Pathological study of thimerosal in mice. (1st Report).
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概要
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Thimerosal (ethylmercuric thiosalicylic acid, sodium salt) in an organic mercury compound which has been used as a preservative in some vaccines and human immunoglobulin products for intramuscular use. This study was designed to examine the safety of thimerosal for mice. Thimerosal solutions of 0.2 ml at 0.01% (the concentration used in vaccines) or at 0.1% were injected twice a week into the intraperitoneal (IP) cavity or subcutaneous (SC) tissue of BALB/c mice. Clinical signs and symptoms such as crossing hind legs were observed in animals injected more than 17 times with the 0.1% thimerosal solution (total thimerosal dose; 70μg Hg/g body weight) into the IP cavity. But the IP administrations of 0.01% thimerosal did not effect the animals even after 35 injections, nor the SC administrations at any dose. At autopsy, nervous system, kidney, liver, heart, lung, spleen, intestine, and skin were examined under light-microscopy with hematoxylin and eosin stain and mercury-histochemistry by photoemulsion method. Peritonitis was observed in all animals that received IP injections with 0.1% thimerosal. Mercury granules were present in the kidney and spleen of the animals receiving IP injections of 7μg Hg/g body weight. Histochemically, mildly positive reaction to mercury was detected in the brain and the liver in the same group of mice. No peritonitis was found in this group of mice. The positive results observed in this series of experiments were obtained only with multiple injections of the high dose thimerosal solution. No toxic effects were found with the 0.01% dosis, which is the same concentration used in commercial vaccines. Thimerosal administered in mice was biotransformed into inorganic mercury, and it was readily degradated into inorganic mercury by four well-known reactive oxygen-producing systems, and the amounts of inorganic mercury produced from thimerosal were the same as those from ethyl mercury and were higher than those from methyl mercury.
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