The Importance of Endocrine Disruptor Testing

Many substances, including agrochemicals, industrial chemicals, biocides, and pharmaceutical products now require evaluation and testing for their potential to affect the endocrine systems of mammals and non-mammalian species. This could impact endocrine-related pathways, reproduction, development, and overall health status; necessitating comprehensive substance assessments. Endocrine disruptor testing aims to measure potential endocrine activity and/or endocrine adversity to determine the overall risk.

A substance is considered an endocrine disruptor if endocrine disruptor screening or testing confirms that it meets all of the following criteria:

  • It is known to cause an adverse effect relevant for human health and/or non-target organisms
  • It has an endocrine mode of action, i.e., it alters the function(s) of the endocrine system
  • The adverse effect relevant for human health / the non-target organism at the population level is a consequence of the endocrine mode of action
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Our Experience with Endocrine Disruptors

Since 2010, Charles River has been designing, validating, and executing endocrine disruptor testing focused on investigating the potential impact of substances on estrogen, androgen, thyroid, and steroidogenesis (EAST) activity and adversity. Active in groups such as EU_NETVAL, validating alternative methods including endocrine disruptor screening assays, we are at the forefront of method development. You can rely on our experience in endocrine disruptor testing across plant protection products, biocides, chemical substances, and drugs.

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Endocrine disruption infographic of in vitro toxicology experience.
Endocrine disruption infographic of in vivo toxicology experience.
Endocrine disruption infographic of regulatory services experience.

 

Endocrine Disruptor Screening and Testing Options

Endocrine disruptor testing solutions are based on the OECD conceptual framework for the assessment of endocrine disruptors (OECD 150) which outlines testing levels, increasing in both cost and complexity, from level 1 up to level 5.

  • Level 1: Existing Data / In Silico Modelling
    • Physical and chemical properties
    • Ecotoxicology
    • Read across and models including QSAR and DEREK
  • Level 2: In Vitro Assays (Endocrine Disruptor Screening for Mechanisms and Pathways)
    • The Freyberger-Wilson In Vitro Estrogen Receptor Binding Assay using Full Length Recombinant ERα (OECD 493)
    • Estrogen Receptor (ER) Binding Assay - Rat Uterine Cytosol (US EPA OPPTS 890.1250)
    • Human Estrogen Receptor-a Transactivation Assay for Detection of Estrogenic Agonist and Antagonist Activity (hERα-HeLa-9903 Cell Line & ER-CALUX cell line) (OECD 455)
    • Human Androgen Receptor Transcriptional Activation Assay for Detection of Androgenic Agonist and Antagonist Activity (AR-EcoScreen™ & AR-CALUX cell line) (OECD 458)
    • AR Binding Assay - Rat Prostate Cytosol (US EPA OPPTS 890.1150)
    • H295R Steroidogenesis Assay (OECD 456 / US EPA OPPTS 890.1550)
    • Aromatase Assay (Human Recombinant) (US EPA OPPTS 890.1200)
    • Thyroid Receptor Transactivation Assays – TR-CALUX (OECD scoping doc. 207)
    • TTR Binding Assay (OECD scoping doc. 207)
    • Thyroperoxydase (TPO) Inhibition Assay (OECD scoping doc. 207)
    • Sodium Iodide Symporter (NIS) Activity Assay (OECD scoping doc. 207)
    • Deiodinase I inhibition assay (OECD scoping doc. 207)
    • In-vitro and ex-vivo UDPGT induction assay (OECD scoping doc 207)
  • Level 3: In Vivo Assays (Endocrine Disruptor Testing for Mechanisms and Pathways)
    • Uterotrophic Bioassay in Rodents (OPPTS 890.1600, OECD 440)
    • Hershberger Bioassay in Rats (OPPTS 890.1400, OECD 441)
    • Fish Short-Term Reproduction Assay (OPPTS 890.1350, OECD 229)
    • 21-Day Fish Assay (OECD 230)
    • Amphibian Metamorphosis Assay (OPPTS 890.1100, OECD 231)
    • Xenopus Embryonic Thyroid Signalling Assay (XETA) (OECD 248)
  • Level 4: In Vivo Assays (Adverse Effects on Relevant Endocrine Endpoints)
    • Repeated Dose 28-Day Oral Toxicity Study in Rodents (OECD 407)
    • Repeated Dose 90-Day Oral Toxicity Study (OECD 408)
    • Carcinogenicity Study (OECD 451)
    • Chronic Toxicity Study (OECD 452)
    • Combined Chronic Toxicity/Carcinogenicity Studies (OECD 453)
    • Reproduction/Developmental Toxicity Screening Test (OECD 421)
    • Combined Repeated Dose Toxicity Study with the Reproduction/Developmental Toxicity Screening Test (OECD 422)
    • Prenatal Developmental Toxicity Study (OECD 414)
    • Developmental Neurotoxicity Study (OECD 426)
    • Repeated Dose Dermal Toxicity: 21/28-Day Study (OECD 410)
    • Subchronic Dermal Toxicity: 90-Day Study (OECD 411)
    • 28-Day (Subacute) Inhalation Toxicity Study (OECD 412)
    • Subchronic Inhalation Toxicity: 90-Day Study (OECD 413)
    • Repeated Dose 90-Day Oral Toxicity Study in Non-Rodents (OECD 409)
    • Pubertal Development and Thyroid Function Assay in Peripubertal Male Rats (US EPA OPPTS 890.1500)
    • Pubertal Development and Thyroid Function Assay in Peripubertal Female Rats (US EPA OPPTS 890.1450)
    • Fish Early Life Stage Toxicity Test (OECD 210)
    • Avian Reproduction Test (OECD 206)
    • Lymnaea stagnalis Reproduction Test (OECD 243)
    • Chironomid Toxicity Test using spiked sediment (OECD 218)
    • Chironomid Toxicity Test using spiked water (OECD 219)
    • Daphnia Reproduction Test (OECD 211)
    • One-Generation Reproduction Toxicity Study (OECD 415)
    • Earthworm Reproduction Test (Eisenia fetida/Eisenia andrei) (OECD 222)
    • Sediment-Water Lumbriculus Toxicity Test Using Spiked Sediment (OECD 225)
    • Predatory mite (Hypoaspis (Geolaelaps) aculeifer) reproduction test in soil (OECD 226)
    • Collembolan Reproduction Test in Soil (OECD 232)
  • Level 5: In Vivo Assays – Further Extensive Testing of Relevant Endocrine End Points
    • Two-Generation Reproduction Toxicity Study (OECD 416)
    • Extended One-Generation Reproductive Toxicity Study (OECD 443)
    • Avian Two-Generation Toxicity Test in the Japanese Quail (US EPA OCSPP 890.2100/ 740-C-15-003)
    • Sediment Water Chironomid Life Cycle Toxicity Test (OECD 233)
    • Daphnia Multigeneration Test for Assessment of EDCs (DMGT)
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Endocrine Disruptor Regulatory Frameworks and Support Services

