Ex vivo perfusion of the human term placenta is a method to study placental transfer without extrapolation from animal to human and with no ethical concerns for mother and child. However, ex vivo placenta perfusion has a limited potential within chemical screening and testing as the method is time-consuming. This study was an attempt to construct data needed to develop quantitative structure-activity relationship (QSAR) models that are able to predict placental transfer of new compounds. Placental transfer is a biological activity that statistically may be related to the physiochemical properties of a given group of compounds. Benzoic acid, caffeine, and glyphosate were chosen as model compounds because they are small molecules with large differences in physiochemical properties. Caffeine crossed the placenta by passive diffusion. The initial transfer rate of benzoic acid was more limited in the first part of the perfusion compared to caffeine, but reached the same steady-state level by the end of perfusion. The transfer of glyphosate was restricted throughout perfusion, with a lower permeation rate, and only around 15% glyphosate in maternal circulation crossed to the fetal circulation during the study period.

No abstract

The effect of various alkanols on the central nervous system was studied by using rat brain synaptosomal membranes as an in vitro model. The activity of (Ca2+/Mg2+)ATPase and the membrane fluidity were determined. The n-alkanols exhibited an increased molar inhibition of the ATPase activity with an increase in the carbon chain length up to 1-octanol. 1-octanol and 1-decanol caused a biphasic effect on the ATPase activity depending on the alkanol concentration, whereas 1-dodecanol caused a stimulation of the ATPase activity. All alkanols studied caused an increased fluidity of the membrane. Our results indicate that the effect of alkanols on the ATPase activity depends on changes in the border layer between the membrane and the surrounding medium and on a binding of the alkanols to the enzyme molecule. Furthermore, the two-way effect of 1-octanol and 1-decanol and the stimulatory effect of 1-dodecanol indicate that more mechanisms are involved. In addition, the results indicate that changes in the membrane fluidity do not seem to be a prerequisite of the ATPase inhibition.

The effect of toluene on the central nerve system was studied by using rat brain synaptosomal membranes as in vitro and in vivo models. The activity of Ca2+/Mg2+ ATPase and the membrane fluidity were determined. Short-term exposure in vivo to 500 p.p.m. of toluene had an inhibitory effect on the enzyme studied whereas long-term exposure to toluene caused an increased activity. Exposure to toluene had no effect at all on the membrane fluidity. The in vitro experiment showed an effect of toluene on both parameters. The alteration in the enzyme activity and membrane fluidity was parallel in the exposed animals as well as those of control. Our results show that long-term exposure to toluene affects nerve cell membranes by other mechanisms than those observed under in vitro conditions.

The distribution of lithium, and the effect of lithium on sodium and potassium in various parts of the rat brain were investigated. For this purpose a technique was developed by which the rat brain could be dissected in reproducible anatomical brain parts. Lithium was distributed unequally in the various brain parts. The concentration in hemispheres, cerebellum, thalamus and grey matter from the hemispheres was at the serum level, i. e. about 0.5 meq./kg of fresh tissue. The concentration in the hypothalamus and in white matter from the hemispheres was about 1.0 meq./kg of fresh tissue. Treatment with lithium had no influence on the potassium content in the brain whereas the sodium concentration was lowered about ten per cent in the hypothalamus and in the white matter of the hemispheres.