1,7-Naphthalenedisulfonic acid, 2-[[4-chloro-6-(cyanoamino)-1,3,5-triazin-2-yl]amino]-5-hydroxy-6-[2-[2-methoxy-5-[[2-(sulfooxy)ethyl]sulfonyl]phenyl]diazenyl]-, lithium sodium salt (1:?:?)

Endpoint summary

Description of key information

The available data for test substance indicates a low potential for acute oral (LD50 >2,000 mg/kg bw) and dermal toxicity (LD50 >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 Jul. 01, 1999 to Oct. 19, 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 (incl. QA statement)

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

Sprague-Dawley

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 wk
- Weight at study initiation: 212± 3.8 g (males); 189± 8.7 g (females)
- Fasting period before study: Yes, 16 h
- Housing: MacroIon cages (type 4) on soft wood granulate in groups of 5 animals
- Diet (e.g. ad libitum): ssnif R/M-H (V 1534), ad libitum
- Water (e.g. ad libitum): Tap water in plastic bottles, ad libitum
- Acclimation period: At least 7 d

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

IN-LIFE DATES: From: Jul. 01, 1999 To: Jul. 15, 1999

Route of administration:

oral: gavage

Vehicle:

water

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 20 % suspension in deionized water
- Justification for choice of vehicle: Test substance is soluble in water


MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg bw

DOSAGE PREPARATION (if unusual): 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:

2000 mg/kg bw

No. of animals per sex per dose:

5/sex/dose

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 d
- Frequency of observations and weighing: Symptoms were recorded twice every day (in the morning and in the afternoon), on weekends
and public holidays only once. The animals were weighed weekly.
- Necropsy of survivors performed: yes; animals were killed by carbon dioxide
asphyxiation, dissected and examined for macroscopically visible changes.
- Other examinations performed: clinical signs, body weight- Yes

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

not determinable due to absence of adverse toxic effects

Mortality:

No mortalities occurred during the whole study.

Clinical signs:

other: With exception of discolored orange feces, no clinical signs were observed until the end of the study.

Gross pathology:

No gross pathology changes observed

Interpretation of results:

GHS criteria not met

Conclusions:

Under the test conditions, the acute oral LD50 of the test substance was found to be >2,000 mg/kg in Sprague-Dawley SD rats.

Executive summary:

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

Following a range-finding study, a group of 10 fasted rats (five males and five females) were given a single oral dose of the test substance as a 20 % suspension in deionized water, at a dose level of 2,000 mg/kg. The animals were observed for 14 d after the day of dosing and were then killed and subjected to gross pathological examination. One hour up to 5 d after administration of test substance discolored orange feces and diarrhea were noted. No deaths occurred within the observation period. Development of body weight was not impaired. No abnormalities were noted at necropsy.

 

Under the test conditions, the acute oral LD50 of the test substance was found to be >2,000 mg/kg in Sprague-Dawley SD rats.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 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:

From Jul. 08, 1999 to Oct. 01, 1999

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

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

no

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

Sprague-Dawley

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 wk
- Weight at study initiation: 228± 4.3 g (males); 215± 14.3 g (females)
- Fasting period before study: No
- Housing: MacroIon cages (type 4) on soft wood granulate, one animal per cage
- Diet (e.g. ad libitum): ssnif R/M-H (V 1534), ad libitum
- Water (e.g. ad libitum): Tap water in plastic bottles, ad libitum
- Acclimation period: At least 7 d

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

IN-LIFE DATES: From: Jul. 08, 1999 To: Jul. 22, 1999

Type of coverage:

semiocclusive

Vehicle:

water

Remarks:

0.5 mL deionized water

Details on dermal exposure:

TEST SITE
- Area of exposure: Dorsal skin of the area (30 cm2)
- Type of wrap if used: Elastic plaster bandage fixed around the animal's body (Fixomull and Elastoplast, 8 cm in width)

REMOVAL OF TEST SUBSTANCE
- Washing (if done): Yes, with warm water
- Time after start of exposure: 24 h

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 g
- Concentration (if solution): 0.5 g of test substance was moistened with 0.5 mL deionized water
- Constant volume or concentration used: yes
- For solids, paste formed: yes

VEHICLE
- Amount(s) applied (volume or weight with unit): 0.5 mL deionized water.

