SECTION 10.2: Chemical Stability

Overview

This subsection addresses the inherent stability of substances/mixtures under normal storage and handling conditions, identifying factors that may compromise chemical integrity. Chemical stability assessment is critical for determining safe storage lifetimes and appropriate containment strategies.

Key Stability Factors

Physical State Considerations:

  • Solid vs. liquid vs. gaseous forms (e.g., hygroscopic solids may destabilize)
  • Polymorphic transformations (e.g., metastable crystalline forms)
  • Phase separation in emulsions/suspensions

Environmental Influences

  • Temperature thresholds for decomposition (e.g., ≤40°C for peroxides)
  • Humidity sensitivity (e.g., deliquescent materials)
  • Light exposure (UV degradation pathways)
  • Oxygen presence (oxidative stability)

Stability Assessment Methods

Test Type Parameters Measured CLP Reference Standard
DSC/TGA Analysis Exothermic peaks, mass loss UN GHS Ch. 2.9
ARC (Adiabatic Calorimetry) Self-heating rates, SADT* determination OECD 54
Isothermal Storage Degradation products over time ECHA Ch. 2.9.3.3

*SADT: Self-Accelerating Decomposition Temperature

Stability Classifications

  1. Inherently Stable: No decomposition under 40°C for 48h (UN Test N.1)
  2. Marginally Stable: Requires stabilizers (e.g., hydroquinone in acrylic acid)
  3. Thermally Unstable: Decomposition onset <50°C (Category A self-reactives)

Stabilization Strategies

Common Stabilizers:

  • Radical Scavengers: BHT (Butylated hydroxytoluene) for monomers
  • pH Buffers: Citrate buffers for hydrolysis-prone compounds
  • Oxygen Scavengers: Ascorbic acid in oxygen-sensitive formulations
  • UV Absorbers: Benzophenones in light-sensitive products

Stability Monitoring Protocol

  1. Initial accelerated testing (40°C/75% RH for 6 months)
  2. Real-time stability studies (25°C/60% RH for 24 months)
  3. Periodic requalification (every 5 years or after formulation changes)

Example: Stabilized Ethylene Oxide

Stability Profile:

  • Decomposition Pathway: C₂H₄O → CH₄ + CO + H₂O (ΔH = −215 kJ mol)
  • Stabilization System: 0.1% water + nitrogen blanket
  • Critical Parameters: Storage ≤30°C, pressure ≤1.5 bar
Parameter Test Method Result CLP Classification
SADT ARC 35°C Self-reactive A
Hydrolytic Stability OECD 111 t₁/₂ = 8y @ pH7 Stable

Stability Documentation Requirements

Technical Dossier Elements:

  • Accelerated degradation kinetics (Arrhenius plots)
  • Compatibility matrices with packaging materials
  • Stabilizer depletion rates
  • Worst-case impurity profiles