Dose-effect curves determined for 5 days-old ZFE following reference (solid lines) and UHDR (dash-dotted lines) irradiation with 225 MeV protons (circles, left column), in a proton SOBP (crosses, middle column) and with 30 MeV electrons (squares, right column). The rows show the different endpoints: the fraction of ZFE with a pericardial edema (a), the fraction with a curved spine (b), the deficit of embryo length compared to unirradiated controls (average length ∼ 3900 µm) (c) and the deficit of eye diameter compared to unirradiated controls (average diameter ∼ 240 µm) (d). The electron datapoints in panel (c) were already shown in a recent letter [21] as a preview on the full dataset presented here. The statistical significance of the sparing effect at UHDR is indicated by ns (non-significant), * (significant), ** (very significant) and *** (highly significant).

Panel (a) and (b): Dose-effect curves determined for 5 days-old ZFE following irradiation with 225 MeV protons (solid lines and circles), in a proton SOBP (dashed lines and crosses) and 30 MeV electrons (dotted lines and squares) at reference dose rate (between 6 and 32 Gy/min). Panel (c) and (d): Dose-effect curves for irradiation at reference dose rate with 225 MeV protons (solid lines and circles) and in a proton SOBP (dashed lines and dark crosses) compared to the proton SOBP dose–effect curve at UHDR (dot-dashed lines and light crosses). Panel (a) and (c) show data for the curved spine endpoint and panel (b) and (d) for the embryo length deficit endpoint. The *** symbol indicates a highly significant RBE increase of the SOBP compared to the monoenergetic 225 MeV protons and 30 MeV electrons.

Panel (a): FLASH modifying factor (FMF) as a function of dose obtained from the dose–effect curves of ZFE irradiated with 30 MeV electrons at UHDR and reference dose rate for four different endpoints: pericardial edema (squares), curved spine (inverted triangles), embryo length deficit (triangles) and eye diameter deficit (diamonds). Panel (b): FMF for the curved spine endpoint as a function of dose for ZFE irradiated with 225 MeV protons at 240 Gy/s (circles), in a proton SOBP at 600 Gy/s (diamonds) and with 30 MeV electrons at 0.9 x 105 Gy/s (squares). The ZFE data is compared with rodent FMF data derived by Böhlen et al. [6] from dose-effect curves found in the literature [1], [32], [39], [40], [41], [42], [43], [44], [45], [46], [47], [48], [49], [50] (light dots). The error bars indicate the uncertainty of the FMF calculated from the dose–effect curves.