3-Pyridinemethanesulfonic acid, 5-[2-[5-[[4-chloro-6-[(4-sulfophenyl)amino]-1,3,5-triazin-2-yl]amino]-2-sulfophenyl]diazenyl]-1-ethyl-1,6-dihydro-2-hydroxy-4-methyl-6-oxo-, potassium sodium salt (1:?:?)

Endpoint summary

Description of key information

A LD50 of > 5000 mg/kg bw and >2000mg/kg bw was observed in the acute oral and acute dermal toxicity study, respectively. 

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

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP compliant guideline study, available as unpublished report, no restrictions, fully adequate for assessment.

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Qualifier:

according to guideline

Guideline:

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

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: Kleintierfarm Madoerin AG, CH 4414 Fuellinsdorf, / Switzerland
- Age at study initiation: 9 to 11 weeks
- Weight at study initiation: Males: 196 - 211g, Females: 184-199g
- Fasting period before study: 12-18 hours
- Housing: Groups of five in Makrolon type-3 cages with standard softwood bedding ("Lignocel", Schill AG, 4132 Muttenz, Switzerland).
- Diet (e.g. ad libitum): Pelleted standard Kliba 343, Batch 62/86 rat maintenance diet ("Kliba", Klingentalmuehle AG, 4303 Kaiseraugst, Switzerland)
available ad libitum.
- Water (e.g. ad libitum): Community tap water from Itingen, available ad libitum.
- Acclimation period: At least one week under laboratory conditions, after veterinary examination

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22±3
- Humidity (%): 40-70
- Air changes (per hr): 10-15
- Photoperiod (hrs dark / hrs light): 12/12

Route of administration:

oral: gavage

Vehicle:

CMC (carboxymethyl cellulose)

Remarks:

4% in distilled water

Details on oral exposure:

MAXIMUM DOSE VOLUME APPLIED: 20mL/kg bw

Doses:

5000 mg/kg bw

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Mortality / Viability: Four times during test day 1, and daily during days 2-15, Body Weights: Test days 1 (pre-administration), 8 and 15, Symptoms: Each animal was examined for changes in appearance and behavior four times during day 1, and daily during days 2-15.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs (general behaviour, respiration, eye, nose, motility, body posture, motor susceptibility, skin), gross pathology

Statistics:

The LOGIT-Model could not be applied to the observed rates of death. The toxicity was estimated without the use of a statistical model.

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 5 000 mg/kg bw

Based on:

test mat.

Mortality:

0%

Clinical signs:

other: No finding were observed in any animal.

Gross pathology:

No macroscopic organ changes were observed in any animal.

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Based on the observations the toxicity of the test substance was estimated to be greater than 5000 mg/kg bw.

Executive summary:

In a GLP compliant oral toxicity study, performed according to OECD guideline 401, Wistar rats (5/sex/dose) were administered the test substance (5000 mg/kg bw) by oral gavage followed by a 14-day observation period. Mortality did not occur. No symptoms or macroscopic organ changes were observed. Based on these observations, the acute oral toxicity of the test substance in rats of both sexes observed for a period of 14 days was greater than 5000 mg/kg bw.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Quality of whole database:

GLP compliant guideline study, klimisch 1

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Endpoint:

acute toxicity: inhalation

Data waiving:

other justification

Justification for data waiving:

other:

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

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP compliant guideline study, available as unpublished report, no restrictions, fully adequate for assessment.

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Qualifier:

according to guideline

Guideline:

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

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: Kleintierfarm Madoerin AG, CH 4414 Fuellinsdorf, / Switzerland
- Age at study initiation: 9 to 11 weeks
- Weight at study initiation: Males: 216 - 238g, Females: 200-221g
- Housing: Individually in Makrolon type-2 cages with standard softwood bedding ("Lignocel", Schill AG, 4132 Muttenz, Switzerland).
- Diet (e.g. ad libitum): Pelleted standard Kliba 343, Batch 62/86 rat maintenance diet ("Kliba", Klingentalmuehle AG, 4303 Kaiseraugst, Switzerland), available ad libitum.
- Water (e.g. ad libitum): Community tap water from Itingen, available ad libitum.
- Acclimation period: At least one week under laboratory conditions, after veterinary examination

