ABSTRACT
Ferric hexacyanoferrate(II) (Fe4[Fe(CN)6]3), i.e. Prussian blue (PB) has been used for many years to remove from the body the two toxic isotopes of cesium and thallium following irradiation. Recently, potassium cobalt hexacyanoferrate(II) (K2COFe(CN)6), which has shown a better efficacy for decontamination, is also being considered for use to enhance the elimination of cesium isotopes. In view to its preclinical and clinical development, in vitro and in vivo GLP-compliant genotoxicity studies were carried out on this product as well as on PB for comparison. Several tests dissecting the main events leading to genotoxicity, i.e. mutagenicity and chromosomal aberrations, both structural and quantitative were implemented. In vitro, no mutagenic effect was observed in the Ames test but both compounds were positive in the mouse lymphoma assay on TK locus and induced clastogenic effects in the in vitro chromosomal aberrations test on human lymphocytes, either in absence or in presence of metabolic activation. K-Co-ferrocyanide was also assayed in vivo in the mouse bone marrow micronucleus assay and PB was assessed for DNA fragmentation in the rodent Comet assay in both glandular stomach and colon. In the in vivo micronucleus mouse bone marrow, K-Co-ferrocyanide did not display any genotoxic activity up to 2000 mg/kg/d (x2) by oral route. In opposite, PB induced a significant increase in DNA fragmentation both in the glandular stomach and in the colon of rat treated 3 times with intake ranging from 2000 to 500 mg/kg. PB should be considered as an in vivo mutagen as well as Potassium cobalt hexacyanoferrate(II) since the in vitro genotoxicity profiles of both ferrocyanides are quite similar. Their use as cesium/ thallium decontamination agents in human should be assessed following a benefit/risk approach to enable a robust decision-making.
Subject(s)
Cobalt/toxicity , Ferrocyanides/toxicity , Mutagenicity Tests/methods , Animals , Cell Line, Tumor , Chromosome Aberrations/drug effects , Cobalt/chemistry , Comet Assay/methods , DNA Fragmentation/drug effects , Female , Ferrocyanides/chemistry , Lymphocytes/drug effects , Lymphocytes/metabolism , Male , Mice , Micronucleus Tests/methods , Rats, Sprague-DawleyABSTRACT
Male condoms are undoubtedly the best protection against sexually transmitted diseases. The French Military Health Service buys condoms from civilian manufacturers using a public purchasing process. This process includes strict technical analysis that allows selection of the best supplier. In addition each batch of condoms delivered to French armed forces undergoes quality testing in the laboratory of the Armed Services Central Pharmacy before being distributed to troops. Despite these strict control measures, several isss remain unclear. One issue involves the shelf life of condoms stored in warm humid tropical conditions. Another issue involves the effect of lubricants on condom quality. The purpose of this report is to describe a study designed to gain insight into these two issues. This study was conducted by the Armed Services Central Pharmacy in colaboration with the Procuremnt and Central Establishment Directorate. Findings showed that stage conditions have no negative effects on the intrinsic physico-chemial properties of condoms supplied by two different manufacturers. Conversely use of inadequate lubricants (alimentary or cosmetic compounds) appeared to have extremely deleterious effects on condom quality. Laboratory tests showed that lubricants composed mainly of fatty acids dramatically decreased the effectiveness of condoms.
