Gadolinium uptake rognkjeks
Purpose: The aim of the proposed study is to generate empirical datasets on uptake and retention of different variants of a rare earth element, gadolinium (Gd). Gadolinium is commonly used in medical applications as MRI contrast agent. Due to the toxicity of Gd as a free ion it is chelated in medical applications which reduces toxicity, and improves solubility (Penfield & Reilly 2007). However, Gd-chelates used in medicine are passing through the human body, are excreted (Penfield & Reilly 2007) and end up in our rivers and fjords. The chemical interactions of Gd-chelates are virtually unknown and there is no indication that the chelates are stable in seawater: Gd might regain its toxicity.
1. Distress: We do not expect any distress of the fish regarding the treatments. Fish will be kept in state-of-the-art tanks, always supplied with fresh sea water, and fed high quality diets. The 'treatment' groups will receive water with either (A) two different doses of GdCl3, or (B) the same Gd doses in the form of a gadolinium-based contrast agent (GBCA) as it is used in humane medical applications, or (C) the corresponding concentrations of DOTA, the chelator. The treatment will be repeated 10 times for 3 hours on 10 consecutive days. We will tag the fish to investigate individual growth rates, which must be considered as a moderate stress for the fish.
2. Expected benefit: This study will help understanding if a chemical, to date simply discarded into the nature in abundance, has a toxic effect on fish. Such knowledge could initiate investigation if Gd can be transferred via trophic pathways posing a risk for human sea food consumers.
3. Number of animals, and what kind: Juvenile lumpsucker (Cyclopterus lumpus), ca. 200 g wet weight. We will use 108 fish. We choose lumpsucker, as these are relatively stationary fish and are likely to be exposed to toxics released by waste-water plants. In the case of results suggesting a real risk involved studies needs to be repeated with more mobile fish.
4. How to adhere to 3R: Replacement: Since we are studying bioaccumulation in several fish organs, we need to work on whole organism and cannot replace the study organism (lumpsucker) by e.g. tissue cultures or non-vertebrate animals. Reduction: The experimental design is set up to use minimum number of fish to produce enough biomass to analyse Gd and potential effects on growth and gene expression as a response to the Gd. Refinement: We will not apply distress to the fish during the exposure. The tagging poses a distress. We will use tiny T-bar tags to individually mark fish, which is the least harmful tag possible in this application. If we wouldn't tag the fish to follow individual growth, we would have to use more fish to smooth out individual variability (in fish biology, typically it would be around 10 times the amount of fish).
Penfield JG, Reilly RF. 2007. What nephrologists need to know about gadolinium. Nature Clinical Practice Nephrology 3: 654-68
1. Distress: We do not expect any distress of the fish regarding the treatments. Fish will be kept in state-of-the-art tanks, always supplied with fresh sea water, and fed high quality diets. The 'treatment' groups will receive water with either (A) two different doses of GdCl3, or (B) the same Gd doses in the form of a gadolinium-based contrast agent (GBCA) as it is used in humane medical applications, or (C) the corresponding concentrations of DOTA, the chelator. The treatment will be repeated 10 times for 3 hours on 10 consecutive days. We will tag the fish to investigate individual growth rates, which must be considered as a moderate stress for the fish.
2. Expected benefit: This study will help understanding if a chemical, to date simply discarded into the nature in abundance, has a toxic effect on fish. Such knowledge could initiate investigation if Gd can be transferred via trophic pathways posing a risk for human sea food consumers.
3. Number of animals, and what kind: Juvenile lumpsucker (Cyclopterus lumpus), ca. 200 g wet weight. We will use 108 fish. We choose lumpsucker, as these are relatively stationary fish and are likely to be exposed to toxics released by waste-water plants. In the case of results suggesting a real risk involved studies needs to be repeated with more mobile fish.
4. How to adhere to 3R: Replacement: Since we are studying bioaccumulation in several fish organs, we need to work on whole organism and cannot replace the study organism (lumpsucker) by e.g. tissue cultures or non-vertebrate animals. Reduction: The experimental design is set up to use minimum number of fish to produce enough biomass to analyse Gd and potential effects on growth and gene expression as a response to the Gd. Refinement: We will not apply distress to the fish during the exposure. The tagging poses a distress. We will use tiny T-bar tags to individually mark fish, which is the least harmful tag possible in this application. If we wouldn't tag the fish to follow individual growth, we would have to use more fish to smooth out individual variability (in fish biology, typically it would be around 10 times the amount of fish).
Penfield JG, Reilly RF. 2007. What nephrologists need to know about gadolinium. Nature Clinical Practice Nephrology 3: 654-68