Registration Dossier

Diss Factsheets

Administrative data

Description of key information

Acute Toxicity:
- oral:        LD50: 189 -550 mg/kg bw (rat) ; Cat.3
- inhalation:  LC50: 1.15 mg/L air 4 h (rat) ; Cat.2
- dermal:      LD50: 768 mg/kg bw (rabbit)   ; Cat.3

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Referenceopen allclose all

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Data only given as summary tables but acceptable for assessment.
Qualifier:
no guideline followed
Principles of method if other than guideline:
Single oral dose toxicity is estimated by the gastric intubation of groups of five non-fasted, male rats four to five weeks of age and 90 to 120 grams. The dosages are arranged in a logarithmic series differing by a factor of two. The most probable LD50 value and its fiducial range are estimated by the method of Thompson.
GLP compliance:
no
Remarks:
predating GLP
Limit test:
no
Species:
rat
Strain:
other: Carworth-Wistar
Sex:
male
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: own breeding
- Age at study initiation: 4 - 5 w
- Weight at study initiation: 90 - 120 g
- Fasting period before study: unfasted
- Diet: Rockland rat diet

Route of administration:
oral: gavage
Doses:
No data; dosages were in a logartitmic series
No. of animals per sex per dose:
5
Control animals:
not specified
Details on study design:
- Duration of observation period following administration: 14 days
Statistics:
moving average method according to Thompson (1947) and Weil (1952)
Key result
Sex:
male
Dose descriptor:
LD50
Effect level:
550 mg/kg bw
Based on:
test mat.
Mortality:
no data
Clinical signs:
no data
Body weight:
no data
Gross pathology:
no data
Interpretation of results:
Category 4 based on GHS criteria
Conclusions:
The LD50 of the test substance after single oral administration was found to be 550 mg/kg bw in male rats.
Executive summary:

The test article was administered to a group of 5 non-fasted male Carworth-Wistar rats by intubation of dosages in a logartithmic series. After 14 days of observation the LD50 was calculated to be 550 mg/kg bw.

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Poorly documented study report but acceptable for classification
Qualifier:
no guideline followed
Principles of method if other than guideline:
Single oral dose
GLP compliance:
not specified
Species:
rat
Route of administration:
oral: unspecified
Vehicle:
not specified
Doses:
no data
No. of animals per sex per dose:
6 (sex unspecified)
Control animals:
not specified
Details on study design:
- single oral dose
- dose levels: 250ppm, 500ppm
Key result
Sex:
not specified
Dose descriptor:
LD50
Effect level:
360 mg/kg bw
Based on:
test mat.
Mortality:
250 ppm 0/6
50 ppm 6/6
Clinical signs:
no data
Body weight:
no data
Gross pathology:
no data
Interpretation of results:
Category 4 based on GHS criteria
Conclusions:
The LD50 of the test substance after single oral administration was found to be 360 mg/kg bw in rats.
Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Poorly documented study report but acceptable for classification
Reason / purpose for cross-reference:
reference to same study
Remarks:
Main study (MNT)
Qualifier:
no guideline followed
Principles of method if other than guideline:
Single oral dose to male and female mice. Animals were observed for mortality and clinical signs for two days.
The results were used as a range finder for a consecutive micronucleus assay.
GLP compliance:
not specified
Species:
mouse
Strain:
ICR
Sex:
male/female
Route of administration:
oral: gavage
Vehicle:
corn oil
Doses:
100, 160, 250, 400 and 500 mg/kg bw
No. of animals per sex per dose:
5
Control animals:
not specified
Details on study design:
- Duration of observation period following administration: 3 days
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
305 mg/kg bw
Mortality:
Mortality occurred within two days of dose administration as follows: 2/5 female mice at 250 mg/kg, 2/5 male mice and 5/5 female mice at 400 mg/kg and 5/5 male mice and 5/5 female mice at 500 mg/kg.
Clinical signs:
no data
Body weight:
no data
Gross pathology:
no data
Interpretation of results:
Category 4 based on GHS criteria
Conclusions:
The LD50 of the test substance after single oral administration was found to be 305 mg/kg bw in mice.
Executive summary:

