2,2',3',4,4'5,5'-Hepatachlorobiphenyl (PCB 180)--on its toxicokinetics, biotransformation and porphyrinogenic action in female rats.
The toxicokinetics and biotransformation of 2,2',3',4,4',5,5'-heptachlorobiphenyl, as well as its influence on the activity of microsomal and cytosolic enzymes and on the porphyrin pathway in the liver were studied in female rats following oral treatment with 7 mg/kg every other day for 3 months. One day after cessation of treatment the concentration of the compound in liver, spleen, CNS and blood was 100-500 times and in the trachea it was only 5 times less than in the adipose tissue. The daily excretion with the feces and urine amounted to 35 and 1.5 micrograms, respectively. In both excreta, heptachlorobiphenylol was identified as a metabolite. The biotransformation rate was estimated to be about 5%. Investigations of the liver revealed increases in the relative liver weight, total cytochrome P-450 content, O-deethylation of 7-ethoxycoumarin and in the activity of glutathione S-transferases. Disturbances of the hepatic porphyrin pathway were not detected. Only at the end of a post-dosing period of 12 months did the hepatic uroporphyrinogen decarboxylase show diminished activity. Only one of these animals with diminished enzyme activity showed drastically elevated porphyrins. In these animals, the fecal and urinary porphyrins did not differ from controls. At no time did heptachlorobiphenyl influence the urinary excretion of delta-aminolevulinic acid and porphobilinogen. The results indicate 1) that this congener shows expected toxicokinetics with the exception of being accumulated in the trachea and 2) that this congener induces disturbances of the hepatic porphyrin pathway several months after cessation of treatment.
Koss
G
G
Department of Labor, Health and Social Affairs, Hamburg, Germany.
Meyer-Rogge
D
D
Seubert
S
S
Seubert
A
A
Losekam
M
M
D000818:Animals; D001711:Biotransformation; D001835:Body Weight / Q000187:drug effects; D003577:Cytochrome P-450 Enzyme System / Q000187:drug effects; D004789:Enzyme Activation / Q000187:drug effects; D005260:Female; D005982:Glutathione Transferase / Q000187:drug effects; D008099:Liver / Q000187:drug effects / Q000201:enzymology; D009929:Organ Size / Q000187:drug effects; D011165:Porphyrinogens / Q000096:biosynthesis / Q000493:pharmacokinetics* / Q000633:toxicity*; D011166:Porphyrins / Q000096:biosynthesis*; D051381:Rats; D017208:Rats, Wistar
D011165:Porphyrinogens; D011166:Porphyrins; D003577:Cytochrome P-450 Enzyme System; D005982:Glutathione Transferase