Chronic inhalation effects of ethylene oxide on porphyrin-heme metabolism.

The effects of chronic ethylene oxide (EtO) inhalation on porphyrin-heme metabolism were investigated. When Wistar male rats were exposed to 500 ppm EtO for 6 h a day, 3 times a week for 13 weeks, hemoglobin content significantly decreased, and a normocytic and normochromic anemia was found. In the liver, cytochrome P-450 and protoheme significantly decreased but wet weight, microsomal protein and cytochrome b5 were not affected. The activity of delta-aminolevulinic acid (ALA) synthase increased while ALA dehydratase did not change. The activity of hepatic ferrochelatase decreased time-dependently. Uroporphyrin increased 37% and coproporphyrin tended to increase in the liver. The concentration of protoporphyrin in the liver and erythrocytes tended to increase. Coproporphyrin excretion in the urine showed a 5-6-fold increase while there was no significant increase in urinary ALA excretion. These results indicate that chronic inhalation of EtO causes alterations of hepatic porphyrin-heme metabolism as well as anemia and may affect mechanisms of adaptation to xenobiotics.