Registration Dossier

Diss Factsheets

Administrative data

Description of key information

The test substance is practically non-toxic.

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:
25.05. to 08.06. 1982
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Comparable to guideline study with acceptable restrictions
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Principles of method if other than guideline:
Internal Guideline Hoechst AG
GLP compliance:
no
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
Wistar
Sex:
female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Hoechst AG
- Age at study initiation: -
- Weight at study initiation: 191 to 202 g
- Fasting period before study: 16 hours before to 2 hours after dosing
- Housing: group-caging (10/cage)
- Diet: Altromin 1324 ad libitum
- Water: tap ad libitum
- Acclimation period: -


IN-LIFE DATES: From: 25. May To: 08. June 1982
Route of administration:
oral: gavage
Vehicle:
water
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 25%
- Amount of vehicle (if gavage): 20 mL/kg
Doses:
5000 mg/kg bw
No. of animals per sex per dose:
10
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: body weight: weekly; clinical signs: at least daily
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight
Statistics:
-
Preliminary study:
NA
Sex:
female
Dose descriptor:
LD50
Effect level:
> 5 000 mg/kg bw
Mortality:
no deaths
Clinical signs:
other: no effects
Gross pathology:
no effects
Other findings:
Within 15 minutes after dosing all animals showed bluish discoloration of skin, apathia, bluish discoloration of feces and diarrhea. 25 minutes after application the animals showed hunched and prone position and piloerection as well as bluish urine. All effects were fully reversible within 24 hours.
Behaviour and gain of body weight were not effected during the recovery period.
Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
LD50 above 5000 mg/kg bw.
No classification necessary
Executive summary:

A study was conducted to assess the acute oral toxicity of the test substance in rats after a single dose with a 14-day post observation period. Ten fasted female Wistar rats received a single oral (gavage) dose of 5000 mg/kg bw. A 25% suspension of test substance was prepared in softened water and administered at a volume of 20 mL/kg bw.

No mortality occurred. Fifteen minutes after test substance administration,all treated rats showed apathia, blue skin blue faeces and diarrhea. After 25 minutes, hunched posture, prone position, piloerection and bluish discoloured urine was observed.

No clinical signs of toxicity were observed from 24 hours onward and no significant macroscopic abnormalities were seen at necropsy.

 

Under the study conditions, the oral LD50 was found to be >5000 mg/kg bw in rats.

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:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Study period:
From June 05, 2002 to June 19, 2002
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: The study was conducted according to OECD Guideline 402, EU Method B.3 and EPA OPPTS 870.1200 Method, in compliance with GLP.
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=266.2 g (=100%) (S.D.=±12.7 g); female animals: mean=219.4 g (= 100%) (S.D.=±7.5 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 5 d
-Animal identification: Cage numbering
-Randomization procedure: Computer generated algorithm (archived with raw data) randomization schemes 2001.0453 and 2001.0455
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: June 05, 2002 to June 19, 2002
Type of coverage:
occlusive
Vehicle:
other: sesame oil
Details on dermal exposure:
TEST SITE
Before dermal treatment the fur was mechanically removed from the dorsal skin of the animals over an area of approximately 30 cm². The appropriate amountof 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).

REMOVAL OF TEST SUBSTANCE
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.

PREPARATION OF THE TEST SUBSTANCE
0.5 g of test substance was moistened with 0.25 mL sesame oil
Duration of exposure:
24 h
Doses:
2,000 mg/kg bw
No. of animals per sex per dose:
Five/sex/dose
Control animals:
not specified
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.
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: No symptoms were observed after administration of test substance. The skin of the animals was discolored by the test substance from 2 d onwards. However, in most animals the discoloration disappeared at 6 d of the study. Only two females showed persistent
Gross pathology:
The animals killed at the end of the observation period showed no macroscopically visible changes.
Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
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 402, EU Method B.3. 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 was moistened with 0.25 mL sesame oil and was applied topically under occlusive conditions for 24 h.

 

No mortality occurred, no clinical symptoms were observed and no significant macroscopic abnormalities were seen at necropsy. Body weight was also not impaired. However, the skin of the animals was discolored by the test substance from 2 d onwards. Except in two females, discoloration disappeared in all other treated animals at 6 d of the study.

 

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:
LD50
Value:
2 000 mg/kg bw

Additional information

A study was conducted to assess the acute oral toxicity of Reactive Blue 203 in rats after a single dose with a 14-day post observation period. Ten fasted female Wistar rats received a single oral (gavage) dose of 5000 mg/kg bw. A 25% suspension of test substance was prepared in softened water and administered at a volume of 20 mL/kg bw.

No mortality occurred. Fifteen minutes after test substance administration,all treated rats showed apathia, blue skin blue faeces and diarrhea. After 25 minutes, hunched posture, prone position, piloerection and bluish discoloured urine was observed.

No clinical signs of toxicity were observed from 24 hours onward and no significant macroscopic abnormalities were seen at necropsy.

Under the study conditions, the oral LD50 was found to be >5000 mg/kg bw in rats.

 

The acute dermal toxicity of Reactive Blue 203 was assessed via read-across from Structural Analogue 01 performed according to OECD 402. Groups of five female and five male rats received a single dermal dose of 2000 mg/kg bw. 

500 mg of test substance was moistened with 0.25 mL sesame oil and was applied topically under occlusive conditions for 24 h.

No mortality occurred, no clinical symptoms were observed and no significant macroscopic abnormalities were seen at necropsy. Body weight was also not impaired. However, the skin of the animals was discolored by the test substance from 2 day onwards. Except in two females, discoloration disappeared in all other treated animals at 6 d of the study.

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

Inhalative exposure of workers to Reactive Blue 203 is very unlikely, as production and spray drying is done in a closed process without isolation of reaction products. The isolated products are liquid, dust free granules or dedusted powders (non-dusty solid) therefore inhalative exposure of down-stream users is very unlikely.

Justification for classification or non-classification

No classification necessary.