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• W2790493049 abstract "Abstract A no‐significant‐risk‐level of 20 mg day –1 was derived for tetrabromobisphenol A (TBBPA). Uterine tumors (adenomas, adenocarcinomas, and malignant mixed Müllerian) observed in female Wistar Han rats from a National Toxicology Program 2‐year cancer bioassay were identified as the critical effect. Studies suggest that TBBPA is acting through a non‐mutagenic mode of action. Thus, the most appropriate approach to derivation of a cancer risk value based on US Environmental Protection Agency guidelines is a threshold approach, akin to a cancer safe dose (RfD cancer ). Using the National Toxicology Program data, we utilized Benchmark dose software to derive a benchmark dose lower limit (BMDL 10 ) as the point of departure (POD) of 103 mg kg –1 day –1 . The POD was adjusted to a human equivalent dose of 25.6 mg kg –1 day –1 using allometric scaling. We applied a composite adjustment factor of 100 to the POD to derive an RfD cancer of 0.26 mg kg –1 day –1 . Based on a human body weight of 70 kg, the RfD cancer was adjusted to a no‐significant‐risk‐level of 20 mg day –1 . This was compared to other available non‐cancer and cancer risk values, and aligns well with our understanding of the underlying biology based on the toxicology data. Overall, the weight of evidence from animal studies indicates that TBBPA has low toxicity and suggests that high doses over long exposure durations are needed to induce uterine tumor formation. Future research needs include a thorough and detailed vetting of the proposed adverse outcome pathway, including further support for key events leading to uterine tumor formation and a quantitative weight of evidence analysis." @default.
• W2790493049 created "2018-03-29" @default.
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• W2790493049 date "2018-02-13" @default.
• W2790493049 modified "2023-09-26" @default.
• W2790493049 title "Derivation of a no‐significant‐risk‐level for tetrabromobisphenol A based on a threshold non‐mutagenic cancer mode of action" @default.
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• W2790493049 doi "https://doi.org/10.1002/jat.3594" @default.
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