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Description of key information

The lowest acute oral LD50 obtained for the test item was found to be 526 mg/kg bw for male and female rats. 

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:
1982-09-20 to 1982-10-06
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Version / remarks:
adopted 1981
Deviations:
no
GLP compliance:
not specified
Test type:
standard acute method
Limit test:
no
Specific details on test material used for the study:
- Code No.: TK10363
- Batch No.: 42.29
- Physical state: Powder
Species:
rat
Strain:
other: Tif:RAIF (SPF)
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: 151 - 211 g
- Housing: Animals were caged in groups of 5 in Macrolon cages type 3 with standardised soft wood bedding (Societe Parisienne des sciures, Pantin).
- Diet: Rat food, NAPAG No. 890, NAPAG AG Gossau, Switzerland, provided ad libitum
- Water: Drinking water, provided ad libitum

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:
VEHICLE
- Concentration in vehicle: 25, 50, 100 mg/mL vehicle
- Amount of vehicle: 10 mL


Doses:
250, 500, 1000 mg/kg bw
No. of animals per sex per dose:
5 males and 5 females
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: daily
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, gross pathology
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/female
Dose descriptor:
LD50
Effect level:
525 mg/kg bw
Based on:
test mat.
95% CL:
> 417 - < 688
Sex:
male
Dose descriptor:
LD50
Effect level:
525 mg/kg bw
Based on:
test mat.
95% CL:
> 345 - < 871
Sex:
female
Dose descriptor:
LD50
Effect level:
525 mg/kg bw
Based on:
test mat.
95% CL:
> 345 - < 871
Mortality:
Males
250 mg/kg bw: no mortalities
500 mg/kg bw: 2 mortalities, both 2 h after treatment
1000 mg/kg bw: 5 mortalities, one at 1h after treatment, four at 2 h after treatment.

Females
250 mg/kg bw: no mortalities
500 mg/kg bw: 2 mortalities, both 2 h after treatment
1000 mg/kg bw: 5 mortalities, one at 1h after treatment, four at 2 h after treatment.
Clinical signs:
No specific symptoms were seen, except for transient clonic- tonic muscle spasms in the animals treated with 500 mg/kg.
Body weight:
No significant changes to the body weights were observed.
Gross pathology:
No compound related gross organ changes were observed. However, due to the colour of the test item, a red discoloration of the whole body was observed during 9 days in the animals treated with 250 mg/kg and during the whole observation period in the animals treated with 500 mg/kg.
Other findings:
The surviving animals recovered within 10 days.
Interpretation of results:
Category 4 based on GHS criteria
Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
Value:
526 mg/kg bw
Quality of whole database:
Guideline compliant study.

Acute toxicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no study available

Acute toxicity: via dermal route

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Acute oral toxicity

Key study

In an oral toxicity study (Ciba-Geigy, 1982) conducted according to OECD 401, the test item was administered to five male and female rats per sex per dose via gavage followed by a 14 -day observation period. The dose levels were as follows: 250, 500 and 1000 mg/kg bw. After the administration, the following mortalities were observed:

Males

250 mg/kg bw: no mortalities 500 mg/kg bw: 2 mortalities, both 2 h after treatment 1000 mg/kg bw: 5 mortalities, one at 1h after treatment, four at 2 h after treatment.  

Females

250 mg/kg bw: no mortalities 500 mg/kg bw: 2 mortalities, both 2 h after treatment 1000 mg/kg bw: 5 mortalities, one at 1h after treatment, four at 2 h after treatment.

No compound related changes in body weight and no specific symptoms were observed, except for transient clonic- tonic muscle spasms in the animals treated with 500 mg/kg. A red discoloration of the whole body was observed during 9 days in the animals treated with 250 mg/kg and during the whole observation period in the animals treated with 500 mg/kg bw. The LD50 values were determined to be 525 mg/kg bw for male and female rats and a combined LD50 of 526 mg/kg bw was determined for both sexes.

Supporting studies

The three independent supporting studies conducted with male and female rats are of limited reliability, In these studies the test substance is of low acute toxicity and the respective LD50 values were above the value determined in the key study. In this studies the LD50 values were determined to be 1800 mg/kg bw (Ciba-Geigy Ltd..1972), >= 4000 mg/kg bw (Unknown.Acute toxicity: oral_rat.1969) and >= 5000 mg/kg bw ( Unknown. 1970).

Justification for classification or non-classification

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

The available experimental test data are reliable and suitable forclassification purposes under Regulation (EC) No 1272/2008. Based on the result obtained in the key acute oral toxicity study (LD50, rat = 526 mg/kg bw) the test item has to be classified in acute toxicity category 4 (H302: Harmful if swallowed) according to Regulation (EC) No 1272/2008 (GHS), as amended for the sixth time in Regulation EC 944/2013