Trimethyl Phosphite (alias of 121-45-9)

CAS RN:121-45-9

Toxicity Summary

IDENTIFICATION AND USE: Trimethyl phosphite (TMP) is a colorless liquid. It is used primarily as an intermediate in the manufacture of pesticides. It is also used as a fireproofing agent in the production of textiles, as an intermediate in the production of flame-retardant polymers for polyurethane foams, and as a catalyst. HUMAN EXPOSURE AND TOXICITY: Examination of 179 employees involved in manufacturing of TMP failed to reveal any indications of ocular changes or other adverse effects on worker health associated with occupational exposure to trimethyl phosphite. It is only moderately toxic by oral ingestion and an irritant to eyes, skin and upper respiratory system. ANIMAL STUDIES: Topical application of trimethyl phosphite produced moderately severe but persistent irritation on rabbit skin. Instillation of undiluted trimethyl phosphite into the rabbit eye caused severe ocular irritation and swelling, which lasted for several days. No permanent damage to the eye could be detected. Marked mortality (> 70%) /was demonstrated/ among rats exposed at 600 ppm, 6 hours/day, 5 days/week for 4 weeks. Ten percent of the rats exposed at 300 ppm also died. Gross histological evidence of lung inflammation was observed in the animals exposed at 600 ppm, but no such changes occurred in those subjected to 300 or 100 ppm. Clinical signs of ocular irritation occurred in the animals exposed at 100 ppm or higher concentrations. Severe cataract developed in the 600 ppm exposure group, and mild cataracts from 300 ppm; 100 ppm exposures caused mild, reversible "striate opacities" of the lenses of a few animals. TMP was administered by gavage to pregnant rats at rates of 16, 49, or 164 mg/kg/day, on gestation Days 6 through 15. Acetyl salicylic acid (250 mg/kg/day) was also administered to a group of rats as a positive control. Teratologic evaluation revealed gross fetal abnormalities, skeletal defects, and soft tissue defects at a dose rate of 164 mg/kg/day of trimethyl phosphite, but not at the two lesser rates. An increased frequency of fetal resorption was also observed at 164 mg/kg/day. Trimethyl phosphite was genotoxic in three separate mouse lymphoma assays, either with or without microsomal activation. Trimethyl phosphite was also positive in a battery of Drosophila melanogaster mutagenicity assays and in a bacterial DNA damage/repair suspension assay using various strains of Escherichia coli and Salmonella typhimurium. Trimethyl phosphite failed to show evidence for genetic toxicity in Salmonella and Saccharomyces strains, in a cell transformation assay, in a bacterial DNA repair assay (Escherichia coli, Salmonella typhimurium) or in two Salmonella/mammalian-microsome preincubation assays.
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