Registration Dossier

Diss Factsheets

Administrative data

Description of key information

Acute Oral toxicity
Rat:

LD50 = 1348 mg/kg bw (comp. OECD 401; BASF, 1979)
LD50 = 3920 mg/kg bw (BASF, 1958)
LD50 = 2773 mg/kg bw (Smyth & Carpenter, 1962)

LD50 = 2830 mg/kg bw (Benya & Raymond in Clayton: Patty’s Industrial Hygiene Toxicology, 4th ed., 1994)

LD50 = 2800 mg/kg bw (American Cyanamide Co., 1954, Val. 4)
Mouse:

LD50 = 4250 mg/kg bw (American Cyanamide Co., 1954, Val. 4)

Acute Inhalation toxicity
Rat:

IHT: 1h: LC50 >16.4 mg/L air (BASF, 1979)

IHT: 8h: no mortality in a saturated vapour atmosphere (BASF, 1958)

IHT: 8h: no mortality in a saturated vapour atmosphere (Smyth & Carpenter, 1962)

IHT: 6h: no mortality in a saturated vapour atmosphere (American Cyanamide Co., 1954, Val. 4)

Acute Dermal toxicity
Rat:

LD50 >2000 mg/kg bw (BASF AG, 1979)
Rabbit:

LD50 ca.1250 mg/kg bw (Smyth & Carpenter, 1962)

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
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
comparable to guideline study
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
GLP compliance:
not specified
Test type:
standard acute method
Limit test:
no
Specific details on test material used for the study:
SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: Substance-ID: 78/701
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: WIGA
- Weight at study initiation: male: 220-260 g, female: 160-180 g
- Fasting period before study: 15-20 h
Route of administration:
oral: gavage
Vehicle:
water
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 4.64, 6.85, 10, 14.7, 21.5 %

MAXIMUM DOSE VOLUME APPLIED: 10 ml/kg
Doses:
464, 681, 1000, 1470, 2150 mg/kg
No. of animals per sex per dose:
5 male and 5 female animals per dose
Control animals:
not specified
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of weighing: before study, after 2-4 days, 7 days and 13 days
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, gross pathology
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
1 348 mg/kg bw
Based on:
test mat.
Mortality:
1 of 10 animals died at 464 mg/kg
1 of 10 animals died at 681 mg/kg
no animals died at 1000 mg/kg
5 of 10 animals died at 1470 mg/kg
all animals died at 2150 mg/kg
Clinical signs:
clinical signs included: apathy, dyspnoea, stertorous respiration, gasping, apathy, staggering, urine of strong yellow colour, scrubby fur, anaemic paleness, blood in nose and saliva, bad general condition. Most of these clinical signs were only observed in the two highest dose groups.
Gross pathology:
The sacrificed animals were without findings.
The following findings were made in animals that died during the study:
heart: acute right dilation
liver: circumferential delineation of the liver lobes
stomach: atonic, reddened mucosa
intestine: reddened mucosa
lung: slight emphysema
Interpretation of results:
Category 4 based on GHS criteria
Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
Value:
1 348 mg/kg bw
Quality of whole database:
similar to OECD TG 401

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
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment
Qualifier:
no guideline followed
Principles of method if other than guideline:
Inhalation hazard test, animals exposed for 1 hour
GLP compliance:
not specified
Test type:
traditional method
Limit test:
no
Specific details on test material used for the study:
SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: Substance-ID: 78/701

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: MUS RATTUS, Brunnthal
- Weight at study initiation: 185 +/- 15 g
- Diet: Herilan MRH, ad libitum
- Water: Tap water, ad libitum
Route of administration:
inhalation: aerosol
Type of inhalation exposure:
nose/head only
Vehicle:
air
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: head-nose inhalation system
- Method of holding animals in test chamber: animals are held in a tube, the head/nose being exposed to the inhalation chamber

TEST ATMOSPHERE
- Brief description of analytical method used: gas chromatography
- Samples taken from breathing zone: yes
Analytical verification of test atmosphere concentrations:
yes
Remarks:
gas chromatography
Duration of exposure:
1 h
Concentrations:
0, 6.64, and 16.35 mg/L analytical concentration
No. of animals per sex per dose:
10 male and 10 female animals per dose
Control animals:
yes
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of weighing: day 0, 7 and 14
- Frequency of observations: daily
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight
Statistics:
Data were anlysed according to the "Binominaltest" (Wittig H, Mathematische Statisik, 1974, pp 32-35)
Key result
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 16.4 mg/L air (analytical)
Based on:
test mat.
Exp. duration:
1 h
Mortality:
no death occurred
Clinical signs:
other: aqueous, reddish eye and nose secretion, irregular respiration, scrubby and clotted fur, hairless necrotic areas with bloody eschar. The animals were not free of symptoms at the end of the observation period (14 days).
Body weight:
male and female animals of the 16.35 mg/L dose group showed no differences compared to the control group. Male animals of the 6.64 mg/L dose group showed no differences compared to the control group. The female animals of the 6.64 mg/L dose group showed a slight weight loss after 7 days and decreased body weight gain after 14 days compared to controls.
Gross pathology:
nothing abnormal detected
Interpretation of results:
GHS criteria not met
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
discriminating conc.
Value:
16 400 mg/m³
Quality of whole database:
Inhalation hazard test