The test substance was administered orally (gavage) to male and female mice (ICR) at 100, 160, 250, 400 and 500 mg test article/kg bw which was administered in a total volume of 20 ml test article-vehicle (corn oil) mixture/kg body weight. 5 animals per sex per dose were used. Mortality occurred within two days of dose administration as follows: 2/5 female mice at 250 mg/kg, 2/5 male mice and 5/5 female mice at 400 mg/kg and 5/5 male mice and 5/5 female mice at 500 mg/kg. The LD50 of the test substance after single oral administration was found to be 305 mg/kg bw in mice.

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Poorly documented study report but acceptable for classification
Qualifier:
no guideline followed
Principles of method if other than guideline:
no data
GLP compliance:
not specified
Species:
rat
Strain:
Wistar
Sex:
male/female
Route of administration:
oral: unspecified
Vehicle:
other: "vegetable" oil containing 8.4 % of the TS
Doses:
no data
No. of animals per sex per dose:
10
Control animals:
not specified
Sex:
male
Dose descriptor:
LD50
Effect level:
189 mg/kg bw
Sex:
female
Dose descriptor:
LD50
Effect level:
239 mg/kg bw
The values represent the LD50 for male (189 mg/kg bw) and female rats (239 mg/kg bw).
Interpretation of results:
Category 3 based on GHS criteria
Conclusions:
The LD50 of the test substance after single oral administration were found to be 189 mg/kg bw in male rats as well as 239 mg/kg bw in female rats.
Executive summary:

Male and female Wistar rats (10 animals per sex per dose) were treated orally with 8.4 % of the test substance in "vegetable" oil. The LD50 value for male rats was 189 mg/kg bw and for female rats 239 mg/kg bw.

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
GLP compliance:
not specified
Test type:
standard acute method
Species:
rat
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Staatliche Zentralstelle für Versuchstierzuch und -versorgung, Berlin-Lichtenberg
- Weight at study initiation (mean): females: 167g, males 230g
- Fasting period before study: yes, 18h
- Housing: in groups of 10
- Diet (e.g. ad libitum): ad lib, rat standard food (Sorte K)
- Water (e.g. ad libitum): ad lib.
Route of administration:
oral: gavage
Vehicle:
peanut oil
Details on oral exposure:
Dosage volume: 5ml/kg
Doses:
6 (females) and 7 (males) different doses, no details given
No. of animals per sex per dose:
10
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of weighing: weekly
- Necropsy of survivors performed: yes
Sex:
female
Dose descriptor:
LD50
Effect level:
220 mg/kg bw
Based on:
test mat.
95% CL:
>= 191 - <= 253
Sex:
male
Dose descriptor:
LD50
Effect level:
310 mg/kg bw
Based on:
test mat.
95% CL:
>= 251 - <= 382
Mortality:
Mortality occured on day 1.
Interpretation of results:
Category 3 based on GHS criteria
Conclusions:
The LD50 of the test substance after single oral administration were found to be 310 mg/kg bw in male rats as well as 220 mg/kg bw in female rats.
Executive summary:

Male and female Wistar rats (10 animals per sex per dose) were treated orally with the test substance in peanut oil. The LD50 value for male rats was 310 mg/kg bw and for female rats 220 mg/kg bw.

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

Acute toxicity: via inhalation route

Link to relevant study records

Referenceopen allclose all

Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
Deviations:
no
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Charles River UK Ltd, Margate, Kent, England
- Age at study initiation: 6-8 weeks old
- Weight at study initiation: 200g
- Fasting period before study: no except during exposure
- Housing: 5 animals of the same sex per cage
- Diet (e.g. ad libitum): ad libitum (Labsure LAD1)
- Water (e.g. ad libitum): ad libitum tap water
- Acclimation period: at least 5 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-23
- Humidity (%): 40-43
Route of administration:
inhalation: vapour
Type of inhalation exposure:
whole body
Vehicle:
other: unchanged (no vehicle)
Details on inhalation exposure:
The test substance was supplied to an atomiser in the generator from a syringe driven at a constant rate by a syringe pump.
The compressed air supply to the generator was dried, filtered and oil-free.

