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Absence of genotoxicity of sulfur dioxide (SO2) in a bone marrow micronucleus test with NMRI mice, complemented with several hematological endpoints

 
: Ziemann, C.; Hansen, T.; Pohlmann, G.; Farrar, D.; Pohlenz-Michel, C.; Mangelsdorf, I.

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46th Congress of the European Societies of Toxicology 2009. Abstracts : Dresden, Germany, 13th - 16th September 2009; EUROTOX 2009
Amsterdam: Elsevier, 2009 (Toxicology letters 189.2009, Supplement 1)
ISSN: 0378-4274
pp.S258
European Societies of Toxicology (EUROTOX Congress) <46, 2009, Dresden>
English
Abstract
Fraunhofer ITEM ()
sulphur dioxide; Genotoxicology

Abstract
Sulfur dioxide (SO2) is a common air pollutant. The limited in vitro data indicate lack of genotoxicity of SO2, while for sulfite salts some positive results have been reported. Recent in vivo studies from one workgroup, using Kunming albino mice, pointed to in vivo clastogenicity of SO2. To re-evaluate these positive findings a bone marrow micronucleus test according to OECD Guideline 474 was performed. NMRI mice (m/f) were exposed by whole-body inhalation to 0 (clean air), 2.7, 8, 27, or 80 mg/m3 SO2 for 4 h/day for 7 consecutive days. Animals were sacrificed 24 h after the start of the last exposure and blood samples (complementing hematology) and bone marrow smears (analysis of micronuclei) were prepared. In the present study, SO2-exposure caused no acute toxicity, mortality, or reduction in body weight. Compared to the clean-air controls, hematological parameters like hematocrit, hemoglobin, erythrocyte-/platelet-/total leukocyte-counts (all Sysmex KX-21N), differential white blood cell-counts, and blood formation (reticulocyte-counts, ratio of polychromatic/normochromatic erythrocytes in the bone marrow) remained unchanged by SO2-treatment. Unlike the re-evaluated micronucleus studies, SO2 did not induce micronucleus formation in polychromatic erythrocytes of the bone marrow, whereas the positive control cyclophosphamide was quite effective. Interestingly, SO2-treatment significantly enhanced malondialdehyde levels in erythrocyte lysates (TBARS-method), indicating SO2-mediated oxidative stress, but also pointing to systemic availability of the inhaled SO2. In conclusion, the present study could not reproduce the positive findings of the former studies. Under the conditions and in the concentrations used, SO2 is thus considered non-mutagenic in bone marrow polychromatic erythrocytes of NMRI mice.

: http://publica.fraunhofer.de/documents/N-109924.html