Teratogenic evaluation of 2‐nitro‐p‐phenylenediamine, 4‐nitro‐o‐phenylenediamine, and 2,5‐toluenediamine sulfate in the mouse

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Abstract
Pregnant outbred albino (CD-1) mice were given 2-nitro-p-phenylenediamine (2NPPD; 32–256 mg/kg/day), 4-nitro-o-phenylenediamine (4NOPD; 16–1024 mg/kg/day) or 2,5-toluenediamine sulfate (2,5TDS; 16–64 mg/kg/day) by subcutaneous injection on Days 6–15 of gestation. The mice were killed on Day 18, the general health and reproductive health of the dams evaluated, and the fetuses examined and processed in order to characterize external, visceral, and skeletal malformations. The 32 and 128 through 256 mg/kg/day dose levels of 2NPPD produced a significant (p < 0.05) reduction in average weight gain by the dam during pregnancy. There was also a significant reduction in average fetal weight at 128 mg/kg/day and above. Although 2NPPD administration led to a significant increase in the average percentage of malformed fetuses at 160 mg/kg/day and above, these effects occurred only at dosages which produced significant maternal toxicity. Teratogenic effects were observed with 4NOPD, as administration of this dye led to a significant increase in the average percent of malformed fetuses at 256 mg/kg/day and above. A significant reduction in average weight gain by the dam during pregnancy also was observed at these dose levels, as well as a significant reduction in average fetal weight. Although 2,5TDS killed 4 of 31 dams at 48 mg/kg/day, and 9 of 11 dams at 64 mg/kg/day, this compound did not cause a significant increase in the average percent of malformed fetuses. There were indications of embryotoxicity, however, as dosages of 32 mg/kg/day and above led to significant reductions in average fetal weight.