TABLE 10.
In vitro genotoxicity studies on TBBPA and TBBPA‐bDiBPrE published since the previous Opinion.
| Type of test experimental test system | Test substance | Exposure conditions | Result | Reference |
|---|---|---|---|---|
|
Reverse gene mutation assay (Ames test) S. Typhimurium TA98, TA100, TA1535, TA1537 and E. coli WP2 uvrA |
TBBPA Purity: NR Vehicle: NR |
± S9 mix −S9: tested up to 156 μg/plate, with TA1537, up to 625 μg/plate with TA1535, and over 2500 μg/plate with other strains +S9: tested up to 313 μg/plate with TA1537 and up to 5000 μg/plate with other strains Metabolic activation from liver S9 fraction from phenobarbital and 5,6‐benzoflavone‐induced rats Positive and negative controls: used |
Negative | Shibuya (2001 as described in NICNAS, 2020) |
|
Reverse gene mutation assay (Ames test) S. Typhimurium strains TA98, TA100, TA1535, TA1537 and TA1538 |
TBBPA Purity: NR Vehicle: DMSO |
± S9 mix Tested up to 500 μg/plate Metabolic activation with liver S9 fraction from Aroclor 1254‐induced rats Positive and negative controls: used |
Negative | Curren et al. (1981 as described in NICNAS, 2020) |
|
Reverse gene mutation assay (Ames test) S. Typhimurium TA98, TA100, TA1535 or TA1537 |
TBBPA Purity: 99% Vehicle: DMSO |
Preincubation method ± S9 mix 0, 100, 333, 1000, 3333 or 10,000 μg/plate Metabolic activation with S9 fraction from Aroclor 1254‐induced rat and hamster liver Positive and negative controls: used |
Negative | NTP (2014) |
|
Reverse gene mutation assay (Ames test) S. Typhimurium strains TA98 or TA100, or in E. coli strain WP2 uvrA/pKM101 |
TBBPA Purity: 99% Vehicle: DMSO |
Preincubation method ± S9 mix 0, 50, 100, 250, 500, 1000, 3000 or 6000 μg/plate Metabolic activation with S9 fraction from Aroclor 1254‐induced rat liver Positive and negative controls: used |
Negative | NTP (2014) |
|
Chromosomal aberration test Chinese hamster lung cells |
TBBPA Purity: NR Vehicle: DMSO |
± S9 mix Exposure: −S9: 6h expo. up to 6.5 μg/mL, 24h expo; up to 60 μg/mL +S9: 6h expo. up to 30 μg/mL Metabolic activation with liver S9 fraction from phenobarbital and 5,6‐benzoflavone‐induced rats Positive controls: MMC and CP |
Negative | Yamakage (2001, as described in NICNAS, 2020) |
|
Chromosomal aberration test Human peripheral lymphocytes |
TBBPA Purity: NR Vehicle: DMSO |
± S9 mix Exposure: −S9: 4‐h expo up to 100 μ/mL, 20‐h expo: up to 75 μg/mL +S9: 4‐h expo up to 50 μg/mL Harvesting: 20 h after initiation of treatment Metabolic activation with liver S9 fraction from Aroclor 1254‐induced rats Positive controls: MMC and CP |
Negative | Gudi (2001, as described in NICNAS, 2020) |
|
γH2AX Metabolically competent HepaRG cells |
TBBPA Purity: NR Vehicle: DMSO |
0, 2.5, 10 or 20 μM Measures using automated in situ detection of γH2AX positive cells after 1, 7 and 14 days Cytotoxicity: MTT assay |
Negative No cytotoxicity |
Quesnot et al. (2016) |
|
Comet assay (alkaline) Human acute monocytic leukaemia (THP‐1) |
TBBPA Purity: > 98% Vehicle: DMSO |
−S9 mix 0, 5, 20, 40, 60, 80 or 100 μg/mL Exposure: 1 h Positive control: no |
Positive at all concentrations Concentration related increase of % tail DNA |
Wang et al. (2020) |
|
Comet assay (alkaline) Human peripheral blood mononuclear cells |
TBBPA Purity: 99% Vehicle: DMSO |
−S9 mix 0, 0.01, 0.1, 1, 10 μg/mL Exposure: 24 h Positive control: H2O2 |
Positive Concentration‐related increases in SSB or DSB (as measured by the % DNA in the Comet tail) from 0.1 μg/mL Oxidative damage to DNA pyrimidines (at 0.1 and 1 μg/mL) or purines (from 0.01 μg/mL) using the enzymes endo III or hOGG1, respectively |
Barańska, Woźniak, et al. (2022) |
|
Comet assay (neutral) Human peripheral blood mononuclear cells |
TBBPA Purity: 99% Vehicle: DMSO |
−S9 mix 0, 0.01, 0.1, 1, 10 μg/mL Exposure: 24 h |
Positive Increases in DSB at 1 and 10 μg/mL |
Barańska, Woźniak, et al. (2022) |
|
Reverse gene mutation assay (Ames test) S. Typhimurium strains TA98, TA100 or TA102 |
TBBPA‐bDiBPrE Purity: 94% Vehicle: DMSO |
Preincubation method ± S9 mix 0, 100, 333, 1000, 3333, 10,000 μg/plate Metabolic activation: Aroclor 1254‐induced male Sprague–Dawley rat liver Positive and negative controls used |
Negative | NTP (2017) |
Abbreviations: CP, cyclophosphamide monohydrate; DMSO, dimethyl sulfoxide; DSB, double strand breaks; H2O2, hydrogen peroxide; MMC, cross‐linking agent mitomycin C; MTT, tetrazolium salt (3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide); NR, not reported; SSB, single strand break.