Registration Dossier

Administrative data

Description of key information

No acute oral toxicity studies are available for the substance but for the read across source substance there are three acute oral toxicity studies, of which two are validity 2, the other being only supportive data.  In the study considered most relevant to the classification of this substnace the LD50 values (plus 95% confidence limits) were 1500 (1100-2000) mg/kg bw for males, and 1200 (900-1600) mg/kg bw for females. Based on a mean vlaue 1350mg/kg will be used for classification etc.

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 from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Study period:
January-February 1984
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Basic data given; comparable to guidelines/standards
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 425 (Acute Oral Toxicity: Up-and-Down Procedure)
Principles of method if other than guideline:
At the time of performance, OECD 425 was not available.
GLP compliance:
yes
Remarks:
in house quality system
Test type:
up-and-down procedure
Species:
rat
Strain:
other: HC/HFY (remote Sprague-Dawley)
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Hacking and Churchill Ltd., Huntingdon, UK
- Age at study initiation: ca. 4-6 weeks
- Weight at study initiation: 81-132 g
- Fasting period before study: overnight prior to dosing until ca. 4 hours after dosing
- Housing: individually in metal cages with wire mesh floors
- Diet (e.g. ad libitum): ad lib
- Water (e.g. ad libitum): ad lib
- Acclimation period: at least 5 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21-23
- Humidity (%): mean 42
- Air changes (per hr): ca. 15
- Photoperiod (hrs dark / hrs light): 12/12


IN-LIFE DATES: From: 10 January To: 13 February 1984
Route of administration:
oral: gavage
Vehicle:
CMC (carboxymethyl cellulose)
Details on oral exposure:
VEHICLE: methyl celluose (1%)
- Concentration in vehicle: various concentrations in vehicle to obtain dose volumes of 10.0 ml/kg


MAXIMUM DOSE VOLUME APPLIED: 10.0 ml/kg bw

Doses:
800, 1000, 1260, 1600, 2000, 2500, 4000, 5000 mg/kg bw
No. of animals per sex per dose:
1 at each dose level in time (11 males and 12 females in total)
Control animals:
no
Details on study design:
- Duration of observation period following administration: 7 days
- Frequency of observations and weighing:soon after dosing, frequently on the remainder of the day of dosing. At least twice per
day thereafter. BW were monitored on day 0 and day and at death.
- Necropsy of survivors performed: yes
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 derived by adding and subtracting 1.96 times the standard
error of the (log.) LD50 estimate.
Sex:
male
Dose descriptor:
LD50
Effect level:
1 500 mg/kg bw
95% CL:
1 100 - 2 000
Sex:
female
Dose descriptor:
LD50
Effect level:
1 200 mg/kg bw
95% CL:
900 - 1 600
Mortality:
Deaths occurred amongst rats treated at 1.26 g/kg and above from within two and three days of dosing. Autopsy revealed
haemorrhage or congestion of the lungs in the majority of animals. These findings were usually accompanied by pallor of the liver,
kidneys and spleen. Congestion of the blood vessels of the stomach was observed in one female rat treated at 1.6 g/kg and
congestion of the blood vessels of the intestine in one female rat treated at 5.0 g/kg. All rats that died showed a bodyweight loss.
Clinical signs:
Signs of reaction to treatment observed shortly after dosing in all rats included pilo-erection and abnormal body carriage (hunched
posture). Abnormal gait (waddling), lethargy and pallor of the extremities were observed in the majority of rats in all treatment
groups. Incidences of ptosis, diarrhoea and increased salivation were seen at dose levels of 1.0 g/kg and above. These signs
were accompanied by a decreased respiratory rate in rats dosed at 1.26 g/kg and above. One female rat treated at 2.0 g/kg had an abnormal gait (walking on toes). In the surviving animals, recovery as judged by external appearance and behaviour, was
apparently complete by Day 5 to 8. Pilo-erection was still observed in one male rat dosed at 1.26 g/kg and one female rat dosed at
1.0 g/kg on Day 8. This finding was not considered to be of toxicological importance and the observation period was not
extended.
Body weight:
No abnormalities in BW gain in surviving rats.
Gross pathology:
Necropsy findings in survivors were normal.
Other findings:
No data.

Mortality data

Sex

Dose (mg/kg)

Mortality data on each occasion

No. of deaths

1

2

3

4

5

6

7

8

9

10

11

12

M

1000

0

0

0/2

1260

0

0

0

0/3

1600

1

1

2/2

2000

1

1/1

2500

1

1/1

4000

1

1/1

5000

1

1/1

F

800

0

0/1

1000

0

0

0

0/3

1260

1

1/1

1600

1

1

2/2

2000

1

1

2/2

2500

1

1/1

4000

1

1/1

5000

1

1/1

0 = animal survived; 1 animal died

Interpretation of results:
Category 4 based on GHS criteria
Remarks:
Migrated information
Conclusions:
The LD50 values (plus 95% confidence limits) were 1500 (1100-2000) mg/kg bw for males, and 1200 (900-1600) mg/kg bw for
females. The test compound was therefore classified in Category IV according to OECD-GHS.
Executive summary:

