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Administrative data

Description of key information

Oral
In a study similar to OECD guideline 401, MPMD was administered via oral gavage to 10 male CD rats per dose group. The LD 50 value was calculated to be 1690 mg/kg bw. Clinical signs included salivation, lung noise, diarrhea and stained perineum.
In 2 studies similar to OECD guideline 401, DCH was administered via oral gavage to male and female rats. The LD 50 value was calculated to be 1170 mg/kg bw in the one and 2200 mg/kg bw in the other study.
Using HMD as test material in a reliable study resulted in a LD50 = 1160 mg/kg bw in rats.
Inhalation:
In a reliable study (Klimisch 2) male and female rats were subjected to a 1 hour inhalation exposure to aerosol/vapour mixture with various MPMD concentrations. Clinical signs of toxicity could be found in all dose groups in different severity. Mortality was observed once during the exposure and more often within the 14 day observation period. Under the conditions of this test, the one-hour LC50 of the test material was 4.9 mg/L for male and female rats (95% CI 3.1 to 7.2 mg/L).
In another study five groups of either 10 or 6 male Crl:CD*BR rats were exposed, nose-only, to atmospheres of DCH with different purities for a single 4-hour period. Mixed aerosol/vapour test atmospheres were generated by vaporising the liquid and were characterised by gas chromatography and particle size analysis. Mean total DCH concentration ranged from 3.09 to 4.73 mg/L in the 5 separate experiments. Under the conditions of this test, no 4-hour median lethal dose could be determined. A LClo was found to be 3.2 mg/l using 98% pure DCH as test material.
Dermal
In a study similar to OECD guideline 402, DCH was administered under occlusive conditions for 24 h to the skin of 5 male and 5 female Sprague-Dawley rats per dose group.The LD 50 value was calculated to be to be 1870 mg/kg bw.
In a reliable study conducted with HMD the rat LD50 was identified to be 1900 mg/kg bw.

Key value for chemical safety assessment

Acute toxicity: via oral route

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
Value:
1 170 mg/kg bw
Quality of whole database:
Various studies for two different members of the amine heads category, which present comparable results. The quality of the datbase is therefor high.

Acute toxicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LC50
Value:
1 230 mg/m³
Quality of whole database:
One study for each of two different members of the amine heads category, which present comparable results. The quality of the datbase is therefor high.

Acute toxicity: via dermal route

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
Value:
1 870 mg/kg bw
Quality of whole database:
One study for each of two different members of the amine heads category, which present comparable results. The quality of the datbase is therefor high.

Additional information

There are reliable studies for acute oral toxicity for all category members, i.e. DCH, MPMD as well as HMD. In studies conducted similar to OECD 401 LD50 values in the range of approx. 1170 to 2200 mg/kg bw for all test materials were observed.

Considering acute toxicity after inhalation exposure there is one reliable study for MPMD which can be used for classification. The LC50 value estimated after 1 hour aerosol/vapour exposure was 4.9 mg/L for male and female rats. According to Regulation (EC) No 1272/2008 Annex I section 3.1.2.1.c this value has to be divided by 4 in order to receive a proper value for classification purposes. Thus in the end a LC50 value of 1.23 mg/L has to be used for classification.

For acute dermal toxicity, taking the data from reliable studies in DCH and MPMD the LD50 values presented range in between 1870 and 1900 mg/kg bw.

No specific toxic effects were observed after acute oral, inhalative or dermal exposure indicative of a specific target organ toxicity (remark: red nasal and ocular discharges after inhalational exposure was not used as effect leading to STOT classification, because it is a clinical sign that is common for rats under restraint. This is also obvious in the 14 -day inhalation studies presented for DCH and MPMD were these clinical signs could also be observed in the restraint rats of the control group. However apart from rather systemic effects only local irritating effects were observed after repeated inhalation exposure to the members of the amine heads category (see respective section for further details). And the local effects observed are clearly due to the corrosivity of the substances. Based on this fact the classification STOT – single exposure category 3 is proposed.).


Justification for selection of acute toxicity – oral endpoint
reliable study (Klimisch 1)

Justification for selection of acute toxicity – inhalation endpoint
reliable study (Klimisch 2)

Justification for selection of acute toxicity – dermal endpoint
reliable study (Klimisch 1)

Justification for classification or non-classification

Based on the LD and LC values presented above the amines of this category have to be classified for acute oral, dermal and inhalative toxicity according to Regulation (EC) No 1272/2008 (i. e. category 4 for each route of exposure) and Council Directive 67/548/EEC (i. e. R20/21/22). Furthermore, the members of the amine heads category are going to be classified for specific target organ toxicity – single exposure category 3 according to Regulation (EC) No 1272/2008. This characteristic is also reflected in classification as irritating to the respiratory tract according to Council Directive 67/548/EEC (i.e. R37).