7-azatridecane-1,13-diamine

Endpoint summary

Description of key information

In an oral acute toxicity study the LD50 identified in rats was 1170 mg/kg bw.

In a dermal acute toxicity study the LD50 identified in rats was approx. 1200 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:

1978

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Remarks:

similar to OECD Guideline 401, but no single animal data presented

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:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

yes

Remarks:

no single animal data presented

GLP compliance:

no

Remarks:

study performed before GLP 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: Oncins, IFFA CREDO, France
- Weight at study initiation: 130-160 g

ENVIRONMENTAL CONDITIONS
no further details

Route of administration:

oral: gavage

Vehicle:

water

Remarks:

distilled

Details on oral exposure:

MAXIMUM DOSE VOLUME APPLIED: 5 ml/kg

Doses:

390, 590, 890, 1330, and 2000 mg/kg bw

No. of animals per sex per dose:

5

Control animals:

other: one group of vehicle treated animals were kept in order to determine normal body weight development.

Details on study design:

- Duration of observation period following administration: 15 days
- Frequency of observations and weighing: every 5th day (i.e. study day 0, 5, 10 and 15; weighing was done only the dose group which produced less than 10% mortality - here 390 mg/kg bw)
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs,

Statistics:

LD50 value was calculated using the method of Litchfield and Wilcoxon.

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

1 170 mg/kg bw

Based on:

test mat.

95% CL:

740 - 1 850

Remarks on result:

other: Within the 14 days observation period 1/10, 3/10, 1/10, 5/10 and 9/10 animals died using 390, 590, 890, 1330, and 2000 mg/kg bw respectively.Deaths occurred within day 1 to day 5 post dosing.

Mortality:

390 mg/kg bw: 1/10 animals died, death occurred at day 7 after administration
590 mg/kg bw: 3/10 animals died, death occurred at day 2 after administration
890 mg/kg bw: 1/10 animals died, death occurred at day 5 after administration
1330 mg/kg bw: 5/10 animals died, death occurred within 1 day after administration
2000 mg/kg bw: 9/10 animals died, death occurred within 1 day after administration
All animals that died were dead within 1 to 5 days after administration

Clinical signs:

other: no clinical signs were observed

Interpretation of results:

Category 4 based on GHS criteria

Conclusions:

After single application of either 390, 590, 890, 1330, or 2000 mg test substance per kg into male and female rats lethality could be observed during the 14 day observation period, resulting in a LD50 of 1170 mg/kg bw.

Executive summary:

Acute oral toxicity was investigated using male and female Sprague-Dawley rats in a test similar to acute standard method (i.e. OECD TG 401, non GLP). The test substance was administered by gavage at doses of 390, 590, 890, 1330 or 2000 mg/kg bw to groups of 10 animals (5 animals/sex). Within the 14 days observation period 1/10, 3/10, 1/10, 5/10 and 9/10 animals died using 390, 590, 890, 1330, and 2000 mg/kg bw, respectively. Deaths occurred within 1 to 5 days post dosing. Having this results a median lethal dose (LD50) of approximately 1170 mg/kg bw (CI: 740 to 1850 mg/kg bw) was identified .

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

1 170 mg/kg bw

Quality of whole database:

Reliable study available (Klimisch 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:

1978

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Remarks:

(mostly due to reduced reporting in times before GLP, e.g. no single animal data presented, results of preliminary test not reported, lacking information on animal husbandry, occlusive conditions)

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:

equivalent or similar to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

yes

Remarks:

mostly due to reduced reporting in times before GLP, e.g. no single animal data presented, results of preliminary test not reported, lacking information on animal husbandry, occlusive conditions

GLP compliance:

no

Remarks:

study performed before GLP 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: Oncins, IFFA CREDO, France
- Weight at study initiation: 120-150 g

ENVIRONMENTAL CONDITIONS
no further details

Type of coverage:

occlusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Area of exposure: 6cm x 6cm
- Type of wrap if used: aluminium foil and adhesive tape

REMOVAL OF TEST SUBSTANCE
- Washing (if done): with lukewarm soap water
- Time after start of exposure: 24 h (directly after patch removal)

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.93 ml/kg
- Other: as the test material was solid at 24 °C as well as in between 32 and 34°C, the test material was heated to 37 °C, became fluid and was administered pure to the skin of test animals

Duration of exposure:

24 hours

Doses:

740, 1110, 1670, and 2500 mg/kg bw

No. of animals per sex per dose:

5

Control animals:

other: one group of vehicle treated animals were kept in order to determine normal body weight development.

Details on study design:

- Duration of observation period following administration: 15 days
- Frequency of observations and weighing: every 5th day (i.e. study day 0, 5, 10 and 15) for vehicle treated groups and animals treated with 740 mg/kg bw (which is the highest dose which did not produce deaths)
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight and gross pathology

Statistics:

LD50 value was calculated using the method of Dragstedt and Lang.

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

ca. 1 200 mg/kg bw

Based on:

test mat.

Remarks on result:

other: Within the 14 days observation period no animals died after single application of 740 mg/kg bw. 4/10, 10/10 and 10/10 animals died using 1110, 1670 and 2500 mg/kg bw respectively. Deaths occurred within 1 to 3 days post application.

