Relative effect potency estimates of dioxin-like activity for dioxins, furans, and dioxin-like PCBs in adults based on cytochrome P450 1A1 and 1B1 gene expression in blood

Abstract

Background In the risk assessment of PCDDs, PCDFs, and dioxin-like (DL) PCBs, regulatory authorities support the use of the toxic equivalency factor (TEF)-scheme derived from a heterogeneous data set of the relative effect potency (REPs) estimates. Objectives We sought to determine REPs for dioxin-like compounds (DLCs) using expression of cytochrome P450 (CYP) 1A1 and 1B1 mRNA in human peripheral blood mononuclear cells representing two different pathways. Methods We used a sex and age adjusted regression-based approach comparing the strength of association between each DLC and the cytochrome P450 (CYP) 1A1 and 1B1 mRNA expression in 320 adults residing in an organochlorine-polluted area of eastern Slovakia. Results We calculated REPs based on CYP1A1 expression for 4 PCDDs, 8 PCDFs, and 1 PCB congener, and based on CYP1B1 expression for 5 PCDFs and 11 PCB congeners. REPs from CYP1A1 correlated with REPs previously derived from thyroid volume (ρ = 0.85; p < 0.001) and serum FT4 (ρ = 0.77; p = 0.009). The 13 log REPs from CYP1A1 correlated with log WHO-TEFs (r = 0.63; p = 0.015) and 11 log PCB REPs with PCB consensus toxicity factors (CTFs) for compounds with WHO-TEFs (r = 0.80; p = 0.003). The complete set of derived 56 log REPs correlated with the log CTFs (r = 0.77; p = 0.001) and log WHO-TEFs (r = 0.81; p < 0.001). Conclusions REPs calculated from thyroid and cytochrome P450 endpoints realistically reflect human exposure scenarios because they are based on human chronic and low-dose exposures. While the CYP 1A1 seems more suitable for toxicity evaluation of PCDD/Fs, the CYP 1B1 is more apt for PCDFs and PCBs and reflects different pathways.

Effects of quercetin on Aroclor 1254-induced expression of CYP450 and cytokines in pregnant rats

“…Of all the isozymes, CYP1 and CYP2 are the major forms involved in PCB metabolism (Hirakawa et al 2018). Because of this, CYP1A1 is often used a biomarker of host exposure to certain persistent organic pollutants (POP) (Foltz et al 2014;Wimmerov a et al 2016). This use as a biomarker is valid in that other studies have previously shown that in the hepatic microsomes of untreated (control) rats, CYP1A1 protein was undetectable (Sidorova et al 2016).…”

Risk for animal and human health related to the presence of dioxins and dioxin‐like PCBs in feed and food

“…Wimmerová et al. () studied correlations between relative potencies (REPs) of PCDD/Fs and DL‐PCBs for thyroid impacts (thyroid volume and free T4) and those for CYP1A1 and CYP1B1 gene expression in human peripheral blood mononuclear cells. The authors concluded that while CYP1A1 seems well‐suited for toxicity evaluation of PCDD/F mixtures, CYP1B1 is more apt for that of PCDF/PCB mixtures.…”

Neurological and Neurophysiological Findings in Workers with Chronic 2,3,7,8‐Tetrachlorodibenzo‐p‐Dioxin Intoxication 50 Years After Exposure

“…Brodmann's Area 7 receives a great deal of visual input and sensory information from hands, concurrently TMT and Digit Symbol are both dependent on visual attention and graphomotor skills [35]. Experimentally, TCDD can damage nervous tissue by oxidative stress associated with the AhR-mediated induction of CYP1B1 isoenzyme [36][37][38][39], and the elevation of oxidative stress markers was also found in our patients [17].…”