Liver, kidney, and central nervous system toxicity of aluminum given intraperitoneally to rats: a multiple-dose subchronic study using aluminum nitrilotriacetate.

In the first test, aluminum nitrilotriacetate (Al-NTA), aluminum chloride, aluminum potassium sulfate, or saline was injected ip, employing male Wistar rats. Each group consisted of ten rats. Al was given in a dose of 5 mg Al/kg body wt/day, for 14 days. Only those rats given Al-NTA showed morphological damage of the liver and kidney. Damages included diffuse midzonal coagulation necrosis of hepatocytes and acute proximal tubular necrosis of the kidney at Day 4. Seven of ten rats given Al-NTA died within 5 days. The second test was performed in metabolic cages. Al-NTA, in a dose of 1.5 to 2.0 mg Al/kg body wt/day, and NTA, of an equivalent dose, were injected ip for 54 days. Midzonal coagulation necrosis and some regenerative changes were observed in the hepatic parenchyma at Day 8. At the end of the study, complete regeneration occurred in the liver. Biochemical tests at Days 6, 13, and 28 showed high amounts of GOT, GPT, LDH, gamma-GTP, and ALP. Necrosis of proximal tubular cells of the kidney and some regeneration was noted at Day 8. Metabolic acidosis was demonstrated at Days 6, 13, and 28. Moreover, from Day 38 on, atrophy of the nerve cells of the cerebrum and demyelination of the brain stem were observed. Control rats given NTA did not exhibit any organ damage. It is concluded that a relatively small dose of Al can produce toxicosis when given with certain metal chelators.