ABSTRACT
1,2-Dimethylhydrazine (DMH) was administered to both genders of mice and rats by oral gavage for 3 days. Twenty-four hours later, an assessment of the incidence of micronucleated cells was made in the bone marrow and sections of the gastrointestinal tract. An increase in micronucleated cells was observed in the colon of both genders of both species of rodent. Negative responses were observed in the forestomach, stomach, duodenum, intestine of both species. The bone marrow micronucleus assays were essentially negative, but the absence of a precise definition of the MTD precludes a definitive conclusion from being drawn. These results are consistent with the selective carcinogenicity of DMH to the colon of the rodent GI-tract. DMH is also known to be carcinogenic to rat and mouse liver and, although it is known to induce micronuclei in the hepatocytes of rats, no such data exist for the mouse. Consequently, mice were administered DMH on 13 successive days, followed by 2/3 partial hepatectomy and assessment of micronucleated hepatocytes. A strong positive liver micronucleus assay response was observed. Thus, DMH selectively induces micronuclei in the colon and liver of rats and mice, consistent with its carcinogenicity to these two tissues. No qualitative differences between the genders was observed in any of the assays. These results indicate that the assessment of genetic toxicity in rodents should not rely solely on assays made in bone marrow.
Subject(s)
Bone Marrow/drug effects , Digestive System/drug effects , Dimethylhydrazines/toxicity , Liver/drug effects , Mutagens/toxicity , 1,2-Dimethylhydrazine , Administration, Oral , Animals , Bone Marrow Cells , Digestive System/cytology , Dimethylhydrazines/administration & dosage , Dose-Response Relationship, Drug , Female , Lethal Dose 50 , Liver/cytology , Male , Mice , Mice, Inbred CBA , Micronucleus Tests , Mutagens/administration & dosage , RatsABSTRACT
The activities of 1,2-dibromopropane (DBP) and 1,1,3-tribromopropane (TBP) were studied in seven genotoxicity assays, (i) SOS-induction in E. coli, (ii) DNA repair in primary rat hepatocyte culture, (iii) the Salmonella/microsome assay, (iv) a host-mediated assay using Salmonella, (v) the somatic mutation and recombination assay in Drosophila melanogaster, (vi) HGPRT-mutagenesis assay in ARL 18 cells, and (vii) micronucleus formation assay in mouse polychromatophylic erythrocytes (PCE), forestomach (FS), glandular stomach (GS), duodenum (D), jejunum (J), cecum (C) and liver (L). The halopropanes were also tested for tumor formation in the fish Danio rerio. DBP was active in assays (ii), (v), (vii FS) and (vii L). TBP was positive in assays (ii) and (iii), strongly positive in (vii L) and borderline positive in (iv). However, neither DBP nor TBP induced tumors in fish, in contrast to the carcinogenic 1,2-dibromo-3-chloropropane. The genotoxicity and potential carcinogenicity of DBP and TBP in mammals is discussed.
Subject(s)
Carcinogens/toxicity , Mutagens/toxicity , Propane/analogs & derivatives , Animals , Carcinogenicity Tests , Cells, Cultured , DNA Damage , DNA Repair , Fishes , Mice , Micronucleus Tests , Mutagenicity Tests , Propane/toxicity , Rats , SOS Response, GeneticsSubject(s)
Carcinogens , Propane/analogs & derivatives , Animals , Male , Mice , Organ Specificity , Rats , Species SpecificityABSTRACT
Maximum allowable concentrations of Realon and zinc complex IOMC-1 in water were recommended at levels, accordingly, 0.04 and 2.0 mg/1 with organoleptic signs of action.