Divine Aleru is an accomplished biochemist and researcher with a specialized background in environmental toxicology, focusing on the impacts of heavy metals on human health. With deep-rooted expertise in microbiome signatures analysis, Divine seamlessly blends rigorous scientific training with her passion for deciphering the intricate relationships between environmental exposures and the human microbiome. Her career is distinguished by a commitment to advancing integrative health interventions, leveraging cutting-edge microbiome research to illuminate how toxic metals shape biological systems. Driven by curiosity and innovation, Divine is dedicated to translating complex environmental findings into actionable insights that improve individual and public health outcomes. 
Divine Aleru is an accomplished biochemist and researcher with a specialized background in environmental toxicology, focusing on the impacts of heavy metals on human health. With deep-rooted expertise in microbiome signatures analysis, Divine seamlessly blends rigorous scientific training with her passion for deciphering the intricate relationships between environmental exposures and the human microbiome. Her career is distinguished by a commitment to advancing integrative health interventions, leveraging cutting-edge microbiome research to illuminate how toxic metals shape biological systems. Driven by curiosity and innovation, Divine is dedicated to translating complex environmental findings into actionable insights that improve individual and public health outcomes. What was reviewed?
This chromium exposure routes toxicogenomic review synthesises evidence on how chromium (Cr)—especially hexavalent chromium, Cr(VI) shows adverse human health effects of chromium by exposure routes in humans across dermal, inhalation, and ingestion pathways, using transcriptomic datasets (GEO: GSE16394, GSE24025, GSE36684, GSE120146) and network/GO enrichment analyses alongside epidemiology and mechanistic literature. The review characterises shared and route-specific molecular signatures (e.g., DNA damage, cell-adhesion disruption) and proposes hub genes as candidate biomarkers to support surveillance and certification decisions.
Who was reviewed?
The authors integrate in vitro human dermal fibroblasts exposed to potassium dichromate (GSE16394), in vitro human bronchial epithelial BEAS-2B cells exposed to Cr(VI) (GSE24025, GSE36684), and in vivo mouse duodenum after oral Cr(VI) (GSE120146). These models are interpreted in the context of real-world exposure. Adverse human health effects of chromium by exposure investigated included: consumer/leather/cement-related skin contact, occupational airborne chromates, and community drinking-water/food ingestion, with occupational and environmental studies used to map health outcomes.
Adverse Human Health Effects of Chromium
Across all routes, DNA damage and metastasis-linked signalling emerged as common toxic mechanisms, with consistent disruption of cell-adhesion biology (suppressed focal adhesion/cell–substrate junction terms), supporting a mechanistic bridge to carcinogenicity. For dermal exposure, hub genes (CXCL8, PTGS2, FOS, HMOX1, ATF3, IRS1, E2F1) aligned with sensitisation/irritation, Nrf2-driven stress responses, and replication stress; enriched processes included RNA/tRNA and sterol/cholesterol biosynthesis, while DNA replication and intrinsic apoptosis pathways were suppressed, consistent with skin damage, ulceration, and allergic contact dermatitis. Inhalation exposure activated ribosome biogenesis and protein-synthesis programs with suppressed adhesion, and identified TLR4, TGM2, TNFRSF11B, BDKRB1, KIT, and ZEB1 as hubs tied to inflammation, EMT, drug resistance, and tumour progression—mechanistically consistent with the long-recognised elevation in lung cancer risk among chromate-exposed workers.
Key implications
To strengthen the Heavy Metal Tested and Certified (HTMC) program, chromium risk assessment should extend beyond total/speciated measurements to include route-specific mechanistic biomarkers. This approach allows the program to move from a simple “present/absent” determination toward a mechanism-informed certification framework, integrating dermal, inhalation, and ingestion pathways with cross-route anchors. The following table summarizes the key implications.
| Exposure Route / Anchor | Key HTMC Implications |
|---|---|
| Dermal | Use ex vivo keratinocyte/dendritic-cell assays to monitor HMOX1 and CXCL8 induction, as well as Nrf2 pathway activation. These assays can identify sensitising Cr(VI) leachates from products such as leather or cement-containing materials. |
| Inhalation | Pair workplace Cr(VI) air concentration measurements with BEAS-2B transcriptomic panels (TLR4, TGM2, ZEB1) and adhesion marker tracking. This expands evaluation beyond simple mass concentration to better reflect carcinogenic risk potential. |
| Ingestion | Monitor intestinal integrity markers (brush-border enzymes), proliferative and angiogenic signals (VEGFA, EGFR, SGK1), and abnormalities in lipid/steroid metabolism. Combine with speciation-aware water and food chromium limits. Abnormalities should trigger liver-focused follow-up. |
| Cross-Route Anchor: DNA Damage | Integrate DNA damage indicators (e.g., γH2AX and nucleotide excision repair pathway readouts) into the certification framework to assess genotoxic risk across exposure pathways. |
| Cross-Route Anchor: Adhesion Pathway Suppression | Include suppression of adhesion-related pathways as a universal mechanistic anchor to reflect systemic chromium toxicity risk across dermal, inhalation, and ingestion routes. |
Citation
Shin, D. Y., Lee, S. M., Jang, Y., Lee, J., Lee, C. M., Cho, E., & Seo, Y. R. (2023). Adverse Human Health Effects of Chromium by Exposure Route: A Comprehensive Review Based on Toxicogenomic Approach.International Journal of Molecular Sciences, 24(4), 3410. https://doi.org/10.3390/ijms24043410
