2,2'-[(1-methylethylidene)bis(4,1-phenyleneoxymethylene)]bisoxirane

Specific investigations: other studies

Administrative data

Endpoint:

mechanistic studies

Type of information:

experimental study

Adequacy of study:

supporting study

Study period:

not specified

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: The study was not conducted according to guideline/s and GLP but the report contains sufficient data for interpretation of study results

Cross-reference

Cross-reference 1

Reason / purpose for cross-reference:

reference to same study

Cross-reference 2

Reason / purpose for cross-reference:

reference to other study

Data source

Reference

Reference Type:

publication

Title:

Unnamed

Year:

1989

Materials and methods

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

examined hydrolysis and DNA binding of bisphenol A by microsomal and cytosolic fractions of mouse liver and skin in vitro

GLP compliance:

no

Type of method:

in vitro

Endpoint addressed:

not applicable

Test material

Test material information

Constituent 1

Reference substance name:

4,4'-Isopropylidenediphenol, oligomeric reaction products with 1-chloro-2,3-epoxypropane

EC Number:

500-033-5

EC Name:

4,4'-Isopropylidenediphenol, oligomeric reaction products with 1-chloro-2,3-epoxypropane

Cas Number:

25068-38-6

Molecular formula:

(C15 H16 O2 . C3 H5 Cl O)x

IUPAC Name:

4,4'-Isopropylidenediphenol, oligomeric reaction products with 1-chloro-2,3-epoxypropane

Constituent 2

Reference substance name:

2,2'-[(1-methylethylidene)bis(4,1-phenyleneoxymethylene)]bisoxirane

EC Number:

216-823-5

EC Name:

2,2'-[(1-methylethylidene)bis(4,1-phenyleneoxymethylene)]bisoxirane

Cas Number:

1675-54-3

Molecular formula:

C21H24O4

IUPAC Name:

2,2'-[propane-2,2-diylbis(4,1-phenyleneoxymethylene)]dioxirane

Details on test material:

Test substance: 1675-54-3, Ciba-Geigy, bisphenol A diglycidyl ether (BPADGE)
14C-BPADGE labeled in the glycidyl side chain or at the central carbon atom, Sp. Act. 21 mCi/mmol, radiochemical purity >99% via radio-TLC and HPLC

Test animals

Species:

mouse

Strain:

other: C3H andC57BL6 strains

Sex:

not specified

Administration / exposure

Route of administration:

other: in vitro

Vehicle:

acetone

Analytical verification of doses or concentrations:

not specified

Duration of treatment / exposure:

10-60 minutes in vitro

Frequency of treatment:

once

Post exposure period:

not applicable

No. of animals per sex per dose:

not applicable

Details on study design:

To elucidate the mechanism of a synergistic effect of BADGE and bis epoxycyclopentylether on carcinogenicity, the authors have investigated the effects of bis epoxycyclopentylether upon the hydrolysis and DNA-binding of BADGE.

Results and discussion

Details on results:

BADGE was rapidly hydrolyzed by microsomal and cytosolic fractions of mouse liver and skin in 2 mouse strains. Epoxide hydrolase activity in skin cytosolic fractions was demonstrated experimentally. In addition, bis epoxycyclopentylether inhibited the microsomal activities. The inhibition appeared to be slightly more effective with microsomal fractions from the liver.

When high doses of BADGE were applied to mouse skin, one major DNA adduct was observed which was identified as a glycidaldehyde adduct. The adduct was not detectable at the lowest BADGE dose unless epoxycyclopentylether was applied simultaneously. The findings suggest that glycidaldehyde may be formed from BADGE. At low doses, however, the epoxide groups are hydrolyzed before glycidaldehyde can be formed, unless the epoxide hydrolase is inhibited. Such inhibition and the associated increased production of glycidaldehyde may account for the potentiation of the carcinogenic response of the mixture.

Any other information on results incl. tables

Bisphenol A diglycidylether was sequentially hydrolysed to the bis diol via the diol epoxide which showed a transitory accumulation. BADGE is an excellent substrate for mouse liver cytosolic and microsomal epoxide.

Applicant's summary and conclusion

Conclusions:

The findings suggest that glycidaldehyde may be formed from BADGE. At low doses, however, the epoxide groups are hydrolyzed before glycidaldehyde can be formed, unless the epoxide hydrolase is inhibited. Such inhibition and the associated increased production of glycidaldehyde may account for the potentiation of the carcinogenic response of the mixture.

Executive summary:

Hydrolysis of BADGE by microsomal and cytosolic fractions of mouse liver and skin was examined. The findings suggest that glycidaldehyde may be formed from BADGE. At low doses, however, the epoxide groups are hydrolyzed before glycidaldehyde can be formed, unless the epoxide hydrolase is inhibited. Such inhibition and the associated increased production of glycidaldehyde may account for the potentiation of the carcinogenic response of the mixture.