Twenty-eight day nose-only inhalation toxicity study of resorcinol bis-diphenylphosphate (Fyrolflex RDP) in rats

Abstract

To evaluate the effects of repeated inhalation exposure to resorcinol bis-diphenylphosphate (Fyrolflex RDP), male and female Sprague-Dawley rats received nose-only inhalation exposure to Fyrolflex RDP for 6 h/day, 5 days/week for 4 weeks. Concentrations of Fyrolflex RDP tested were 0 (filtered air control), 0.1, 0.5, and 2.0 mg/l air. Ten rats/sex/group were euthanized on day 29; 10 additional rats/sex in the control and high-dose groups were euthanized after a 60-day recovery period. RDP induced no mortality or overt toxicity during the exposure or recovery periods. Body weight and body weight gain were reduced in high-dose male rats during exposure, but returned to control levels after 5 weeks of recovery. Absolute and relative lung weights were increased in mid- and high-dose groups after exposure, and in the high-dose group at the end of the recovery period. Relative liver weights were increased after exposure in mid- and high-dose females and in high-dose males. Gross pathology was limited to confluent white foci in the lungs of all high-dose animals after exposure, and in 80% of high-dose animals after the recovery period. Underlying lung histopathology after exposure consisted of alveolar histiocytosis in mid- and high-dose groups; this progressed to chronic foreign body inflammation in high-dose rats after recovery. This response is characteristic of a noncytotoxic, water-insoluble foreign material that reaches the alveolar region of the lung. On this basis, although the observed lung lesions were exposure-related, they were not considered to reflect a specific toxic response to Fyrolflex RDP. No exposure-related gross or microscopic pathology was identified in any other organ in any experimental group. The no-observed-effect level (NOEL) for RDP in this study was 0.1 mg/l.