Amines, polyethylenepoly-, tetraethylenepentamine fraction

Acute Toxicity: oral

Administrative data

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.

Cross-reference

Cross-reference 1

Reason / purpose for cross-reference:

reference to same study

Reference

Endpoint:

short-term repeated dose toxicity: oral

Remarks:

7-day study

Type of information:

experimental study

Adequacy of study:

supporting study

Study period:

1974-1975

Reliability:

3 (not reliable)

Rationale for reliability incl. deficiencies:

significant methodological deficiencies

Remarks:

only limited observations, no GLP, no data on composition of the test substance, no analytical verification of the dose levels

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:

The test substance was added to ground Purina Chow and fed in the diet for 7 days. In the first part of the study 4 groups of Wistar rats were used, one control and 3 test groups. Because no effects were observed, a higher dose group and a control group were included in the second part of the study.

GLP compliance:

no

Remarks:

Before GLP

Limit test:

no

Species:

rat

Strain:

Wistar

Sex:

male/female

Route of administration:

oral: feed

Vehicle:

unchanged (no vehicle)

Analytical verification of doses or concentrations:

no

Duration of treatment / exposure:

7 days

Frequency of treatment:

via the diet for 7 days

Dose / conc.:

500 mg/kg bw/day (nominal)

Remarks:

first study

Dose / conc.:

1 250 mg/kg bw/day (nominal)

Remarks:

first study

Dose / conc.:

3 150 mg/kg bw/day (nominal)

Remarks:

first study

Dose / conc.:

5 000 mg/kg bw/day (nominal)

Remarks:

second study

No. of animals per sex per dose:

5

Control animals:

yes, plain diet

Observations and examinations performed and frequency:

Parameters examined:
- BW gain on days 1, 4 and 7
- Food intake
- Calculated dosage attained
- Absolute and relative liver and kidneys weight
- Mortality

Details on results:

First study
Males: target 0.50 g/kg, 0.42 g/kg attained; target 1.25 g/kg, 1.05 g/kg attained; target 3.15 g/kg, 2.80 g/kg attained
Females: target 0.50 g/kg, 0.47 g/kg attained; target 1.25 g/kg, 1.26 g/kg attained; target 3.15 g/kg, 3.14 g/kg attained
Second study
Males: target 5.00 g/kg, 3.99 g/kg attained
Females: target 5.00 g/kg, 3.63 g/kg attained

Mortality: 0
Food intake: decreased at 5.00 g/kg bw
Body weight: body weight loss at 5.00 g/kg bw
Absolute and relative liver weight: statistically significantly decreased at 5.00 g/kg bw
Relative kidney weight: statistically significantly decreased at 5.00 g/kg bw.

Dose descriptor:

NOAEL

Effect level:

2 800 mg/kg bw/day (nominal)

Based on:

test mat.

Sex:

male

Basis for effect level:

other: Body and organ weight changes

Dose descriptor:

NOAEL

Effect level:

3 140 mg/kg bw/day (nominal)

Based on:

test mat.

Sex:

female

Basis for effect level:

other: Body and organ weight changes

Critical effects observed:

no

Conclusions:

The NOAEL of this 7-day diet study, based on a limited numbers of parameters was 2.80 and 3.14 g/kg bw for males and females, respectively.

Executive summary:

The test substance was added to the diet and fed to groups of 5 Wistar rats (30 days of age) per sex for 7 days. In the first part of the study 4 groups were used, these were dosed at 0, 0.50, 1.25 and 3.15 g/kg bw. Because no effects were observed on body weight gain, food intake and liver and kidneys weights, in the second part of the study, 2 groups were used, these were dosed at 0 and 5.00 g/kg bw. Dosages attained (calculated based on nominal levels and food intake) were: 0, 0, 0.42, 1.05, 2.80 and 3.99 g/kg bw for males, and 0, 0, 0.47, 1.26, 3.14 and 3.63 g/kg bw for females. Animals treated at the highest dose showed a decrease in food intake, body weight loss, and decreased absolute and relative liver weight and decreased relative kidney weight. The NOAELs, therefore, were, 2.80 and 3.14 g/kg bw for males and females, respectively.

