Registration Dossier

Administrative data

Description of key information

The acute oral toxicity of the registration substance, 2,2'-(C12-14 evennumbered alkyl imino) diethanol, is derived based on the read-across approach. The LD50 for oral routes is estimated to be 1500 mg/kg bw, which corresponds to the EU CLP (GHS) classification as category 4 for acute oral toxicity. 

Key value for chemical safety assessment

Acute toxicity: via oral route

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

Assessment of the acute oral toxicity

The acute oral toxicity of the registration substance is derived based on the read-acrosss approach.

There are four studies on read-across supporting substance CAS 71786 -60 -2. The obtained results are consistently indicative that the LD50 for the registration substance is likely to be in the range of 1500 mg/kg bw.

- 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.

- Male and female rats (2 -6 per group) were administered a single dose of the test substance by gavage ranging from 0 to 10 ml/kg bw. The test compound was prepared as a graded series of concentrations in corn oil, so that a constant dosage volume of 10 ml/kg was administered. The animals were observed for two weeks and bodyweights were determined weekly. Gross necropsy was performed on all animals. At doses of 2.0 ml/kg and higher animals died. Non-specific signs of reaction consisted of varying degrees of lethargy accompanied by pilo-erection and perspiration. Later especially at the higher dosage levels, increased salivation, lachrymation and nasal discharge, diuresis, diarrhoea and dyspnoea were observed. Death was preceded by hypothermia, tremors, ataxy and coma, and generally occurred within 1 - 2 days after dosing. Survivors recovered within 4 days; body weight gain was low in the first week and normal during the second week of observation. There was no apparent difference in susceptibility between the sexes. Autopsy of survivors revealed no treatment related effects; autopsy of rats that died revealed inflammation, with occasional haemorrhage, of the lungs and alimentary tract and areas of discolouration in the liver.

The LD50 is beween 1.0 and 5.0 ml/kg. As no mortality was observed at 1.0 ml/kg bw, 50% of the animals died at 2.0 ml/kg bw, and 100% at 3.2 ml/kg bw, the LD50 value is most probably (slightly) lower than 2000 mg/kg bw.

- 3 groups of ten fasted rats each (five males and five females per group) were given a single, oral dose of the test material at dose levels of 1.6, 2.5 or 4.0 g/kg bw. The animals were observed for 14 days after the day of dosing and were then killed for gross pathological examination. Deaths occurred at 1.6 g/kg bw and above. Clinical signs of toxicity noted were pilo-erection, hunched posture, increased salivation, abnormal gait, lethargy, pallor of the extremities, decreased respiratory rate, ptosis, and diarrhoea. Recovery was apparently complete bay day 4 (1.6 g/kg bw) or day 11 (2.5 g/kg bw). Low bodweight gains were recorded on Day 8 amongst female rats at 1.6 and 2.5 g/kg; normal bodyweight gains were recorded for these rats on Day 15. Bodyweight gains were recorded for all other surviving rats on Days 8 and 15. No abnormalities were noted at necropsy in survivors; deceased animals showed congestion of the lungs and pallor of the spleen and kidneys. The acute median lethal dose (LD50) was found to be 2.1 (1.7 -2.5) g/kg bw for males and females combined. For males only: 2.0 (1.6 -2.5) g/kg bw, for females only: 2.2 (1.7 -2.8) g/kg bw.

-Ten female rats per dose group were treated at doses of 1000, 3000 and 5000 mg/kg bw. All rats treated at 5000 mg/kg bw, nine rats at 3000 mg/kg bw and one rat at 1000 mg/kg bw did not survive the treatment. The LD50 of 1720 mg/kg bw was obtained.


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 classification or non-classification

The acute oral toxicity of the registration substance, 2,2'-(C12-14 evennumbered alkyl imino) diethanol, is derived based on the read-across approach. The LD50 for oral routes is estimated to be 1500 mg/kg bw, which corresponds to the EU CLP (GHS) classification as category 4 for acute oral toxicity.