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Description of key information

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

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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:
guideline study
Justification for type of information:
To minimize the number of animals, the up and down procedure adopted by OECD (2008a) for acute toxicity testing strives to use a maximum of five animals, starting with a single dose to a single rat. After a period of observation, the dose may or may not be adjusted up or down before dosing the next animal. As the test substance is not expected to have potent toxicity, the intent of this study was to test at the maximum dose of 2000 mg/kg bw. Thus, this test is characterized as a limit test.
Qualifier:
according to
Guideline:
OECD Guideline 425 (Acute Oral Toxicity: Up-and-Down Procedure)
Version / remarks:
Up and Down Procedure
Deviations:
no
GLP compliance:
yes
Test type:
up-and-down procedure
Limit test:
yes
Species:
rat
Strain:
Sprague-Dawley
Sex:
female
Details on test animals and environmental conditions:
Sprague-Dawley rats (Vivo Bio Tech Ltd), age: 6–7 weeks
Route of administration:
oral: gavage
Vehicle:
not specified
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
5
Control animals:
not specified
Details on study design:
5 females Sprague-Dawley rats were used for the study.
Observation of clinical signs: at 10, 30 min, 1, 2, and 4 h after dosing, and thereafter daily until day 15. Each animal was subjected to gross pathology.
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
The test substance did not induce any mortality at the limit dose of 2000 mg/kg bw.
Clinical signs:
No abnormal clinical signs were noted in any of the five test animals observed at 10 and 30 min, 1, 2, and 4 h, and thereafter daily until day 15 postdosing.
Body weight:
Not specified.
Gross pathology:
No gross pathological abnormalities were found.
Interpretation of results:
GHS criteria not met
Conclusions:
Under the study conditions, the LD50 of the test substance was >2000 mg/kg bw after single oral administration to Sprague-Dawley rats.
Executive summary:

A study was conducted to determine the acute oral toxicity of the test substance in female Sprague-Dawley rats using the “Up and Down Procedure” according to OECD Guideline 425 (2008a). As the substance was not expected to have potent toxicity, it was administered at the maximum dose of 2000 mg/kg bw (limit test) to 5 female rats. The test substance did not induce any mortality or abnormal clinical signs in any of the animals observed at 10 and 30 min, 1, 2, and 4 h, and thereafter daily until Day 15 post-dosing. Each animal was subjected to gross necropsy and no gross pathological abnormalities were found. Microscopic pathology was not conducted in the absence of any gross pathological changes. Under the study conditions, the LD50 of the test substance was >2000 mg/kg bw after single oral administration to Sprague-Dawley rats (Nestmann, 2017).

Endpoint:
acute toxicity: oral
Type of information:
read-across based on grouping of substances (category approach)
Adequacy of study:
key study
Study period:
From February 20, 1996 to April 4, 1996
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Read across study
Justification for type of information:
Refer to the section 13 for details on the read across justification.
Reason / purpose:
read-across source
Qualifier:
according to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.1 (Acute Toxicity (Oral))
Deviations:
no
GLP compliance:
yes (incl. certificate)
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: Charles River (UK) Ltd., Margate, Kent, UK
- Age at study initiation: 5-8 wk
- Weight at study initiation: Males - 152 - 182 g, females - 140-156 g
- Fasting period before study: Overnight
- Housing: Groups of up to five by sex in solid-floor polypropylene cages
- Diet: Rat and mouse expanded diet no. 1, ad libitum
- Water: Drinking water, ad libitum
- Acclimation period: Atleast 5 d

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-21
- Humidity (%): 44-65
- Air changes (per h): 15
- Photoperiod (h dark/h light): 12/12

Route of administration:
oral: gavage
Vehicle:
arachis oil
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 200 mg/mL

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg


Doses:
2,000 mg/kg in both range-finding and main study
No. of animals per sex per dose:
one in range-finding study and five in main study
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 d
- Frequency of clinical observation: 0.5, 1, 2 and 4 h after dosing and subsequently once daily for 14 d
- Frequency of weighing: On Days 0, 7 and 14
- Necropsy of survivors performed: Yes
- Examinations performed: Clinical signs, body weight and gross pathological examination
Preliminary study:
No deaths or clinical signs of toxicity
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality
Clinical signs:
No signs of systemic toxicity
Body weight:
All animals showed an expected gain in body weight except one female which showed reduced body weight gain during the second week of observation
Gross pathology:
No abnormalities noted at necropsy
Interpretation of results:
GHS criteria not met
Conclusions:
Under the study conditions, the LD50 of the test substance in rat was found to be >2000 mg/kg.
Executive summary:

A study was conducted to determine the acute oral toxicity of the read across substance, amides, C8-18 (even numbered) and C18-unsatd., N-(hydroxyethyl), to Sprague Dawley rats according to OECD Guideline 401 and EU Method B.1, in compliance with GLP. Following a range-finding study, a group of 10 fasted rats (five males and five females) were given a single oral dose of the test substance as a solution in arachis oil BP at a dose level of 2000 mg/kg. The animals were observed for 14 d after dosing and were then killed and subjected to gross pathological examination. There was no mortality in the study and no signs of systemic toxicity were noted. All animals showed an expected gain in body weight apart from one female which showed reduced body weight gain during the second week. No abnormalities were noted at necropsy. Under the study conditions,the LD50 of the test substance in rat was found to be >2000 mg/kg (Hempstock, 1996).

