Decoding the perplexing mystery of para-chloroaniline formation: A systematic review

Abstract

A BSTRACT Objective: 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. Materials and Methods: 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. Results: 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. Conclusion: 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.

The para-chloroaniline prevention after the use of sodium thiosulfate as an intermediary irrigator between sodium hypochlorite and chlorhexidine

“…The pH of the samples after the mixture varied from 8 to 9. The authors highlighted that as higher TSF concentration, higher the whitish turbidity of the final sample, as also the presence of a characteristic sulfur odor was higher [34][35][36]. In this study, was not evaluated the presence of chlorate in the samples, and neither the turbidity of the samples quantitatively or qualitatively neither the generated odor, although both were noted.…”

“…The pH of the final samples varies between 8 and 9 (alkaline). When most of the micro-organisms involved in the endodontic infections do not reproduce in alkaline environment [33][34][35][36], possible residues into RCS will not favor the multiplication of pathogens.…”

“…The use of TSF to neutralize solutions of NaOCl with an 8 to 10 pH, can result in the formation of shorter levels of chlorate [34][35][36]. The chlorate is a contaminant that can be present in the water and is in the list of undesirable substances of the Environmental Protection Agency of United States.…”

“…The brown precipitate was analyzed and compared to signals obtained from 4.99% NaOCl solutions commercially available, 2% solutions and 98% PCA in the form of powder. After studies, the authors observed that the chromatographic and spectroscopic analysis demonstrates that the brown precipitate do not contains free PCA [35,36].…”

What does not form after accidental sodium hypochlorite contact with chlorhexidine?

“…In addition, Orhan and Irmak (2019) highlighted the misinterpretation of results of the study by Arslan et al (2015) which claimed the presence of free PCA in the precipitate. In a recent review about analytic methods used for evaluation of the precipitate, it has been concluded that the precipitate does not contain free PCA (Khatib et al, 2020).…”