Hepatic effects of tartrazine (E 102) after systemic exposure are independent of oestrogen receptor interactions in the mouse

Stephanie K Meyer,Philip M.E Probert,Anne F Lakey,Andrew R Axon,Alistair C Leitch,Faith M Williams,Paul A Jowsey,Peter G Blain,George E.N Kass,Matthew C Wright

doi:10.1016/j.toxlet.2017.03.024

Stephanie K Meyer, Philip M.E Probert + Show 8 more

Open Access

https://doi.org/10.1016/j.toxlet.2017.03.024

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Abstract

Tartrazine is a food colour that activates the transcriptional function of the human oestrogen receptor alpha in an in vitro cell model. Since oestrogens are cholestatic, we hypothesised tartrazine will cause periportal injury to the liver in vivo. To test this hypothesis, tartrazine was initially administered systemically to mice resulting in a periportal recruitment of inflammatory cells, increased serum alkaline phosphatase activity and mild periportal fibrosis. To determine whether an oestrogenic effect may be a key event in this response, tartrazine, sulphonated metabolites and a food additive contaminant were screened for their ability to interact with murine oestrogen receptors. In all cases, there were no interactions as agonists or antagonists and further, no oestrogenicity was observed with tartrazine in an in vivo uterine growth assay. To examine the relevance of the hepatic effects of tartrazine to its use as a food additive, tartrazine was orally administered to transgenic NF-κB-Luc mice. Pre- and concurrent oral treatment with alcohol was incorporated given its potential to promote gut permeability and hepatic inflammation. Tartrazine alone induced NF- κB activities in the colon and liver but there was no periportal recruitment of inflammatory cells or fibrosis. Tartrazine, its sulphonated metabolites and the contaminant inhibited sulphotransferase activities in murine hepatic S9 extracts. Given the role of sulfotransferases in bile acid excretion, the initiating event giving rise to periportal inflammation and subsequent hepatic pathology through systemic tartrazine exposure is therefore potentially associated an inhibition of bile acid sulphation and excretion and not on oestrogen receptor-mediated transcriptional function. However, these effects were restricted to systemic exposures to tartrazine and did not occur to any significant effect after oral exposure.

Highlights

Many consumer products including food and personal care items contain endocrine disrupting chemicals (EDCs) which may potentially interfere with the endocrine system in animals and humans (DiamantiKandarakis et al, 2009; Zoeller et al, 2012)
To investigate the effects that direct exposure to tartrazine may have on the liver, tartrazine was administered to mice by intraperitoneal injection at 50 mg/kg bw/day, 6.7 times the current EU ADI
It is known to elicit intolerance reactions in a small fraction of the exposed population and that sensitive individuals may react to tartrazine at dose levels within the ADI (EFSA Panel on Food Additives and Nutrient Sources added to Food (ANS), 2009)

Summary

Introduction

Many consumer products including food and personal care items contain endocrine disrupting chemicals (EDCs) which may potentially interfere with the endocrine system in animals and humans (DiamantiKandarakis et al, 2009; Zoeller et al, 2012). A large number of EDCs have oestrogenic properties in that they mimic the biological effects of endogenous oestrogens. These chemicals are termed xenoestrogens and they may modulate endogenous oestrogen activity by interfering with endogenous oestrogen signalling or by disrupting synthesis, metabolism and transport of oestrogens (Shanle and Xu, 2011). Two isoforms of the ER exist; the ERα (Green et al, 1986) and ERβ (Mosselman et al, 1996; Kuiper et al, 1996; Moore et al, 1998) Both ER isoforms are ligand-activated by oestrogens such as endogenous 17β-estradiol (E2) and mediate ER-regulated changes in gene expres-

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