Toxicokinetics and molecular interaction of [¹⁴C]-formaldehyde in rats

The excretion, tissue distribution, and binding of [¹⁴C]-formaldehyde were studied at different time intervals in male rats following a single intraperitoneal injection of 72 mg CH₂O (14.7 μCi)/ kg body weight. Within 30 min, 10% of the total dose was recovered in expired air as¹⁴CO₂ and by the end of 72 hr, 41% of the administered dose was eliminated through expired air. The total elimination of¹⁴CH₂O activity in urine and feces in 72 hr was 15%. Erythrocytes retained significant amounts of radioactivity, even at the end of 72 hr. Substantial levels of radioactivity were detected in most tissues one hr after administration, indicating a fast absorption and rapid distribution. Subcellular fractionation of the tissues showed that the highest levels of relative percent binding was in the microsomal fraction, whereas cytosol fractions contained lowest levels of bound radioactivity. DNA, RNA, protein and lipid fractions of liver and spleen tissues showed significantly elevated levels of¹⁴C-incorporation as compared to other tissues. The in vivo incorporation of¹⁴C-activity showed an increased association of¹⁴CH₂O with RNA in all the tissues. The maximum registration of radioactivity in RNA was at 48 hr after administration. Significantly higher amounts of¹⁴C-activity were registered in DNA of all tissues. The maximum registration of radiolabel in DNA of most tissues was at 12 hr after the¹⁴CH₂O administration. The liver DNA showed maximal levels at 3 hr with a second peak at 48 hr. Substantial amounts of bound radioactivity in nucleic acids of all the tissues were observed even 72 hr after dosing. The relationship between macromolecular association and formaldehyde toxicity has been discussed.