Table 4.

Reference points/health‐based guidance values for impurities and constituents potentially present in E 445

Impurity/constituent/HBGV/RP (ug/kg bw)	Basis/Reference
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 intelligence quotient (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).
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 per week, expressed as mercury was established. EFSA CONTAM Panel (2012)
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 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 (2009a)
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, i.e. an MOE of 1,000 would be sufficient. EFSA CONTAM Panel (2009b); EFSA Scientific Committee (2012a,b)

HBGV: health‐based guidance value; RP: reference point; BMDL₀₁: benchmark dose (lower confidence limit); TWI: tolerable weekly intake.