The chamber was made of Perspex and had an internal volume of approx. 130l.
The chamber was divided by wire mesh partitions to provide 10 separate animal compartments.

A supply of clean dried air was connected to the vapour generator and the supply pressure was adjusted to give a flow rate of 0.03-0.06 ml/min. An in-line flow meter was used to monitor airflow throughout the exposure.

A syringe filled with dibutylamine was fitted to the syringe pump and connected to the generator with PTFE tubing. The flow rate was set at 0.18ml/min.

After 4 hours exposure, the supply of the test substance was discontinued and the exposure chamber was allowed to clear before rats were removed for examination.
Analytical verification of test atmosphere concentrations:
yes
Remarks:
Five air samples were taken from the chamber during the exposure to determine to concentration of dibutylamine in gas chromatography.
Duration of exposure:
4 h
Concentrations:
0.76, 1.08, 1.18, 1.39, 3.91 mg/l
No. of animals per sex per dose:
5
Control animals:
yes
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: daily until 14 days
- Necropsy of survivors performed: yes
- Other examinations performed:
clinical signs: continuously during exposure and twice daily until the observation period
body weight: daily
organ weights: lungs
Sex:
male/female
Dose descriptor:
LC50
Effect level:
218 ppm
Exp. duration:
4 h
Remarks on result:
other: equivalent to 1,15 mg/l
Mortality:
Deaths occurred during exposure to the test substance at 1.39 mg/l or at 3.91 mg/l (see table 1).
Clinical signs:
other: During exposure The signs seen in rats exposed to the test substance were considered to be due to the irritant nature of the vapour. The signs evident in exposed rats included closing or partial closing of the eyes, reduced respiratory rate, abnormal resp
Body weight:
The rats surviving exposure to the test substance lost weight or had a reduced rate of bodyweight gain for up to 2 days following exposure. Subsequently, the rate of bodyweight gain was similar to control rats.
Gross pathology:
Lungs of rats that died were congested. A viscous fluid was found in the trachea of 2 deceased rats in group 1.18 mg/l.
Other findings:
The lung weights of the majority of the rats that died following exposure were higher than normal.
The lung weights for rats that survived were within normal limits.

Table 1: Mortality after test substance treatment

  Mortality (Nb dead/Nb exposed)
Concentration in air (mg/l) Male Female Total
Control 0/5 0/5 0/10
Control 0/5 0/5 0/10
3,91 5/5 5/5 10/10
1,39 5/5 5/5 10/10
1,18 3/5 1/5 4/10
1,08 0/5 0/5 0/10
0,76 2/5 0/5 2/10
Interpretation of results:
Category 2 based on GHS criteria
Conclusions:
The LC50 value of the test substance after vapour inhalation for 4h was found to be 218 ppm (equivalent to 1,15 mg/l) in rats.
Executive summary:

In an acute toxicity inhalation study, male and female rats (Sprague-Dawley) were treated with the vapour of the test substance for 4h. 5 animals per sex per concentration (0.76, 1.08, 1.18, 1.39, 3.91 mg/l)

and no vehicle were used.

Deaths occurred during exposure to the test substance at 1.39 mg/l or at 3.91 mg/l. The signs seen in rats exposed to the test substance were considered to be due to the irritant nature of the vapour. The signs evident in exposed rats included closing or partial closing of the eyes, reduced respiratory rate, abnormal respiratory movements and adoption of an anormal body posture. Gasping, exessive salivation, lacrimation, and convulsions were observed less frequently.

After the removal from the test chamber, rats exposed to the test substance showed abnormal breathing, lethargy, ataxia, prone posture and intermittent convulsions.

Clinical signs evident for 2 days following exposure included abnormal breathing, rales, brown staining or yellow staining in the urogenital area and sneezing.

