Endocrine Disruptor (ED) Testing across the World
The regulatory environment for endocrine disruptor (ED) testing varies around the world and is evolving. The EU has a well-established approach for ED testing which many other countries look to for guidance. The U.S. did have the Endocrine Disruptor Screening Program (EDSP), but this was shelved for a more flexible, substance-specific approach. Even in the absence of specific ED regulation, all regulators are sensitive to ED potential and are watchful for any such signals in safety data. For substance registrants however, this leaves a lot of ambiguity in terms of both scientific testing and regulatory requirements.
Covance has been at the forefront of ED testing and continues to innovate today through technical developments and regulatory advances. Partner with us and we can help you navigate the ED scientific and regulatory ambiguity round the globe.
- Extensive experience in performing endocrine disruptor assays to OECD regulatory standards. Active member of EU-NETVAL (European Union Network of Validation Laboratories for Alternative Methods) and participant in the inter-laboratory validation of the AR-Calux® Androgen Receptor Transactivation Assay for inclusion in revised OECD 458 (2020)
- A dedicated team of experts built round your ED assay needs will support you through every step of your European ED journey from study design to dossier completion and beyond
- A comprehensive suite of in vitro and in vivo assays and innovative analytics integrated to characterize the ED potential of your substance in a cost-efficient and scientifically rigorous way
Identifying the best testing approach for regulators can be complex
The OECD’s conceptual framework for ED testing is well established under guidance document 150(2018). It is the basis for ED assessment in the EU, which includes additional evidence requirements on key events and postulated modes of action. There are five levels:
- level 1: basic physiochemical properties of the substance
- level 2: in vitro mechanistic information
- level 3: in vivo mechanistic evidence
- levels 4 and 5: in vivo reproductive and developmental toxicity
Understanding how best to navigate through the levels and select applicable tests can be challenging as it is driven by both science and regulation.
Study programs tailored to regulatory requirements
Covance has been working with global regulators and scientific bodies on ED testing for many years. From the outset it is important to understand the science and regulation relevant to your substance, to optimize its regulatory journey. Our study directors and regulatory experts combine their expert insight and knowledge to advise on the optimum approach. That may mean leveraging existing data and QSARs to make weight of evidence arguments or it may require a new study program for your substance. Our dedicated technical team ensure any studies run efficiently and to the necessary standards, and our analytical chemists deliver verifiably results. This is then wrapped into a final dossier with our team supporting your final submission. Beyond submission, our regulatory team can support you by engaging with regulators to advocate for your substance.
Find out more about our ED regulatory consultancy service by clicking here.
Conceptual level 1 testing capabilities
QSAR modelling and read-across form a vital part of weight of evidence arguments for endocrine disruptor endpoints. They also signal appropriate in vitro and in vivo testing strategies. Data-driven insights are key to the successful use of QSAR model predictions. You can rely on our expertise and experience in leveraging model predictions in your submissions. Find out more about our in silico capabilities here.
Expertise in conceptual level 2 ED testing
A suite of in vitro assays suitable for Level 2 ED testing are available in house:
- OECD 455 Estrogen Receptor Transcriptional Activation (ERTA)
- OECD 456 H295R Steroidogenesis
- OECD 458 Androgen Receptor Transcriptional Activation (ARTA - AR Calux®)
- OPPTS 890.1200 Aromatase Assay
Expertise in conceptual level 3 ED testing
Routine level 3 in vivo ED tests available are:
- OECD 440: Uterotrophic assay
- OECD 441: Hershberger assay
- OECD 229: Fish Short Term Reproduction Assay (FSTRA)
- OECD 230: 21-Day Fish Assay
- OECD 231: Amphibian Metamorphosis Assay (AMA)
Expertise in conceptual levels 4 and 5 ED testing
We can employ a suite of suite of in vivo assays suitable for Level 4 and 5 ED testing:
- OECD 407: Repeated Dose 28-day Oral Toxicity Study in Rodents
- OECD 408: Repeated Dose 90-Day Oral Toxicity Study in Rodents
- OECD 414: Prenatal Development Toxicity Study
- OECD 421: Reproduction/Developmental Toxicity Screening Test
- OECD 422: Combined Repeated Dose Toxicity Study with the Reproduction/Developmental Toxicity Screening Test
- OECD 426: Developmental Neurotoxicity Study
- OECD 451-3: Combined Chronic Toxicity/Carcinogenicity Study
- OECD 443: Extended One-Generation Reproductive Toxicity Study
Results of studies in conceptual levels 1 through 5 together with published literature can also be used to determine an appropriate Mode of Action of a test item, should adversity need further investigation.
Staying ahead of the scientific and regulatory curve
With scientific approaches and regulatory standards related to EDs evolving, it is vital to stay ahead of the curve. That means building our capability and capacity in a strategic way so that it is ready when customers need it. Covance are actively building services for OECD test guidelines that are in development including:
- OECD Draft TG: Xenopus Embryonic Thyroid Assay (XETA) which utilizes free-living transgenic Xenopus embryonic stage tadpoles in a multi-well format with fluorescence endpoint to screen for thyroid active chemicals
- OECD Draft TG: transgenic zebrafish embryo assay (EASZY) is a mechanism-based in vivo screening assay designed to detect endocrine active chemical acting through estrogen receptors (ERs) to induce the expression of the green fluorescent protein (GFP) driven by the cyp19a1b promoter
- OECD TG in development: Rapid Androgen Disruption Animal Replacement assay (RADAR) is a medaka embryo androgen screening assay