Inhalation TTC values: A new integrative grouping approach considering structural, toxicological and mechanistic...

Area of Science:

• Toxicology
• Chemical Risk Assessment
• Inhalation Exposure

Background:

• Establishing reliable threshold values for chemical inhalation exposure is crucial for risk assessment.
• Existing classification schemes may not fully capture toxicological potency differences.
• The Threshold of Toxicological Concern (TTC) concept requires robust data for various exposure routes.

Purpose of the Study:

• To develop an integrative grouping concept for deriving threshold values for inhalation exposure.
• To classify organic compounds into toxic (T-group) and low toxic (L-group) categories based on toxicological potency.
• To refine the TTC concept for inhalation exposure using a comprehensive dataset.

Main Methods:

• Utilized the TTC RepDose dataset comprising 296 organic compounds and 608 repeated-dose inhalation studies.
• Identified and refined 21 structural features (SFs) associated with NOEC values.
• Grouped compounds into 28 distinct categories (19 T-groups, 9 L-groups) considering potency, structure, and toxicological data.

Main Results:

• Developed a classification scheme with 19 toxic (T-group) and 9 low toxic (L-group) categories.
• Derived distinct threshold values for T-groups (2 × 10⁻⁵ ppm) and L-groups (0.05 ppm).
• Compared the new classification and thresholds with existing structure-driven groupings and Cramer classification.

Conclusions:

• The proposed integrative grouping concept provides a refined approach for setting inhalation exposure thresholds.
• The derived thresholds offer valuable data for chemical safety assessments and regulatory applications.
• This classification scheme enhances the application of the TTC concept for inhalation exposure scenarios.