Sodium 6-amino-5-[[2-[(cyclohexylmethylamino)sulphonyl]phenyl]azo]-4-hydroxynaphthalene-2-sulphonate

Endpoint summary

Description of key information

The oral LD50 for Acid Red 361 was found to be >5000 mg/kg bw, while the dermal LD50 was >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:

experimental study

Adequacy of study:

key study

Study period:

1984

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

no

GLP compliance:

no

Test type:

standard acute method

Limit test:

yes

Specific details on test material used for the study:

Code No: FAT 20003/G
Batch NO: EN 200106.49
Stability: guaranteed by the sponsor until June 1989
Description: solid
Contents of active ingredient: 80.5 %
Test Article Received: July 5, 1984

Species:

rat

Strain:

other: Tif: RAIf (SPF), F3-crosses of RII 1/Tif x RII 2/Tif

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Age at study initiation: 7-8 weeks
- Weight at study initiation: 170-198 g
- Fasting period before study: Overnight fasting
- Housing: The animals were kept under conventional laboratory conditions. They were caged in groups of 5 in Macrolon cages type 4 with standardized soft wood bedding (Societe Parisienne des sciures, Pantin).
- Diet: Rat food, NAFAG No. 890, NAFAG AG, Gossau, SG (Switzerland), ad libitum
- Water: ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature: 22±3°C
- Humidity: 5515%
- Air changes: 15 air changes/h
- Photoperiod: 12 h light/12 h day

IN-LIFE DATES: From: July 10, 1984 to: July 24, 1984

Route of administration:

oral: gavage

Vehicle:

arachis oil

Details on oral exposure:

MAXIMUM DOSE VOLUME APPLIED: 20 mL

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 or until all symptoms have disappeared, whichever lasts longer
- Frequency of observations:
Mortality: daily; a.m. and p.m. on working days, a.m. on weekend days;
Signs and symptoms: daily
Body weight: on Days 1, 7, 14 and at death
- Necropsy of survivors performed: Yes; spontaneously dying animals were submitted to gross necropsy as soon as possible; survivors at the end of the observation period.

Statistics:

From the body weights, the group means and their standard deviations were calculated.
Where feasible, the LD50 including the 95 % confidence limits were computed by the logit method (J. Berkson, J.Am. Stat. Ass. 39. 357-65, 1944).

Preliminary study:

not applicable

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 5 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortality was observed throughout the observation period.

Clinical signs:

other: Dyspnoea, exophthalmos, ruffled fur, and curved body position were seen. In addition, a slight sedation and diarrhoea were observed shortly after the application. The animals recovered within 11 days.

Gross pathology:

No treatment-related deviations from normal morphology could be detected.

Other findings:

none

Interpretation of results:

GHS criteria not met

Conclusions:

The oral LD50 of the test substance was >5000 mg/kg bw.

Executive summary:

A study was conducted on FAT 20003/G to assess the acute oral toxicity of the test substance in Tif: RAIf (SPF) rats according to OECD Guideline 401.

A group of 10 fasted animals (5/sex/dose) received a single oral (gavage) dose of 5000 mg/kg bw of the test substance. Parameters assessed included mortality, clinical observations, body weight and necropsy findings in all animals during a 14 d observation period.

No mortality was observed throughout the observation period. Normal body weight gains were recorded in all the animals throughout the study. Dyspnoea, exophthalmos, ruffled fur, and curved body position were seen. In addition, a slight sedation and diarrhoea were observed shortly after dosing. The animals recovered within 11 days. Terminal necropsy findings were normal.

Under the study conditions, the oral LD50 of the test substance was >5000 mg/kg bw in male and female rats.

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

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

the study does not need to be conducted because exposure of humans via inhalation is not likely taking into account the vapour pressure of the substance and/or the possibility of exposure to aerosols, particles or droplets of an inhalable size

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:

1979

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:

Sample Name : Tectilon Red 2B KWL
Product # : 01-135303-100-0
Batch # : E 525, DCT #80220
Material received : 9/25/78

Species:

rabbit

Strain:

New Zealand White

Sex:

male/female

Details on test animals or test system and environmental conditions:

New Zealand White rabbits approximately 8 to 11 weeks of age were, received in good health from our local supplier and remained in good health during the equilibration period in this laboratory. The rabbits were equilibrated for at least 7 days. The rabbits were individually housed in elevated wire mesh cages in temperature-controlled rooms reserved exclusively for rabbits on acute tests.
Each animal was identified by a uniquely numbered metal tag affixed to its ear. Purina Rabbit Chow and water from bottles were available ad libitum.

Type of coverage:

occlusive

Vehicle:

water

Remarks:

Red Powder-used as 50 % weight/volume suspension in distilled water

Details on dermal exposure:

Twenty-four hours prior to dosing the backs of the rabbits were clipped free of fur with an Oster ANG-RA clipper head designed specifically for clipping rabbits. The rabbits were returned to their cages overnight. Just prior to dosing, the backs of even-numbered rabbits were abraded with a 21-gauge bent tip needle. The abrasions, made every 2 to 3 cm longitudinally, scratched the stratum corneum, but did not disturb the derma or produce bleeding.

