Amines, polyethylenepoly-, tetraethylenepentamine fraction

Endpoint summary

Description of key information

oral (similar to OECD 401, rat, RL2): LD50 = 3221 mg/kg bw

dermal (similar to OECD 402, rabbit, RL2): LD50 = 1260 mg/kg bw

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:

1974-1975

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

test procedure in accordance with national standard methods with acceptable restrictions

Remarks:

The study was performed pre-GLP and pre-guideline. Limited reporting. No information on the composition or purity of the test substance.

Reason / purpose for cross-reference:

reference to same study

Reason / purpose for cross-reference:

reference to same study

Reason / purpose for cross-reference:

reference to same study

Reason / purpose for cross-reference:

reference to same study

Reason / purpose for cross-reference:

reference to same study

Qualifier:

no guideline available

Principles of method if other than guideline:

5 non-fasted animals per group were dosed by a single gavage application. Observation period was 14 days.

GLP compliance:

no

Remarks:

Before GLP

Test type:

standard acute method

Limit test:

no

Species:

rat

Strain:

Wistar

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Age at study initiation: stated to be 3 -4 weeks old
- Weight at study initiation: stated to be 90 -120 g

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Doses:

2.0, 4.0 and 8.0 mL/kg
The values were converted based on the given relative density of 0.991 - 0.9994. The following doses were calculated based on the lowest relative density value: 1982, 3964 and 7928 mg/kg bw.

No. of animals per sex per dose:

5 males/dose

Control animals:

no

Details on study design:

No details available

Sex:

male

Dose descriptor:

LD50

Effect level:

3.25 mL/kg bw

Based on:

test mat.

95% CL:

>= 2.36 - <= 4.47

Remarks on result:

other: LD50 calculated by the moving average method; LD50 = 3.25 mL/kg bw corresponds to 3221 mg/kg bw.

Mortality:

0/5, 4/5 and 5/5 at 2, 4 and 8 mL/kg bw, respectively.

Clinical signs:

other: - 2 mL/kg bw: no signs - 4 mL/kg bw: slightly sluggish 6 min, prostrate 2 h, death 2 -3 h - 8 mL/kg bw: sluggish 2 min, prostrate 30 min, death 2 -3 h

Gross pathology:

- lungs with petechiae, liver and spleens mottled, stomachs liquid-filled and red, intestines distended and liquid-filled and red or slightly yellow, dark kidneys, bladders fluid-filled (in victims)
- livers mottled (in survivors)

Interpretation of results:

other: CLP/EU GHS criteria are not met, no classification required according to Regulation (EC) No 1272/2008

Conclusions:

Because of the LD50 value of 3221 mg/kg bw the test material is not considered to be harmful.

Executive summary:

Five male rats per group were dosed by intubation with the undiluted test substance. Three groups were used; dose levels were 2.0, 4.0 and 8.0 mL/kg bw. 0/5, 4/5 and 5/5 of the animals died, respectively. The LD50 was calculated to be 3.25 mL/kg bw (3221 mg/kg bw) with 95% confidence limits of 2.36 and 4.47 mL/kg bw. , indicating classification in OECD-GHS category V.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

3 221 mg/kg bw

Quality of whole database:

The study was performed pre-GLP and pre-guideline, and has Klimisch score 2.

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

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:

1974-1975

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

test procedure in accordance with national standard methods with acceptable restrictions

Remarks:

Short summary of acute dermal toxicity study, no GLP, no data on the composition of the test substance

Reason / purpose for cross-reference:

reference to same study

Reason / purpose for cross-reference:

reference to same study

Reason / purpose for cross-reference:

reference to same study

Reason / purpose for cross-reference:

reference to same study

Reason / purpose for cross-reference:

reference to same study

Qualifier:

no guideline available

Principles of method if other than guideline:

Rabbits were dosed using covered dermal application

GLP compliance:

no

Remarks:

Before GLP

Test type:

standard acute method

Limit test:

no

Species:

rabbit

Strain:

New Zealand White

Sex:

male

Type of coverage:

occlusive

Vehicle:

unchanged (no vehicle)

Duration of exposure:

24-h contact with the test substance retained under impervious (polyethylene) sheeting on the clipped intact skin of the trunk.

Doses:

1.0, 2.0 and 4.0 mL/kg bw

No. of animals per sex per dose:

4 males at 1.0 and 2.0 mL/kg bw, 2 males at 4.0 mL/kg bw

Control animals:

no

Sex:

male

Dose descriptor:

LD50

Effect level:

1.26 mL/kg bw

Based on:

test mat.

