Sodium 1-amino-4-[[3-[(benzoylamino)methyl]-2,4,6-trimethylphenyl]amino]-9,10-dihydro-9,10-dioxoanthracene-2-sulphonate

Endpoint summary

Description of key information

LD50 oral = 8850 mg/Kg bw

LC50 inhal. > 6 mg/m³

LD50 dermal > 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:

July 7, 1976

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

GLP compliance:

no

Remarks:

pre GLP

Test type:

standard acute method

Limit test:

no

Species:

rat

Strain:

other: TIF RAIF

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Weight at study initiation: the mean initial body weight of the groups ranged from 80 to 110 grams
- Diet: standard diet of pellets - No. 890, Nafag Gossau SG. Fasted overnight before treatment
- Water: ad libitum
- Acclimation period: minimum 5 days
- Housing: During the treatment and observation period the animals were housed in groups of 5 in Macrolon cages.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22±1°C
- Humidity (%): 55*5 %
- Photoperiod (hrs dark / hrs light): 14 hours light cycle day

Route of administration:

oral: gavage

Vehicle:

other: sesame oil

Details on oral exposure:

Concentrations of substance in vehicle:
- 10 % (1000mg/kg)
- 30 % (3000mg/kg)
- 20 % (8000mg/kg)
- 25 % (10000mg/kg)
- 25 % (15000mg/kg)

Doses:

1000, 3000, 5000, 8000, 10000, 15000 (mg/kg)

No. of animals per sex per dose:

5 per sex per dose

Control animals:

no

Details on study design:

Physical condition and rate of death were monitored throughout the whole observation period.
Post observation period = 15 days

Sex:

male/female

Dose descriptor:

LD50

Effect level:

ca. 8 850 mg/kg bw

Based on:

test mat.

95% CL:

> 7 960 - < 9 900

Sex:

male/female

Dose descriptor:

LD50

Effect level:

ca. 5 664 mg/kg bw

Based on:

act. ingr.

Mortality:

1000, 3000 mg/Kg bw: no death occurs
8000 mg/Kg bw: 1 female died in a day
10000 mg/Kg bw: 4 male and 5 female died in a day
15000 mg/Kg bw: all animals died in a day

Clinical signs:

other: 1000 mg/Kg bw: none 3000 mg/Kg bw: diarrhea, after 24 hours no symptoms 8000 mg/Kg bw: ditto, reduction in spontaneous motility, ataxia, ventricumbency, muscular hypotonia, hypoventilation. After 2 days no symptoms 10000 mg/Kg bw: ditto 15000 mg/Kg bw: di

Interpretation of results:

GHS criteria not met

Conclusions:

LD50 = 8850 mg/Kg bw

Executive summary:

Method:

Similar to OECD guideline 401.

 

Observations:

At a concentrations of 8000 mg/Kg a death occured after a day. At 10000 mg/Kg bw nine animals death after a day and at 15000 mg/Kg bw ten animals death after a day.

All animals died in respiratory failure.

 

Results:

LD50 = 8850 mg/Kg bw (LD50 = 5664 mg/kg bw based on active ingredient).

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

8 850 mg/kg bw

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LC50

Value:

6 mg/m³ air

Quality of whole database:

low reliability test

Acute toxicity: via dermal route

Link to relevant study records

Reference

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

weight of evidence

Study period:

From July 19 to August 2, 1979

Reliability:

4 (not assignable)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Qualifier:

according to guideline

Guideline:

other: standards of AAALAC 16 CFR 1500.3

Principles of method if other than guideline:

Similar to OECD guideline 402 with substancial deviation related to number of animals used.

GLP compliance:

no

Remarks:

pre GLP

Test type:

fixed dose procedure

Limit test:

yes

Species:

rabbit

Strain:

New Zealand White

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Ace Animals
- Age at study initiation: at least 8 weeks old when received.
- Weight at study initiation: 2.3 - 2.6 Kg.
- Housing: suspended wire mesh cages (30" x 18" x 18").
- Diet: Fresh Purina rabbit chow ad libitum.
- Water: ad libitum.
- Acclimation period: at least one week.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 - 21°C

Type of coverage:

semiocclusive

Vehicle:

not specified

Details on dermal exposure:

TEST SITE
- Area of exposure: 200 square cm.
- % coverage: 10%
- Type of wrap if used: gauze patches.

