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Toxicological information

Specific investigations: other studies

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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-referenceopen allclose all
Reason / purpose:
reference to same study
Reason / purpose:
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

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
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.