*Flame Retardants: New and Old Environmental Contaminants DOI: http://dx.doi.org/10.5772/intechopen.104886*

#### **Table 5.**

*Chemical structure and some physicochemical properties of novel halogenated organophosphate flame retardants.*

A study analyzed sediment samples from the Bohai and Yellow Seas (China), to detect organophosphate FRs [130]. The authors identified halogenates as being more abundant than non-halogenated FRs [130]. In addition, TCEP was detected at the highest concentration (from 7 to 671 pg./g of dry weight) [130]. Another study evaluated sediments from rivers in Austria and found TCPP as the most abundant compound in the samples, with a maximum concentration of 1300 μg/kg [131].

Thus, evaluating FRs in sediments is important because, if they are present therein, they will be continuously ingested by aquatic organisms and will eventually accumulate in the food chain, thereby being a potential risk to aquatic organisms [4].

Organophosphate FRs are not completely removed during the wastewater treatment process. Besides that, chlorinated FRs (halogenated group) are more difficult to degrade than non-chlorinated ones [132]. Thus, halogenated FRs have the greatest potential to harm water quality and aquatic health [4, 133].

A study conducted in Germany evaluated the surface waters of the Elbe and Rhine rivers, to detect organophosphate FRs in the samples [134]. In the Elbe River, TCPP and TCEP were measured at concentrations between 40 and 250 ng/l and between 5 and 20 ng/l, respectively [134]. On the other hand, the Rhine river contained smaller concentrations of TCPP (75–160 ng/l) and TCEP (12–25 ng/l) [134].

A study evaluated samples from the Santa Clara River in Los Angeles (California, United States), to find halogenated organophosphate FRs as the main compounds, including TCPP (3.3 μg/l), TDCPP (1.4 μg/l), and TCEP (0.81 μg/l) [135].

Other works have evaluated the presence of halogenated compounds in seawater [136]. A study conducted in China analyzed samples from the Yellow Sea and the East China Sea and detected TCEP (134.44 ng/l), TCPP (84.12 ng/l), TDCPP (109.28 ng/l), and TDBPP (96.70 ng/l) [24]. The authors concluded that the source of these compounds is the municipal and industrial effluent of wastewater treatment plants [136].

Another study conducted in China evaluated types of drinking water samples including tap water, filtered drinking water, bottled water, barreled water, and well water in both urban and rural areas in Eastern China [137]. The authors identified TCPP as being more abundant in barreled water (8.04 ng/l) and well water (2.49 ng/ l). The authors found TCEP in low amounts in all types of drinking water, making its carcinogenic risk unlikely [137]. The authors concluded that exposure to organophosphate FRs in drinking water in Eastern China poses no risk to human health [137].

Because halogenated FRs are not fully degraded during wastewater treatment, as already discussed above, they may occur in environmental compartments including air, sediments, and water [125, 130, 132, 137]. Therefore, investigating whether these compounds bioaccumulate in organisms is relevant, as it could damage the ecosystem and human health [138]. The appearance of halogenated FRs in mussels has already been reported in a study conducted in Maizuru Bay (Japan) [139], with TDCPP (18 ng/l), TCP (11 ng/l), and TCEP (11 ng/l) being detected. According to the study authors, these concentrations would not be able to promote adverse effects in the organisms [139]. Another study analyzed fish samples collected from the Pearl River in southern China and domestic birds (chicken and ducks) purchased from farmers living in Qingyuan County [28]. TCEP (82.7–4692 ng/g lipid weight in fish and 33.7– 162 ng/g lipid weight in the bird) and TCPP (62.7–883 ng/g lipid weight in fish and 3.89–21.4 ng/g lipid weight in the bird) were detected in all the samples [140].

