Registration Dossier

Administrative data

Description of key information

Oral: An LD50 of ca. 1815 mg/kg was determined after an oral administration of the test substance to rats via gavage.

Inhalation: In an IHT test no mortalities were observed when rats were exposed for 8 hours to an atmosphere enriched with the test substance vapour generated at 20°C (13.75 mg/L) and 100°C (43.36 mg/L).

Dermal: No information available.

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:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: no guideline was followed, observation period was only 7 days, acceptable for assessment
Principles of method if other than guideline:
Method: BASF test
GLP compliance:
no
Remarks:
GLP was not compulsatory at this time
Limit test:
no
Specific details on test material used for the study:
- appearance: liquid
- content: 50% in water
Species:
rat
Strain:
not specified
Remarks:
Gassner
Sex:
male/female
Route of administration:
oral: gavage
Vehicle:
water
Doses:
Doses: 8000, 6400, 5000, 4000, 3200, 2500 cmm/kg.
Concentration: 30% (v/v) aqueous solution
No. of animals per sex per dose:
10
Control animals:
no
Details on study design:
- Duration of observation period following administration: 7 days.
- Frequency of observations and weighing: not specified
- Necropsy of survivors performed: yes.
- Other examinations performed: clinical signs, body weights.
Sex:
male/female
Dose descriptor:
LD50
Effect level:
ca. 3 300 other: mm3/kg
Remarks on result:
other: worst case assumption: equivalent to LD50 = 1815 mg/kg considering the substance density and the 50% content of the substance in the test material
Mortality:
See table 1.
All animals exposed to 5000 cmm/kg and above deceased within 15 minutes. Surviving animals showed accelerated breathing and hunched position 2 hours after application, but no adverse effects were observed at day 3 and thereafter.
Clinical signs:
Directly after application accelerated breathing, tremors, apathy, abdominal position and clonic convulsions were observed.
Body weight:
Mean body weights wre determined to be 241.2 g for males and 167.1 g for females.
Gross pathology:
venous congestion

Table 1: Mortalities

Dose
cmm/kg
Concentration Number of animals Number of deceased animals within
1 h 24 h 48 h 7 d
8000 30% 10 M 10/10 10/10 10/10 10/10
10 F 10/10 10/10 10/10 10/10
6400 30% 10 M 10/10 10/10 10/10 10/10
10 F 10/10 10/10 10/10 10/10
5000 30% 10 M 10/10 10/10 10/10 10/10
10 F 10/10 10/10 10/10 10/10
4000 30% 10 M 9/10 9/10 9/10 9/10
10 F 9/10 10/10 10/10 10/10
3200 30% 10 M 3/10 3/10 3/10 3/10
10 F 5/10 5/10 5/10 5/10
2500 30% 10 M 0/10 0/10 0/10 0/10
10 F 0/10 2/10 2/10 2/10
Interpretation of results:
Category 4 based on GHS criteria
Conclusions:
oral LD50 (rat) = 1815 mg/kg bw
Executive summary:

10 rats per sex and dose were exposed to single doses of 2500, 3200, 4000, 5000, 6400 and 8000 cmm/kg test substance/kg via gavage. Directly after application accelerated breathing, tremors, apathy, abdominal position and clonic convulsions were observed. Within a 7 -day observation period, 2/20, 8/20, 19/20, 20/20, 20/20 and 20/20 animals died in the dose groups of 2500, 3200, 4000, 5000, 6400 and 8000 cmm/kg. Necropsy revealed venous congestion in deceased animals. A LD50 of 3300 cmm/kg was determined. The test material was an aqueous solution of the test subtance, containing 50% test substance. It is unclear whether the LD50 refers to the test material or pure test substance. Considering the test substance density, the LD50 of 3300 cmm/kg was converted to 3630 mg/kg. Applying a worst case approach, the LD50 was corrected to 1815 mg/kg bw accounting for the water content in the test material.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
Value:
1 815 mg/kg bw

