N,N'-bis(3-aminopropyl)propane-1,3-diamine

Endpoint summary

Description of key information

oral:

The oral LD50 value of the test substance was determined to be 736 mg/kg bw (1970, reliability 2).

inhalation:

After 8 h exposure to a saturated vapor atmosphere of the test substance no animals died (1970, reliability 2).

dermal:

Based on a weight of evidence-approach (CAS 107 -15 -3, 56 -18 -8, 111 -40 -0, 112 -24 -3, 109 -76 -2) the substance is classified as acute tocix via the dermal route cat. 3.

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:

19 Aug - 27 Aug 1969

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Remarks:

study protocol is in principle similar to OECD TG 401, limited documentation

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Principles of method if other than guideline:

BASF-Test: Animals were treated by single gavage application with an aqueous solution of the test substance. The animals were observed for mortality and for clinical symptoms of toxicity. At the end of the observation period of 7 days, the surviving animals were sacrificed for the purpose of necropsy; animals that died during the observations period also were subjected to necropsy.

GLP compliance:

no

Test type:

other: BASF-Test

Limit test:

no

Species:

rat

Strain:

other: Gassner rat

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Willi Gassner, Sulzfeld, Germany
- Age at study initiation: young adults
- Weight at study initiation: 142 - 188 g

Route of administration:

oral: gavage

Vehicle:

water

Remarks:

aqueous emulsion with Traganth

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 20%, 10%, 8%, 4%, 2% aqueous emulsion with Traganth

Doses:

200, 400, 500, 640, 800, 1000, 1250, 1600 mm3/kg bw (corresponding to 184, 386, 460, 588.8, 736, 920, 1150, 1472 mg/kg bw; calculated using the density of 0.92 g/cm³)

No. of animals per sex per dose:

10

Control animals:

no

Details on study design:

- Duration of observation period following administration: 7 days
- Other examinations performed: clinical signs
- Frequency of observations: several times on the day of application and daily thereafter
- Pathologically investigated: heart, lung, liver, kidney, adrenal gland, stomach, intestine, bladder, genitals, trachea, central nervous system, bone marrow, tumor, blood, urine

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

736 mg/kg bw

Mortality:

1472 mg/kg 10/10 m, 10/10 w
1150 mg/kg 4/10 m, 10/10 w
920 mg/kg 4/10 m, 5/10 w
736 mg/kg 1/10 m, 9/10 w
588.8 mg/kg 0/10 m, 0/10 w
460 mg/kg 0/10 m, 2/10 w
386 mg/kg 0/10 m, 0/10 w
184 mg/kg 0/10 m, 0/10 w

Clinical signs:

1472 mg/kg bw: No symptoms on the first day of the trial, the following day rough fur, irregular breathing, apathy. Within 24 hours post applicaion, all animals died
1150 - 460 mg/kg : Huddled together about 10 minutes after application, quiet restrained, shock or irregular breathing and semi-closed eyes. The first six animals died within the first 24 hours,
386 - 184 mg/kg: No symptoms on the first day of the trial, but on the second day rough fur and irregular breathing.

Body weight:

no data

Gross pathology:

Sacrificed animals: Frequently strongly dilated stomachs and sagging intestinal tract. Rot.

Interpretation of results:

Category 4 based on GHS criteria

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

736 mg/kg bw

Quality of whole database:

Scientifically acceptable study report, comparable to guideline with acceptable restrictions (mostly due to reduced reporting in times before GLP).

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Study period:

18 Aug - 27 Aug 1969

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Remarks:

study protocol is in principle similar to OECD TG 403, limited documentation

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

Principles of method if other than guideline:

The test demonstrates the toxicity of an atmosphere saturated with vapours of the volatile components of a test substance at the temperature chosen for vapour generation (20 °C). 6 rats per sex were exposed to the vapours or aerosol, generated by bubbling 200 L air/h through a substance column of about 5 cm above a fritted glassdisc in a glass cylinder for 8 h. The documentation of clinical signs was performed over a period of 7 days.

