tetrasodium 2-(4-fluoro-6-(methyl-(2-(sulfatoethylsulfonyl)ethyl)amino)-1,3,5-triazin-2-ylamino)-5-hydroxy-6-(4-methyl-2-sulfonatophenylazo)naphthalene-1,7-disulfonate

Endpoint summary

Description of key information

The test substance is considered to be of low acute (oral and dermal) toxicity with LD50 values >2,000 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:

From June 29, 1999 to July 13, 1999

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

Qualifier:

according to guideline

Guideline:

EU Method B.1 (Acute Toxicity (Oral))

Deviations:

no

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

other: HSD: Sprague Dawley SD

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Harlan Winkelmann, Gartenstr. 27, 33178 Borchen, SPF breeding colony.
- Age at study initiation: 6-10 weeks
- Body weight range at treatment: Males: 192-204 g; Females: 182-192 g
- Housing: In fully air-conditioned rooms in macrolon cages (i.e., type 4) on soft wood granulate in groups of 5 animals
- Diet: Ssnif R/M-H (V 1534), ad libitum
- Water: Tap water in plastic bottles, ad libitum
- Acclimation period: At least 7 d
- Animal identification: Fur marking with KMnO4 and cage numbering
- Randomization procedure: Randomization schemes 98.0691, 98.0690
- Withdrawal of food: From about 16 h before to 3-4 h after treatment

ENVIRONMENTAL CONDITIONS
- Temperature: 22±3°C
- Humidity: 50±20%
- Photoperiod: 12 h light/dark cycle

IN-LIFE DATES: From: To: June 29, 1999 to July 13, 1999

Route of administration:

oral: gavage

Vehicle:

water

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 20 % suspension in deionized water

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg bw

PREPARATION OF THE TEST SUBSTANCE: Test substance was suspended in the stated concentration in deionized water and distributed homogeneously by means of a magnetic stirrer. The stability and the homogeneity of the test substance in the vehicle was determined by analytical methods

Doses:

2,000 mg/kg bw

No. of animals per sex per dose:

Five/sex/dose

Control animals:

not specified

Details on study design:

Test procedure

- The prepared test substance was administered by gavage to fasted animals at the stated dosage. The observation period following treatment lasted for 14 d.

- Symptoms were recorded twice every day (in the morning and in the afternoon), on weekends and public holidays only once. During this time the animals were weighed weekly.

- At the end of the observation period the animals were killed by carbon dioxide asphyxiation, dissected and examined for macroscopically visible changes.

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No deaths occurred during the whole study.

Clinical signs:

other: Irregular respiration, diarrhea and orange discolored feces were observed after the administration of test substance.

Gross pathology:

The animals killed at the end of the observation period showed no macroscopically visible changes.

Interpretation of results:

GHS criteria not met

Conclusions:

Under the study conditions, the oral LD50 was found to be >2,000 mg/kg bw in rats.

Executive summary:

A study was conducted to assess the acute oral toxicity of the test substance in HSD:Sprague Dawley rats according to OECD Guideline 401 and EU Method B.1, in compliance with GLP.

 

Groups of five female and five male fasted rats received a single oral (gavage) dose of 2,000 mg/kg bw. A 20% suspension of test substance was prepared in deionized water and administered at a volume of 10 mL/kg bw.

 

No mortality occurred, no effect on body weight was observed and no significant macroscopic abnormalities were seen at necropsy. Irregular respiration, diarrhea and orange discolored feces were observed after the administration of the test substance.

 

Under the study conditions, the oral LD50 was found to be >2,000 mg/kg bw in rats.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Quality of whole database:

High quality study.

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Endpoint:

acute toxicity: inhalation

Data waiving:

exposure considerations

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:

From Aug. 11, 1999 to Aug. 25, 1999

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.3 (Acute Toxicity (Dermal))

Deviations:

no

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Type of coverage:

occlusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

REMOVAL OF TEST SUBSTANCE
- Time after start of exposure: 24 h

Duration of exposure:

24 h

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

5

Control animals:

not required

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortality observed

Clinical signs:

other: No adverse effect observed. All animals had an orange discolouration of the skin upto 6 d. In some animals this lasted upto 12 d.

Gross pathology:

No macroscopically visible changes were seen.

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Under the test conditions, the acute dermal LD50 of the test substance was found to be >2000 mg/kg bw.

Executive summary:

A study was performed to assess the acute dermal toxicity of the test substance in Sprague Dawley rats according to the OECD Guideline 402 and EU method B.3 in compliance with GLP.

A group of rats (5 per sex) was exposed at the dose of 2000 mg/kg bw. Exposure lasted 24 h. Animals were observed for clinical signs, signs of irritation and body weight changes over a period of 14 d.

No clinical signs were observed. All animals had an orange discolouration of the skin upto 6 d. In some animals this lasted upto 12 d. No treatment related effect on body weight gain was observed. Gross pathological examination did not reveal any macroscopic abnormalities.

Under the test conditions, the acute oral LD50 of the test substance for male and females rats was determined > 2000 mg/kg bw.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Quality of whole database:

High quality study.

Additional information

Oral route:

A study was conducted to assess the acute oral toxicity of the test substance inHSD: Sprague Dawley rats according to OECD Guideline 401 and EU Method B.1, in compliance with GLP. Group of five female and five male fasted rats received a single oral (gavage) dose of 2,000 mg/kg bw. A 20% suspension of test substance was prepared in deionized water and administered at a volume of 10 mL/kg bw. No mortality occurred, no effect on body weight was observed and no significant macroscopic abnormalities were seen at necropsy. Irregular respiration, diarrhea and orange discolored feces were observed after the administration of the test substance. Under the study conditions, the oral LD50 was found to be >2,000 mg/kg bw in rats (Roth, 1999).

Dermal route:

A study was performed to assess the acute dermal toxicity of the test substance in Sprague Dawley rats according to the OECD Guideline 402 and EU method B.3, in compliance with GLP. A group of rats (5 per sex) was exposed at the dose of 2,000 mg/kg bw. Exposure lasted 24 h. Animals were observed for clinical signs, signs of irritation and body weight changes over a period of 14 d. No clinical signs were recorded. All animals had an orange discolouration of the skin up to 6 d. In some animals this lasted up to 12 d. No treatment related effect on body weight gain was observed. Gross pathological examination did not reveal any macroscopic abnormalities. Under the test conditions, the acute oral LD50 of the test substance for male and females rats was determined > 2,000 mg/kg bw (Seeberger, 1999).

Justification for classification or non-classification

Oral route:

Based on the results of an acute oral toxicity study, the test substance does not need to be classified for acute toxicity according to the EU CLP criteria (EC 1272/2008) as well as EU Directive 67/548/EEC.

Dermal route:

Based on the results of an acute dermal toxicity study, the test substance does not need to be classified for acute toxicity according to the EU CLP criteria (EC 1272/2008) as well as EU Directive 67/548/EEC.