Table 1.
Summary of toxicity studies with melatonin. SD: single Dose. LT: long-term administration. GT: genotoxicity. CG: carcinogenicity. O: other toxicity studies. i.p.: intraperitoneally, s.c. subcutaneously, i.v. intravenously. dw: drinking water.
| Study type | Animal | Route | Duration | Results | Reference |
|---|---|---|---|---|---|
| SD | Rats in vivo | Orally, i.p.,s.c., i.v. | Once-only | At doses >400 mg/kg: vasodilatation, piloerection, ptosis, impairment of righting reflex, lack of motor activity, decrease in body temperature and respiratory problems preceding death | [109] |
| LT | Aged rats and mice in vivo | 10 mg/L in dw | 16 months | Improved health and survival of aged rats and mice | [111,112] |
| LT | Diabetic mice and hypercholestaemia-susceptible rats in vivo | s.c or in dw | Enhanced survival | [114,115] | |
| GT | In vitro non-mammalian cell system | No mutagenicity in bacterial strains. | [113,[116], [117], [118]] | ||
| GT | In vitro mammalian cell system | No chromosome aberrations and no clastogenic activity. Protective anti-clastogenic activity. Nop DNA strand breaks. | [113,117,119] | ||
| GT | In vivo cell system | 5 mg/kg s.c. | Not mutagenic in mouse bone marrow cells; reduced chromosome aberration rates. Not mutagenic in mice sperm head anomaly test; reduced sperm head anomaly rates. |
[120] | |
| GT | In vivo cell system | 10 mg/kg i.p. | No adverse effects on rat peripheral blood micronucleus test. | [121] | |
| GT | In vivo study in rats or mice | 4–10 mg/kg i.p. | Protective effects against genotoxic action of potassium dichromate, cobalt, ethanol, paraquat | [[122], [123], [124], [125]] | |
| GT | In vitro study using human lymphocytes | 0.2 mM | Anti-genotoxic effect on mercuric chloride and gossypol | [110,126] | |
| CG | Transgenic mice at increased risk for prostate adenocarcinoma | 10–20 mcg/L in dw | 18 weeks | Strong prostate cancer inhibitory effect | [127] |
| CG | Transgenic mice susceptible for mammary tumours | 50–200 mcg/kg per day via gavage | 30 weeks | Reduced incidence and growth rate of mammary tumours | [128,144] |
| CG | Rats, mice susceptible for breast cancer | 10–20 mcg/L in dw | >1 yr | No induction of uterine tumours, lower incidence of mammary tumours. | [129,130] |