Registration Dossier

Administrative data

Description of key information

Oral: rat LD50: 1010 mg/kg bw. Reliability = 2

Dermal: rabbit LD50: 400 mg/kg. Standardized test protocol. Reliability = 2

Inhalation: rat 4 -hour LC50: >0.37 mg/L (maximum attainable concentration). OECD 403. Reliability = 1

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:
study well documented, meets generally accepted scientific principles, acceptable for assessment
Remarks:
Acceptable, well documented publication/ study report which meets basic scientific principles.
Principles of method if other than guideline:
The LD50 was determined after a 24-hour fast with free access to tap-water.
GLP compliance:
not specified
Test type:
standard acute method
Species:
rat
Strain:
Wistar
Sex:
male
Details on test animals and environmental conditions:
TEST ANIMALS
- Weight at study initiation: 205-220 g
- Housing: each housed in individual cages
- Diet: commercial standard solid diet (Altromin-R) ad libitum
- Water: ad libitum
Route of administration:
oral: unspecified
Doses:
840-1214 mg/kg
No. of animals per sex per dose:
2 groups of 40 rats each
Control animals:
not specified
Details on study design:
The LD50 was determined after a 24-hour fast with free access to tap-water.
Sex:
not specified
Dose descriptor:
LD50
Effect level:
1 010 mg/kg bw

The minimal lethal dose was 850 mg/kg. After single doses larger than 1000 mg/kg leading to a comatose state with death occurring within 12 -36 h, no liver cell alterations were seen microscopically; livers of rats dying 6 -11 days after 850 -1000 mg/kg showed extensive centrolobular necrosis with inflammatory reactions and appearance of fat ill surviving liver cells.

Interpretation of results:
Category 4 based on GHS criteria
Conclusions:
LD50 (rat): 1010 mg/kg
Executive summary:

The oral LD50 of the test substance was determined after a 24-hour fast with free access to tap-water. The minimal lethal dose was 850 mg/kg. Single doses larger than 1000 mg/kg lead to a comatose state with death occurring within 12 -36 hours with no liver cell alterations observed microscopically. Liver effects were observed in rats dying 6 -11 days after 850 -1000 mg/kg. The LD50 was 1010 mg/kg.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
Value:
1 010 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:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
GLP compliance:
no
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
strain: SPF Wistar/Chbb : THOM ; breeding facility: Dr. K . Thomae GmbH, D-7950 Biberach, FRG)
Mean body weight at the beginning of the study: male animals 285 ± 4.0 g, female animals 188 ± 2 .1 g.
Age at the beginning of the study: approx . 8- 9 weeks
The animals were identified by color marking on the tail.
The animals were offered KLIBA rat/mouse laboratory diet 24-343-4 10 mm pellets, Klingentalmuhle AG, CH-4303 Kaiseraugst, Switzerland, and drinking water ad libitum during the post-exposure observation period.
The animals were kept in fully air-conditioned rooms in which a temperature in the range 20-24°C and relative humidity in the range 30-70% were regulated by means of a central air-conditioning system.
Route of administration:
inhalation: vapour
Type of inhalation exposure:
whole body
Vehicle:
other: unchanged (no vehicle)
Analytical verification of test atmosphere concentrations:
yes
Duration of exposure:
4 h
Concentrations:
0.37 mg/L
No. of animals per sex per dose:
5
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 0.37 mg/L air
Remarks on result:
other: maximum concentration achievable
Mortality:
No mortality was observed during the study.
Clinical signs:
other: Clinical signs included wiping of snouts, restlessness, and attempts to escape. All animals were clear of findings by 2 hours after the beginning of exposure.
Body weight:
The body weight gain of male rats was not affected. The body weight gain of the female rats was retarded in the second week of the observation period.
Gross pathology:
No pathologic findings noted.

Cumulated lethality on day

male

female

0

0/5

0/5

1

0/5

0/5

2

0/5

0/5

7

0/5

0/5

14

0/5

0/5

Total at end of the study

0/5

0/5

Time after beginning of exposure

< ¼ h

¼ h

½ h

1 h

2 h

3 h

4 h

Animals without findings

10

10

10

Wiping of snouts

10

Restlessness

10

10

10

Attempts to escape

10

 

Interpretation of results:
GHS criteria not met
Conclusions:
Regarding the results of the study, the LC50 of the test substance exceeds the maximum concentration that could be technically achieved (0.37 mg/L air).
Executive summary:

