A review of properties, production, human exposure, biomonitoring, toxicity, and regulation of bisphenol A diglycidyl ethers and novolac glycidyl ethers

Although numerous studies have investigated environmental occurrence, human exposure, and toxic effects of bisphenol analogues including bisphenol A (BPA), little is known about closely related chemical classes namely, bisphenol A diglycidyl ethers (BADGEs) and novolac glycidyl ethers (NOGEs), which are widely used in a variety of industrial and consumer products. In this review, we compiled available information on production and usage, analytical challenges, dietary and non-dietary sources of exposure, occurrence in human and environmental matrices, toxicity, and regulations on BADGEs and NOGEs. Human exposure to BADGEs and NOGEs is widespread, with exposure doses in the range of several hundreds of nanograms (ng) to few micrograms (μg) per kilogram (kg) body weight (bw) per day (d) from diet and <10 ng/kg bw/d from inhalation of indoor air and indoor dust ingestion. Canned foods and beverages contain BADGEs and NOGEs at concentrations on the order of several tens to hundreds of nanogram (ng) per g and in some cases up to several thousand ng per g. The highest reported concentration of BADGEs thus far was in canned fish at 12.6 mg/kg. In indoor dust samples, a BADGE concentration of up to 63.2 mg/kg was reported. Among five derivatives of BADGEs analyzed in several studies, BADGE·2H₂O and BADGE·HCl·H₂O were predominant in indoor dust and environmental samples. In human adipose tissue, a concentration of up to 4500 ng/g bisphenol F diglycidyl ether (BFDGE), a building block of NOGE, was reported. The epoxide moieties of BADGEs and NOGEs impart high reactivity of these chemicals, which exhibit toxicity through endocrine disruption, reproductive effects and genotoxicity. Formation of adducts/conjugates and reaction products of BADGEs with DNA and protein was reported, although little is known about the magnitude of their occurrence and toxicity. Regulatory framework for these chemicals is mainly focused on migration limits in canned foods. Despite their high production and widespread usage, studies on environmental transport, toxicity and fate are still limited and further studies should focus on adducts/biotransformation products, toxicological mechanisms, as well as ecological and human health risks of BADGEs and NOGEs.