Registration Dossier

Administrative data

Description of key information

The acute oral LD50 of the a close analogue of the test substance was determined to be 3250 mg/kg bw.

The acute dermal LD50 of the test substance in rats was determined to be >2000 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:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Justification for type of information:
Please refer to the read-across justification attached to section 13.
Reason / purpose:
read-across source
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
3 250 mg/kg bw
Based on:
test mat.
95% CL:
> 2 598 - < 3 902
Remarks on result:
other: Result read-across source CAS No. 12237-23-9
Remarks:
Correction for molecular weight is not considered
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
3 250 mg/kg bw

Acute toxicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no study available

Acute toxicity: via dermal route

Link to relevant study records
Reference
Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
6 Sept. 2016 to 20 Sept. 2016
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Version / remarks:
February 24,1987
Qualifier:
according to
Guideline:
EPA OPPTS 870.1200 (Acute Dermal Toxicity)
Version / remarks:
August 1998
Qualifier:
according to
Guideline:
other: Japan MAFF Testing Guideline of 12 Nousan No. 8147, 2000 as this in line with OECD 402
Qualifier:
according to
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
GLP compliance:
yes (incl. certificate)
Remarks:
Bioassay - Labor für biologische Analytik GmbH, Im Neuenheimer Feld 515-519, 69120 Heidelberg
Test type:
standard acute method
Limit test:
yes
Specific details on test material used for the study:
- Name of test material (as cited in study report): Orasol Black X45
- Test item No.: 16/0051-1
- Batch identification: 002-150504
- EC No.: 916-865-0
- Content: 97.5 g/100 g (100 g/100 g minus water content)
- Homogeneity: The test item was homogeneous by visual inspection.
- Storage stability: Guaranteed by the sponsor, and the sponsor holds this responsibility.
- Expiry date: April 29, 2025
- Storage conditions: Room temperature
- Physical state/ color: Solid / black
Species:
rat
Strain:
Wistar
Remarks:
Crl:Wi (Han) SPF
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Wiga GmbH, Germany
- Reasons for selection of the test species: Rats were selected since this rodent species is recommended in the respective test guidelines. Wistar rats were selected since there is extensive experience available in the laboratory with this strain of rats.
- Females (if applicable) nulliparous and non-pregnant: yes
- Age at study initiation: male animals approx. 8 weeks, female animals approx. 12 weeks
- Weight at study initiation: average 230 g (males); average 207.4 g (females)
- Housing: Makrolon cage, type III
- Diet and water : ad libitum
- Acclimation period: at least 5 days before the beginning of the experimental phase

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3
- Humidity (%): 30 - 70 %
- Air changes (per hr): approx. 10
- Photoperiod (hrs dark / hrs light): 12 h / 12 h
Type of coverage:
semiocclusive
Vehicle:
corn oil
Details on dermal exposure:
TEST SITE
- Area of exposure: dorsal and dorsolateral parts of the trunk
- % coverage: About 40 cm² (corresponds to at least 10% of the body surface)
- Type of wrap if used: air-permeable dressing (4 layers of absorbent gauze (Ph. Eur. supplied by Lohmann GmbH & Co., KG) and stretch bandage (Fixomull® Stretch (adhesive fleece) supplied by Beiersdorf AG).

REMOVAL OF TEST SUBSTANCE
- Washing (if done): Rinse with warm water
- Time after start of exposure: At the end of the exposure time (24 h)

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 10 mL/kg bw
- Concentration (if solution): 20 g / 100 mL

