N-(2-aminoethyl)-1,3-propanediamine

Endpoint summary

Description of key information

Oral LD50 (rat) = 654 mg/kg b.w. (BASF 1977, similar to OECD 401)
Dermal LD50 (rabbit) = 184 mg/kg b.w. (BASF 1977, similar to OECD 402)

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

Study period:

1976 - 1977

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Meets generally accepted scientific standards, well documented and acceptable for assessment

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

not specified

Principles of method if other than guideline:

Method: BASF-Test, see details in the section "Any other information on materials and methods incl. tables".

GLP compliance:

no

Remarks:

study was performed prior to GLP

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: male: 196 g (mean); female: 166 g (mean)

Route of administration:

oral: gavage

Vehicle:

water

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 4.64 % - 46.4 % in aqua. dest

Doses:

4640, 1470, 1000, 681, 464 µL/kg bw (corresponding to 426.9, 626.5, 920.0, 1352.4 and 4268.8 mg/kg bw, calculated assuming test substance density of 0.92 g/mL)

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, histopathology

Statistics:

Not indicated.

Preliminary study:

Probit analysis

Sex:

male/female

Dose descriptor:

LD50

Effect level:

654 mg/kg bw

Based on:

test mat.

Remarks on result:

other: Calculated from 0.7 mL/kg assuming a test substance density of 0.92 g/mL

Mortality:

All animals of the lowest dose group (426.9 mg/kg bw) survived (males: 0/5; females: 0/5). In the following dose group (626.5 mg/kg bw) no male animals died (0/5), but female animals (4/5). In higher dose groups (920.0 and 1352.4 mg/kg bw) mortality was also observed (males: 4/5 and 5/5; females: 4/5 and 4/5). No animals survived in the highest dose group (4268.8 mg/kg bw).

Clinical signs:

other: Dyspnea, apathy, abdominal position, lateral position, stagger, atonia, tremor, reduced general condition, diarrhoe, spasctic gait as well as initial body weight loss partially or in some animals of all but the low dose group

Gross pathology:

Heart dilation, congestive hyperemia in the heart , atonic and dilated stomach, diffuse erythema in the gastro-oesophageal vestibule, as well as dilated gut with bloody diarrhea were observed partially or in all animals of all but the low dose group.

Mortality

Dose (µl/kg)	Conc. (%)	male animals	femal animals
4640	46.4	5/5	5/5
1470	14.7	5/5	4/5
1000	10	4/5	4/5
681	6.81	0/5	4/5
464	4.64	0/5	0/5

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

654 mg/kg bw

Quality of whole database:

Estimated Klimisch Rating: 2

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

supporting study

Study period:

1976 - 1977

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Meets generally accepted scientific standards, well documented and acceptable for assessment.

Qualifier:

no guideline followed

Principles of method if other than guideline:

Method: other: according to H.F. Smyth et al.: Am. Ind. Hyg. Ass. J. 23, 95-107, (1962)

GLP compliance:

no

Remarks:

study was performed prior to GLP

Test type:

other: Inhalation hazard test

Limit test:

no

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Weight at study initiation: 226 g (mean)

Route of administration:

inhalation: vapour

Vehicle:

other: unchanged (no vehicle)

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Temperature in air chamber: 20°C
- Saturated vapour

Duration of exposure:

8 h

No. of animals per sex per dose:

6

Control animals:

not specified

Details on study design:

- Duration of observation period following administration: 1 days

Mortality:

No mortality was observed.

Clinical signs:

other: attempt to escape, closure eyelid, eye irritation

Body weight:

No adverse effects observed.

Gross pathology:

Nothing abnormal detected.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Quality of whole database:

Estimated Klimisch Rating: 2

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

Study period:

1976 - 1977

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Meets generally accepted scientific standards, well documented and acceptable for assessment

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

yes

Remarks:

only one dose level

GLP compliance:

no

Remarks:

study was performed prior to GLP

Test type:

standard acute method

Limit test:

no

Species:

rabbit

Strain:

Vienna White

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Weight at study initiation: male: 3.29 kg (mean); female: 3.44 kg (mean)

Type of coverage:

occlusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Area of exposure: 50 cm²

TEST MATERIAL
- Concentration: 100 %

Duration of exposure:

once

Doses:

200 µL/kg equivalent to 184 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: daily
- Necropsy of survivors performed: yes

Statistics:

None

Sex:

male/female

Dose descriptor:

LD50

Effect level:

184 mg/kg bw

Based on:

test mat.

