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To investigate the influence of polychlorinated biphenyls (PCB) on porphyrin metabolism, Wistar rats were orally administered KC‐400. The mean value of liver/body weight ratio in normal rats was 3.86%, with a range of 3.44% to 5.22%. Their mean blood protoporphyrin level was 23.3 μg/dl packed cell volume (p.c.v.), with a range of 11.8 to 64.4 μg/dl p.c.v., and their mean liver protoporphyrin level was 0.17 μg/gm wet weight, with a range of 0.03 to 0.40 μg/gm wet weight. A feed containing KC‐400 (140–160 ppm) was given for 2 to 20 weeks to 20 rats. The mean value of liver/body weight ratio was 5.00%, with a range of 3.80% to 6.16%. The mean erythrocyte protoporphyrin level was 47.4 μg/dl p.c.v., with a range of 19.7 to 83.2 μg/dl p.c.v., and the mean liver protoporphyrin level was 0.36 μg/gm wet weight, with a range of 0.04 to 0.67 μg/gm wet weight. The liver coproporphyrin level showed abnormalities in 2 of 20 rats fed the feed containing KC‐400, with values of 0.71 and 9.89 μg/gm wet weight, respectively. After administration of KC‐400 feed for 43 weeks, the mean value of blood coproporphyrin level rose to 32.1 μg/dl p.c.v., with a range of 11.4 to 54.6 μg/dl p.c.v. The mean erythrocyte protoporphyrin level was 74.3 μg/dl p.c.v., with a range of 49.5 to 102.1 μg/dl p.c.v. The mean liver coproporphyrin level was elevated to 5.15 μg/gm wet weight, with a range of 0.45 to 9.48 μg/gm wet weight, and the mean liver protoporphyrin level was 0.65 μg/gm wet weight, with a range of 0.43 to 9.88 μg/gm wet weight. Thus, there was an increase in both liver porphyrin and coproporphyrin following KC‐400 feeding. Liver cells in the rats with abnormal porphyrin levels exhibited a red fluorescence. From these results, we can deduce that KC‐400 may induce abnormalities in porphyrin metabolism, when it is fed orally for a long period of time. These abnormalities in porphyrin metabolism are limited to the liver only.

In order to determine the lowest concentration of griseofulvin (GF) needed to induce abnormal porphyrin metabolism, D‐D strain mice were fed with a feed containing GF in concentrations of 0.1%, 0.5%, and 1.0%. The liver and blood porphyrin levels were analyzed, and the red fluorescence of the liver and blood observed with a fluorescent microscope. In the 0.5% GF and 1.0% GF groups, a swelling of the liver was observed, and coproporphyrin and protoporphyrin levels in the liver and the blood increased markedly. However, the increase in protoporphyrin levels was more prominent than the increase of coproporphyrin levels. The increase in the liver protoporphyrin was more marked than that in the blood porphyrin. Comparisons of the 0.5% GF and 1.0% GF groups revealed that liver swelling was more prominent in the 1.0% GF group. A high degree of metabolic abnormality in blood protoporphyrin was found in 1.0% GF animals whose feeding period was rather short. In the 0.1% GF group, liver swelling was hardly noticeable, and there were no differences between the short feeding and long feeding groups. Although no abnormalities in blood porphyrins were noticed in comparison with the normal group, abnormally high levels of liver porphyrins were found in 3 out of the 34 treated mice. No differences from the normal group were noted in the remaining 31 animals. In the 0.5% GF and 1.0% GF groups, red fluorescence of the liver was seen in all cases, while in the 0.1% GF group, reticular red fluorescence was noted in only one animal. From these findings, it appears that a marked increase in porphyrin occurs at a concentration above 0.5% in D‐D strain mice, whereas, at the concentration of 0.1%, the majority of the treated mice remain within normal limits. Only a few showed any abnormality of porphyrin metabolism. We feel that, for this reason, it would be better to use a GF concentration of 0.1% for the lowest concentration experiments involving GF‐induced protoporphyria in D‐D strain mice and especially for investigations of the interaction of other chemicals with GF, and investigations of initial changes of porphyrin metabolism.

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