Duration of exposure:

24 h

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

5/sex/dose

Control animals:

not required

Details on study design:

- Duration of observation period following administration: 14 d
- Frequency of observations and weighing: Symptoms were recorded twice every day (in the morning and in the afternoon), on weekends
and public holidays only once. The animals were weighed weekly
- Necropsy of survivors performed: yes; animals were killed by carbon dioxide asphyxiation, dissected and examined for macroscopically visible changes.
- Other examinations performed: Clinical signs and body weight

Statistics:

No data

Preliminary study:

Not applicable

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: -

Mortality:

No mortalities occurred during the whole study.

Clinical signs:

other: No symptoms were observed after administration of 2000 mg/kg body weight. The skin of the animals showed no signs of irritation. The skin of the animals was discolored orange in a large area from removal of the test substance until the end of the study.

Gross pathology:

No gross pathological changes were observed

Other findings:

No data

None

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 >2,000 mg/kg in Sprague-Dawley SD rats

Executive summary:

A study was conducted to assess the acute dermal toxicity of test substance in Sprague-Dawley CD rats according EU Method B.3. and OECD guideline 402 in compliance with GLP.

Following a range-finding study, a group of 10 rats (five males and five females) were applied 0.5 g of test substance moistened with 0.5 mL deionised water, at a dose level of 2,000 mg/kg. Following the 24 h exposure period, animals were observed for mortality, skin response and general behavior for 14 d and were then killed and subjected to gross pathological examination.

No mortality was observed in the study. All animals appeared normal throughout the 24 h exposure period and the 14 d post-exposure observation period. The skin of the animals was discolored orange in a large area from removal of the test substance until the end of the study without any signs of irritation.

The overall body weight gain was not impaired in both sexes. Two female animals showed a transient slight body weight loss in the first study week. The animals killed at the end of the observation period showed no macroscopically visible changes.

Under the test conditions, the acute dermal LD50 of the test substance was found to be >2,000 mg/kg in Sprague-Dawley SD rats.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Additional information

Oral

A study was conducted to assess the acute oral toxicity of test substance in Sprague-Dawley CD rats according OECD guideline 401 and EU Method B.1.

Following a range-finding study, a group of 10 fasted rats (five males and five females) were given a single oral dose of the test substance as a 20 % suspension in deionized water, at a dose level of 2,000 mg/kg. The animals were observed for 14 d after the day of dosing and were then killed and subjected to gross pathological examination. One hour up to 5 d after administration of test substance discolored orange feces and diarrhea were noted. No deaths occurred within the observation period. Development of body weight was not impaired. No abnormalities were noted at necropsy. The acute oral LD50 of the test substance was found to be >2,000 mg/kg in Sprague-Dawley SD rats (Dr. Seeberger A, 1999).

Dermal

A study was conducted to assess the acute dermal toxicity of test substance in Sprague-Dawley CD rats according OECD guideline 402 and EU Method B.3.

Following a range-finding study, a group of 10 rats (five males and five females) were applied 0.5 g of test substance moistened with 0.5 mL deionised water, at a dose level of 2,000 mg/kg. Following the 24 h exposure period, animals were observed for mortality, skin response and general behavior for 14 d and were then killed and subjected to gross pathological examination. No mortality was observed in the study. All animals appeared normal throughout the 24 h exposure period and the 14 d post-exposure observation period. The skin of the animals was discolored orange in a large area from removal of the test substance until the end of the study without any signs of irritation.

The overall body weight gain was not impaired in both sexes. Two female animals showed a transient slight body weight loss in the first study week. The animals killed at the end of the observation period showed no macroscopically visible changes. The acute dermal LD50 of the test substance was found to be >2,000 mg/kg in Sprague-Dawley SD rats (Dr. Seeberger A, 1999).

The available data for test substance indicates a low potential for acute oral (LD50 >2,000 mg/kg bw) and dermal toxicity (LD50 >2,000 mg/kg bw) and does not meet the requirement for classification according to EC criteria (67/548/EEC) and according to CLP criteria (EC 1272/2008).

Justification for classification or non-classification

The available data for test substance indicates a low potential for acute oral (LD50 >2,000 mg/kg bw) and dermal toxicity (LD50 >2,000 mg/kg bw) and does not meet the requirement for classification according to EC criteria (67/548/EEC) and according to CLP criteria (EC 1272/2008).