The study was performed to assess the acute toxicity of the test material following a single oral administration to the HC/CFY (remote Sprague-Dawley) strain rat. The study was performed equivalent to OECD 425. A group of 11 fasted males and 12 fasted female was given a single, oral dose of the test material at dose levels between 800 and 5000 mg/kg bodyweight. The animals were observed for 7 days after the day of dosing and were then killed for gross pathological examination. Deaths were observed at levels 1260 mg/kg bw and higher. Clinical signs of toxicity noted were pilo-erection, hunched posture, abnormal gait, lethargy, pallor of the extremities, ptosis, diarrhoea, increased salivation, and decreased respiratory rate. Recovery was apparently complete by day 5 -8 (day 1 is day of dosing). All surviving animals showed expected gains in bodyweight over the study period. No abnormalities were noted in survivors at necropsy. Non-survivors generally showed haemorrhage or congestion of the lungs, and pallor of the liver, kidneys and spleen. The acute median lethal dose (LD50) of the test material (with 95% confidence limits) was found to be 1500 (1100 -2000) mg/kg bw in males, and 1200 (900 -1600) mg/kg bw in females. The test compound was therefore classified in Category IV according to OECD-GHS.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
1 350 mg/kg bw
Quality of whole database:
Sufficient.

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 is no acute oral toxicity data for Propanol, iminobis-, N-C16-C18 (evennumbered), C18 unsatd. alkyl) derivs. CAS No 1309955 -79 -0. There are three studies available that have derived oral LD50 values for the read across source substance Ethanol, 2,2’-iminobis-, N-tallow alkyl derives CAS No 61791-44-4 registered under 2,2’-(C16-18 (evennumbered, C18 unsaturated) alkyl imino) diethanol CAS 1218787-32-6. None of the studies are of validity 1. Two of the studies are validity 2, and these form the basis of the acute oral LD50 for this substance. The most recent study was a CESIO study carried out in 1991 to OECD401, in this study Ethanol, 2,2’-iminobis-, N-tallow alkyl derives CAS No 61791-44-4, was tested up to 2000mg/kg and no deaths were seen at this level. The vehicle in this study was arachis oil. In an older study carried out in 1984 to OECD Guideline 425 on Ethanol, 2,2’-iminobis-, N-tallow alkyl derives CAS No 61791-44-4 dose levels up to 5000 mg/kg were tested. This study showed a much higher levels of toxicity, The LD50 values (plus 95% confidence limits) were 1500 (1100-2000) mg/kg bw for males, and 1200 (900-1600) mg/kg bw for females. This may be explained by the use of the aqueous vehicle carboxymethyl cellulose at 1% in water compared to arachis oil used in the 1991 study.  As there was clear lethality in this validity 2 study, this will be used as the basis for the classification etc. The Ethanol, 2, 2’-iminobis-, N-tallow alkyl derives was therefore classified in Category IV according to OECD-GHS.

 

There is a third study carried out in 1988 to an OECD 401 protocol, however this was testing of a polypropylene powder with 60% of the Ethanol, 2,2’-iminobis-, N-tallow alkyl derives using an aqueous vehicle with 0.5% carboxymethyl cellulose. In this study the LD50 was greater than the 2000mg/kg dose level used where no toxic effects were seen. It is not possible to know what impact the polypropylene powder had on this result other than reducing the exposure to the Ethanol, 2, 2’-iminobis-, N-tallow alkyl derives. This study was therefore not considered suitable for classification etc. purposes.

 

Justification for selection of acute toxicity – oral endpoint

Most relevant read across study.

Justification for classification or non-classification

There is no acute oral toxicty data for Propanol, iminobis-, N-C16-C18 (evennumbered), C18 unsatd. alkyl) derivs but there is data for the read across substance. There was clear lethality in a validity 2 study this will be used as the basis for the classification etc. The Ethanol, 2, 2’-iminobis-, N-tallow alkyl derives was therefore classified in Category IV according to OECD-GHS. The lack of toxicity in the other validity 2 study may have been due to the use or arachis oil rather than a aqueous vehicle so it is considered appropriate to use the study showing the lethality. Based on this read across Propanol, iminobis-, N-C16-C18 (evennumbered), C18 unsatd. alkyl) derivs will be classified as Category IV according to OECD-GHS.

There is no dermal LD 50 value for Propanol, iminobis-, N-C16-C18 (evennumbered), C18 unsatd. alkyl) derivs. also there is no data for the read across substnace Ethanol, 2, 2’-iminobis-, N-tallow alkyl derives CAS No 61791-44-4 but due to the corrosive nature of the substance it is not ethical to carry out this animal study. The corrosive classification of the Propanol, iminobis-, N-C16-C18 (evennumbered), C18 unsatd. alkyl) derivs

based on Ethanol, 2, 2’-iminobis-, N-tallow alkyl derives 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

We also have no inhalation LC50 data for Propanol, iminobis-, N-C16-C18 (evennumbered), C18 unsatd. alkyl) derivs. or for the read across source substance Ethanol, 2,2’-iminobis-, N-tallow alkyl derives CAS No 61791-44-4, however it is a paste with a low vapour pressure 0.73 mPa at 20ºC (1.2 mPa at 25ºC), 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.

Due to the physical form of the Propanol, iminobis-, N-C16-C18 (evennumbered), C18 unsatd. alkyl) derivs. being a solid/paste at ambient temperature, the is no aspiration hazard for this substance.