Effect of particle size distribution on hexamethylmelamine toxicity in rats

Single oral dose toxicities of six hexamethylmelamine samples with different particle size distributions were evaluated in Osborne-Mendel rats. The calculated LD50 values for the 6 samples were 1706 to 2150 mg/kg )10,236 to 12,900 mg/m2). The two samples with median particle size less than 40 micron were more toxic than the other 4 samples. Among the latter samples, severity of toxic effects was not correlated with particle size. Leukocytes, lymphocytes, platelets and body weight showed dose-related decreases for all samples. Particle size appeared to have a minimal effect on these variables. The drug produced toxic effects on rapidly proliferating tissues: lymphoid, hematopoietic and germinal epithelium. At lethal doses, microscopic lesions were lymphoid tissue hypoplasia, bone marrow hypoplasia with elevated myeloid:erythroid ratios and spermatogenic arrest. The major target organs at nonlethal doses were bone marrow and germ cells, with germinal epithelium showing the most severe lesions.