Calcium 3-hydroxy-4-[(4-methyl-2-sulphonatophenyl)azo]-2-naphthoate

Endpoint summary

Description of key information

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

Oral LD50 >5000 mg/kg bw

Inhalation LD50 >1518 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

Study period:

1987

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

comparable to guideline study

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)

Deviations:

no

GLP compliance:

yes

Test type:

acute toxic class method

Limit test:

yes

Specific details on test material used for the study:

- Pigment Red 57 content: 89%

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

SPF animals

Route of administration:

oral: gavage

Vehicle:

CMC (carboxymethyl cellulose)

Doses:

5000 mg/kg bw

No. of animals per sex per dose:

5 males and 5 females

Control animals:

no

Sex:

male/female

Dose descriptor:

LD0

Effect level:

>= 5 000 mg/kg bw

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

>= 5 000 mg/kg bw

Other findings:

Red stained faeces were seen 24 hours after administration of test article in all animals. All animals had recovered 48 hours after administration of test article.

Interpretation of results:

GHS criteria not met

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

5 000 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:

1976

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Remarks:

Non GLP, no details on test material other than batch and substance code. As pigments are very stable substances and the composition for this substance code is available elsewhere, this is considered acceptable. Some experimental details not described in the report. Overall sufficient details and adequate study design.

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

Deviations:

yes

Remarks:

Posttreatment observation did not include body weight. No information on frequency of cage-side observations.

GLP compliance:

no

Test type:

acute toxic class method

Limit test:

yes

Specific details on test material used for the study:

- Name of test material (as cited in study report): TK 10338
- Substance type: pigment
- Physical state: solid
- Analytical purity: no data in report, TK 10338 refers to a commercial product with 91% Pigment Red 57:1 and 9% additives.
- Lot/batch No.: EN 42374.76
- Expiration date of the lot/batch: no data
- Storage condition of test material: not indicated

Species:

rat

Strain:

other: Tif: RAIf (SPF)

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Ciba-Geigy Limited, bred on the premises
- Age at study initiation: no data
- Weight at study initiation: 180 to 185 g
- Fasting period before study: none
- Housing: in groups of 9 animals per cage
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 4 days for inhalation tubes


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22°C
- Humidity (%): 55%
- Air changes (per hr): not indicated
- Photoperiod (hrs dark / hrs light): 14 light cycle


IN-LIFE DATES: not given

Route of administration:

inhalation: dust

Type of inhalation exposure:

nose only

Remarks:

snout and nostrils

Vehicle:

air

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: The dust was generated by injecting the test material with the help of a "Grafix Exaktomat Injector" into an air stream which was discharged into the exposure chamber through a nozzle under a pressure of 2 atm. at a rate of 20 L/min.
- Exposure chamber volume: not applicable, as nose-only exposure
- Method of holding animals in test chamber: Rats were kept on separate PVC tubes positioned radially around the exposure chamber such that snout and nostrils of the animals only were exposed to the dust.
- Source and rate of air: 17.5 L/min
- Method of conditioning air: not indicated
- System of generating particulates/aerosols: The dust was generated by injecting the test material with the help of a "Grafix Exaktomat Injector" into an air stream which was discharged into the exposure chamber through a nozzle under a pressure of 2 atm. at a rate of 20 L/min.
- Method of particle size determination: The concentration and the particle size distribution of the dust in the vicinity of the animals was monitored at 1 hour intervals throughout the dust exposure. The size distribution of the dust particles was measured with a Cascade Impactor with selectron filters of 25 mm diameter and with a pore size of 0.2micrometer (Schleicher and Schuell) at an air flow rate of 17.5 L/min.
- Treatment of exhaust air: not indicated
- Temperature, humidity, pressure in air chamber: not indicated


TEST ATMOSPHERE
- Brief description of analytical method used: The concentration was determined gravimetrically by sampling the test atmosphere through a selectron filter of 50 mm diameter and with a pore size of 0.2 micrometer (Schleicher and Schuell, Feldbach, Switzerland) at an air flow rate of 10 L/min.
- Samples taken from breathing zone: indicated as "in the vicinity of the animals"


