Decoding the Perplexing Mystery of Para-Chloroaniline Formation: A Systematic Review

The objective of this article was to understand and decode the mystery of the formation of para-chloroaniline (PCA). The ingredient of the brown precipitate after mixing sodium hypochlorite (NaOCl) and chlorhexidine gluconate (CHX) is still in debate.

Various studies adopt a different methodology to substantiate that it may contain PCA, which is a carcinogenic agent. The purpose of this systematic review is to evaluate the relationship between PCA and brown precipitate. Two reviewers independently conducted a comprehensive literature search. The MEDLINE, Embase, Cochrane, and PubMed databases were searched. In addition, the bibliographies were manually searched. There was no disagreement between the two reviewers. This review was reported and conducted in step with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines.

Of 233 articles, only 13 articles met the inclusion criteria. Available scientific evidence was more supportive that the brown precipitate form after mixing NaOCl and CHX may form para-chloroamide moiety rather than free PCA, and PCA may be the by-product of CHX degradation.

On the basis of the current evidence and data extracted from the various databases, it can be concluded that the mixture of sodium hypochlorite and chlorhexidine does not form PCA, and PCA may be the by-product of high concentrated chlorhexidine. Further studies are required to substantiate the evidence.