Risk characterisation of constituents present in jamu to promote its safe use

Figures & data

Table 1. Reported adulteration of jamu with APIs and associated hazards and health risks.

References	Associated hazards
Adulteration with phenylbutazone
EFSA/EMA (2013) and Lees and Toutain (2013)	Blood dyscrasias
Sperling (1969) and Faich (1987)	Nausea, vomiting, skin rash, oedema, stomatitis and peptic ulcer, haematological disturbances such as agranulocytosis, leukopoenia, anaemia, and thrombocytopenia
Giam et al. (1986)	Erythroderma with hepatitis, and Steven Johnson syndrome
Paul et al. (2005)	Agranulocytosis
Doshi et al. (2009)	Neutropenia and necrotising fasciitis
Adulteration with paracetamol/acetaminophen
James et al. (2003) and Ye et al. (2018)	Drug-induced liver injury (DILI)
Agrawal and Khazaeni (2020)	Skin reactions like Stevens-Johnson syndrome, toxic epidermal necrolysis, and acute generalised exanthematous pustulosis are the side effects of paracetamol which are extremely painful and can lead to blindness and death
Adulteration with piroxicam
Aronson (2016)	Gastrointestinal upset and a more serious side effect is the onset of peptic ulcers
Lipscomb et al. (1998) and Aronson (2016)	Headache, dizziness, drowsiness, fatigue, and sweating
Murray and Brater (1993)	Blurred vision, burning eyes, permanent sensorineural hearing loss, tinnitus, thrombocytopenia, leukopoenia, agranulocytosis, renal, and liver toxicity
Adulteration with methampyrone
Levy et al. (1995)	Vomiting and excreting red urine
Andrade et al. (1998)	Gastrointestinal disorders, such as somnolence, gastric discomfort and nausea, agranulocytosis, aplastic anaemia, anaphylaxis, and serious upper gastrointestinal complications
EMA (2018a)	Fetotoxicity because its metabolite can pass into breastmilk
Adulteration with mefenamic acid
McKillop and Canning (1987) and Kamour et al. 2017)	Central nervous system toxicity, especially convulsions, altered conscious level, agitation, aggression, confusion, or disorientation
Baker et al. (1984)	Interstitial nephritis and renal failure
Adulteration with prednisone
Ton et al. (2004) and Lim and Pranata (2020)	Steroid-dependence which can cause an acutely life-threatening condition in a sudden cessation
White (2019)	Adrenal crisis, resulting in vomiting, diarrhoea, flu-like illness, infective gastro-enteritis, and even death
Paul et al. (2016)	Bone loss, osteoporosis, Cushing syndrome, cataract, hypertension, dyslipidaemia, skin atrophy, failure to thrive, hypo-thalamo-pituitary-adrenal axis suppression, striae, glaucoma, and a predisposition to life-threatening infections
Adulteration with sibutramine hydrochloride
James et al. (2000) and de Simone and D'Addeo (2008)	Increase of systemic pressure and heart rate, which are symptoms associated with cardiovascular effects
Chong (2010)	Psychosis
Adulteration with sildenafil citrate
McMurray (2007)	Headache, dyspepsia, rhinitis, flushing, abnormal vision, and dizziness
Nissan et al. (2016)	Acute liver toxicity
Kloner (2007), Boden et al. (2012), and EMA (2016)	A risk for people using antihypertensives such as nitrates (e.g. nitroglycerine, doxazosin, and terazosin) and patients suffering from hypotension for whom use of PDE-5 inhibitors is contra-indicated
Adulteration with glibenclamide
EMA (2018b)	Abdominal pain, pain at the upper gastrointestinal tract, diarrhoea, vomiting, dyspepsia, gastroenteritis, and hypoglycaemia.
Ching et al. (2012) and Holt and Johnston (2019)	Lactic acidosis and heart failure

Figure 1. Risk characterisation of adulteration of jamu with APIs based on Δ values obtained by Equation (2)(2) $$\mathrm{\Delta }=\frac{(\mathrm{EDI}-\mathrm{RD})\mathrm{ }}{\mathrm{RD}}\mathrm{ }\times 100\mathrm{\%}$$(2) , using the EDIs and the existing reference doses (RD) (Supplemental material 1). The vertical dashed line represents the RD value of 0 as a threshold for risk evaluation. The inserted graph shows the Δ value for prednisone. Note that there is a different X axis.

Figure 2. Risk characterisation of jamu based on MOE values obtained for the consumption of the preparations based on daily lifetime exposure (grey bars) and 2 weeks a year during a lifetime (shaded bars). The vertical dashed line represents the MOE value of 10 000 as a threshold for risk management action (EFSA 2005).

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