Registration Dossier

Administrative data

Description of key information

The available data for amides, C8-18 and C18-unsatd., N,N-bis(hydroxyethyl) indicates a low potential for acute oral (LD50  > 5,000 mg/kg bw) and dermal (LD50 > 2,000 mg/kg bw) toxicity.

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 February 20, 1996 to April 11, 1996
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Guideline study with GLP
Justification for data waiving:
other:
Reason / purpose:
reference to same study
Reason / purpose:
reference to other study
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
Principles of method if other than guideline:
Not applicable
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: 152-174 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 (%): 39-65
- Air changes (per h): 15
- Photoperiod (h dark/h light): 12/12

Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
MAXIMUM DOSE VOLUME APPLIED: 1.99 mL/kg
Doses:
2,000 mg/kg
No. of animals per sex per dose:
Five
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
Statistics:
None
Preliminary study:
No deaths or clinical signs of toxicity were observed
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Remarks on result:
other: None
Mortality:
No mortality
Clinical signs:
No signs of systemic toxicity
Body weight:
All animals showed expected gain in body weight
Gross pathology:
No abnormalities noted at necropsy
Other findings:
None

None

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The LD50 of the test material in the Sprague-Dawley CD rat was found to be greater than 2,000 mg/kg. Thus, no symbol and risk phrase are required according to EU regulations.
Executive summary:

A study was performed to assess the acute oral toxicity of the test material in the Sprague-Dawley CD rat according to OECD Guideline 401and EU Method B1 of Commission Directive 92/69/EEC.

A group of 10 fasted animals (five males and five females) was administered a single oral dose of undiluted test material at a dose level of 2,000 mg/kg. The animals were observed for 14 d after the day of dosing and were then sacrificed and subjected to gross pathological examination.

No mortalities were observed in the study. No signs of systemic toxicity were noted during the study. All animals showed expected gain in body weight during the study. No abnormalities were observed at necropsy.

The LD50 of the test material in the Sprague-Dawley CD rat was found to be greater than 2,000 mg/kg. Thus, no symbol and risk phrase are required according to EU regulations.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
5 000 mg/kg bw
Quality of whole database:
Sufficient good quality data available.

Acute toxicity: via inhalation route

Link to relevant study records
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

Link to relevant study records
Reference
Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
Not available
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Acceptable, well-documented publication that meets basic scientific principles
Justification for data waiving:
other:
Reason / purpose:
reference to same study
Reason / purpose:
reference to other study
Qualifier:
according to
Guideline:
other: Modification of the techniques described in Appraisal of the Safety of Chemicals in Foods, Drugs & Cosmetics, compiled by staff of the Division of Pharmacology, Food and Drug Administration
Principles of method if other than guideline:
Not applicable
GLP compliance:
not specified
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
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 g/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
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Mortality:
No deaths were observed.
Clinical signs:
All animals appeared normal throughout the 24 h exposure period and the 14 d post-exposure observation period.

None

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Under the conditions of the test, the dermal LD50 value was found to be > 2000 mg/kg bw.
Executive summary:

A study was conducted to determine the acute dermal toxicity of amides, C8-18 and C18-unsatd., N,N-bis(hydroxyethyl) in male/female albino rabbit. The procedure was the 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.

2000 mg/kg bw of test material was applied (single application) to the abraded and intact skin of the test animals. The trunk of each animal was then encased in a sleeve of plasticized material to ensure contact of the test material for a 24 h period. 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.

No mortality was observed in this study. All animals appeared normal throughout the 24 h exposure period and the 14 d post-exposure observation period.

Under the conditions of the test, the dermal LD50 value was found to be > 2 g/kg bw.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
2 000 mg/kg bw
Quality of whole database:
Sufficient data available.

Additional information

Oral

In two acute oral toxicity OECD guideline studies, single dose levels of 2,000 and 5,000 mg/kg bw of amides, C8-18 and C18-unsatd., N,N-bis(hydroxyethyl) administered to rats resulted in no mortalities, no signs of systemic toxicity and no abnormalities or macroscopic changes in the organs at necropsy. The oral LD50of the substance was found to be > 2,000 mg/kg bw in Sprague-Dawley CD rat (Hempstock C, 1996) and > 5,000 mg/kg bw in Wistar rat (Skydsgaard K, 1985). Both studies suggest that amides, C8-18 and C18-unsatd., N,N-bis(hydroxyethyl) has low acute toxicity when administered via the oral route.

Dermal

A single application of 2,000 mg/kg bw of amides, C8-18 and C18-unsatd., N,N-bis(hydroxyethyl) to the abraded and intact skin of rabbits resulted in no mortality. All animals appeared normal throughout the 24 hours exposure and the 14 days post-exposure observation periods. The dermal LD50was determined to be > 2,000 mg/kg bw, which indicates low acute dermal toxicity (Palanker AL, 1976).

Inhalation

Due to the physical-chemical properties (i.e. low vapour pressure and high viscosity) of amides, C8-18 and C18-unsatd., N,N-bis(hydroxyethyl), inhalatory exposure is not expected to occur under the conditions of normal and foreseeable handling and use and therefore acute inhalation toxicity to humans from amides, C8-18 and C18-unsatd., N,N-bis(hydroxyethyl) is considered unlikely.

 


Justification for selection of acute toxicity – oral endpoint
Good quality KL1 study.

Justification for selection of acute toxicity – dermal endpoint
One study available.

Justification for classification or non-classification

The available data for amides, C8-18 and C18-unsatd., N,N-bis(hydroxyethyl) indicates a low potential for acute toxicity (oral and dermal LD50of > 5,000 and > 2,000 mg/kg bw, respectively). The substance does not meet the requirement for classification according to EC (67/548/EEC) and CLP (EC 1272/2008) criteria.