Registration Dossier

Administrative data

Description of key information

oral:  LD50 = ca. 1300 mg/kg bw (pre-GLP study similar to OECD 401 in male and female rats);

inhalation: LC50 (8 h exposure) > 49 mg/L air (pre-GLP, IRT in male and female rats);

dermal: LD50 = 430 mg/kg bw (pre-GLP study according to the one-day cuff method of Draize and associates, rabbit)

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Referenceopen allclose all

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
14 Dec 1965 - 11 Jan 1966
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Principles of method if other than guideline:
The study was conducted according to an internal BASF method which in principle is comparable to the OECD Guideline 401. A test group consisting of 5 animals/sex was 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 14 days, the surviving animals were sacrificed for the purpose of necropsy; animals that died during the observations period also were subjected to necropsy. The LD50 value was estimated on the basis of the observed mortalities.
GLP compliance:
no
Limit test:
no
Species:
rat
Strain:
other: US-rats
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Weight at study initiation: male: 235 - 305 g; female: 124- 206 g
Route of administration:
oral: gavage
Vehicle:
water
Details on oral exposure:
VEHICLE
- Aqua dest.
- Concentration in vehicle: 2 % and 20 %
Doses:
200, 800, 1000, 1250, 1600, 3200 mg/kg bw
No. of animals per sex per dose:
5
Control animals:
not specified
Details on study design:
- Duration of observation period following administration: 12-14 days
- Frequency of observations: daily
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs
Sex:
male/female
Dose descriptor:
LD50
Effect level:
ca. 1 300 mg/kg bw
Mortality:
Observed; for details please refer to "Any other information on results incl. tables".
Clinical signs:
Staggering, prone and side positions, intermittent respiraton, ruffled fur.
Body weight:
no data
Gross pathology:
Animals that died: gastrorectasis and corrosion.

Sacrificed animals: no abnormalities.

Mortality:

  Dose (mg/kg bw)  conc. (%) Gender  1 h  24 h  48 h  day 7  day 14
3200 20 male 0/5 5/5 5/5 5/5 5/5
3200 20 female 0/5 5/5 5/5 5/5 5/5
1600 20 male  0/5  2/5  2/5  2/5  2/5
1600 20 female  0/5  4/5  4/5  4/5  4/5
1250 20 male  0/5  0/5  0/5  0/5  0/5
1250 20 female  0/5  3/5  3/5  3/5  3/5
1000 20  male  0/5  0/5  0/5  0/5  0/5
1000 20 female 0/5  1/5  1/5  1/5  1/5
800 20 male  0/5  0/5  0/5  0/5  0/5
800 20 female 0/5  1/5  1/5  1/5  1/5
200 2  male  0/5 0/5  0/5 0/5 0/5
200 2  female  0/5  0/5  0/5  0/5  0/5

The application of the test substance caused toxicity (including mortality) in a dose dependent matter.

Interpretation of results:
Category 4 based on GHS criteria
Conclusions:
The LD50 for oral acute toxicity in rats was calculated as 1.5 ml/kg bw which corresponds to ca. 1300 mg/kg bw based on the density 0.86 g/cm3 .
Executive summary:

In a study which was in large parts equivalent to methods described in OECD guideline 401, doses of 200, 800, 1000, 1250, 1600, 3200 mg/kg bw of an aqueous solution of the test substance were applied by gavage to male and female US-rats (5 animals per sex per dose). The animals were observed for mortality and for clinical symptoms of toxicity. At the end of the observation period of 14 days, the surviving animals were sacrificed for the purpose of necropsy; animals that died during the observation period also were subjected to necropsy. Mortality occurred at doses of 800 mg/kg bw and higher. At 3200 mg/kg bw all animals died within 24 h. The main clinical signs were staggering, prone and side positions, intermittent respiration and ruffled fur. At necropsy, gastrorectasis and corrosion effects were observed in animals that died during the observation period.

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
data from handbook or collection of data
Principles of method if other than guideline:
Single oral dose toxicity was estimated by the gastric intubation of groups of five non-fasted, rats four to five weeks of age and 90 to 120 grams. The dosages were arranged in a logarithmic series differing by a factor of two. Whenever possible, the chemical was administered undiluted. Based upon mortalities during a 14-day observation period, the most probable LD50 value and its fiducial range were estimated by the method of Thompson.
GLP compliance:
no
Species:
rat
Strain:
Wistar
Sex:
female
Route of administration:
oral: gavage
Vehicle:
not specified
Doses:
no data
No. of animals per sex per dose:
5
Control animals:
not specified
Details on study design:
- Duration of observation period following administration: 14 days
Sex:
female
Dose descriptor:
LD50
Effect level:
2 230 mg/kg bw
95% CL:
1 900 - 2 620
Mortality:
no data
Clinical signs:
no data
Body weight:
no data
Gross pathology:
no data
Interpretation of results:
Category 5 based on GHS criteria
Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
Value:
1 300 mg/kg bw

