Neem products and by-products contain antinutritional and toxic factors. A comprehensive review of the literature on this aspect published up to 2003 has been written by Boeke et al., 2004.
Limonoids
Neem leaves and seeds contain limonoids (azadirachtin, salanin, nimbin, nimbidiol, etc.), which are triterpernoid compounds that are both bitter and toxic to many animal species.
Neem leaves and neem leaf extracts
Neem leaves contain large amounts of tannins (11%) and saponins (2.5%). In ruminants, condensed tannins and saponins may be used to improve rumen ecology (Suchitra et al., 2008), but they are detrimental in monogastric species. Neem leaves have been shown to be toxic in humans and many animal species. Traditional neem leaf-based medicines taken to treat febrile illness, abdominal upset or to induce abortion or infertility had been shown to have acute toxic effects in humans (Boeke et al., 2004). Acute toxicity followed by death was reported in a sheep that ate neem leaves (Ali et al., 1982). Subacute and semi-chronic effects on male reproduction have been reported in rats (Boeke et al., 2004). Leaves fed to poultry at 2-5% of the diet resulted in many histopathological changes (Ibrahim et al., 1992a).
Alcoholic extracts of neem leaves (obtained with solvents such as ethanol, methanol, etc.) have been found toxic in mice, rats and rabbits (Boeke et al., 2004). Aqueous extracts (obtained after soaking the plant into water) were reported to cause health problems in goats and guinea pigs at levels above 50 mg/kg BW. At higher doses, goats had tremors and ataxia with histopathological lesions (Ali, 1987). In chicks, the LD50 for aqueous extracts was 4800 mg/kg BW (Biu et al., 2010).
Neem oil
Though neem oil is widely used in traditional pharmacopoeia, several cases of morbidity and mortality have been reported in humans. Ingestion of neem oil has been associated with toxic encephalopathy, Reye's syndrome and metabolic acidosis (Jindal et al., 2012; Sundaravalli et al., 1982). Many studies have observed acute and subacute toxicity of neem oil in rats, mice and rabbits. Doses of 14 and 24 mL/kg BW for rats and rabbits, respectively, resulted in acute toxicity, though one long-term study on rats fed 10% neem oil over 3 generations found the oil safe (Boeke et al., 2004). Processed oil (hydrogenated, treated with KOH, solvent extracted) might be safer (Reddy et al., 1988 cited by Puri, 1999; Rukmini, 1987).
Neem seeds and fruits
Chicks fed on neem fruits were reported to suffer from hepato-nephropathy (Ibrahim et al., 1992b). Seed extracts have been reported toxic in rats (Boeke et al., 2004).