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Description of key information

The available data suggests that amides, C16-18 (even numbered) and C18-unsatd., N,N-bis(hydroxyethyl) has a low potential for acute oral (LD50 >3,000 mg/kg bw) and dermal toxicity (LD50 >2,000 mg/kg bw, based on a study tested with read across substance, C8-18 and C18- unsatd., N,N-bis(hydroxyethyl).

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 December 12, 1989 to February 14, 1990
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: The study was conducted according to OECD 401 guideline study, but not in compliance with GLP.
Reason / purpose for cross-reference:
reference to same study
Reason / purpose for cross-reference:
reference to other study
Qualifier:
according to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
not specified
GLP compliance:
no
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
other: Bor:WISW (SPF Cpb)
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: F. Winkelmann, 4799 Borchen, Germany
- Weight at study initiation: 249 g
- Fasting period before study: > 16 h
- Housing: Groups of up to five by sex in solid-floor polypropylene cages
- Diet: R10 Alleindiät for rats, Ssniff Spezialfutter GmbH, 4770 Soest, ad libitum
- Water: Drinking water, ad libitum
- Acclimation period: 5-8 d

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-21
- Humidity (%): 60 +/- 5%
- 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: 3.09 cm3/kg
Doses:
3,000 mg/kg
No. of animals per sex per dose:
10
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 d
- Frequency of clinical observation: Continuously up to 6 h post-treatment and subsequently once daily for 14 d
- Frequency of weighing: Pre-treatment , then on Days 1, 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 were observed
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 3 000 mg/kg bw
Mortality:
No mortality
Clinical signs:
other: All animals were in resting position 30 minutes after dosing. Three had slightly rough fur. Thirty minutes later, no symptoms were seen anymore.
Gross pathology:
Six animals showed local thickenings of the mucous membrane of the forestomach; in three of these animals, the mucous membrane of the stomach was slightly reddened.
Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Under the study conditions, the LD50 of the test susbtance in rat was found to be > 3,000 mg/kg bw. Hence, it does not warrant a classification according to EU CLP.
Executive summary:

A study was performed to assess the acute oral toxicity of amides, C16-18 (even-numbered) and C18-unsatd., N,N-bis(hydroxyethyl) in Bor:WISW rat according to OECD Guideline 401.

A group of 20 fasted animals (10 males and 10 females) was administered a single oral dose of undiluted test substance at 3,000 mg/kg bw. The animals were observed for 14 d and were then sacrificed and subjected to gross pathological examination.

There were no mortalities. Transient signs of toxicity were observed 30 minutes after dosing, but no longer after that time point. Upon necropsy, thickening of the mucous membrane of the forestomach and slight reddening of the mucous membrane of the stomach was seen in some animals.

Under the study conditions, the LD50 of the test susbtance in rat was found to be > 3,000 mg/kg bw. Hence, it does not warrant a classification according to EU CLP.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
3 000 mg/kg bw
Quality of whole database:
The study was conducted according to OECD 401 guideline study, but not in compliance with GLP.

Acute toxicity: via inhalation route

Link to relevant study records
Reference
Endpoint:
acute toxicity: inhalation
Data waiving:
other justification
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:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Read across study hence maximum reliability rating of 2 assigned according to ECHA guidance, although study is acceptable, well-documented and meets basic scientific principles.
Justification for data waiving:
other:
Reason / purpose for cross-reference:
reference to same study
Reason / purpose for cross-reference:
reference to other study
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
Principles of method if other than guideline:
Not applicable
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 or test system 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
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Mortality:
No mortalities observed

Clinical signs:
other: All animals appeared normal throughout the 24 h exposure period and the 14 d post-exposure observation period.
Gross pathology:
Not applicable
Other findings:
None

None

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Under the test conditions, the acute dermal LD50 of structurally similar 'amides, C8-18 (even-numbered) and C18-unsatd., N,N-bis(hydroxyethyl)' was found to be > 2,000 mg/kg bw in albino rabbits, indicating a low toxicity.

Executive summary:

A study was conducted to determine the acute dermal toxicity of structurally similar 'amides, C8-18 (even-numbered) 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.

 

2 g/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 test conditions, the acute dermal LD50 of 'amides, C8-18 (even-numbered) and C18-unsatd., N,N-bis(hydroxyethyl)' was found to be > 2,000 mg/kg bw in albino rabbits indicating a low toxicity. 

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
2 000 mg/kg bw
Quality of whole database:
The KL2 rated read across study was well-documented and meets the basic scientific principles.

Additional information

Oral

A study was performed to assess the acute oral toxicity of amides, C16-18 (even-numbered) and C18-unsatd., N,N-bis(hydroxyethyl) in Bor: WISW rat according to OECD guideline 401. A group of 20 fasted animals (10 males and 10 females) were administered a single oral dose of undiluted test substance at 3,000 mg/kg bw. The animals were observed for 14 days and were then sacrificed and subjected to gross pathological examination. There were no mortalities. Transient signs of toxicity were observed 30 minutes after dosing, but no longer after that time point. Upon necropsy, thickening of the mucous membrane of the forestomach and slight reddening of the mucous membrane of the stomach was seen in some animals. Under the study conditions, the LD50was > 3,000 mg/kg bw (Mürmann P, 1990).

Dermal

A single application of 2,000 mg/kg bw of structurally similar amides, C8-18 and C18-unsatd., N,N-bis(hydroxyethyl) applied to the abraded and intact skin of the test animals resulted in no mortality. All animals appeared normal throughout the 24 hour exposure period and during the 14 day post-exposure observation period. The dermal LD50was determined to be >2,000 mg/kg bw, which indicates a low acute dermal toxicity (Palanker AL, 1976) . Amides, C16-18 (even numbered) and C18-unsatd., N,N-bis(hydroxyethyl) is therefore also expected to have low acute dermal toxicity.

Inhalation

The test substance has a very low vapor pressure, so the potential for the generation of inhalable forms is low. Also, the use of this substance will not result in aerosols, particles or droplets of an inhalable size, therefore exposure to humans via the inhalatory route is unlikely to occur under the conditions of normal and foreseeable handling and use.

Justification for selection of acute toxicity – oral endpoint

Only one relevant guideline compliant study was available.

Justification for selection of acute toxicity – inhalation endpoint

The test substance has very low vapor pressure, so the potential for the generation of inhalable forms is low, also the use of this substance will not result in aerosols, particles or droplets of an inhalable size, so exposure to humans via the inhalatory route is unlikely to occur under the conditions of normal and foreseeable handling and use.

Justification for selection of acute toxicity – dermal endpoint

Only one relevant RA study was available.

Justification for classification or non-classification

The available data indicates a low potential for acute toxicity (oral and dermal LD50of >3,000 and >2,000 mg/kg bw respectively) and does not meet the requirement for classification according to according to EC criteria (67/548/EEC) and according to CLP criteria (EC 1272/2008).