Molecular Mechanism of Indoor Exposure to Airborne Halogenated Flame Retardants TCIPP (Tris(1,3-Dichloro-2-Propyl) Phosphate) and TCEP Tris(2-chloroethyl) Phosphate and Their Hazardous Effects on Biological Systems

Abstract

TCIPP (tris(1,3-dichloro-2-propyl) phosphate) and TCEP (tris(2-chloroethyl) phosphate) are organophosphate ester flame retardants found in various consumer products, posing significant health and environmental risks through inhalation, ingestion, and dermal exposure. Research reveals these compounds cause oxidative stress, inflammation, endocrine disruption, genotoxicity, neurotoxicity, and potentially hepatotoxicity, nephrotoxicity, cardiotoxicity, developmental, reproductive, and immunotoxicity. This review summarizes the current knowledge on the toxicological mechanisms of TCIPP and TCEP and presents the latest data on their toxicological effects obtained in vitro and in vivo, using omic systems, and on the basis of computational modelling. It also elaborates on the scope of further toxicities and highlights the necessity of ongoing mechanistic research, integration of new technologies, and successful transfer of the acquired knowledge into risk evaluation, policies and regulations, and the creation of safer products. Since flame retardants are already present in homes, schools, offices, and daycare centres, efforts to scale back the exposure to these chemicals, most especially the hazardous ones, must be made to protect human health and the environment. Therefore, effective and timely prevention, based upon a deep knowledge of the entire toxicological profile of these substances, is the only way to face this difficult toxicological issue and provide for a healthy and safe future.

Keywords: TCEP (tris(2-chloroethyl) phosphate); TCIPP (tris(1,3-dichloro-2-propyl) phosphate); airborne halogenated flame retardants; flame retardants; human exposure; indoor air quality.

Figure 1

The processes of the flame retardants TCIPP and TCEP in the human body are depicted in this diagram: absorption, distribution, metabolism, and excretion. It outlines the main pathways for absorption (ingestion, inhalation, and dermal absorption), the distribution of the substance to different tissues and bodily fluids (blood, urine, breast milk, and adipose tissue), the metabolic pathways involving Phase I and Phase II reactions, and the pathways for excretion (urine and feces). By giving a thorough description of how these substances are metabolized within the body, the diagram aims to advance knowledge of their toxicokinetic characteristics and potential health hazards.

Figure 2

For endocrine disruption, TCEP and TCIPP effects are shown in Figure 2. It highlights the procedure of interaction between these compounds and three central hormone receptors such as thyroid hormone receptors (THRs), androgen receptors (ARs) and estrogen receptors (ERs). The result is a summary of the main outcomes of these interactions which shows that alteration to ERs may lead to fertility problems in both men and women, changes to ARs lead to male reproductive defects, while alterations in THRs have growth defects and metabolic disorders.

Figure 3

Genotoxic and carcinogenic mechanisms of TCIPP and TCEP. This figure shows genotoxicity, oxidative stress, inhibition of DNA repair, and Epigenetic Modifications as the four major pathways. The different types of DNA damage and cellular effects, such as mutations, chromosomal aberrations, oxidative DNA damage, and impaired DNA repair, are caused by these pathways. They can lead to mutagenesis, genomic instability, altered gene expression, and ultimately carcinogenesis.