Genotoxicity profiles of common alkyl halides and esters with alkylating activity.

Drug synthesis and/or formulation can generate genotoxic impurities. For instance, strong acid/alcohol interactions during the process of drug salt formation produce alkylating agents such as alkyl halides and alkyl esters of alkyl sulfonic acids. The genotoxicity of a few classic alkylating agents such as methyl and ethyl methanesulfonate have been previously well characterized, whereas the majority of compounds from this class have only been tested in the Salmonella reversion assay. Therefore, the goal of this study was to investigate clastogenicity and DEL recombination profiles of 22 halogenated alkanes and alkylesters of sulfuric and alkane-, aryl-sulfonic acids using a battery of cellular and molecular assays. The in-vitro micronucleus assay in CHO cells was used to measure clastogenicity and the deletion recombination (DEL) assay in S. cerevisiae provided a measure of DNA deletions. We also examined the compounds' reactivity towards 4-(p-nitrobenzyl)pyridine (NBP), a surrogate molecule for biological ring nitrogens. Methylating agents were most potent in all three assays and the alkyl chlorides evaluated in our study were negative in all three assays. Also, a strong correlation was found between the MN, DEL and NBP assays. In summary, this study contributes to a better understanding of the genotoxic properties of common alkyl halides and alkyl esters with alkylating activity and might provide guidance for managing risk of genotoxic process-related impurities of drug substances and products.

An assessment of comparative methods for approaching electrode polarization in dielectric permittivity measurements.

We examine the validity of three common methods for analysis and correction of the electrode polarization (EP) effect in dielectric spectroscopy measurements of conductive liquid samples. The methods considered are (i) algorithmic treatment by modeling the EP behavior at constant phase angle, (ii) varying the size of the electrode gap, and (iii) polypyrrole (PPyPss) layered electrodes. The latter is a relatively recent innovation suggested to be an efficient solution. We demonstrate that PPyPss coated electrodes do not diminish the effect of EP, and even add relaxation processes of its own. Our conclusion is that these polymer coated electrodes are not suitable for the correction of electrode polarization.

Suggestion for a physical-chemical assessment of the sea coastal waters pollution on the basis of the analysis of the examination on the Gdansk Bay waters.

The study presents the results of physical-chemical examinations of the coastal water of the Baltic Sea, carried out from 1984-1988 on 18 sampling stations located in the region of Gdynia and Gdansk, and along the Hel Peninsula. The samples were collected weekly from the surface of water in the distance of about 5 m from the shore during 5 years. The results indicated a considerable physical and chemical pollution of the coastal water of Gdansk Bay. Noted is the absence of the criteria of sanitary evaluation of the sea water regarding its usability for recreation. Mean concentration values of phosphates, ammonia compounds and nitrites as well as BOD5 in the coastal water of Gdansk Bay were on the average 5-10 times higher than in the water of the open Baltic Sea. If the level of reference is the open sea water, it must be assumed that the coastal water of the Gdansk Bay is strongly polluted. Useful seems to be the determination of the level of the physical and chemical pollution of the sea coastal water by comparison of certain indices with the values characteristic for open, clean sea or by relating them to the values making the "background" for the sea area examined. There is a need to elaborate evaluation criteria of physical and chemical pollution of sea coastal waters.