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Description of key information

Studies investigating oral, inhalation, and dermal acute toxicity are available.

Oral LD50 >6400 mg/kg bw

Inhalation LD50 >4760 mg/m3

Dermal LD50 >2500 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
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
GLP compliance:
no
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): C.I.Pigmentred 48:1, Monoazofarbstoff / Litholscharlach 3700
- Analytical purity: 100 %
Species:
rat
Strain:
not specified
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
-Source: Gassner (Breeder)
- Mean weight at study initiation: males 204 g; females 174 g

ENVIRONMENTAL CONDITIONS
not reported
Route of administration:
oral: gavage
Vehicle:
CMC (carboxymethyl cellulose)
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 20 % aequeous suspension of CMC. A higher concentration than 20 % could not be applicated for technical reasons.
Doses:
3200 mg/kg b.w.; 6400 mg/kg b.w.
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: Weighing was only performed at the beginning of the study for dose calculation. Observation of clinical signs was several times on the day of administration and once daily afterwards with the exception of weekends and on holidays.
- Necropsy of survivors performed: yes
Statistics:
No statistics were perfomed because (not necessary)
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 6 400 mg/kg bw
Mortality:
no mortality observed
Clinical signs:
Red feces.
Gross pathology:
no abnormalities detected
Interpretation of results:
GHS criteria not met
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
6 400 mg/kg bw

Acute toxicity: via inhalation route

Link to relevant study records
Reference
Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1993
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Test type:
standard acute method
Limit test:
yes
Specific details on test material used for the study:
- Substance type: red powder
- Physical state: solid
- Name of test material (as cited in study report): 4812 C-93/1068
- Purity: > 95%
- Expiry date: > 5 years (1998)
- Lot/batch No.: 93/1068
- Storage condition of test material: room temperature
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Charles River (UK) Ltd., Manston, Kent (UK)
- Age at study initiation:
- Weight at study initiation: malles weighed 237 - 264g, and the females 200 - 207g
- Fasting period before study: not applicable
- Housing: groups of five by sex in
- Diet and water (e.g. ad libitum): With the exception of the exposure period, free access to mains drinking water and food (Rat and Mouse Expanded Diet No. 1, Special Diet Services Limited, Witham, Essex, U.K.)
- Acclimation period: 5 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18 - 23°C
- Humidity (%): 46 - 61%.
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12


IN-LIFE DATES: From: 12 August 1993 To: 31 August 1993
Route of administration:
inhalation: dust
Type of inhalation exposure:
nose only
Vehicle:
air
Mass median aerodynamic diameter (MMAD):
1.4 µm
Geometric standard deviation (GSD):
0.34
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: Nose-only apparatus
- Exposure chamber volume: 30 Litres
- Method of holding animals in test chamber: tapered, polycarbonate restraining tube fitted onto a single tier of the exposure chamber and sealed by means of a rubber '0' ring
- Source and rate of air: Compressed air was supplied by means of a Gast oil free compressor and was passed through a water trap and respiratory quality filters which removed particulate material above 0.005 μm before it was introduced to the dust feed. Flow rate was 8 litres/min providing 36 air changes per hour.
- Method of conditioning air: Compressed air was supplied by means of a Gast oil free compressor and was passed through a water trap and respiratory quality filters which removed particulate material above 0.005 μm before it was introduced to the dust feed.
- System of generating aerosols: Wright Dust Feed' mechanism located at the top of the exposure chamber and driven by a variable speed motor. The dust feed was connected to a metered compressed air supply.
- Method of particle size determination: Cascade Impactor (10, 6, 3.5, 1.6, 0.9 and 0.5 μm cut-off points)
- Treatment of exhaust air: Extract from the exposure chamber passed through a 'scrubber' trap and was connected with a high efficiency filter to a metered exhaust system.
- Temperature, humidity, pressure in air chamber: negative pressure, humidity 41 - 50%, temperature 20 - 23°C


TEST ATMOSPHERE
- Brief description of analytical method used: Gravimetric method, employed glass fibre filters (Gelman type A/E 25 mm) placed in a filter holder. The holder was temporarily sealed in a vacant port in the exposure chamber in the animals' breathing zone. Exposure chamber air was drawn through the filter at a measured rate using a vacuum pump for a suitable time period.
- Samples taken from breathing zone: yes


TEST ATMOSPHERE
- Particle size distribution: 83.1% < 4 μm; 100% < 10 μm
- MMAD (Mass median aerodynamic diameter) / GSD (Geometric st. dev.): 1.4 μm / 0.34

