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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.

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:
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 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:
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 and autopsied after an observation period of 7 days.
Body weight:
No data
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

Endpoint conclusion
Endpoint conclusion:
no study available

Acute toxicity: via dermal route

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Acute dermal toxicity was studied with Pigment Red 144 in rabbits (MBRL1978). The study was performed prior to the introduction of GLP, but is reported in adequate detail for evaluation. In deviation to the current OECD testing guideline, only 4 animals (2 male and 2 female) were used and abraded skin was treated in 2 animals. The size of application area is not reported. These differences are minor, and considering survival of all four animals the outcome of the study would not have been different in a fully OECD 402 guideline compliant study. The dose of 2000 mg/kg bw was applied using water for moistioning with occlusive wrapping for 24h. No local effects were observed. One animal with intact skin showed transient clinical signs.

A second study report is available which cannot be assigned as to its validity as it was performed at a CRO which had in part falsified study reports: No acute dermal toxicity was observed for each one single rat tested at 300, 1000 and 3000 mg/kg bw of Pigment Red 221 (IBT 1975). A summary value of > 5000 mg/kg bw is provided for Pigment Brown 41 (Sandoz 1975). It refers to a study for which no details on the experimental procedure are provided and which is assigned a validity score of 4.

The available data is considered representative for all disazo condensation red pigments. The pigments are very large and bulky molecules with calculated diameters of more than 10 Angström. According to ECHA guidance, a reduction in dermal uptake to 10% may be applied if the molecular weight is higher than 500 Da and if the log Pow is less than -1 or higher than 4. The molecular weight ranges from 781.7 g/mol (Pigment Red 262) to 930.5 g/mol (Pigment Red 242) which is well above the threshold of 500 g/mol generally considered for low dermal uptake in the ECHA guidance document. The criterium for log Pow is not fulfilled, but it is not considering helpful for cases where the substances are equally poorly soluble in organic and inorganic solvents. Transport processes require some solubility and these pigments are overall poorly soluble (< 0.1 mg/L) in octanol and water. As the dermal uptake is predicted to be very low and there is no indication of acute oral toxicity up to limit doses, it is safe to assume that no acute dermal hazard exists for all disazo condensation red pigments.

Regarding acute inhalation toxicity, a study with whole-body exposure to Pigment Red 220 was performed at the CRO which was later sued for having falsified study reports (IBT 1972).  This report itself appears to be plausible, since the findings regarding the focal red discoloration and the particle sizes make sense.The test concentration in testing atmosphere was 2.2 mg/l. Details on analytical verification of test atmosphere concentration are not provided.The method of particle size determination is described as follows: A sample of airborne dust was collected from the test atmosphere for the purpose of conducting a microscopic determination of particle size distribution. Particles were counted with respect to three size ranges, viz. 5 µm or smaller (considered to be respirable), 6-25 µm and >25 µm. The smallest particle which could be detected by the light-field technique employed was approximately one µm. The largest particle observed was also recorded. 55% of the particles were in the range of less than 5 µm and 35% were in the range of 6-25 µm. No deaths were noted during the four-hour exposure period or 14-day observation period which followed. Necropsy, performed on all animals at the end of the two-week observation period, revealed slight to moderate diffuse focal red discoloration of the lungs in six rats. There were no other gross pathologic alterations in any of the other tissues and organs examined.

The reported procedure and findings are plausible and would be expected for red inert pigments that are too large for passive permeation through biological membranes.

The pigments are not have irritating or sensitizing properties and are expected to cause effects via excessive deposition at high doses. Based on experience with inert organic pigments, these do not result in mortality in acute inhalation exposure studies. Exposure to inhalable dust must be controlled, and at acceptable levels (3 mg/m3) no substance-specific acute inhalation hazard is expected. Further testing of acute inhalation testing was therefore not performed.  

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.