High resolution rodent bone marrow micronucleus assays of 1,2-dimethylhydrazine: implication of systemic toxicity and individual responders.
1,2-Dimethylhydrazine (DMH) is confirmed as active in male CBA mouse bone marrow micronucleus (MN) assays conducted at non-toxic dose-levels between 25 and 45 mg/kg. Previous reports of the activity of DMH in rodent bone marrow MN assays are reviewed. By the design of the present experiments it has been possible to confirm the advice offered by the United Kingdom Environmental Mutagen Society (UKEMS) that once 2000 polychromatic erythrocytes have been assessed per animal, the use of larger animal group sizes becomes the critical means to increase assay sensitivity. Also, the use of historical control data is shown to enhance assay sensitivity at low dose-levels by enabling recognition of individual animals responding to the test chemical. These outliers are seen before the group mean MPE value has been increased enough to attain group statistical significance. It is concluded that careful consideration of test data, within the context of concurrent and historical control data, is sufficient to discern activity in the assay.
Morrison
V
V
Zeneca Central Toxicology Laboratory, Nr Macclesfield, Cheshire, UK.
Ashby
J
J
D019813:1,2-Dimethylhydrazine; D000818:Animals; D001853:Bone Marrow / Q000187:drug effects*; D002273:Carcinogens / Q000633:toxicity; D004127:Dimethylhydrazines / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D004912:Erythrocytes / Q000187:drug effects / Q000502:physiology; D008297:Male; D008452:Maximum Allowable Concentration; D051379:Mice; D008808:Mice, Inbred CBA; D015162:Micronucleus Tests / Q000379:methods*; D009153:Mutagens / Q000633:toxicity
D002273:Carcinogens; D004127:Dimethylhydrazines; D009153:Mutagens; D019813:1,2-Dimethylhydrazine