This study quantifies some major physico-chemical factors that influence the validity of MRI (PAGAT) polymer gel dosimetry: temperature history (pre-, during and post-irradiation), oxygen exposure (post-irradiation) and volumetric effects (experiment with phantom in which a small test tube is inserted). Present results confirm the effects of thermal history prior to irradiation. By exposing a polymer gel sample to a linear temperature gradient of ∼2.8°Ccm-1 and following the dose deviation as a function of post-irradiation time new insights into temporal variations were added. A clear influence of the temperature treatment on the measured dose distribution is seen during the first hours post-irradiation (resulting in dose deviations up to 12%). This effect diminishes to 5% after 54h post-irradiation. Imposing a temperature offset (maximum 6°C for 3h) during and following irradiation on a series of calibration phantoms results in only a small dose deviation of maximum 4%. Surprisingly, oxygen diffusing in a gel dosimeter up to 48h post-irradiation was shown to have no effect. Volumetric effects were studied by comparing the dose distribution in a homogeneous phantom compared to the dose distribution in a phantom in which a small test tube was inserted. This study showed that the dose measured inside the test tube was closer to the ion chamber measurement in comparison to the reference phantom without test tube by almost 7%. It is demonstrated that physico-chemical effects are not the major causes for the dose discrepancies encountered in the reproducibility study discussed in the concurrent paper (Vandecasteele and De Deene 2013a Phys. Med. Biol. 58 19-42). However, it is concluded that these physico-chemical effects are important factors that should be addressed to further improve the dosimetric accuracy of 3D MRI polymer gel dosimetry.