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EC number: 204-500-1 | CAS number: 121-82-4
The administration of RDX to male and female F344 rats resulted in a reduction in the survival rate for both sexes given 40 mg/kg/day.
Those animals that died often demonstrated convulsions prior to death. Surviving animals at this dose were hyperreactive to approach and appeared to fight with their cagemates to a greater extent than that seen for animals at lower doses. Histologic evaluation failed to detect treatment-related lesions of the central nervous system.
Anemia consisting of reduced hematocrit, hemoglobin and RBC's was seen for males and females receiving 40 mg/kg/day. The effect was mild and none of the usual physiologic compensatory responses were in evidence. The anemia appeared to be peripheral in origin as bone marrow appeared within normal limits and secondary splenic lesions including extramedullary hematopoiesis, sinusoidal congestion, and increased quantities of a hemosiderin-like pigment were seen. Although gross necropsy observations suggested enlarged spleens, organ weight analysis failed to substantiate this.
Liver injury, primarily at 40 mg/kg/day, was evidence by several observations. Hepatomegaly was seen at 40 mg/kg/day and to a much lesser extent for females at 8 mg/kg/day although histologic changes were not apparent. Hepatotoxicity was also suggested by hypocholesterolemia, hypotriglyceridemia, reduced serum albumin/total protein levels, and possibly by increased alkaline phosphatase activity.
RDX-induced renal damage occurred primarily at the 40 mg/kg/day dose level. Kidney weights were elevated at this dose and possibly for 8 mg/kg/day females. Lesions of this organ included dark brown kidneys with medullary papillary necrosis for males receiving 40 mg/kg/day for longer than 6 months. Additional toxic effects on the urogenital system, primarily seen at 40 mg/kg/day, included urinary bladder distention with luminal distention and cystitis, testicular atrophy with germinal cell degeneration and enlarged seminal vesicles. In addition, enlarged prostate accompanied by spermatic granuloma and suppurative inflammation occurred for male rats administered 1.5 mg/kg/day or greater following 24 months of treatment.
Additional toxic effects seen primarily at 40 mg/kg/day included cataracts (females only), hypoglycemia, thrombocytosis and enlarged adrenals although microscopic changes were not seen. RDX was not found to be carcinogenic under the conditions of the present study.
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