Table XVIII

Summary of Reported Occurrences for the ICH Q3D Class 1 Metals (As, Cd, Hg, Pb) in Material Extracts

Type of Test	Concentration (mg/kg unless noted)	Extraction Conditions		Material and Sample Type	Ref.
Type of Test	Concentration (mg/kg unless noted)	Solvent	Conditions	Material and Sample Type	Ref.
Arsenic (As)
Extraction	0.55 ng/mL	Water	Glass syringe, 70 °C for 96 h	Mean result for multiple glass syringes	25
	0.01	pH 2.5	Sealed vessel, 121 °C for 1 h, 0.025 g/mL solvent	Plasticized PVC resin	35
	<0.01	pH 9.5	Sealed vessel, 121 °C for 1 h, 0.025 g/mL solvent	Plasticized PVC resin	35
	1–38 ng/mL	Ethanol	Filled portions of silicone tubing, 55 °C for 24 h	6 commercially available silicone materials	54
Cadmium (Cd): No reported values
Lead (Pb)
Extraction	NR^¹–4.1	Low pH (≈3)	Sealed vessel, 55 °C for 4 days, 0.1–1.0 g sample/mL solvent	5 glass materials tested; vials and parts	12
	NR–2.6	High pH (≈9)
	NR	Ethanol/water
	60 ng/mL	0.1% EDTA	Filled vials, 60 °C for 23 weeks	Type 1 clear glass vials	23
	20 ng/mL	Water
	40 ng/mL	pH 6.8 buffer
	40 ng/mL	0.1% EDTA	Filled vials, 60 °C for 23 weeks	Type 1 amber glass vials	23
	30 ng/mL	pH 6.8 buffer	Filled vials, 60 °C for 23 weeks	Type 1 amber glass vials	23
	20 ng/mL	0.1% EDTA	Filled vials, 60 °C for 23 weeks	Type 1 SiO₂-coated glass vial	23
	10 ng/mL	Water
	10 ng/mL	pH 6.8 buffer
	10 ng/mL	Water	Sealed vessel, 60 °C for 23 weeks, 0.25 cm²/mL solvent	Low-density polyethylene resin	23
	10 ng/mL	pH 6.8 buffer
	10 ng/mL	0.2% Polysorbate 80
	10 ng/mL	Water	Sealed vessel, 60 °C for 23 weeks, 0.25 cm²/mL solvent	High-density polyethylene resin	23
	30 ng/mL	pH 6.8 buffer
	30 ng/mL	0.2% Polysorbate 80
	1.6 mg/L	Aqueous buffers	Cut strips extracted at 60 °C for 10 days, 1 cm²/2 mL solvent	Plasticized PVC blood transfusion bag	16
	0.01	pH 2.5	Sealed vessel, 121 °C for 1 h, 0.025 g/mL solvent	Plasticized PVC resin	35
	<0.01	pH 9.5	Sealed vessel, 121 °C for 1 h, 0.025 g/mL solvent	Plasticized PVC resin	35
	1.4	pH 2.5	Various extraction methods, 0.02–0.04 g/mL solvent	Plasticized PVC resin	56
	30 ng/mL	0.1% EDTA	40 °C for 23 weeks, 10 mL solvent in 75 mL bottle	Polyethylene terephthalate bottle	23
Mercury (Hg): No reported values

Note:
↵1 NR = Not reported: not extracted in reportable quantities, generally less than 0.05 mg/L or 0.1 mg/kg.