Eurotox’s program boasts over 30 industry sessions and workshops that will offer a chance to tackle the burning chemical safety challenges of the next decade. The theme of the 2019 Congress is “Toxicology – Science Providing Solutions.”
Charles River presented at industry sessions:
- Extended One-Generation Reproductive Toxicity Study (OECD TG 443, EOGRTS)
- How to Navigate and Interpret EC Regulations on Endocrine Disruption Testing Using Available Guidance and Testing Platforms
Charles River provides a comprehensive service in safety assessment for the progression of your product. Studies are performed in multiple species using a wide range of administration routes. Our range of capabilities, combined with leading scientific expertise results in timely, nonclinical toxicology programs compliant with regulatory guidelines.
We are excited to welcome our Citoxlab colleagues to our world-class team, to help us better support your development programs. We would be delighted to discuss your needs at any time.
Chair: Manon Beekhuijzen | Speakers: Manon Beekhuijzen, Pragati S. Coder, Sylvia Pelgrom
Our EOGRTS Experience – Regulatory & Practical Considerations
The Extended One-Generation Reproductive Toxicity Study (OECD TG 443, EOGRTS) is being conducted routinely in laboratories in Europe and North America. In the past few years, Charles River Laboratories has conducted close to 30 such studies. Under REACH, the information requirements for reproductive toxicity has been amended since 20 February 2015, by replacing the two-generation-toxicity test with the EOGRT.
TG 443 provides a detailed description of the operational conduct of an EOGRTS and is aimed at understanding the reproductive, neuro- and immunotoxicity of test chemicals. Regulatory aspects of the design and triggered decisions on an EOGRTS are described in OECD Guidance Document 117. However, the internal triggers do not apply for testing chemicals under REACH and for classification according to CLP.
This session will begin with an introduction to Charles River Laboratories, the history and design of the EOGRTS, and our experience conducting these studies for clients across Europe and North America, for submission to various health authorities, including ECHA and the US EPA.
The second presentation will cover nuances of study conduct and execution, selection of routes of administration, and the challenges of each cohort and the F2 extension, including interpretation, reliability and reproducibility of these studies. The last presentation will cover specific regulatory aspects of study design and decisions regarding inclusion of each cohort and/or the F2 extension.
Specific case studies will be included in each session. The session will conclude with a discussion and Q&A session to allow audience participation and sharing of experiences and ideas surrounding the logistics of study design and conduct.
How to Navigate and Interpret EC Regulations on Endocrine Disruption Testing Using Available Guidance and Testing Platforms
Presenter 1: Gregory Lemkine, WatchFrog, France
Weight of evidence brought by OECD level 3 test methods using in vitro aquatic embryos.
To specifically reveal endocrine disrupting activity, it is essential to use tests which reproduce vertebrate physiology in its complexity. The association of embryo-larval developmental stages of fish or amphibians with the use of genetic markers is a highly advantageous ethical alternative. Several models, specific for the estrogen, androgen, and thyroid axes, have been validated in recent years.
As explained in the OECD guidance document 150, these assays are performed applying an in vitro mode of exposure using whole embryonic organisms and provide non-mammalian data which are informative for human hazard assessment.
The ECHA/EFSA guidance document recommends implementation of these tests in assessment strategies as “this will reduce the uncertainty linked to the extrapolation of mechanistic information from mammalian to other vertebrate species and from cells to whole organisms.”
Presenter 2: Pramila Singh, Citoxlab, France
Combining smart study design in regulatory toxicology with targeted investigations to determine endocrine disruption potential and human relevance.
During each program of regulatory safety testing, a chemical is subject to a large number of rodent toxicology tests, of which most are supported by OECD testing guidelines that specify the study design and the objectives of the tests.
Recently, many of the OECD test guidelines for repeat administration and reproductive or multigeneration toxicity potential have been updated in order to allow for identification of endocrine disruption potential.
Although these guideline modifications do help facilitate the compliance with EC regulation on endocrine disruption testing, there remains a lot of confusion concerning which tests to use either at early stages of safety testing or as follow-up investigations following indications of potential endocrine disrupting effects observed in required studies.
This presentation will provide an overview of the 2018 EC regulation laying out the scientific criteria for determination of endocrine disrupting properties and several case examples will be provided to demonstrate how to navigate the available testing platforms in order to generate the most relevant data for human health assessments.
Electronic copies of all posters are available at the links below. If you'd like to discuss the poster content or have questions, contact us to connect with our presenters.
P16-028 | Regulatory Toxicology
Nonclinical development of products intended for treatment of damaged skin
P16-053 | Regulatory Toxicology
Comparison of single, paired and group housing effects on cardiovascular parameters and body temperature in telemetered large animal* (Available in The Source℠)
P16-060 | Regulatory Toxicology
Comparison of two commercially available systems proposed for oral administration of capsules in rats (Available in The Source℠)
P16-073 | Regulatory Toxicology
Evaluation of Sexual Maturity in the RasH2 Mouse Model
P18-011 | Reproduction
Optimizing the Design of Minipig Embryofetal Studies (Available in The Source℠)
P22-011 | Toxicology of the Immune System
TDAR and splenic lymphocyte subpopulation analysis in extended one-generation reproductive toxicity studies (OECD 443)
P22-012 | Toxicology of the Immune System
Validation of three flow cytometry panels for blood cell subpopulation analyses in Göttingen Minipigs
P22-014 | Toxicology of the immune system
Skin Immune System In The Juvenile Göttingen Minipig
*Title has been changed to reflect sensitive content.