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
2 000 mg/kg bw

Acute toxicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no study available

Acute toxicity: via dermal route

Link to relevant study records
Reference
Endpoint:
acute toxicity: dermal
Type of information:
read-across based on grouping of substances (category approach)
Adequacy of study:
key study
Study period:
Not reported
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Read across study
Justification for type of information:
Refer to the section 13 for details on the read across justification.
Reason / purpose:
read-across source
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:
standard acute method
Limit test:
yes
Species:
rabbit
Strain:
New Zealand White
Sex:
male/female
Details on test animals and environmental conditions:
- Weight at study initiation: 1.9-2.7 kg

No further information avaialble.
Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
Prior to dosing, the trunk of each animal was clipped free of hair. Three of the animals (two male, one female) were further prepared by introducing epidermal abrasions over the clipped skin surface to enhance penetrability of the test substance through the stratum corneum. After test substance application the trunk of each animal was encased in a sleeve of plasticized material for 24 h. Following the 24 h exposure period the sleeve was removed and the skin sites gently cleansed.
Duration of exposure:
24 h
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
3
Details on study design:
All animals were observed daily thereafter for 14 d for mortality, skin response and general behavior.
Preliminary study:
Not applicable
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Mortality:
No mortalities observed
Clinical signs:
All animals appeared normal through Day 14.
Body weight:
Two females that had abraded skin lost weight (0.01 and 0.25 kg) over the 14 d post-exposure period. All remaining rabbits gained weight through Day 14.
Interpretation of results:
GHS criteria not met
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Under the study conditions, the acute dermal LD50 in rabbit was found to be >2,000 mg/kg bw.
Executive summary:

A limit test was conducted to determine the acute dermal toxicity of the read across substance, Amides, C8-18 (even numbered) and C18-unsatd., N-(hydroxyethyl), to albino rabbits. Three male and three female rabbits were administered a single dose of the test substance at a level of 2000 mg/kg bw. Prior to dosing, the trunk of each animal was clipped free of hair. Three of the animals (two males and one female) were further prepared by introducing epidermal abrasions over the clipped skin surface to enhance penetrability of the test substance through the stratum corneum. After test substance application, the trunk of each animal was encased in a sleeve of plasticized material for 24 h. Following the exposure period, the sleeve was removed and the skin sites gently cleansed. All animals were observed daily thereafter for 14 d for mortality, skin response and general behavior. All animals survived and appeared normal through to Day 14. Two females that had abraded skin lost weight over the 14 d post-exposure period. All remaining rabbits gained weight. Under the study conditions, the acute dermal LD50 in rabbit was found to be >2,000 mg/kg bw (Palanker, 1976).

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
2 000 mg/kg bw

Additional information

Acute toxicity, oral

A study was conducted to determine the acute oral toxicity of the test substance in female Sprague-Dawley rats using the “Up and Down Procedure” according to OECD Guideline 425 (2008a). As the substance was not expected to have potent toxicity, it was administered at the maximum dose of 2000 mg/kg bw (limit test) to 5 female rats. The test substance did not induce any mortality or abnormal clinical signs in any of the animals observed at 10 and 30 min, 1, 2, and 4 h, and thereafter daily until Day 15 post-dosing. Each animal was subjected to gross necropsy and no gross pathological abnormalities were found. Microscopic pathology was not conducted in the absence of any gross pathological changes. Under the study conditions, the LD50 of the test substance was >2000 mg/kg bw after single oral administration to Sprague-Dawley rats (Nestmann, 2017).

A study was conducted to determine the acute oral toxicity of the read across substance, amides, C8-18 (even numbered) and C18-unsatd., N-(hydroxyethyl), to Sprague Dawley rats according to OECD Guideline 401 and EU Method B.1, in compliance with GLP. Following a range-finding study, a group of 10 fasted rats (five males and five females) were given a single oral dose of the test substance as a solution in arachis oil BP at a dose level of 2000 mg/kg. The animals were observed for 14 d after dosing and were then killed and subjected to gross pathological examination. There was no mortality in the study and no signs of systemic toxicity were noted. All animals showed an expected gain in body weight apart from one female which showed reduced body weight gain during the second week. No abnormalities were noted at necropsy. Under the study conditions, the LD50 of the test substance in rat was found to be >2000 mg/kg (Hempstock, 1996).

 

Acute toxicity, dermal

A limit test was conducted to determine the acute dermal toxicity of the read across substance, amides, C8-18 (even numbered) and C18-unsatd., N-(hydroxyethyl), to albino rabbits. Three male and three female rabbits were administered a single dose of the test material at a level of 2000 mg/kg bw. Prior to dosing, the trunk of each animal was clipped free of hair. Three of the animals (two males and one female) were further prepared by introducing epidermal abrasions over the clipped skin surface to enhance penetrability of the test substance through the stratum corneum. After test substance application, the trunk of each animal was encased in a sleeve of plasticized material for 24 h. Following the exposure period, the sleeve was removed and the skin sites gently cleansed. All animals were observed daily thereafter for 14 d for mortality, skin response and general behavior. All animals survived and appeared normal through to Day 14. Two females that had abraded skin lost weight over the 14 d post-exposure period. All remaining rabbits gained weight. Under the study conditions, the acute dermal LD50 in rabbit was found to be >2,000 mg/kg bw (Palanker, 1976).

Justification for classification or non-classification

The available data on the substance itself and on the structurally similar amides, C8-18 (even numbered) and C18-unsatd., N-(hydroxyethyl) indicates a low potential for acute toxicity (oral and dermal LD50 of >2,000 mg/kg bw). The substance therefore does not meet the requirement for classification according to CLP (EC 1272/2008) criteria.