Reproductive toxicity studies of ademetionine.
S-Adenosyl-L-methionine sulphate-p-toluene sulphonate (ademetionine, SAMe), a donor of methyl groups, was examined for effects upon embryofoetal toxicity following both premating treatment and treatment during pregnancy and for peri- and post-natal toxicity in the rat at dosages of 0, 100, 200 and 400 mg/kg/d SAMe ion by subcutaneous or intravenous administration. Embryofoetal toxicity was also examined in the New Zealand White rabbit at dosages of 0, 10, 20 and 40 mg/kg/d SAMe by intravenous administration. Treatment was considered to be without adverse effect upon any of the reproductive parameters examined on either F0 or on the untreated F1 generations. There was no indication that treatment adversely affected the litter parameters including the incidences of malformations, anomalies and skeletal variants. Some slight changes in the activity of the F1 females derived from F0 animals given 400 mg/kg/d were considered to be of minimal importance. In contrast to the above, adverse effects upon the parents were noted at 400 mg/kg/d including local tissue reaction at the injection sites and retardation of body weight gain. In the intravenous studies some rigidity and dyspnoea were noted following administration. Following subcutaneous premating treatment there was also evidence of histopathological change to the kidney of the female rat. Increased water consumption was noted in this latter study and amongst females rearing offspring in the embryo foetal toxicity study in which the compound was administered intravenously. At the lower dosages administered to the rat some local tissue reaction was evident as was some retardation of body weight gain, minimal at the lowest intravenous dose.(ABSTRACT TRUNCATED AT 250 WORDS)
Cozens
D D
DD
Huntingdon Research Centre Ltd., Cambridgeshire, England.
Barton
S J
SJ
Clark
R
R
Gibson
W A
WA
Hughes
E W
EW
Masters
R E
RE
Offer
J M
JM
Perkin
C J
CJ
Stramentinoli
G
G
D000014:Abnormalities, Drug-Induced; D000818:Animals; D001724:Birth Weight / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D004326:Drinking / Q000187:drug effects; D005260:Female; D005298:Fertility / Q000187:drug effects; D007275:Injections, Intravenous; D007279:Injections, Subcutaneous; D008098:Litter Size / Q000187:drug effects; D008297:Male; D009929:Organ Size / Q000187:drug effects; D011817:Rabbits; D051381:Rats; D012436:S-Adenosylmethionine / Q000008:administration & dosage / Q000633:toxicity*
D012436:S-Adenosylmethionine