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:
comparable to guideline study with acceptable restrictions
Qualifier:
no guideline followed
Principles of method if other than guideline:
3 male and 3 female animals were subjected to a limit test. The test substance was applied to a 2.5 x 2.5 cm application site for 20 h under occlusive conditions. The skin was either intact or abraded. After the application time, the skin was washed with water which may have contained a mild detergent. Animals were observed for 8 days and skin changes were observed on working days. Findings were recorded and graded as described in OECD test guideline 404.
GLP compliance:
no
Test type:
standard acute method
Limit test:
yes
Specific details on test material used for the study:
SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: Substance-ID: 78/701

Species:
rat
Strain:
not specified
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Wiga
- Weight at study initiation: average weight male animals: 210 g; female animals: 183 g
Type of coverage:
not specified
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: 48 cm²

TEST MATERIAL
- Amount applied: 2.02 ml/kg bw

Duration of exposure:
not applicable, test substance was not washed off 24 hours after application as recommended in the OECD guideline 402.
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
3 male and 3 female animals were used
Control animals:
not specified
Details on study design:
- Duration of observation period following administration: 14 days
Statistics:
not applicable
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Mortality:
no deaths occurred
Clinical signs:
no signs of general toxicity could be observed;
Body weight:
mean weight male animals: day 0: 210 g, day 4: 202g, day 6: 220 g, day 8: 227 g, day 11: 239 g, day 13: 238 g
mean weight female animals: day 0: 183 g; day 4: 179 g, day 6: 193 g, day 8: 197 g, day 11: 198 g, day 13: 192 g
Gross pathology:
Skin necrosis pathologically confined
Other findings:
Necrosis were observed at the site of applicatation on the day following substance application.

The skin irritation properties of the test substance seem to be the limiting factor of acute dermal toxicity. No further clinical signs of toxicity were observed.

Interpretation of results:
GHS criteria not met
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
2 000 mg/kg bw

Additional information

Oral

In an acute oral toxicity study comparable to OECD guideline 401 5 male and 5 female Sprague Dawley rats per dose were treated with up to 2150 mg/kg bw under standardized conditions. The animals were observed for 14 d, necropsy was performed even with the survivors. The LD50 was calculated to about 1350 mg/kg bw for male and female rats. Mortalities were observed at all dose levels except the 1000 mg/kg dose level, clinical signs included apathy, dyspnoea, stertorous respiration, gasping, apathy, staggering, urine of strong yellow color, scrubby fur, anaemic paleness, blood in nose and saliva and a bad general condition. Necropsy findings included circumferential delineation of the liver lobes, atonic and reddened gastric mucosa as well as reddened intestinal mucosa in the deceased animals; all survivors displayed no abnormal pathological findings.

Interestingly, previous investigations to that study using an aqueous solution of the test compound that was neutralized to pH 7 resulted in much higher tolerability of the test substance with LD50 values calculated to ca. 3920 mg/kg bw. In addition, no signs of intestinal or gastric mucosal irritation were reported, suggesting that the alkaline properties of the test substance might influence the toxicity of the test substance. On the other hand, in previous studies in cats and rabbits (BASF, 1961, val. 3) using also a neutralized aqueous solution signs of gastric mucosal irritation was also observed in both species. But these data cannot be taken into account, since the animals have been repeatedly dosed with the test substance two weeks after the initial exposure.

Supporting information on the acute oral toxicity of 3-amino-1-propanol is further provided by several authors, but all of these references only provide basic data and no further details on the study or the study design are available. LD50 values found in these studies are in the range of 2800 mg/kg bw (Smyth et al. 1962 and Benya et al., in Clayton: Patty’s Industrial hygiene Toxicology, fourth ed. 1994). 

Inhalation

In an acute inhalation test (nose/head only) 10 male and 10 female rats were exposed to various concentrations of 3-aminopropan-1-ol. At the highest concentration tested clinical signs observed included aqueous, reddish eye and nose secretion, irregular respiration, scrubby and clotted fur, hairless necrotic areas with bloody eschar formation. Mortalities did not occur and no pathological abnormalities were detected in post mortem necropsy (BASF 1979). In a standardized inhalation hazard test with a saturated vapour atmosphere, 0/6 rats died after 8 h exposure (BASF 1958). No abnormal clinical signs of toxicity or abnormal pathological findings were reported in that study. Similar results were reported by Smyth et al. (1962) after 8 h whole body exposure and American Cyanamide Co. (1954) after an exposure of 6h.

Dermal

In a limit test 3 male and 3 female rats were exposed to a dose of 2000 mg/kg bw (BASF, 1979). No animal died and no signs of general toxicity could be observed. The most frequent observed clinical sign were necrosis at the site of substance application, suggesting that the irritative/corrosive property of the test substance represents the most toxic principle of 3-amino-1-propanol. Penetration of rabbit skin was estimated by a technique closely akin to the one-day cuff method of Draize et al. using groups of four male albino rabbits. The LD50 was calculated to be 1250 mg/kg bw (Smyth 1962). Further data on mortality, clinical signs of toxicity or post mortem necropsy were not provided.

Justification for classification or non-classification

Classification, Labeling, and Packaging Regulation (EC) No. 1272/2008

The available experimental test data are reliable and suitable for classification purposes under Regulation 1272/2008. The substance is considered to be classified as Acute Tox. oral Cat. 4 (H302: Harmful if swallowed) according to Regulation (EC) No 1272/2008 (CLP), as amended for the tenth time in Regulation (EU) No 2017/776.