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Administrative data

Description of key information

Acute oral and dermal toxicity determined using OECD test guideline 401 & 402.
Oral LD50 > 5000 mg/kg bw
Dermal LD50 > 2000 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:
1986
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: guideline study performed under GLP-like quality controlled conditions with QAU statement
Qualifier:
according to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
GLP compliance:
no
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
other: Tif: RAIf(SPF), F3-hybrid of RII 1/Tif x RII 2/Tif
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: CIBA-GEIGY LTD. Tierfarm, 4334 Sisseln, Switzerland
- Age at study initiation: 7-8 weeks
- Weight at study initiation: 168 to 201 g
- Fasting period before study: overnight
- Housing: in groups of 5 in Macrolon cages type 4 with standardized soft wood bedding
- Diet: Rat food, NAFAG No. 890, NAFAG AG, Gossau, SG (Switzerland), ad libitum
- Water: ad libitum
- Acclimation period: 6 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22+/-3
- Humidity (%): 55+/-15
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12
Route of administration:
oral: gavage
Vehicle:
other: distilled water containing 0.5% carboxymethylcellulose and 0.1% polysorbate 80
Details on oral exposure:
MAXIMUM DOSE VOLUME APPLIED: 20 ml/kg bodyweight
Doses:
5000 mg/kg bodyweight
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: daily
- Frequency of weighing: on days 1, 7, and 14
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, mortality
Statistics:
From the body weights, the group means and their standard deviations were calculated.
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 5 000 mg/kg bw
Mortality:
No mortalities observed.
Clinical signs:
other: Dyspnea, ruffled fur and curved body position. The animals recovered within 11 days.
Gross pathology:
No deviations from normal morphology were found.

Body weights and standard deviations

   males              females
 dose (mg/kg)  day 1 day 7  day 14  day 1  day 7  day 14 
 5000  193g / 6.6 260g / 7.6  307g / 11.8  179g / 11.7  211g / 10.1  222g / 4.3 
Interpretation of results:
not classified
Remarks:
Migrated information
Conclusions:
The acute oral LD50 of the test substance in male and female rats is greater than 5000 mg/kg body weight.
Executive summary:

Five male and five female Tif: RAIf(SPF) rats were treated with the test substance by oral gavage administration at a dosage of 5000 mg/kg body weight. The test item was diluted in distilled water containing 0.5% carboxymethylcellulose and 0.1% polysorbate 80 and administered at a volume dosage of 20 mL/kg. All animals survived until the end of the study period. Clinical signs were dyspnea, ruffled fur, and curved body position, being common symptoms in acute tests. The animals recovered within 11 days. Body weight gains were normal, no macroscopic findings were recorded at necropsy. In conclusion, the median lethal dose of the test substance after single oral administration to male and female rats, observed over a period of 14 days is greater than 5000 mg/kg body weight.

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
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: guideline study according to GLP
Qualifier:
according to guideline
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
yes
Remarks:
Due to the physical-chemical properties, the test substance had to be applied by weight.
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
other: (Tif: RAI f (SPF)
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: CIBA-GEIGY Limited Animal Production 4332 Stein / Switzerland
- Age at study initiation: not specified
- Weight at study initiation: 207 to 273 g
- Housing: individually in Macrolon cages type 3, with standardized soft wood bedding (Societe Parisienne des Sciures, Pantin, France)
- Diet: NAFAG 890 Tox, NAFAG, Gossau/SG, Switzerland (ad libitum)
- Water: ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 2
- Humidity (%): 55 +/- 10
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12
Type of coverage:
semiocclusive
Vehicle:
other: 0.5 % (w/v) carboxymethylcellulose in 0.1 % (w/v) aqueous polysorbate 80
Details on dermal exposure:
TEST SITE
- Area of exposure: back of the rat
- % coverage: 10
- Type of wrap if used: gauze-lined semiocclusive dressing fastened around the trunk with an adhesive elastic bandage.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): with lukewarm water
- Time after start of exposure: 24 hours

TEST MATERIAL
- Amount applied (ml/kg body weight): 4 g (corresponding approximately to 4 ml).
Duration of exposure:
24 h
Doses:
2000 mg/kg body weight
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: daily
- Frequency of weighing: immediately before application and on days 7 and 14
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, mortality
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Mortality:
no mortalities
Clinical signs:
other: Piloerection and hunched posture were seen, the animals recovered within 2 days.
Gross pathology:
At necropsy, no deviations from normal morphology were found.

 Animal number Body weights (g) Day 0  Body weights (g) Day 7   Body weights (g) Day 14

 MALES dosed with 2000 mg/kg bodyweight         

 1 264 307   350
 2 273 301  333 
 3 256 290  319 
 4 265 291  317 
 5 260 288  316 
 mean 264 295  327 
 SD 6.3 8.2   14.6

 FEMALES dosed with 2000 mg/kg bodyweight         

 1 254 253 291
 2 232  241  252 
 3 229 247  240 
 4 207 212  235 
 5 221 226  235 
 mean 229 236  251 
 SD 17.2 16.7  23.6 
Interpretation of results:
practically nontoxic
Remarks:
Migrated information
Conclusions:
The acute dermal LD50 of the test substance in rats of both sexes is greater than 2000 mg/kg body weight.
Executive summary:

Five male and five female (Tif: RAI f (SPF)) rats were treated with the test substance at 2000 mg/kg by dermal application. The test item was diluted in 0.5 % (w/v) carboxymethylcellulose in 0.1 % (w/v) aqueous polysorbate 80 and applied at a dosage of 2 g/kg. The application period was 24 hours. No deaths occurred during the study. Clinical signs were piloerection and hunched posture, being common symptoms in acute dermal tests. No macroscopic findings were observed at necropsy. In conclusion, the median lethal dose of the test substance after single dermal administration to rats of both sexes, observed over a period of 14 days is greater than 2000 mg/kg body weight.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
2 000 mg/kg bw

Additional information

Justification for selection of acute toxicity – oral endpoint
Key value determined using OECD test guidance 401.

Justification for selection of acute toxicity – dermal endpoint
Key value determined using OECD test guideline 402.

Justification for classification or non-classification

Based on the data available the substance does not trigger any of the requirements for classification.

The registered substance is therefore not classified.