U.S. flag

An official website of the United States government

Dot gov

The .gov means it's official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you're on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Developmental Immunotoxicity Study of Tris(chloropropyl) phosphate (TCPP) in Hsd:Sprague Dawley SD Rats Exposed Through Dosed Feed

Victor J. Johnson1, Kristen Ryan2, Michael I. Luster1, Arun Pandiri2, Kristen Hobbie5, Michelle Cora2, Keith R. Shockley3, Gary R. Burleson1, Guanhua Xie4, Dori R. Germolec2

1Burleson Research Technologies, Inc., Morrisville, NC, USA
2Division of Translational Toxicology, National Institute of Environmental Health Sciences, NIH, Research Triangle Park, NC, USA
3Division of Intramural Research, National Institute of Environmental Health Sciences, NIH, Research Triangle Park, NC, USA
4DLH, LLC, Bethesda, MD, USA
5Inotiv, Inc., Morrisville, NC, USA

DOI: https://doi.org/10.22427/NTP-DATA-500-002-002-000-9

Abstract

Tris(Chloropropyl) phosphate (TCPP) is a member of organophosphate flame retardants (OPFRs) used commonly as a replacement for polybrominated diphenyl ethers in consumer and commercial products. While limited toxicology data are available, TCPP is considered a major contaminant due to high-water solubility and potential for leaching from host materials. A major concern for OPFRs is their burden in daily use materials such as infant mattresses and furniture as well as household dust contamination. This high burden poses a significant risk of maternal, perinatal, fetal, and infant exposure, thereby warranting investigation of potential effects on the developing immune system. Developmental immunotoxicology studies were conducted by administering 0, 2500, 5000 or 10000 ppm TCPP in feed to pregnant Hsd:Sprague Dawley® SD® rats from gestation day (GD) 6 through weaning of offspring on postnatal day (PND) 28. Feed exposure to TCPP was continued in the F1 offspring until terminal sacrifice at approximately 16-21 weeks of age when assessments for developmental immunotoxicity were conducted in the adult F1 rats. Food consumption was negatively impacted in the 5000 and 10000 ppm treatment groups in male F1 rats and at 10000 ppm in female F1 rats which resulted in a corresponding effect on relative food consumption. This impacted bodyweight gains which were significantly decreased at all dose levels for male and female F1 rats prior to weaning and in male (5000 and 10000 ppm) and female (10000 ppm) F1 rats post-weaning. Innate, humoral, and cell mediated immune function were assessed in the F1 adults. The antibody forming cells (AFC) response to sheep red blood cells (SRBC) was markedly reduced in male and female F1 rats in the 10000 ppm treatment group but coincided with reduced bodyweights. The AFC response was also significantly reduced in male rats treated with 5000 ppm where only moderate effects on bodyweights occurred. TCPP exposure affected baseline T-cell proliferation without stimulation; however, the relevance of this change for immunotoxicity risk is unknown. TCPP treatment did not affect cytotoxic T-lymphocyte activity. Only minor and inconsistent treatment related effects on hematology, innate NK cell function, and immune cell population distributions in the spleen were observed in F1 rats following TCPP exposure. Taken together, these data indicate that TCPP has the potential to impact humoral immune responses following developmental exposure.

Study Tables