Activation of Avian Aryl Hydrocarbon Receptor and Inter-species Sensitivity Variations by Polychlorinated Diphenylsulfides

Abstract

It was hypothesized that polychlorinated diphenyl sulfides (PCDPSs) can potentially interact with an aryl hydrocarbon receptor (AHR) and thereby cause adverse effects in wildlife like birds. A recently developed avian AHR1-luciferase report gene (LRG) assay was used to assess the interaction between avian AHR1 and 18 PCDPSs and to compare the interspecies sensitivity among chicken, ring-necked pheasant, and Japanese quail by PCDPSs. Most of the tested PCDPSs could activate the AHR1-mediated pathways in avian species, and the relative potency (ReP) of the PCDPSs increased with the increasing number of substituted Cl atoms. The rank orders of PCDPSs potency were generally similar among birds, although the ReP varied. In addition, not all the sensitivity rank orders of avian AHR1 constructs for PCDPSs were consistent with that of TCDD. ReP values of PCDPSs suggested that some PCDPSs like 2,3,3',4,5,6-hexa-CDPS and 2,2',3,3',4,5,6-hepta-CDPS are higher than the avian WHO-TEFs of OctaCDD, OctaCDF, and most of the coplanar PCBs. Our results report for the first time the activation of an AHR1-mediated molecular toxicological mechanism by PCDPSs, and provide the ranking of ReP and relative sensitivity values of different congeners, which could guide the further toxicity test of this group of potential high priority environmental pollutants.

Predicting Early Life Stage Mortality in Birds and Fishes from Exposure to Low‐Potency Agonists of the Aryl Hydrocarbon Receptor: A Cross‐Species Quantitative Adverse Outcome Pathway Approach

“…Thus, the revised qAOP using EC Threshold could also be used as a tool to more rapidly assess the potential for cross‐species differences in sensitivity to lower‐potency DLCs. In addition, there are currently only a few studies that have investigated the sensitivity to other agonists of the AhR across species; therefore, the extent of cross‐species differences in sensitivity to these chemicals warrants further investigation (Zhang et al 2014, 2016; Head et al 2015; Franci et al 2018; Bak et al 2019). The revised qAOP using EC Threshold could enable the chemical applicability domain of the qAOP to be better defined regarding inclusion of other agonists of the AhR, which are often lower‐potency agonists, such as PAHs, OH‐/MeO‐PBDEs, or PCDPSs.…”

“…For example, maximal response is often not reached in this in vitro AhR transactivation assay for PCBs, including all mono‐ ortho PCBs, which can be more than 3 orders of magnitude less potent than the prototypical reference compound, 2,3,7,8‐tetrachlorodibenzo‐ p ‐dioxin (2,3,7,8‐TCDD), but can still represent a risk to wildlife (Van den Berg et al 1998; Manning et al 2012). Further, certain polycyclic aromatic hydrocarbons (PAHs) and some contaminants of emerging concern, such as hydroxylated and methoxylated polybrominated diphenyl ethers (OH‐/MeO‐PBDEs) and polychlorinated diphenylsulfides (PCDPSs), can be agonists of the AhR but typically do not elicit maximal response in this in vitro AhR transactivation assay (Zhang et al 2014, 2016, 2018; Bak et al 2019). Because these low‐potency agonists do not reach maximal response in this in vitro AhR transactivation assay, the current qAOP cannot be reliably used to predict dose–response curves of early life stage mortality.…”

“…Various methods have been employed in prior studies to compare responses measured in this in vitro AhR transactivation assay when a reliable EC50 cannot be calculated. One commonly used method is to calculate the percentage concentration (PC x ), which is the concentration of chemical that elicits a response equal to x % (usually 20, 50, or 80%) of a positive control, which is typically 300 nM of 2,3,7,8‐TCDD (Manning et al 2012; Zhang et al 2014, 2016, 2018; Bak et al 2019). A prior study demonstrated a highly significant linear relationship ( R 2 = 0.93, p < 0.0001) between the PC20 in this in vitro AhR transactivation assay and the dose to cause 50% lethality (LD50) in early life stages across 9 species of birds and 4 PCDDs and PCBs (Manning et al 2012).…”

Relative sensitivities among avian species to individual and mixtures of aryl hydrocarbon receptor–active compounds

“…Among birds, chicken is the most sensitive to DLCs . For TCDD, the sensitivity of Japanese quail is 100‐fold less than that of chicken . Although a complete understanding of the reasons underling differences in sensitivities among species is not yet available , a factor is differential binding of DLCs to the ligand binding domain of the AhR caused by differences among sequences of amino acids of the ligand binding domain, especially at positions 324 and 380 of the AhR1–ligand binding domain of birds .…”

Occurrence of Polychlorinated Diphenyl Sulfides (PCDPSs) in Surface Sediments and Surface Water from the Nanjing Section of the Yangtze River

“…7,8 In addition, Zhang et al examined the aromatic hydrocarbon receptor (AhR) effect of 18 types of PCDPSs, and the results demonstrated that the relative potency (relative to 2,3,7,8-TCDD) values of 2,4,4′,5-tetra-CDPS, 2,2′,3′,4,5-penta-CDPS and 2,2′,3,3′,4,5,6-hepta-CDPS are 1.0 × 10 −4 , 1.1 × 10 −4 and 6.8 × 10 −4 , respectively. 9 The relative potency values of the three PCDPSs are higher than those of several dioxin-like PCBs (DL-PCBs), such as PCB-118 and PCB-189, whose TEF values proposed by the World Health Organization (WHO) in 2005 are all 3.0 × 10 −5 . 10 These studies provided evidence that PCDPSs had certain ecological and health risks.…”