REAKTIVE GELB F 97494

Endpoint summary

Description of key information

No deaths or adverse effects were observed in the acute oral or dermal toxicity study in rats.

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 October 24, 2001 to November 08, 2001

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)

Deviations:

no

GLP compliance:

yes

Test type:

acute toxic class 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 GmbH, Gartenstrasse 27, D-33178 Borchen
- Age at study initiation: 6 to 10 weeks
- Weight at study initiation: Males: mean=199 g (=100%) (S.D.=±11.5 g); female animals: mean=180 g (= 100%) (S.D.=±7.5 g)
- Housing: in transparent macrolon® cages (type IV) on soft wood granulate in an air-conditioned room, 3 animals per cage
- Diet: ssniff® R/M-H (V 1534), ad libitum
- Water: tap water in plastic bottles, ad libitum
- Acclimation period: at least 5 d
-Animal identification: fur marking with KMnO4 and cage numbering
-Randomization procedure: Computer generated algorithm (archived with raw data) randomization schemes 2001.0529, 2001.0530

ENVIRONMENTAL CONDITIONS
- Temperature: 22±3°C (except short lasting deviations due to disturbances of air condition)
- Humidity: 50±20 % (except short lasting deviations due to disturbances of air condition)
- Photoperiod: 12 h light/dark cycle

IN-LIFE DATES: From: To: October 24, 2001 to November 08, 2001

Route of administration:

oral: gavage

Vehicle:

water

Remarks:

deionized

Details on oral exposure:

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

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg body weight

DOSAGE PREPARATION :Test substance was dissolved 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.

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: limit test (according to toxicity data of related compounds)

-Duration of treatment: single dose

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

3

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. 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.

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 deaths occurred during the study.

Clinical signs:

other: No symptoms were observed in male animals. Few clinical signs stilted gait and yellowish discoloured urine were observed after the administration of the test substance in female animals. However, from 2 d until the end of the study no symptoms were obser

Gross pathology:

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

Interpretation of results:

GHS criteria not met

Conclusions:

Under the study conditions, the oral LD50 of the test substance 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 (SD) rats according to OECD Guideline 423 and EU Method B.1, in compliance with GLP.

 

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

 

No mortality occurred, no clinical signs were observed in male and no significant macroscopic abnormalities were seen at necropsy. Stilted gait and yellowish discolored urine were observed after the administration of test substance in female animals. However, there were no symptoms in female rats from Day 2 until the end of the study.

 

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

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD0

Value:

2 000 mg/kg bw

Quality of whole database:

High quality study.

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 October 31, 2001 to November 14, 2001

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

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1200 (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 GmbH, Gartenstrasse 27, D-33178 Borchen
- Age at study initiation: 6 to 10 weeks
- Weight at study initiation: Males: mean=262 g (=100%) (S.D.=±12.6 g); female animals: mean=210 g (=100%) (S.D.=±12.2 g)
- Housing: in transparent macrolon® cages (type III) on soft wood granulate in an air-conditioned room, 1 animal per cage
- Diet: ssniff® R/M-H (V 1534), ad libitum
- Water: tap water in plastic bottles, ad libitum
- Acclimation period: at least 7 d
-Animal identification: cage numbering
Randomization procedure: Computer generated algorithm (archived with raw data) randomization schemes 2001.0529, 2001.0530

ENVIRONMENTAL CONDITIONS
- Temperature: 22±3°C (except short lasting deviations due to disturbances of air condition)
- Humidity: 50±20 % (except short lasting deviations due to disturbances of air condition)
- Photoperiod: 12 h light/dark cycle

IN-LIFE DATES: From: To: October 31, 2001 to November 14, 2001

Type of coverage:

occlusive

Vehicle:

water

Remarks:

moistened with deionized water to form a paste

Details on dermal exposure:

Before dermal treatment the fur was mechanically removed from the dorsal skin of the animals over an area of approximately 30 cm².

