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Description of key information

The substance is a classified skin corrosive (Cat 1A), and acute toxicity testing is not required according to REACH, Annex VII, No. 8.5.1, column 2.
LD50-values: oral, rat: 385 mg/kg bw; inhalation, rat, 4-hr: 5.3 mg/L; dermal, rabbit: >200 mg/kg bw

Key value for chemical safety assessment

Acute toxicity: via oral route

Endpoint conclusion
Dose descriptor:
LD50
Value:
385 mg/kg bw

Acute toxicity: via inhalation route

Endpoint conclusion
Dose descriptor:
LC50
Value:
5.3 mg/m³

Acute toxicity: via dermal route

Endpoint conclusion
Dose descriptor:
LD50
Value:
200 mg/kg bw

Additional information

The substance is highly corrosive. It is a classified skin corrosive (Cat 1A), and acute toxicity testing is not required according to REACH, Annex VII, No. 8.5.1, column 2. Existing studies are discussed below.

Oral

The oral LD50was 385 mg/kg bw in the rat when Butylethylamine was administered as an aqueous solution (containing 2 and 8% of the test substance) by oral gavage to rats. Clinical signs included dyspnea, atony, apathy, and convulsions. Necropsy revealed hyperaemia of the stomach and diarrhea (BASF AG, 1972).

In a study that was comparable to OECD TG 401, butylethylamine was administered as such in range finding studies and dissolved in arachis oil a(at 500 mg/ml) to male and female rats (Sprague Dawley, 5 per sex and dose in the main study). The observation period was 14 days. With the neat test material deaths occurred at all dose levels. Dissolved in arachis oil, the LD50was 23.5 mg/kg (Safepharm, 1980).

The acute oral toxicity of Ethylbutylamine was examined in rats (5/sex and dose; dose levels 200, 271, 368, 500, and 679 mg/kg bw. Test material was administered as an emulsion (50% in arachis oil) by oral gavage. The study was conducted similar to OECD TG 401 and under GLP conditions. The purity of the test material was not reported. Mortalities occurred within one day after dosing in groups at 368 mg/kg bw and above. The LD50was 467 mg/kg bw in this study (Safepharm, 1982).

A similar result was obtained in another study where the test substance was administered in arachis oil. The acute oral toxicity of Butylethylamine (200, 317. 504, 800 mg/kg bw, based on preliminary study) was examined in male and female Wistar rats in a study that was conducted similar to the OECD TG 401 (5 rats/sex and dose; observation period 14 days) and under GLP. The tests substance was dissolved in arachis oil at concentration of 500 mg/mL. Deaths occurred in groups receiving 504 and 800 mg/kg bw on the day of treatment. The combined LD50was 600 (95% c.i. 500-720) mg/kg bw. Clinical signs observed included hunched posture, lethargy, piloerection, ptosis, decreased respiration rate, and at the higher doses, additionally convulsions, ataxia, gasping respiration, tremor, pallor of extremities. Survivors showed apparently normal appearance after day 4 and day 14, apart from the one survivor at dose 800 mg/kg bw (Safepharm, 1982).

To summarise, corrosivity was seen in experimental studies as expected. The LD50values cover a wide range from 23.5, 467 and 600 mg/kg when the substance was suspended in oil (concentration 50%) or in water (LD50= 385 mg/kg; concentration 2% and 8%). The toxicity is obviously governed by the corrosivity of the substance, not by any systemic toxicity. This is also supported by the located necropsy findings. Information on the test substance purity was not provided in any of the studies. Differences in test substance purity possibly contribute to the observed wide range of LD50values. Given the fact that the LD50 in 3 studies is comparable it is assumed that the lowest LD50is an outlier, and that the LD50of the diluted test material is considered to be > 385 mg/kg bw.

Inhalation

10 male and female Wistar rats were exposed (head-nose only) to Butylethylamine for 1 hour at analytical concentrations of 2.45 to 11.87 mg/L. All females survived whereas male mortality increased with dose up to 80% at the top dose. The LC50, 1hrwas 10.6 mg/L for the male rat (BASF, 1979). The study may be used for assessment using the LC50 (1hr)-value for male rats. There is no explanation why no deaths occurred in females.

The LC50 (1hr)of 10.6 mg/L can be transformed into a LC50 (4hr)of 5.3 mg/L, by using a factor of 0.5, according to the regulation 1272/2008/EC, section 3.1.2.1 b).

Dermal

The acute dermal toxicity of butylethylamine was tested in a limit dose study that was designed to meet the DOT regulation. Five male and female rabbits received 200 mg/kg bw on the shaved intact skin (occlusive, 24 hr) and were observed for 8 days. There were no clinical signs of toxicity or deaths. Local skin irritation was seen, along with full thickness necrosis at day 8 after treatment. Thus, the dermal LD50was >200 mg/kg bw in this study (BASF, 1979).

 

 

Justification for classification or non-classification

Classification according to the regulation 1272/2008/EC is suggested as follows:

 

Acute oral toxicity Cat 4. Basis: 385 mg/kg bw

Acute inhalation toxicity Cat 4: Basis: 5.3 mg/L