Amberg, Alexander; Harvey, James S.; Czich, Andreas; Spirkl, Hans-Peter; Robinson, Sharon; White, Angela; Elder, David P. published the artcile< Do Carboxylic/Sulfonic Acid Halides Really Present a Mutagenic and Carcinogenic Risk as Impurities in Final Drug Products?>, Safety of 3-Chloro-4-methylbenzene-1-sulfonyl chloride, the main research area is mutagenesis carboxylic sulfonic acid halide.
A substantial amount of mutagenicity data on acyl/sulfonyl halides is available in the public domain, and these data are the basis for many in silico models of mutagenicity (e.g., Derek Nexus and Leadscope). A review of these data indicates that the perceived mutagenic potential of this class of compounds is based on a number of nonreproducible pos. findings in the bacterial mutagenicity assay and pos. bacterial mutagenicity data on a series of compounds where formation of reactive halodimethyl sulfides (HDMSs) in DMSO may have compromised the interpretation of the Ames data (HDMSs are typically mutagenic). The only genuine mutagenic, genotoxic, and carcinogenic compound within the 50+ acyl/sulfonyl halides described herein is dimethylcarbamic chloride, which is appropriately considered to be a potential human carcinogen. Some in silico systems, such as Derek Nexus, contain rules detailing that the activity of this class should be considered a false pos. flag for mutagenicity, and ideally, any in silico structure-activity rules for mutagenicity in other systems should likewise be addressed. The data presented here support the view that these alerts should currently be interpreted as a false pos. flag for mutagenicity and that the entire class should be viewed as a low concern from a mutagenicity perspective. The formation of these reactive HDMSs is an example of the classical Pummerer rearrangement. The chem. reactivity of this class of compounds also supports the contention that they are of limited concern from a mutagenic and carcinogenic impurity risk perspective when used in the synthesis of drug products. They can be expected to rapidly purge from any reaction sequence with generic predicted purge factors in the range from 1 × 103 to 3 × 105 per stage and hence should be effectively eliminated at the stage of introduction. We would therefore recommend avoiding the use of DMSO as the solvent for mutagenicity tests with acyl/sulfonyl halides because of the potential for false pos. results arising from DMSO reaction products, which are not relevant under aqueous, physiol. conditions. Furthermore, as indicated by the Ames test data for mesyl chloride/2-fluorobenzoyl chloride, even non-DMSO organic solvents may not be appropriate for certain members of this class (acyl/sulfonyl halides), suggesting that they may not be amenable to adequate testing in the Ames assay.
Organic Process Research & Development published new progress about Acid halides Role: ADV (Adverse Effect, Including Toxicity), BSU (Biological Study, Unclassified), BIOL (Biological Study). 42413-03-6 belongs to class chlorides-buliding-blocks, and the molecular formula is C7H6Cl2O2S, Safety of 3-Chloro-4-methylbenzene-1-sulfonyl chloride.
Referemce:
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics