Sequestration of 2,3,7,8‐tetrachlorodibenzo‐p‐dioxin by activated carbon eliminates bioavailability and the suppression of immune function in mice

Abstract

The effectiveness of activated carbon in reducing the bioavailability of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) was examined from the context of using in situ sorbent amendments to remediate soils/sediments contaminated with polychlorinated dibenzo-p-dioxins/dibenzofurans (PCDD/Fs). This technology has gained rapid acceptance based on observations that activated carbon amendments predictably lower PCDD/F concentrations in water and bioaccumulation by simple aquatic organisms and earthworms; it has been assumed that bioavailability to mammals is similarly reduced, although this has been disproven for other sorbent materials. In the present study TCDD was absorbed to a microporous activated carbon (TCDD-AC) using the incipient wetness method. An aqueous suspension of TCDD-AC and an equivalent dosage of TCDD in corn oil were administered by oral gavage to B6C3F1 mice. The relative bioavailability of TCDD-AC was determined by quantifying and comparing the hepatic induction of cyp1A1 (messenger ribonucleic acid) and suppression of the immunoglobulin M antibody-forming cell immune response by the 2 forms of TCDD. A concentration-dependent response was observed for both assays when TCDD in corn oil was administered to mice. However, when equivalent masses of TCDD were administered as TCDD-AC, no induction of cyp1A1 or suppression of the immunoglobulin M antibody-forming cell response was observed. The absence of these 2 sensitive aryl hydrocarbon receptor-mediated responses in mice provides the first direct evidence that activated carbon can sequester TCDD in a form that eliminates its bioavailability to mammals. These results support the premise that activated carbon can be used to reduce the bioeffective dose of TCDD delivered to mammals and that activated carbon amendments may provide a low-cost alternative to traditional remediation technologies. Environ Toxicol Chem 2017;36:2671-2678. © 2017 SETAC.

TCDD administered on activated carbon eliminates bioavailability and subsequent shifts to a key murine gut commensal

“…S2). Concordant with previously described studies, TCDD administered on AC eliminated both the toxic response in mice (Boyd et al 2017) and the subsequent effect on a key member of the gut microbiome. However, a concentration-dependent dose response that was previously observed with host bioassays was not observed with SFB.…”

“…Pathogen-free female B6C3F1 mice that were 5 to 8 weeks old were purchased from Charles River Breeding Laboratories (Portage, MI, USA) and handled as previously described (Boyd et al 2017). Briefly, 45 mice were randomly separated, five per cage into nine separate cages, one for each experimental group.…”

“…Five mice were placed in each group for replication. Food grade WPC coconut AC (Calgon Carbon Corp) was characterized and adsorbed with TCDD as described previously (Boyd et al 2017). Briefly, for AC-TCDD, 156.25 mg of AC loaded with TCDD via the incipient wetness method (Boyd et al 2011; Kaplan et al 2011) and confirmed through analysis using pyrolysis gas chromatography mass spectrometry was suspended in 5 ml deionized water prior to dosing.…”

“…This question was addressed, in part, in a recent study that examined the availability of 2,3,7,8-tetrachlorodibenzo- p -dioxin (TCDD) amended to AC (AC-TCDD) in a murine model (Boyd et al 2017). Classic markers of TCDD-induced toxicity were measured including modulation of the IgM antibody-forming cell (AFC) and the dioxin-inducible cytochrome P450 family cyp1a1 messenger RNA (mRNA) gene expression.…”

“…Experiments performed by our group and others suggest that gut commensal response is the result of TCDD-induced toxicity to the host, mediated in part, through the aryl hydrocarbon receptor (AhR), and not the direct influence of TCDD on bacteria (Lefever et al 2016; Stedtfeld et al 2017). Given the recently demonstrated limited bioavailability of AC-TCDD to hallmark responses in mice (Boyd et al 2017), we hypothesized that the response of key gut commensals would also be muted. To test this hypothesis, the transcriptomic response of SFB was examined, which has previously been shown to respond to the toxicity induced by TCDD (Bhaduri 2015; Stedtfeld et al 2017) and other AhR ligands (Zhang et al 2015).…”