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In this volume we summarize the programme's main achievements so far. In chapter 1 (Bioconcentration of pharmaceuticals, by Jerker Fick, Roman Gra- bic, Richard Lindberg, Joakim Larsson and Mats Tysklind) an essential part of the MistraPharma research approach is described, namely the procedure of prioritizing pharmaceuticals based on empirical bioconcentration studies and the "plasma model"1. The plasma model is based on the assumption that two species sharing the same drug target, i.e. a receptor or an enzyme, will require about the same plasma concentrations of a pharmaceutical to activate a pharmacological response. Comparing the human therapeutic plasma concentration for a particular pharmaceutical to the measured steady state levels in fish blood plasma inition co uk buy tramadol online thus makes it phentermine order phentermine from uk possible to estimate the likelihood that the fish is pharmacologically affected by that drug. Within MistraPhar- ma all the 1200 active pharmaceutical ingredients available on the Swedish market were initially considered. Using a theoretical model, risk estimates for these substances were calculated and based on this 120 active pharmaceutical ingredients were prioritized inition co uk buy tramadol online for further scrutiny. Empirical determination of bioconcentration for 25 of these pharmaceuticals was investigated in rainbow trout exposed to effluent water from three Swedish sewage treatment plants.

Out of the 25 selected pharmaceuticals, 17 were detected in fish plasma.

One of the pharmaceuticals, levonorgestrel, was detected in fish plasma at levels that exceeded the human therapeutic plasma concentration2. Levonorgestrel is a synthetic progestin used in different types of contraceptives. Other researchers recently showed that exposure to as little as 0.8 nanogram (10-9 gram) levonorgestrel per litre water significantly reduced the fertility of fish3. showed that an effluent concentration of 1 nanogram per litre water resulted in a plasma concentration in exposed fish that was higher than the human therapeutic plasma concentration. This significant finding will certainly be further investigated within MistraPharma. One type of investigation that will be applied to the substances identified as potential environmental risks is biological testing. In chapter 2 (The frog test system, by Cecilia Berg) the frog test model is introduced. In the frog test system larvae are exposed to the test substances from hatching until completed metamorphosis. Effects are evaluated at certain larval stages, at metamorphosis and when the frogs have reached sexual maturity. Major endpoints are expression of genes important for sex differentiation and development, aromatase activity (aromatase catalyses the conversion of androgens into estrogens), and the activity of specific neurotransmitters in the brain. The testicles, ovaries, oviducts, thyroid gland and other suspected target organs are evaluated for structural changes using microscopy. Fertility studies include endpoints such as sexual behaviour, egg production, hatchability, embryo mortality, and sperm quality.

Results obtained within MistraPharma show that frogs are more sensitive to estrogenic environmental pollutants than what was previously known.

Larval exposure to the estrogenic pharmaceutical ethynylestradiol (EE2) at concentrations found in the environment caused permanent male-to-female sex-reversal and reduced fertility. This demonstrates that also for amphibians the differentiation of the gonads is sensitive to disturbance by estrogenic environmental inition co uk buy tramadol online pollutants. Overall it is concluded that the frog is a promising model for research on developmental reproductive toxicity.

In chapter 3 (Genomics as a guide for environmental risk assessments of pharmaceuticals, by Filip Cuklev, Lina Gunnarsson, and Joakim Larsson) genomics is introduced as inition co uk buy tramadol online a method for risk identification and risk assessment. Genomics includes studies of the genome on a large scale. The genome is the sum of an organism's genetic information, encoded in the DNA molecule. The DNA contains the genes, and the genes will generate proteins via mRNA. Proteins determine the structure and function of the cells, and as a result, everything that occurs in an organism is inition co uk buy tramadol online related to an effect of a protein.



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