Acute toxicity: via inhalation route

Link to relevant study records

Referenceopen allclose all

Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions
Principles of method if other than guideline:
BASF-Test. The test demonstrates the toxicity of an atmosphere saturated with vapours of the volatile components of the test substance at the temperature chosen for vapour generation (20 °C). 3 rats per sex were exposed sequentially to the vapours, generated by bubbling 200 l/h air through a substance column of about 5 cm above a fritted glassdisc in a glass cylinder for 30 min,1 h, 2 h and 2.5 h. For a 8 h exposure a desiccator was used as exposure chamber.The documentation of clinical signs was performed over a period of 14 days.
GLP compliance:
no
Species:
rat
Strain:
not specified
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Weight at study initiation: 210 g (mean)
Route of administration:
inhalation: mixture of vapour and aerosol / mist
Type of inhalation exposure:
nose/head only
Remarks:
except 8h exposure, which was a whole body exposure
Vehicle:
air
Analytical verification of test atmosphere concentrations:
no
Duration of exposure:
> 0.5 - < 8 h
Remarks on duration:
several exposure times: 30min, 1 h, 2 h, 2.5 h and 8 h
Concentrations:
30 min exposure: 26 mg/L air
1 h exposure: 30 mg/L air
2 h exposure: 26 mg/L air
2.5 h exposure: 25,2 mg/L air
8 h exposure: 18 mg/L air, 49 mg/L air
Nominal concentrations based on the substance loss.
No. of animals per sex per dose:
30 min exposure: 3
1 h exposure: 3
2 h exposure: 6
2.5 h exposure: 3
8 h exposure: 6
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations: several times on the day of exposure and daily afterwards.
- Frequency of weighing: before the treatment and at the end of the observation period.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 49 mg/L air
Exp. duration:
8 h
Remarks on result:
other: theoretical saturated vapour concentration is 32.8mg/L. Higher value likely results from substance loss in the experimental setup describes as severe fogging.
Mortality:
30 min exposure: 0/6 (head/nose only)
1 h exposure: 0/6 (head/nose only)
2 h exposure: 2/12 (head/nose only)
2.5 h exposure: 2/6 (head/nose only)
8 h exposure: 0/12 (whole body, exsikkator)
Clinical signs:
other: At the beginning of the test: impetuous attempts to escape, bloody eye and nose discharge, severe irritation of mucous membranes. During the post exposure period: severe corrosion of the exposed tissues (face, eyes, fore limbs).
Body weight:
The surviving animals gained weight
Gross pathology:
2.5 h exposure: pulmonary emphysema in one animal

The inhalation of a highly saturated vapor-air-mixture caused mortality after 2 h of exposure. The substance caused severe corrosion at exposed tissues.

Interpretation of results:
GHS criteria not met
Conclusions:
No mortality was observed after an 8-h exposure at the saturated vapour concentration.
Executive summary:

To evaluate the acute toxicity after inhalation an inhalation risk test was conducted. Male and female rats (strain not specified) were exposed to vapours of the test substance for various exposure durations (30 min, 1 h, 2 h, 2.5 h, 8 h). The vapours were generated by bubbling air through a column which contained the test substance. The vapour concentrations were calculated based on the substance loss.

At the beginning of the exposure the animals showed impetuous attempts to escape. Bloody eye and nose discharge and severe dyspnea and reduced breathing were observed during the exposure duration.

After the exposure period the animals developed severe corrosion of the exposed tissues (face, eyes, fore limbs). Two animals of the 2-h and the 2.5 -h exposure group died within 4 days after exposure (head/nose only, app. 25mg/L)

No mortality was observed after an 8-h exposure (whole body, 49mg/L).

Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
data from handbook or collection of data
Principles of method if other than guideline:
Concentrated vapor inhalation consisted of subjecting groups of six male albino rats to a flowing stream of vapour-ladened air. The vapour-air mixture was generated by passing dried air at room temperature through a gas-washing bottle. Inhalations were continued for time periods in a logarithmic series with a ratio of two extending to eight hours, until the inhalation period killing about half the number of rats within 14 days is defined.
GLP compliance:
no
Species:
rat
Strain:
not specified
Sex:
male
Route of administration:
inhalation: vapour
Type of inhalation exposure:
not specified
Vehicle:
air
Analytical verification of test atmosphere concentrations:
no
Duration of exposure:
4 h
Concentrations:
saturated vapour
(calculated by registrant as 32.8mg/L)
No. of animals per sex per dose:
6
Control animals:
not specified
Sex:
not specified
Dose descriptor:
LC50
Effect level:
> 32.8 mg/L air
Based on:
other: theoretic saturated vapour concentration (calculated)
Exp. duration:
4 h
Mortality:
none
Body weight:
no data
Gross pathology:
no data
Interpretation of results:
GHS criteria not met
Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
discriminating conc.
Value:
49 000 mg/m³

