Registration Dossier

Administrative data

Description of key information

Oral: LD50 > 5000 mg/kg bw (BASF: 80/404, 1981), rat (equivalent or similar to OECD 401). No adverse effects were observed.
Intraperitoneal: LD50 > 2000 mg/kg bw (BASF: 80/404, 1981), mouse. No adverse effects were observed. Based on the absence of mortality upon intraperitonel injection, testing of acute dermal toxicity was not considered necessary.

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:
other: Comparable to guideline study with acceptable restrictions (mostly due to reduced reporting in times before GLP)
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
yes
Remarks:
The application volume was not calculated by the individual weight, but by the mean weight per sex
Principles of method if other than guideline:
Standardized test method (BASF-Test)
GLP compliance:
no
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Willi Gassner, Sulzfeld, Germany
- Age at study initiation: about 12 weeks
- Mean weight at study initiation: males 170 g, females 180 g
- Fasting period before study: 16 hours
- Housing: 5 animals per cage; Type DK-Ill stainless steel wire mesh cages (Becker & Co., Castrop-Rauxel, Germany)
- Diet: Herilan, mouse/rat/hamster maintenance diet; H. Eggersmann KG, Rinteln, Germany, ad libitum
- Water: Fully demineralized water each workday ad libitum; on holidays tap water ad libitum
- Acclimation period: at least one week

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 - 26
- Humidity (%): 45 - 75
- Photoperiod (hrs dark / hrs light): 12 / 12
Route of administration:
oral: gavage
Vehicle:
CMC (carboxymethyl cellulose)
Remarks:
0.5 % aqueous carboxymethyl cellulose
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 31.6 % (w/v)
- Amount of vehicle (if gavage): 2.69 mL/male; 2.84 mL/female
- Justification for choice of vehicle: Aqueous formulation corresponds to the physiological medium

MAXIMUM DOSE VOLUME APPLIED: 15.8 mL/kg bw

DOSAGE PREPARATION (if unusual):
- Form of administration: Suspension

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: Recording of signs < 15, 15 and 30 minutes, 1 h, 2 h, 4 h and 5 h after administration of test substance and then once each workday. Check for moribund and dead animals twice each workday and once on weekends and public holidays.
- Frequency of weighing: Animals of comparable weights (± 10 g) in one cage. Group weighing before administration, 2nd weighing on days 2 - 4, 3rd weighing on day 7, 4th weighing on day 13 after administration.
- Necropsy of survivors performed: yes, withdrawal of feed 16 hours before sacrifice with CO2, then necropsy with gross-pathological
assessment. All animals that died are necropsied as early as possible.
- Other examinations performed: clinical signs, body weight
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 5 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: No mortality.
Mortality:
No mortality detected (0/10 animals).
Clinical signs:
No abnormalities detected.
Body weight:
No abnormalities in body weight gain detected.
mean body weight:
- day 0: males: 170 g, females: 180 g;
- day 2-4: males: 194 g, females: 201 g;
- day 7: males: 240 g, females: 224 g;
- day 13: males: 268 g, females: 231 g.
Gross pathology:
No abnormalities in sacrificed animals detected.
Interpretation of results:
practically nontoxic
Remarks:
Migrated information
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed

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 oral toxicity

In the BASF study (80/404, 1981) the acute oral toxicity of the test substance was determined after a single oral administration to rats. The study was a limit test conducted similar to the OECD-Guideline 401. The test substance in 0.5 % aqueous carboxymethyl cellulose was administered once orally via gavage to 5 Sprague-Dawley rats of each sex at a dose of 5000 mg/kg bw. The clinical signs were recorded up to 15 and 30 min, and 1, 2, 4, and 5 h after test substance administration, as well as once each workday at the following time until the end of the observation period of 14 days.

Body weight was determined on the day of study initiation and on day 2 - 4, 7, and 13 after gavage of the test substance.

No mortality occurred and no clinical signs were observed. Furthermore, no abnormalities were observed in body weight gain. Sacrificed animals did not show any gross-pathological changes, and hence, the oral LD50 was determined to be > 5000 mg/kg bw.

Acute inhalation toxicity

No data is available concerning acute inhalation toxicity. Inhalation is not a relevant route of exposure.

 

Acute dermal toxicity

No data is available concerning acute dermal toxicity.

In accordance with Annex XI (1.1.2) of the REACH legislation EC 1907/2006, testing may not appear scientifically necessary based on the use of existing data from experiments not carried out according to GLP or the test methods referred to in Article 13(3). In this case, an acute toxicity study with intraperitoneal application in mice is available (BASF, 80/404, 1981). This study is considered to represent the worst case in regard to systemic availability and to represent an adequate assessment for systemic toxicity upon inhalation or dermal toxicity. 5 NMRI mice of each sex received single i. p. injection of 2000 mg/kg bw test material. No mortality occurred and no effects on body weight gain were observed. Clinical signs were reported for both sexes and described as dyspnea, apathy, staggering, stretching, ruffled fur, and poor general state 5 hours after treatment up to 2 days. At necropsy, pathology revealed deposits of the substance in the intraperitoneal cavity indicating that the substance does not undergo significant metabolism. This is in line with the overall insolubility of the pigment.

 

Justification for classification or non-classification

Dangerous Substance Directive (67/548/EEC)

The available studies are considered reliable and suitable for classification purposes under 67/548/EEC. As a result the substance is not considered to be classified for acute oral or dermal or inhalation toxicity under Directive 67/548/EEC, as amended for the 31st time in Directive 2009/2/EG.

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 or inhalation toxicity under Regulation (EC) No. 1272/2008, as amended for the second time in Directive (EC 286/2011).