4,4'-isopropylidenebis[2-allylphenol]

Basic toxicokinetics

Administrative data

Endpoint:

basic toxicokinetics

Type of information:

other: Assessment report

Adequacy of study:

key study

Study period:

Assessment was conducted in June 2015

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Study conducted in accordance with generally accepted scientific principles, possibly with incomplete reporting or methodological deficiencies, which do not affect the quality of relevant results.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2015

Report date:

2015

Materials and methods

Objective of study:

toxicokinetics

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

In accordance with Annex VIII (point 8.8) of Regulation (EC) No 1907/2006 (REACH), a paper-based toxicokinetic assessment has been conducted for the substance, TK 11907. Summaries of studies were reviewed by a qualified toxicologist with a view to fulfilling the requirements of Annex VIII, point 8.8 of REACH.

The assessment of the likely toxicokinetic behaviour of the substance was provided to the extent that can be derived from the relevant available information at the time of the assessment. The assessment is based on the Guidance on information requirements and chemical safety assessment Chapter R.7c: Endpoint specific guidance (ECHA, November 2012).

GLP compliance:

no

Test material

Test material information

Constituent 1

Reference substance name:

4,4'-isopropylidenebis[2-allylphenol]

EC Number:

217-121-1

EC Name:

4,4'-isopropylidenebis[2-allylphenol]

Cas Number:

1745-89-7

Molecular formula:

C21H24O2

IUPAC Name:

4-{1-[4-hydroxy-3-(prop-2-en-1-yl)phenyl]propyl}-2-(prop-2-en-1-yl)phenol

Test material form:

liquid: viscous

Details on test material:

- Identification: TK 11907.
-Appearance: Straw coloured viscous liquid.

Radiolabelling:

no

Test animals

Species:

other: Not applicable, a paper-based toxicokinetic assessment has been conducted for the substance at the current tonnage level.

Strain:

other: Not applicable, a paper-based toxicokinetic assessment has been conducted for the substance at the current tonnage level.

Details on test animals or test system and environmental conditions:

Not applicable, a paper-based toxicokinetic assessment has been conducted for the substance at the current tonnage level.

Administration / exposure

Route of administration:

other: Not applicable, a paper-based toxicokinetic assessment has been conducted for the substance at the current tonnage level.

Vehicle:

other: Not applicable, a paper-based toxicokinetic assessment has been conducted for the substance at the current tonnage level.

Details on exposure:

Not applicable, a paper-based toxicokinetic assessment has been conducted for the substance at the current tonnage level.

Duration and frequency of treatment / exposure:

Not applicable, a paper-based toxicokinetic assessment has been conducted for the substance at the current tonnage level.

Doses / concentrations

Remarks:

Doses / Concentrations:
Not applicable, a paper-based toxicokinetic assessment has been conducted for the substance at the current tonnage level.

No. of animals per sex per dose / concentration:

Not applicable, a paper-based toxicokinetic assessment has been conducted for the substance at the current tonnage level.

Control animals:

other: Not applicable, a paper-based toxicokinetic assessment has been conducted for the substance at the current tonnage level.

Results and discussion

Main ADME results

Results:

Not applicable, a paper-based toxicokinetic assessment has been conducted for the substance at the current tonnage level.

Toxicokinetic / pharmacokinetic studies

Details on absorption:

The lipophilic nature of the substance (Log Pow 4.12, O'Connor, 2014) would suggest that the gastro-intestinal tract provides a route of absorption, following oral administration, before entering the circulatory system via the blood. Limited absoption may also take place via the skin as the test item was shown to be sensitizer (Henzell, 2014) and the test item could penetrate the dermal membrane through damaged skin.

Details on distribution in tissues:

There was evidence of systemic toxicity following the conduct of a repeated dose reproductive screening study in the rat (Fulcher, 2014).
Furthermore the positive response in a sensitization study suggests that the test item nmay bind to carrier proteins in the circulatory systems (Henzell, 2014), thereby facilitating systemic distribution.

Details on excretion:

There is no evidence to indicate the route of excretion but low water-soluble products are not favourable for urinary excretion and therefore biliary excretion may be the most plausible route of excretion of the test item via the faeces. Metabolism of the parent material may involve rendering it
more water soluble thereby enhancing renal excretion. The neprotoxicity identified in the reproductive/developmental toxicity screening study (Fulcher, 2014) may therefore have been a consequence of the renal route being a point of excretion.

Metabolite characterisation studies

Metabolites identified:

not specified

Details on metabolites:

The results of the reproductive/developmental toxicity screening study performed in male and female rats exposed to the test item at dosage up to 750 (reduced to 500) mg/kg bw/day elicited histopathological evidence of abnormal hepatic metabolism, a condition associated with enhanced metabolism, a condition associated with enhanced metbolism. A dditionally, nephrotoxicity was identified at 250 mg/kg bw/day.

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information): low bioaccumulation potential based on study results
The available information suggests that absorption of the test substance would take place from the gastrointestinal tract. Some limited absorption may also be possible through the skin. Once absorbed, the substance would be distributed via circulatory system and the faeces is the most probable route of excretion.

Executive summary:

The available information suggests that absorption of the test substance would take place from the gastrointestinal tract. Some limited absorption may also be possible through the skin. Once absorbed, the substance would be distributed via circulatory system and the faeces is the most probable route of excretion.