Registration Dossier

Administrative data

Description of key information

The substance is highly corrosive to the skin. Deaths occurred following oral and inhalation exposure. Local effects but no systemic effects or deaths were seen following dermal exposure up to 2000 mg/kg bw.

Key value for chemical safety assessment

Acute toxicity: via oral route

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
184 mg/kg bw
Quality of whole database:
Good and suitable for assessment.

Acute toxicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Quality of whole database:
Low but suitable for assessment. 2 mg/L < LC50 < 200 mg/L

Acute toxicity: via dermal route

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
2 000 mg/kg bw
Quality of whole database:
Suitable for assessment.

Additional information

The pH-value of N,N-dimethylbutylamine is considered to be >11.5 (see also section 4.20 of this dossier). According to OECD 404 (adopted 2002) the test substance is therefore considered to be corrosive to the intact skin and classification is proposed accordingly. In accordance with EC/1907/2006, No. 8.5 column 2, testing of substances that are corrosive to the skin for the acute toxicity endpoints is not needed. However, valid studies exist and can be taken into consideration whereas new studies are not required.

The substance was highly corrosive to the skin in-vivo and produced irreversible skin lesions within 3 minutes, i.e. the consideration based on the pKa value was correct. Outlines of the most valid available acute toxicity studies are given below. It should be noted that only the free base is corrosive, whereas the salt is generally not corrosive and consequently much less toxic. The studies below were all conducted with the free base.

Acute oral toxicity

The acute oral toxicity of N,N-dimethylbutylamine (160, 200, 250, 315 mg/kg bw; suspended in sesame oil) was examined in a guideline study (OECD 401) under GLP conditions. Young Wistar rats (5 per dose and sex) were treated and reactions were observed during the 14-day observation period.

Deaths occurred within 2 hours after dosing. The LD50 was 258 mg/kg bw in males and 184 mg/kg bw in females. A combined LD50 value could not be calculated.Signs of corrosion were seen in the gastro-intestinal tract of victims but not in animals that were sacrificed at the end of the observation period (Markert and Weigand, 1985)

 

Deviations from the test guideline include the use of a vehicle (sesame oil) instead of water. The dose volume varied largely across groups (0.8 to 3.2 mL/kg bw) and exceeded the recommended volume (1.0 mL/kg bw; OECD 401) in the low dose groups. The study is, however, considered to be valid and suitable for assessment, taking the lower LD50 value (184 mg/kg bw) for both male and female rats into consideration.

Acute inhalation toxicity

The acute inhalation toxicity was determined in CD1 rats (5 per sex and dose) in a pre-guideline study without monitoring of the test substance concentration. All rats exposed at 2 mg/L survived until the end of the observation period while all rats exposed to nominal 200 mg/L died within 10 minutes after exposure initiation. Clinical signs indicated irritating effects both in the low dose and the high dose group (ocular and nasal discharge, corneal opacity in surviving animals; lung congestion and lung edema in victims). Thus the (LC50(4 hrs) was between 2 mg/L and 200 mg/l in this study (Wazeter and Goldenthal, 1975).

The study does not allow estimating the LC50-value. However, the described signs of toxicity clearly indicate that the primary mode of action is the irritating and corrosive effect of Dimethylbutylamine. The study is therefore considered to be supportive for assessment.

Acute dermal toxicity

The acute dermal toxicity of N,N-dimethylbutylamine (2000 mg/kg bw; free base) was examined in a rat study (5 male and female Sprague Dawley rats) that was conducted according to OECD 402 and under GLP conditions. There were no deaths or clinical signs of toxicity including body weight in any of the rats within the 14-day observation period. Local skin effects were not reported but must be assumed because of the corrosivity of the free base. Thus the dermal LD50 in the rat was >2000 mg/kg bw in this study (Hewitt and Collier,1985). This study is considered to be valid and suitable for assessment.


Justification for selection of acute toxicity – oral endpoint
GLP guideline study: Lowest LD50 value

Justification for selection of acute toxicity – inhalation endpoint
The substance is corrosive to the skin. Results from a screening inhalation study are also available though a LD50-value was not derived.

Justification for selection of acute toxicity – dermal endpoint
The substance is corrosive to the skin. Local effects but no systemic effects were seen up to 2000 mg/kg bw.

Justification for classification or non-classification

Acute toxicity classification according to EC/1272/2008 and 2nd ATP (EC/286/2011 dated 2011 -03 -10) table 3.1.1 is proposed as follows, based on the effect levels described above.

 

Endpoint

Effect level

Category

according to EC/286/2011,

Table 3.1.1.

Acute oral toxicity

LD50: 184 mg/kg bw

3

Acute inhalation toxicity

LC50: 2 mg/L < LC50 < 200 mg/L

3 (vapour)

EU071: corrosion to the respiratory tract

Acute dermal toxicity

LD50 > 2000 mg/kg bw

No classification