Subacute toxicity of alpha-ergocryptine in Sprague-Dawley rats. 1: general toxicological effects.
The dietary subacute toxicity of the ergot alkaloid alpha-ergocryptine was studied in Sprague-Dawley rats. Rats were fed 0, 4, 20, 100 or 500 mg ergocryptine/kg diet for 28-32 days (equal to 0, 0.36, 1.7, 8.9 and 60 mg ergocryptine/kg body weight/day for females and 0, 0.34, 1.4, 6.6 and 44 mg ergocryptine/kg body weight/day for males). The present study describes the general toxicological effects; the effects on metabolic and hormonal parameters will be reported separately. Body weight, body weight gain, food intake and food efficiency were all decreased with a U-shaped dose-response curve, as in both sexes the ranking severity of effects was in the order 100-20-500 and 4 mg/kg diet. Other changes with a U-shaped dose-response relationship included: hematological parameters (decreased MCV and MCH), serum enzyme activities (slightly increased/decreased ALAT, ASAT, GGT), increased serum urea concentrations, decreased glomular filtration (creatinine and urea clearances), decreased absolute organ weights, increased and decreased relative organ weights, atrophy of thymus and in females atrophy of ovary and uterus with in the mid-dose groups no detectable morphological features of an oestric cycle in the uterus. Other parameters, including increased relative liver, heart and ovarian weights and necrosis of the tail, were influenced in a dose-related manner or only in the high dose group. The U-shaped changes for the parameters mentioned above might be caused by the U-shaped dose-response relationship for food intake, which may be explained by the dopaminergic properties of alpha-ergocryptine. It is concluded that in rats fed ergocryptine for 28 days the dose-effect curve is rather steep and that the NOAEL is 4 mg/kg diet.
Janssen
G B
GB
Centre Substances and Risk Assessment, National Institute of Public Health and the Environment, PO Box 1, 3720 BA Bilthoven, The Netherlands.
Beems
R B
RB
Speijers
G J
GJ
van Egmond
H P
HP
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D019963:Clinical Chemistry Tests; D018491:Dopamine Agonists / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D004435:Eating / Q000187:drug effects; D004734:Energy Metabolism / Q000187:drug effects; D004873:Ergolines / Q000633:toxicity*; D004971:Estrus / Q000187:drug effects; D005260:Female; D008297:Male; D019055:No-Observed-Adverse-Effect Level; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D015430:Weight Gain / Q000187:drug effects
D018491:Dopamine Agonists; D004873:Ergolines; C100269:ergocryptine