Table 2.

Summary of reproductive and developmental toxicity studies with melatonin. s.c.: subcutaneous. dw: drinking water.

	Dose	Period of administration	Results	Reference
Male Wistar rats	110 mcg s.c. Daily	Age 20–45 days	Reduced pituitary GnRH receptor content at 70 days of age	[150]
Pre-pubertal female Sprague–Dawley rats	110 mcg s.c. Daily	Age 20–70 days	Normal sexual maturation	[151]
Female Holzman rats	10 mcg/L in dw	Age 10–380 days	Delayed vaginal opening, no effect on oestrus cycle	[131]
Adult rats	4 mg/l in dw	12 weeks	No adverse effect on sexual behaviour	[152]
Sexually active male Wistar rats	10–100 mcg/kg intraperitoneally	Once before mating	No adverse effect on sexual behaviour	[153]
Embryonic in vitro studies in rat, mouse, and pig	10(-5) M to 10(-13) M for 48 or 72 h		No adverse effect on in vitro fertilisation and early embryonic development	[139,154,155]
Pregnant Sprague–Dawley rats	200 mcg/kg gavage	Gestational days 6–19	No toxic effect on embryo-foetal development	[139]
Pregnant rats	300 mcg/rat s.c.	Gestational days 8–21	No effect on litter size, live young birth weights and incidence of stillbirths	[155]