Registration Dossier

Administrative data

Description of key information

The only available study is read across to the oral LD50 study on 2,2’-(C16-18 (evennumbered), alkyl imino) diethanol (tested under CAS No 90367-28-5) which shows LD50 to be >2000 mg/kg.  As 2,2’-(Octadecylimino)bisethanol) is a skin irritant but not corrosive, dermal absorption would be expected to be lower than oral, so the LD50 would also be expected to be > 2000mg/kg.  There is no study for an inhalation LC50, but the physical form of the substance as a waxy solid at ambient temperatures and its low vapour pressure mean that an inhalation LC50 study is not scientifically justified as inhalation exposure is not anticipated.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records
Reference
Endpoint:
acute toxicity: oral
Type of information:
migrated information: read-across based on grouping of substances (category approach)
Adequacy of study:
key study
Study period:
1989-1990
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Substance: CESIO 19. No data on batch no. and composition. Basic data given; comparable to guidelines/standards. No information on concentration/dose volume
Reason / purpose:
reference to same study
Qualifier:
according to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
GLP compliance:
yes
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: Natin & Kingman Ltd., Grimston, Hull, UK
- Age at study initiation: ca. 5-8 weeks
- Weight at study initiation: 120-132 g (males), 122-136 g (females)
- Fasting period before study: overnight prior to dosing until 2-3.5 h after dosing
- Housing: 5/sex in solid floor propylene cages with sawdust bedding
- Diet (e.g. ad libitum): ad lib
- Water (e.g. ad libitum): ad lib
- Acclimation period: at least 5 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-24
- Humidity (%): 30-70
- Air changes (per hr): ca. 15
- Photoperiod (hrs dark / hrs light): 12/12


IN-LIFE DATES: no data
Route of administration:
oral: gavage
Vehicle:
other: methylcellulose (1%)
Details on oral exposure:
VEHICLE
- 1% methylcellulose
- Concentration in vehicle: not indicated
- Amount of vehicle (if gavage): not indicated
- Justification for choice of vehicle: not indicated

MAXIMUM DOSE VOLUME APPLIED: not indicated, based on fasted bw at the time of dosing
Doses:
25, 200, 2000, 5000 mg/kg bw (range-finding study)
2000 mg/kg bw (main study)
No. of animals per sex per dose:
1/sex (range-finding study): 8 in total
5/sex (main study): 10 in total
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days (5 days in rang-finding study)
- Frequency of observations and weighing: 1 and 4 h after dosing, once daily therafter. BW weekly
- Necropsy of survivors performed: yes (not on animals of the range-finding study)
Statistics:
Not required.
Preliminary study:
1 out of 2 animals died at 5000 mg/kg bw (range-finding study); therefore 2000 mg/kg bw was chosen as target level in main study.
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Remarks on result:
other: 1/5 females was found dead
Mortality:
One female was found dead 2 days after treatment.
Clinical signs:
All animals showed hunched posture and pilo-erection 1 and 4 h after treatment.
Body weight:
Surviving animals (7/9) showed expected bw gains. One female (1/9) showed reduced bw gain at the end of the 2nd week,
another female (1/9) showed slight bw loss at that time.
Gross pathology:
Necropsy findings in the deceased animal consisted of abnormally red lungs, dark liver and kidneys and haemorrhage of the gastric mucosa. No abnormalities were noted in survivors.
Other findings:
No.
Interpretation of results:
Category 5 based on GHS criteria
Remarks:
Migrated information
Conclusions:
The oral LD50 is larger than 2000 mg/kg bw. However, based on 10% mortality at this level and 1/2 rats dying at 5000 mg/kg bw
(range-finding study), the LD50 is expected to be close to 5000 mg/kg bw. Therefore classification in Category V, according to
OECD-GHS criteria.
Executive summary:

The study was performed to assess the acute toxicity of the test material following a single oral administration to the Sprague-Dawley strain rat. The study was performed according to OECD guideline 401. Following a range-finding study, a group of ten fasted animals (five male and five female) was given a single, oral dose of the test material at a dose level 2000 mg/kg bodyweight. The animals were observed for 14 days after the day of dosing and were then killed for gross pathological examination. One female was found dead 2 days after dosing. Clinical signs of toxicity noted were hunched posture and pilo-erection 1 and 4 h after dosing. Most survivors showed expected gains in bodyweight over the study period; in 2 female rats bw gain was reduced or slight body weight loss was observed. No abnormalities were noted in survivors at necropsy; the deceased animal showed abnormally red lungs, dark liver and kidneys and haemorrhage of the gastric mucosa. The acute median lethal dose (LD50) of the test material was found to be greater than 2000 mg/kg bodyweight. The test material was considered not to have significant acute toxicity and does require classification in Category V, according to OECD-GHS (based on 10% mortality at 2000 mg/kg bw and 1/2 dead animals at 5000 mg/kg bw).

