Initial Submission: Letter from FMC Corp. to USEPA re: Preliminary, Unaudited Results from 1-Generation Reproduction Study in Rats of Hydroxyphospnonoacetic Acid, dated 11/22/1995

摘要

On November 22, 1995, FMC Corporation informed the Agency of adverse effects observed during a 1-Generation Reproduction Study conducted in rats with Hydroxyphosphonoacetic acid, CAS Registry Number 23783-26-8. The specific reportable effect was the high level of mortality of females post parturition. Continuing with this same study, FMC now wishes to notify the Agency of a further adverse finding: Hydroxyphosphonoacetic acid (HPA) was evaluated for potential reproductive toxicity in a one generation study. Groups of Sprague-Dawley rats were dosed orally by gavage for ten weeks prior to mating and throughout mating, gestation and lactation periods. Dose levels were 0, 1, 10, 50, 150 and 500 mg/kg/day. The test material is a phosphonate and is expected to deplete calcium levels. Because the females were pregnant and had a higher calcium requirement for the developing fetuses and for the nursing pups, depletion of calicum stores may have contributed to the toxicity of the parents and the decreased viabiliity/survival of the pups. During late gestation there were maternal deaths at the top two dose levels, reported previously in a TSCA 8(e) report.