Registration Dossier

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Administrative data

Description of key information

A combined short-term toxicity and screening for toxicity to reproduction study was performed on BPA-5EO according to OECD Testing Guideline 422. On the basis of the significant effects observed on bodyweight at 1,000 mg/kg bw/d it is proposed a NOAEL of 500 mg/kg bw.


4,4-isopropylidenediphenol, ethoxylated (BPA-4EO) is being assessed for the purpose of the evaluation of the sunbchronic toxicity (90 days) via the oral route in rats. The study, according to the OECD TG 408, has been planned and commissioned to Covance Laboratories Limited, Woolley Road, Alconbury, Huntingdon, Cambridgeshire, PE28 4HS, UK
The testing is split into 3 phases
1) Validation of the analytical method: Experimental starting date 29 October 2020, expected completion date 04 December 2020 and expected draft report date 15 January 2021
2) Dose range finding study Study: dates TBC
3) OECD 408: dates TBC


The reason for such a delay in reference to ECHA 30 November 2020 deadline (Refs: TPE- D-2114489554-35-01/F), are explained in a separate letter, attached to this dossier.

Key value for chemical safety assessment

Toxic effect type:
dose-dependent

Repeated dose toxicity: via oral route - systemic effects

Link to relevant study records
Reference
Endpoint:
sub-chronic toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
The testing is split into 3 phases
1) Validation of the analytical method: Experimental starting date 29 October 2020
Experimental completion date 04 December 2020
Draft report date 15 January 2021
2) Dose range finding study Study: TBC
3) OECD 408: TBC
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 408 (Repeated Dose 90-Day Oral Toxicity Study in Rodents)
GLP compliance:
yes
Limit test:
no
Specific details on test material used for the study:
SOURCE OF TEST MATERIAL
- Source and lot/batch number of test material: I0348349AW
- Expiration date of the lot/batch: 27 March 2024
- Purity test date: UVCB
- Storage: Ambient temperature (15 to 25ºC)
Species:
rat
Strain:
Sprague-Dawley
Route of administration:
oral: gavage
Vehicle:
corn oil
Analytical verification of doses or concentrations:
yes
Remarks:
Establishment and validation of an analytical method which will be used for the measurement of 4,4’-Isopropylidenediphenol, etoxylated in corn oil was started on the 29th of October 2020.
Details on analytical verification of doses or concentrations:
• The analytical method will be validated by determining the specificity, limit of detection, limit of quantification, linearity of detector response, injection system precision, method accuracy and precision, standard stability and extracted solution stability.
• Preparation of liquid formulations containing 4,4’-Isopropylidenediphenol, etoxylated at nominal concentrations of 1 mg/mL and 250 mg/mL and evaluation of the suitability of the formulation procedure by determining accuracy of the formulations.
• Determination of the homogeneity and stability of the liquid formulations from preparation to completion of use.
Duration of treatment / exposure:
90 days
Remarks:
Dose range finding test commissioned, study Study Plan 4,4'-Isopropylidenediphenol, ethoxylated :Preliminary Toxicity Study by Oral GavageAdministration to Sprague Dawley Rats for 28 Days, we have reviewed the first draft of the study plan for this phase (see attached reviewed draft for reference)
Details on results:
Study planned and commissioned. Expected completion and results phase 1, January 2021.
Dose descriptor:
other: Study planned and commissioned. Expected completion and results phase 1, January 2021.
Remarks on result:
other: Study planned and commissioned. Expected completion and results phase 1, January 2021.
Critical effects observed:
not specified
Organ:
other: Study planned and commissioned. Expected completion and results phase 1, January 2021.

See attached signed study plan for the validation of the analytical method and study plan draft for the range findig test

Executive summary:

4,4-isopropylidenediphenol, ethoxylated (BPA-4EO) (EC 500-082-2) is being assessed for the purpose of the evaluation of the sunbchronic toxicity (90 days) via the oral route in rats.
The study, according to the OECD TG 408, has been planned and commissioned to Covance Laboratories Limited, Woolley Road, Alconbury, Huntingdon, Cambridgeshire, PE28 4HS, UK
The testing is split into 3 phases
1) Validation of the analytical method: Experimental starting date 29 October 2020, expected completion date 04 December 2020 and expected draft report date 15 January 2021
2) Dose range finding study Study: dates TBC
3) OECD 408: dates TBC


The reason for such a delay in reference to ECHA 30 November 2020 deadline (Refs: TPE- D-2114489554-35-01/F), are explained in a separate letter, attached in background material.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEL
500 mg/kg bw/day
Study duration:
subacute

Additional information

Justification for classification or non-classification

No critical effect on specific target organs were observed.