The test material was applied to the backs of two male and two female rabbits at a dose of 2000 mg/kg. The test site was covered with gauze and the trunk was wrapped with impervious material for 24 hours. Following removal of the binder at 24 hours, the test site was washed with warm tap water. One hour after washing, the test sites were graded for skin irritation. Skin sites were read again at 7 and 14 days.

Duration of exposure:

24 hours

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

2 males and 2 females

Control animals:

no

Details on study design:

Body weights were recorded pretest and at 7 and 14 days. The rabbits were observed daily for 14 days for signs of toxicity and mortality. Necropsies were performed on all rabbits.

Statistics:

None

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

One (animal #4) out of the 4 animals was found dead on day 8.

Clinical signs:

other: Yellow nasal discharge - Animal #2, days 4-6, 11-13 Mucus in stool - Animal #4, days 3-6 Diarrhea - Animal #4, days 3-7 Ptosis - Animal #4, days 6 & 7 Lethargy - Animal #4, day

Gross pathology:

Animal #1 and 3 - No gross pathological observations.
Animal #2 : yellow exudate, nose/mouth; dark areas on lungs.
Animal #4 - yellow areas on intestines; red areas on stomach; mottled liver; dark lungs; mottled and pale kidney, dark and small spleen.

Interpretation of results:

GHS criteria not met

Conclusions:

The acute dermal LD50 was found to be greater than 2000 mg/kg bw.

Executive summary:

FAT 20003 was tested for acute dermal toxicity potential (LD50) using methodology similar to OECD Guideline 402. The test substance was applied to back of two male and two female rabbits at a dose of 2000 mg/kg bw (1 intact and 1 abraded animal/ sex/ group). The test site was covered with gauze and trunk was wrapped with impervious material for 24 hours. After patch removal, animals were observed for 14 days for mortality, clinical signs and changes in bodyweight. They were submitted at random to a necropsy whenever they died, survivors at the end of the observation period. One animal (#4) with abraded skin was found dead on day 8. No other mortality was observed. Hence, the acute dermal LD50 was found to be greater than 2000 mg/kg bw.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Additional information

Oral:

Several acute oral toxicity studies are available with Acid Red 361.

In the study designated as key, and conducted in accordance with OECD Guideline 401, no mortality was observed at 5000 mg/kg bw. Normal body weight gains were recorded in all the animals throughout the study. Dyspnoea, exophthalmos, ruffled fur, and curved body position were seen. In addition, a slight sedation and diarrhoea were observed shortly after dosing. The animals recovered within 11 days. Terminal necropsy findings were normal. Hence, the oral LD50 of the test substance was considered to be >5000 mg/kg bw in male/female rats.

Three more supporting studies are available and were conducted using methodology similar to OECD Guideline 401. In the study with FAT 20003 (1973), 4/5 males and 1/5 females were found dead on second day of observation at the dose of 10000 mg/kg bw. No clinical signs were observed at the dose of 1000 mg/kg bw. At the doses of 3000 and 10000 mg/kg bw, clinical signs observed included reduction'in spontaneous motility, slight hyperreflexia and diarrhea. Symptoms lasted for more than 3 hours. After 24 hours, no symptoms were observed. No substance related gross pathological changes were observed. Hence, based on these findings, LD50 was estimated to be 10000 mg/kg bw.

In the two other supporting studies conducte with FAT 20003/A (1973) and FAT 20003/F (1980), no mortality was seen with the highest dose (15000 mg/kg bw for FAT 20003/A) or limit dose (5000 mg/kg bw for FAT 20003/F). Hence, the LD50 reported in those studies were >5000 and >15000 mg/kg bw respectively.

Inhalation:

Currently no study to assess the acute inhalation toxicity potential of Acid Red 361 is available. However, the vapour pressure for the substance can be considered low owing to the high melting point (>298 °C). Hence the substance is considered to have low volatility. Synthesis and spray drying of this chemical is performed in a closed process; the final product consists of non-dusty granules. Hence, the use of this substance will not result in aerosols, particles or droplets of an inhalable size, so exposure to humans via the inhalation route will be unlikely to occur. Further the chemical was found to have low acute toxicity when tested via oral route with no mortality when tested up to 5000 mg/kg bw. Hence, considering all the above arguments, it is considered that Acid Red 361 has a low toxicity potential via inhalation route and thus the study on acute inhalation toxicity is considered scientifically not necessary.

Dermal:

FAT 20003 was tested for acute dermal toxicity potential (LD50) using methodology similar to OECD Guideline 402. The test substance was applied to back of two male and two female rabbits at a dose of 2000 mg/kg bw (1 intact and 1 abraded animal/ sex/ group). The test site was covered with gauze and trunk was wrapped with impervious material for 24 hours. After patch removal, animals were observed for 14 days for mortality, clinical signs and changes in bodyweight. They were submitted at random to a necropsy whenever they died, survivors at the end of the observation period. One animal (#4) with abraded skin was found dead on day 8. No other mortality was observed. Hence, the acute dermal LD50 was found to be greater than 2000 mg/kg bw.

Justification for classification or non-classification

Based on the available acute toxicity data with Acid Red 361, it does not warrant classification for acute toxicity as per the criteria of Regulation (EC) No. 1272/2008.