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Administrative data

Description of key information

- Acute oral toxicity (OECD guideline 401 & GLP): LD50 > 5000 mg/kg bw

- Acute dermal toxicity (OECD guideline 402): 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:
03.02. - 25.03.1986
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Version / remarks:
adopted May 12, 1984
Deviations:
no
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
other: CRL:CD (SD) BR
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: CIBA-GEIGY Limited, Animal Production, 4332 Stein, Switzerland
- Age at study initiation: between 6 weeks
- Weight at study initiation: females and males: 150 -160 g
- Fasting period before study: overnight, prior to dosing
- Housing: five animals per cage in Macrolon cages type 4 with ALTROMIN - soft wood bedding type 3/4
- Diet: ALTROMIN standard diet 1324, ad libitum with exception of the fasting period before treatment start
- Water: ad libitum
- Acclimation period: 1 week

ENVIRONMENTAL CONDITIONS
- Temperature: 22 ± 2 °C
- Humidity: 55 ± 10 %
- Air changes: 15 - 20 changes/hour
- Photoperiod: 12 hours dark / 12 hours light

IN-LIFE DATES: from 03 to 25 February 1986
Route of administration:
oral: gavage
Vehicle:
olive oil
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 500 mg/mL
- Amount of vehicle: 10 mL/kg bw
Doses:
5000 mg/kg bw
No. of animals per sex per dose:
10 rats
Control animals:
yes
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations: daily
- Necropsy of survivors performed: yes
- Other examinations performed:
Clinical signs: After compound administration the animals were observed for clinical signs of toxicity. Time schedule: 5, 15, 30, 60 minutes; 3, 6 and 24 hours post application, then at least twice daily for a period of 14 days. The onset, duration and intensity of clinical signs of toxicity were recorded.
Mortality check: On administration day several times, then twice daily on 7 days/week.
Body weight: Body weight was recorded before treatment, at week 1 and week 2 after compound administration.
Food consumption: Food consumption was recorded at week 1 and week 2 after compound administration.
Statistics:
Routine evaluation of the data for significance of differences was done by t-test.
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 5 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality occurred.
Clinical signs:
In relation to the controls no clinical signs of toxicity were observed in the rats treated with 5000 mg/kg bw.
Body weight:
In comparison to control no statistically significant difference in body weight gain was found in the treated rats.
Gross pathology:
All organs of the rats in the control and dose groups were normal. No effects were observed.
Other findings:
Food consumption:
No difference was found in food consumption between control group and rats treated with 5000 mg/kg bw.
Interpretation of results:
GHS criteria not met
Conclusions:
The oral LD50 in male and female Sprague-dawley rats is greater than 5000 mg/kg body weight.
Executive summary:

The acute oral toxicity and the lethal dose (LD50) of the test substance in Sprague-Dawley rats were determined in an OECD 401 guideline study compliant with GLP principles. Two groups of males and females (5/sex/group) were dosed by gavage with 0 and 5000 mg/kg bw of the test substance, controls received the vehicle (olive oil) only. All rats were at least observed twice daily for mortality and clinical signs of toxicity. Body weights were recorded before treatment, at week 1 and week 2 after compound administration; food consumption was recorded at week 1 and week 2 after compound administration. All rats were sacrificed 2 weeks after dosing and a gross post mortem examination was performed. No clinical signs of toxicity were found in the treated animals in relation to the control. All animals survived until the end of the study. No statistical differences were found in body weight gain and no deviations were seen in food consumption between controls and rats treated with 5000 mg/kg bw. At necropsy no alterations were observed in the treated rats. The LD50 in female and male rats was therefore set at > 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
Study period:
26.02. - 25.03.1986
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Version / remarks:
adopted December 17, 1985
Deviations:
no
GLP compliance:
no
Remarks:
but performed under quality control, QAU statement included
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 and environmental conditions:
TEST ANIMALS
- Source: Ciba-Geigy Ltd. Tierfarm, 4334 Sisseln, Switzerland
- Age at study initiation: 7 to 8 weeks
- Weight at study initiation: 209 to 252 g
- Housing: individually in Macrolon cages type 3 with standardized soft wood bedding
- Diet: Rat food, NAFAG No. 890, ad libitum
- Water: ad libitum
- Acclimation period: at least 5 days before exposure

ENVIRONMENTAL CONDITIONS
- Temperature: 22 ± 3 °C
- Humidity: 55 ± 15 %
- Air changes: 15 changes/hour
- Photoperiod: 12 hours dark/12 hours light

IN-LIFE DATES: from 26 February to 18 March 1986
Type of coverage:
semiocclusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: area on the back of the rat
- % coverage: at least 10% of the body surface area
- Type of wrap: gauze-lined semiocclusive dressing fastened around the trunk with an adhesive elastic bandage.

