N-(3-aminopropyl)-N-dodecylpropane-1,3-diamine

Endpoint summary

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Reference 1

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

From December 07, 1987 to January 27, 1988

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

GLP compliance:

yes (incl. QA statement)

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
- Source: Interfauna UK Limimted, Wyton, Huntingdon Cambridgeshire
- Age at study initiation: 5-8 weeks
- Assigned to test groups randomly: Yes
- Housing: Up to 5 per cage
- Diet : Ad libitum
- Water: Ad libitum
- Acclimation period: At least 5 d

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-22
- Humidity (%): 40-60
- Air changes (per hr): approximately 15 times
- Photoperiod (hrs dark / hrs light): 12/12

Route of administration:

oral: gavage

Vehicle:

water

Details on oral exposure:

- Concentration in vehicle: 30%

Doses:

Dose-range finding study: 500, 1,000, 2,000, 3,000 and 5,000 mg/kg bw (as 30% aqueous solution)
Main study: 250, 500, 1,000, 2,000 mg/kg bw as 30% aqueous solution, (i.e., equivalent to 75, 150, 300, 600 mg a.i./kg bw)

No. of animals per sex per dose:

1/sex/dose in the dose-range finding study; 5/sex/dose in the main study.

Control animals:

no

Details on study design:

- Duration of observation period following administration: 5 d in the dose-range finding study; 14 d in the main study.
- Frequency of observations and weighing: 1 and 4 h after dosing and then daily. In the dose-range finding study bodyweight was recorded on the day of dosing. In the main study individual bodyweights were recorded on the day of treatment (Day 0), Days 7 and 14 and at death.
- Necropsy of survivors performed: Yes in the main study. In the dose-range finding study no necropsies were performed.
- Other examinations performed: Clinical signs, body weight, gross pathology.

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

871 mg/kg bw

Based on:

test mat.

95% CL:

704 - 1 076

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

261 mg/kg bw

Based on:

act. ingr.

Remarks on result:

other: based on 30% purity

Key result

Sex:

male

Dose descriptor:

LD50

Effect level:

933 mg/kg bw

Based on:

test mat.

95% CL:

664 - 1 310

Key result

Sex:

male

Dose descriptor:

LD50

Effect level:

280 mg/kg bw

Based on:

act. ingr.

Remarks on result:

other: based on 30% purity

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

812 mg/kg bw

Based on:

test mat.

95% CL:

616 - 1 072

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

243.6 mg/kg bw

Based on:

act. ingr.

Remarks on result:

other: based on 30% purity

Mortality:

In the dose-range finding study: Both animals survived at the 500 mg/kg bw dose level and one animal at the 1,000 mg/kg bw dose level.
In the main study: All animals dosed at 2,000 mg/kg bw died within 24 h of dosing. Three males and four females dosed at 1,000 mg/kg bw died within 24 h of dosing.

Clinical signs:

other: All treated animals showed systemic signs of toxicity, such as piloerection, hunched posture and decreased respiratory rate between 1 and 4 h of dosing. Those animals treated at 1,000 and 2,000 mg/kg bw showed additional signs of increased salivation.

Gross pathology:

Necropsy findings showed that all animals that died during the study had similar abnormalities in the lungs, liver and kidneys, gastric mucosa and intestines. Surviving animals did not show any abnormalities at necropsy.

Interpretation of results:

Category 3 based on GHS criteria

Conclusions:

Under the study conditions, the oral LD50 value for all animals was determined to be 261 mg a.i./kg bw (280 mg a.i./kg bw for males and 243.6 mg a.i./kg bw for females).

Executive summary:

A study was conducted to determine the acute oral toxicity of the test substance according to OECD Guideline 401, in compliance with GLP. Groups of 5 male and 5 female Sprague Dawley rats were administered oral gavage doses of a 30% aqueous solution of the test substance at 250, 500, 1000, 2000 mg/kg bw (equivalent to 75, 150, 300, 600 mg a.i./kg bw). Parameters evaluated included survival, clinical observations, bodyweight and necropsy findings in all animals after a 14 day observation period. The LD50 and 95% confidence intervals were calculated separately for males and females using the method of Thompson WR. All animals in the 600 mg a.i./kg bw dose group and 7 of 10 animals (3 males and 4 females) in the 300 mg a.i./kg bw dose group died within 24 h of dosing. All treated animals showed systemic signs of toxicity such as pilo-erection, hunched posture and decreased respiratory rate between 1 and 4 h after dosing. Animals treated at 300 and 600 mg a.i./kg bw showed additional signs of increased salivation. Further, reduced bodyweight gain was observed during the first week after dosing in some animals in the 75 and 150 mg a.i./kg bw dose group and all animals in the 300 mg a.i./kg bw dose group. Necropsy findings showed that all animals that died during the study had similar abnormalities in the lungs, liver and kidneys, gastric mucosa and intestines. Under the study conditions, the oral LD50 value for all animals was determined to be 261 mg a.i./kg bw (280 mg a.i./kg bw for males and 243.6 mg a.i./kg bw for females) (Jones, 1988).

