Nasal toxicity, carcinogenicity, and olfactory uptake of metals.
Occupational exposures to inhalation of certain metal dusts or aerosols can cause loss of olfactory acuity, atrophy of the nasal mucosa, mucosal ulcers, perforated nasal septum, or sinonasal cancer. Anosmia and hyposmia have been observed in workers exposed to Ni- or Cd-containing dusts in alkaline battery factories, nickel refineries, and cadmium industries. Ulcers of the nasal mucosa and perforated nasal septum have been reported in workers exposed to Cr(VI) in chromate production and chrome plating, or to As(III) in arsenic smelters. Atrophy of the olfactory epithelium has been observed in rodents following inhalation of NiSO4 or alphaNi3S2. Cancers of the nose and nasal sinuses have been reported in workers exposed to Ni compounds in nickel refining, cutlery factories, and alkaline battery manufacture, or to Cr(VI) in chromate production and chrome plating. In animals, several metals (eg, Al, Cd, Co, Hg, Mn, Ni, Zn) have been shown to pass via olfactory receptor neurons from the nasal lumen through the cribriform plate to the olfactory bulb. Some metals (eg, Mn, Ni, Zn) can cross synapses in the olfactory bulb and migrate via secondary olfactory neurons to distant nuclei of the brain. After nasal instillation of a metal-containing solution, transport of the metal via olfactory axons can occur rapidly, within hours or a few days (eg, Mn), or slowly over days or weeks (eg, Ni). The olfactory bulb tends to accumulate certain metals (eg, Al, Bi, Cu, Mn, Zn) with greater avidity than other regions of the brain. The molecular mechanisms responsible for metal translocation in olfactory neurons and deposition in the olfactory bulb are unclear, but complexation by metal-binding molecules such as carnosine (beta-alanyl-L-histidine) may be involved.
Sunderman
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Department of Chemistry and Biochemistry, Middlebury College, Middlebury, Vermont, USA. 103040.3027@compuserve.com
D000818:Animals; D002273:Carcinogens / Q000493:pharmacokinetics* / Q000633:toxicity*; D006801:Humans; D008670:Metals / Q000493:pharmacokinetics* / Q000633:toxicity*; D009297:Nasal Mucosa / Q000473:pathology / Q000502:physiology; D019636:Neurodegenerative Diseases / Q000139:chemically induced* / Q000503:physiopathology; D009474:Neurons / Q000502:physiology; D009669:Nose Neoplasms / Q000139:chemically induced*; D016273:Occupational Exposure; D009830:Olfactory Bulb / Q000502:physiology; D010255:Paranasal Sinus Neoplasms / Q000139:chemically induced*; D014018:Tissue Distribution
D002273:Carcinogens; D008670:Metals