Registration Dossier

Administrative data

Description of key information

Oral LD50 rat > 2000 mg/kg bw; transient signs of toxicity: Piloerection, hunched posture, exophthalmos, and dyspnea (OECD 401; 1989)

Dermal LD50 rat > 2000 mg/kg bw; transient signs of toxicity: Piloerection, abnormal body positions, and dyspnea (OECD 402; 1989)

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:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes
Specific details on test material used for the study:
STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: room temperature
Species:
other: rat, Tif:RAI f (SPF)
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: CIBA-GEIGY Limited, Animal Production, Switzerland
- Age at study initiation: Young adult 6 to 8 weeks
- Weight at study initiation: 177 to 205 g
- Fasting period before study: fasted overnight
- Housing: group-housed = 5 animals per cage
- Diet (e.g. ad libitum): Rat chow (NAFAG 890 Tox, NAFAG,Gossau, Switzerland) was provided ad libitum.
- Water (e.g. ad libitum): water were provided ad libitum
- Acclimation period: at least for 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 + 2
- Humidity (%): 55 + 10 %.
- Air changes (per hr): approximately 15
- Photoperiod (hrs dark / hrs light): 12 hour/12 hour
Route of administration:
oral: gavage
Vehicle:
other: 0.5 % (w/v) carboxymethylcellulose in 0.1 % (w/v) aqueous polysorbate 80 (prepared by Pharmaceuticals Division, Ciba-Geigy Ltd,, Basel)
Details on oral exposure:
MAXIMUM DOSE VOLUME APPLIED: 10 ml/kg body weight
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
- Frequency of observations and weighing: Mortality was observed twice daily at a.m. and p.m. on working days and a.m. on weekend days. Signs and symptoms were noticed daily. Body weight was examined immediately before administration and on days 7 and 14.
- Necropsy of survivors performed: yes, at the end of the observation period.
Statistics:
From the body weights, the group means and their standard deviations were calculated.
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: No signs of specific toxicity
Mortality:
Male: 2000 mg/kg bw; Number of animals: 5; Number of deaths: 0
Female: 2000 mg/kg bw; Number of animals: 5; Number of deaths: 0
Clinical signs:
Piloerection, hunched posture, exophthalmos, and dyspnea were seen, being common symptoms in acute tests. The animals recovered within 5 to 6 days.
Body weight:
The mean body weights of the animals were in the normal range throughout the study period.
Gross pathology:
At autopsy, no deviations from normal morphology were found.
Interpretation of results:
GHS criteria not met
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
2 000 mg/kg bw
Quality of whole database:
guideline 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
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes
Species:
other: rat, Tif:RAIf (SPF)
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: CIBA-GEIGY Limited, Animal Production, Switzerland
- Age at study initiation: Young adult initial age 7 to 8 weeks
- Weight at study initiation: 211 to 235 g
- Housing: individually housed
- Diet (e.g. ad libitum): Rat chow (NAFAG 890 Tox, NAFAG,Gossau, Switzerland) was provided ad libitum.
- Water (e.g. ad libitum): water was provided ad libitum
- Acclimation period: for at least 5 days before exposure

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 2
- Humidity (%): 55 +/- 10
- Air changes (per hr): approximately 15
- Photoperiod (hrs dark / hrs light): 12/12
Type of coverage:
semiocclusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- % coverage: at least 10% of the body surface

REMOVAL OF TEST SUBSTANCE
- Washing (if done): cleaned with lukewarm water

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2 ml/kg body weight
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 and weighing: Mortality was observed twice on working days and once on weekend days. Signs and symptoms were noticed daily. Body weight was observed immediately before application and on days 7 and 14.
- Necropsy of survivors performed: yes, at the end of the observation period.
Statistics:
From the body weights, the group means and their standard deviations were calculated.
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: No signs of specific toxicity.
Mortality:
No mortality occurred in this study.
Clinical signs:
Piloerection, abnormal body positions, and dyspnea were seen,
being common symptoms in acute dermal tests.
The animals recovered within 5 days.
Body weight:
The mean body weights of the animals were in the normal range throughout the study period.
Gross pathology:
At autopsy, no deviations from normal morphology were found.
Interpretation of results:
GHS criteria not met
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
2 000 mg/kg bw
Quality of whole database:
guideline study

Additional information

Oral

 A GLP conform study was performed to assess the acute toxicity following oral administration of the test substance in albino rats (Tif: RAI f) according to OECD guideline 401 (1989). To a group of ten fasted animals (five males and five females) a single oral dose of the test material preparation (dose volume: 10 ml/kg bw) in 0.5% (w/v) carboxymethylcellulose in 0.1 % (w/v) aqueous polysorbate 80 at a dose level of 2000 mg/kg body weight was given. Piloerection, hunched posture, exophthalmos, and dyspnea were seen, being unspecific symptoms in acute tests. The animals recovered within 5 to 6 days. The expected body weight gain was observed in the course of the study. No mortality occurred in this study. At autopsy, no deviations from normal morphology were found. Under the conditions of this study the median lethal dose of the test substance after oral application was found to be greater than 2000 mg/kg body weight for the male and female animals.

Dermal

A GLP conform study was performed to assess the acute toxicity following dermal administration of the test substance in albino rats (Tif: RAI f) according to OECD guideline 402 (CIBA-Geigy, 1989). To a group of ten animals (five males and five females) a single dermal dose of the test material preparation (dose volume: 2 ml/kg bw) was given undiluted at a dose level of 2000 mg/kg body weight. Piloerection, abnormal body positions, and dyspnea were seen, being unspecific symptoms in acute dermal tests. The animals recovered within 5 days. The expected body weight gain was observed in the course of the study. No mortality occurred. At autopsy, no deviations from normal morphology were found. Under the conditions of this study the median lethal dose of the test substance after oral application was found to be greater than 2000 mg/kg body weight for the male and female animals.

 

Inhalation

not performed

Justification for classification or non-classification

Classification, Labelling, and Packaging Regulation (EC) No 1272/2008
The available experimental test data are reliable and suitable for classification purposes under Regulation (EC) No 1272/2008. LD50 for acute oral toxicity was greater than 2000 mg/kg bw. As a result the substance is not considered to be classified for acute toxicity under Regulation (EC) No 1272/2008.