Remarks on result:

other: Calculated from 0.2 mL/kg assuming a test substance density of 0.92 g/mL

Mortality:

2 male animals and 1 female animal died after 7 days.

Clinical signs:

other: slight apathy in all animals, apathy in 3 animals, urine tinged with blood in 3 of the 3 animals that died

Gross pathology:

- Animals that died spontaneously: Kidney (renal pelvis and urinary bladder filled with blood); Liver (focal mass necroses); lung (severe edema); heart (dilatation bilaterally)
- Animals sacrificed after 14 days: no adverse effects observed

Other findings:

Necrosis was observed in all animals

Mortality

Dose (µl/kg)	Conc. (%)	No. of Animals	died within1 h	24 h	48 h	7 d	14 d
200	100	3 male	0/3	0/3	0/3	2/3	2/3
200	100	3 female	0/3	0/3	0/3	1/3	1/3

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

184 mg/kg bw

Quality of whole database:

Estimated Klimisch Rating: 2

Additional information

Acute toxicity: oral

The acute oral toxicity of the test substance in the rat was examined in an in-house study following the principles of OECD TG 401 (BASF AG, 1977). Sprague Dawley rats were given a single oral dose of N3-amine (4640, 1470, 1000, 681, 464 µL/kg bw (corresponding to 426.9, 626.5, 920.0, 1352.4 and 4268.8 mg/kg bw, calculated assuming test substance density of 0.92 g/mL)). Animals were then observed for mortality and for clinical symptoms of toxicity for 14 days. All animals were subjected to necropsy. The oral LD50 was estimated as 654 mg/kg bw. This acute oral toxicity study is classified as acceptable.

 

Acute toxicity: inhalation (inhalation hazard test, BASF AG, 1977)

In an acute inhalation toxicity study according to H.F. Smyth et al. (Am. Ind. Hyg. Ass. J. 23, 95-107, 1962) male and female rats were exposed to N3-amine saturated vapour for a period of 8 hours and observed for 1 day. All animals were subjected to necropsy. Closure eye lid and eye irritation were observed. No mortality was observed when 12 rats were exposed for 8 hours to an atmosphere that has been saturated at 20 degrees centigrade with the volatile part of the compound.

 

Acute toxicity: dermal

The acute dermal toxicity of the test substance was examined in an in-house study following in principle of OECD TG 402, only one dose level was tested (BASF AG, 1977). Vienna White rabbits (3 m/f) were dermally exposed to unaltered N3-amine at a dosage of 200 µL/kg. Animals were then observed for mortality and for clinical symptoms of toxicity for 14 days. Two male animals and 1 female animal died after 7 days. All animals were subjected to necropsy.As clinical signs slight apathy in all animals, apathy in 3 animals, and urine tinged with blood in 3 of the 3 animals that died were observed. The oral LD50 was estimated as 184 mg/kg bw (calculated from 0.2 mL/kg assuming a test substance density of 0.92 g/mL). This acute dermal toxicity study is classified as acceptable.

In a supporting study (TCSAT, 1992) performed with rabbits, a LD50 of approximately 126 mg/kg bw was observed. The test substance was readily absorbed through skin in toxic amounts.

Further study (i.p. route)

The test substance was applied i.p. in mice (BASF AG, 1977). A LD50 value of 158 mg/kg bw was estimated, corresponding to 170 µL test substance/kg. Intraabdominal adherence was observed in gross pathology.

Justification for selection of acute toxicity – oral endpoint
Reliable study classified as key study. Only one study available.

Justification for selection of acute toxicity – dermal endpoint
Reliable study classified as key study.

Justification for classification or non-classification

Based on the results for acute oral (LD50 rat = 654 mg/kg bw), acute dermal (LD50 rabbit = 154 mg/kg bw) and inhalation toxicity (no mortality) the test substance is classified as follows:

 

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

The available experimental test data are reliable and suitable for classification purposes under EU Regulation 1272/2008 (CLP). As a result the substance is considered to be classified for acute oral and dermal toxicity as follows:

acute toxicity: cat. 4, (H302, harmful if swallowed), cat. 2, (H310, fatal in contact with skin).