Trisodium 5-[[4-chloro-6-(methylphenylamino)-1,3,5-triazin-2-yl]amino]-4-hydroxy-3-[(2-sulphonatophenyl)azo]naphthalene-2,7-disulphonate

Endpoint summary

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Reference 1

Endpoint:

acute toxicity: oral

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

test procedure in accordance with national standard methods with acceptable restrictions

Justification for type of information:

REPORTING FORMAT FOR THE ANALOGUE APPROACH
1. HYPOTHESIS FOR THE ANALOGUE APPROACH
This read-across is based on the hypothesis that the source and the target substance have very similar physicochemical and (eco)toxicological properties because their chemical structures are nearly identical. An analogue approach has thus been employed. The target substance is Reactive Red 24 carrying a methyl group, while the source chemical is Reactive Red 24:1 carrying an ethyl group.
The presence of sulphonate groups make both dyes highly water soluble and therefore less critical for human health and environmental issues. Based on their chemical similarity, similar properties are expected in both humans and the environment.
2. SOURCE AND TARGET CHEMICAL(S)
Source: Reactive Red 24:1 (CAS# 72829-25-5 / EC# 276-911-4)
Target: Reactive Red 24 (CAS# 70210-20-7 / EC# 274-417-3)
3. ANALOGUE APPROACH JUSTIFICATION
see attachment under 4.12 Auto flammability

Reason / purpose for cross-reference:

read-across source

Reason / purpose for cross-reference:

read-across source

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 5 000 mg/kg bw

Based on:

test mat.

Interpretation of results:

GHS criteria not met

Conclusions:

The acute oral LD50 in rats is >5000 mg/kg bw.

Executive summary:

The key study on acute oral toxicity showed that the source substance did not cause mortality in rats at the limit dose of 5000 mg/kg bw. In the supporting study the LD50 was determined to be 8600 mg/kg bw (95% CI: 7900 -9300), based on the absence of mortality at 1000, 3000 and 6000 mg/kg bw. At 10000 mg/kg bw, all 5 male rats died while 3 out of 5 female rats died, after 1 -2 days after treatment.

The structurally related target substance will show similar behaviour, and therefore it is anticipated that the LD50 will be >5000 mg/kg bw as well.

Reference 2

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

supporting study

Study period:

1972

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

test procedure in accordance with national standard methods with acceptable restrictions

Justification for type of information:

None

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

no

Principles of method if other than guideline:

None

GLP compliance:

no

Test type:

standard acute method

Limit test:

no

Specific details on test material used for the study:

None

Species:

rat

Strain:

other: Tif RAI

Sex:

male/female

Details on test animals or test system and environmental conditions:

The experiments were performed on healthy, young, random-bred rats of the Tif RAI strain purchased from the breeder. Their mean initial body weight was between 100 and 140 g. The animals had previously been acclimatized in the laboratories for at least 5 days to a constant room temperature of 22±1°C, a relative humidity of 55±5% and a 12-hour light period. They were housed in groups of 5 in macrolon cages.

The animals were fed a standard diet of Nafag ad libitum and had free access of drinking water.

In order to determine the dose/response relationship of FAT 2302 groups of 5 male and 5 female rats, were after having been fasted overnight, given various single doses of the compound, suspended in distilled water by gavage. Symptoms and mortality after administration were recorded during an observation period of 8 days. The LD50 was calculated by the method of Miller-Tainter (Proc. Soc. Exp. Biol. Med. J57, 261, 1944).

Route of administration:

oral: gavage

Vehicle:

water

Details on oral exposure:

In order to determine the dose/response relationship of FAT 2302 groups of 5 male and 5 female rats, were after having been fasted overnight, given various single doses of the compound, suspended in distilled water by gavage.

Doses:

1000, 3000, 6000 and 10000 mg/kg bw

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

None

Statistics:

None

Preliminary study:

None

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

8 600 mg/kg bw

Based on:

test mat.

95% CL:

> 7 900 - < 9 300

Mortality:

5 males and 3 females at the dose rate of 10000 mg/kg bw were found dead after 1-2 days.

Clinical signs:

Doses of 1000 mg/kg bw were tolerated without symptoms. Higher doses caused ataxia, muscular hypotonia, hypoventilation, dyspnoea inhibition of the response to pain (pinching) and convulsions.

