as carriers for radionuclides in bone cancer treatments (see samarium-153-ethylene diamine tetramethylene phosphonate). Concrete admixtures Phosphonates are also used as concrete retarder. They delay the cement setting time, allowing a longer time to place the concrete or to spread the cement hydration heat on a longer period of time to avoid too high temperature and resulting cracks. They also have favourable dispersing properties and so are investigated as a possible new class of superplasticizers. However, presently, phosphonates are not commercially available as superplasticizers. Superplasticizers are concrete admixtures designed to increase the concrete fluidity and workability of concrete or to decrease its water-to-cement (w/c) ratio. By reducing the water content in concrete, it decreases its porosity, improving so the mechanical properties (compressive and tensile strength) and the durability of concrete (lower water, gas and solutes transport properties). Medicine In medicine, phosphonates and bisphosphonates are commonly used as inhibitors of enzymes which utilize phosphates and diphosphates as substrates. Most notably, these enzymes include those that produce the intermediates of cholesterol biosynthesis. Phosphonate nucleotide analogues such as tenofovir, cidofovir and adefovir are critical antiviral medications, which in various pro-drug forms are used for the treatment of HIV, hepatitis B and others. Niche uses In conjunction with organosilicates, phosphonates are also used to treat "sudden oak death", which is caused by the fungus-like eukaryote Phytophthora ramorum. Toxicology The toxicity of phosphonates to organisms living in water is low. Reported values for 48-hour LC50 values for fish are between 0.1 and 1.1 mM. Also the bioconcentration factor for fish is very low. Biodegradation In nature bacteria play a major role in the degradation of phosphonates. Due to the presence of natural phosphonates in the environment, bacteria have evolved the ability to metabolize phosphonates as nutrient sources. Some bacteria use phosphonates as a phosphorus source for growth. Aminophosphonates can also be used as sole nitrogen source by some bacteria. The polyphosphonates used in industry differ greatly from natural phosphonates such as 2-aminoethylphosphonic acid, because they are much larger, carry a high negative charge and are complexed with metals. Biodegradation tests with sludge from municipal sewage treatment plants with HEDP and NTMP showed no indication for any degradation. An investigation of HEDP, NTMP, EDTMP and DTPMP in standard biodegradation tests also failed to identify any biodegradation. It was noted, however, that in some tests due to the high sludge to phosphonate ratio, removal of the test substance