REMOVAL OF TEST SUBSTANCE
- Washing: exposure site washed with warm tap water.
- Time after start of exposure: 24 hours.

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2.0 g/Kg.

Duration of exposure:

24 hours

Doses:

2.0 g/Kg

No. of animals per sex per dose:

2 per sex per dose

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: daily for 14 days for signs of toxicity, pharmacological effects and mortality. Body weights were recorded pretest and in the survivors at 7 and 14 days.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, gross pathology.

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

All animals survived at a limit dose of 2.0 g/Kg

Clinical signs:

other: very slight edema was noted in all animals at 24 h.

Toxic Signs:

All animals appeared normal at all times.

 

Necropsy observations:

All animals were normal during the observation period.

Interpretation of results:

GHS criteria not met

Conclusions:

LD50 > 2000 mg/Kg bw

Executive summary:

Method:

Standards of AAALAC 16 CFR 1500.3. Similar to OECD guideline 402 with substancial deviation related to the number of animals used.

 

Observation:

All animals survived this test in good health. Erythema scores could not be determined at 24 hours. All other erythema scores were zero. Very slight edema was noted at 24 hours. All other edema scores were zero. All animals were normal at necropsy.

 

Results:

LD50 > 2000 mg/Kg bw

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Additional information

The test substance was evaluated for its potential acute toxicity in rats.

 

Acute Toxicity: Oral

The study was performed according to internal standard procedure similar to OECD guideline 401, following oral administration of multiples doses to the rats. No mortality occurred during the study and no abnormalities were observed. There was no effect on body weight gain. The gross necropsy conducted at termination of the study revealed no observable abnormalities.

The acute oral LD50 was determined to be 8850 mg/kg bw.

This result is in line with that achieved by other tests (reliability = 4), listed in the table below.

 

Acute Toxicity: Inhalation

The evaluation of acute inhalation toxicity has been performed according to standards of AAALAC 16 CFR 1500.3, similar to OECD Guideline 403 with substancial deviation related to the limit test. No mortality occurred during the study. An animal exhibited ptosis and dyspnea on Day 2. A second animal exhibited grooming at hour 1. At all other times all animals appeared normal. There was no effect on body weight gain.

The acute LC50 was determined to be greater than 6 mg/m³.

 

Acute Toxicity: Dermal

The evaluation of acute dermal toxicity has been performed according to standards of AAALAC 16 CFR 1500.3, similar to OECD guideline 402 with substancial deviation related to the number of animals used.

No mortality occurred during the study. Only a very slight edema was noted in all animals at 24 h. No effect on body weight gain. The gross necropsy conducted at termination of the study revealed no observable abnormalities.

The acute LD50 was determined to be greater than 2000 mg/Kg bw.

Justification for classification or non-classification

According to the CLP Regulation (EC n. 1272/2008), 3.1 Acute toxicity section, substances can be allocated to one of four toxicity categories based on acute toxicity by the oral, dermal or inhalation route according to numeric criteria. Acute toxicity values are expressed as (approximate) LD50 (oral, dermal) or LC50 (inhalation) values or as acute toxicity estimates (ATE).

 

The oral LD50 value was established to be 8850 mg/Kg body weight, therefore the test substance is out of any classification limit for acute oral toxicity (oral acute toxicity Category 4: 300 < ATE ≤ 2000 mg/Kg bw).

 

The dermal LD50 value was established to be higher than 2000 mg/Kg body weight, which exceeded the highest CLP limit for classification (dermal acute toxicity Category 4: 1000 < ATE ≤ 2000 mg/Kg bw).

 

The inhalation LC50 value is higher than 0.006 mg/L, that is the limit of the tested concentration, which doesn’t give sufficient information about the CLP classifications because lower than the treshold limit for the classification ( for vapours, inhalation acute toxicity Category 1: ATE ≤ 0.5 mg/L).

 

In conclusion, using the data obtained from oral and dermal acute toxicity, it is possible to conclude that the test substance is not classified for acute toxicity, according to the CLP Regulation (EC n. 1272/2008).