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Description of key information

Key value for chemical safety assessment

Acute toxicity: via oral route

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Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
test procedure in accordance with generally accepted scientific standards and described in sufficient detail
Principles of method if other than guideline:
Groups of 6 males were administered 0, 5000, 10000 and 20000 mg/kg bw of the test substance by stomach intubation. The animals were observed for 14 d.
GLP compliance:
no
Test type:
standard acute method
Limit test:
no
Species:
rat
Strain:
Sprague-Dawley
Sex:
male
Details on test animals and environmental conditions:
TEST ANIMALS
- Weight at study initiation: male: 150-250 g
- Fasting period before study: 24 h
- Housing: Screen bottom cages
- Diet (e.g. ad libitum): Laboratory chow (ad libitum)
- Water (e.g. ad libitum): ad libitum
Route of administration:
oral: gavage
Vehicle:
not specified
Details on oral exposure:
Six adult SD rats per dose group were given the test substance by stomach intubation.
Doses:
0, 5,000, 10,000 and 20,000 mg/kg.
No. of animals per sex per dose:
Males: 6/dose/group
Control animals:
not specified
Details on study design:
Male SD rats were fasted for 24 h and then administered single doses of the test substance by stomach intubation followed by 14 d of observation period.
Statistics:
No data
Key result
Sex:
male
Dose descriptor:
LD50
Effect level:
10 000 mg/kg bw
Based on:
test mat.
Mortality:
Number of dead/number dosed:
- No mortality occured at lowest dose of 5,000 mg/kg, i.e., 0/6
- 50% mortality was observed In the mid dose group of 10,000 mg/kg, i.e., 3/6
- Almost all animals died in the highest dose group of 20,000 mg/kg, i.e., 5/6.
Interpretation of results:
GHS criteria not met
Conclusions:
The oral LD50 of the test substance in SD rats was found to be 10000 mg/kg bw.
Executive summary:

A study was conducted to determine the acute oral toxicity of the test substance in Sprague Dawley rats. Groups of 6 males were administered 0, 5000, 10000 and 20000 mg/kg bw by stomach intubation and observed for 14 d. Approximately 50% mortality occurred at the mid dose. Under the study conditions, the oral LD50 was therefore 10000 mg/kg bw (Casey, 1976).

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
1979
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
test procedure in accordance with generally accepted scientific standards and described in sufficient detail
Principles of method if other than guideline:
Groups of 20 fasted animals (10 males and 10 females) were exposed via oral gavage to 0, 10.0, 12.6, 16.0 and 20.0 mL/kg bw. The animals were observed for 14 d, then sacrificed and subjected to gross pathological examination.
GLP compliance:
no
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: W. Gassner, Sulzfeld, Germany
- Weight at study initiation: males: 95 - 115 g; females: 90 - 110 g
- Fasting period before study: ca. 16 h
- Temperature: 22 +/- 1°C
- Housing: 5 animals/cage
- Lighting cycle (light:dark): 12:12
- Feed: Ssniff (pellets)
- Water: ad libitum
Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Doses:
0, 10.0, 12.6, 16.0 and 20.0 mL/kg bw
No. of animals per sex per dose:
10
Control animals:
yes
Details on study design:
- Duration of observation period following administration: 14 d
- Necropsy of survivors performed: Yes
- Examinations performed: Clinical signs, body weight and gross pathological examination
Statistics:
LD50 was calculated according to Kärber (Toxikologie für Veterinärmediziner, H.J. Hapke, 1975) and S.C. Weil (Biometrics 8, 249; 1952).
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
14.21 mL/kg bw
Based on:
test mat.
Remarks on result:
other: Equivalent to 14210 mg/kg bw; assuming the density to be approx. 1 g/cm3
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
13.82 mL/kg bw
Based on:
test mat.
Remarks on result:
other: Equivalent to 13820 mg/kg bw; assuming the density to be approx. 1 g/cm3
Mortality:
0% at 0 and 10.0 ml/kg bw
40% at 12.6 mL/kg bw
70% at 16.0 mL/kg bw
100% at 20.0 mL/kg bw
Clinical signs:
Rough fur, pale extremities, diarrhea, increased lacrimation and slight to middle-strong lethargy and ataxia.
Body weight:
Bodyweight gain was in the normal range for all groups, compared to controls.
Gross pathology:
ANIMALS DYING DURING THE STUDY:
- Light to medium hyperemia and hemorragic edema in the lung.
- Light to medium hyperemia of the liver
- Light to medium hyperemia of the mucous membrane of the glands and the cutaneous mucous membrane of the stoimach
- Light to medium hyperemia of the mucous membrane of the duodenum

