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Plasma concentrations of tris(1-chloro-2-propyl) phosphate and a metabolite bis(2-chloroisopropyl) 1-carboxyethyl phosphate in Sprague-Dawley rats and B6C3F1/N mice from a chronic study of tris(chloropropyl) phosphate via feed

BJ Collins, D Slade, K Aillon, M Stout, L Betz, S Waidyanatha, K Ryan
Toxicology Reports (2022) DOI: https://doi.org/10.1016/j.toxrep.2022.03.025

DOI: https://doi.org/10.22427/NTP-DATA-002-03220-0026-0000-7

Publication

Abstract

Tris(chloropropyl) phosphate (TCPP) is an organophosphorus flame retardant and plasticizer used in manufacturing and multiple consumer products. Commercial TCPP is a ubiquitous environmental contaminant and TCPP or its metabolites have been detected in human plasma and urine. In response to the demonstrated widespread human exposure and lack of toxicity data, the Division of the National Toxicology Program is investigating the chronic toxicity of TCPP following perinatal exposure in HSD:Sprague Dawley®SD® (HSD) rats (up to 20,000 ppm) and adult exposure in B6C3F1/N mice (females, up to 10,000 ppm; males up to 5000 ppm) to TCPP via feed. Systemic exposure and bioaccumulation were assessed by measuring plasma concentrations of tris(1-chloro-2-propyl)phosphate (TCIPP), the most abundant TCPP isomer. TCIPP concentrations in TCPP-exposed rats and mice ranged from 3.43 to 1180 ng/mL and increased with exposure concentration at all time points. No sex differences were observed in rats, but male mice had higher TCIPP concentrations than females. TCIPP did not bioaccumulate in rats or mice over the course of the study. Low TCIPP concentrations were seen in some control rats and mice that were attributed to background TCPP present during sample collection, preparation and/or analysis. Bis(2-chloroisopropyl) 1-carboxyethyl phosphate (BCPCP), a TCPP metabolite, was quantified in plasma from control and selected exposed animals. Results showed increases in BCPCP concentration that were proportional to exposure concentration in rats and mice at concentrations much higher than TCIPP, indicating that BCPCP might be a more suitable biomarker of TCPP exposure.

Study Data - Rats

Mean Body Weights and Survival Table

Weekly mean body weights of male and female rats administered TCPP via dosed-feed for 2 years

Growth Curve

Clinical Observations Summary

Incidence of clinical observations in male and female rats administered TCPP via dosed-feed for 2 years

Feed and Compound Consumption Table

Weekly measurements of feed consumption and estimated chemical intake (Dose/Day) in male and female rats administered TCPP via dosed-feed for 2 years.

Summary of Tissue Concentration

Mean levels of TCIPP in plasma from dams and offspring at weaning (PND28) and select timepoints in male and female rats administered TCPP via dosed-feed for 2 years

Study Data - Mice

Mean Body Weights and Survival Table

Weekly mean body weights of male and female rats administered TCPP via dosed-feed for 2 years

Growth Curve

Clinical Observations Summary

Incidence of clinical observations in male and female rats administered TCPP via dosed-feed for 2 years

Feed and Compound Consumption Table

Weekly measurements of feed consumption and estimated chemical intake (Dose/Day) in male and female rats administered TCPP via dosed-feed for 2 years.

Summary of Tissue Concentration

Mean levels of TCIPP in plasma from dams and offspring at weaning (PND28) and select timepoints in male and female rats administered TCPP via dosed-feed for 2 years

Supplemental Information

Related Information

NTP Testing Status Page for TCPP
NTP Subchronic and Chronic Studies of TCPP: Study Data

Related Publications

B J Collins, D Slade, K Ryan, R Mathias, A Shan, J Algaier, K Aillon, S Waidyanatha, Development and Validation of an Analytical Method to Quantitate Tris(chloroisopropyl)phosphate in Rat and Mouse Plasma using Gas Chromatography with Flame Photometric Detection, Journal of Analytical Toxicology, Volume 43, Issue 1, January 2019, Pages 36–44, https://doi.org/10.1093/jat/bky048