Table 2.
Cytotoxicity and number of significantly deregulated probe sets in compound-exposed cells in the UKN1 test.
| Compounds | Abbreviation | Cytotoxicity b | Number of Up-/Downregulated Probe Sets c | ||||
|---|---|---|---|---|---|---|---|
| 1-Fold Cmax a | 20-Fold Cmax a | ||||||
| 1-Fold Cmax a | 20-Fold Cmax a | Up | Down | Up | Down | ||
| Non-teratogens | |||||||
| Ampicillin | AMP | No | No | 0 | 0 | 0 | 0 |
| Ascorbic acid | ASC | No | No | 0 | 0 | 0 | 0 |
| Buspirone | BSP | No | No | 0 | 0 | 0 | 0 |
| Chlorpheniramine | CPA | No | No | 0 | 0 | 0 | 0 |
| Dextromethorphan | DEX | No | No | 0 | 0 | 0 | 0 |
| Diphenhydramine | DPH | No | No | 0 | 0 | 0 | 0 |
| Doxylamine | DOA | No | No | 0 | 0 | 0 | 0 |
| Famotidine | FAM | No | No | 0 | 0 | 0 | 0 |
| Folic acid | FOA | No | No | 0 | 0 | 0 | 0 |
| Levothyroxine | LEV | No | No | 18 | 20 | 0 | 0 |
| Liothyronine | LIO | No | No | 0 | 0 | 27 | 57 |
| Magnesium chloride | MAG | No | No | 0 | 0 | 13 | 3 |
| Methicillin | MET | No | No | 0 | 0 | 0 | 2 |
| Ranitidine | RAN | No | No | 0 | 0 | 0 | 0 |
| Retinol e | RET | No | -- e | 0 e | 0 e | -- e | -- e |
| Sucralose | SUC | No | No | 0 | 0 | 0 | 0 |
| Teratogens | |||||||
| 9-cis-retinoic acid | 9RA | No | No | 1956 | 1785 | 2426 | 1887 |
| Acitretin | ACI | No | No | 1803 | 1604 | 2309 | 1795 |
| Actinomycin D | ACD | Yes | Yes | toxic | toxic | toxic | toxic |
| Atorvastatin | ATO | Yes | Yes | toxic | toxic | toxic | toxic |
| Carbamazepine | CMZ | No | No d | 0 | 0 | 910 d | 591 d |
| Doxorubicin | DXR | Yes | Yes | toxic | toxic | toxic | toxic |
| Entinostat | ENT | No | Yes | 48 | 30 | toxic | toxic |
| Favipiravir | FPV | No | No | 0 | 0 | 1551 | 1290 |
| Isotretinoin | ISO | No | Yes | 1029 | 703 | toxic | toxic |
| Leflunomide | LFL | No | --- d | 614 | 415 | --- d | --- d |
| Lithium chloride | LTH | No | Yes | 0 | 0 | toxic | toxic |
| Methotrexate | MTX | No | No | 435 | 209 | 687 | 622 |
| Methylmercury | MEM | No | No | 0 | 0 | 0 | 0 |
| Panobinostat | PAN | Yes | Yes | toxic | toxic | toxic | toxic |
| Paroxetine | PAX | No | Yes | 0 | 0 | toxic | toxic |
| Phenytoin | PHE | No | --- d | 0 | 0 | --- d | --- d |
| Retinol e | RET | -- e | No | -- e | -- e | 1032 e | 936 e |
| Teriflunomide | TER | No | --- d | 1829 | 1394 | --- d | --- d |
| Thalidomide | THD | No | No | 41 | 21 | 0 | 0 |
| Trichostatin A | TSA | No | Yes | 4 | 0 | toxic | toxic |
| Valproic acid | VPA | No | No d | 630 | 364 | 878 d | 685 d |
| Vinblastine | VIN | Yes | Yes | toxic | toxic | toxic | toxic |
| Vismodegib | VIS | No | --- d | 0 | 0 | --- d | --- d |
| Vorinostat | VST | Yes | Yes | toxic | toxic | toxic | toxic |
a Maximal plasma or blood concentrations after administration of therapeutic compound dose; b Yes, if the compound was highly cytotoxic; no, if the compound showed no cytotoxicity; c Gene array-probe sets that were deregulated with an FDR-adjusted p-value < 0.05 and an absolute fold-change > 2 compared to untreated control cells; d Carbamazepine and VPA were tested at 10-fold and 1.67-fold Cmax, respectively, instead of 20-fold Cmax; leflunomide, phenytoin, teriflunomide, and vismodegib were only tested at 1-fold Cmax due to limited solubility; e Retinol was considered as a non-teratogen at 1-fold Cmax and as a teratogen at 20-fold Cmax. Rationale is given in the supplemental information.