With the exception of 1 female rat with damaged tail all rats surviving exposure to the test substance were of normal appearance and behaviour by day 3 of the observation period.

 The rats surviving exposure to the test substance lost weight or had a reduced rate of bodyweight gain for up to 2 days following exposure. Subsequently, the rat of bodyweight gain was similar to control rats.

 Lungs of rats that died were congested. A viscous fluid was found in the trachea of 2 deceased rats in group 1.18 mg/l. The lung weights of the majority of the rats that died following exposure were higher than normal. The lung weights for rats that survived were within normal limits.

The LC50 value of the test substance was found to be 218 ppm (equivalent to 1,15 mg/l) in rats.

Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
Deviations:
yes
Remarks:
1 hour exposure
GLP compliance:
yes
Test type:
standard acute method
Limit test:
no
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Charles River UK Ltd, Margate, Kent, England
- Age at study initiation: 6-8 weeks old
- Weight at study initiation: 155g (males) 172g (females)
- Fasting period before study: no except during exposure
- Housing: 5 animals of the same sex per cage
- Diet (e.g. ad libitum): ad libitum (Labsure LAD1)
- Water (e.g. ad libitum): ad libitum tap water
- Acclimation period: 9 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19.7-22.6
- Humidity (%): 51+/-6.5
Route of administration:
inhalation: vapour
Type of inhalation exposure:
whole body
Vehicle:
other: unchanged (no vehicle)
Details on inhalation exposure:
The test substance was supplied to an atomiser in the generator from a syringe driven at a constant rate by a syringe pump.
The compressed air supply to the generator was dried, filtered and oil-free.

The chamber was made of Perspex and had an internal volume of approx. 115l.
The chamber was divided by wire mesh partitions to provide 10 separate animal compartments.

A supply of clean dried air was connected to the vapour generator and the supply pressure was adjusted to give a flow rate of 25 l/min. An in-line flow meter was used to monitor airflow throughout the exposure.

A syringe filled with dibutylamine was fitted to the syringe pump and connected to the generator with PTFE tubing. The flow rate was set at 0.099ml/min.

After 1 hour exposure, the supply of the test substance was discontinued and the exposure chamber was allowed to clear before rats were removed for examination.
Analytical verification of test atmosphere concentrations:
yes
Remarks:
Three air samples were taken from the chamber during the exposure to determine to concentration of dibutylamine in gas chromatography.
Duration of exposure:
1 h
Concentrations:
target concentration 530-580 ppm
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: daily until 14 days
- Necropsy of survivors performed: yes
- Other examinations performed:
clinical signs: continuously during exposure and twice daily until the observation period
body weight: daily
organ weights: lungs
food and water consumption/cage
Sex:
male/female
Dose descriptor:
LC50
Effect level:
573 ppm
Exp. duration:
1 h
Remarks on result:
other: equivalent to 3,028 mg/l
Mortality:
No mortality was observed.
Clinical signs:
other: During exposure The signs seen in rats exposed to the test substance were considered to be due to the irritant nature of the vapour. The signs evident in exposed rats included partial closing of the eyes, reduced respiratory rates, exaggerated respiratory
Body weight:
The rats exposed to the test substance lost weight or had a reduced rate of bodyweight gain for up to 2 days following exposure. Subsequently, the rate of bodyweight gain was within normal limits.
Gross pathology:
No macroscopic abnormalities was observed.
Other findings:
Food and water consumptions were reduced for 1 day and 2 days after exposure, respectively.
The lung weights of exposed rats were within standard limits.

The nominal concentration calculated from the amount of material used was 2,997 mg/l.

The particle count indicated that less particles were present in the chamber air than in the room air. There were therefore no droplets of test substance in the chamber.

