Kanetoshi A, Katsura E, Ogawa H, Ohyama T, Kaneshima H, Miura T
Hokkaido Institute of Public Health, Japan.
Arch Environ Contam Toxicol. 1992 Jul;23(1):91-8. doi: 10.1007/BF00226000.
Acute toxicity of 2,4,4'-trichloro-2'-hydroxydiphenyl ether (Irgasan DP300) (I) and its three chlorinated derivatives, 2',3,4,4'-tetrachloro-2-hydroxydiphenyl ether (II), 2',4,4',5-tetrachloro-2-hydroxydiphenyl ether (III) and 2',3,4,4',5-pentachloro-2-hydroxydiphenyl ether (IV), in mice were examined by intraperitoneal injection. The LD50 values of Irgasan DP300, II, III and IV were 1,090, 710, 650 and 430 mg/kg, respectively. The percutaneous absorptions of these tritiated compounds were also examined by the application on the backs of mice. The radioactivities in most tissues reached to the maximal levels at 12 h or 18 h after dosing, which corresponded to 11-76% of the maximal levels given by the oral administration (Kanetoshi et al. 1988a). These results show the high percutaneous absorbability of Irgasan DP300 and its chlorinated derivatives. The intraperitoneal administrations of III and IV to rats induced hepatic microsomal aminopyrine N-demethylase and aniline 4-hydroxylase activities similarly to phenobarbital. These chlorinated derivatives also increased cytochrome P-450 content, and the activities of aminopyrine N-demethylase and N-methylaniline N-demethylase in hepatic microsomes from mice. The extents of the increases were similar to those by phenobarbital and 3-methylcholanthrene.
通过腹腔注射法检测了2,4,4'-三氯-2'-羟基二苯醚（三氯生，Irgasan DP300）（I）及其三种氯化衍生物2',3,4,4'-四氯-2-羟基二苯醚（II）、2',4,4',5-四氯-2-羟基二苯醚（III）和2',3,4,4',5-五氯-2-羟基二苯醚（IV）对小鼠的急性毒性。三氯生、II、III和IV的半数致死量（LD50）值分别为1,090、710、650和430 mg/kg。还通过将这些氚标记化合物涂抹于小鼠背部来检测其经皮吸收情况。给药后12小时或18小时，大多数组织中的放射性达到最高水平，相当于口服给药最高水平的11 - 76%（Kanetoshi等人，1988a）。这些结果表明三氯生及其氯化衍生物具有较高的经皮吸收性。对大鼠腹腔注射III和IV会诱导肝微粒体氨基比林N - 脱甲基酶和苯胺4 - 羟化酶活性，与苯巴比妥的作用相似。这些氯化衍生物还增加了细胞色素P - 450含量，以及小鼠肝微粒体中氨基比林N - 脱甲基酶和N - 甲基苯胺N - 脱甲基酶的活性。增加程度与苯巴比妥和3 - 甲基胆蒽相似。
