Reaction mass of lithium sodium hydrogen 4-amino-6-({5-[(5-chloro-2,6-difluoropyrimidin-4-yl)amino]-2-sulfonatophenyl}diazenyl)-5-hydroxy-3-[(4-{[2-(sulfonatooxy)ethyl]sulfonyl}phenyl)diazenyl]naphthalene-2,7-disulfonate and lithium sodium hydrogen 4-amino-6-({5-[(5-chloro-2,6-difluoropyrimidin-4-yl)amino]-2-sulfonatophenyl}diazenyl)-5-hydroxy-3-{[4-(vinylsulfonyl)phenyl]diazenyl}naphthalene-2,7-disulfonate

Endpoint summary

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 May 23, 1986 to September 23, 1986

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

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:

Wistar

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: 9 (males) - 14 (females) weeks
- Average body weight at treatment: Males: 171 g; Females: 176 g (less than 20% deviation to average)
- Housing: Macrolon cages (i.e., type 3) on soft wood granulate
- Diet: Altromin 1324, ad libitum
- Water: Tap water, ad libitum
- Acclimation period: At least 5 d
- Animal identification: Fur marking and cage numbering
- Withdrawal of food: From about 16 h before to 3-4 h after treatment

ENVIRONMENTAL CONDITIONS
- Temperature: 22±2°C
- Humidity: 50±10%
- Photoperiod: 12 h light/dark cycle

IN-LIFE DATES: From: To: June 10, 1986 to June 24, 1986

Route of administration:

oral: gavage

Vehicle:

water

Doses:

3,100 and 5,000 mg/kg bw

No. of animals per sex per dose:

Five/sex/dose

Control animals:

no

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.

- The animals were weighed before treatment, after Week 1 and at the end of Week 2.

- At the end of the observation period the animals were killed using diethylether, dissected and examined for macroscopically visible changes.

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 5 000 mg/kg bw

Based on:

test mat.

Mortality:

There was no mortality at 3,100 mg/kg bw. One male (Day 2) and one female (8 h) died at 5,000 mg/kg bw.

Clinical signs:

other: Degradation of general condition, rough fur.

Gross pathology:

Blue discoloration of stomach mucous and abdominal organs were seen in the animals which died during the course of the study.
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 acute oral LD50 of the test substance to the rats was found to be >5,000 mg/kg bw in rats.

Executive summary:

A study was conducted to assess the acute oral toxicity of the test substance in Wistar rats according to EU Method B.1, in compliance with GLP. Groups of five female and five male fasted rats received a single oral (gavage) dose of 3100 or 5000 mg/kg bw. A suspension of test substance was prepared in deionized water and administered at a volume of 10 mL/kg bw. No mortality occurred at 3100 mg/kg bw. One male (Day 2) and one female (8 h) died at 5000 mg/kg bw. Blue discoloration of stomach mucous and abdominal organs was seen in the animals which died in the course of the study. The animals killed at the end of the observation period showed no macroscopically visible changes. Clinical signs after administration of the test substance included degradation of the general condition and rough fur. Under the study conditions, the oral LD50 of the test substance was found to be >5000 mg/kg bw in rats (Ramm, 1986a).

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

Link to relevant study records

Reference

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

10.06.86 to 24.06.86

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

GLP compliance:

yes

Test type:

fixed dose procedure

Limit test:

yes

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Age at study initiation: male - 13 wk and female - 15 wk
- Weight at study initiation: male - 280 g and female - 181 g
- Diet (e.g. ad libitum): Altromin 1324 pellet feed
- Water (e.g. ad libitum): tap water
- Acclimation period: 5 d

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18-22°C
- Humidity (%): 40-60%
- Photoperiod (hrs dark / hrs light): 16:8 light-dark cycle

IN-LIFE DATES: From: 10.06.86 To: 24.06.86

Type of coverage:

occlusive

Vehicle:

water

Details on dermal exposure:

A homogeneous mixture of the test substance in water was obtained by stirring on a magnetic stirrer. Approx. 24 h before the beginning of the experiment, the fur of the test animals is removed on the back and the shoulders by shaving. In the case of shearing, care is taken that the skin is not injured as this could lead to a change in the permeability. The test substance was then applied on the shaved area and covered with a bandage.

Duration of exposure:

24 h

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

Five

Control animals:

yes

Details on study design:

Following 24 h exposure with the test substance, the bandages were removed and the treated skin areas were rinsed with water. On the day of the application, the animals were examined several times and during the following 14-day observation period the nature, duration and intensity of the clinical symptoms were recorded. Immediately before the application, after a week and at the end of the 14-day observation period, the surviving animals were individually weighed.

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

There was no mortality.

Clinical signs:

other: No adverse effects were observed.

Gross pathology:

No local gross lesions on the skin were visible.

Interpretation of results:

GHS criteria not met

Conclusions:

Under the study conditions, the dermal LD50 of the test substance to Wistar rats was determined to be >2000 mg/kg bw.

Executive summary:

A study was conducted to determine the acute dermal toxicity of the test substance in Wistar rats according to the EU Method B.3, in compliance with GLP. Male and female Wistar rats were exposed to a single dose of the test substance as a dermal application in this limit test. There were 5 rats per sex, exposed to a nominal concentration of 2000 mg/kg bw. The animals were then observed during 14 d for mortality and clinical signs. Body weights were recorded weekly. Following sacrifice, all surviving rats were dissected and evaluated macroscopically at the end of the study. No mortality, clinical signs and effect on body weight were observed in this study. At test end, no macroscopic lesions were found. Under the study conditions, the dermal LD50 of the test substance was determined to be >2000 mg/kg bw (Ramm, 1986b).

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Additional information

A study was conducted to assess the acute oral toxicity of the test substance in Wistar rats according to EU Method B.1, in compliance with GLP. Groups of five female and five male fasted rats received a single oral (gavage) dose of 3100 or 5000 mg/kg bw. A suspension of test substance was prepared in deionized water and administered at a volume of 10 mL/kg bw. No mortality occurred at 3100 mg/kg bw. One male (Day 2) and one female (8 h) died at 5000 mg/kg bw.Blue discoloration of stomach mucous and abdominal organs was seen in the animals which died in the course of the study. The animals killed at the end of the observation period showed no macroscopically visible changes. Clinical signs after administration of the test substance included degradation of the general condition and rough fur. Under the study conditions, the oral LD50 was found to be >5000 mg/kg bw in rats (Ramm, 1986a).

A study was conducted to determine the acute dermal toxicity of the test substance in Wistar rats according to the EU Method B.3, in compliance with GLP. Male and female Wistar rats were exposed to a single dose of the test substance as a dermal application in this limit test. There were 5 rats per sex, exposed to a nominal concentration of 2000 mg/kg bw. The animals were then observed during 14 days for mortality and clinical signs. Bodyweights were recorded weekly. Following sacrifice, all surviving rats were dissected and evaluated macroscopically at the end of the study. No mortality, clinical signs and effect on body weight were observed in this study. At test end, no macroscopic lesions were found. Under the study conditions, the dermal LD50 was determined to be >2000 mg/kg bw (Ramm, 1986b).

Justification for classification or non-classification

Based on the results of acute oral and acute dermal toxicity studies in rat, no classification is warranted for the test substance according to CLP (EC 1272/2008) criteria.