ANIMALS SACRIFICED AT THE END OF THE STUDY:
- Medium hyperemia and light hemorragic edema of the lungs
- Light to medium hyperemia of the liver
- Local thickeniung of the cutaneous mucous membrane of the stomach



Interpretation of results:
GHS criteria not met
Conclusions:
Under the study conditions, the LD50 of the test substance was found to be equivalent to 14.21 mL/kg bw (according to Kärber) or 13.82 ml/kg bw (according to Weil). These LD50 values are equivalent to 14210 and 13820 mg/kg bw, assuming a density of approximately 1 g/cm3.
Executive summary:

A study was performed to assess the acute oral toxicity of the test substance in Sprague Dawley rats. Groups of 20 fasted animals (10 males and 10 females) were exposed via oral gavage to 0, 10.0, 12.6, 16.0 and 20.0 mL/kg bw. The animals were observed for 14 d, then sacrificed and subjected to gross pathological examination. Mortality occured at 12.6 mL/kg bw. Signs of toxicity included rough fur, pale extremities, diarrhea, increased lacrimation and slight to middle-strong lethargy and ataxia. Animals dying during the study showed slight to medium effects in the lung, liver, glands, stomach and duodenum. In animals sacrificed at the end of the study, light to medium effects were observed in the lungs, liver and stomach. Under the study conditions, the LD50 of the test substance was found to be equivalent to 14.21 mL/kg bw (according to Kärber) or 13.82 ml/kg bw (according to Weil). These LD50 values are equivalent to 14210 and 13820 mg/kg bw, assuming a density of approximately 1 g/cm3 (Sandhowe-Grote, 1979).

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
Value:
10 000 mg/kg bw
Quality of whole database:
The information requirements for this tonnage band is sufficiently met with the available data.

Acute toxicity: via inhalation route

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Reference
Endpoint:
acute toxicity: inhalation
Data waiving:
study scientifically not necessary / other information available
Justification for data waiving:
other:
Endpoint conclusion
Endpoint conclusion:
no study available

Acute toxicity: via dermal route

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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:
test procedure in accordance with generally accepted scientific standards and described in sufficient detail
Qualifier:
according to
Guideline:
other: A modification of the techniques described in Appraisal of the Safety of Chemicals in Foods, Drugs and Cosmetics, compiled by the staff of the Division of Pharmacology, Food and Drug Administration.
Deviations:
not specified
GLP compliance:
no
Test type:
other: LD50 limit test
Limit test:
yes
Species:
rabbit
Strain:
New Zealand White
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Weight at study initiation: 1.9 to 2.7 kg

No further information available.
Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Type of wrap if used: The trunk of each animal was encased in a sleeve of plasticized material after application of test material




Duration of exposure:
24 h
Doses:
2,000 mg/kg bw
No. of animals per sex per dose:
Three animals with abraded skin and three animals with intact skin

Control animals:
yes, concurrent no treatment
Details on study design:
- Duration of observation period following administration: Animals were observed immediately after dosing, and at 1, 6 and 24 h post-dosing. Following the 24 h exposure period, animals were observed for mortality, skin response and general behavior for 14 d



Statistics:
Not reported
Preliminary study:
Not applicable
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortalities observed

Clinical signs:
All animals appeared normal throughout the 24 h exposure period and the 14 d post-exposure observation period.
Body weight:
Not reported
Gross pathology:
Not applicable
Other findings:
None
Interpretation of results:
GHS criteria not met
Conclusions:
Under the conditions of the study, the acute dermal LD50 was found to be >2,000 mg/kg bw in albino rabbits.