VEHICLE
- Vehicle: Corn oil Ph.Eur.
- Reason for the vehicle: Good homogeneity in corn oil Ph.Eur.
- Form of application: Suspension
Duration of exposure:
24 h
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
5 males and 5 females
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
- weighing: shortly before application, weekly thereafter and on the last day of observation;
- clinical observations: several times on the day of application and at least once during each workday thereafter;
- scoring of skin findings: 30-60 minutes after removal of the dressing, several times thereafter and the last day of observation;
- mortality: at least once each workday
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, local effects (skin reactions), gross pathology
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality occurred.
Clinical signs:
No systemic clinical signs were observed during clinical examination
Body weight:
The body weight of the male animals increased within the normal range throughout the study period. The body weight of the female animals increased within the normal range throughout the study period with one exception. One female did not adequately gain weight during the first week, but gained weight in a normal range during the second week. Due to the fact that stagnation of body weight is commonly known for females after dermal applications, this stagnation is considered to be unspecific.
Gross pathology:
No macroscopic pathologic abnormalities were noted in the animals (5 males and 5 females) examined on the last day of observation.
Other findings:
Local effects:
Due to the black discoloration of the application site no erythema was assessable in the male animals from study day 1 until study day 3 after administration. Thereafter no erythema was observed.
Due to the black discoloration of the application site no erythema was assessable in the female animals on study day 1 after administration. Thereafter no erythema was observed.
Interpretation of results:
GHS criteria not met
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
2 000 mg/kg bw

Additional information

An acute dermal toxicity test is available for the substance itself. As no acute oral toxicity test is available for the substance itself, a read-across is made to a structural analogue of the substance.

Acute toxicity: Oral (Orasol Black CN, CAS 12237-23-9)

No acute oral study was available for the test substance. A very close analogue of the test substance, consisting of the same constituents in slightly different ratios, was tested and this substance was used as a source substance. The test item was studied in a study similar to OECD test guideline 401. Male (3 -5) and female (2 -5) rats (strain: RAI outdred SPF) were orally administrated via gavage at concentrations of 2.5%; 5%; 15%; 25%; 50% in CMC (carboxymethyl cellulose) as vehicle. The rats were observed for 8 days and examinations of clinical signs, body weight, organ weights were performed. 1/5 males and 2/5 females died at a dose of 3000 mg/kg bw (15%), 5/5 males and 3/5 females at 5000 mg/kg bw (25%) and all animals at 10000 mg/kg bw (50%). In addition, local effects (skin and feces black stained at 500 at concentration of 2.5% and 5%; ataxia, stiff movements, eyes, skin, feces black stained at 15%, 25% and 50%, at the concentration of 25% and 50% also piloerection) were observed with increasing concentration of the test item used. The acute oral LD50 in rats was calculated to be 3250 mg/kg. Based on the available information the test item is not considered to cause acute toxicity via the oral route (Ciba-Geiga Ltd, 1972).

Acute toxicity: Dermal (substance itself, EC 916-865-0)

In an acute dermal toxicity study (Limit Test), according to OECD guideline 402, young adult Wistar rats (5 males and 5 females) were dermally exposed to a single dose of 2000 mg/kg bw of Orasol Black X45 (as suspension in corn oil Ph.Eur.). The clipped application site (dorsal and dorso-lateral parts of the trunk, comprising at least 10% of the total body surface) was covered by semi-occlusive dressing during the 24-hour exposure period. The animals were observed for 14 days. No mortality or signs of systemic toxicity occurred. Due to the black discoloration of the application site erythema could not be assessed in the male animals from the first till the third study day and in the female animals on first study day after application. Thereafter, no erythema was observed. The body weight of the male and female animals increased within the normal range throughout the study period. However, one female animal did not adequately gain weight during the first week, but gained weight in a normal range during the second week. Due to the fact that stagnation of body weight is commonly known for females after dermal applications, this stagnation is considered to be unspecific. No macroscopic pathologic abnormalities were noted in the animals examined at the end of the study. The LD50 was determined to be > 2000 mg/kg bw. Based on the available information, the test item is not considered to cause acute toxicity via the dermal route (Bioassay, 2016).

Justification for classification or non-classification

Based on the available information classification for acute oral, inhalation or dermal toxicity is not warranted in accordance with EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation No. 1272/2008.