1,2-Propanediamine, N1-(2-aminoethyl)-3-(4-ethoxyphenyl)-, hydrochloride (1:2), (2S)-

Endpoint summary

Description of key information

LD50 oral (rat):> 300 < 2000 mg/kg bw [draft report, Kurth 1996]
LD50 dermal (rat): > 2000 mg/kg bw [draft report, Kurth 1996]

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:

from January to February 1996

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

1996

Deviations:

yes

Remarks:

- According to Annex 3c the lower dose (200 mg) should be applied first to the same sex that was treated with 2000 mg/kg

GLP compliance:

no

Test type:

acute toxic class method

Limit test:

no

Species:

rat

Strain:

other: HAN: WIST (SPF)

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Schering AG, Germany
- Mean weight at study initiation: 105-113 g (males) or 89-91 g (females)
- Housing: 1 animal per cage
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: at least 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21 - 23
- rel. Humidity (%): 50 - 58
- Photoperiod (hrs dark / hrs light): 12 / 12

Route of administration:

oral: gavage

Vehicle:

other: 900 mg NaCl + 85 mg Myrj 53 ad 100 ml bidist. water

Details on oral exposure:

VEHICLE
- Concentration in vehicle: l: 200 mg/mL, II+III 20 mg/mL
- Amount of vehicle (if gavage): 10 mL/kg

MAXIMUM DOSE VOLUME APPLIED: 2000 mg/kg bw

Doses:

2000 and 200 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: on Day 1, 8, and 14
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 300 - < 500 mg/kg bw

Based on:

test mat.

Remarks on result:

other: The effect level was determined according to Annex 3c of the replaced OECD Test Guideline 423 (1996), according to the classification scheme of Regulation (EU) No. 1272/2008 (CLP) the effect level is > 300 - < 2000 mg/kg bw

Mortality:

After 2000 mg/kg bw all animals died within 3 hours on day 1 of the test. No mortality was observed after adiministration of 200 mg/kg bw in both sexes.

Clinical signs:

other: The main clinical findings after administration of 2000 mg/kg were apathy, prone position, unconsciousness, disturbances in gait, total and spontaneous twitches and a bluish discolouration of all hairless parts of the body prior to death. All animals trea

Gross pathology:

Autopsy revealed reddening of the glandular mucosa of the stomach in only one animal which died after application of 2000 mg/kg and no compound-related or suspected compound-related findings in the two other animals which died or in the animals which were sacrificed at the end of the study.

Interpretation of results:

Category 4 based on GHS criteria

Conclusions:

The acute oral toxicity of the test item was moderate with an LD50 value of > 300 < 500 mg/kg bw in rats according to ANNEX 3c of OECD TG 423 (1996). All males died after oral ingestion of 2000 mg/kg bw. All males and females dosed with 200 mg/kg bw survived. Clinical findings were limited to the 2000 mg/kg bw dose group. Body weight development was not affected. During autopsy reddening of the glandular mucosa of the stomach was described in only one animal which died after application of 2000 mg/kg

Executive summary:

In an acute oral toxicity study according to OECD guideline 423 (1996), groups of, adult WST (SPF) rat (3/sex) were given a single oral dose of Triamine Dihydrochloride in 900 mg NaCl + 85 mg Myrj 53 ad 100 ml bidist. water at doses 2000 and 200 mg/kg bw and observed for 14 days.

Oral LD50 Combined = > 300 mg/kg bw and < 500 mg/kg bw (in accordance with Annex 3c of OECD TG 423 (1996))

Oral LD50 Combined = > 300 mg/kg bw and < 2000 mg/kg bw (in accordance with Regulation (EU) No. 1272/2008 (CLP))

All males died after oral ingestion of 2000 mg/kg bw. All males and females dosed with 200 mg/kg bw survived. Clinical findings were limited to the 2000 mg/kg bw dose group. Body weight development was not affected. During autopsy reddening of the glandular mucosa of the stomach was described in only one animal which died after application of 2000 mg/kg

 

Triamine Dihydrochloride is of low Toxicity based on the LD50 in WIST (SPF) rats. The substance is classified according to Regulation (EU) No. 1272/2008 (CLP) and the Globally Harmonized System for Classification and Labelling of Chemicals (GHS) as Category 4 ‘harmful if swallowed’.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

discriminating dose

Value:

