Registration Dossier

Diss Factsheets

Administrative data

Description of key information

CAS 35869 -64 -8 was found to be non toxic upon acute oral toxicity testing in rats with 10 000 mg/kg bw.

A study for acute inhalation toxicity in rats (OECD 403) is ongoing. Read-across assessment shows absence of adverse effects of > 1.7 mg/m3.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records
Reference
Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
yes
Remarks:
7-day observation period; body weights determined only at study start, TS purity not specified
GLP compliance:
no
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
not specified
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Tif. RAI SPF own breeeding rats from Ciba-Geigy Ltd.
- Age at study initiation: 6-7 weeks
- Weight at study initiation: 160-180 g
- Fasting period before study: during one night prior to dosing
- Housing: caged in groups of 5 (segregated in males and females) in Macrolon cages type 3
- Diet (e.g. ad libitum): Rat food, NAFAG, Gossau, SG; ad libitum
- Water (e.g. ad libitum): drinking water; ad libitum
- Acclimation period: no data

ENVIRONMENTAL CONDITIONS (the animal room was air conditioned)
- Temperature (°C): 22±1°C
- Humidity (%): approx. 50%
Route of administration:
oral: gavage
Vehicle:
CMC (carboxymethyl cellulose)
Remarks:
2%
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 50% (w/v)

DOSAGE PREPARATION (if unusual):
The test substance was weighed into an Erlenmeyer flask on a Mettler balance. It was suspended at 50 % with CMC (2%). Before treatment the suspension was homogeneously dispersed with an Ultra-Turrax and during treatment it was kept stable with a magnetic stirrer.
Doses:
6000 and 10000 mg/kg bw
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
- Duration of observation period following administration: 7 days
- Frequency of observations and weighing: daily for mortality and clinical signs of toxicity; body weights were not determined
- Necropsy of survivors performed: yes; the animals were killed and autopsied at the end of the observation period.
Statistics:
None conducted
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 10 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: No mortality was observed up to this dose level
Mortality:
No mortality occurred
Clinical signs:
other: Within 2 hours after treatment the rats of both dosage groups showed dyspnoea, exophthalmus, curved position and ruffled fur. These symptoms became more accentuated as the dose was increased. The animals had recovered within 3 to 6 days. They were killed
Gross pathology:
No substance related gross organ changes were seen.
Interpretation of results:
practically nontoxic
Remarks:
Migrated information
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
discriminating dose
Value:
10 000 mg/kg bw

Acute toxicity: via inhalation route

Link to relevant study records
Reference
Endpoint:
acute toxicity: inhalation
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Justification for type of information:
READ ACROSS ANALOGUE APPROACH

The read-across hypothesis is based on the inertness of both read-across (CAS 5580-57-4) and target substance. Both pigments are insoluble, are not irritating to mucous membranes and do not cause toxicity by the oral route up to the limit dose. It is predicted that the target substance does not require classification for acute inhalation toxicity.

Structural similarity/ functional groups
Both substances share the same core structure. The core structure includes all functional groups which might be relevant for metabolism (eg. azo, carboxamide). Structural differences are the substituents on the phenylene or phenyl part. The substituents are non-polar and are therefore predicted to decrease systemic uptake by both increasing the size and the hydrophobicity of the molecule.
Physico-chemical properties and toxicokinetics
The molecular weight of both substances is almost identical, as is their relative density. Both decompose before melting at temperatures above 300 °C. They are of low solubility in water and in octanol. On the basis of the measured solubility in water and octanol, the partitioning coefficient is zero or less.
In a study on solubility (static and dynamic) and on particle reactivity, all disazo concensation red pigments were found to be insoluble and passive (BASF 2021, see attached report).
In acute oral toxicity studies performed with the substances, common clinical signs as dyspnea, exophthalmos, ruffled fur, curved body position, diarrhea and sedation were seen when the substances were applied in high concentrations. These systemic toxic effects were all transient. No indication of a substance specific systemic toxicity can be found in any other study. Therefore, absorption and bioavailability of the test substance after oral administration is not expected.

Consistency of data
Neither substance shows adverse effects at the limit dose in valid acute or subacute studies. For the target substance, an acute inhalation toxicity study showing absence of a hazard is available. As this study was performed at a CRO with unacceptable reputation, it is assigned the validity score of 4 and read-across is applied.

Data quality
The validity scores of the experimental data are provided in the data matrix. Relevant data is at least valid with restriction (K2) or comes from GLP and OECD guideline compliant studies (K1).


Please find the complete Read-across justification text including the data matrix in the attachment.
Reason / purpose for cross-reference:
read-across source
Key result
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 1.7 mg/L air
Based on:
test mat.
Exp. duration:
4 h
Remarks on result:
other: No mortality and clinical signs
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed

Acute toxicity: via dermal route

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Pigment Brown 23 (CAS 35869-64-8, 850 g/mol), acute oral toxicity in rat

Pigment Brown 23 was tested in a valid study in rats (Ciba-Geigy Ltd 1973) that was performed prior to the introduction in GLP, but according to procedures similar to OECD guidelines for acute oral toxicity. The design included only a 7-day observation period and body weights determined only at study start. Each five male and female rats received a single dose of 6000 or 10000 mg/kg bw. Within 2 hours after treatment the rats of both dosage groups showed dyspnoea, exophthalmus, curved position and ruffled fur. These symptoms became more accentuated as the dose was increased. The animals had recovered within 3 to 6 days. No mortality occurred. No substance related gross organ changes were seen at necropsy.

 

Justification for classification or non-classification

Classification, Labelling, and Packaging Regulation (EC) No. 1272/2008

The available experimental test data are reliable and suitable for classification purposes under Regulation 1272/2008. As a result the substance is not considered to be classified for acute oral or dermal toxicity under Regulation (EC) No. 1272/2008, as amended for the thirteenth time in Regulation (EC) No. 2018/1480.