Studies on the in vitro and in vivo genotoxicity of [2,2-dimethyl-6- (4-chlorophenyl)-7-phenyl-2,3-dihydro-1H-pyrrolizine-5-yl]-acetic acid

Arzneimittelforschung. 1995 Apr;45(4):486-90.

Abstract

[2,2-Dimethyl-6-(4-chlorophenyl)-7-phenyl-2,3-dihydro-1H-pyrrolizine-5- yl]-acetic acid (CAS 156897-06-2, ML 3000) was examined for genotoxic activity in bacteria and mammalian cells in vitro as well as in vivo. The substance did not increase gene mutation frequencies either in a bacterial system or in a cultured V79 cell line of the Chinese hamster. Both in vitro tests were conducted in the presence and absence of S9-mix. In the unscheduled DNA synthesis assay in vitro with primary rat hepatocytes, negative results were also obtained. A cytogenetic analysis of the bone marrow of male and female Wistar rats was performed. After oral application ML 3000 did not increase the number of cells with structural chromosomal aberrations. The results suggest that ML 3000 has no genotoxic potential in vitro and in vivo.

MeSH terms

  • Acetates / toxicity*
  • Animals
  • Bone Marrow / drug effects
  • Bone Marrow Cells
  • Cells, Cultured
  • Chromosome Aberrations
  • Cricetinae
  • Cricetulus
  • DNA Repair / drug effects
  • Female
  • Lipoxygenase Inhibitors / toxicity*
  • Male
  • Mutagenicity Tests
  • Mutagens / toxicity*
  • Pyrroles / toxicity*
  • Rats
  • Rats, Wistar
  • Salmonella typhimurium / drug effects
  • Salmonella typhimurium / genetics

Substances

  • Acetates
  • Lipoxygenase Inhibitors
  • Mutagens
  • Pyrroles
  • licofelone