a no observed effect level (NOEL) of 10 mg/kg/day in mice and a lowest observed effect level (LOEL) of 10 mg/kg/day in rats. The lowest oral dose which caused cancer (LOAEL) in B6C3F1-mice was 70 mg/kg/day. These are 1–3 orders of magnitude higher than human exposure, which is principally dermal rather than oral.<ref>Sections 4.1.1.5 & 4.1.3.5, European Union Risk Assessment Report, pp. 57 and 109–110.</ref> Environmental concerns The first concerns about musk xylene arose in the early 1980s, with the detection of musk xylene residues in fish from the Tama River near Tokyo, and subsequently in the river water itself, especially at the outlets of sewage treatment plants. This led to a voluntary moratorium on the use of musk xylene in Japan from 1982. Similar residues were subsequently found in European waters such as the Elbe, Stör and Ruhr rivers in Germany, the German Bight area of the North Sea and sewage treatment plant outlets in Sweden.Section 3.1.2.4, European Union Risk Assessment Report (2005), pp. 21–24. Typical concentrations were >0.001 µg/L in sea water, 0.001–0.01 µg/L in river water and 0.01–0.1 µg/L (sometimes higher) in the effluent from sewage treatment plants. These findings indicate that musk xylene is not completely removed from wastewater by the sewage treatment process. Two studies in Germany found compared musk xylene concentrations in incoming wastewater and sewage treatment plant effluent, and found removal rates of 82% and 58%.Later studies have found higher rates of removal of musk xylene by sewage treatment plants, around 95%: European Chemicals Agency (2008). However, they are not concentrations which are expected to be toxic to aquatic life. The European Union Risk Assessment Report reviewed more than a dozen studies of the toxicity of musk xylene to algae and to aquatic vertebrates and invertebrates, and all found no observed effect concentrations greater than 10 µg/L, the chronic aquatic toxicity threshold in the EU REACH Regulation. The biodegradation of musk xylene in sea water and in mixed sea water/sediment systems was studied in laboratory simulations using carbon-14 labelled musk xylene, and the results discussed in an addendum to the European Union Risk Assessment Report. The half-life in marine sediment was estimated to be 60 days or less, with biodegradation occurring by anaerobic reduction of the nitro groups. The half-life in sediment-free sea water was estimated to be more than 150 days, far above the "very persistent" threshold of 60 days. The 2008