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: LD50 > 1000 and < 2000 mg/kg bw  (rat)

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Principles of method if other than guideline:

Internal test method, see details in "Any other information on materials and methods incl. tables"

GLP compliance:

no

Test type:

standard acute method

Limit test:

no

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Weight at study initiation: males: 266 g (mean), females: 200 g (mean)
- Fasting period before study: 16-20 h
- Diet: Herlian MRH-Haltung, ad libitum

Route of administration:

oral: gavage

Vehicle:

water

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 6.81, 10.0, 14.7, 21.5, 31.60 %

Doses:

681, 1000, 1470, 2150, 3160 mg/kg bw

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations: several times on the day of application and daily thereafter
- Frequency of weighing: days 0, 2-4, 7 and 14
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight

Sex:

male/female

Dose descriptor:

LD50

Effect level:

1 270 mg/kg bw

95% CL:

1 035 - 1 551

Mortality:

See details in table in "Any other information on results incl. tables".

Clinical signs:

other: Dyspnoea, apathy, staggering, atony, tremor, spastic gait, convulsions, ruffled fur, cyanosis, exsiccosis, salivation, poor general state

Body weight:

other body weight observations

Remarks:

initially weight loss; see details in table in remarks on results

Gross pathology:

Heart: dilatation (right), congestion hyperemia;
Stomach: strong, diffuse redding, bloody content;
Gut: dark-diffuse redding of mucosa, diarrhoea;

Mortality:

Dose mg/kg bw	Conc. %	Dead animals
3160	31.6	5/5 m, 5/5 f
2150	21.5	5/5 m, 3/5 f
1470	14.7	4/5 m, 4/5 f
1000	10	1/5 m, 2/5 f
681	6.81	0/5 m, 0/5 f

Weight:

Dose (mg/kg bw)	gender	day 0	day 2-4	day 7	day 14
3160	m	290	-	-	-
3160	f	210	-	-	-
2150	m	240	-	-	-
2150	f	180	184	207	223
1470	m	250	235	277	312
1470	f	200	193	215	232
1000	m	260	244	295	328
1000	f	200	199	214	231
681	m	290	309	364	348
681	f	210	224	269	242

Interpretation of results:

Category 4 based on GHS criteria

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

1 270 mg/kg bw

Quality of whole database:

The quality of the whole database is good.

Acute toxicity: via dermal route

Link to relevant study records

Reference

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Principles of method if other than guideline:

Internal test method, see details in "Any other information on materials and methods incl. tables"

GLP compliance:

no

Test type:

standard acute method

Limit test:

no

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Type of coverage:

occlusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Area of exposure: ca. 50 cm2

REMOVAL OF TEST SUBSTANCE
- Washing (if done): water/Lutrol (1:1)
- Time after start of exposure: 24 h

Duration of exposure:

14 days

Doses:

1000, 2000 mg/kg bw

No. of animals per sex per dose:

3

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: several times on the day of application and daily thereafter
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 1 000 - < 2 000 mg/kg bw

Mortality:

see details in table in remarks on results.

Clinical signs:

other:

Body weight:

other body weight observations

Remarks:

no data

Gross pathology:

Animals that died:
Heart: acute dilatation of the ventricle acute congestion;
Stomach: bloody ulcerations;
Liver: grey-colored lobular periphery;

Mortality:

Dose mg/kg	Conc. %	Animal	1 h	24 h	48 h	7 days	14 days
2000	100	3 m 3 f	0/3 0/3	2/3 3/3	3/3 3/3	3/3 3/3	3/3 3/3
1000	100	3 m 3 f	0/3 0/3	0/3 0/3	0/3 1/3	0/3 1/3	0/3 1/3

Interpretation of results:

Category 4 based on GHS criteria

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

> 1 000 - < 2 000 mg/kg bw

Quality of whole database:

The quality of the whole database is good.

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 the test substance 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 the test substance in rats was calculated as 2380 mg/kg bw (BASF AG, 1975; Val. 2). In both studies dyspnoea, apathy, staggering, atony, tremor, spastic gait, convulsions, ruffled fur, cyanosis, exsiccosis, salivation and poor general state of the animals were observed. At necropsy, dilatation and congestive hyperemia of the heart and haemorrhagic stomachs were observed.  

In a further study with only limited data provided, the test substance 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 of the test substance 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 of 4000 ppm of the test substance for 4 h caused no mortality (Smyth et al. 1962; Val. 2).

 

 

Dermal:

The test substance was applied by to the skin of groups of 3 rats/sex at doses of 1000 and 2000 mg/kg bw in an 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 group died within 48 h and one female died in the 1000 mg/kg bw dose group. As a result an acute dermal LD50: > 1000 and < 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 of the test substance 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

Classification, Labelling, and Packaging Regulation (EC) No. 1272/2008

The available experimental test data are reliable and suitable for classification purposes under Regulation 1272/2008. Based on the determined LD50 values in the acute oral and dermal toxicity studies, the substance is classified for acute oral and dermal toxicity Cat. 4 (H302 and H312) under Regulation (EC) No. 1272/2008, as amended for the seventeenth time in Regulation (EC) No. 2021/849.

The available studies on acute toxicity by inhalation are not suitable to assess this route of exposure, but the results suggest a LC 50 value greater than 20 mg/L.