Review of the toxicology, human exposure and safety assessment for bisphenol A diglycidylether (BADGE)

Abstract

BADGE (whose chemical names are bisphenol A diglycidylether and 2,2-bis(4-(2,3-epoxypropyl)phenyl)propane) is the lowest molecular weight oligomer in commercial epoxy resins and the major component in commercial liquid epoxy resins. The major application areas for epoxy resins are protective coatings and civil engineering. Additional applications include printed circuit boards, composites, adhesives and tooling, while a relatively small amount of epoxy resins (< 10%) finds use in protective coatings inside food and drink cans. The use of BADGE in food-contact applications was first regulated through EC Directive 2002/16/EC and amended in EC Directive 2004/13/EC with migration levels in food-contact applications being generally well below the regulatory thresholds. The paper discusses the commercial use of BADGE focusing on the current knowledge of human exposure from canned food applications. To assess the safety of this application, the exposure data are compared with no adverse effect levels (NOAEL) from various toxicological investigations with BADGE including reproductive and developmental assays, endocrine toxicity investigations, and sub-chronic and chronic assays. Consumer exposure to BADGE is almost exclusively from migration of BADGE from can coatings into food. Using a worst-case scenario that assumes BADGE migrates at the same level into all types of food, the estimated per capita daily intake for a 60-kg individual is approximately 0.16 microg kg(-1) body weight day(-1). A review of one- and two-generation reproduction studies and developmental investigations found no evidence of reproductive or endocrine toxicity, the upper ranges of dosing being determined by maternal toxicity. The lack of endocrine toxicity in the reproductive and developmental toxicological tests is supported by negative results from both in vivo and in vitro assays designed specifically to detect oestrogenic and androgenic properties of BADGE. An examination of data from sub-chronic and chronic toxicological studies support a NOAEL of 50 mg kg(-1) body weight day(-1) from the 90-day study, and a NOAEL of 15 mg kg(-1) body weight day(-1) (male rats) from the 2-year carcinogenicity study. Both NOAELS are considered appropriate for risk assessment. Comparing the estimated daily human intake of 0.16 microg kg(-1) body weight day(-1) with the NOAELS of 50 and 15 mg kg(-1) body weight day(-1) shows human exposure to BADGE from can coatings is between 250,000 and 100,000-fold lower than the NOAELs from the most sensitive toxicology tests. These large margins of safety together with lack of reproductive, developmental, endocrine and carcinogenic effects supports the continued use of BADGE for use in articles intended to come into contact with foodstuffs.

Concentrations of Bisphenol A, Bisphenol A Diglycidyl Ether, and Their Derivatives in Canned Foods in Japanese Markets

“…In the simulation with BADGE in NaCl with acetic acid, the level (31) states that the specific migration limit (SML) of the sum of BADGE · H 2 O and BADGE · 2H 2 O and of chlorohydroxy compounds of BADGE should be restricted to below 9 and 1 mg/kg in food, respectively. As the sum of BADGE and its derivatives in canned foods in this survey was far lower than the SML, we can conclude that it is probably safe to use the materials currently used for can linings with regard to the carcinogenicity and toxicological effects of BADGE and its derivatives, as reviewed by Poole at al (19). In previous papers by other researchers (32), very high BADGE levels in fish in oil (exceeding 1 mg/kg) were due to the use of organosol PVC lacquers for can linings.…”

Widespread Occurrence and Distribution of Bisphenol A Diglycidyl Ether (BADGE) and its Derivatives in Human Urine from the United States and China

“…Knowledge of the toxic potential of BADGE and its derivatives is limited. 1,9,10,17,18 In general, it has been recognized that the toxicity of epoxy compounds is related to the degree of epoxidation of the molecule. 1 Therefore, divergence of p D values among individuals suggests differences in risks from exposure to BADGEs.…”

“…7 BADGE has been reported to form DNA adducts, 8 and to elicit teratogenic and mutagenic effects in vitro. 9,10 In addition to genotoxic effects of BADGEs, cytotoxicity, developmental, and reproductive toxicity have been reported in laboratory animals. 9,11−13 Male workers exposed to BADGE had lower levels of follicle stimulating hormone than the reference population.…”

New Cyclodextrin Hydrogels Cross-Linked with Diglycidylethers with a High Drug Loading and Controlled Release Ability

“…This paper reports on a new cyclodextrin cross-linking procedure, carried out in water, under mild conditions, and uses ethyleneglycol diglycidylether (EGDE) as cross-linker, which has two epoxy groups in its structure, both of similar reactivity and able to react simultaneously with the hydroxyl groups of cyclodextrins. EGDE has been shown to be an adequate crosslinker of polysaccharides and of DNA (27Y29), and its low toxicity makes its use in the preparation of protective coatings inside food and drink cans common (30,31). This cross-linking method does not require any modification in the cyclodextrin structure, thereby avoiding the use of acrylic or vinyl monomers in the preparation in which the number and the position of the polymerizable groups are hardly foreseeable (32).…”