Hexavalent Chromium Oropharyngeal Aspiration Induced Behavior Effects and Essential Metal Dyshomeostasis in Young Hartley Guinea Pigs

Hexavalent chromium [Cr(VI)] is the toxic form of chromium often used in industry for its hardness, bright colors, and anticorrosive properties. Cr(VI) is a known human lung carcinogen, making its inhalation an occupational hazard. Growing evidence emphasizes the neurotoxic potential of Cr(VI), though it is not linked to brain cancers. Few studies consider neurotoxicity in chromate workers, reporting impaired olfactory discrimination and an increased risk of death from mental health disorders. A major factor limiting translation of most rodent Cr(VI) studies to human populations has to do with vitamin C, which can reduce the toxic Cr(VI) to non-toxic Cr(III). Rats and mice synthesize vitamin C and are likely more resistant to Cr(VI) than humans. Here, we considered Cr(VI) neurotoxicity in guinea pigs (Cavia porcellus), which do not endogenously synthesize vitamin C. We exposed Hartley guinea pigs (both sexes) to occupationally relevant concentrations of Cr(VI) via oropharyngeal aspiration weekly for 90 days. We observed behavioral effects in the open field assay, elevated plus maze, Y-maze, and novel object recognition test during weeks 9–12 of exposure. After euthanasia, we assessed Cr accumulation and essential metal dyshomeostasis in the hippocampus. We observed significantly increased hippocampal Cr accumulation in females, while males exhibited essential metal dyshomeostasis.