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.
D006585:Altretamine / Q000008:administration & dosage / Q000633:toxicity*; D000818:Animals; D001772:Blood Cell Count; D001835:Body Weight / Q000187:drug effects; D003864:Depression, Chemical; D004305:Dose-Response Relationship, Drug; D007441:Intubation, Gastrointestinal; D007928:Lethal Dose 50; D007958:Leukocyte Count; D008297:Male; D008938:Mitosis / Q000187:drug effects; D010316:Particle Size; D051381:Rats; D014227:Triazines / Q000633:toxicity*
D014227:Triazines; D006585:Altretamine