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50

Acute toxicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no study available

Acute toxicity: via dermal route

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

The available read across study is acceptable for classification and labelling purposes being of Klimisch 2 validity, there were some deaths seen at 2000 and 5000mg/kg but the oral LD50 was greater than 2000mg/kg so it is not classified based on EU CLP(GHS) it is however classified as Category V for acute toxicity for the Global GHS purposes.

There is no dermal LD 50 value as we have no data for acute skin toxicity of 2,2’-(Octadecylimino)bisethanol) or for the read across substance 2,2’-(C16-18 (evennumbered), alkyl imino) diethanol CAS No 1218787-30-4. But due to the skin irritant nature of the substance it is not ethical to carry out this animal study. The irritant classification of the 2,2’-(Octadecylimino)bisethanol) and the required risk management methods with minimise the potential for skin contact, so the lack of a dermal LD50 will not affect the safe handling of the substance . The physical properties of the substance as a waxy solid with a relatively high Log octanol water partition coefficient of 3.8, will reduce the potential for skin absorption so it is expected that the dermal LD50 would higher than the oral LD50 which itself was >2000 mg/kg i.e. not classified for EU CLP(GHS).

We have no inhalation LC50 data for 2,2’-(Octadecylimino)bisethanol) or the read across substance 2,2’-(C16-18 (evennumbered), alkyl imino) diethanol CAS No 1218787-30-4, however it is a waxy solid with a low vapour pressure, expected to be lower than 0.73 mPa at 20°C (1.2 mPa at 25°C), significant exposure to vapours would not be expected at ambient temperatures so the lack of an inhalation LC50 is not considered significant as inhalation is not an expected route of exposure.

Due to the physical form of the 2,2’-(Octadecylimino)bisethanol) CAS No 10213-78-2 being a waxy solid at ambient temperature, the is no aspiration hazard for this substance.

Justification for selection of acute toxicity – oral endpoint

The available study is which is read across to Ethanol 2,2’-iminobis-, N-(hydrogenated tallow alkyl) CAS No 90367-28-5 is acceptable for classification and labelling purposes being of Klimisch 2 validity and as it is predominantly C16-18 it can be considered unlikely to underestimate the toxicity of 2,2’-(Octadecylimino)bisethanol) which is predominantly C18, there were some deaths seen at 2000 and 5000mg/kg but the oral LD50 was greater than 2000mg/kg so it is not classified based on EU CLP(GHS) it is however classified as Category V for acute toxicity for the Global GHS purposes.

Justification for selection of acute toxicity – inhalation endpoint

We have no inhalation LC50 data for 2,2’-(Octadecylimino)bisethanol or for the read across substance 2,2’-(C16-18 (evennumbered), alkyl imino) diethanol CAS No 1218787-30-4,  however it is a waxy solid with a low vapour pressure, expected to be lower than 0.73 mPa at 20°C (1.2 mPa at 25°C) , which is based on read across to Bis(2-hydroxyethyl) coco amine CAS No 61791-31-9 which is a worst case.  Significant exposure to vapours would not be expected at ambient temperatures so the lack of an inhalation LD50 is not considered significant as inhalation is not an expected route of exposure

Justification for selection of acute toxicity – dermal endpoint

There is no dermal LD 50 value as we have no data for acute skin toxicity of 2,2’-(Octadecylimino)bisethanol  or the read across substance 2,2’-(C16-18 (evennumbered), alkyl imino) diethanol CAS No 1218787-30-4.  But due to the skin irritant nature of the substance it is not ethical to carry out this animal study. The irritant classification of 2,2’-(Octadecylimino)bisethanol and the required risk management methods with minimise the potential for skin contact, so the lack of a dermal LD50 will not affect the safe handling of the substance .  The physical properties of the substance as a waxy solid with a relatively high Log octanol water partition coefficient of 3.8, will reduce the potential for skin absorption so it is expected that the dermal LD50 would higher than the oral LD50 which itself was >2000 mg/kg i.e. not classified for EU CLP(GHS).

Justification for classification or non-classification

The oral LD50 was established by read across to be greater than 2000mg/kg, we do not have a dermal study but it would be expected to be less toxic by the dermal route, therefore also > 2000mg/kg. We have no inhalation LC50 data for 2,2’- (Octadecylimino)bisethanol) CAS No 10213-78-2, however it is a waxy solid with a low vapour pressure expected to be lower than 0.73 mPa at 20°C (1.2 mPa at 25°C), significant exposure to vapours would not be expected at ambient temperatures so the lack of an inhalation LC50 is not considered significant as inhalation is not an expected route of exposure.