TEST ATMOSPHERE (if not tabulated)
- Particle size distribution: 15% > 7 micrometer, 68% 3 - 7 micrometer, 8% 1 - 3 micrometer and 9% < 1 micrometer
- MMAD (Mass median aerodynamic diameter) / GSD (Geometric st. dev.): not calculated


CLASS METHOD (if applicable)
- Rationale for the selection of the starting concentration:

Analytical verification of test atmosphere concentrations:

yes

Duration of exposure:

4 h

Concentrations:

1518 + 176 mg/m3 air

No. of animals per sex per dose:

9 males and 9 females

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: not indicated
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, gross pathology

Statistics:

not applicable

Sex:

male/female

Dose descriptor:

LC0

Effect level:

>= 1 518 mg/m³ air (analytical)

Exp. duration:

4 h

Remarks on result:

other: ± 176 mg/m3 air

Key result

Sex:

male/female

Dose descriptor:

LC50

Effect level:

> 1 518 mg/m³ air (analytical)

Exp. duration:

4 h

Remarks on result:

other: ± 176 mg/m3 air

Mortality:

No mortality observed

Clinical signs:

other: No effects observed

Body weight:

Not determined

Gross pathology:

No adverse findings

Other findings:

None recorded

Interpretation of results:

study cannot be used for classification

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LC50

Value:

1 518 mg/m³ air

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:

1973

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Remarks:

The study is comparable to OECD 402 with acceptable restrictions mostly due to reduced reporting in times prior to GLP.

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): Litholrubin 4630

C.I. Pigment Red 57:1, with "Harzseife" (resinate)
- Analytical purity: 100 %
- Physical state: solid

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: breeder (Wiga)
- Mean weight at study initiation: males: 133 g, females: 114g

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 solution
- 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:

None

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 500 mg/kg bw

Sex:

male/female

Dose descriptor:

LD0

Effect level:

>= 2 500 mg/kg bw

Mortality:

0/10 animals died after the 24 h exposure

Clinical signs:

other: no abnormalities detected

Gross pathology:

no abnormalities detected

Other findings:

- Other observations: after 24h red substance residues, redness not detectable, after 8 days red 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

Pigment Red 57:1 is of low acute oral toxicity as determined in several studies with rats performed between 1972 and 1987. The study performed in 1987 was chosen as key study because it was performed with a commercial sample according to the OECD testing guideline 423 (2001) and GLP and contains detailed sample information such as composition, origin and storage conditions in the study report. The commercial product had a sufficiently high pigment content and caused no indication any adverse acute effect with a limit dose of 5000 mg/kg bw. Rats showed red faeces during the first day which indicates excretion of the red pigment. In the older studies, commercial products with doses exceeding 5000 mg/kg bw were tested. In all studies LD50s exceeded the highest dosages tested. Overall, Pigment Red 57:1 is not acutely toxic after oral ingestion.

Acute inhalation toxicity

One valid study is available for assessment of the acute inhalation hazard (BASF 1976). This study was performed in rats with a commercial product following a protocol which is comparable to OECD testing guideline 403 (2009). It was performed prior to the introduction of GLP but the study is documented adequately. The commercial product had a sufficiently high pigment content. A limit test was performed with the highest concentration of dust that was technically achievable (1518 ± 176 mg/m3 air). The particle size was in the respirable range (60% in the range of 3 – 7 micrometer). No mortality, no clinical signs and no findings upon necropsy were observed. Body weight is only given for the beginning of the study. As no mortality occurred, the LD50 was determined to be >1518 mg/m3.

Acute dermal toxicity

The studies for acute dermal toxicity were performed with doses of commercial products ranging from 2000 to 8300 mg/kg bw. The key study was chosen based on the extent of reporting details. This study (BASF 1973) was performed in rats with a commercial product following a BASF protocol which is comparable to OECD testing guideline 402 (1987). It was performed prior to the introduction of GLP but is documented adequately. The commercial product contained an unknown amount of resin which is acceptable as a dose of 2500 mg/kg bw was applied. No indication of adverse findings was observed.

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.