Toxicology Letters 151 (2004) 459–466 Acute exposure to cobalt induces transient methemoglobinuria in rats Hyogo Horiguchi ∗ , Etsuko Oguma, Satoshi Nomoto, Yukitomo Arao, Kazuhiro Ikeda, Fujio Kayama Department of Health Science, Division of Environmental Immunology and Toxicology, Jichi Medical School, 3311-1 Yakushiji, Minami-Kawachimachi, Kawachi-Gun, Tochigi 329-0498, Japan Received 16 February 2004; received in revised form 21 March 2004; accepted 21 March 2004 Available online 6 May 2004 Abstract We observed transient excretion of dark-brown urine after acute exposure to cobalt in rats and investigated the mechanism of it. We injected cobalt into rats s.c. at a dose of 15 mg/kg and collected urine, peripheral blood, and organ samples at the indicated times after injection. Biochemical and histopathological examinations of these samples were conducted. Obvious macroscopic and biochemical methemoglobinuria was observed just after injection of cobalt, but the level of urinary methemoglobin decreased gradually, almost disappearing by 24h. The levels of cobalt in peripheral blood and urine showed a very similar pattern to that of methemoglobinuria. Neither anemia nor bilirubinemia was observed, indicating no extrarenal intravascular hemolysis. Pathological examination of the kidneys revealed that the glomerular capillaries were filled with red blood cells at 1 h after injection. Electron microscopy showed deformed red blood cells in the glomerular capillaries and condensed hemoglobin in Bowman’s capsule that passed through the basement membrane. There were no trends toward increases in plasma levels of creatinine or blood urea nitrogen. These results indicate that exposure to cobalt induces transient methemoglobinuria through the lysis of red blood cells and oxidation of iron in hemoglobin at the glomerular capillaries without causing renal dysfunction. © 2004 Elsevier Ireland Ltd. All rights reserved. Keywords: Cobalt; Methemoglobinuria; Hemolysis; Glomerular capillary; Rat 1. Introduction Cobalt (Co) is one of the essential metals. Cyanocobalamin (Vitamin B 12 ), which is necessary for the maturation of red blood cells and the mainte- nance of myelin, contains Co in its tetrapyrrolic ring ∗ Corresponding author. Tel.: +81-285-58-7336; fax: +81-285-44-8465. E-mail address: hhyogo@jichi.ac.jp (H. Horiguchi). (Lee and Herbert, 1999). Normally, Co is absorbed from the stomach in the form of Vitamin B 12 through interaction with an intrinsic factor and excreted via the urinary tract, maintaining a total body content of about 0.2 mg, which is equivalent to about 5 mg of Vi- tamin B 12 (Elinder and Friberg, 1986). Exposure to an excessive amount of Co can have deleterious effects on the human body, however (ATSDR, 2001). After several years of inhaling Co-containing dust, severe pneumoconiosis were reported among workers in the 0378-4274/$ – see front matter © 2004 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.toxlet.2004.03.018