Reference 2

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

supporting study

Study period:

From December 20, 2001 to July 29, 2002

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

EU Method B.1 bis (Acute Oral Toxicity - Fixed Dose Procedure)

Version / remarks:

Cited as Directive 92/69/EEC, B.1 bis

Qualifier:

according to guideline

Guideline:

OECD Guideline 420 (Acute Oral Toxicity - Fixed Dose Method)

GLP compliance:

yes (incl. QA statement)

Test type:

fixed dose procedure

Limit test:

no

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River laboratories, L' Arbresle, France
- Age at study initiation: approximately 6 weeks old
- Weight at study initiation: 174 ± 5g (m) and 149 ± 6g (f)

Route of administration:

oral: gavage

Vehicle:

water

Details on oral exposure:

VEHICLE
- Amount of vehicle (if gavage): 20 mL/kg; the volume administered to each animal was adjusted according to body weight determined on the day of treatment.

Doses:

Sighting test:
50 mg/kg bw
500 mg/kg bw

Main Study:
50 mg/kg bw
5 mg/kg bw

No. of animals per sex per dose:

5/sex/dose in main study; 1 female/dose in sighting test

Control animals:

other: historical controls

Details on study design:

- Duration of observation period following administration: 7-d (sighting test) or 14-d (main experiment)
- Frequency of observations and weighing: The animals were observed frequently during the hours following administration of the test substance, for detection of possible treatment-related clinical signs. Thereafter, observation of the animals was made at least once a day. The animals were weighed individually just before administration of the test substance on Day 1 and then on Days 8 and 15. The body weight gain of the treated animals was compared to that of CIT control animals with a similar initial body weight.
- Necropsy of survivors performed: Yes
- Other examinations performed: Clinical signs, body weight, gross pathology of digestive tract, heart, kidneys, liver, lungs, pancreas, spleen and any other organs with obvious abnormalities

Preliminary study:

Mortality:
At 50 mg/kg bw: No deaths
At 500 mg/kg bw: Death occurred after 2 h

Clinical signs:
At 50 mg/kg bw: No clinical signs were noted.
At 500 mg/kg bw: No clinical signs were observed within 1 h of treatment.

Key result

Sex:

male/female

Dose descriptor:

LD0

Effect level:

> 5 mg/kg bw

Based on:

test mat.

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 50 - < 500 mg/kg bw

Based on:

test mat.

Remarks on result:

other: Less than 100% (=80%) but more than 50% survival was recorded at the dose-level of 50 mg/kg bw, and 100% survival was recorded at the dose-level of 5 mg/kg bw.

Mortality:

Main test:
- At 50 mg/kg bw: One male found dead 30 minutes after treatment and one female found dead on Day 12.
- At 5 mg/kg bw: No deaths.

Clinical signs:

other: Main test: At 50 mg/kg bw : - Dyspnea (Day 1 in all animals; Day 2 in 8/9 animals; from Day 8 to the death of the female on Day 12 and on Day 15 in 1/8 animals), - Hypoactivity (1/9 animals on Day 1; in 5/9 animals on Day 2; on Days 8 and 9 in the fem

Gross pathology:

Macroscopic examination of the main organs of the animals revealed no apparent abnormalities.

Interpretation of results:

Category 3 based on GHS criteria

Conclusions:

Under the conditions of the study, the LD50 was higher than 50 mg/kg bw and lower than 500 mg/kg bw.

Executive summary:

A study was conducted to determine the acute oral toxicity of the test substance to rats according to OECD Guideline 420 and EU Method B.1 bis, in compliance with GLP. A sighting test was performed first, in which 1 female rat was administered an oral gavage dose of 50 and 500 mg/kg bw. Mortality occurred 2 h after dosing at 500 mg/kg bw. Based on this, groups of 5 male and 5 female Sprague Dawley rats were gavaged at 5 and 50 mg/kg bw of the test substance in the main study. Less than 100% (80%) but more than 50% survival was recorded at 50 mg/kg bw and 100% survival was recorded at 5 mg/kg bw. Clinical signs at 50 mg/kg bw included dyspnea, hypoactivity, soft faeces, abdomen swelling and piloerection. Macroscopic examination of the main organs of all the treated animals revealed no apparent abnormalities. Under the study conditions, the LD50 was higher than 50 mg/kg bw and lower than 500 mg/kg bw (Pelcot, 2002a).