Cross-reference 2

Reason / purpose for cross-reference:

reference to same study

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.

Cross-reference 3

Reason / purpose for cross-reference:

reference to same study

Reference

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

disregarded due to major methodological deficiencies

Study period:

1974-1975

Reliability:

3 (not reliable)

Rationale for reliability incl. deficiencies:

unsuitable test system

Remarks:

Short summary of acute inhalation study, saturated vapor concentration test, no GLP, no information 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:

Saturated vapour was generated at 22°C by spreading 50-100 g of chemical over a 200 cm² area on a shallow tray placed near the top of a 120-L plexiglass chamber which is then sealed for at least 16 h while an intermittently operated fan agitated the internal chamber atmosphere. Rats were then introduced in a gasketed drawer-type cage designed and operated to minimize vapour loss.

GLP compliance:

no

Test type:

other: saturated vapor concentration test

Limit test:

yes

Species:

rat

Strain:

not specified

Sex:

not specified

Route of administration:

inhalation: vapour

Type of inhalation exposure:

whole body

Vehicle:

other: unchanged (no vehicle)

Analytical verification of test atmosphere concentrations:

no

Duration of exposure:

8 h

Concentrations:

Rats were exposed to a static test atmosphere generated following a 16-h period in which the liquid was allowed to evaporate at 22rees C. It is not clear whether the maximum attainable vapour concentration had been reached as no analytical measurements were done.

No. of animals per sex per dose:

6 (sex unknown)

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days

Sex:

not specified

Dose descriptor:

LC50

Exp. duration:

8 h

Remarks on result:

not determinable because of methodological limitations

Mortality:

No mortality occurred

Clinical signs:

other: Animals showed no clinical signs

Body weight:

Animals showed normal BW gain

Gross pathology:

Nothing remarkable at necropsy

Interpretation of results:

study cannot be used for classification

Conclusions:

A static test atmosphere generated as a vapour over a 16-h period was not toxic to rats. It should, however, be noted that this corresponds to a very low concentration of maximally 0.00147 mg/L.

Executive summary:

A saturated vapour was generated at 22 degrees C by spreading 50 -100 g of the test substance, tetraethylenepentamine, over a 200 cm2 area on a shallow tray placed near the top of a 120-L plexiglass chamber which was then sealed for at least 16 h while an intermittently operated fan agitated the internal chamber atmosphere. A group of 6 rats was then introduced in a gasketed drawer-type cage designed and operated to minimize vapour loss. They were exposed for 8 h. Animals showed no clinical signs and normal BW gain. Nothing remarkable was observed at necropsy 14 days after exposure. Taking into account a vapour pressure of 0.0189 Pa (IUCLID Section 4.6) and a MW of 189.3, the maximum vapour concentration was calculated to be 0.00147 mg/L, which is very low concentration. This study, therefore, cannot be used for classification and labelling purposes.

Cross-reference 4

Reason / purpose for cross-reference:

reference to same study

Reference

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

supporting study

Study period:

1974-1975

Reliability:

4 (not assignable)

Rationale for reliability incl. deficiencies:

documentation insufficient for assessment

Remarks:

available, no GLP, no data on 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:

Chemical was applied in 0.01 mL amounts to clipped uncovered intact skin of 5 rabbit bellies either undiluted or in progressive dilutions of 10, 1, 0.1 or 0.01% in solvent. One of 10 grades were assigned based on appearance of moderate or marked capillary injection, erythema, edema or necrosis within 24 h. No injury from undiluted is considered grade 1.

GLP compliance:

no

Remarks:

Before GLP

Species:

rabbit

Strain:

not specified

Type of coverage:

open

Preparation of test site:

clipped

Vehicle:

water

Controls:

no

Duration of treatment / exposure:

Not indicated, because of the limited volume used and the open application it is assumed that the test substance stayed there and was not removed at all.

Observation period:

Not indicated, at least up to 24 h.

