Similarities in the Endocrine-Disrupting Potencies of Indoor Dust and Flame Retardants by Using Human Osteosarcoma (U2OS) Cell-Based Reporter Gene Assays

Abstract

Indoor dust is a sink for many kinds of pollutants, including flame retardants (FRs), plasticizers, and their contaminants and degradation products. These pollutants can be migrated to indoor dust from household items such as televisions and computers. To reveal high-priority end points of and contaminant candidates in indoor dust, using CALUX reporter gene assays based on human osteosarcoma (U2OS) cell lines, we evaluated and characterized the endocrine-disrupting potencies of crude extracts of indoor dust collected from Japan (n = 8), the United States (n = 21), Vietnam (n = 10), the Philippines (n = 17), and Indonesia (n = 10) and for 23 selected FRs. The CALUX reporter gene assays used were specific for compounds interacting with the human androgen receptor (AR), estrogen receptor α (ERα), progesterone receptor (PR), glucocorticoid receptor (GR), and peroxisome proliferator-activated receptor γ2 (PPARγ2). Indoor dust extracts were agonistic to ERα, GR, and PPARγ2 and antagonistic against AR, PR, GR, and PPARγ2. In comparison, a majority of FRs was agonistic to ERα and PPARγ2 only, and some FRs demonstrated receptor-specific antagonism against all tested nuclear receptors. Hierarchical clustering clearly indicated that agonism of ERα and antagonism of AR and PR were common, frequently detected end points for indoor dust and tested FRs. Given our previous results regarding the concentrations of FRs in indoor dust and in light of our current results, candidate contributors to these effects include not only internationally controlled brominated FRs but also alternatives such as some phosphorus-containing FRs. In the context of indoor pollution, high-frequency effects of FRs such as agonism of ERα and antagonism of AR and PR are candidate high-priority end points for further investigation.

Detection of Hormone-Like and Genotoxic Activities in Indoor Dust from Taiwan Using a Battery of in Vitro Bioassays

“…The 4-and 5-ring benz[a]anthracene and benzo[k]fluoranthene were principal AhR agonist activity contributors owing to their higher TEFs (7 and 11, respectively). Nonetheless, 9 AhR agonistic PAHs only accounted for a small portion of the AhR agonist activities in indoor dust (2.1-6.2%), which were similar to other studies (Louiz et al, 2008;Muusse et al, 2012;Tue et al, 2013). Our results indicated that further investigation is necessary to identify unknown xenobiotic AhR agonist contaminants in indoor dust from Taiwan.…”

“…Higher AhR agonist activities were detected in the indoor dust samples collected from computer room (16112 ng BaP EQ/g dust dry weight (dw)) and laboratory (9686 ng BaP EQ/g dust dw), which were further fractionated by HPLC to isolate active HPLC fractions. The AhR agonist activities in Taiwanese indoor dust (3448-16112 ng BaP EQ/g dust dw) were similar to or greater than those detected in indoor dust from New York State (30-8000 pg TCDD EQ/g, equivalent to 67-17778 ng BaP EQ/g) and Japan (38-1400 pg TCDD EQ/g, equivalent to 84-3111 ng BaP EQ/g), but lower than those in street dust collected from Vietnam and India (11-68 ng TCDD EQ/g, equivalent to 24-151 µg BaP EQ/g) using DR-CALUX assay (Suzuki et al, 2007;Tue et al, 2013;Tuyen et al, 2014). The variations in AhR agonist activities suggested area-specific sources of AhR agonist contaminants in different regions.…”

“…3(c) and 3(d)). Suzuki et al (2013) reported that AR antagonist activities were frequently found in indoor dust from Japan, the United States, Vietnam, the Philippines, and Indonesia, and several flame retardants exhibited antiandrogenic activity in the AR-CALUX assay. In addition, several synthetic compounds widely used in our daily lives, such as triclosan, parabens, and phthalates have been shown to elicit antiandrogenic or antithyroid hormonal activities (Chen et al, 2007;Shen et al, 2009;Christen, 2012), and these compounds have been detected in indoor dust as well (Bornehag et al, 2005;Fan et al, 2010).…”

“…Maertens et al (2004) summarized that mutagenic activities could be found in settled house dust, in which PAHs ranged from 0.5 and to 500 µg/g dust equivalent. Tue et al (2013) reported that a significant portion of the dioxin-like activities in indoor dust could be related to unknown pollutants by using a combination of Dioxin-Related Chemical-Activated LUciferase gene eXpression (DR-CALUX) assay and instrumental chemical analysis. Vandermarken et al (2015) have also used an estrogen responsive elements-CALUX assay to evaluate the estrogenic activities in dust samples from kindergartens in Belgium, and the results showed that phthalate concentrations were well correlated with the estrogenic activities.…”

Detection of glucocorticoid receptor agonists in effluents from sewage treatment plants in Japan

“…The assay procedure has been described previously (Suzuki et al, 2013). Briefly, GR-CALUX cells were cultured at 37°C under 5% CO 2 and high humidity in DF (1:1 mixture of Dulbecco's Modified Eagle's Medium and Ham's F12 [DMEM-F12]) medium supplemented with 7.5% fetal calf serum (FCS).…”