In vitro and in vivo testing methods of epigenomic endpoints for evaluating endocrine disruptors

Abstract

SummaryDisclaimer: This paper is published under the sole responsibility of the authors and may not be considered as an EFSA output and is not intended to represent the views of EFSA. The paper is based on the annex of OECD (2012) The use of trade names is for identification only and does not constitute endorsement by the authors, EFSA, OECD, or the Albert Einstein College of Medicine. 1 Abbreviations BPA, bisphenol A; CG/CpG, cytosine-guanine dinucleotide; ChIP, chromatin immunoprecipitation; DNMT, DNA methyltransferase; ED, endocrine disruptor; EDTA-AG, OECD Endocrine Disruptor Testing and Assessment Advisory Group; ENCODE, ENCyclopedia Of DNA Elements; ES, embryonic stem; EZH2, enhancer of zeste homolog 2; IAP, intracisternal A particle; IUGR, intrauterine growth restriction; miRNA, micro RNA; MPS, massively-parallel sequencing; OECD, Organisation for Economic Cooperation and Development; TG, Test Guideline toxicology and safety assessment. At the research level, these efforts currently aim to elucidate the involvement of chemicalinduced epigenetic changes in adverse health effects, as well as to enable the exploitation of epigenetics particularly in the area of in vitro and in vivo modeling. While there have been plenty of reports linking endocrine disruptors with phenotypic abnormalities in wildlife, there are currently no publications describing epigenetic studies in wildlife undergoing these exposures.

Gender and Age Related Modulation of Xenoestrogen-Induced Tumorigenesis

“…Robust methods to screen and assess the impact of chemicals on epigenetic modulation are also urgently needed [104].…”

International regulatory needs for development ofan IATA for non-genotoxic carcinogenic chemical substances

“…They also include "epigenetic" carcinogens, where the term "epigenetic" is sometimes used to encompass the full spectrum of transcriptional regulatory processes that appear to mediate environmental influences and change a cellular state to reflect past and current (chemical) exposures (Greally and Jacobs, 2013). Here we consider that epigenetic changes comprise changes in chromatin (DNA methylation and/or histone modifications) and non-coding RNAs, including microRNAs.…”

Annual report of the Emerging Risks Exchange Network 2013

“…In their reviews, the OECD (2012) and Greally and Jacobs (2013) included an evaluation of the potential role of chemically-induced epigenetic modifications to endocrine signalling pathways, during sensitive windows of exposure, as a mechanism of endocrine disruption, along with the examination of potential methods for assessing such disruption. Many food and feed ingredients, contaminants, packaging materials, pesticides and biocides are putatively endocrine active substances, and some are potentially also endocrine disruptors.…”

“…"Epigenome" represents the collective noun to describe the sum of the epigenetic modifications throughout the genome. See Greally and Jacobs, 2013. in the body, allowing new tissues to grow. 3D food printers are now available as well 19 .…”