Number of animals:

5

Irritation parameter:

erythema score

Basis:

mean

Time point:

other: 24 h

Score:

6

Max. score:

10

Reversibility:

no data

Irritant / corrosive response data:

Only a description of the results was given:
- Undiluted test substance: moderate erythema (1/5), marked erythema (1/5), moderate necrosis (3/5)
- 10% dilution: no irritation (5/5)

Other effects:

No info

Interpretation of results:

study cannot be used for classification

Conclusions:

Because 3 out of 5 rabbits showed moderate necrosis following treatment with the undiluted test substance, classification in Cat. 1 can be assumed. Because of unknown exposure duration and unkown observation period, classification in subcategories (1A, 1B, 1C) is not possible.

Executive summary:

The belly of each of 5 rabbits was clipped, the test substance, Amines, polyethylenepoly-, tetraethylenepentamine fraction, was applied undiluted to the uncovered intact skin at a volume of 0.01 mL. The skin was observed for at least up to 24 h. One rabbit showed moderate erythema, a second rabbit showed marked erythema whereas the other 3 showed moderate necrosis. A 10% dilution in distilled water did not show irritation. Because 3 out of 5 rabbits showed moderate necrosis following treatment with the undiluted test substance, classification in OECD-GHS Cat. 1 is assumed. Because of unknown exposure duration and unkown observation period, classification in subcategories (1A, 1B, 1C) is not possible.

Cross-reference 5

Reason / purpose for cross-reference:

reference to same study

Reference

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

supporting study

Study period:

1974-1975

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

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

Remarks:

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

Qualifier:

no guideline available

Principles of method if other than guideline:

Eyes not staining with 5% fluorescein in 20 sec contact were accepted. Single installation of 0.005, 0.02, 0.10 or 0.5 mL undiluted or 0.5 mL of 40, 15, 5 or 1% dilutions were made into conjunctival sac of 5 rabbits. Read immediately unstained and after fluorescein at 24 h, with one of 10 grades assigned. Trace or no injury from 0.5 mL undiluted is grade 1.

GLP compliance:

no

Remarks:

Before GLP

Species:

rabbit

Strain:

not specified

Vehicle:

unchanged (no vehicle)

Controls:

no

Duration of treatment / exposure:

Single instillation

Observation period (in vivo):

No info, at least up to 24 h.

Number of animals or in vitro replicates:

5

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

other: 24 h

Score:

5

Max. score:

10

Reversibility:

not specified

Remarks on result:

other: moderate corneal injury

Only a description of the results was given:

- 0.02 mL per eye: moderate corneal injury with iritis in 1/5 rabbits

- 0.005 mL per eye: minor injury

Interpretation of results:

study cannot be used for classification

Conclusions:

Because 0.02 mL of the undiluted test substance caused moderate corneal injury, it is expected that the amount required according the current OECD guideline (0.1 mL) will induce more severe eye injury and the test substance is therefore considered to be at least 'highly irritating'.

Executive summary:

The test substance, Amines, polyethylenepoly-, tetraethylenepentamine fraction, was applied undiluted at a volume of 0.02 mL to the conjunctival sac of 5 rabbits. Rabbits showed moderate corneal injury, 1/5 rabbits showed iritis. A volume of 0.005 mL per eye showed minor injury. Because a volume of 0.02 mL was used, it is expected that the amount required according the current OECD guideline (0.1 mL) will induce more severe eye injury and the test substance is therefore considered to be at least 'highly irritating'. Because of lack on info when using a volume of 0.1 mL, and on reversibility, classification in OECD-GHS categories is not possible.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1979

Report date:

1979

Materials and methods

Test guideline

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

Test material

Test material information

Constituent 1

Reference substance name:

Amines, polyethylenepoly-, tetraethylenepentamine fraction

EC Number:

292-587-7

EC Name:

Amines, polyethylenepoly-, tetraethylenepentamine fraction

Cas Number:

90640-66-7

Molecular formula:

C8H23N5, C10H25N5

IUPAC Name:

(2-aminoethyl)[2-({2-[(2-aminoethyl)amino]ethyl}amino)ethyl]amine; bis(2-aminoethyl)({2-[(2-aminoethyl)amino]ethyl})amine

Test material form:

liquid

Test animals

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

Administration / exposure

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

Results and discussion

Effect levels

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)

Applicant's summary and conclusion

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.