Mortality:

740 mg/kg bw: 0 males and 0 females died
1110 mg/kg bw: 4/10 animals died, death occurred within 1 to 3 days after administration
1670 mg/kg bw: 10/10 animals died, death occurred within 1 to 3 days after administration
2500 mg/kg bw: 10/10 animals; death occurred with day 1 and 2 after administration
All animals that died were dead within 1 to 3 days after administration

Clinical signs:

other: 740 mg/kg bw: only squeeking of the animals at the time of administration was noted 1110 mg/kg bw: same symptoms as decribed in the higher dose groups 1670 mg/kg bw: same symptoms as described in the high dose group, in addition staggering gait was obser

Gross pathology:

- 1670 and 2500 mg/kg bw: thickening of the skin at the site of application
- 1110 mg/kg bw: In surviving animals thickening of the skin at the site of application was noted and on day 4 and 5 eschar formation was observed at these sites. Cicatrisation of this eschar was observed starting at day 10 and at the end of the observation period a wound slightly healed with thick crust was seen in these animals, except for one animal which presented deeper lesions that can be attributed to a mutilation.
- 740 mg/kg bw: Same observations as mentioned above, but the mutilation phenomena were observed up to three hours after the dressing was removed in three females. Healing of these wounds sarts on day 4. In the other animals (females and males) eschar formation was noted on day 10, which began to heal on day 14 after start of exposure.

Bodyweight development: Bodyweights given as group mean [g]+/- standard deviation after "n" days in observation  Dose level n=0   n= 5  n=10  n=15  Control (untreated)  143 +/- 4.2 172 +/- 7.2   198.2 +/- 20.4  217 +/-27.8  740 mg/kg bw of test item  142.5 +/-4.2 t = 0.26 n.s. 153.0 +/-10.3 t = 4.9 s.s.   186.3 +/-12.3 t = 1.6 n.s. 207.0 +/-21.0 t = 0.9 n.s.

n.s. difference to control group not statistically significant

s.s. difference to control group statistically significant

Interpretation of results:

Category 4 based on GHS criteria

Conclusions:

After single dermal application of either 740, 1110, 1670 or 2500 mg test substance per kg onto the skin of male and female rats lethality could be observed during the 14 day observation period, resulting in a LD50 of approximately 1200 mg/kg bw.

Executive summary:

Acute dermal toxicity was investigated using male and female Sprague-Dawley rats in a test similar to acute standard method (i.e. OECD TG 402, non GLP). The test substance was administered to the skin for 24 hours under occlusive conditions at doses of 740, 1110, 1670 and 2500 mg/kg bw to 4 groups of 10 animals (5animals/sex).

Clinical signs were observed starting from the mid-dose group. Within the 14 days observation period no animals died after single application of 740 mg/kg bw. 4/10, 10/10 and 10/10 animals died using 1110, 1670 and 2500 mg/kg bw respectively. Deaths occurred within 1 to 3 days post application. Having this results a median lethal dose (LD50) of approximately 1200 mg/kg bw was identified for acute dermal toxicity.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

1 200 mg/kg bw

Quality of whole database:

Reliable study available (Klimisch 2)

Additional information

Acute oral toxicity was investigated using male and female Sprague-Dawley rats in a test similar to acute standard method (i.e. OECD TG 401, non GLP). The test substance was administered by gavage at doses of 390, 590, 890, 1330 or 2000 mg/kg bw to groups of 10 animals (5 animals/sex). Within the 14 days observation period 1/10, 3/10, 1/10, 5/10 and 9/10 animals died using 390, 590, 890, 1330, and 2000 mg/kg bw, respectively. Deaths occurred within 1 to 5 days post dosing. Having this results a median lethal dose (LD50) of approximately 1170 mg/kg bw (CI: 740 to 1850 mg/kg bw) was identified .

As supporting evidence a study which determined an approximate lethal dose (ALD) for the test item is given. The test material was administered as a single oral dose by intragastric intubation to male rats (one rat/dose). The rats dosed at 1500, 2300, or 3400 mg/kg were found dead at day 1 after dosing. Under the conditions of this test, the ALD was 1500 mg/kg of body weight. The ALD is defined as the lowest dose adminisered which causes death either on the day of dosing or within 14 days.

Acute dermal toxicity was investigated using male and female Sprague-Dawley rats in a test similar to acute standard method (i.e. OECD TG 402, non GLP). The test substance was administered to the skin for 24 hours under occlusive conditions at doses of 740, 1110, 1670 and 2500 mg/kg bw to 4 groups of 10 animals (5animals/sex).

Clinical signs were observed starting from the mid-dose group. Within the 14 days observation period no animals died after single application of 740 mg/kg bw. 4/10, 10/10 and 10/10 animals died using 1110, 1670 and 2500 mg/kg bw respectively. Deaths occurred within 1 to 3 days post application. Having this results a median lethal dose (LD50) of approximately 1200 mg/kg bw was identified for acute dermal toxicity.

Justification for classification or non-classification

Based on the results obtained in acute oral and dermal toxicity studies and the criteria set in Regulation (EC) No. 1272/2008 the submission substance is classified for acute oral and dermal toxicity category 4.