Registration Dossier

Diss Factsheets

Administrative data

Description of key information

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
Study period:
From January 23, 2018 to February 9, 2018
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 425 (Acute Oral Toxicity: 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 or test system and environmental conditions:
Female rates were selected for the test because they are frequently more sensitive to the toxicity of test compound than males. The rats were housed individually in stainless steel cages in a temperature 66-77oF, humidity 30-70% and light controlled 12 hr/cycle room. Each animal were assigned test number which appeared on a cage card visible on the front of each cage. The rats were maintained according to the recommendations contained in National academy press 2011: "Guide for care and use of Laboratory animals". Purina Laboratory Rat Chow and water were available ad libitum. The rats were acclimated at least five days prior to treatment.
Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
All test animals were fasted overnight prior to dosing. The test substance, was warmed in a water bath prior to dosing and administered orally as an amber coloured liquid to fasted animals according to individual body weights. Dosage volumes were administered via a metal dosing cannula.
Doses:
An initial limit dose of 5000mg/kg was administered to one rat. Due to the absence of mortality in this rat, 2 additional rats received the same dose level; simultaneously. There were mortality in one of the 2 additional animals. Two more animals were dosed at the 5000mg/kg level to fulfil the study requirement. There was no mortality observed in the additional 2 animals.
No. of animals per sex per dose:
5 animals
Control animals:
no
Details on study design:
A limit test is planned for the study. One rat was dosed at 5000mg/kg, if the rat dies the main test will be conducted starting at an appropriate dose level (usually 175mg/kg) to determine LD50. If the rat survives at 5000mg/kg, 2 additional rats will be dosed and if both survive the LD50 will be considered greater than the limit dose and the study will be terminated. (I.e. carried out to 14 days observation without dosing further rats). If one or both rats die. 2 additional rats will be dosed one at a time. Results will be evaluated. The LD50 is considered to be greater than 5000mg/kg if 3 or more animals survive. If the LD50 is determined to be less than 5000mg/kg, the main test is conducted.
Statistics:
At the end of the observation period the calculation of the LD50was conducted according to the agency’s developed software package (AOT425StatPgm).
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
> 5 000 mg/kg bw
Based on:
test mat.
Mortality:
One animal died out of 5 animals tested.
Clinical signs:
Staining around anal area observed for one animal.
Body weight:
Body weights were obtained at study initiation and at 7 & 14 days post-administration
Gross pathology:
Staining around anal area observed for one animal. No ghross changes observed
Interpretation of results:
other: CLP criteria not met
Conclusions:
Under the study conditions, the LD50 for the test substance was determined to be >5000 mg/kg bw.
Executive summary:

A study was conducted to determine the acute oral toxicity of the test substance, amides, C18-unsatd., N-hydroxyethyl, using the up-and-down procedure according to the OECD Guideline 425, in compliance with GLP. Five female Sprague-Dawley rats were randomly selected for an acute oral toxicity study. Fasted rats were given a single dose of the test substance warmed in a water bath prior to dosing and administered orally as an amber coloured liquid according to individual body weights. An initial limit dose of 5000 mg/kg was administered to one rat. Due to the absence of mortality in this rat, 2 additional rats received the same dose level simultaneously. There was mortality in one of the 2 additional animals. Two more animals were dosed at the 5000 mg/kg level to fulfil the study requirement. There was no mortality in the additional 2 animals. Under the study conditions, the LD50 for the test substance was determined to be >5000 mg/kg bw (Michael, 2018).

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
5 000 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:
Remarks:
Read across study
Justification for type of information:
Refer to section 13 of IUCLID for details on the read-across justification.
Reason / purpose for cross-reference:
read-across source
Qualifier:
according to guideline
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 or test system 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

Oral

A study was conducted to determine the acute oral toxicity of the test substance, amides, C18-unsatd., N-hydroxyethyl, using the up-and-down procedure according to the OECD Guideline 425, in compliance with GLP. Five female Sprague-Dawley rats were randomly selected for an acute oral toxicity study. Fasted rats were given a single dose of the test substance warmed in a water bath prior to dosing and administered orally as an amber coloured liquid according to individual body weights. An initial limit dose of 5000 mg/kg was administered to one rat. Due to the absence of mortality in this rat, 2 additional rats received the same dose level simultaneously. There was mortality in one of the 2 additional animals. Two more animals were dosed at the 5000 mg/kg level to fulfil the study requirement. There was no mortality in the additional 2 animals. Under the study conditions, the LD50 for the test substance was determined to be >5000 mg/kg bw (Michael, 2018).

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 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).

Justification for classification or non-classification

Based on results from acute oral and dermal studies on the substance itself or on the read across substance, amides, C8-18 (even numbered) and C18-unsatd., N-(hydroxyethyl), no classification for acute toxicity is proposed according to CLP (EC 1272/2008/EC) criteria.