Abstract
Zebrafish embryos were exposed to concentration ranges of selected thyroid-active model compounds in order to assess the applicability of zebrafish-based developmental scoring systems withinan alternative testing strategy to detect the developmental toxicity ofthyroid-active compounds. Model compounds tested included triiodothyronine (T3), propylthiouracil (PTU), methimazole (MMI), sodium perchlorate (NaClO4) and amiodarone hydrochloride (AMI), selected to represent different modes of action affecting thyroid activity. Tested time windows included 48-120 hours post fertilization (hpf), 0-72 hpf and 0-120 hpf. All tested compounds resulted in developmental changes, with T3 being the most potent. The developmental parameters affected included reflective iridophores, beat and glide swimming, inflated swim bladders, as well as resorbed yolk sacs. These effects are only evident by 120 hpf and therefore an existing General Morphology Score (GMS) system was extended to create a General Developmental Score(GDS) that extends beyond the 72 hpfscoring limit of GMS and includes additional parameters that are affected by exposure to model thyroid-active compounds. Moreover, the GDS is cumulative as it includes not only the scoring of developmental morphologies but also integrates developmental dysmorphologies. Exposures from 48-120 hpf did not provide additional information to exposures from 0-120 hpf. The results indicate that the zebrafish GDS can detect the developmental toxicity of thyroid toxicants and may be of use in an integrated testing strategy to reduce, refine and in certain cases replace animal testing.
Highlights
The EU Regulation on the Registration, Evaluation, Authorisation and Restriction of Chemicals (REACH) requires all substances marketed or manufactured in quantities above 10 tons per annum to be tested for developmental toxicity (OECD 421 or OECD 422)
Based on data on chemical production from 1991 to 1994, the EU estimates that 2.6 million animals will be needed for all REACH testing or a total of 9 million when offspring produced during reproductive and developmental toxicity testing are taken into account
Given that alterations in the thyroid system can have severe effects on development (Boyages and Halpern, 1993; Haddow et al, 1999; Utiger, 1999), the aim of the present study was to investigate whether a zebrafish-based developmental toxicity assay would be able to detect thyroid hormone-active compounds
Summary
The EU Regulation on the Registration, Evaluation, Authorisation and Restriction of Chemicals (REACH) requires all substances marketed or manufactured in quantities above 10 tons per annum to be tested for developmental toxicity (OECD 421 or OECD 422). Substances that are marketed or manufactured in quantities above 100 tons per annum are required to be tested for pre-natal developmental toxicity (OECD 414) (REACH, 2006). The issues associated with these tests include ethical acceptability considerations, high costs and long duration. This has prompted research into the development of suitable high-throughput alternative tests that, once validated, could reduce animal testing within an integrated testing strategy (ITS)
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
