Immunotoxicity Evaluation of Resorcinol Bis-Diphenylphosphate (Fyrolflex RDP) in B6C3F1 Mice

Abstract

RDP was administered daily to groups of female B6C3F1 mice by oral gavage for 28 days at dose levels of 500, 1500, or 5000 mg/kg/day body weight (BW). Control animals were sham dosed. Animals were euthanized 1 day following final exposure or following a 60-day recovery period. End point observations included necropsy and histopathology, spleen and thymus weights and cellularity, peritoneal cell numbers and differential cell analysis, splenic natural killer (NK) cell activity, lymphocyte blastogenesis, antibody-forming cell (AFC) response, peritoneal macrophage phagocytic activity, and host susceptibility to Listeria monocytogenes infection. In-life observations included weekly clinical examinations and body weights. No adverse clinical signs were noted and the only significant finding was an increase in body weight in high dose mice on week 4 as compared to sham controls. Small changes in body weight gain were seen in all dose groups as compared to sham controls after completion of dosing on weeks 5 and 6 and in mid-dose mice on weeks 7 and 12. No significant differences were found in spleen and thymus weights or in cellularity. No changes were found in peritoneal cell numbers or cell types, peritoneal macrophage phagocytic activity, or host susceptibility to infection. Likewise, splenic NK cell activity, lymphocyte blastogenesis, and AFC function were also unaffected. No histopathologic changes were observed. All animals that received positive-control substances demonstrated a significant effect in the respective tests. In conclusion, a standardized and validated battery of immune function tests demonstrated no immunotoxicity following daily oral exposure to up to 5000 mg/kg BW of RDP for 28 days.