The tested concentration was the highest attainable concentration.
Analytical verification of test atmosphere concentrations:
yes
Duration of exposure:
4 h
Concentrations:
4.76 mg/L
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
Key result
Sex:
male/female
Dose descriptor:
LC50
Effect level:
>= 4.76 mg/L air (analytical)
Exp. duration:
4 h
Remarks on result:
other: range between 3.24 and 6.34 mg/L; 1/10 rats died.
Mortality:
One male was found dead approximately 186 minutes after the start of the exposure.
Clinical signs:
other: During exposure animals commonly showed wet fur, laboured, decreased or increased respiratory rate and red staining of the fur from the test material. On removal from the chamber and one hour after completion of exposure additional signs of toxicity noted
Body weight:
A marginal reduction in bodyweight gain was noted in several animals during the first week of the study. Expected bodyweight development was observed during week two.
Gross pathology:
The male that died during the study showed swollen and abnormally dark lungs and pink contents in the small intestine at necropsy. No abnormalities were detected in surviving animals at the end of the study.
Interpretation of results:
GHS criteria not met
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LC50
Value:
4 760 mg/m³

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
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 402 (Acute Dermal Toxicity)
GLP compliance:
no
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): Litholscharlach 3700 / C.I.Pigmentred 48:1, Monoazofarbstoff.
- Analytical purity: 100 %
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Wiga, Ottobrunn, D.
- Mean weight at study initiation: males 137 g, females 123 g

ENVIRONMENTAL CONDITIONS
not reported
Type of coverage:
occlusive
Vehicle:
water
Details on dermal exposure:
TEST SITE
- Area of exposure: dorsal, p.c., 50 cm2

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2.5 g/kg animal
- Concentration (if solution): 50 % aequous suspension
- For solids, paste formed: yes

Duration of exposure:
24 h
Doses:
2500 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: No weighing was done. Observation was several times at the day of exposure and presumably daily exception of weekends and holidays afterwards.
- Necropsy of survivors performed: yes
Statistics:
LD50 was estimated approximately
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 500 mg/kg bw
Mortality:
0/10 animals died after the 24h h exposure
Clinical signs:
no abnormalities detected
Body weight:
Not reported
Gross pathology:
No abnormalities detected
Other findings:
- After 24 hours: 10/10 red substance residues, local erythema not detectable.
- After 8 days: 10/10 animals: pink-coloured substance residues
Interpretation of results:
GHS criteria not met
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
2 500 mg/kg bw

Additional information

Acute oral toxicity

Two valid rat studies are available for acute oral toxicity. In one study, a product of adequately high purity was tested at doses of up to 6400 mg/kg bw (BASF 1974). In the other study, a commercial product of unknown purity was tested at doses of 5000 and 10000 mg/kg bw (BASF 1972). The procedures are comparable to OECD testing guideline 423 (2001) with the exception that the observation period is only 7 or 8 days rather than 14 days and that no necropsy was performed in the older study. The studies were performed prior to introduction of GLP, but are described in adequate detail.

Data on the sulfonated amine moiety of Pigment Red 48:1 is also available (4-amino-6-chlorotoluene-3-sulphonic acid; CAS 88-51-7). This moiety is not acutely toxic via the oral route (LD50 >7500 mg/kg bw).

Acute inhalation toxicity

The key study for acute inhalation toxicity (Capelle 1993) was performed in rats following OECD testing guideline 403 and GLP. Rats were exposed to an aerosol at a concentration of 4.76 mg/L (MMAD 1.4  μm / GSD 0.34). Material with adequately high purity was used and the particle size was in the respirable range as appropriate for rats. One male was found dead 3h after the start of the exposure. During exposure animals commonly showed wet fur, laboured, decreased or increased respiratory rate and red staining of the fur from the test material. On removal from the chamber and one hour after completion of exposure additional signs of toxicity noted in surviving animals included hunched posture, lethargy, pilo-erection, gasping and noisy respiration, ptosis and ataxia. One female showed tiptoe gait one hour after completion of exposure. Signs of toxicity including respiratory abnormalities were apparent for several days after exposure but with the exception of stained fur surviving animals appeared normal six to eight days after exposure.The male that died during the study showed swollen and abnormally dark lungs and pink contents in the small intestine at necropsy. No abnormalities were detected in surviving animals at the end of the study.

Data on the sulfonated amine moiety of Pigment Red 48:1 is also available (4-amino-6-chlorotoluene-3-sulphonic acid; CAS 88-51-7).This moiety is not acutely toxic via the inhalation route (LC50 >13.0 mg/L).

Acute dermal toxicity

The key study for acute dermal toxicity (BASF 1974) was performed in rats following a protocol which is comparable to OECD testing guideline 402 (1987). It was performed prior to the introduction of GLP but is documented adequately. Test material purity was adequate. No indication of adverse findings was observed during the 14-day observation period after single dermal application of a dose of 2500 mg/kg bw Pigment Red 48:1. Remnants of coloured test material interfered with the scoring of local irritation in all ten animals.

Justification for classification or non-classification

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, dermal or inhalation toxicity according to Classification, Labelling, and Packaging Regulation (EC) No. 1272/2008.