Registration Dossier

Administrative data

Description of key information

Ethanol, 2,2’-iminobis-, N-coco alkyl derives CAS No 61791-31-9 will be registered for REACH as 2, 2’-(C12-18 evennumbered alkyl imino) diethanol  CAS No 71786-60-2.  The only available information is on acute oral toxicity, testing by the inhalation and dermal routes is waived.

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:
Between 7 December 1983 and 7 January 1984
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: No data on composition. Basic data given; the method followed is comparable with OECD 425.
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 425 (Acute Oral Toxicity: Up-and-Down Procedure)
GLP compliance:
not specified
Remarks:
in-house quality assurance was in place
Test type:
up-and-down procedure
Limit test:
no
Species:
rat
Strain:
other: HC/CFY (remote Sprague-Dawley)
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Hacking and Churchill Limited, England
- Age at study initiation: 4-6 weeks
- Weight at study initiation: 80 to 129 g
- Fasting period before study: Access to food only was prevented overnight prior to and approximately 4 hours after dosing
- Housing: individually housed in metal cages with wire mesh floors
- Diet (e.g. ad libitum): ad libitum, Laboratory Diet No. 1, Spratt's Rodent Breeding Diet (LAD 1)
- Water (e.g. ad libitum): ad libitum
- Acclimation period: minimum 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22-23
- Humidity (%): 45
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12


IN-LIFE DATES: Between 7 December 1983 and 7 January 1984
Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
MAXIMUM DOSE VOLUME APPLIED:
2.9 ml/kg
Doses:
1.0, 1.26, 1.6, 2.0, 2.5 g/kg
No. of animals per sex per dose:
The study continued until 6 animals per sex had been dosed after reversal of the initial outcome; 11 males and 11 females were
used in total.
Control animals:
no
Details on study design:
- Duration of observation period following administration: 7 days
- Frequency of observations and weighing: twice daily observations and individual bodyweights of rats were measured on Days 1 (day of dosing), 8 and at death.
- Necropsy of survivors performed: yes
- Other examinations performed: none
Statistics:
LD50 values were estimated by probit analysis, using a slope estimated from background data. The probit model was fitted by
maximum likelihood, with a slope of 8.333 (equivalent to a standard deviation of 0.12 units for the distribution of individual (log.)
tolerance levels). Approximate confidence intervals (95% level) were determined by adding and subtracting 1.96 times the standarderror of the (log.) LD50 estimate.
Sex:
male
Dose descriptor:
LD50
Effect level:
1 700 mg/kg bw
95% CL:
1 300 - 1 600
Sex:
female
Dose descriptor:
LD50
Effect level:
1 300 mg/kg bw
95% CL:
1 000 - 1 600
Mortality:
see: remarks on results including tables and figures
Clinical signs:
Signs in all rats after dosing included piloerection, hunched posture and abnormal gait (waddling). These signs were accompanied
by: lethargy, decreased respiratory rate, ptosis and pallor of the extremities amongst rats at all the dose levels, increased salivation amongst rats dosed at 1.0, 1.26, 1.6 and 2.5 g/kg. Diarrhoea in one female rat treated at 1.26 g/kg and one male at 1.6 g/kg.
Recovery of survivors as judged by external appearance and behaviour was apparantly complete 5 to 7 days after dosing.
Body weight:
All rats that died showed a bodyweight loss. No effects on the survivors.
Gross pathology:
No effects observed in survivors. Autopsy of animals that died revealed congestion of the lungs and pallor of the liver, kidneys and spleen.

Mortality data

0 = survival

1 = death

                                   mortality data on each dosing occasion
 sex  dose (g/kg)  1 10  11 
 m  1.0  0                    
 m  1.26        0    0    0      
 m  1.6      1    1    1    0    
 m 2.0                     1  
 m  2.5    1                  1
 f  1.0  0        0    0        
 f  1.26        1    0    0    1  
 f  1.6      1            1    1
 f 2.0                       
 f  2.5    1                  

Time and number of deaths

 sex  dose (g/kg) No. of deaths                                 Day
       1     2     3     4     5    6 -8
     No. Dosed  0.5 -6 h after dosing  a  b  a  b  a  b  a  b  a  b
 m  1.0  0/1                      
 m  1.26  0/3                      
 m  1.6  3/4        2        1      
 m  2  1/1          1            
m  2.5  2/2        2              
 f  1.0  0/3                      
 f  1.26  2/4      1    1            
 f  1.6  3/3      1  2              
 f  2.5  1/1        1              

a First observation

b Second observation

Interpretation of results:
Category 4 based on GHS criteria
Remarks:
Migrated information
Conclusions:
The acute median lethal oral doses (LD50) and their 95% confidence limits were estimated to be:
Males: 1.7 (1.3 to 2.1) g/kg bodyweight
Females: 1.3 (1.0 to 1.6) g/kq bodyweight
According to these results the substance should be classified as Category IV according to OECD-GHS.
Executive summary:

