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Administrative data

Description of key information

The key studies provided were conducted to recognised testing guidelines and with GLP certification.

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:
1983
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
GLP compliance:
no
Remarks:
prior to GLP
Test type:
standard acute method
Limit test:
no
Species:
rat
Strain:
other: Tif:RAIf(SPF), F3-crosses of RII 1/Tif x RII 2/Tif
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: CIBA-GEIGY LTD. Tierfarm, 4334 Sisseln, Switzerland
- Age at study initiation: 7-8 weeks
- Weight at study initiation: 159 - 215 g
- Fasting period before study: overnight
- Housing: groups of 5
- Diet (e.g. ad libitum): Rat food, NAFAG No. 890, NAFAG AG, Gossau, SG (Switzerland), provided ad libitum
- Water (e.g. ad libitum): ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22+/- 3
- Humidity (%): 55+/- 15
- Air changes (per hr): approximately 15
- Photoperiod (hrs dark / hrs light): 12 hours/12 hours
Route of administration:
oral: gavage
Vehicle:
other: water containing 0.5% carboxymethylcellulose and 0.1% polysorbate 80
Details on oral exposure:
MAXIMUM DOSE VOLUME APPLIED: 20 ml/kg body weight
Doses:
1000, 2000, 4000 mg/kg bw
No. of animals per sex per dose:
5 animals
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days or until all symptoms have disappeared, whichever lasts longer
- Frequency of observations and weighing: Mortality = daily; a.m. and p.m. on working days, a.m. on weekend days; Signs and Symptoms = daily; Body weight = on days 1, 7, 14, 28 and at death
- Necropsy of survivors performed: yes, Spontaneously dying animals were submitted to a gross necropsy as soon as possible; survivors at the end of the observation period.
Statistics:
From the body weights, the group means and their standard deviations were calculated.
Where feasable, the LD50 including the 95% confidence limit were computed by the logit method (J. Berkson, J.Am. Stat. Ass. 39. 357-65, 1944)
Sex:
male
Dose descriptor:
LD50
Effect level:
2 756 mg/kg bw
Based on:
test mat.
Sex:
female
Dose descriptor:
LD50
Effect level:
1 340 mg/kg bw
Based on:
test mat.
Remarks on result:
other: estimated value
Sex:
male/female
Dose descriptor:
LD50
Effect level:
1 984 mg/kg bw
Based on:
test mat.
Remarks on result:
other: average value of both sexes
Mortality:
males:
1000 mg/kg/bw: 0/5 animals died
2000 mg/kg/bw: 1/5 animals died
4000 mg/kg/bw: 4/5 animals died

females:
1000 mg/kg/bw: 2/5 animals died
2000 mg/kg/bw: 3/5 animals died
4000 mg/kg/bw: 5/5 animals died
Clinical signs:
Dyspnoea, exophthalmus, ruffled fur and curved body position were seen, being common symptoms in acute tests. In addition sedation, lateral and ventral body position, chromodacryorrhea, diarrhea, tonic clonic convulsions and bilateral paresis of the hindlimbs were observed. Extended skin erythema and reversible alopecia was noted in several animals.
From day 6 onward some animals in the 1000 and 2000 mg/kg groups showed skin erythema for several days and alopecia in either the dorsal or ventral body area. After 3 weeks the fur started to grow again and by the end of the observation period the fur appeared to be normal.
In the 2000 mg/kg group one female showed bilateral ocular opacity which did not reverse until the end of the experiment.
The surviving animals recovered within 28 days.
Body weight:
Body weights were in the normal range
Gross pathology:
Besides two cases of spotted lung in the high dose group no findings were made at necropsy.
Interpretation of results:
Category 4 based on GHS criteria
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The acute oral LD50 of the test material to male and female rats was determined to be 1984 mg/kg bw.
Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
Value:
1 984 mg/kg bw