GLP compliance:

no

Test type:

other: inhalation hazard test

Species:

rat

Strain:

other: Gassner rat

Sex:

male/female

Route of administration:

inhalation: vapour

Type of inhalation exposure:

not specified

Vehicle:

air

Analytical verification of test atmosphere concentrations:

not specified

Duration of exposure:

8 h

Concentrations:

saturated vapor atmosphere

No. of animals per sex per dose:

6

Control animals:

no

Details on study design:

- Duration of observation period following administration: 7 days
- Other examinations performed: clinical signs
- Frequency of observations: several times on the day of application and daily thereafter
- 7 days post exposure animals were sacrificed and underwent necropsy.
- Pathologically investigated: heart, lung, liver, kidney, adrenal gland, stomach, intestine, bladder, genitals, traches, central nervous system, bone marrow, tumor, blood, urine

Sex:

male/female

Dose descriptor:

other: Inhalation Risk Test

Exp. duration:

8 h

Remarks on result:

other: no mortality occured

Mortality:

No deaths

Clinical signs:

other: violent escape attempts, mucosal irritation

Body weight:

no evaluable data

Gross pathology:

no findings

Conclusions:

The inhalation of a highly saturated vapor-air-mixture caused no mortality but clincal signs, after 8 h of exposure.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Quality of whole database:

orientating information of inhalation toxicity; inhalation exposure duration: 8 hours; extrapolation of an exact LD50 (4h) is not possible

Acute toxicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Additional information

oral:

An acute oral toxicicty study in rats is available (1970). The study was conducted according to acceptable scientific principles. The oral LD50 value of the test substance was determined to be 736 mg/kg bw (reliability 2).

inhalation:

After 8 h exposure to a saturated vapor atmosphere of the test substance no animals died (study year: 1970). The study was conducted according to BASF standard (inhalation hazard test) (reliability 2).

dermal:

An acute dermal toxicity study is available (1970). In this dermal toxicity study on rabbits the LD50 of the test substance was determined to be < 200 mg/kg bw (reliability 4). However, there is no specification of test substance identity available. The todays substance specification has changed. Previous purity was approximately 80 to 90%. Todays new technical processes lead to an increased purity of approximately 99.7%. N,N'-Bis(3-aminopropyl)propane-1,3-diamine is a corrosive substance and is classified and labelled as Skin Corrosion Category 1B, H314. The albino rabbit is the preferable laboratory animal for testing of dermal irritation/ corrosivity because it is highly sensitive to irritating/ corrosive effects. Thus, rabbits are not the preferred species for acute dermal toxicity studies with corrosive substances. It is unclear if death of rabbits was due to systemic toxicity following dermal administration, or due to severe local effects (destroyed skin tissue as corrosion response), and in addition, if damage of the skin facilitated increased systemic exposure to the substance. In contrast, the oral LD50 in rats was determined to be 736 mg/kg, indicating that N,N'-Bis(3-aminopropyl)propane-1,3-diamine is of low toxicity after single ingestion. A retrospective analysis of data from acute oral and dermal toxicity testing, performed on pesticide active substances and new chemical entities submitted for the Notification of New Substances Regulations (a total of 240 substances), has demonstrated that there is a relationship between dermal acute toxicity and oral acute toxicity, and there are no significant numbers of compounds that are classified as a potential hazard only via the dermal route (Creton et al. 2010 Acute toxicity testing of chemicals - Opportunities to avoid redundant testing and use alternative approaches. Critical Reviews in Toxicology; 40(1), 50-83). Thus, the availablae study is not used for classification and a weight of evidence approach is used. The following substances have been taken for the weight of evidence approach: CAS 107-15-3 (1,2-Ethanediamine), CAS 111-40-0 (1,2 -Ethanediamine, N1 -(2 -aminoethyl)-), CAS 112 -24 -3 (1,2-Ethanediamine, N1,N2-bis(2-aminoethyl)-), CAS 109-76-2 (1,3-Propanediamine), CAS 56-18-8 (1,3-Propanediamine, N1-(3-aminopropyl)-). With increasing chain length, no significant changes can be seen in acute oral and dermal toxicity.

intraperitoneal:

After intraperitoneal administration, the LD50 of the test substance was determined to be 32,2 mg/kg bw (1970) The study was conducted according to BASF standard.

Justification for classification or non-classification

Based on the available data N,N'-Bis(3-aminopropyl)propane-1,3-diamine needs to be classified as acute toxic via the oral route category 4, and acute toxic via the dermal route category 3 according to Regulation (EC)No 1272/2008 (CLP).

The acute inhalation toxicity study (inhalation hazard test) performed could not be used for classification according to Regulation (EC) No 1272/2008 (CLP).