Final Report on the Reproductive Toxicity of ELMIRON (CAS No. 37319-17-8)Administered by Gavage to Sprague-Dawley Rats

摘要

The potential reproductive toxicity of Elmiron (sodium pentosan polysulfate) inSprague-Dawley rats was evaluated using the Reproductive Assessment by Continuous Breeding (RACB) protocol. Elmiron has been given orphan drug status in the United States for the compassionate treatment of interstititial cystitis. This study was designed to produce some publicly-accessible data on the potential of Elmiron to produce repdroductive toxicity in rats. Dose levels for the continuous breeding phase for this study were set at 111,333, and 1000 mg/kg based on the information obtained from a previous 90-day gavage study with Elmiron. F0 female and male body weight were unchanged. Body weights of the F1 1000 mg/kg males and females were significantly decreased as early as Postanatal Day (PND) 4 and continued to be lower than the control group throughout the majority of Task 4. F0 and F1 male and female feed consumption values were unchanged. Exposure to Elmiron by gavage (20 rats/sex/group) did not affect the reproductive performance of F0 rats (Task 2) or F1 rats (Task 4). No breeding, fertility, or necropsy endpoint related to reproduction was altered by Elmiron exposure. No differences were noted in the F0 or F1 epididymal sperm morphology, epididymal sperm density, sperm motion parameters, testicular spermatid head counts, percent normal sperm, or F1 estrous cyclicity.