Reaction mass of (2S,6S)-2,6-Dimethylmorpholine and (2R,6R)-2,6-Dimethylmorpholine

Endpoint summary

Description of key information

Acute Toxicity:
- oral: LD50: 1270 mg/kg bw (rat);
- inhalation: Inhalation Risk Test: mortality after 3 h exposure to saturated vapor;
- dermal: >= 1000 <= 2000 mg/kg bw  (rat);

Key value for chemical safety assessment

Acute toxicity: via oral route

Endpoint conclusion

Dose descriptor:

LD50

Value:

1 270 mg/kg bw

Acute toxicity: via dermal route

Endpoint conclusion

Dose descriptor:

LD50

Value:

1 000 mg/kg bw

Additional information

Oral:

In a study which was in large parts equivalent to methods described in OECD guideline 401, the LD50 for oral acute toxicity in rats was calculated as 1270 mg/kg body weight (BASF AG, 1981; Val. 2). Doses of 681, 1000, 1470, 2150, 3160 mg/kg bw of a 75% cis / 25% trans-isomer mixture (CAS 6485-55-8) were applied by gavage followed by a post dose observation period of 14 days. In an earlier, similar study a LD50 for oral acute toxicity of 2,6-dimethylmorpholine (CAS 141-91-3) in rats was calculated as 2380 mg/kg body weight (BASF AG, 1975; Val. 2). In both studies the dyspnoea, apathy, staggering, atony, tremor, spastic gait, convulsions, ruffled fur, cyanosis, exsiccosis, salivation and poor general state. At necropsy, dilatation and congestive hyperemia of the heart and haemorrhagic stomachs were observed.  

In a further study with only limited data provided, 2,6-dimethylmorpholine (CAS 141-91-3) caused likewise moderate toxicity after a single ingestion (LD50 = 2830 mg/kg bw; Smyth et al.1962; Val. 2).

 

Inhalation:

Data is available from an inhalation risk test (IRT) which meets generally accepted scientific principles (BASF AG, 1981; Val. 2). The inhalation of a saturated vapor-air mixture (75% cis / 25% trans-isomer mixture; CAS 6485-55-8) for 3 hours caused mortality. Clinical signs were escape attempts, eyelid closure, dyspnea, loss of pain reflex, tremor, irregular gait, ruffled fur.

In a second IRT the inhalation of a saturated vapor-air-mixture or 4000 ppm 2,6-dimethylmorpholine (CAS 141-91-3) for 4 h caused no mortality (Smyth et al. 1962; Val. 2).

 

Dermal:

2,6-dimethylmorpholine as a 75% cis / 25% trans-isomer mixture (CAS 6485-55-8) was applied by to the skin of groups of 3 rats/sex at doses of 1000 mg/kg and 2000 mg/kg bw in a occlusive dressing for 24 hours (BASF AG, 1981; Val. 2). Following treatment, rats were observed daily and a gross necropsy examination was performed at the time of scheduled euthanasia (day 14). All animals in the 2000 mg/kg bw dose died within 48 h and one female died in the 1000 mg/kg bw dose group. As a result an acute dermal LD50: >= 1000 <= 2000 mg/kg bw was determined. Main clinical signs observed were dyspnoea, apathy, staggering, tremor, spastic gait, ruffled fur, diarrhea, cyanosis, exsiccosis, eyelid closure and poor general state. Additionally severe cutaneous reactions (necrosis associated with edema) were noted. At necropsy, dilatation and congestive hyperemia of the heart, haemorrhagic stomachs and grey-colored lobular periphery of the liver were observed.

 

In a further study with only limited data provided, an acute dermal LD50 for 2,6-dimethylmorpholine (CAS 141-91-3) for rabbits of 662 mg/kg bw (710 ml/kg bw) was calculated (Smyth et al.1962; Val. 2).

Justification for classification or non-classification

EU classification according to Annex VI of Directive 67/548/EEC: Xn, R21/22

GHS classification: Acute Toxicity, oral: Cat. 4; acute toxicity, dermal: Cat. 4

The available studies on acute toxicity by inhalation are not fully suitable to assess this route of exposure, but the results suggest a LC 50 value greater than 20 mg/L (= no classification).