The acute inhalation toxicity potential of the test substance was studied in accordance with OECD Guideline 403. Five male and five female rats were exposed to the test substance for 4 hours at a concentration of 0.37 mg/L (maximum attainable concentration). No mortality or gross pathologic findings were noted was observed.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed

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
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment
Qualifier:
no guideline followed
Principles of method if other than guideline:
Standardized test (BASF-Test) to assess the acute dermal toxicity in rabbits.
GLP compliance:
no
Test type:
standard acute method
Limit test:
no
Species:
rabbit
Strain:
Vienna White
Sex:
male/female
Details on test animals and environmental conditions:
Breeder: GAUKLER, 6050 Offenbach
Mean weight for - males: 3.0 kg - females: 3.0 kg
The animals had Ssniff K, standard laboratory diet for rabbits and guinea pigs, INTERMAST GMBH, Soest and water ad libitum.
Type of coverage:
occlusive
Vehicle:
water
Duration of exposure:
24 h
Doses:
200 and 400 mg/kg (50% in water)
No. of animals per sex per dose:
3
Control animals:
no
Sex:
male/female
Dose descriptor:
LD50
Effect level:
400 mg/kg bw
Mortality:
see table below
Clinical signs:
Apathy, diarrhoea
Gross pathology:
Dead animals: acute dilatation of the heart (right), degeneration; loamy liver with acute dystrophy; sandy kidneys with nephrosis
Killed animals: no substance-related pathological findings

Mortality

Dose mg/kg

Conc. %

Animal

1 h

24 h

48 h

7 days

14 days

400

200

50

50

3 m

3 f

3 m

3 f

0/3

0/3

0/3

0/3

0/3

0/3

0/3

0/3

0/3

0/3

0/3

0/3

1/3

2/3

0/3

0/3

1/3

2/3

Interpretation of results:
Category 3 based on GHS criteria
Conclusions:
LD50 (rabbit): 400 mg/kg
Executive summary:

A standardized test (BASF-Test) to assess the acute dermal toxicity in rabbits was performed. Three male and female rabbits per dose were exposed to the test substance under occlusive conditions for 24 hours to doses of 200 and 400 mg/kg (50% in water). The dermal LD50 in rabbits was 400 mg/kg.

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

Additional information

In a study using the standard acute method, several dose levels between 840 and 1214 mg/kg bw of the test substance (purity unknown) were administered once orally to groups of 40 rats. The LD50 was 1010 mg/kg bw. The minimal lethal dose was 850 mg/kg bw. After single doses larger than 1000 mg/kg bw leading to a comatose state with death occurring within 12 -36 h, no liver cell alterations were seen microscopically; livers of rats dying 6 -11 days after 850 -1000 mg/kg bw showed extensive centrolobular necrosis with inflammatory reactions and appearance of fat ill surviving liver cells.

In a limit test according to OECD Guideline 403, five male and female Wistar rats were whole-body exposed for 4 hours to a dynamically produced vapour with an analytical concentration of 0.37 mg/L (purity 100%). This concentration is the maximum concentration that could be achieved technically. There were no mortalities and no necropsy findings observed. Clinical signs (wiping of snouts, restlessness and attempts to escape) were only observed during exposure. The body weight gain of the males was not affected while the body weight gain of the females was retarded in the second week of the observation period. The LC50 of this study is > 0.37 mg/L.

Following a standardized test protocol (BASF test), groups of three male and three female Vienna White rabbits were treated for 24 hours with doses of 200 mg/kg bw or 400 mg/kg bw of the test substance (purity unknown, prepared in 50% water) epicutaneously under occlusive conditions. Three of six animals died in the high dose treatment and 0/6 in the low dose treatment, leading to a LD50 of 400 mg/kg bw. Clinical signs were apathy and diarrhoea. At necropsy, acute dilatation of the heart (right), degeneration, loamy liver with acute dystrophy and sandy kidneys with nephrosis were observed in animals that died; sacrificed animals were found without substance-related findings.

Justification for classification or non-classification

Based on an oral LD50 in rats of 1010 mg/kg, the test substance is classified for acute oral toxicity as Cat 4 (H302: Harmful if swallowed) according to EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008.

 

Based on a dermal LD50 in rabbits of 400 mg/kg, the test substance is classified for acute dermal toxicity as Cat 3 (H311: Toxic in contact with skin) according to EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008.

 

Based on a 4-hour inhalation LC50 in rats of >0.37 mg/L (highest attainable concentration) the test substance is not classified for acute inhalation toxicity according to EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008.