1,8-bis[(4-methylphenyl)amino]anthraquinone

Repeated dose toxicity: oral

Administrative data

Endpoint:

short-term repeated dose toxicity: oral

Data waiving:

other justification

Justification for data waiving:

other:

Justification for type of information:

JUSTIFICATION FOR DATA WAIVING
An OECD 422 study will be performed on Solvent Violet 36. Within the dose range finding stage, a proof-of-concept toxicokinetic evaluation will be included. Both elements of the study will also support the Category approach.
The laboratory timeline indicates draft reporting of the main study at the end of Q2 2023. The dossier will be updated with the new study as soon at it becomes available (during Q3 2023).

Details on study design / methodology proposed:
1/ 14-day dose range finder pilot study for the OECD 422 study with in vivo toxicokinetic
- Compliance: non-GLP
- Species/Strain/Sex: Rat / Wistar / 4 Females per dose level
- Dosing Regimen: Once daily, for 14 days in oil vehicle or CMC (both types to be evaluated in formulation trials)
- Route of Administration: Oral (Gavage)
- Dose levels: 100, 300, 1000 mg/kg bw/day
- Mortality/Clinical Observations: Twice-daily
- Body Weight: At least twice weekly; fasted before scheduled necropsy
- Food Consumption: Twice weekly.
- Toxicokinetics: Tail vein samples will be taken at appropriate time intervals after final dosing (200 μL).
At necropsy, samples of appropriate organs for determination of ADME profile will be taken (e.g. blood, liver, kidney, brain and stomach). Following extraction with lipophilic solvent, analysis by LC/MS method for the test item (including pre-defined Limit Of Quantification) will be undertaken for control and high dose groups. It is expected that a positive result will be obtained from sites of local exposure (stomach), but not from other organs sampled. If positive results are found, then Mid, Low & Control samples analysed.
- Clinical pathology: Day 14, prior to necropsy, basic haematology, and clinical chemistry.
- Terminal procedures: Day 14 (of when terminated) All rats - Full macroscopic examination, performed with preservation of any tissues showing macroscopic abnormality.
Selected organ weights (Liver, Kidney, Spleen, Adrenals, Thymus, Prostate, Brain)

2/ combined repeat dose toxicity study with the reproduction / developmental toxicity screening test is rats, oral gavage: complete or limit test depending on the outcome of the range-finder pilot study. OECD 422 (July 2016 version).