EFSA CEF Panel (Panel on Food Contac t Materials, Enzymes, Flavourings and Processing Aids , 2013. Scientific Opinion on Flavouring Group Evaluation 2 07 (FGE.2 07 )

International audienc

Inhibition of aromatase activity and growth suppression by 4-methoxy-4-androstene-3,17-dione in an androgen sensitive human prostatic carcinoma cell line

Aromatization of testosterone to estradiol was investigated in a human prostatic carcinoma cell line, LNCaP. A saturable, dose and time-dependent aromatization of testosterone was observed. Kinetic parameters, K m (201 nM) and V max (0.76 pmol/h per mg) and also the inhibition constants ( K i) for various aromatase inhibitors were calculated from standard Lineweaver-Burke plots. The steroidal aromatase inhibitor 4-hydroxy-4-androstene-3,17-dione (4-OHA) and its derivative, 4-methoxy-4-androstene-3,17-dione (4-OMA), inhibited aromatization of testosterone in a competitive pattern of inhibition. The derivative 4-OMA is the stronger inhibitor of the two, with an apparent K i of 1.12 μM, whereas the apparent K i of 4-OHA is 3.28 μM. Long term incubation with 4-OMA suppressed proliferative activity of LNCaP cells in the presence of physiological levels of testosterone (10 −10 M to 10 −7 M). In contrast, 4-OHA was a growth promoter. These results suggest a potential role for aromatase in hormone responsive prostate cancer

Guidelines for Timing Contraction Joint Sawing and Earliest Loading for Concrete Pavements: Volume I - Final Report

DTFH61-88-C-00062A study with the objectives of providing guidelines for timing of contraction joint saw cutting to avert uncontrolled pavement cracking and providing guidelines for early loading of pavements by construction traffic has been conducted. A laboratory study of early age (4 to 24 hours) and early pavement loading (1 to 28 days) concrete strength properties for a range of highway concrete mixes was made. Sawcutting tests were made to determine earliest contraction joint sawcutting. Earliest sawcut timing was correlated on basis of sawcut ratings to concrete strength properties and non-destructive test results that can be used for determining earliest sawcutting time. Concrete pavement placement and joint sawcutting were observed at three highway construction sites to verify test results. Latest sawcutting time was targeted on basis of buildup ofrestraint stresses attributable to slab cooling. Guidelines for sawcut timing are presented to facilitate construction site decision making based on nondestructive test methods. Early loading by construction traffic was analyzed using ILLI-SLAB finite element models. Load tests were made at two pavement sites to verify that analytical model results are applicable to new pavements. Guidelines are presented to facilitate construction site decision making for early trafficking of new pavements based on nondestructive test methods. This is the first of two volumes. The second volume is FHWA-RD-91-080, Guidelines for Timing Construction Joint Sawing and Earliest Loading for Concrete Pavements - Volume II -Appendix