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
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
data from handbook or collection of data
Principles of method if other than guideline:
Penetration of rabbit skin was estimated by a technique closely to the one-day cuff method of Draize and associates, using groups of four male albino rabbits weighing 2.5 to 3.5 kg. The fur was removed from the entire trunk by clipping, and the dose was retained beneath an impervious plastic film. The animals were immobilized during the 24 hour contact period, after which the film was removed and the rabbits were caged for the subsequent 14 day observation period.
GLP compliance:
no
Species:
rabbit
Strain:
New Zealand White
Sex:
male
Type of coverage:
occlusive
Vehicle:
not specified
Duration of exposure:
24 h
Doses:
no data
No. of animals per sex per dose:
4
Control animals:
not specified
Details on study design:
- Duration of observation period following administration: 14 days
Sex:
male
Dose descriptor:
LD50
Effect level:
430 mg/kg bw
Remarks on result:
other: conversion into mg/kg is based on the density of 0.86 g/cm3 (according to BASF internal data).
Mortality:
no data
Clinical signs:
no data
Body weight:
no data
Gross pathology:
no data
Interpretation of results:
Category 3 based on GHS criteria
Conclusions:
A dermal LD50 value for propylenediamine of 0.5 ml/kg bw, equivalent to 430 mg/kg bw (based on a density of 0.86 g/cm³) was reported for rabbits.
Executive summary:

Penetration of rabbit skin was estimated by a technique closely to the one-day cuff method of Draize and associates, using groups of four male albino rabbits weighing 2.5 to 3.5 kg. The fur was removed from the entire trunk by clipping, and the dose was retained beneath an impervious plastic film. The animals were immobilized during the 24 hour contact period, after which the film was removed and the rabbits were caged for the subsequent 14 day observation period. No data regarding mortality, clinical signs and body weight changes are given. The reported LD50 for the penetration of rabbit skin is 0.5 ml/kg bw.

Endpoint conclusion
Dose descriptor:
LD50
Value:
430 mg/kg bw

Additional information

Oral:

In a study which was in large parts equivalent to methods described in OECD guideline 401, the LD50 for oral acute toxicity in rats was calculated as ca. 1300 mg/kg body weight. Doses of 200, 800, 1000, 1250, 1600 and 3200 mg/kg bw of an aqueous solution of the test substance were applied by gavage to male and female US-rats (5 animals per sex per dose) followed by a post dose observation period of 14 days.

Mortality occurred at doses of 800 mg/kg bw and higher. At 3200 mg/kg bw all animals died within 24 h. The main clinical signs were staggering, prone and side positions, intermittent respiraton and ruffled fur. At necropsy, gastrorectasis and corrosion effects were observed in animals that died during the observation period. The LD50 for oral acute toxicity in rats was calculated as 1.5 ml/kg bw which corresponds to ca. 1300 mg/kg bw based on the density 0.86 g/cm3.

In a further study with only limited data provided, the test substance caused likewise moderate toxicity after a single ingestion (LD50 = 2230 mg/kg bw).

Inhalation:

Data is available from an inhalation risk test (IRT) which meets generally accepted scientific principles. Male and female rats (strain not specified) were exposed to vapours of the test substance for various exposure durations (30 min, 1 h, 2 h, 2.5 h, 8 h). The vapours were generated by bubbling air through a column which contained the test substance. The vapour concentrations were calculated based on the substance loss. At the beginning of the exposure the animals showed impetuous attempts to escape. Bloody eye and nose discharge and severe dyspnea and reduced breathing were observed during the exposure duration.

After the exposure period the animals developed severe corrosion of the exposed tissues (face, eyes, fore limbs). Two animals of the 2-h and the 2.5 -h exposure group died within 4 days after exposure (head/nose only, app. 25mg/L). No mortality was observed after an 8 -h exposure to a vapour concentration of 49 mg/L air (whole body). Therefore, the LC50 was not reached at saturated vapour concentrations.

Smyth et al. also reported no mortalities in rats after 4h exposure to the saturated vapour concentration.

 

Dermal:

Penetration of rabbit skin was estimated by a technique closely to the one-day cuff method of Draize and associates, using groups of four male albino rabbits weighing 2.5 to 3.5 kg. The fur was removed from the entire trunk by clipping, and the dose was retained beneath an impervious plastic film. The animals were immobilized during the 24 hour contact period, after which the film was removed and the rabbits were caged for the subsequent 14 day observation period. No data regarding mortality, clinical signs and body weight changes are given.

A dermal LD50 value for propylenediamine of 0.5 ml/kg bw, equivalent to 430 mg/kg bw (based on a density of 0.86 g/cm3) was reported for rabbits, with no further details provided.

Justification for classification or non-classification

The available experimental test data are reliable and suitable for classification purposes under Regulation 1272/2008. As a result the substance has to be classified for acute oral toxicity cat. 4 and acute dermal toxicity cat. 3 under Regulation (EC) No. 1272/2008, as amended for the 13th time in Regulation (EU) 2018/1480.