Hydroquinone toxicity in different animal models

Hydroquinone (HQ) is an important benzene metabolite with a broad range of toxicological effects observed in animal models and in vitro systems. The review is based on studies conducted in rodents, invertebrates, and human cell lines that outline the dose- and time-dependent effects of HQ on organ systems such as the hematopoietic, hepatic, renal, retinal, immune, and reproductive. Chronic dietary or gavage exposure in rodents frequently caused renal tubular lesions, aggravated chronic progressive nephropathy, and triggered or accelerated tumor development, particularly in male Fischer 344 rats. Alterations in progenitor cell function, chromosomal deletions (e.g. −7, 5q31-), and leukemic transformation in TK6 and HL-60 cell models supported the claim of hematopoietic toxicity. Mechanistic studies of cells show that HQ causes oxidative stress through quinone/semiquinone redox cycling, DNA damage (strand breaks, micronuclei), disruption of DNA-repair mechanisms (e.g. Pol η, Rad6B/Rad18, PARP-1), dysregulation of epigenetic processes through DNMT1-mediated promoter methylation and aberrant cell signaling (e.g. AhR activation, ferroptosis). Studies of systemic uptake following dermal absorption have shown that topical application results in a significant systemic uptake, highlighting the importance of dermal exposure in humans. The data show that HQ is a multi-organ toxicant and a tumor promoter, and that its susceptibility depends on species, sex, and strain. In light of these results, future studies ought to focus on mechanistic cross-species comparisons, low-dose chronic exposure studies, genetic and epigenetic susceptibility paradigms and the efficacy of protective agent. These findings have significant implications for assessing regulatory risks and ensuring the safe use of HQ in industrial or cosmetic settings.