Table 1.

Summary of carcinogenicity for Cr(III) and Cr(VI)

Category	Cr(III)	Cr(VI)
In vitro studies	• Causes DNA damage and genetic mutations in cells22 • Less toxic than Cr(VI) in HepG2 cells and human fibroblasts;51,52 more toxic than Cr(VI) in yeast and Jurkat cells22	• Causes DNA damage and genetic mutations in cells, different mechanisms than Cr(III)27,28 • Cannot damage DNA directly: requires reductive activation in cells29,30 • Chronic exposure to Cr(VI):  ○ Induces DNA lesions (SSB, alkali-labile sites, DPCs, DNA–amino acid cross-links, chromium–DNA adducts, formation of protein–Cr[III]–DNA cross-links)33–36  ○ Increases generation of miR21, decreases expression of PDCD4 in BEAS-2B cells47,48  ○ Cytotoxic and genotoxic to hawksbill sea turtle cells, causes chromosome aberrations in metaphases43  ○ Zinc chromate/lead chromate causes DNA DSBs, chromosome aberrations, aneuploidy in WTHBF6 cells (also in human bronchial fibroblasts for ZnCrO4), resulting in chromosome instability, gene mutations, progression toward tumorigenesis37–40,42
In vivo studies	• Carcinogenicity in animals is uncertain • Chronic exposure provides little evidence of adverse effects, did not induce in-life toxicity or increase in nonneoplastic lesion incidence48	• Chronic exposure to potassium dichromate, lead chromate, SDD accounted for high carcinogenic activity in animal models:  ○ DNA damage53  ○ Hepatic oxidative stress/hepatocyte apoptosis53  ○ Development of fibrosarcomas or rhabdomyosarcomas54  ○ Renal tumors54  ○ Small intestinal adenoma/carcinoma55,56  ○ Squamous-cell papilloma or carcinoma of oral mucosa55
Epidemiology studies	• Evidence inadequate to indicate human exposure associated with increased cancer risk63,64	• Cr(VI) exposure can occur at:  ○ High concentrations occupationally (chromate production, chromate-pigment production, chromium-plating industries)38,60,61  ○ Chronic low concentrations via inhalation from ambient air pollution or ingestion from contaminated water62 • Occupational exposure to high concentrations increases risk of lung and sinonasal cavity cancers in humans, may also be stomach carcinogen60,61 • Absorption into human lung cells brings about BDAs, ODD in P53 gene, and adenine/guanine mutations59 • Zinc chromate is potent carcinogen38 • Exposure to lead chromate may not contribute to lung cancer60

Abbreviations: Cr(VI), hexavalent chromium; Cr(III), trivalent chromium; SSB, single-strand breaks; DPCs, DNA–protein cross-links; DSBs, DNA double-strand breaks; SDD, sodium dichromate dehydrate; BDAs, bulky DNA adducts; ODD, oxidative DNA damage.