Genetic toxicology assessment of HI-6 dichloride

Environmental and Molecular Mutagenesis
D L PutmanD Jacobson-Kram

Abstract

The oxime HI-6 dichloride [1-(2 hydroxyiminomethyl -1-pyridino)-3-(4-carbamoyl-1-pyridino)-2-oxapropane dichloride monohydrate] has shown to be a potent reactivator of cholinesterase activity and may have efficacy for the treatment of organophosphate intoxication [SIPRI, 1976; Schenk et al.; Arch Toxicol 36:71-81, 1976]. As part of a preclinical safety assessment program, the genetic toxicology of HI-6 dichloride was evaluated in a series of assays designed to measure induction of gene mutations and chromosomal aberrations. HI-6 dichloride gave negative responses in the Salmonella mutagenicity assay and in the CHO/HGPRT gene mutation assay. Dose-dependent increases in the frequency of chromosomal aberrations were noted when HI-6 dichloride was tested in cultured CHO cells and in cultured human peripheral blood lymphocytes. The mouse lymphoma gene mutation assay, reputed to measure both gene mutations and chromosomal deletions, was negative in the absence of metabolic activation. Depending on the criteria employed, a negative or equivocal response was seen in the presence of rat liver-derived S-9 mix. An in vivo rat bone marrow metaphase assay performed to further investigate the in vitro clastogenic responses was negative. The ...Continue Reading

References

Jan 1, 1990·Proceedings of the National Academy of Sciences of the United States of America·M L ApplegateJ C Hozier
Jan 1, 1989·Mutation Research·T MoritaK Okumura
Dec 1, 1986·Archives of Toxicology·R Klimmek, P Eyer
Mar 1, 1981·Fundamental and Applied Toxicology : Official Journal of the Society of Toxicology·O L WolthuisE Meeter
Nov 1, 1983·Fundamental and Applied Toxicology : Official Journal of the Society of Toxicology·J G Clement
Jun 1, 1994·Mutation Research·C S AaronE Thompson
Sep 1, 1994·Mutagenesis·E ZeigerT G Deaton

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Citations

Jun 26, 2001·Mutation Research·J J ClarkeD Jacobson-Kram
Feb 10, 2007·Toxicological Reviews·Timothy C MarrsJ Allister Vale
Feb 19, 2014·Mutation Research. Genetic Toxicology and Environmental Mutagenesis·Lauren NakabFabrice Nesslany

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