Methyl methanesulphonate (MMS) as a resource conserving and reliable positive control agent for male rat and male mouse dominant lethal assays.
A single i.p. injection of methyl methanesulphonate (MMS; 40 mg/kg) to male rats, followed by their sequential mating over 4-28 days post-dosing, was shown to induce dominant lethal (DL) effects in two strains of rats and in four separate experiments. Activity was evident between 4 days post-dosing (sampling treated spermatozoa) and 28 days post-dosing (sampling treated early spermatids). The highest incidences of resorptions were seen between days 15 and 21 post-dosing, being approximately 1 week later than the peak of activity in the mouse. The DL effects seen were strong and could be detected as early as 4-10 days post-dosing, at which time only small reductions in pregnancy rates and total implantation numbers were seen. Similar, but weaker, mutagenic effects have been reported by Ehling et al. for MMS in mouse DL assays. These data indicate, therefore, that MMS provides a convenient positive control agent for both male rat and male mouse dominant lethal assays, requiring only approximately five treated males, each mated to two females at around 14 days post-dosing.
Ashby
J
J
Zeneca Central Toxicology Laboratory, Macclesfield, Cheshire, UK.
Lefevre
P A
PA
Elliott
B M
BM
Clapp
M J
MJ
D000818:Animals; D010064:Embryo Implantation / Q000187:drug effects*; D020964:Embryo Loss / Q000139:chemically induced*; D005260:Female; D008297:Male; D008741:Methyl Methanesulfonate / Q000633:toxicity*; D051379:Mice; D009152:Mutagenicity Tests; D009153:Mutagens / Q000633:toxicity*; D011247:Pregnancy; D018873:Pregnancy Rate; D051381:Rats; D012680:Sensitivity and Specificity; D013045:Species Specificity
D009153:Mutagens; D008741:Methyl Methanesulfonate