Metabolomics as read-across tool: A case study with phenoxy herbicides.

Area of Science:

• Toxicology
• Metabolomics
• Computational Chemistry

Background:

• Chemical risk assessment often relies on extensive animal testing.
• Read-across methodologies aim to reduce animal use by extrapolating data from similar substances.
• Metabolomics offers a biological perspective to support chemical grouping and read-across.

Purpose of the Study:

• To evaluate the utility of metabolomics in substantiating read-across for chemical safety assessment.
• To determine if metabolomics data can support waiving a 90-day toxicity study for MCPP.
• To identify suitable source substances for read-across to MCPP.

Main Methods:

• A virtual case study using MCPP as the target substance and MCPA and 2,4-DP as source substances.
• Metabolomics analysis of blood samples from 28-day toxicity studies.
• Comparison of metabolomic profiles to assess qualitative and quantitative similarity.
• Prediction of MCPP toxicity based on 90-day study data of the best-matched source substance (2,4-DP).

Main Results:

• Metabolomics indicated liver and kidneys as target organs for MCPP, MCPA, and 2,4-DP.
• 2,4-DP was identified as the most suitable source substance for read-across to MCPP.
• Predicted MCPP toxicity profile (reduced food consumption, body weight gain, liver/kidney effects, RBC changes) closely matched actual study findings.
• Predicted NOAEL for MCPP (150 ppm) was similar to the actual NOAEL (≤500 ppm) and NOEL (75 ppm).

Conclusions:

• Metabolomics data can effectively support chemical read-across by demonstrating biological similarity.
• The use of metabolomics and read-across can potentially waive the need for 90-day toxicity studies.
• This approach offers a more efficient and potentially animal-sparing alternative for substance safety evaluation.