Biotransformation of bisphenol A analogues by the biphenyl-degrading bacterium Cupriavidusbasilensis - a structure-biotransformation relationship.

Comparative analyses determined the relationship between the structure of bisphenol A (BPA) as well as of seven bisphenol analogues (bisphenol B (BPB), bisphenol C (BPC), bisphenol E (BPE), bisphenol F (BPF), bisphenol Z (BPZ), bisphenol AP (BPAP), bisphenol PH (BPPH)) and their biotransformability by the biphenyl-degrading bacterium Cupriavidus basilensis SBUG 290. All bisphenols were substrates for bacterial transformation with conversion rates ranging from 6 to 98% within 216 h and 36 different metabolites were characterized. Transformation by biphenyl-grown cells comprised four different pathways: (a) formation of ortho-hydroxylated bisphenols, hydroxylating either one or both phenols of the compounds; (b) ring fission; (c) transamination followed by acetylation or dimerization; and (d) oxidation of ring substituents, such as methyl groups and aromatic ring systems, present on the 3-position. However, the microbial attack of bisphenols by C. basilensis was limited to the phenol rings and its substituents, while substituents on the carbon bridge connecting the rings were not oxidized. All bisphenol analogues with modifications at the carbon bridge could be oxidized up to ring cleavage, while substituents at the 3-position of the phenol ring other than hydroxyl groups did not allow this reaction. Replacing one methyl group at the carbon bridge of BPA by a hydrophobic aromatic or alicyclic ring system inhibited both dimerization and transamination followed by acetylation. While most of the bisphenol analogues exhibited estrogenic activity, four biotransformation products tested were not estrogenically active.

Effects of storage temperature and duration on release of antimony and bisphenol A from polyethylene terephthalate drinking water bottles of China.

We investigated effects of storage temperature and duration on release of antimony (Sb) and bisphenol A (BPA) from 16 brands of polyethylene terephthalate (PET) drinking water bottles in China. After 1-week storage, Sb release increased from 1.88-8.32 ng/L at 4 °C, to 2.10-18.4 ng/L at 25 °C and to 20.3-2604 ng/L at 70 °C. The corresponding releases for BPA were less at 0.26-18.7, 0.62-22.6, and 2.89-38.9 ng/L. Both Sb and BPA release increased with storage duration up to 4-week, but their releasing rates decreased with storage time, indicating that Sb and BPA release from PET bottles may become stable under long term storage. Human health risk was evaluated based on the worst case, i.e., storage at 70 °C for 4-week. Chronic daily intake (CDI) caused by BPA release was below USEPA regulation, Sb release in one brand exceeded USEPA regulated CDI (400 ng/kg bw/d) with values of 409 and 1430 ng/kg bw/d for adult and children.

Mutagenicity and DNA damage of bisphenol A and its structural analogues in HepG2 cells.

Environmental oestrogen bisphenol A (BPA) and its analogues are widespread in our living environment. Because their production and use are increasing, exposure of humans to bisphenols is becoming a significant issue. We evaluated the mutagenic and genotoxic potential of eight BPA structural analogues (BPF, BPAF, BPZ, BPS, DMBPA, DMBPS, BP-1, and BP-2) using the Ames and comet assay, respectively. None of the tested bisphenols showed a mutagenic effect in Salmonella typhimurium strains TA98 and TA100 in either the presence or absence of external S9-mediated metabolic activation (Aroclor 1254-induced male rat liver). Potential genotoxicity of bisphenols was determined in the human hepatoma cell line (HepG2) at non-cytotoxic concentrations (0.1 µmol L(-1) to 10 µmol L(-1)) after 4-hour and 24-hour exposure. In the comet assay, BPA and its analogue BPS induced significant DNA damage only after the 24-hour exposure, while analogues DMBPS, BP-1, and BP-2 induced a transient increase in DNA strand breaks.

Enhanced OECD TG 407 in detection of endocrine-mediated effects of 4,4'-(octahydro-4,7-methano-5H-inden-5-ylidene)bisphenol.

The purpose of this study was to investigate whether the estrogenic effects were detected in the enhanced TG 407 if the estrogenic property was not so strong in the uterotrophic assay. The estrogenic property of 4,4'-(octahydro-4,7-methano-5H-inden-5-ylidene)bisphenol in the uterotrophic assay was slightly stronger than that of genistein or nonylphenol, but weaker than that of ethinyl estradiol. We performed a 28-day repeated-dose toxicity study (enhanced OECD test guideline No. 407) on 4,4'-(octahydro-4,7-methano-5H-inden-5-ylidene)bisphenol based on the OECD draft protocol. The test chemical, administered orally at doses of 0, 10, 50, and 250 mg/kg per day for at least 28 days, caused such estrogenic effects as abnormal estrous cycle, increased ovarian follicles, increased uterine epithelial height, and vaginal mucification in the 50 and/or 250 mg/kg groups. Moreover, follicular epithelial cell hyperplasia of the thyroid was detected in all male rats given the test chemical and in female rats in the 250 mg/kg group. It was concluded that the estrogenic effects were detected in growing rats given 4,4'-(octahydro-4,7-methano-5H-inden-5-ylidene)bisphenol, and thyroid dysfunction was also observed as the endocrine-mediated effects.