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Mutagenesis, Vol. 14, No. 2, 207-215, March 1999
© 1999 UK Environmental Mutagen Society/Oxford University Press

Evaluation of 10 aliphatic halogenated hydrocarbons in the mouse bone marrow micronucleus test

Riccardo Crebelli1,4, Angelo Carere1, Paola Leopardi1, Luigi Conti1, Franca Fassio2, Francesca Raiteri2, Domenico Barone2, Paola Ciliutti3, Serena Cinelli3 and J.A. Vericat3,5

1 Istituto Superiore di Sanita', Laboratory of Comparative Toxicology and Ecotoxicology, Viale Regina Elena, 299-00161 Rome, Italy, 2 Istituto di Ricerche Biomediche `Antoine Marxer' RBM S.p.A., 10010 Colleretto Giacosa, Italy and 3 Research Toxicology Centre S.p.A., Via Tito Speri, 12-00040 Pomezia, Italy

Ten halogenated aliphatic hydrocarbons (carbon tetrachloride, 1-chlorohexane, 2,3-dichlorobutane, 1,2-dichloroethane, 1,2-dichloroethylene, 1,3-dichloropropane, hexachloroethane, 1,1,2-trichloroethane, 1,2,3-trichloropropane and 1,1,3-trichloropropene), previously assayed in genetic assays in fungi, were evaluated in the mouse bone marrow micronucleus test in order to assess their genotoxicity in vivo. All chemicals were administered once i.p. at 40 and 70–80% of their respective LD50 to male and female CD-1 mice, 24 and 48 h before killing. All treatments produced evident clinical symptoms, but no marked depression of bone marrow proliferation. No statistically significant increases in the incidence of micronucleated polychromatic erythrocytes over the control values were observed at any sampling time with any of the 10 halogenated hydrocarbons assayed. The comparison of the results obtained in this study with the findings provided by in vitro micronucleus assays on the same chemicals, reported by other authors, indicate that mouse bone marrow is weakly sensitive to the genotoxic effects induced by halogenated hydrocarbons in other test systems. This suggests that the role of such an assay in carcinogen screening may be questionable for this chemical class. An examination of mouse bone marrow micronucleus test results with the halogenated aliphatic hydrocarbons classified as carcinogens by IARC supports this conclusion.

4 To whom correspondence should be addressed. Tel: +39 6 4990 2840; Fax: +39 6 4938 7139; Email: crebelli{at}net.iss.it

5 Present address: Synthélabo Recherche, Z.I. Limay/Porcheville, 78440 Gargenville, France


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