Formaldehyde in pathology services: from molecular toxicity to histopathological change and occupational risk.

BACKGROUND AND

OBJECTIVE

Formaldehyde (FA), classified as a Group 1 human carcinogen by the International Agency for Research on Cancer (IARC), constitutes a significant occupational hazard within hospital pathology service, where it remains the "gold standard" fixative for tissue preservation. Despite widespread recognition of its toxicological properties, the specific carcinogenic and non-carcinogenic health risks confronting pathology personnel subjected to chronic, low-level, and intermittent exposures remain incompletely characterized. This review synthesizes the current body of evidence regarding the cellular and molecular mechanisms of FA toxicity, histopathological (HP) alterations in target tissues, and associated occupational health risks among pathology staff. Study selection for review: A comprehensive literature search was conducted across PubMed∕MEDLINE, Web of Science, and Scopus databases, encompassing publications through December 2025. Studies were selected based on relevance to FA toxicity mechanisms, HP effects, and occupational exposure in pathology settings. Given the heterogeneity of study designs and outcomes, a narrative synthesis approach was adopted.

EVIDENCE SYNTHESIS: The synthesized evidence demonstrates that pathology personnel are routinely exposed to FA concentrations exceeding recommended occupational exposure limits (OELs). At the cellular level, FA exerts toxicity through deoxyribonucleic acid (DNA)-protein crosslink formation, oxidative stress induction, and inflammatory pathway activation. HP examination of exposed individuals reveals a characteristic progression from ciliary loss and goblet cell hyperplasia through squamous metaplasia to epithelial dysplasia in the nasal mucosa. Non-carcinogenic health effects, including respiratory symptoms and genotoxicity biomarker elevation, are highly prevalent. However, direct epidemiological evidence substantiating elevated cancer risk within this specific occupational cohort remains limited, mainly due to improper (occupational medicine) reporting.

CONCLUSIONS

This review confirms substantial non-carcinogenic health effects among pathology personnel, with documented HP alterations representing preneoplastic changes at the portal of entry. The mechanistic evidence supports biological plausibility for carcinogenic risk, though epidemiological confirmation specific to this workforce remains lacking, highlighting a critical research gap.