Acute toxicity: via inhalation route

Link to relevant study records
Reference
Endpoint:
acute toxicity: inhalation
Data waiving:
study scientifically not necessary / other information available
Justification for data waiving:
the study does not need to be conducted because exposure of humans via inhalation is not likely taking into account the vapour pressure of the substance and/or the possibility of exposure to aerosols, particles or droplets of an inhalable size
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
Study period:
1983
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
GLP compliance:
no
Remarks:
prior to GLP
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
other: Rat, Tif:RAIf (SPF), F3-crosses ot RII 1/Tif X RII 2/Tif
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: CIBA-GEIGY LTD. Tierfarm, 4334 Sisseln, Switzerland
- Age at study initiation: 7-8 weeks
- Weight at study initiation: 177-241 g
- Housing: individually
- Diet (e.g. ad libitum): Rat food, NAFAG No. 890, NAFAG AG, Gossau, SG (Switzerland), ad libitum
- Water (e.g. ad libitum): water, ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22±3
- Humidity (%): 55±15
- Air changes (per hr): approximately 15
- Photoperiod (hrs dark / hrs light): 12 hours/12 hours
Type of coverage:
occlusive
Vehicle:
other: Distilled water containing 0.5% carboxymethylcellulose and 0.1% polysorbate 80 (prepared by Pharmaceutical Division, Ciba-Geigy Ltd.).
Details on dermal exposure:
TEST SITE
- Type of wrap: gauze lined occlusive dressing

REMOVAL OF TEST SUBSTANCE
- Washing: dressing was removed and the skin was cleaned with lukewarm water
- Time after start of exposure: 24 hours

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 4 ml/kg body weight
Duration of exposure:
24 hours
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
5 animals
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days or until all symptoms have disappeared, whichever lasts longer
- Frequency of observations and weighing: Mortalitv = daily, a.m. and p.m. on working days, a.m. on weekends; Signs and Symptoms = daily; Body weight = on days 1, 7, 14 and at death
- Necropsy of survivors performed: yes, spontaneously dying animals were submitted to a gross necropsy as soon as possible; survivors at the end of the observation period.
Statistics:
From the body weights, the group means and their standard deviations were calculated.
Where reasable, the LD50 including the 95% confidence limit were computed by the logit method (J. Berkson, J.Am. Stat. Ass. 39. 357-65, 1944).
Sex:
male
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
male: 0/5 animals
female: 0/5 animals
Clinical signs:
Dyspnoea, exophthalmus, ruffled fur and curved and ventral body positions were seen. The surviving animals recovered within 8 days.
Body weight:
No abnormalities were observed.
Gross pathology:
No gross lesions were found at necropsy.
Interpretation of results:
GHS criteria not met
Remarks:
Migrated information Criteria used for interpretation of results: EU
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
2 000 mg/kg bw

Additional information

Method

A single dose of the test item was administered by gavage to male and female rats at concentrations up to 4000 mg/kg bw. The animals were observed for 14 or 28 days, respectively. Mortality, body weight and clinical signs were recorded continuously. Organ weighing and gross necropsy was performed after scheduled sacrifice.

A single dose of the test item was applied onto skin of male and female Wistar rats at concentrations of 2000 mg/kg bw. The animals were observed for 14 days. Mortality, body weight and clinical signs were recorded continuously. Organ weighing and gross necropsy was performed after scheduled sacrifice.

Results

When administered orally 9/10 animals of the high dose group died within 6 days after treatment, 4/10 animals of the mid dose group and 2 animals of the low dose group died as well. From day 6 onward some animals in the 1000 and 2000 mg/kg groups showed skin erythema for several days and alopecia in either the dorsal or ventral body area. After 3 weeks the fur started to grow again and by the end of the observation period the fur appeared to be normal . In the 2000 mg/kg group one female showed bilateral ocular opacity which did not reverse until the end of the experiment. Bilateral paresis of the hindlimbs was noted in animals of the mid dose group. The surviving animals recovered within 28 days.

After single dermal application no mortality occurred, body weight and body weight gain were comparable to control animals. Ventral body position and ruffled fur was observed during tne period at administration. No local reaction was noted on the site of application. The LD50 is therefore considered to be > 2000 mg/kg bw.

Conclusion

Single oral administration resulted in mortality, skin lesions and paresis of the hindlimbs; the LD50 is considered to be 1984 mg/kg bw and the substance has to be classified as harmful if swallowed. Single dermal application caused slight, transient clinical signs, the LD50 is > 2000 mg/kg bw.

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 1272/2008. As a result the substance is considered to be classified for acute oral toxicity under Regulation (EC) No. 1272/2008.