This CropLife Europe-funded study pooled data from regulatory studies across agrochemical companies to evaluate whether cell proliferation in cultured human hepatocytes can reliably distinguish chemicals that drive liver tumor formation in rodents from those that do not. Using 39 cryopreserved human hepatocyte preparations spanning donors aged 10 months to 80 years, two independent laboratories confirmed that the growth factors EGF and HGF consistently stimulated hepatocyte proliferation across all donor demographics — demonstrating that the assay works. In stark contrast, the CAR activators phenobarbital and CITCO, and the PPARα activator WY-14,643 — all potent rodent liver carcinogens — produced no increase in human hepatocyte proliferation at any concentration tested, confirming a fundamental species difference. Reproducibility was validated by testing a single donor preparation fourteen times across both laboratories under different conditions, with entirely consistent results.
The qualitative response pattern was independent of donor sex, age, and, based on limited sampling, ethnicity, though inter-individual variability in response magnitude was noted. The authors conclude that this method is sufficiently established and ready for formal validation under OECD Guidance Document 34, which would support its broader regulatory uptake as a New Approach Method for non-genotoxic carcinogenicity assessment.”
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