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Abstract for RACB92040

Reproductive Toxicity of Tris(2-chloroethyl)phosphate in CD-1 Swiss Mice

CASRN: 115-96-8
Chemical Formula: C6H12Cl3O4P
Molecular Weight: 285.482
Report Date: June 1991

Abstract

The following abstract presents results of a study conducted by a contract laboratory for the National Toxicology Program. The findings were not evaluated in accordance with the levels of evidence for reproductive or developmental criteria established by NTP in March 2009. The findings and conclusions for this study should not be construed to represent the views of NTP or the U.S. Government.

Tris(2-chloroethyl)phosphate (TCEP) is one of the class of tris organophosphates. It is used as a flame-retardant for plastics and synthetic fibers. TCEP was tested for its effects on fertility and reproduction in Swiss CD-1 mice according to the Continuous Breeding Protocol. It was administered via gavage. Based on results of previous data and a dose-finding study, 175, 350, and 700 mg/kg b.wt. where chosen to investigate effects on fertility and reproduction. Male and female mice (F0) were continuously exposed for a 7- day precohabitation and a 98-day cohabitation period (Task 2).

Male and female body weights in Task 2 were within 10% of the control body weights. The water consumption values in all three treated groups were similar to the control values. In the F0 generation, TCEP decreased the number of litters per pair and the number of live pups per litter. Task 3, designed to determine the affected sex, showed that both sexes were adversely affected but the males were relatively more sensitive. All sperm endpoints (concentration, motility and percent abnormal) were adversely affected.

The F1 pups from the last litter in the control and all three treated groups were weaned. Due to poor fertility in the 700 mg/kg/day dose group, only one F0 pair delivered a litter in the holding period (after the cohabitation phase). None of these pups survived to postnatal day 4. Although the pregnancy index for F1 mice in the 350 mg/kg dose group was not significantly decreased, in Task 4 that group delivered fewer pups per litter and both groups of TCEP-exposed mice had fewer males per litter than did controls.

These data document changes in fertility in the presence of altered kidney weights, indicating that TCEP is not a selective reproductive toxicant. Nonetheless, this study clearly shows that TCEP is a reproductive toxicant in both generations of Swiss CD-1 mice and produces changes at doses as low as 175 mg/kg/day.

NTIS # PB920129170