95% CL:

>= 0.772 - <= 2.06

Remarks on result:

other: LD50 calculated by the moving average method; 1.26 mL corresponds to about 1260 mg

Mortality:

1/4, 4/4 and 2/2 at 1.0, 2.0 and 4.0 mL/kg bw, respectively

Clinical signs:

other: - 1.0 mL/kg bw: necrosis - 2.0 mL/kg bw: necrosis, prostate at 1 day - 4.0 mL/kg bw: necrosis

Gross pathology:

lungs and kidneys reddened in victims, no abnormalties in survivors

Interpretation of results:

other: CLP/EU GHS Category 4 (H302) according to Regulation (EC) No 1272/2008

Conclusions:

Based on a LD50 value of 1.26 mL/kg bw which corresponds to about 1260 mg/kg bw, the test substance should be classified in Cat. 4 according to OECD-GHS

Executive summary:

Two to four male rabbits per group were dosed by a 24 -h dermal application under occlusive conditions with the undiluted test substance. Three groups were used; dose levels were 1.0, 2.0, and 4.0 mL/kg bw. 1/4, 4/4 and 2/2 of the animals died, respectively. The LD50 was calculated to be 1.26 mL/kg bw with 95% confidence limits of 0.772 and 2.06 mL/kg bw, indicating classification in CLP/EU GHS Category 4.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

1 260 mg/kg bw

Quality of whole database:

The study was performed pre-GLP and pre-guideline, and has Klimisch score 2.

Additional information

Oral toxicity:

An acute oral toxicity study with Amines, polyethylenepoly-, tetraethylenepentamine fraction was carried out in male Wistar rats (Myers, 1979, reliability 2). The study was performed before GLP and guidelines were set in place. Groups of 5 rats were treated via gavage of 2000, 4000 or 8000 mL/kg bw of the test substance and were observed for 14 days thereafter. The mortality rate was 0, 80 and 100%, respectively. Dying animals were sluggish and protstrate. The animals in the low dose group showed no signs of toxicity. Gross pathology revealed lungs with petechiae, liver and spleens mottled, stomachs liquid-filled and red, intestines distended and liquid-filled and red or slightly yellow, dark kidneys and bladders fluid-filled. The survivors showed mottled livers. The acute oral LD50 for males, was determined to be 3250 (2360 - 4470) mL/kg bw. This corresponds to about 3221 mg/kg bw.

One supporting study performed in female rats with only limited information resulted in a LD50 of 2140 mg/kg bw (Dow, 1964). Further supporting information is given in a secondary literature in which a LD50 of 2100 mg/kg bw for Amines, polyethylenepoly-, tetraethylenepentamine fraction is described (Spitz, 1979).

Taking all data together, Amines, polyethylenepoly-, tetraethylenepentamine fraction is considered to be of low acute toxicity.

 

Dermal toxicity:

An acute dermal toxicity study with Amines, polyethylenepoly-, tetraethylenepentamine fraction which is pre-GLP and similar to OECD guideline 402, with male New Zealand White rabbits, is available and has been used as a key study (Myers, 1979, reliability 2). Groups of 4 or 2 rabbits were treated for 24 hours under occlusive conditions at 1000, 2000, or 4000 mg/kg bw. Mortality was 25, 100, and 100%, respectively. Necrosis was observed in all animals. Necropsy of the animals that died during the study revealed reddened lungs and kidneys. Terminal necropsy revealed no abnormalities. Based on the observations made in this study, the acute dermal LD50 in males for the test substance was determined to be 1260 (772 - 2060) mg/kg bw.

Inhalation:

One old inhalation study is available in which rats had been exposed to the vapour of the registration substance generated at 22°C (Myers, 1979). No mortality occurred. The concentration has not been measured. A static test atmosphere generated as a vapour over a 16-h period was not toxic to rats. From a toxicologists point of view it is therefore doubtful if the animals were exposed to the test substance by inhalation and which concentration the generated vapour was of because the vapour pressure of the test substance is very low (0.0189 Pa at 20°C) which would result in a vapour saturation of 1.47 mg/m³. This is the maximum concentration which the animals were probably exposed to. This is far below the the concentration level which is needed for classification. Since the substance is classified as corrosive to skin no further acute inhalation toxicity test is required according to Reach Regulation Annex VIII point 8.5.

Justification for classification or non-classification

The available data on acute oral toxicity do not meet the criteria for classification according to Regulation (EC) 1272/2008, and are therefore conclusive but not sufficient for classification.

The available data on acute dermal toxicity meet the criteria for classification according to Regulation (EC) 1272/2008, and is therefore classified as acute toxic Category 4 (H312).