Review of the toxicology, human exposure and safety assessment for bisphenol A diglycidylether (BADGE).
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.
Poole
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Dow Europe GmbH, Bachtobelstrasse 3, CH-8810 Horgen, Switzerland. apoole@dow.com
van Herwijnen
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Weideli
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H
Thomas
M C
MC
Ransbotyn
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G
Vance
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C
D000818:Animals; D001559:Benzhydryl Compounds; D002273:Carcinogens / Q000493:pharmacokinetics / Q000633:toxicity*; D004781:Environmental Exposure / Q000009:adverse effects; D004852:Epoxy Compounds / Q000493:pharmacokinetics / Q000633:toxicity*; D004967:Estrogens / Q000378:metabolism; D005298:Fertility / Q000187:drug effects; D005506:Food Contamination / Q000331:legislation & jurisprudence; D006128:Growth / Q000187:drug effects; D006801:Humans; D051381:Rats; D012098:Reproduction / Q000187:drug effects; D000098826:Bisphenol A Compounds
D001559:Benzhydryl Compounds; D002273:Carcinogens; D004852:Epoxy Compounds; D004967:Estrogens; C019273:bisphenol A diglycidyl ether; D000098826:Bisphenol A Compounds