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Nadira De Abrew, K. ; Natoli, Ted ; Lester, Cathy C. , et al. Toxicol. Sci.,2022,190(2):227-241. DOI: 10.1093/toxsci/kfac099 PubMed ID: 36161505
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Abstract: Butylated hydroxytoluene (BHT) is a synthetic antioxidant widely used in many industrial sectors. BHT is a well-studied compound for which there are many favorable regulatory decisions. However, a recent opinion by the French Agency for Food, Environmental and Occupational Health and Safety (ANSES) hypothesizes a role for BHT in endocrine disruption ANSES (2021). This opinion is based on observations in mostly rat studies where changes to thyroid physiol. are observed Enzymic induction of Cytochrome P 450-mediated thyroid hormone catabolism has been proposed as a mechanism for these observations, however, a causal relationship has not been proven. Other evidence proposed in the document includes a read across argument to butylated hydroxyanisole (BHA), another Community Rolling Action Plan (CoRAP)-listed substance with endocrine disruption concerns. We tested the hypothesis that BHT is an endocrine disruptor by using a Next Generation Risk Assessment (NGRA) method. Four different cell lines: A549, HCC1428, HepG2, and MCF7 were treated with BHT and a series of BHT analogs at 5 different concentrations, RNA was isolated from cell extracts and run on the L1000 gene array platform. A toxicogenomics-based assessment was performed by comparing BHT′s unique genomic signature to a large external database containing signatures of other compounds (including many known endocrine disruptors) to identify if any endocrine disruption-related modes of action (MoAs) are prevalent among BHT and other compounds with similar genomic signatures. In addition, we performed a toxicogenomics-based structure activity relationship (SAR) assessment of BHT and a series of structurally similar analogs to understand if endocrine disruption is a relevant MoA for chems. that are considered suitable analogs to BHT using the P&G read across framework (Wu et al., 2010). Neither BHT nor any of its analogs connected to compounds that had endocrine activity for estrogens, androgens, thyroid, or steroidogenesis.
Keywords: estrogen, androgen, or thyroid hormone receptors, or proteins integral to steroidogenesis (EATS) ; connectivity mapping ; toxicogenomics ; read across ; New Approach Methodologies (NAM) ; Next Generation Risk Assessment (NGRA) ...More
CAS No. : | 6386-38-5 | MDL No. : | MFCD00210461 |
Formula : | C18H28O3 | Boiling Point : | - |
Linear Structure Formula : | HOC6H2(C(CH3)3)2C2H4CO2CH3 | InChI Key : | PXMJCECEFTYEKE-UHFFFAOYSA-N |
M.W : | 292.41 | Pubchem ID : | 62603 |
Synonyms : |
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Signal Word: | Warning | Class: | N/A |
Precautionary Statements: | P261-P305+P351+P338 | UN#: | N/A |
Hazard Statements: | H302-H315-H319-H335 | Packing Group: | N/A |
GHS Pictogram: |
* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.
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