A mixture of: N-(4-chlorophenyl)-4-(2,5-dichloro-4-(dimethylsulfamoyl)phenylazo)-3-hydroxy-2-naphthalenecarboxamide; N-(4-chlorophenyl)-4-(2,5-dichloro-4-(methylsulfamoyl)phenylazo)-3-hydroxy-2-naphthalenecarboxamide

Endpoint summary

Description of key information

acute oral toxicity (KEY_401_1990_RCC_263946): LD50 >2000 mg/kg bw
acute dermal toxicity (KEY_402_1993_Pharmakon_67492): LD50 >2000 mg/kg bw
acute inhalation toxicity: No study available

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:

other: well performed GLP and OECD guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

no

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: BRL, Biological Research Laboratories Ltd., Wölferstrasse 4, CH-4414 Füllinsdorf
- Age at study initiation: males: 9 weeks, females: 11 weeks
- Weight at study initiation: males: 188 - 197 g, females: 170 - 182 g
- Fasting period before study: 12 to 18 hours
- Housing: Groups of five in Makrolon type-3 cages with standard softwood bedding
- Diet (e.g. ad libitum): Pelleted standard Kliba 343, rat maintenance diet, ad libitum
- Water (e.g. ad libitum): Community tap water, ad libitum
- Acclimation period:

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22+/-3
- Humidity (%): 40-70
- Air changes (per hr): 10-15 air changes per hour
- Photoperiod (hrs dark / hrs light): 12/12

Route of administration:

oral: gavage

Vehicle:

polyethylene glycol

Remarks:

PEG 400

Details on oral exposure:

VEHICLE
- Application Volume / kg body weight: 10 ml at 2000 mg/kg

Doses:

2000 mg/kg

No. of animals per sex per dose:

5

Control animals:

no

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

Male: 2000 mg/kg bw; Number of animals: 5; Number of deaths: 1
Female: 2000 mg/kg bw; Number of animals: 5; Number of deaths: 0

Clinical signs:

other: 2000 mg/kg: males - breathing: rales (1), males - no clinical signs (4) females - no clinical signs (5)

Gross pathology:

2000 mg/kg:

dead: lungs: discoloration, pale (1)

sacrificed: lungs: discoloration, dark red (1)
no macroscopical organ changes (8)

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

LD50 > 2000 mg/kg bw
The test item is not subject to classification and labelling.

Executive summary:

In accordance with OECD TG 401 the test article was administered to rats of both sexes by oral gavage, at a single dose of 2000 mg/kg.

DEATH RATE:

10% at 2000 mg/kg (i.e. 1/10).

CLINICAL SIGNS:

males:

- breathing: rales (1)

- no clinical signs (4)

females

- no clinical signs (5)

The male animal had recovered after 2 observation days.

BODY WEIGHTS:

The body weight gain of the animals was not affected by the test article treatment throughout the entire study period.

MACROSCOPICAL FINDINGS:

dead:

- lungs: discoloration, pale (1)

sacrificed:

- lungs: discoloration, dark red (1)

- no macroscopical organ changes were observed (8)

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

discriminating dose

Value:

2 000 mg/kg bw

Quality of whole database:

Reliable quality without any restrictions.

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

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: well performed GLP and OECD guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

no

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Iffo-Credo, B.P. 0109 (69592 L'Arbresle Cedex - France)
- Age at study initiation: 5 to 7 weeks
- Weight at study initiation: 200 to 300 g
- Housing: in on air-conditioned building, individually in polycarbonate cages type FI (305 x 180 x 184 mm).
- Diet (e.g. ad libitum): pelleted complete Diet (rat -mouse Diet), ad libitum
- Water (e.g. ad libitum): filtered mains drinking water, ad libitum
- Acclimation period: 5 days minimum between animal arival and start of treatment

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 to 25°C (target range)
- Humidity (%): 30 to 70 % RH (target range)
- Air changes (per hr): minimum 8 air changes per hour

Type of coverage:

semiocclusive

Vehicle:

corn oil

Details on dermal exposure:

TEST SITE
- Area of exposure: not be less than 10 % of the total body surface
- Type of wrap if used: semi-occlusive bandage

REMOVAL OF TEST SUBSTANCE
- Washing (if done): wiped clean of residual test article using water or other convenient means
- Time after start of exposure: 24 h

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2000 mg/kg bw
- Concentration (if solution): 29.69 % (W/V) in the vehicle (forming a paste)
- For solids, paste formed: yes

Duration of exposure:

24 h

Doses:

once 2000 mg/kg bw in corn oil (29.69 % W/V)

No. of animals per sex per dose:

5 males / 5 females

Details on study design:

- Duration of observation period following administration: 15 days
- Frequency of observations and weighing: Examinations for mortality and abnormal clinical signs were performed 15 minutes after application, then at 1, 2 and 4 hours, and then daily for the 14 day study period. Cutaneous examinations were performed from day 2 to 15.
- Frequency of weighing: D1, D8, D15
- Necropsy of survivors performed: yes

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

Male: 2000 mg/kg bw; Number of animals: 5; Number of deaths: 0
Female: 2000 mg/kg bw; Number of animals: 5; Number of deaths: 0

Clinical signs:

other: No changes in behaviour or clinical signs in any of the treated animals during the observation period.

Gross pathology:

There were no macroscopic findings that could be associated with treatment.

Other findings:

No oedema and erythema were noted to the application site of the test article during the observation period (reading of the erythematous lesions were impossible from Day 2 to Day 5 because of a reddish colour observed to the cutaneous fur). Desquamation was noted on Days 6 and 7.

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The LD50 was estimated to be >= 2000 mg/kg bw for male and female rats.

Not subject of classification and labelling

Executive summary:

The test article was applied, once only as a paste in corn oil at a dose level of 2000 mg/kg, by the cutaneous route, in the Sprague- Dawley rat (5 males + 5 females). Examinations for mortality and abnormal clinical signs were performed 15 minutes after application, then at 1, 2 and 4 hours, and then daily for the 14 day study period. Cutaneous examinations were performed from day 2 to 15. All the animals were weighed immediately before application of the test article (Day 1), on Days 8 and 15. A necropsy was performed for all the animals after the final in vivo observation on Day 15.

There were no changes in behaviour or clinical signs in any of the treated animals during the observation period.

No oedema and erythema were noted to the application site of the test article during the observation period. Desquamation was noted on Days 6 and 7.

Body weight changes in the treated animals were not influenced by treatment.

At necropsy there were no macroscopic findings that could be associated with treatment.

The LD50 was estimated to be >= 2000 mg/kg bw for male and female rats.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

discriminating dose

Value:

2 000 mg/kg bw

Quality of whole database:

Reliable quality without any restrictions.

Additional information

Justification for selection of acute toxicity – oral endpoint
well performed GLP and OECD guideline study / no other study available

Justification for selection of acute toxicity – dermal endpoint
well performed GLP and OECD guideline study / no other study available

Justification for classification or non-classification

After oral and dermal exposure at doses up to 2000 mg/kg bw LD50 values were determined to be above 2000 mg/kg bw. Also no specific targed organ toxicity was observed. Therefore Pigment Orange 74 is considered not to be acutely toxic and does not have to be classified regarding acute toxicity or STOT SE according to the criteria laid down in Directive 67/548/EEC and in Regulation (EC) No 1272/2008.