PUBLICATION

Fish embryo toxicity test, threshold approach, and moribund as approaches to implement 3R principles to the acute fish toxicity test

Authors
Dang, Z., van der Ven, L.T.M., Kienhuis, A.S.
ID
ZDB-PUB-170819-7
Date
2017
Source
Chemosphere   186: 677-685 (Journal)
Registered Authors
van der Ven, Leo
Keywords
3Rs, Alternative testing, Animal welfare, Threshold approach, Zebrafish embryo
MeSH Terms
  • Animals
  • Embryo, Nonmammalian/metabolism
  • Embryo, Nonmammalian/physiology*
  • Toxicity Tests
  • Toxicity Tests, Acute/methods*
  • Zebrafish/embryology*
  • Zebrafish/growth & development
PubMed
28818595 Full text @ Chemosphere
Abstract
The acute fish toxicity test (AFT) is requested by EU legal frameworks for hazard classification and risk assessment. AFT is one of the few regulatory required tests using death as an endpoint. This paper reviews efforts made to reduce, refine and replace (3Rs) AFT. We make an inventory of information requirements for AFT, summarize studies on 3Rs of AFT and give recommendations. The fish embryo toxicity test (FET) is proposed as a replacement of AFT and analyses have focused on two aspects: assessing the capacity of FET in predicting AFT and defining the applicability domain of FET. Six comparison studies have consistently shown a strong correlation of FET and AFT. In contrast, the applicability domain of FET has not yet been fully defined. FET has not yet been accepted as a replacement of AFT by any EU legal frameworks to fulfill information requirements because FET is insensitive to some chemicals. It is recommended that the outlier chemicals that do not correlate between FET and AFT should be further investigated. When necessary, additional FET data should be generated. Another effort to reduce and refine AFT is incorporation of FET into the threshold approach. Furthermore, moribund as an endpoint of fish death has been introduced in revising AFT guideline to reduce the duration of suffering for refinement. This endpoint, however, needs further work on the link of moribund and death. Global regulatory acceptance of the moribund endpoint would be critical for this development.
Genes / Markers
Figures
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping