Plastic extractables and leachables (E&L) analysis is a critical chemical safety evaluation used to identify and quantify substances that migrate from plastic materials into food, pharmaceuticals, medical devices, and consumer products. This technical article outlines the analytical framework, sample types, target analytes, testing methodologies, and international standards—including ISO 10993, EU Regulation 10/2011, and the GB 4806 series—commonly applied by accredited third-party laboratories for regulatory compliance and toxicological risk assessment.
Technical Overview
Plastic extractables and leachables analysis refers to the systematic chemical characterization of substances that can be released from polymeric materials under controlled laboratory extraction or real-world service conditions. Extractables are compounds that can be drawn out of a plastic using aggressive solvents, elevated temperatures, or extended contact times, representing the worst-case chemical profile of the material. Leachables are the subset of those compounds that actually migrate into the contacted product—such as a food item, drug formulation, or biological fluid—under normal conditions of storage and use.
The discipline has become central to regulatory compliance across multiple industries. For food contact materials, EU Regulation (EU) No 10/2011, the GB 4806 series in China, and FDA 21 CFR 170–190 in the United States establish overall and specific migration limits for plastics. For medical devices and pharmaceutical packaging, ISO 10993-18 governs the chemical characterization of materials as part of the overall biological evaluation described in ISO 10993-1, while ISO 10993-17 provides the framework for toxicological risk assessment of leachables. Toy safety standards such as EN 71-3 and ISO 8124-3 address the migration of certain elements from plastic components.
Modern E&L studies follow a risk-based, tiered strategy: initial extraction and broad screening, structural identification of detected compounds, accurate quantification against reference standards, and finally toxicological evaluation against safety thresholds such as the Safety Concern Threshold (SCT) of 0.15 µg/day or compound-specific derived allowable limits. This approach ensures that analytical effort is proportionate to actual patient, consumer, and regulatory exposure risk.
Testing Samples
Food Contact Materials and Packaging
This category includes plastic films and laminates, rigid and semi-rigid containers, PET bottles, closures, cap liners and gaskets, sealing films, straws, disposable tableware, kitchen utensils, and food processing equipment such as tubing, conveyor belting, and pump components. Multilayer structures with printing inks, adhesives, and coatings are also evaluated because secondary components frequently contribute significant extractable burden.
Medical Devices and Pharmaceutical Packaging
Representative samples include syringes, needles and hubs, IV infusion bags and administration sets, catheters, dialysis cartridges and tubing, respiratory circuit components, inhalation device parts, prefilled syringe barrels and stoppers, blister films, vials, and closures. Patient-contact duration (limited, prolonged, or permanent per ISO 10993-1) and contact route (blood, tissue, mucosal, indirect) determine the required depth of characterization.
Consumer and Industrial Products
Toys and childcare articles such as teethers, baby bottles, and pacifier shields; cosmetics and personal-care packaging; household storage containers; and water-contact articles are commonly submitted for migration testing against EN 71-3, ISO 8124-3, GB 4806 series, and applicable Japanese food sanitation specifications.
Testing Items
Depending on the regulatory framework and intended use, E&L studies typically cover the following analyte groups:
- Overall migration and total extractables: total mass of non-volatile substances transferred into food simulants or solvents, gravimetrically determined against limits such as the 10 mg/dm² OML defined in EU 10/2011 and GB 4806.7.
- Residual monomers and starting substances: vinyl chloride, styrene, acrylonitrile, 1,3-butadiene, vinylidene chloride, bisphenol A, caprolactam, melamine, formaldehyde, terephthalic acid, ethylene glycol, and antimony residues from polycondensation catalysts.
- Plasticizers: regulated phthalates (DEHP, DBP, BBP, DINP, DIDP, DNOP) together with replacement plasticizers such as DINCH, acetyl tributyl citrate (ATBC), and adipate esters.
- Antioxidants and stabilizers: hindered phenolic antioxidants, phosphite processing stabilizers, thioester synergists, hindered amine light stabilizers (HALS), and benzophenone- or benzotriazole-type UV absorbers.
- Primary aromatic amines (PAAs): migration products of polyurethane adhesives and isocyanate-cured systems, tightly restricted in food contact and pharma applications.
- Elemental impurities: lead, cadmium, mercury, hexavalent chromium, antimony, arsenic, barium, cobalt, copper, iron, lithium, manganese, nickel, and zinc, consistent with element-specific migration limits in EU 10/2011.
- Volatile and semi-volatile organic compounds: residual solvents, oligomers, degradation products, aldehydes, ketones, and slip agents such as oleamide and erucamide.
Testing Methods
Extraction and Migration Study Design
Test design begins with the selection of simulants and conditions that reflect the intended contact scenario. Food-contact studies use aqueous, acidic (3% acetic acid), alcoholic (10–50% ethanol, 95% ethanol, or isooctane), and fatty oil simulants, with time–temperature combinations defined by EU 10/2011 and the GB 31604.1 / GB 5009.156 methodological standards. Medical device extractions follow ISO 10993-12, employing polar (water, saline), non-polar, and mixed media at standardized ratios and conditions such as 37 °C for 72 hours, 50 °C for 72 hours, 70 °C for 24 hours, or 121 °C for 1 hour, scaled to clinical exposure. Exaggerated extraction (Soxhlet, reflux, accelerated solvent extraction) is reserved for extractables profiling when a worst-case material inventory is required.
Chromatographic and Spectrometric Techniques
Volatile compounds are screened by headspace GC-MS and direct-injection GC-MS, while semi-volatiles are analyzed by GC-MS, often with derivatization for polar species. Thermally labile and non-volatile targets—bisphenol A, phenolic antioxidants, aromatic amines, and dye-related species—are quantified by HPLC and LC-MS/MS. Unknown compound identification applies library mass-spectral matching, accurate-mass QTOF or Orbitrap analysis, and FTIR, followed by confirmation with authentic reference standards. Semi-quantitation using surrogate standards is applied where standards do not exist, and results are interpreted against an Analytical Evaluation Threshold (AET) derived from the Safety Concern Threshold and the dosing or exposure parameters of the product.
Elemental and Residual Analysis
Metals are quantified by ICP-MS, ICP-OES, or atomic absorption spectrometry after microwave acid digestion of the material or direct analysis of the migration solution. Non-volatile residue (NVR) is determined gravimetrically, total organic carbon (TOC) analyzers quantify water-soluble extractables, and ion chromatography addresses inorganic anions and cations. ExtractpH, acidity/alkalinity, and ultraviolet absorbance of extracts provide additional screening data required by certain pharmacopoeial and device-sector specifications.
Applications
- Regulatory compliance and market access: demonstrating conformity with EU 10/2011, FDA food contact notifications, GB 4806/GB 31604 series, EN 71-3, and ISO 8124-3 for products exported to major markets.
- Biological evaluation support: generating the chemical characterization data required by ISO 10993-18 and the toxicological risk assessment per ISO 10993-17 as part of medical device biocompatibility files.
- Material qualification and change control: comparing candidate polymers, additives, or suppliers before production release and verifying equivalence after formulation or process changes.
- Pharmaceutical packaging safety: E&L studies supporting drug product stability programs, container closure qualification, and submission-ready safety assessments.
- Failure and contamination investigation: diagnosing odor issues, discoloration, visible particulates, and unexpected migrant findings through targeted and non-targeted analysis.
FAQ
What is the difference between extractables and leachables?
Extractables are compounds released from a plastic under exaggerated laboratory conditions—strong solvents, high temperature, or long duration—and represent the complete potential chemical inventory. Leachables are the compounds that actually migrate into the finished product under normal storage and use conditions and are therefore the direct basis for exposure and safety assessment.
How long does a typical E&L study take?
Targeted migration testing against established limits generally takes two to six weeks, whereas a full extractables profiling and leachables confirmation study with unknown identification, method validation, and toxicological interpretation may require three to six months depending on sample complexity and regulatory scope.
How are unknown compounds handled when no reference standard exists?
Unknowns are first identified using mass spectral libraries and accurate-mass analysis, then semi-quantified using structurally related surrogate standards with conservative response-factor assumptions. Confirmation with authentic standards is performed only for compounds exceeding the analytical evaluation threshold, focusing resources on toxicologically relevant findings.
What are the most common acceptance criteria?
For food contact plastics, the overall migration limit of 10 mg/dm² (or 60 mg/kg) and substance-specific migration limits in EU 10/2011 and GB 4806.7 govern acceptance. For medical and pharma applications, results are compared against ISO 10993-17-derived allowable limits or the 0.15 µg/day safety concern threshold, combined with element-specific limits for heavy metals.
Which sample information should be provided before testing?
Accredited third-party laboratories require the full formulation disclosure where available, including polymer type, additives, colorants, adhesives, and coatings, together with intended use conditions: contact medium, contact ratio, maximum temperature, contact duration, and target markets, since these parameters define the extraction design and applicable regulatory limits.
