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Endpoint:
basic toxicokinetics
Data waiving:
study scientifically not necessary / other information available
Justification for data waiving:
other:
Justification for type of information:
Only a theoretical assessment of the toxicokinetic behaviour of the substance is required.Since no exposure to elemental Dysprosium occurs no assessment of the toxicokinetic behaviour is possible.The Lanthanide elements own a very high affinity for oxygen; they exhibit the highest free energy for oxide formation of all elements in the periodic table, accounting for the exceptional thermodynamic stability of the oxides. In consequence the metals will react with air, building up an oxide layer on the surface. This implies the technical unfeasibility of exposure to “free” Dysprosium metal (powder form), which is a prerequisite for absorption of Dysprosium metal. For studying the toxicokinetic behaviour of the substance, appropriate application of „free“ Dysprosium metal is not possible since the particles would react in contact with water and air. The readily formed oxides and hydroxides are insoluble in water. In the following an overall summary of available literature data for the toxicokinetic behaviour of lanthanides is given.Absorption, accumulation and excretion of lanthanidesAccording to C.H. Evans (C. H. Evans: “Biochemistry of the lanthanides”, Plenum Press New York and London, 285-389, 1990) the absorption of soluble lanthanide salts in the gastrointestinal tract is only marginal. Overall, the systemic absorption of soluble lanthanide salts increases as follows:Oral << subcutanueous < intramuscular < intraperitoneal < inhalativ << intravenous, where the oral absorption is smaller than 1 % and absorption after intravenous injection is 100 %. Excretion takes place via faeces and urine.Although the lanthanides are chemically very similar accumulation in the body is different. Light lanthanide elements are accumulated preferentially in the liver whereas heavier lanthanide elements are accumulated in the skeleton.Absorption differs significantly when organic lanthanide complexes (e.g. chelates) are administered. After administration of these substances increased absorption and excretion rates are observed.The metabolism characteristics of insoluble lanthanide particles are those of insoluble particles in general. After having been injected intravenously, parenterally administered particles tend to remain at the site of application over periods of several months. After intravenous injection, particles are removed from the circulation by cells of the reticuloendothelial system.Pulmonary retention of inhaled lanthanide particles is high. Particles of 144Ce had a half-life of 170 days in the lungs of beagles. Excretion was correspondingly slow. 200-300 days after inhalation, over 80 % remained in the lung with small amounts in the lymph nodes, liver and skeleton.Durbin et al. (P. W. Durbin, M. H. Williams, M. Gee, R. H. Newman and J. G. Hamilton: Metabolism of the Lanthanons in the rat, Proceedings of the Society for Experimental Biology and Medicine 91, 78-85, 1956) determined for soluble lanthanide compounds (chelates) only insignificant absorption rates. After intramuscular injection accumulation takes place in the liver (50 %) and in the skeleton (25 %).Elimination from the liver takes place with a half-life of 15 days, whereas in the skeleton 2/3 of the initial concentration can still be measured after 2 months.Heavy lanthanides are accumulated in the skeleton (65 %) with a half-life of 2.5 years.In a study from Nakamura et al. (Y. Nakamura, Y. Tsumura-Hasegawa, Y. Tonogai, M. Kanamoto, N. Tsuboi, K. Murakami and Y. Ito: Studies on the biological effects of rare earth elements. II. Distribution and the histological effects of Dy, Eu, Yb and Y in the rat after intravenous administration, Eisei Kagaku 37, 479-506, 1991) a close relation of the toxicological behaviour with the relative atomic mass of the lanthanides is described. Light lanthanide elements reveal severe hepatoxicity, whereas lanthanide elements with medium atomic weight are accumulated in the lung and the spleen.

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