[Preliminary studies on the retention of hydroxylated PCDF metabolites in rat blood].
We recently reported that certain hydroxylated PCB (OH-CB) metabolites were selectively retained in blood of rats experimentally dosed with PCB (Aroclor 1254), and also in blood of seals and humans environmentally exposed to PCBs. We also showed that metabolism in vivo of polychlorinated dibenzofurans (PCDFs) gave rise to a large number of hydroxylated PCDF (OH-CDF) metabolites, excreted in faeces, after oral administration to rats of PCDFs mixture (1, 2, 7, 8-tetraCDF 14%, 2, 3, 7, 8-tetraCDF 35%, 1, 2, 3, 7, 8-pentaCDF 48%). These results suggest that OH-CDFs could be present in blood. In the present study, potential retention of OH-CDF metabolites in blood (serum) was investigated in a female Wistar rat exposed to the PCDFs mixture. Serum was analyzed for the methylated OH-CDFs by gas chromatography (GC) and GC-mass spectrometry. Two major metabolites were determined in serum 1 day after oral administration. These were identified to be 3-OH-2, 4, 7, 8-tetraCDF (A) and 3-OH-2, 4, 7, 8, 9-pentaCDF (B) by comparison with synthesized reference compounds. 3-OH-2, 4, 7, 8-tetraCDF and 1, 2, 3, 7, 8-pentaCDF, respectively, via 3, 4(6, 7)-epoxide intermediate and subsequent NIH-shift of the 3(7)-chlorine to the 4(6)-position. The amounts of 3-OH-2, 4, 7, 8-tetraCDF and 3-OH-2, 4, 7, 8, 9-pentaCDF in the serum (5.72 g) analyzed accounted for 0.018% of 2, 3, 7, 8-tetraCDF and 0.003% of 1, 2, 3, 7, 8-pentaCDF dosed, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
Kuroki
H
H
Daiichi College of Pharmaceutical Sciences, Fukuoka.
Ishimura
N
N
Masuda
Y
Y
Klasson-Wehler
E
E
Bergman
A
A
D000818:Animals; D001572:Benzofurans / Q000097:blood / Q000378:metabolism*; D000072338:Dibenzofurans, Polychlorinated; D004350:Drug Residues; D005260:Female; D006801:Humans; D006900:Hydroxylation; D051381:Rats; D017208:Rats, Wistar; D046048:Seals, Earless
D001572:Benzofurans; D000072338:Dibenzofurans, Polychlorinated