N-ethylpropylamine

Endpoint summary

Description of key information

- oral: LD50 496 mg/kg bw (rat; BASF AG 1980)
- inhalation risk test: 100% mortality within or very shortly after a 3 min exposure(rat; BASF AG 1980, sat. vapour conc. app. 300mg/L) 
- dermal: LD50 > 200 mg/kg bw (rabbit; BASF AG 1980); 

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

Qualifier:

no guideline followed

Principles of method if other than guideline:

Male and female rats were treated by single gavage application with the test substance (solved in 0.5% CMC). The animals were observed for mortality and for clinical symptoms of toxicity. At the end of the observation period of 14 days, the surviving animals were sacrificed for the purpose of necropsy; animals that died during the observations period also were subjected to necropsy. The LD50 value was estimated on the basis of the observed mortalities.

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: 147 g (mean), females: 133 g (mean).
- Fasting period before study: 16 h.
- Housing: Makrolon Typ III (max. 5 animals per cage).
- Diet: standard pellet-feed ad libitum.
- Water: ad libitum.
- Acclimation period: 3 - 7 days.


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21- 23 °C
- Humidity (%): 50 - 70 %
- Photoperiod (hrs dark / hrs light): 12/12

Route of administration:

oral: gavage

Vehicle:

other: 0.5% CMC (carboxymethyl cellulose) aqueous solution

Details on oral exposure:

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg bw

Doses:

237, 348, 511, 750, 2370, 7500 mg/kg bw

No. of animals per sex per dose:

5 female animals (237, 2370, 7500 mg/kg bw); 5 male and 5 female animals (348, 511, 750 mg/kg bw)

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: daily
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight

Statistics:

Probit-analysis according to Finney

Sex:

male/female

Dose descriptor:

LD50

Effect level:

496 mg/kg bw

Based on:

test mat.

95% CL:

>= 456 - <= 540

Remarks on result:

other: Mortality and different clinical signs (inclusive local effects) occurred;

Mortality:

237 and 348 mg/kg bw: No mortality occurred.
511 mg/kg bw: 2 males and 2 females died within 24 h and a further animal each within 7 days.
750 mg/kg bw: All animals died within 24 h.
2370 mg/kg bw (females only): 1 female died within 1 h and all other female animals died within 24 h.
7500 mg/kg bw (females only): 4 females died within 1 h and the other female animal died within 24 h.

Clinical signs:

other: From 348 mg/kg bw onwards: apathy, ataxia and reduced pain reactions. 511, 750 and 2370 mg/kg bw: 2 h post application: catalepsia (until > 5 h and < 24 h) 7500 mg/kg bw: immediately post application: tonic-clonic convulsions. Sporadic breathing difficul

Gross pathology:

511 and 750 mg/kg bw: stomach filled with yellow-reddish liquid. Stomach mucosa reddened or peeled off, partially blood in stomach and bowel.
2370 and 7500 mg/kg bw: Stomach and overlaying organs appear to be fixated, partially dark red lungs.

Sacrificed animals: No abnormalities.

Mortality:

Dose (mg/kg bw)	gender	dead within 1h	dead within 1 day	dead within 2 days	dead within 7 days	dead within 14 days
237	male	-	-	-	-	-
237	female	0/5	0/5	0/5	0/5	0/5
348	male	0/5	0/5	0/5	0/5	0/5
348	female	0/5	0/5	0/5	0/5	0/5
511	male	0/5	2/5	2/5	3/5	3/5
511	female	0/5	2/5	2/5	3/5	3/5
750	male	0/	5/5	5/5	5/5	5/5
750	female	0/5	5/5	5/5	5/5	5/5
2370	male	-	-	-	-	-
2370	female	1/5	5/5	5/5	5/5	5/5
7500	male	-	-	-	-	-
7500	female	4/5	5/5	5/5	5/5	5/5

Interpretation of results:

Category 4 based on GHS criteria

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

496 mg/kg bw

Quality of whole database:

Available data is reliable and sufficient for assessment.

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Endpoint:

acute toxicity: inhalation

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

Qualifier:

no guideline followed

Principles of method if other than guideline:

BASF-Test:
In principle similar to H.F. Smyth et al., Am. Ind. Hyg. Ass. J. 23, 95 - 107, 1962:
The test demonstrates the toxicity of an atmosphere saturated with vapours of the volatile components of a test substance at the temperature chosen for vapour generation (20 °C). 6 rats per sex were exposed sequentially to the vapours, generated by bubbling 200 L/h air through a substance column of about 5 cm above a fritted glass disc in a glass cylinder for 3 min.

GLP compliance:

no

Test type:

standard acute method

Limit test:

yes

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: 221 g (mean), females: 193 g (mean)

Route of administration:

inhalation: vapour

Type of inhalation exposure:

not specified

Vehicle:

air

Analytical verification of test atmosphere concentrations:

no

Duration of exposure:

3 min

Concentrations:

375 mg/L (saturated vapour)

No. of animals per sex per dose:

6

Control animals:

no

Details on study design:

- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs

Sex:

male/female

Dose descriptor:

LC100

Effect level:

375 mg/L air (nominal)

Based on:

test mat.

Exp. duration:

3 min

Mortality:

4/12 animals died during the exposure period. 5/12 animals at the end of the exposure and 2 animals 3-4 min post exposure. 1 animal died 2 days post exposure.