Regulatory requirements for endocrine disruptor testing vary depending on country of sale/registration and product type. Our regulatory affairs specialists can help with every step of your dossier preparation ensuring you include the right data to meet your deadlines. Our endocrine disruptor regulatory experts are on hand to guide you in designing the most efficient and effective testing program to comply with the various global frameworks that include, but are not limited to:

  • Plant Protection Products: European Commission Regulation (EU) 2018/605 of 19 April 2018
  • Biocides: European Commission Delegated Regulation (EU) 2017/2100 of 4 September 2017
  • Guidance for identification of endocrine disputers published jointly by EFSA and ECHA on 5 June 2018
  • Endocrine Disruptor Screening Program (EDSP) published by EPA

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Frequently Asked Questions (FAQs) About Endocrine Disruptor Testing

  • Are there planned changes to Endocrine Disruptor testing?

    The long-term vision for the EU’s chemical policy, the chemicals strategy for sustainability, includes endocrine disruption as one of its focus points. The criteria for the identification of endocrine disruptors have already been developed for pesticides and biocides. Building on these criteria, the information requirements across legislations, including REACH, will be updated to facilitate the identification of endocrine disruptors for other sectors including industrial chemicals.

  • What is the Endocrine Disruptor Screening Program?

    The Endocrine Disruptor Screening Program (EDSP) is used to screen pesticides, chemicals, and other environmental contaminants for their potential to impact the androgen, estrogen, and thyroid hormone systems. The program was launched by EPA in the USA. For Endocrine Disruptor testing in Europe, please visit our dedicated page.

  • What tests are required for the EPA Endocrine Disruptor Screening Program?

    The endocrine disruptor screening program (ESDP) utilizes a range of in vitro and in vivo studies to determine adverse effects, dose-response as well as assess and manage risk. Initial assays are outlined in the EPAs Tier 1 Screening Battery.