Table 3: Overview of the readiness levels of exemplary DNT test methods.
Different DNT test methods were scored according to the criteria presented in Table I and Figure 3. The readiness levels for Phase I –III varied from D (not at all ready, red), over C (orange), B (yellow) to A (largely ready, green). Detailed data are found in supplementary table 1. The overall readiness was estimated semi-quantitatively from the pattern of readiness in the different phases. Notably, the term overall readiness has to be used with care, as readiness depends on the purpose, and it is given here only to provide an orientation on the availability of methods in the field. This is exemplified by the cMINC (UKN2 method) which scores A in phase I and B in phase II. According to this, the method is not ready for regulatory risk assessment. However, it scores A for screening, and is thus ready for initial prioritization of compounds. List of abbreviations: UKN1 - PSC differentiation into NPC/NSC embryonic phase differentiation, NPC1 – hNPC proliferation, NPC2 – hNPC migration, NPC3 – hNPC neuronal differentiation, NPC4 – hNPC differentiated neurons, NPC5 – hNPC oligodendrocyte differentiation, NPC6 – hNPC oligodendrocyte maturation and TH disruption, UKN2 - NCC proliferation and migration, MESn - Morphological ESC to neurons, 3Dr - astrocytes, oligodendrocytes, myelination, microglia in 3D rat, 3Dh - astrocytes, oligodendrocytes, myelination, microglia in 3D human, foetal phase: UKN4 (NeuriTox) –neurite outgrowth of central neurons, UKN5 (PeriTox) – neurite outgrowth peripheral neurons, NSR neuronal subtype ratio, neuronal maturation: Syn – synaptogenesis, Nnff – neuronal network formation and function, ZFE – zebrafish
| Readiness/ Test method |
Phase I | Phase II | Phase III | Overall readiness |
|---|---|---|---|---|
| UKN1 | A | B | B | B+ |
| NPC1 | A | A | A | A |
| NPC2 | A | A | A | A |
| NPC3 | A | A | B | A- |
| NPC4 | A | B | C | B |
| NPC5 | A | A | B | A- |
| NPC6 | A | B | B | B+ |
| UKN2 (cMINC) | A | B | A | A- |
| MESn | C | D | D | D+ |
| UKN4 (NeuriTox) | A | A | A | A |
| UKN5 (PeriTox) | A | B | A | A- |
| NSR | C | D | D | D+ |
| SYN | B | B | B | B |
| Nnff | B | A | B | B+ |
| 3Dr | A | A | A | A |
| 3Dh | B | C | C | C+ |
| ZFE | B | B | A | B+ |