Carbonic acid, diphenyl ester, reaction products with bisphenol A

Developmental toxicity / teratogenicity

Administrative data

Endpoint:

developmental toxicity

Type of information:

migrated information: read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

supporting study

Reliability:

4 (not assignable)

Rationale for reliability incl. deficiencies:

other: Secondary literature: EU Risk Assessment Report Bisphenol A (review)

Data source

Reference

Reference 1

Reference Type:

publication

Title:

4,4'-Isopropylidenediphenol (Bisphenol A) (CAS-No. 108-95-2)

Author:

European Chemicals Bureau (ECB)

Year:

2003

Bibliographic source:

EU Risk Assessment Report, 3rd Priority List, Volume 37

Reference 2

Reference Type:

publication

Title:

4,4´-Isopropylidenediphenol (bisphenol-A)

Author:

European Chemicals Bureau (ECB)

Year:

2008

Bibliographic source:

EU Risk Assessment Report, Human Health Addendum of April 2008 (to be read in conjunction with published EU RAR of BPA, 2003)

Reference 3

Reference Type:

other company data

Title:

Unnamed

Year:

2010

Report date:

2010

Materials and methods

Test material

Test material information

Constituent 1

Reference substance name:

4,4'-isopropylidenediphenol

EC Number:

201-245-8

EC Name:

4,4'-isopropylidenediphenol

Cas Number:

80-05-7

Molecular formula:

C15H16O2

IUPAC Name:

2,2-bis(4-hydroxyphenyl)propane

Results and discussion

Results (fetuses)

Fetal abnormalities

Abnormalities:

not specified

Overall developmental toxicity

Developmental effects observed:

not specified

Applicant's summary and conclusion

Executive summary:

The 2003 EU RAR concluded:

"No human data on reproductive toxicity of BPA are available. BPA has been shown to have endocrine modulating activity in a number of screening assays, with a potency that generally ranged from 3 to 5 orders of magnitude less than that of oestradiol. The effects of BPA on fertility and reproductive performance have been investigated in two-generation and multi-generation studies in the rat and a continuous breeding study in mice. Effects were seen in both species at approximately the same dose level and it is considered that the NOAEL of 50 mg/kg/day identified in the rat multi-generation study is also likely to produce no adverse effects in mice for which there is only a LOAEL of 300 mg/kg/day for a small decrease in epididymal weight in F1 males. The NOAEL of 50 mg/kg/day from the multi-generation study will be used for risk characterisation purposes, in relation to effects on fertility."

The 2008 updated EU RAR concluded:

"A new two-generation study in mice by Tyl et al. (published in 2008) provides a comprehensive and definitive investigation on the effects of BPA on reproduction at exposure levels spanning the low (ug/kg/day) to high (mg/kg/day) ranges. This study showed that BPA causes adverse effects on pregnancy and the offspring at 600 mg/kg/day, an exposure level that also caused mild parental toxicity. Fertility was not affected by BPA exposure. A NOAEL for reproductive toxicity of 50 mg/kd/day was identified and should be used in the risk assessment."

There is no reliable and significant new information on the reproductive or developmental toxicity of Bisphenol A.

The 2003 EU RAR concluded that in standard developmental studies in rodents, there is no convincing evidence that Bisphenol A is a developmental toxicant. Available and apparently conflicting data from studies conducted using low doses raise uncertainties that the Competent Authorities required to be resolved through further testing. A provisional NOAEL of 50 mg/kg/day for developmental effects, derived from a rat multi-generation study, should be used in the risk characterisation in the interim while awaiting the outcome of further testing.

The 2008 updated EU RAR concluded that no conclusions could be drawn from new developmental toxicity studies or from a human study investigating recurrent miscarriage and Bisphenol A exposure, so these studies do not influence the conclusions of the original risk assessment report.

There is no significant and reliable new information on the reproductive or developmental toxicity of Bisphenol A that was not discussed in the 2003 or 2008 EU RARs. 

 

Bisphenol A is classified Repr. Cat.3; R62 according to Annex 1 of Regulation 67/548/EEC and Repr. 2 according to Annex VI of Regulation (EC) No 1272/2008.