Table 1: Concentrations of the test substance

Sample Time (min) Test substance (mg/l)
1 15 2,825
2 30 2,860
3 53 3,400
Mean 3,028

Table 2: Clinical signs during exposure

Sex Signs Number showing signs
Time in hour
0 0,25 0,5 1
Male Wet around the eyes       5
Partially closing of the eyes 5 5    
Reduced respiratory rates 5 5 5 5
Exaggerated respiratory movement 5 5 5 5
Hunched posture 5 5    
Restless behaviour     5 5
Female Wet around the eyes       5
Partially closing of the eyes 5 5    
Reduced respiratory rates 5 5 5 5
Exaggerated respiratory movement 5 5 5 5
Hunched posture 4 5    
Restless behaviour     5 5

Table 3: Clinical signs during the obsevration period

Sex Signs Number showing signs
Day of observation
0 1 2 3 4 5 6 7 8 9 10 11 12 13 14
Male Normal appearance and behaviour         5 5 5 5 5 5 5 5 5 5 5
Ataxia 5                            
Reduced respiratory rate 5 5 5 5                      
Exaggerated respiratory movement 5                            
Wet fur around urogenital region 5 5                          
Female Normal appearance and behaviour           5 5 5 5 5 5 5 5 5 5
Ataxia 5                            
Reduced respiratory rates 5 5 5 5 5                    
Exaggerated respiratory movement 5                            
Lethargic     5 5                      
Interpretation of results:
Category 2 based on GHS criteria
Conclusions:
The LC50 value of the test substance after vapour inhalation for 1h was found to be 573 ppm (equivalent to 3,028 mg/l) in rats.
Executive summary:

In an acute toxicity inhalation study, male and female rats (Sprague-Dawley) were treated with the vapour of the test substance for 1h. 5 animals per sex per concentration and no vehicle were used.

No mortality was observed. The signs seen in rats exposed to the test substance were considered to be due to the irritant nature of the vapour. The signs evident in exposed rats included partial closing of the eyes, reduced respiratory rates, exaggerated respiratory movements and adoption of a hunched posture. After the removal from the test chamber, rats exposed to the test substance showed ataxia, reduced respiratory rates, exaggerated respiratory movements. There were disturbances to the respiratory pattern for a further 3 days in male rats and 4 days in female rats. Subsequently the rats were normal in appearance and behaviour. The rats exposed to the test substance lost weight or had a reduced rate of bodyweight gain for up to 2 days following exposure. Subsequently, the rat of bodyweight gain was within normal limits. No macroscopic abnormalities was observed. Food and water consumptions were reduced for 1 day and 2 days after exposure, respectively. The lung weights of exposed rats were within standard limits.

The LC50 value of the test substance was found to be 573 ppm (equivalent to 3,028 mg/l) in rats.

Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Short study report which meets basic standard principles.
Qualifier:
no guideline followed
Principles of method if other than guideline:
A group of ten male albino rats was used in this study. The rats were placed in a 70 liter, all glass-exposure chamber and exposed to a saturated atmosphere of the test material in air for one hour. The material was administered as an aerosol with particles 3-5 microns in diameter. The rate of flow was 5.2 liters per minute at a temperature of 22°C.
The air was passed through a desicant prior to being passed through the test material. By differential weighing it was calculated that the rats were subjected to a concentration of 2.01 mg/liter during the exposure period. This is an average value over the one hour period.
GLP compliance:
not specified
Species:
rat
Strain:
other: albino rats
Sex:
male
Route of administration:
inhalation: vapour
Type of inhalation exposure:
not specified
Vehicle:
other: unchanged (no vehicle)
Analytical verification of test atmosphere concentrations:
not specified
Duration of exposure:
1 h
Concentrations:
saturated atmosphere
No. of animals per sex per dose:
10
Control animals:
not specified
Sex:
male
Dose descriptor:
LC50
Effect level:
> 2 mg/L air
Exp. duration:
1 h
Remarks on result:
other: The given value corresponds to the highest concentration tested.
Mortality:
No mortality occured
Clinical signs:
other: The rats exhibited huddling during the exposure period.
Body weight:
no data
Gross pathology:
no data
Interpretation of results:
Category 2 based on GHS criteria
Conclusions:
The LC50 value of the test substance after vapour inhalation for 1h was found to be ˃ 2 mg/L in rats.
Executive summary:

In an acute toxicity inhalation study, 10 male abino rats were treated with the test substance for 1 h. No mortality occured. The rats exhibited huddling during the exposure period.

