Registration Dossier

Administrative data

Description of key information

Acute oral toxicity: LD50 > 2000 mg/kg bw; Ciba-Geigy 1991, OECD Guideline Study
Acute dermal toxicity: LD50 > 2000 mg/kg bw; Ciba-Geigy 1991, OECD Guideline Study

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:
19.09. - 17.10.1991
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: OECD guideline study, GLP
Qualifier:
according to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Version / remarks:
adopted 24. February 1987
Deviations:
no
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
other: Tif:RAIf
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: CIBA-GEIGY Limited, Animal Production, 4332 Stein, Switzerland
- Weight at study initiation: 183 to 200 g
- Fasting period before study: Prior to dosing, the animals were fasted overnight.
- Housing: Macrolon cages type 4
- Diet: ad libitum
- Water: ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 2°C
- Humidity (%): 55 +/- 10 %
- Air changes (per hr): 15
- Photoperiod: 12 hrs dark / 12 hrs light

IN-LIFE DATES: From: 01.10. to 17.10.1991
Route of administration:
oral: gavage
Vehicle:
CMC (carboxymethyl cellulose)
Remarks:
0.5 % (w/v) in 0.1 % (w/v) aqueous polysorbate 80
Details on oral exposure:
Volume applied: 10 mL/kg body weight
Doses:
2000 mg/kg bw (males and females)
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Necropsy of survivors performed: yes
- Other examinations performed:
Mortality : daily; a.m. and p.m. on working days, a.m. on weekend days
Signs and symptoms: daily for 14 days
Body weight: immediately before administration and on days 7 and 14
Statistics:
Group means and respective standard deviations were calculated of body weights.
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: No mortality occurred
Mortality:
No mortality occurred in this study.
Clinical signs:
Piloerection, hunched posture and dyspnea were seen, being common symptoms in acute tests. The animals recovered within 5 days.
Body weight:
The body weight was not affected adversely.
Gross pathology:
At autopsy, no deviations from normal morphology were found
Interpretation of results:
practically nontoxic
Remarks:
Migrated information
Conclusions:
The oral LD50 value of the test article in rats was established to exceed 2000 mg/kg body weight.
Executive summary:

In an oral toxicity study according to OECD guideline 401, five male and five female Tif: RAIf rats were dosed once with the test article in the vehicle (0.5 % (w/v) carboxymethylcellulose in 0.1 % (w/v) aqueous polysorbate80) by gastric intubation at a dose level of 2000 mg/kg body weight and observed for 14 days. Animals were subjected to daily observations and weekly determination of body weight. Macroscopic examination was performed at the end of the observation period. No mortalities were recorded. Piloerection, hunched posture and dyspnea were seen, being common symptoms in acute tests. The animals recovered within 5 days. At autopsy, no deviations from normal morphology were found. The oral LD50 value of the test article was established to exceed 2000 mg/kg body weight.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
2 000 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
Study period:
01.10. - 29.10.1991
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: OECD Guideline study, GLP
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
no
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
other: Tif:RAIf
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: CIBA-GEIGY Limited, Animal Production, 4332 Stein, Switzerland
- Weight at study initiation: 217 to 248 g
- Fasting period before study: Prior to dosing, the animals were fasted overnight.
- Housing: Macrolon cages type 3
- Diet: ad libitum
- Water: ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 2°C
- Humidity (%): 55 +/- 10 %
- Air changes (per hr): 15
- Photoperiod: 12 hrs dark / 12 hrs light

IN-LIFE DATES: From: 01.10. to 17.10.1991
Type of coverage:
semiocclusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: on the back of the animals
- % coverage: 10
- Type of wrap if used: a gauze-lined semiocclusive dressing fastened around the trunk with an adhesive elastic bandage.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): the skin was cleaned with lukewarm water.
- Time after start of exposure: 24 hrs

TEST MATERIAL
- Amount applied: 2 mL
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:
- Duration of observation period following administration: 14 days
- Necropsy of survivors performed: yes
- Other examinations performed:
Mortality : daily; a.m. and p.m. on working days, a.m. on weekend days
Signs and symptoms: daily for 14 days
Body weight: immediately before administration and on days 7 and 14
Statistics:
From the body weights, the group means and their standard deviations were calculated.
Preliminary study:
Not applicable.
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: No mortality occurred.
Mortality:
No mortality occurred in this study.
Clinical signs:
Slight piloerection was observed in both, female and male animals. The animals recovered within 2 days.
Body weight:
The body weight was not affected.
Gross pathology:
At autopsy, no deviations from normal morphology were found.
Other findings:
None.
Interpretation of results:
practically nontoxic
Remarks:
Migrated information
Conclusions:
The dermal LD50 value of the test article in Wistar rats was established to exceed 2000 mg/kg body weight.
Executive summary:

The acute dermal toxicity of the test substance was assessed in a toxicity study following OECD guideline 402 and in compliance with GLP. The test article was administered to five TIF:RAIf rats of each sex by dermal application at 2000 mg/kg body weight for 24 hours. Animals were subjected to daily observations and weekly determination of body weight. Macroscopic examination was performed at the end of the observation period. No mortality occurred. Piloerection was seen, being a common symptom in acute dermal tests. The animals recovered within 2 days. At autopsy, no deviations from normal morphology were found. The dermal LD50 value of the test substance in Wistar rats was established to exceed 2000 mg/kg body weight.

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

Additional information

Oral

In a GLP-compliant acute oral toxicity study (OECD 401, Ciba-Geigy 1991), the test substance in the vehicle ( 0.5 % (w/v) carboxymethylcellulose in 0.1 % (w/v) aqueous polysorbate 80) was administered by oral gavage to five Tif: RAIf rats of each sex at 2000 mg/kg body weight. Animals were subjected to daily observations and weekly determination of body weight. Macroscopic examination was performed at the end of the observation period. No mortalities were recorded. Piloerection, hunched posture and dyspnea were seen, being common symptoms in acute tests. The animals recovered within 5 days. At autopsy, no deviations from normal morphology were found. The oral LD50 value of the test article was established to exceed 2000 mg/kg body weight.

A supporting study (Ciba-Geigy, 1989) showed similar results.

Dermal

In a GLP-compliant acute dermal toxicity study (OECD 402, Ciba-Geigy 1991) the test article was administered unchanged (no vehicle) to five TIF:RAIf rats of each sex by dermal application at 2000 mg/kg body weight for 24 hours. Animals were subjected to daily observations and weekly determination of body weight. Macroscopic examination was performed at the end of the observation period. No mortality occurred. Piloerection was seen, being a common symptom in acute dermal tests. The animals recovered within 2 days. At autopsy, no deviations from normal morphology were found. The dermal LD50 value of the test substance in Wistar rats was established to exceed 2000 mg/kg body weight.


Justification for selection of acute toxicity – oral endpoint
GLP-compliant guideline study

Justification for selection of acute toxicity – dermal endpoint
GLP-compliant guideline study

Justification for classification or non-classification

Dangerous Substance Directive (67/548/EEC)

The available experimental test data is reliable and suitable for the purpose of classification under Directive 67/548/EEC. Based on the data, classification for acute toxicity is not warranted under Directive 67/548/EEC.

 

Classification, Labeling, and Packaging Regulation (EC) No. 1272/2008

The available experimental test data are reliable and suitable for the purpose of classification under Regulation (EC) No.1272/2008. Based on the data, classification for acute toxicity is not warranted under Regulation (EC) No.1272/2008.