Human sentinel evidence of delayed hepatocellular injury associated with chloroform and HCFC-123: implications for occupational toxicology and risk management.

Occupational case reports and workplace outbreaks can reveal delayed toxic phenotypes that are not readily anticipated from standard exposure metrics. This structured critical review examined human occupational or work-like reports of hepatocellular injury associated with chloroform and 2,2-dichloro-1,1,1-trifluoroethane (HCFC-123), using Pubmed/MEDLINE searching, citation tracking, reference-list screening, and targeted searches. The aim was not to estimate incidence or derive exposure thresholds, but to evaluate how human sentinel reports may inform occupational toxicology and risk management. Across reports, liver injury was often delayed or recognized only after repeated exposure, occurred in only a subset of described or investigated workers, improved after exposure withdrawal, or worsened after continued exposure or return to work. Available exposure estimates were important but often insufficient to characterize timing, apparent selectivity, and recurrence patterns. HCFC-123 reports provided more visible immune-compatible evidence, whereas chloroform reports primarily supported clinical phenotype recognition through workplace clustering, viral hepatitis mimicry, sentinel investigation, and selected host-susceptibility contexts. Idiosyncratic solvent-induced liver injury is proposed as a cautious interpretive framework, not as a validated diagnosis or proven mechanism. This framework may support latency-aware monitoring, early exposure cessation, cautious return-to-work decision, re-exposure avoidance, and future mechanistic evaluation.