Reference 3

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

supporting study

Study period:

From December 20, 2001 to July 29, 2002

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)

Version / remarks:

Cited as Directive 96/54/EC, B.1 tris

Qualifier:

according to guideline

Guideline:

OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)

GLP compliance:

yes (incl. QA statement)

Test type:

acute toxic class method

Limit test:

no

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River laboratories, L' Arbresle, France
- Age at study initiation: Approximately 6 weeks old
- Weight at study initiation: 163 ± 8g (m) and 137 ± 8g (f)

Route of administration:

oral: gavage

Vehicle:

water

Details on oral exposure:

VEHICLE
- Amount of vehicle (if gavage): 10 mL/kg; the volume administered to each animal was adjusted according to body weight determined on the day of treatment.

Doses:

2,000, 200 and 25 mg/kg bw

No. of animals per sex per dose:

3/sex/dose (except for dose level of 2,000 mg/kg bw which was 3 males only)

Control animals:

other: historical controls

Details on study design:

- Duration of observation period following administration: 14 d
- Frequency of observations and weighing: The animals were observed frequently during the hours following administration of the test substance, for detection of possible treatment-related clinical signs. Thereafter, observation of the animals was made at least once a day. The animals were weighed individually just before administration of the test substance on Day 1 and then on Days 8 and 15. Individual weights of animals found dead during the study were measured at necropsy when survival exceeded 24 h and if no signs of "cannibalism" were present. The body weight gain of the treated animals was compared to that of CIT control animals with the same initial body weight.
- Necropsy of survivors performed: Yes
- Other examinations performed: Clinical signs, body weight, gross pathology (digestive tract, heart, kidneys, liver, lungs, pancreas, spleen and any other organs with obvious abnormalities)

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 25 - < 200 mg/kg bw

Based on:

test mat.

Mortality:

- Time of death:
Dose-level of 2,000 mg/kg bw (3 males): 1h 45 min after treatment
Dose-level of 200 mg/kg bw (3 males and 3 females): One female on Day 1; one male and one female on Day 2 and one female on Day 12.
Dose-level of 25 mg/kg bw (3 males and 3 females): None

- Number of deaths at each dose:
Dose-level of 2,000 mg/kg bw (3 males): All males died
Dose-level of 200 mg/kg bw (3 males and 3 females): One male and three females died during the study
Dose-level of 25 mg/kg bw (3 males and 3 females): No deaths occurred.

Clinical signs:

other: Dose-level of 2,000 mg/kg bw (3 males): Sedation, dyspnea and piloerection were observed prior to death. Dose-level of 200 mg/kg bw (3 males and 3 females): Dyspnea, hypersalivation and piloerection were the clinical signs observed in the males within 6

Gross pathology:

Macroscopic examination of the main organs of the animals revealed no apparent abnormalities.

Interpretation of results:

Toxicity Category III

Conclusions:

Under the study conditions, the LD50 of the test substance was higher than 25 mg/kg bw and lower than 200 mg/kg bw.

Executive summary:

A study was conducted to determine the acute oral toxicity of the test substance to rats according to the OECD Guideline 423 and EU Method B.1 tris, in compliance with GLP. Groups of 3 male and 3 female Sprague Dawley rats were administered oral gavage doses of 0, 25, 200 and 2000 mg/kg bw (with the exception of the high dose group, in which only 3 males were used). All animals of the high dose group died within 2 h post-treatment. In the mid dose, one male and all females died within 12 d. No deaths were observed in the low dose group. Clinical signs included dyspnea, hypersalivation and piloerection, as well as hypoactivity and sedation. Macroscopic examination of the main organs of the animals performed at necropsy revealed no apparent abnormalities. Under the study conditions, the LD50 was higher than 25 mg/kg bw and lower than 200 mg/kg bw (Pelcot, 2002b).

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

261 mg/kg bw

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Endpoint:

acute toxicity: inhalation

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

the study does not need to be conducted because the substance is classified as corrosive to the skin

other:

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:

1989

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

EU Method B.3 (Acute Toxicity (Dermal))

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Type of coverage:

semiocclusive

Vehicle:

unchanged (no vehicle)

Duration of exposure:

24 h

Doses:

2000 mg/kg bw corresponding to 600 mg a.i./kg bw (undiluted test substance)

No. of animals per sex per dose:

5 per sex per dose.

Control animals:

no

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 600 mg/kg bw

Based on:

act. ingr.

Remarks on result:

other: based on 30% purity

Interpretation of results:

Category 3 based on GHS criteria

Conclusions:

Under the study conditions, the LD50 of the test substance in Sprague-Dawley rats was established at >600.0 mg a.i./kg bw. It must however be noted that the animals were sacrificed due to severe suffering linked to skin corrosion and that toxicity was not of systemic nature.

