4,4'-Isopropylidenediphenol, ethoxylated

Endpoint summary

Link to relevant study record(s)

Reference

Endpoint:

basic toxicokinetics

Type of information:

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

Adequacy of study:

key study

Justification for type of information:

4,4'-Isopropylidenediphenol, ethoxylated (CAS 32492-61-8 / EC 500-082-2) also known as BPA-EO is a chemical substance of unknown or variable composition, complex reaction products or of biological materials (UVCB). It is composed of ethoxylated isopropylidenediphenol of various chain-lengths, with a mean number of ethoxy groups ranging from 1 to 4.5.
2,2’-isopropylidenebis(p-phenyleneoxy)diethanol (CAS 901-44-0 / EC 212-985-6) also known as BPA-2EO is the major constituent of BPA-EO (concentration range reported in the registration dossier: 50 – 95 % (w/w)) and is an ethoxylated isopropylidenediphenol with a fixed number of one ethoxy group on each side. Therefore, the properties of BPA-EO and BPA-2EO are expected to be closely related.
Furthermore, in addition to being chemically/structurally similar, both substances have similar vapour pressure, water solubility and octanol/water partition coefficient. It is therefore expected that the two substances will have similar toxicokinetic behaviour and bioavailability and thus a similar (eco-)toxicological profile.

Reason / purpose for cross-reference:

read-across source

Preliminary studies:

Substance appears to be absorbed orally, with metabolic activity based on transitory changes in liver function

Type:

absorption

Results:

Orally, but no evidence of dermal or inhalation absorption

Type:

distribution

Results:

Effects seen in liver suggesting distribution

Type:

metabolism

Results:

Increased liver function suggesting metabolism

Type:

excretion

Results:

No evidence

Details on absorption:

There was no evidence of systemic effects reported in the data provided on the acute oral or dermal toxicity studies, but blood parameter changes observed in the repeat dose oral toxicity study would suggest that absorption does take place orally.

The low water solubility and potential high fat solubility suggests that it is likely that a significant proportion is excreted without being absorbed.

Details on distribution in tissues:

Systemic effects were observed in the subacute oral toxicity study with changes in blood chemistry and minor findings in the liver and kidneys. It is therefore possible to conclude that the substance, or the metabolites, are transported.

Details on excretion:

There is no evidence from testing performed that there is subsequent excretion of the absorbed substance or any metabolites formed. Slight transient effects in the kidney suggest some exposure to the kidney to the substance of metabolites.

Metabolites identified:

not measured

Conclusions:

Low bioaccumulation potential based on study results
Assessed that some absorption occurs and there is evidence of metabolism.

Executive summary:

The absence of specific toxicokinetic data from animal testing means that it is not possible to make firm conclusions concerning the absorption, distribution, metabolism or excretion of the substance. However, there is sufficient evidence from other testing to show that some oral absorption takes place and there are likely to be adaptive changes to the animals following transportation and metabolism.

It is not considered appropriate to perform further animal studies on this substance.

This information is used in a read-across approach in the assessment of the target substance. For details and justification of read-across please refer to the section 'Justification for type of information' above.

Description of key information

Appears to be absorbed following ingestion, with transitory effects in the liver.  Recovery groups (2 weeks post-dosing) show no effects, suggesting metabolic processes. 

Key value for chemical safety assessment

Bioaccumulation potential:

no bioaccumulation potential