note the rigidity and dyspnoea following intravaneous admin.
Reproductive toxicity studies of ademetionine.
Cozens DD, Barton SJ, Clark R, Gibson WA, Hughes EW, Masters RE, Offer JM,
Perkin CJ, Stramentinoli G
Huntingdon Research Centre Ltd., Cambridgeshire, England.
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