Clinical signs:

other: Immediately heavy escape attempts, eyelids closed, wattery and reddish nose discharge, no pain reflex, dyspnoea, bloody nose discharge, cyanosis, corroded noses, apathy, ventral position, corneal opacity, gasping; At the end of exposure squeaking respirat

Body weight:

no data

Gross pathology:

Heart: dilatation, congestion
Lung: acute swelling, distinct pulmonary emphysema

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

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

Qualifier:

no guideline followed

Principles of method if other than guideline:

A test group consisting of 5 animals/sex was treated by single dermal application of the test substance. No more than 16 hours prior to the dermal applications, the backs of the rabbits were shaved free of hair with electric clippers. On the testing day, the dermal applications (200 mg/kg bw) of the test material were made in undiluted form on the exposure sites (ca. 50 cm²) of the rabbits. After application, the exposure site was covered by wrapping the trunk of the animal with an parchment paper which was securely taped in place. The test material remained in contact with the skin for 24 hours. Observations for mortality, local reactions, and behavioral abnormalities were continued for a total of 5 days following the skin applications.

GLP compliance:

no

Test type:

standard acute method

Limit test:

yes

Species:

rabbit

Strain:

not specified

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Weight at study initiation: 2-3 kg
- Housing: individually
- Diet: Standard-pellet feed for rabbits ad libitum
- Water: tap water ad libitum
- Acclimation period: > 7 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 2 °C
- Humidity (%): 55 ± 10 %
- Photoperiod (hrs dark / hrs light): 12/12

Type of coverage:

occlusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Area of exposure: 7 x 7 cm = ca. 50 cm²
- Type of wrap if used: The exposure site was covered by wrapping the trunk of the animal with a parchment paper which was securely taped in place (Gazofix, No. 2938, Beiersdorf)

Duration of exposure:

24 h

Doses:

200 mg/kg bw

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

- Duration of observation period following administration: 5 days
- Frequency of observations: 1 h, 24 h, 48 h, 72 h
- Necropsy of survivors performed: no
- Other examinations performed: clinical signs

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 200 mg/kg bw

Based on:

test mat.

Remarks on result:

other: No mortality observed. Exposed area was leathery, coarse, dry and heavy scabbed with a dark red to black colour (5 days post-application).

Mortality:

No mortality occurred.

Clinical signs:

other: 5 days post application the exposed area is leathery, coarse, dry and heavy scabbed with a dark red to black colour.

Gross pathology:

not performed

Endpoint conclusion

Dose descriptor:

discriminating dose

Value:

200 mg/kg bw

Additional information

Oral:

In an acute oral toxicity study (BASF AG 1977a; reliability score 2) groups of fasted Sprague-Dawley rats (5 female animals in all dose groups; additionally: 5 male dose groups in three dose groups) were given a single oral dose of the test substance in a 0.5% aqueous CMC (carboxymethyl cellulose) solution at doses of 237, 348, 511, 750, 2370 and 7500 mg/kg bw and observed for 14 days.

Oral LD₅₀Combined = 496 mg/kg bw (95% C.I.: 456 - 540 mg/kg bw)

 

Main clinical signs observed were apathy, ataxia and reduced pain reactions, catalepsia, tonic-clonic convulsions. Three days post application animals were considered as normal. At necropsy, partially blood filled and reddened stomachs and bowels were observed.

 

Inhalation:

 

Data were available from inhalation risk tests (IRT) which meets generally accepted scientific principles.

The inhalation of a saturated vapor-air mixture (375 mg/L; nominal) caused mortality during an exposure periods of 3 min and after exposure. All 12 Sprague-Dawley rats (6 males and 6 females) were dead within 2 days after exposure. Symptoms described included signs of irritation of the mucous membranes, dyspnoea, cyanosis, opacity. Post mortems showed dilatation of the right heart ventricle, general congestion and pulmonary emphysema (BASF AG 1979; reliability score 2).

The inhalation of a saturated vapor-air mixture in another IRT (435 mg/L; nominal) caused mortality in all 12 Sprague-Dawley rats (6 males and 6 females) within 20 min of exposure. Immediately after beginning of exposure defending moves, turns in the glass cylinders, gasping, lacrimation and bloody snouts were seen. The gross pathological observation showed indurated, deep red noses (BASF AG 1977; reliability score 2).

These studies show that exposure of highly saturated vapour-air mixtures represents a severe hazard.

 

 

Dermal:

 

In an acute dermal toxicity study (BASF AG 1978; reliability score 2) groups of rabbits (5/sex) were dermally exposed to the test substance (without vehicle) for 24 h at a dose of 200 mg/kg bw. Animals then were observed for 5 days. No mortality and systemic toxicity was observed at this dose. There is indication that the test substance causes local irritation.

Dermal LD₅₀Combined > 200 mg/kg bw

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.

Due to the LD50 value for acute oral toxicity of 496 mg/kg bw/day (male and female rats, the substance is classified for acute oral toxicity Cat. 4 according to Regulation (EC) No.1272/2008, as amended for the fifteenth time in Regulation (EC) No. 2020/1182.

Data on acute inhalation toxicity are insufficient for classification but indicate a health hazard after inhalation. 100% mortality were observed within or very shortly after a 3 min exposure in an inhalation risk test with a saturated vapour of the test substance of approximately 300mg/L. Until further information becomes available, the classification based on structurally related and similarly corrosive secondary amines is retained. Based on the data for Diethylamine (CAS 109-89-7), Dipropylamine (CAS 142-84-7), and Dibutylamine (CAS 111-92-2), the registered substance is classification according to the Regulation (EC) No.1272/2008 for acute inhalation toxicity Cat. 4 according to Regulation (EC) No.1272/2008, as amended for the fifteenth time in Regulation (EC) No. 2020/1182.

No mortality was observed after dermal exposure to 200mg/kg. Due to the corrosive properties of the substance, no further studies are justified. Consequently, the test substance is not classified for acute dermal toxicity under Regulation (EC) No. 1272/2008, as amended for the fifteenth time in Regulation (EC) No. 2020/1182.