The LC50 value was found to be ˃ 2 mg/L in rats.

Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Data only given as summary tables but acceptable for assessment.
Qualifier:
no guideline followed
Principles of method if other than guideline:
Screening study: An air stream of 2.5 l/min is passed through a fritted glas disc immersed at a depth of at least one inch in approx. 50 ml of the test chemical.
GLP compliance:
no
Limit test:
no
Species:
rat
Strain:
Wistar
Sex:
male
Route of administration:
inhalation: vapour
Type of inhalation exposure:
whole body
Analytical verification of test atmosphere concentrations:
no
Duration of exposure:
4 h
Concentrations:
no data
No. of animals per sex per dose:
6
Sex:
male
Dose descriptor:
LC50
Effect level:
> 1.34 - < 2.68 mg/L air (nominal)
Exp. duration:
4 h
Sex:
male
Dose descriptor:
LC0
Effect level:
1.34 mg/L air (nominal)
Exp. duration:
4 h
Sex:
male
Dose descriptor:
LC100
Effect level:
ca. 2.68 mg/L air (nominal)
Exp. duration:
4 h
Original concentration is given in ppm: Exposure to 500 ppm/4 h (2.68 mg/L) was lethal to 6/6 animals.
Exposure to 250 ppm/4 h (1.34 mg/L) was not lethal (observation time 14 d).
Interpretation of results:
Category 2 based on GHS criteria
Conclusions:
The LC50 value of the test substance after vapour inhalation for 4h was found to be ˃1,34 - <2,68 mg/L in rats.
Executive summary:

In an acute toxicity inhalation study, 6 male Wistar rats were treated with the vapour of the test substance for 4h. The original concentration is given in ppm: Exposure to 500 ppm/4 h (2.68 mg/L) was lethal to 6/6 animals.

Exposure to 250 ppm/4 h (1.34 mg/L) was not lethal (observation time 14 d).

The LC50 value of the test substance was found to be ˃1,34 - <2,68 mg/L in rats.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LC50
Value:
1 150 mg/m³

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:
other: Data only given as summary tables but acceptable for assessment.
Qualifier:
no guideline followed
Principles of method if other than guideline:
according to Draize et al. (1944): J. Pharmacol. & Exper. Therap. 82, 377
Penetration of rabbit skin is estimated by a technique closely skin to the one-day cuff method of Draize and associates, using groups of four male albinorabbits weighing 2.5 to 3.5 kg. The fur is removed from the entire trunk by clipping, and the dose is retained beneath an impervious plastic film.The animals are immobilized during the 24 hour contact period, after which the film is removed and the rabbits are caged for the subsequent 14 day observation period.
GLP compliance:
no
Species:
rabbit
Strain:
New Zealand White
Sex:
male
Type of coverage:
occlusive
Vehicle:
not specified
Details on dermal exposure:
Method according to Draize (Draize et al., 1944, Methods for study of irritation an toxicity of substances applied topically to the skin
and mucous membranes; J. Pharmacol. Exper. Therap. 82:377, 1944)
Duration of exposure:
24 h
Doses:
no data
No. of animals per sex per dose:
4 (males only)
Control animals:
not specified
Sex:
male
Dose descriptor:
LD50
Effect level:
768 mg/kg bw
95% CL:
620 - 1 130
Remarks on result:
other: original value: 1.01 ml/kg bw
Mortality:
no data
Clinical signs:
no data
Body weight:
no data
Gross pathology:
no data
Interpretation of results:
Category 3 based on GHS criteria
Conclusions:
The LD50 value of the test substance was found to be 768 mg/kg bw after a contact period of 24 hours.
Executive summary:

Penetration of New Zealand White rabbit skin is estimated by a technique closely skin to the one-day cuff method of Draize and associates, using groups of four male rabbits weighing 2.5 to 3.5 kg. The fur is removed from the entire trunk by clipping, and the dose is retained beneath an impervious plastic film.The animals are immobilized during the 24 hour contact period, after which the film is removed and the rabbits are caged for the subsequent 14 day observation period. The LD50 value of the test substance was found to be 768 mg/kg bw.

