Evaluation of 10 aliphatic halogenated hydrocarbons in the mouse bone marrow micronucleus test.
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.
Crebelli
R
R
Istituto Superiore di Sanita, Laboratory of Comparative Toxicology and Ecotoxicology, Rome, Italy. crebelli@net.iss.it
Carere
A
A
Leopardi
P
P
Conti
L
L
Fassio
F
F
Raiteri
F
F
Barone
D
D
Ciliutti
P
P
Cinelli
S
S
Vericat
J A
JA
D000818:Animals; D001853:Bone Marrow / Q000187:drug effects*; D005260:Female; D006846:Hydrocarbons, Halogenated / Q000008:administration & dosage / Q000633:toxicity*; D007700:Kinetics; D007928:Lethal Dose 50; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D015162:Micronucleus Tests; D009153:Mutagens / Q000494:pharmacology*; D012680:Sensitivity and Specificity
D006846:Hydrocarbons, Halogenated; D009153:Mutagens