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22±3
- Humidity (%): 40-70
- Air changes (per hr): 10-15
- Photoperiod (hrs dark / hrs light): 12/12

Type of coverage:

occlusive

Vehicle:

CMC (carboxymethyl cellulose)

Remarks:

4% in distilled water

Details on dermal exposure:

Approximately 24 hours before treatment, the backs of the animals were shaved with an electric clipper, exposing an area of approximately 10 % of the total body surface. On test day 1, 4mL of the test article was applied evenly on the skin with a syringe and covered with an occlusive dressing. The dressing was wrapped around the abdomen and fixed with an elastic adhesive bandage. Twenty-four hours after the application, the dressing was removed. The treated skin was washed with lukewarm tap water and dried with disposable paper towels and the skin reaction was assessed according to the method of Noakes, D.N. and Sanderson, D.M. "A method for determining the dermal toxicity of pesticides". Brit. J. Industr. Med., 26, 59-64, 1969)

Duration of exposure:

24 hours

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Mortality/viability were measured four times during test day 1 and daily during days 2 - 15.
- Body weights were measured on day 1 (pre administration), 8 and 15.
- All animals were necropsied.
- Each animal had an examination for changes in appearance and behavior four times during day 1, and daily during days 2-15 (general behaviour, respiration, eye, nose, motility, body posture, motor susceptibility, skin), gross pathology.

Statistics:

The Logit model could not be applied to the observed rate of death. The toxicity was estimated without use of a statistical model.

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

0%

Clinical signs:

other: The rats showed yellowish discolored skin at the application site. In addition, the female rats showed erythema, scales, and emaciation during the observation period. All rats recovered from erythema, scales and emaciation at termination of observation.

Gross pathology:

No macroscopic organ changes were observed

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The toxicity of the test substance was estimated to be greater than 2000 mg/kg bw

Executive summary:

In a GLP compliant dermal toxicity study, performed according to OECD guideline 402, Wistar rats (5/sex) were administered test substance (2000 mg/kg bw). The test substance was dissolved in a 4 % CMC solution and applied on the skin with a syringe and covered with an occlusive dressing for 24 hours. The treated skin was washed after 24 hours and a 14-day observation period followed. No mortality was observed during this period. Discoloration of the application area was observed and the female rats showed erythema, scales, and emaciation during the observation period. All rats recovered from the erythema, scales, and emaciation. No macroscopic organ changes were observed. Therefore, the toxicity of the test substance was estimated to be >2000 mg/kg bw.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Quality of whole database:

GLP compliant guideline study, klimisch 1

Additional information

Acute toxicity oral:

In a GLP compliant oral toxicity study, performed according to OECD guideline 401, Wistar rats (5/sex/dose) were administered the test substance (5000 mg/kg bw) by oral gavage followed by a 14-day observation period (RCC 1987). Mortality did not occur. No symptoms or macroscopic organ changes were observed. Based on these observations, the acute oral toxicity of the test substance in rats of both sexes observed for a period of 14 days was greater than 5000 mg/kg bw.

Acute toxicity dermal:

In a GLP compliant dermal toxicity study, performed according to OECD guideline 402, Wistar rats (5/sex) were administered test substance (2000 mg/kg bw) (RCC 1987). The test substance was dissolved in a 4 % CMC solution and applied on the skin with a syringe and covered with an occlusive dressing for 24 hours. The treated skin was washed after 24 hours and a 14-day observation period followed. No mortality was observed during this period. Discoloration of the application area was observed and the female rats showed erythema, scales, and emaciation during the observation period. All rats recovered from the erythema, scales, and emaciation. No macroscopic organ changes were observed. Therefore, the toxicity of the test substance was estimated to be >2000 mg/kg bw.

Justification for selection of acute toxicity – oral endpoint
Only study available.

Justification for selection of acute toxicity – dermal endpoint
Only study available.

Justification for classification or non-classification

Based on the observed LD50 of >5000 and >2000 mg/kg bw in the acute oral and dermal toxicity study, respectively, the test substance does not need to be classified according to Directive 67/548/EEC and according to the EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008.