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

Additional information

Oral:

Acute toxicity of the test substance after oral administration was evaluated by a weight of evidence approach. In one study, male and female Wistar rats (10 animals per sex per dose) were treated orally with the test substance in peanut oil. The LD50 value for male rats was 310 mg/kg bw and for female rats 220 mg/kg bw. (1974; K2) In another study, the test article was administered to a group of 5 non-fasted male Carworth-Wistar rats by intubation of dosages in a logartithmic series. After 14 days of observation, the oral LD50 was calculated to be 550 mg/kg bw. (1954; K2) Next to it, male and female Wistar rats (10 animals per sex per dose) were treated orally with 8.4 % of the test substance in "vegetable" oil. The LD50 value for male rats was 189 mg/kg bw and for female rats 239 mg/kg bw. (1985; K2) One further study in rats revealed that the test substance caused similar toxicity (LD50 = 360 mg/kg bw, 1952; K2). The oral LD50 of 305 mg/kg bw in mice was obtained from a pilot study for a micronucleus assay. For this toxicity study, the test substance was administered by oral gavage to male and female mice at 100, 160, 250, 400 and 500 mg test article/kg administered in a total volume of 20 ml test article-vehicle mixture/kg body weight. (1995; K2)

Inhalation:

Acute inhalation toxicity was evaluated in groups of 5 male and 5 female Sprague-Dawley rats exposed to the test substance at actual concentrations of 0.76, 1.08, 1.18, 1.39 or 3.91 mg/l of air for 4 hours and 1 hour (1987; K2). Mortality was observed after 4h exposure in 2 animals in the 0.76 mg/l dose group, 4 in the 1.18 mg/l dose group, and all 10 in both the 1.39 and 3.91 mg/l dose groups. The LC50 value was calculated to be 1.15 mg/l. Clinical observations included excessive salivation, lacrimation, gasping, convulsions, abnormal breathing, ataxia, lethargy, rales, and staining of the urogenital area. Gross necropsy revealed lung congestion in decedents.

Additional data were available from an inhalation risk test (1954; K2). The exposure to 500 ppm/4 h (2.68 mg/L) was lethal to 6/6 animals, whereas the exposure to 250 ppm/4 h (1.34 mg/L) was not lethal (observation time 14 d). In a second IRT mortality occurred within 17 min of exposure (1954; K2), whereas in a third IRT no mortality occurred after a 1 hour inhalation of 2 mg/l air (1976; K2).

Dermal:

Penetration of New Zealand White rabbit skin is estimated by a technique closely skin to the one-day cuff method of Draize and associates, using groups of four male rabbits weighing 2.5 to 3.5 kg. The fur is removed from the entire trunk by clipping, and the dose is retained beneath an impervious plastic film. The animals are immobilized during the 24 hour contact period, after which the film is removed and the rabbits are caged for the subsequent 14 day observation period. The LD50 value of the test substance was found to be 768 mg/kg bw.

Justification for classification or non-classification

The available experimental test data are reliable and suitable for classification purposes under Regulation 1272/2008. The LD50 after oral expsosure was found to be 189-550 mg/kg bw (rat), the LC50 after inhalative exposure 1.15 mg/L air 4 h (rat) and the LD50 after dermal exposure 768 mg/kg bw (rabbit).

As a result, the test substance is considered to be classified for acute oral toxicity Categorie 3, for acute inhalative toxicity Categorie 2 and for acute dermal toxicity Categorie 3 under Regulation (EC) No. 1272/2008, as amended for the thirteenth time in Regulation (EC) No 2018/1480.