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Author, year [ref.] | Animal model (species; gender) | Intervention details (formulation; dose; frequency; duration; quantitative analysis of content) | Comparator | Quantitation of toxic/safe dose | Description of toxicity findings |
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Akinloye, 2010 [53] | Rat (Wistar; Male) | Air-dried C. papaya leaf decoction; 500 mg/kg; Daily; 21 days; NS | 0.9% sodium chloride | NA | (i) Male reproductive toxicity |
Omonkhua, 2011 [54] | Rabbits (New Zealand; NS) | C. papaya leaf aqueous extract; 200 mg/kg; Daily; 24 weeks; NS | Water | NA | (i) Transient elevation of liver enzymes (ALP, GGT, and bilirubin) at initial periods of treatment (3 to 5 weeks); (ii) Risk of bile duct obstruction |
Halim, 2011 [55] | Rat (Sprague Dawley; female) | Freeze-dried C. papaya leaf aqueous extract; 5, 50, 300, and 2000 mg/kg; Once; Single dose; NS | Water | NS | (i) No mortality and acute adverse events at all doses; (ii) Raised HGB, HCT, RBC, TG, and total protein levels at 2000 mg/kg; (iii) No relative organ weight and gross histopathology changes |
Afzan, 2012 [56] | Rat (Sprague Dawley; male and female) | Lypohilised fresh C. papaya leaf juice; 10, 140, and 2000 mg/kg; Daily; 28 days; NS | Water | NS | (i) No mortality and acute adverse events at all doses; (ii) No abnormalities in serum haematology; (iii) Raised ALT and ALP levels at 10 mg/kg and 140 mg/kg (male and female); (iv) Raised total protein, AST, and HDL at 140 mg/kg (female); (v) No relative organ weight and histopathology changes |
Ismail, 2014 [57] | Rat (Sprague Dawley; male and female) | Freeze-dried fresh C. papaya leaf juice; 10, 140, and 2000 mg/kg; 13 weeks; NS | Water | NOAEL = 2000 mg/kg (male and female) | (i) No mortality and acute adverse events, no changes in body weight and food and water intake at all doses; (ii) No abnormalities in serum haematology; (iii) Raised LDH at 2000 mg/kg (male); (iv) Raised albumin at 140 mg/kg (male); (v) Raised protein and albumin at 140 and 2000 mg/kg (female); (vi) Reduced creatinine at 2000 mg/kg (male and female); (vii) No relative organ weight and histopathology changes |
Ansah, 2015 [58] | Rat (Sprague Dawley; male and female) | Air-dried C. papaya leaf decoction; Acute: 100–5000 mg/kg; Once; Single dose; NS Subacute: 10–500 mg/kg; Once daily; 2 weeks; NS Reproductive: 10–500 mg/kg; 10–500 mg/kg; Once daily; 2 weeks (male), throughout the gestation period (female, duration NS); NS | Distilled water | LD50 > 2000 mg/kg | (i) No mortality and acute adverse events; (ii) No abnormalities in serum haematology; (iii) Hepatotoxicity: abnormalities in liver enzymes and histology (subacute, male and female); (iv) Male and female reproductive toxicity |
Nghonjuyi, 2016 [59] | Chicks (Kabir; male and female) | Air-dried C. papaya leaf 70% hydroethanolic extract; Acute: 40–5120 mg/kg; Once; Single-dose; NS Subchronic: 0–640 mg/kg; Once daily; 6 weeks; NS | Distilled water | LD50 > 5120 mg/kg | (i) No mortality and acute adverse events, no changes in body weight, food, and water intake at all doses; (ii) Transient raised WCC at 640 mg/kg (male, subchronic); (iii) No abnormalities in serum biochemistry |
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