Studying human exposure to aquatic animals that bioaccumulate halogenated compounds is important. A study has evaluated fish, mussels, and breast milk samples [141]. Aquatic organisms were collected from Swedish lakes, and breast milk samples were collected from women in Swedish cities [141]. The authors found that all the

samples contained TCPP at concentrations between 170 and 770 ng/g lipid weight (l.w), and they detected TDCPP only in fish, at a concentration between 49 and 140 ng/g l.w [141]. In addition, they identified TCPP (22–82 ng/g l.w) and TDCPP (1.6–5.3 ng/g l.w) in the breast milk samples [141]. The authors concluded that human exposure to organophosphate FRs via fish and human milk ingestion seems to have minor significance compared to the calculated exposure to these compounds in dust and air [141].

### **4.3 Toxicokinetics**

Humans may be exposed to halogenated organophosphates through inhalation or oral or dermal contact; the general population is exposed to these compounds through food and drinking water [142]. Moreover, occupational exposure to these compounds occurs through vapor inhalation and dermal contact [143]. Consumer exposure includes exposure through vapor inhalation, direct skin contact with halogenated organophosphates on the surface of objects, incidental ingestion of air-suspended particulates or resuspended dust, and ingestion via object-to-mouth behavior by children [144–146].

TCDCPP, TCEP, and TCPP are rapidly absorbed by the oral route of exposure. Furthermore, TDCPP dermal absorption is significant in rats, and TCPP dermal absorption is significant in humans as revealed by in vitro studies [147]. In addition, TCEP is extensively absorbed during nebulized exposure [148]. After halogenated compounds are absorbed, they are distributed throughout the body without specific accumulation in tissue or organs, but TCEP has been reported to be present in breast milk [149].

These compounds are rapidly metabolized during Phase I and Phase II metabolism. TDCPP is metabolized by a combination of hydrolase, MFO (mixed function oxidase), and GST reactions synthesizing glutathione conjugates, so the main metabolite is BDCPP (bis-(1,3-dichloro-2-propyl)phosphate) [147, 150]. TCEP and TCPP are metabolized by hydroxylation possibly by MFO and CYP 450 enzymes conjugated with glucuronic acid [147]. After that, the metabolic products of halogenated organophosphate FRs are rapidly excreted, primarily in the urine [147].

### **4.4 Toxicological effects**

Exposure to halogenated organophosphate compounds may cause some toxic effects in humans. According to Freudenthal and Henrich, chronic exposure to TDCPP causes benign tumors to appear in Sprague–Dawley rats [151]. A study conducted with patients at a Duke Cancer Institute suggested that increased incidence of thyroid cancer may be associated with exposure to TCEP in the home environment [152]. Additionally, under regulation EC 1272/2008, TDCPP is classified as a category 2 carcinogen with hazard statement H351 "suspected of causing cancer" and TCEP is classified as a "potential human carcinogen" by the E.U [145, 153].

In recent years, endocrine disruption effects of halogenated compounds have been observed. Stapleton and Meeker associated TDCPP concentrations in house dust with hormone levels [64]. They analyzed TDCPP in-house dust collected from 50 men recruited through a U.S. infertility clinic, to observe that increased TDCPP was associated with 3% lower free thyroxine concentration and 17% higher prolactin level [64]. Increased prolactin is a positive effect because it serves a number of important functions involving reproduction, metabolism, and angiogenesis [64, 154]. Studies

have also shown that exposure to TDCPP causes thyroid endocrine disruption—exposure of female zebrafish to TDCPP decreases T3 and T4 hormone levels, whereas exposure of Sprague–Dawley rats to TDCPP decreases serum thyroid stimulating hormone [155, 156].

Halogenated FRs and organophosphorus pesticides, such as chlorpyrifos, have similar chemical structures, so these FRs might also exert neurotoxic effects like organophosphate pesticides do [157]. Stapleton performed studies on PC12 cells and observed that TDCPP inhibits DNA synthesis and causes high oxidative stress, without adverse effects on cell viability or growth [157]. Moreover, TDCPP promotes differentiation into dopaminergic and cholinergic neurophenotypes, while TCEP and TCPP only promote the cholinergic phenotype [157].

Finally, there are very limited human health and toxicity data available for organophosphate halogenated FRs, so further studies are needed to understand how they affect humans.
