Table F.1.
Reference points/health‐based guidance value for impurities potentially present in E 959
| Impurity/HBGV/RP (μg/kg bw) | Basis/reference |
|---|---|
| Arsenic (As)/0.3–8 (BMDL01) | The reference point is based on a range of benchmark dose lower confidence limit (BMDL01) values between 0.3 and 8 μg/kg bw per day identified for cancers of the lung, skin and bladder, as well as skin lesions. In general, the MOE should be at least 10,000 if the reference point is based on carcinogenicity in animal studies. However, as the BMDL for As is derived from human studies, an interspecies extrapolation factor (i.e. 10) is not needed (EFSA CONTAM Panel, 2009a; EFSA Scientific Committee, 2012) |
| Lead (Pb)/0.5 (BMDL01) | The reference point is based on a study demonstrating perturbation of intellectual development in children with the critical response size of 1 point reduction in IQ. The EFSA CONTAM Panel mentioned that a 1‐point reduction in IQ is related to a 4.5% increase in the risk of failure to graduate from high school and that a 1 point reduction in IQ in children can be associated with a decrease of later productivity of about 2%. A risk cannot be excluded if the exposure exceeds the BMDL01 (MOE lower than 1) (EFSA CONTAM Panel, 2010) |
| Cadmium (Cd)/2.5 (TWI) | The derivation of the reference point is based on a meta‐analysis to evaluate the dose–response relationship between selected urinary cadmium and urinary beta‐2‐microglobulin (B2M) as the biomarker of tubular damage recognised as the most useful biomarker in relation to tubular effects. A group‐based BMDL5 of 4 μg Cd/g creatinine for humans was derived. A chemical specific adjustment factor of 3.9 was applied to account for human variability in urinary cadmium within each dose subgroup in the analysis resulting in a reference point of 1.0 μg Cd per g creatinine. In order to remain below 1 μg Cd/g creatinine in urine in 95% of the population by age 50, the average daily dietary cadmium intake should not exceed 0.36 μg Cd/kg bw, corresponding to a weekly dietary intake of 2.5 μg Cd/kg bw (EFSA CONTAM Panel, 2009b) |
| Mercury (Hg)/4 (TWI) | The HBGV was set using kidney weight changes in male rats as the pivotal effect. Based on the BMDL10 of 0.06 mg/kg bw per day, expressed as mercury, and an uncertainty factor of 100 to account for inter and intra species differences, with conversion to a weekly basis and rounding to one significant figure, a TWI for inorganic mercury of 4 μg/kg bw, expressed as mercury was established (EFSA CONTAM Panel, 2012) |
| Palladium (Pd)/2 (PDE) | The PDE for oral exposure is based on a LOEL of 1.2 mg/kg bw per day in a lifetime study with mice taking into account 5 modifying factors and a human body weight of 50 kg (ICH, 2019) |
bw: body weight; RP: reference point; HBGV: health‐based guidance value; MOE: margin of exposure; TWI: tolerable weekly intake; PDE: permitted daily exposure.