A New Approach Methodology (NAM) Based Assessment of Butylated hydroxytoluene (BHT) for Endocrine Disruption...

Area of Science:

• Toxicology
• Endocrinology
• Genomics

Background:

• Butylated hydroxytoluene (BHT) is a widely used synthetic antioxidant.
• Recent concerns, notably from ANSES, hypothesize BHT's role in endocrine disruption, citing rat studies on thyroid physiology.
• Proposed mechanisms include Cytochrome P450-mediated thyroid hormone catabolism and read-across arguments to butylated hydroxyanisole (BHA).

Purpose of the Study:

• To investigate the hypothesis that BHT acts as an endocrine disruptor.
• To evaluate BHT and its analogs using a Next Generation Risk Assessment (NGRA) approach.
• To determine if endocrine disruption is a relevant mode of action for BHT and similar chemicals.

Main Methods:

• Utilized a NGRA method involving four cell lines (A549, HCC1428, HepG2, MCF7) treated with BHT and analogs.
• Employed L1000 gene array platform for RNA analysis.
• Performed toxicogenomics-based assessment comparing BHT's genomic signature to a database and conducted a structure-activity relationship (SAR) analysis.

Main Results:

• BHT's genomic signature was compared against a database of known endocrine disruptors.
• Toxicogenomics-based SAR assessment evaluated BHT analogs using the P&G read-across framework.
• Neither BHT nor its analogs showed connections to compounds with endocrine activity related to estrogens, androgens, thyroid, or steroidogenesis.

Conclusions:

• The study found no evidence supporting the hypothesis that BHT is an endocrine disruptor.
• The NGRA and toxicogenomics-based SAR assessments did not link BHT or its analogs to endocrine disruption pathways.
• Results suggest that endocrine disruption is not a relevant mode of action for BHT and its structural analogs.