Registration Dossier

Administrative data

Description of key information

The substance is non-toxic upon single ingestion in rats (OECD 401, GLP).

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:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Version / remarks:
Version August 6, 1987
Deviations:
no
GLP compliance:
no
Test type:
standard acute method
Limit test:
yes
Specific details on test material used for the study:
- Physical state: solide, insoluble in water
- Analytical purity: commercial grade
- Lot/batch No.: EN 81581.62
- Stability under test conditions: guaranteed
- Storage condition of test material: room temperature
Species:
rat
Strain:
other: albino rats
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: RAIf (SPF) hybrids (of RII/1 x RII/2) rats from Ciba-Geigy Ltd. Tierfarm, 4334 Sisseln, Switzerland
- Age at study initiation: 7-8 weeks
- Weight at study initiation: 204-236 g
- Fasting period before study: overnight prior to dosing
- Housing: caged in groups of 5 in Macrolon cages type 4 with standardized soft wood bedding (Societe Parisienne des sciures, Pantin)
- Diet (e.g. ad libitum): Rat food, NAFAG No. 890, NAFAG AG, Gossau, SG (Switzerland); ad libitum
- Water (e.g. ad libitum): drinking water; ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS (the animal room was air conditioned)
- Temperature (°C): 22±3°C
- Humidity (%): 55±15%
- Air changes (per hr): approx. 15 air changes per hour
- Photoperiod (hrs dark / hrs light): 12 / 12
Route of administration:
oral: gavage
Vehicle:
other: distilled water containing 0.5% carboxymethylcellulose and 0.1% polysorbate 80
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 250 mg/mL

MAXIMUM DOSE VOLUME APPLIED:
20 mL/kg bw
Doses:
5000 mg/kg bw
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: mortality twice on working days and once on weekend days; signs and symptoms daily; body weight at start and on days 7 and 14
- Necropsy of survivors performed: yes; at the end of the observation period
Statistics:
From the body weights, the group means and their standard deviations were calculated
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 5 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: No mortality was observed at this unique dose level
Mortality:
No mortality occurred
Clinical signs:
- Dyspnea, exophthalmos, ruffled fur, and curved body position were seen, being common symptoms in acute tests.
- Additionally, a red discoloration of the body was observed from day 1 to 4 after administration.
- The animals recovered within 11 days.
Body weight:
No adverse effects observed (see Table 1)
Gross pathology:
No deviations from normal morphology were found at necropsy

Table 1: Mean body weights (g) and standard deviation

Dose level (mg/kg bw)

Males

Females

Day 1

Day 7

Day 14

Day 1

Day 7

Day 14

5000

227±6.2

265±7.4

306±7.6

212±7.5

211±13.7

224±14.3

 

Interpretation of results:
practically nontoxic
Remarks:
Migrated information
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
discriminating dose
2 000 mg/kg bw
Quality of whole database:
Reliable and valid.

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 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:
read-across source
Reason / purpose:
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 Red 220 (CAS 68259-05-2, 926 g/mol)

Pigment Red 220 was studied for acute oral toxicity in four studies of which only one is reliable and adequate (Ciba-Geigy Ltd 1987). The study was performed according to GLP and OECD guideline 401 with a limit dose of 5000 mg/kg bw. No mortality occurred. Dyspnea, exophthalmos, ruffled fur, and curved body position were seen, being common symptoms in acute tests. Additionally, a red discoloration of the body was observed from day 1 to 4 after administration. The animals recovered within 11 days. The information is consistent with poorly documented data from 1965 and a study run at CRO that was known to have falsified study reports (IBT 1972).

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. No mortality occurred at the limit dose of 2000 mg/kg bw. As a result the substance is not considered to be classified for acute oral or inhalation toxicity under Regulation (EC) No. 1272/2008.