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Description of key information

An OECD 422 study is planned on Solvent Violet 36. The dossier will be updated as soon as the result becomes available.


 


Key information on Category members:


- Reinblau RLW: NOAEL = 1000 mg/kg bw/day (OECD 407, GLP, WoE, rel.2)


- Solvent Green 28: NOAEL = 1000 mg/kg bw/day (OECD 422, GLP, WoE, rel.1)

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:
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).
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEL
1 000 mg/kg bw/day
Study duration:
subacute
Species:
rat
Quality of whole database:
The available studies on Category members are GLP-compliant and of high quality (Klimisch score = 1 or 2). A new study will be conducted on Solvent Violet 36.

Repeated dose toxicity: inhalation - systemic effects

Endpoint conclusion
Endpoint conclusion:
no study available

Repeated dose toxicity: inhalation - local effects

Endpoint conclusion
Endpoint conclusion:
no study available

Repeated dose toxicity: dermal - systemic effects

Endpoint conclusion
Endpoint conclusion:
no study available

Repeated dose toxicity: dermal - local effects

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

No study is available on Solvent Violet 36 at that time. Studies on Category members are summarized below.


 


1/ Reinblau RLW


In a subacute toxicity study performed similarly to OECD TG 407 and in compliance with GLP, Reinblau RLW suspended in CMC-Na solutions was administered to Crl: CD SD IGS rats (6/sex/dose in the control and high dose groups; 6/sex/dose in the other groups) by gavage at dose levels of 0, 8, 40, 200 and 1000 mg/kg bw/day. In addition, 6 rats/sex/dose in the control and 1000 mg/kg bw/day groups were subjected to a recovery period of 14 days.


There were no test substance-related toxic changes in clinical sign, body weight, food consumption, hematology, blood chemistry, urinalysis, organ weight, necropsy, or histopathology.


Therefore, the no-observed-effect-level (NOEL) of Reinblau RLW was considered to be 1000 mg/kg bw/day for male and female rats.


 


2/ Solvent Green 28


In an OECD guideline 422 study (Combined Repeated Dose Toxicity Study and Reproductive/ Developmental Toxicity Screening Study in the Crl:CD(SD) Rat by Oral Gavage Administration) Solvent Green 28 was administered to three groups of ten male and ten female rats by oral gavage administration, for approximately 6 weeks (males) and up to eight weeks (females) (including a two week pre-pairing phase, pairing, gestation and early lactation for females), at dose levels of 100, 300 and 1000 mg/kg bw/day.  A similarly constituted control group received the vehicle, corn oil, at the same volume dose as the treated groups.


The no-observed adverse-effect level (NOAEL) of Solvent Green 28 for systemic toxicity was considered to be 1000 mg/kg/day and the no-observed adverse-effect level (NOAEL) of Solvent Green 28 for reproductive/developmental toxicity was also considered to be 1000 mg/kg/day.


 


3/ Solvent Blue 104 (Source: ECHA disseminated dossier)


Oral administration to Wistar rats at doses of 100, 300 and 1000 mg/kg/day, for 28 days resulted in no substance related deaths, no clinical symptoms (at daily or weekly observations), no clinical symptoms (at the functional observational battery), no effects on food consumption or body weight development, no effects upon hematology and clinical biochemistry parameters, no changes in mean absolute or relative organ weights, and no macroscopical or microscopical findings of toxicological relevance.
Based on the results of this study, 1000 mg/kg body weight/day was established as the no-observed-adverse-effect-level (NOAEL) for the test substance.


 


Conclusion:





The available three short term studies consistently show no toxicity of the anthraquinone dye group; up to the limit dose no adverse effects are reported, and it can be concluded that “no hazard” is identified in any of these studies.




Justification for classification or non-classification

Harmonised classification:


The substance has no harmonised classification according to the Regulation (EC) No. 1272/2008 (CLP). 


 


Self-classification:


None of the category members is classifed for repeated dose toxicity. An OECD 422 study is planned on Solvent Violet 36. The dossier will be updated as soon as the new study becomes available.