1. Exposure Data

1.1. Chemical and physical data

1.1.1. Nomenclature

• Chem. Abstr. Services Reg. No.: 1675-54-3
• Systematic name: 2,2′-[(1-Methylethylidene)bis(4,1-phenyleneoxymethylene)]bis(oxirane)

1.1.2. Structural and molecular formulae and relative molecular mass

2. Studies of Cancer in Humans

No data were available to the Working Group.

3. Studies of Cancer in Experimental Animals

Bisphenol A diglycidyl ether of various technical grades was tested for carcinogenicity by skin application in mice in five studies. In one of the studies, an increased incidence of epidermal tumours was found in C57BL/6 mice, but not in C3H mice. In a study with CF1 mice, a small increase in the incidence of epidermal tumours and small increases in the incidences of kidney tumours in male mice and of lymphoreticular/haematopoietic tumours in female mice were observed. No increase in the incidence of skin tumours was observed in two further studies, one with CF1 mice, the other with C3H mice and the remaining study with C3H mice was inadequate for evaluation. Following subcutaneous injection of technical grade bisphenol A diglycidyl ether to male Long-Evans rats, a small number of local fibrosarcomas was observed. Following application of technical grade bisphenol A diglycidyl ether to the skin of albino rabbits, no skin tumour was observed.

Pure (‘analytical grade’) bisphenol A diglycidyl ether was tested in one experiment by skin application in CF1 mice; no epidermal, but a few dermal tumours were observed in males and there was a small increase in the incidence of lymphoreticular/haematopoietic tumours in females (IARC, 1989). No subsequent studies were available to the Working Group.

It was noted that glycidaldehyde, a metabolite of bisphenol A diglycidyl ether, is carcinogenic to experimental animals and classified as possibly carcinogenic to humans (group 2B) (see this volume).

4. Other Data Relevant to an Evaluation of Carcinogenicity and its Mechanisms

4.1. Absorption, distribution, metabolism and excretion

4.1.1. Humans

No data were available to the Working Group.

4.1.2. Experimental systems

A dose of approximately 55 mg/kg bw [¹⁴C]bisphenol A diglycidyl ether to mice was well absorbed after administration by either the oral or dermal route. Most of the orally administered material was excreted within 24 h. After eight days, 79% was recovered from faeces and 10% from urine following oral dosing. Following dermal dosing, 67% and 11% of the radioactivity could be recovered from the application site after 24 h and 8 days, respectively. Bisphenol A diglycidyl ether is rapidly metabolized in mice, the major route involving hydration to the corresponding bis-diol, which occurs both enzymatically, through the epoxide hydrolase, and nonenzymatically. This hydration is followed by monooxygenase-mediated dealkylation to form a phenol and glyceraldehyde. It also appears that bisphenol A diglycidyl ether may be directly oxidized with the release of glycidaldehyde (Figure 1). Urinary and faecal metabolites include glucuronides and sulfates of the bis-diol and corresponding carboxylic acids (IARC, 1989).

Figure 1

Two possible routes of oxidative dealkylation of the glycidyl moiety of bisphenol A diglycidyl ether.

5. Evaluation

No epidemiological data relevant to the carcinogenicity of bisphenol A diglycidyl ether were available.

There is limited evidence in experimental animals for the carcinogenicity of bisphenol A diglycidyl ether.

6. References

• Bentley P., Bieri F., Kuster H., Muakkassah-Kelly S., Sagelsdorff P., Stäubli W., Waechter F. Hydrolysis of bisphenol A diglycidylether by epoxide hydrolases in cytosolic and microsomal fractions of mouse liver and skin: inhibition by bis epoxycyclopentylether and the effects upon the covalent binding to mouse skin DNA. Carcinogenesis. 1989;10:321–327. [PubMed: 2912584]
• Climie I.J., Hutson D.H., Stoydin G. Metabolism of the epoxy resin component 2,2-bis[4-(2,3-epoxypropoxy)phenyl]propane, the diglycidyl ether of bisphenol A (DGEBPA) in the mouse. Part II. Identification of metabolites in urine and faeces following a single oral dose of ¹⁴C-DGEBPA. Xenobiotica. 1981;11:401–424. [PubMed: 7293231]
• IARC (1976) IARC Monographs on the Evaluation of Carcinogenic Risk of Chemicals to Man, Vol. 11, Cadmium, Nickel, Some Epoxides, Miscellaneous Industrial Chemicals and General Considerations on Volatile Anaesthetics, Lyon, pp. 175–181. [PubMed: 992654]
• IARC (1987) IARC Monographs on the Evaluation of Carcinogenic Risks to Humans, Suppl. 7, Overall Evaluations of Carcinogenicity: An Updating of IARC Monographs Volumes 1 to 42, Lyon, p. 64. [PubMed: 3482203]
• IARC (1989) IARC Monographs on the Evaluation of Carcinogenic Risks to Humans, Vol. 47, Some Organic Solvents, Resin Monomers and Related Compounds, Pigments and Occupational Exposures in Paint Manufacture and Painting, Lyon, pp. 237–261. [PMC free article: PMC7681632] [PubMed: 2636273]
• Morrissey R.E., George J.D., Price C.J., Tyl R.W., Marr M.C., Kimmel C.A. The developmental toxicity of bisphenol A diglycidyl ether in rats and mice. Fundam. appl. Toxicol. 1987;8:571–582. [PubMed: 3609543]
• Steiner S., Crane A.E., Watson W.P. Molecular dosimetry of DNA adducts in C3H mice treated with glycidaldehyde. Carcinogenesis. 1992a;13:119–124. [PubMed: 1733564]
• Steiner S., Hönger G., Sagelsdorff P. Molecular dosimetry of DNA adducts in C3H mice treated with bisphenol A diglycidylether. Carcinogenesis. 1992b;13:969–972. [PubMed: 1600618]