Potential carcinogenic and mutagenic industrial chemicals. I. Alkylating agents

Abstract

A variety of alkylating agents, acylating agents, peroxides, halogenated derivatives, and nitrogen derivatives have been reviewed, principally in terms of their synthesis, areas of utility, stability, distribution, reactivity, levels of exposure, population at risk, metabolism, carcinogenicity, and mutagenicity.

Synthesis of Novel IP Agonists via N-Aminoethyl Cyclic Amines Prepared by Decarboxylative Ring-Opening Reactions

“…Route A is direct and simple, involving the reaction of an amine with a substituted aziridine or its precursor (e.g., N -substituted chloroethylamine) [ 23 ]. However, aziridines are not commercially available at present because of their toxic and carcinogenic properties [ 29 , 30 ], and thus we synthesized N -substituted chloroethylamines by a well-known route [ 31 , 32 ]. Although this route is attractive for preparing various substrates, multiple steps including a reduction step are required.…”

Genotoxic Impurities in Pharmaceutical Manufacturing: Sources, Regulations, and Mitigation

“…Section of this review focuses on GTIs related to starting materials, reagents, reactants, catalysts, and solvents with genotoxic effects and related genotoxic side products. Impurities structurally related to specific APIs (e.g., genotoxic sulfonate ester side products during the synthesis of the steroid mometasone , ) are outside of the scope of this review (Figure ). The book “ Genotoxic ImpuritiesStrategies for Identification and Control ” edited by Teasdale provides an exhaustive discussion on the identification and control of such impurities in API manufacturing …”

Reactivity of mutagenic propylene oxides with deoxynucleosides and DNA

“…Propylene oxides are commercially useful compounds [Fishbein, 1980; Manson, 1980; IARC, 19761 which are mutagenic in the Ames Salmonella iyphimurium reversion assay [wade et al, 1978; Hemminki and Falck, 19791 and cause chromosomal aberrations as well as sister chromatid exchanges in cultured human lymphoAbbreviations used: Po, propylene oxide (1,2 epoxypropane, CAS reg. no.…”

“…Propylene oxides are commercially useful compounds [Fishbein, 1980;Manson, 1980;IARC, 19761 which are mutagenic in the Ames Salmonella iyphimurium reversion assay [wade et al, 1978;Hemminki and Falck, 19791 and cause chromosomal aberrations as well as sister chromatid exchanges in cultured human lympho-cytes [Norppa et al, 19811. In addition, some members of the series have been determined to be carcinogenic in experimental animals [IARC, 19761. Our interest in structure-mutagenicity relationships for aliphatic epoxides [wade et al, 1978;Neau et al, 1982;Frantz and Sinsheimer, 1981;Frantz et al, 19851 has prompted us to extend the existing literature [Hemminki, 1979;Hemminki et al, 1980;Lawley and Harman, 1972;Hemminki and Hesso, 1984;Mazullo et al, 19841 for the reactivity of such epoxides with deoxynucleosides and DNA. Towards this end, we have previously examined the total and specific site reactivity of four aliphatic epoxides-propylene oxide (PO), glycidol (GL), epichlorohydrin (EC) , and trichloropropylene oxide (TCP0)-with deoxycytidine (dCyd) and thymidine (dThd) [Djuric and Sinsheimer, 1984a and b].…”