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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 Hobbie3, Michelle Cora2, Keith R. Shockley4, Gary R. Burleson1, Guanhua Xie5, Dori R. Germolec2

1 Burleson Research Technologies, Inc, Morrisville, NC 27560, United States
2 Division of Translational Toxicology, National Institute of Environmental Health Sciences, NIH, Research Triangle Park, NC 27709, United States
3 Inotiv, Inc, Morrisville, NC 27560, United States
4 Division of Intramural Research, National Institute of Environmental Health Sciences, NIH, Research Triangle Park, NC 27709, United States
5 DLH, LLC, Bethesda, MD 27703, United States

Toxicological Sciences, (2025) DOI: https://doi.org/10.1093/toxsci/kfaf006 PMID: 39908456 PMCID: PMC12038234

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 used commonly as a replacement for polybrominated diphenyl ethers in consumer and commercial products. Flame retardants have been shown to modulate immune function in vivo and in vitro and there is evidence that at least some related compounds such as organophosphate pesticides can cause developmental immunotoxicity. Developmental immunotoxicology studies were conducted by administering 0, 2500, 5000, or 10,000ppm TCPP in feed to pregnant Hsd:Sprague Dawley SD rats from gestation day 6 through weaning on postnatal day 28. Feed exposure to TCPP was continued in the F1 offspring until terminal euthanasia at .16 to 21weeks of age when assessments for developmental immunotoxicity were conducted. Innate, humoral, and cell-mediated immune function were assessed in the F1 adults. The antibody-forming cells (AFCs) response to sheep red blood cells was reduced in male and female F1 rats in the 10,000ppm treatment group but coincided with reduced bodyweights. The AFC response was also significantly reduced in male rats exposed to 5000ppm 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 exposure 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. Taken together, these data indicate that TCPP has the potential to impact humoral immune responses following developmental exposure.

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Updates

Publication DOI details added on July 29th, 2026