Distribution, Accumulation and Excretion of N, N'-Dimonomethylphenyl-p-phenylenediamine in the 2 Year Feeding Test in Rats

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The metabolism, elimination, distribution and accumulation of N, N'-dimonomethylphenyl-p-phenylenediamine (DMPD), a rubber antioxidant/antiozonant, were investigated in male and female Fischer 344 (F344) rats in a feeding study at three dose levels of 0.004,0.02 and 0.1% for 2 years. Two isomers were contained in DMPD as major ingredients which were different in methyl group positions. DMPD and its metabolite in the biological fluids and tissues were determined by GC-MS in the selected ion monitoring-mode. Chronic administration of DMPD resulted in its progressive accumulation in adipose tissues (mesenteric, perirenal, epididymal, and ovarial fat). The ratio of the accumulated amount to the ingested dose (the intake of DMPD in a day) was the highest (1570% in male and 2560% in female) in the 0.02% diet group, suggesting the highest accumulation ratio of DMPD in the adipose tissues during 18 to 24 months. The principal route of excretion was through the feces, with small amounts found in urine. When the amounts of excretion were converted to the ingested dose%, about 10-65% of the ingested dose in male and 30-130% in female rats were progressively excreted into the feces after 24 months. The excretion of a hydroxylated metabolite (the presumed oxidation of a methyl group of DMPD) appeared around 1-2 months and was still found at 6 months in feces. The major metabolite in urine was the hydroxylated compound. On the other hand, the accumulation of DMPD in the adipose tissues was extremely reduced in the one-month withdrawal experiment, but the excretion rates of DMPD from epididymal fat in the 0.02 and 0.1% DMPD treated groups were slower than that in the 0.004% treated group. The blood concentrations of DMPD in the 0.004% and 0.02% withdrawal male rats were higher than those of the treated rat groups.
社団法人日本薬学会の論文
1997-12-31

Distribution, Accumulation and Excretion of N, N'-Dimonomethylphenyl-p-phenylenediamine in the 2 Year Feeding Test in Rats

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