200 mg/kg bw

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:

from January to February 1996

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Reason / purpose for cross-reference:

reference to same study

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Version / remarks:

24 February 1987

Deviations:

yes

Remarks:

- 3 instead of 5 animals/sex used

GLP compliance:

no

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

other: HAN: WIST (SPF)

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Schering AG, Germany
- Mean weight at study initiation: 104-106 g (males) or 98-105 g (females)
- Housing: 1 animal per cage
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: at least 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21 - 23
- rel. Humidity (%): 50 - 58
- Photoperiod (hrs dark / hrs light): 12 / 12

Type of coverage:

occlusive

Vehicle:

other: 900 mg NaCl ad 100 ml bidist. water

Details on dermal exposure:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): I - VI: 98 - 106 + 0.05 mL vehicle
- Constant volume or concentration used: yes

VEHICLE
- Amount(s) applied (volume or weight with unit): 0.05 mL 0.9% NaCl solution

Duration of exposure:

24 hours

Doses:

2000 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:´weighing: on day 1, 8, and 14.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

All treated animals survived

Clinical signs:

other: no clinical findings

Gross pathology:

Autopsy revealed no compound-related findings.

Interpretation of results:

GHS criteria not met

Conclusions:

A single dermal administration of the test substance to male and female rats at the limit-dose 2000 mg/kg was tolerated without mortalities, compound-related clinical findings, effects on body weight gain and gross pathological findings. According to OECD TG 402 the dermal LD50 of the test substance is therefore > 2000 mg/kg body weight.

Executive summary:

In an acute dermal toxicity study similar to OECD TG 402 (adopted 24 February 1987), groups of young adult Wistar rats (3/sex) were dermally exposed to Triamine Dihydrochloride in physiological saline for 24 hours at a dose 2000 mg/kg bw. Animals then were observed for 14 days.

Dermal LD50 Combined = > 2000 mg/kg bw

No mortality occurred during the limit test.

The test item is of low Toxicity based on the combined LD50 value of > 2000 mg/kg bw.

There were no treatment related clinical signs, necropsy findings or changes in body weight.

 

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

discriminating dose

Value:

2 000 mg/kg bw

Additional information

Acute toxicity: oral

In an acute oral toxicity study according to OECD guideline 423 (1996), groups of, adult WST (SPF) rat (3/sex) were given a single oral dose of Triamine Dihydrochloride in 900 mg NaCl + 85 mg Myrj 53 ad 100 ml bidist. water at doses 2000 and 200 mg/kg bw and observed for 14 days.

Oral LD50 Combined = > 300 mg/kg bw and < 2000 mg/kg bw

All males died after oral ingestion of 2000 mg/kg bw. All males and females dosed with 200 mg/kg bw survived. Clinical findings were limited to the 2000 mg/kg bw dose group. Body weight development was not affected. During autopsy reddening of the glandular mucosa of the stomach was described in only one animal which died after application of 2000 mg/kg

 

Triamine Dihydrochloride is of low Toxicity based on the LD50 in WIST (SPF) rats. The substance is classified according to Regulation (EU) No. 1272/2008 (CLP) and the Globally Harmonized System for Classification and Labelling of Chemicals (GHS) as Category 4 ‘harmful if swallowed’.

 

Acute toxicity: dermal

 

In an acute dermal toxicity study similar to OECD TG 402 (adopted 24 February 1987), groups of young adult Wistar rats (3/sex) were dermally exposed to Triamine Dihydrochloride in physiological saline for 24 hours at a dose 2000 mg/kg bw. Animals then were observed for 14 days.

Dermal LD50 Combined = > 2000 mg/kg bw

No mortality occurred during the limit test.

The test item is of low Toxicity based on the combined LD50 value of > 2000 mg/kg bw.

There were no treatment related clinical signs, necropsy findings or changes in body weight.

 

Justification for classification or non-classification

Acute toxicity: oral

LD50: > 300 - < 2000 mg/kg bw (rat, female/male)

According to Regulation (EC) No 1272/2008, Annex I Triamin-Dihydrochlorid shall be allocated to Category 4 (H302)

 

Acute toxicity: inhalation

No data available

 

Acute toxicity: dermal

LD50: > 2000 mg/kg bw (rat, female/male)

No classification required according to Regulation (EC) No 1272/2008, Annex I