Cu-PTSM. / Kostyniak, P. J.; Nakeeb, S. M.; Schopp, E. M.; Maccubbin, A. E.; John, E. K.; Green, Mark; Kung, H. F.

In: Journal of Applied Toxicology, Vol. 10, No. 6, 1990, p. 417-421.

Research output: Contribution to journalArticle

Kostyniak, PJ, Nakeeb, SM, Schopp, EM, Maccubbin, AE, John, EK, Green, M & Kung, HF 1990, 'Acute toxicity and mutagenicity of the copper complex of pyruvaldehyde-bis (N-4-methylthiosemicarbazone), Cu-PTSM', Journal of Applied Toxicology, vol. 10, no. 6, pp. 417-421.
Kostyniak, P. J. ; Nakeeb, S. M. ; Schopp, E. M. ; Maccubbin, A. E. ; John, E. K. ; Green, Mark ; Kung, H. F. / Acute toxicity and mutagenicity of the copper complex of pyruvaldehyde-bis (N-4-methylthiosemicarbazone), Cu-PTSM. In: Journal of Applied Toxicology. 1990 ; Vol. 10, No. 6. pp. 417-421.
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