According to an up-and-down procedure male and female rats were administered a single dose of the undiluted test compound ranging from 1.0 to 2.5 g/kg bw. Clinical signs in all rats after dosing included piloerection, hunched posture and abnormal gait (waddling). These signs were accompanied by lethargy, decreased respiratory rate, ptosis and pallor of the extremities amongst rats at all the dose levels, increased salivation amongst rats dosed at 1.0, 1.26, 1.6 and 2.5 g/kg, and diarrhoea in one female rat treated at 1.26 g/kg and one male at 1.6 g/kg. Recovery of survivors as judged by external appearance and behaviour was apparently complete 5 to 7 days after dosing. Body weight of the survivors was not affected, animals that died had decreased bodyweights. Necropsy findings were normal in survivors; in non-survivors these consisted of congestion of the lungs, and pllaor of the liver, kidneys and spleen. The acute median lethal oral doses (LD50) and their 95% confidence limits were estimated to be 1.7 (1.3 to 2.1) g/kg bw for males, and 1.3 (1.0 to 1.6) g/kq bw for females. According to these results the substance should be classified as Category IV according to OECD-GHS criteria.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
Value:
1 500 mg/kg bw
Quality of whole database:
Adequate for CLP classification and labelling.

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

There are four acute oral toxicity studies available for Ethanol, 2, 2’-iminobis-, N-coco alkyl derives CAS No 61791-31-9. There are three Klimisch 2 studies, the first study Kynock & Chanter 1984, which used the up and down procedure, estimated the acute median dose (LD50) to be 1.7 (1.3-2.1) g/kg/bodyweight for males and 1.3 (1.0-1.6) g/kg/bodyweight for females. The second study Davies and Grummant 1967 in a pre GLP study showed 50% mortality at 2ml/kg (ca. 1.8mg/kg) bodyweight based on a density of 910kg/m3. The third study Hoechst (1979) reported an oral LD50 value in females only of 1720 mg/kg. 

In a fourth study Kynoch 1985, which was Klimisch 4 the LD50 was reported to be 2.1g/kg.

Based on the three Klimisch 2 studies the weight of evidence indicates and LD50 of between 1.3 and 1.8g/kg, ca. 1.5g/kg (1500mg/kg).

There is no data for acute skin toxicity, but due to the corrosive nature of the substance it is not ethical to carry out such an animal study. The corrosive classification of 2, 2’-(C12-18 evennumbered alkyl imino) diethanol CAS No 71786-60-2.and the required risk management measures will minimise the potential for skin contact, so the lack of a dermal LD50 will not affect the safe handling of the substance.

 

2, 2’-(C12-18 evennumbered alkyl imino) diethanol, CAS No 71786-60-2. is a liquid with a low vapour pressure 0.73mPa s at 20ºC, significant exposure to vapours would not be expected at ambient temperatures so the lack of an inhalation LD50 is not considered significant. This test is therefore waived.

 

Based on the viscosity being 150 mPa s at 20ºC and a density of 910kg/m3, the kinematic viscosity would be ca. 165 mm2/s. It is therefore unlikely the kinematic viscosity would be less than 20.5 mm2/s at 40ºC, therefore an aspiration hazard is not expected.

.

Justification for selection of acute toxicity – oral endpoint

Most recent study plus weight of evidence from other Klimisch 2 studies Davies & Grummant 1967 and Hoechst 1979.

Justification for selection of acute toxicity – inhalation endpoint

Due to physical properties of the substnace with its very low vapour pressure, inhalation is not expected at ambient temperatures so the lack of an inhalation LD50 is not considered significant. This test is therefore waived.

Justification for selection of acute toxicity – dermal endpoint

Due to the corrosive properties of the substance to the skin, it is not ethical on animal welfare grounds to carry out an acute dermal toxicty study.  The corrosive classification of 2, 2’-(C12-18 evennumbered alkyl imino) diethanol CAS No 71786-60-2.and the required risk management measures will minimise the potential for  skin contact, so the lack of a dermal LD50 will not affect the safe handling of the substance.

Justification for classification or non-classification

Based on the three Klimisch 2 rated acute oral toxicity studies on Ethanol, 2,2’-iminobis-, N-coco alkyl derives CAS No 61791-31-9, the oral LD50 value of ca, 1500mg/kg is considered correct, this leads to an EU CLP (GHS) classification as category 4 for acute oral toxicity. There is no other data to indicate a need for classification for the other routes of exposure.