Body weight:

None

Gross pathology:

None

Other findings:

None

None

Interpretation of results:

GHS criteria not met

Conclusions:

The acute oral LD50 in rats was calculated to be 8600 mg/kg bw.

Executive summary:

The acute oral toxicity of FAT 40034 was evaluated using Tif. RAI rats according to the method of Miller-Tainter (Proc. Soc. Exp. Biol. Med. J57, 261, 1944). The animals received doses of 1000, 3000, 6000 and 10000 mg/kg bw orally once. Dose of 1000 mg/kg bw was tolerated without symptoms. Higher doses caused ataxia, muscular hypotonia, hypoventilation, dyspnoea, inhibition of the response to pain (pinching) and convulsions. 5 males and 3 females at the dose of 10000 mg/kg bw were found dead after 1-2 days. In conclusion, the acute oral LD50 of FAT 40034 in rats of both sexes observed over a period of 14 days is 8600 mg/kg bw.

Reference 3

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1974

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

test procedure in accordance with national standard methods with acceptable restrictions

Justification for type of information:

None

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

no

Principles of method if other than guideline:

None

GLP compliance:

no

Test type:

standard acute method

Limit test:

yes

Specific details on test material used for the study:

None

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

Animals:
Healthy Sprague-Dawley derived rats, bred on the premises, aged 5 weeks, having an average body weight of 118 g (M) and 118 g (F).

Husbandry:
Rats were caged singly and kept in a room maintained at a temperature of 21°C. (+/-2). Animals were subjected to 12 hours artificial light and 12 hours darkness in each 24 hour period. A commercial pelleted diet (Oakes Special Diet with added Vit. E) was fed ad lib. Water was available at all times.

Route of administration:

oral: gavage

Vehicle:

water

Details on oral exposure:

The compound (as a 50% w/v suspension in water) was administered as a single dose by gavage to rats which had been fasted for 18 hours, at a rate of 10 ml/kg equivalent to 5 g/kg of compound.

Doses:

None

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

After administration of the compound, the animals were observed for 14 days. Deaths and clinical symptoms were recorded. At the end of the observation period, surviving animals were killed by exsanguination under ether anaesthesia and an autopsy performed.

Statistics:

None

Preliminary study:

None

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 5 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: 95% Cl not specified

Mortality:

None

Clinical signs:

No clinical symptoms were recorded and no deaths occurred.

Body weight:

None

Gross pathology:

At autopsy no changes caused by the administration of FAT 40034/A were seen.

Other findings:

None

None

Interpretation of results:

GHS criteria not met

Conclusions:

The acute oral median lethal dose (LD50) of compound FAT 40034/A in rats is greater than 5000 mg/kg bw.

Executive summary:

The acute oral toxicity of FAT 40034 was evaluated in a limit test using Sprague-Dawley rats according to a methodology similar to OECD Guideline 401. 5 males and 5 females were administered a single dose of 5000 mg/kg bw orally. After administration of the compound, the animals were observed for 14 days. Deaths and clinical symptoms were recorded. At the end of the observation period, surviving animals were killed by exsanguination under ether anaesthesia and an autopsy performed. No clinical symptoms were recorded and no deaths occurred. At autopsy no changes caused by the administration of FAT 40034/A were seen. In conclusion, the acute oral LD50 of FAT 40034 in rats of both sexes observed over a period of 14 days is greater than 5000 mg/kg bw.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

5 000 mg/kg bw

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

The key study on acute oral toxicity showed that the source substance did not cause mortality in rats at the limit dose of 5000 mg/kg bw. In the supporting study the LD50 was determined to be 8600 mg/kg bw (95% CI: 7900 -9300), based on the absence of mortality at 1000, 3000 and 6000 mg/kg bw. At 10000 mg/kg bw, all 5 male rats died while 3 out of 5 female rats died, after 1 -2 days after treatment.

The structurally related target substance will show similar behaviour, and therefore it is anticipated that the LD50 will be >5000 mg/kg bw as well.

Justification for classification or non-classification

Based on the above assessment of the acute oral toxicity, the substance does not need to be classified for acute oral toxicity according to CLP.