Examples of MAK values and carcinogenicity classification for mixtures

Area of Science:

• Occupational Health and Safety
• Toxicology
• Chemical Risk Assessment

Background:

• The German Commission for the Investigation of Health Hazards of Chemical Compounds in the Work Area (MAK Commission) primarily establishes MAK values for pure chemical substances.
• MAK values for chemical mixtures are determined only after thorough toxicological evaluation of the specific mixture.
• Exceptions for common MAK values for mixtures include isomer groups (e.g., xylenes) or related compounds (e.g., Kathon) with similar toxicological profiles.

Purpose of the Study:

• To outline the principles and practices of the MAK Commission regarding the establishment of MAK values for chemical mixtures.
• To differentiate the approaches for setting MAK values for mixtures with comparable versus differing toxicological potentials among components.
• To address the challenges in setting safe exposure thresholds for mixtures containing genotoxic and carcinogenic substances.

Main Methods:

• Review of established MAK value setting procedures for single substances and mixtures.
• Analysis of criteria for establishing common MAK values for isomer mixtures and related compounds.
• Examination of categorization strategies for mixtures with genotoxic and carcinogenic components.

Main Results:

• MAK values are generally set for single substances, with mixture evaluations being specific.
• Common MAK values are established for mixtures with comparable toxicological effects (e.g., isomers, related compounds).
• Mixtures with differing isomer toxicities typically receive individual MAK values, with exceptions like hexachlorocyclohexane.
• Mixtures containing genotoxic/carcinogenic substances lack safe thresholds and are categorized by proven carcinogenicity or included carcinogens.

Conclusions:

• The MAK Commission employs a substance-specific approach to toxicological risk assessment.
• Setting MAK values for mixtures necessitates careful consideration of component toxicities and interactions.
• Mixtures with genotoxic or carcinogenic potential require distinct risk management strategies beyond simple threshold setting.