Puerperal Acute Toxicity Indirectly Induced by 4-Amino-N 10 -Methyl-Pteroylglutamic Acid (Methotrexate) in Mice 1

Abstract

Summary

The administration of 100 μg of MTX to newborn mice resulted in fatal intoxication of 50% of untreated mothers. The mortality rate of foster mothers when foster nursing was begun 24 hr after treatment of the newborns was 40%. None of the foster mothers died, however, when the foster nursing began 48 hr after the treatment. MTX is rapidly excreted, largely in the urine, within from 24 to 48 hr after administration. It is assumed that the antifolate entered the mothers' circulatory systems via the excreted urine of the newborns. Both natural and foster mothers died after a maximum of 24 μg/g, which is a manyfold lower dose than that tolerated in adults (LD₅₀ = 300 μg/g per os). It is thought that this striking deviation in tolerance reflects the folic acid deficient state in the immediate postpartum period in mice.