REMOVAL OF TEST SUBSTANCE
- Washing: cleaned with lukewarm water
- Time after start of exposure: 24h

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2 mL/kg bw
Duration of exposure:
24 h
Doses:
2000 mg/kg bw (males and females)
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, the animals were submitted to a gross necropsy at the end of the observation period.
- Other examinations performed:
Signs and symptoms: daily for 14 days
Mortality: daily; a.m. and p.m. on working days, a.m. on weekend days
Body weight: immediately before application and on days 7 and 14
Statistics:
From the body weights, the group means and their standard deviations were calculated.
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality occurred.
Clinical signs:
Dyspnea, ruffled fur, and abnormal body positions were seen, being common symptoms in acute tests. Additionally, sedation was observed on the application day. The animals recovered within 10 days.
Body weight:
All rats achieved anticipated bodyweight gains throughout the study.
Gross pathology:
At autopsy, no deviations from normal morphology were found.
Interpretation of results:
GHS criteria not met
Conclusions:
The dermal LD50 in rats was determined to be greater than 2000 mg/kg body weight.
Executive summary:

In an acute dermal toxicity study following OECD guideline 402, 5 male and 5 female rats were dermally exposed to the test item for 24 hours at a limit dose of 2000 mg/kg body weight. The test article was used undiluted and 2 ml/kg body weight was applied to the clipped back of the animals (10% body surface) under a gauze-lined semiocclusive dressing, which was fastened around the trunk with an adhesive elastic bandage. After 24 hours the dressing was removed and residual test article was washed off with lukewarm water. All animals were observed once daily for 14 days for clinical signs and symptoms and twice daily for mortality. Body weights were recorded on days 1, 7 and 14. All animals were submitted to a gross necropsy at the end of the observation period. All animals survived the 2000 mg/kg dermal application. Dyspnea, ruffled fur, and abnormal body positions were seen, being common symptoms in acute tests. Additionally, sedation was observed on the application day. The animals recovered within 10 days. Body weight changes were normal and no deviations from normal morphology were found during necropsy. Based on these observations, the dermal LD50 value of the test item was greater than 2000 mg/kg bw.

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

Additional information

Acute oral toxicity

The acute oral toxicity of the test substance was assessed in a GLP-compliant study following OECD guideline 401 (Biomedizinische Forschungsanstalt, 851155, 1986). In the limit test, a single dose of 5000 mg/kg bw in olive oil was applied by gavage to five male and five female Sprague-Dawley rats. Ten additional rats (5m/5f) received the vehicle alone (negative control). No mortality occurred within the timeframe of the study. No clinical signs of toxicity were found in the treated animals in relation to the control. All rats were sacrificed 2 weeks after dosing and a grosspost mortem examination was performed. No alterations were observed at necropsy. Overall, under the chosen test conditions, the test substance was not toxic after single oral administration: Oral LD50 > 5000 mg/kg bw

Acute dermal toxicity

As a second exposure route acute dermal toxicity was investigated (CIBA-GEIGY Ltd., 851158, 1986). The study was performed under GLP-like quality control and in accordance with OECD guideline 402. Following the Standard Acute Method, a single dose of 2000 mg/kg bw (without vehicle, undiluted) in a limit test was administered topically under semi-occlusive conditions to five male and five female rats. After an exposure period of 24 hours the dressing was removed, and the skin was cleaned with lukewarm water. No mortality occurred within the timeframe of the study. Dyspnea, ruffled fur, and abnormal body positions were seen, being common symptoms in acute tests. All animals recovered within 10 days. At autopsy, no deviations from normal morphology were found. Overall, under the chosen test conditions, the test substance does not have toxic properties in case of single dermal exposure: Dermal LD50 > 2000 mg/kg bw

Acute inhalation toxicity

No data available.

Justification for classification or non-classification

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.