|
| 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 |
|
| 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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