Executive summary:

A study was conducted to determine the acute dermal toxicity of the test substance according to EU Method B.3, in compliance with GLP. Five rats per sex per dose were exposed to the test substance at a concentration of 2000 mg/kg bw (corresponding to 600 mg a.i./kg bw based on a purity of 30%). Under the study conditions, the LD50 of the test substance in Sprague Dawley rats was established at >600.0 mg a.i./kg bw. It must however be noted that the animals were sacrificed due to severe suffering linked to skin corrosion and that toxicity was not of systemic nature (Jones, 1989).

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

600 mg/kg bw

Additional information

Oral

A study was conducted to determine the acute oral toxicity of the test substance according to OECD Guideline 401, in compliance with GLP. Groups of 5 male and 5 female Sprague Dawley rats were administered oral gavage doses of a 30% aqueous solution of the test substance at 250, 500, 1000, 2000 mg/kg bw (equivalent to 75, 150, 300, 600 mg a.i./kg bw). Parameters evaluated included survival, clinical observations, bodyweight and necropsy findings in all animals after a 14 day observation period. The LD50 and 95% confidence intervals were calculated separately for males and females using the method of Thompson WR. All animals in the 600 mg a.i./kg bw dose group and 7 of 10 animals (3 males and 4 females) in the 300 mg a.i./kg bw dose group died within 24 h of dosing. All treated animals showed systemic signs of toxicity such as pilo-erection, hunched posture and decreased respiratory rate between 1 and 4 h after dosing. Animals treated at 300 and 600 mg a.i./kg bw showed additional signs of increased salivation. Further, reduced bodyweight gain was observed during the first week after dosing in some animals in the 75 and 150 mg a.i./kg bw dose group and all animals in the 300 mg a.i./kg bw dose group. Necropsy findings showed that all animals that died during the study had similar abnormalities in the lungs, liver and kidneys, gastric mucosa and intestines. Under the study conditions, the oral LD50 value for all animals was determined to be 261 mg a.i./kg bw (280 mg a.i./kg bw for males and 243.6 mg a.i./kg bw for females) (Jones, 1988).

A study was conducted to determine the acute oral toxicity of the test substance to rats according to OECD Guideline 420 and EU Method B.1 bis, in compliance with GLP. A sighting test was performed first, in which 1 female rat was administered an oral gavage dose of 50 and 500 mg/kg bw. Mortality occurred 2 h after dosing at 500 mg/kg bw. Based on this, groups of 5 male and 5 female Sprague Dawley rats were gavaged at 5 and 50 mg/kg bw of the test substance in the main study. Less than 100% (80%) but more than 50% survival was recorded at 50 mg/kg bw and 100% survival was recorded at 5 mg/kg bw. Clinical signs at 50 mg/kg bw included dyspnea, hypoactivity, soft faeces, abdomen swelling and piloerection. Macroscopic examination of the main organs of all the treated animals revealed no apparent abnormalities. Under the study conditions, the LD50 was higher than 50 mg/kg bw and lower than 500 mg/kg bw (Pelcot, 2002a).

A study was conducted to determine the acute oral toxicity of the test substance to rats according to the OECD Guideline 423 and EU Method B.1 tris, in compliance with GLP. Groups of 3 male and 3 female Sprague Dawley rats were administered oral gavage doses of 0, 25, 200 and 2000 mg/kg bw (with the exception of the high dose group, in which only 3 males were used). All animals of the high dose group died within 2 h post-treatment. In the mid dose, one male and all females died within 12 d. No deaths were observed in the low dose group. Clinical signs included dyspnea, hypersalivation and piloerection, as well as hypoactivity and sedation. Macroscopic examination of the main organs of the animals performed at necropsy revealed no apparent abnormalities. Under the study conditions, the LD50 was higher than 25 mg/kg bw and lower than 200 mg/kg bw (Pelcot, 2002b).

Dermal

A study was conducted to determine the acute dermal toxicity of the test substance according to EU Method B.3, in compliance with GLP. Five rats per sex per dose were exposed to the test substance at a concentration of 2000 mg/kg bw (corresponding to 600 mg a.i./kg bw based on a purity of 30%). Under the study conditions, the LD50 of the test substance in Sprague Dawley rats was established at >600.0 mg a.i./kg bw. It must however be noted that the animals were sacrificed due to severe suffering linked to skin corrosion and that toxicity was not of systemic nature (Jones, 1989).

Justification for classification or non-classification

Based on the results obtained in an acute oral study (LD50 = 261 mg/kg bw), the substance warrants classification as Acute Tox 3 – H301 (Toxic if swallowed) according to CLP (EC 1272/2008) criteria. Although a dermal LD50 was established as >600 mg/kg bw, no classification for dermal toxicity is proposed since the observed effects were due to the corrosive nature of the substance, not to direct systemic toxicity. Furthermore, toxicokinetic testing indicated that dermal uptake is 80-fold lower that oral uptake(Johnson, 2000; van Miller, 2005), so that the actual dermal LD50 should in fact be well above the classification trigger of the CLP (EC 1272/2008).