Acute toxicity: via inhalation route

Link to relevant study records
Reference
Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Inhalation hazard test, saturated atmosphere was tested, acceptable for assessment
Principles of method if other than guideline:
Method: BASF test
GLP compliance:
no
Remarks:
GLP was not compulsatory at this time
Test type:
other: Inhalation hazard test
Species:
rat
Strain:
other: Gassner
Sex:
not specified
Route of administration:
inhalation: vapour
Details on inhalation exposure:
To generate saturated atmosphere, air was directed though a 5 cm layer of the test material at 20°C and 100°C respectively.
Duration of exposure:
8 h
No. of animals per sex per dose:
20°C vapour: 12 animals
100°C vapour: 12 animals
Control animals:
no
Dose descriptor:
other: LT0
Remarks:
20°C vapour
Effect level:
13.75 mg/L air
Exp. duration:
8 h
Remarks on result:
other: no mortality observed
Dose descriptor:
other: LT0
Remarks:
100°C vapour
Effect level:
43.36 mg/L air
Exp. duration:
8 h
Remarks on result:
other: no mortality observed
Mortality:
No mortalities after 8-hour exposure to an atmosphere enriched with the test substance vapour generated at 20 and 100°C.
Clinical signs:
other: Irritation of mucous membranes was observed.
Gross pathology:
No adverse effects observed.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
discriminating conc.
Value:
43 360 mg/m³

Acute toxicity: via dermal route

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Acute oral toxicity

Three acute oral toxicity studies are available.

In the first study (1972), 10 rats per sex and dose were exposed to single doses of 2500, 3200, 4000, 5000, 6400 and 8000 cmm/kg test substance/kg via gavage. Directly after application accelerated breathing, tremors, apathy, abdominal position and clonic convulsions were observed. Within a 7 -day observation period, 2/20, 8/20, 19/20, 20/20, 20/20 and 20/20 animals died in the dose groups of 2500, 3200, 4000, 5000, 6400 and 8000 cmm/kg. Necropsy revealed venous congestion in deceased animals. A LD50 of 3300 cmm/kg was determined. The test material was an aqueous solution of the test subtance, containing 50% test substance. It is unclear whether the LD50 refers to the test material or pure test substance. Considering the test substance density, the LD50 of 3300 cmm/kg was converted to 3630 mg/kg. Applying a worst case approach, the LD50 was corrected to 1815 mg/kg bw accounting for the water content in the test material.

In the second study, six doses of the test substance were applied to 5-10 rats per sex and dose via gavage (1974). Dyspnea, abdominal position, convulsions, tremors, inbalance, mild atonia were obsrved at 3200 µL/kg and above. No adverse clinical effects were observed up to 1600 µl/kg. Within an 7d observation period, 0/10, 0/20, 6/20, 8/20, 8/10 and 20/20 animals died in the dose groups of 200, 1600, 3200, 4000, 5000 and 6400 µL/kg. Necropsy revealed venous congestion and dilatation of the heart in deceased animals. A LD50 of 4010 µL/kg was determined. The test material was an aqueous solution of the test subtance, containing 50% test substance. It is unclear whether the LD50 refers to the test material or pure test substance.

In the third study (1981), 5 rats per sex and dose were exposed to single doses of 681, 1000, 1470 or 2150 mg test substance/kg via gavage. Mortality and clinical symptoms were recorded within an 14 -day observation period. Deceased and surviving rats were subjected to necropsy. Animals showed dyspnea, apathy, prone position, tumbling, tremors, tonic-clonic convulsions, poor general condition, shaggy hair, alopecia and exsiccose. At 1470 mg/kg and above all animals died within one day. At 1000 mg/kg 2/5 animals died per sex during the course of the study. No animals died in the lowest dose group. Deceased animals showed  venous congestion of the liver and gut atonia with diarrhetic content. No adverse effects were seen in the organs of killed animals. A LD50 of ca. 1000 mg/kg was determined. Since the test material contained other substances in concentrations >5%, this study was disregarded for assessment, because the toxicity could not be clearly attributed to the test substance.

Acute inhalation toxicity

Two hazard inhalation hazard tests have been perfomed, in which vapour of the test substance was administered to rats. To generate saturated atmosphere, air was directed though a 5 cm layer of the test material at 20°C or 100°C, respectively.

In the first test (1972), 12 rats (males and females) were exposed for 8 hours to vapors generated at 20°C or 100°C, equivalent to test substance concentrations of 13.75 and 43.36 mg/L, respectively. No mortality occured during the 8-hour exposure and the 7-day post-exposure observation period but irritation of mucous membranes was observed. No adverse substance-related effects were identified in the course of necropsy.

In the second test (1974), 12 rats (males and females) were exposed for 8 hours to vapors generated at 20°C, equivalent to a test substance concentration of 11.07 mg/L. In line with the results of the first test, no mortality or severe symptoms of toxicity occured during the 8 hour exposure and the 7 -day post-exposure observation period. Only a mild irritation of mocous membranes was observed. Necropsy revealed no adverse substance-related effects.

Acute dermal toxicity

No information available.

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 classified for acute oral toxicity Cat. 4 under Regulation (EC) No. 1272/2008, as amended for the thirteenth time in Regulation (EC) No. 2018/1480.