Executive summary:

A study was conducted to determine the acute dermal toxicity of the test substance in male and female albino rabbit. The procedure was a modification of the techniques described in 'Appraisal of the Safety of Chemicals in Foods, Drugs and Cosmetics, compiled by the staff of the Division of Pharmacology, Food and Drug Administration'. A single dose of 2000 mg/kg bw was applied to the abraded and intact skin of rabbits. The trunk of each animal was then encased in a sleeve of plasticized material to ensure contact of the test material for a period of 24 h. Animals were observed immediately after dosing, and at 1, 6 and 24 h post-dosing. Following the exposure period, animals were observed for mortality, skin response and general behaviour for 14 d. No mortality was observed in this study. All animals appeared normal throughout the study. Under the conditions of the study, the acute dermal LD50 was found to be >2,000 mg/kg bw in albino rabbits (Palanker, 1976).

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
2 000 mg/kg bw
Quality of whole database:
The information requirements for this tonnage band is sufficiently met with the available data.

Additional information

Oral

A study was conducted to determine the acute oral toxicity of the test substance in Sprague Dawley rats. Groups of 6 males were administered 0, 5000, 10000 and 20000 mg/kg bw by stomach intubation and observed for 14 d. Approximately 50% mortality occurred at the mid dose. Under the study conditions, the oral LD50 was therefore 10000 mg/kg bw (Casey, 1976).

A study was performed to assess the acute oral toxicity of the test substance in Sprague Dawley rats. Groups of 20 fasted animals (10 males and 10 females) were exposed via oral gavage to 0, 10.0, 12.6, 16.0 and 20.0 mL/kg bw. The animals were observed for 14 d, then sacrificed and subjected to gross pathological examination. Mortality occured at 12.6 mL/kg bw. Signs of toxicity included rough fur, pale extremities, diarrhea, increased lacrimation and slight to middle-strong lethargy and ataxia. Animals dying during the study showed slight to medium effects in the lung, liver, glands, stomach and duodenum. In animals sacrificed at the end of the study, light to medium effects were observed in the lungs, liver and stomach. Under the study conditions, the LD50 of the test substance was found to be equivalent to 14.21 mL/kg bw (according to Kärber) or 13.82 ml/kg bw (according to Weil). These LD50 values are equivalent to 14210 and 13820 mg/kg bw, assuming a density of approximately 1 g/cm3 (Sandhowe-Grote, 1979).

Dermal

A study was conducted to determine the acute dermal toxicity of the read-across substance, amides, C8-18 (even-numbered) and C18-unsatd., N,N-bis(hydroxyethyl), in male and female albino rabbit. The procedure was a modification of the techniques described in ‘Appraisal of the Safety of Chemicals in Foods, Drugs and Cosmetics, compiled by the staff of the Division of Pharmacology, Food and Drug Administration’. A single dose of 2000 mg/kg bw was applied to the abraded and intact skin of rabbits. The trunk of each animal was then encased in a sleeve of plasticized material to ensure contact of the test material for a period of 24 h. Animals were observed immediately after dosing, and at 1, 6 and 24 h post-dosing. Following the exposure period, animals were observed for mortality, skin response and general behaviour for 14 d. No mortality was observed in this study. All animals appeared normal throughout the study. Under the conditions of the study, the acute dermal LD50 was found to be >2000 mg/kg bw (Palanker, 1976).

Justification for classification or non-classification

The available data indicates that the test substance has a low potential for acute toxicity (oral and dermal LD50 of 10000 and >2000 mg/kg bw, respectively) and does not meet the requirement for classification according to CLP (EC 1272/2008) criteria.