The appropriate amount of the test substance was moistened on a two-ply gauze and an aluminum foil (6 x 8 cm) and distributed as uniformly as possible. Together with the foil the test substance was administered to the shaved and intact dorsal skin. The foil was held in place with an elastic plaster bandage fixed around the animal's body (Fixomull and Elastoplast, 8 cm in width, both manufactured by Beiersdorf Aktiengesellschaft). At the end of the dermal exposure period of 24 h the bandage was removed and the treated skin area washed with warm water in order to remove any unabsorbed remnants of the test substance.

Duration of exposure:

24 h

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

5

Control animals:

not required

Details on study design:

The observation period after the dermal administration 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.

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 deaths occurred during the whole study.

Clinical signs:

other: No symptoms were observed after administration of test substance. The skin of four animals showed slight erythema from Day 2 to Day 5 of the study. However, the skin of the other animals showed no signs of irritation.

Gross pathology:

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

Interpretation of results:

GHS criteria not met

Conclusions:

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

Executive summary:

A study was conducted to assess the acute dermal toxicity of the test substance in Hsd:Sprague Dawley (SD) rats according to OECD Guideline 423, EU Method B.1. and EPA OPPTS 870.1200, in compliance with GLP.

Groups of five female and five male rats received a single dermal dose of 2,000 mg/kg bw. 500 mg of test substance moistened with 0.4 mL deionized water was applied topically under occlusive conditions for 24 h.

 

No mortality occurred, no clinical signs were observed and no significant macroscopic abnormalities were seen at necropsy. Body weight was also not impaired. Only one female showed a very slight loss of weight between Days 1 and 8. However, the body weight gain returned to normal by end of the study (15 d). Although the skin of four animals showed slight erythema from Days 2 to 5 of the study, no signs of irritation were observed in the rest of the animals.

 

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

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD0

Value:

2 000 mg/kg bw

Quality of whole database:

High quality study.

Additional information

A study was conducted to assess the acute oral toxicity of the test substance in Hsd:Sprague Dawley (SD) rats according to OECD Guideline 423 and EU Method B.1, in compliance with GLP. Group of three female and three male fasted rats received a single oral (gavage) dose of 2,000 mg/kg bw. A 20% solution of test substance was prepared in deionized water and administered at a volume of 10 mL/kg bw. No mortality occurred, no clinical signs were observed in male and no significant macroscopic abnormalities were seen at necropsy. Stilted gait and yellowish discolored urine were observed after the administration of test substance in female animals. However, there were no symptoms in female rats from Day 2 until the end of the study. Under the study conditions, the oral LD50 was found to be > 2,000 mg/kg bw in rats.

 

No acute inhalation toxicity study was conducted as exposure via this route is not to be expected.The test substance has a very low vapour pressure and a high melting point and is hence not volatile. Test item synthesis and spray drying is performed in a closed process and the dedusting agents are mixed directly with the wet press cake. Consequently, the final product consists of non-dusty granules or well de-dusted powders and the potential for the generation of inhalable forms is low. In addition the use of this substance will not result in aerosols, particles or droplets of an inhalable size, so exposure to humans via the inhalatory route is unlikely to occur.

 

A study was conducted to assess the acute dermal toxicity of the test substance in Hsd:Sprague Dawley (SD) rats according to OECD Guideline 423, EU Method B.1. and EPA OPPTS 870.1200, in compliance with GLP. Groups of five female and five male rats received a single dermal dose of 2,000 mg/kg bw. 500 mg of test substance moistened with 0.4 mL deionized water was applied topically under occlusive conditions for 24 h. No mortality occurred, no clinical signs were observed and no significant macroscopic abnormalities were seen at necropsy. Body weight was also not impaired. Only one female showed a very slight loss of weight between Days 1 and 8. However, the body weight gain returned to normal by end of the study (15 d). Although the skin of four animals showed slight erythema from Days 2 to 5 of the study, no signs of irritation were observed in the rest of the animals. Under the study conditions, the dermal LD50 of the test substance was found to be > 2,000 mg/kg bw in rats.