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Administrative data

Description of key information

The oral LD50 ranges from 1870, 5400, 6500 to 8000 mg/kg in the rat. For rabbits this value is 2823 mg/kg and for the mouse 5467 mg/kg.
The inhalative LC50 value was determined to be greater than 33.8 mg/l.
The dermal LD50 value is 4052 mg/kg for the 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:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions
Remarks:
(prior to GLP, only two doses tested, post exposure period 7 days)
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
yes
Remarks:
(only two doses tested, study period only 7 days)
GLP compliance:
no
Test type:
standard acute method
Limit test:
no
Specific details on test material used for the study:
- Analytical purity: 99.5%
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals or test system and environmental conditions:
- Source: Gassner
- Mean body weight range at study initiation: 259-262g (male), 174-178g (female)
Route of administration:
oral: gavage
Vehicle:
water
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 35%

MAXIMUM DOSE VOLUME APPLIED:
Doses:
8250 and 10000 µl/kg bw (approx 6,600 and 8000 mg/kg; conversion with density 0.8 g/cm3 (20°C))
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
- Duration of observation period following administration: 7 days
- Frequency of observations and weighing: animals were checked for mortality 1h after application (day 1), then on day 2, day 3 and day 7 of the study. Weighing was performed on day of application (day 1) then on day 4 and day 7. Clinical signs of toxicity were observed several times on day of application then on days 4, 5, 6 and 7
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight
Sex:
male/female
Dose descriptor:
LD50
Effect level:
ca. 8 000 mg/kg bw
Mortality:
see table 1 below
Clinical signs:
other: DAY 1 (similar symptoms in both dose groups) - Immediately after application: irregular and intermittent breathing, apathy, abdominal and lateral position, atony, exsicosis - 1h after application: irregular and intermittent breathing, apathy, abdominal an
Gross pathology:
Animals that died (8250 and 10000 µl/kg bw)
- Heart (acute dilation, acute congestion), Stomach (redness), Intestine (hemorrhagic and diarrhetic contents)

Survivors (till day 7)
- No adverse gross pathological finding observed

Table 1: Mortality of Spraque-Dawley Rats after Single Oral Dosage (gavage) with Propan-1-ol

No. of animals

Death within

1h

24h

48h

7 days

6600 mg/kg bw

5 males

0/5

0/5

0/5

0/5

5 females

0/5

1/5

2/5

2/5

8000 mg/kg bw

5 males

0/5

3/5

3/5

3/5

5 females

0/5

1/5

1/5

1/5

Interpretation of results:
GHS criteria not met
Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
other: secondary literature
Principles of method if other than guideline:
Summarized overview of further data.
GLP compliance:
not specified
Dose descriptor:
LD50
Effect level:
2 823 mg/kg bw
Remarks on result:
other: rabbit
Dose descriptor:
LD50
Effect level:
5 467 mg/kg bw
Remarks on result:
other: mouse
Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
weight of evidence
Study period:
June - July 1962
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
test procedure in accordance with national standard methods with acceptable restrictions
Reason / purpose for cross-reference:
reference to same study
Qualifier:
according to guideline
Guideline:
other: pursuant to Federal Hazardous Substances Labling Act (Fed. Register of August 12, 1961, pages 7333-7341)
GLP compliance:
not specified
Test type:
standard acute method
Limit test:
no
Specific details on test material used for the study:
- Name of test material (as cited in study report): normal propanol
Species:
rat
Strain:
not specified
Sex:
male
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- albino rats
- Weight at study initiation: 200-265 g
- Fasting period before study: none
Route of administration:
oral: gavage
Vehicle:
other: mazola
Details on oral exposure:
- test material was administered undiluted in the 5000, 10000 and 20000 mg/kg bw dosage group (ranging from 1.25 ml/rat to 5.6 ml/rat)
- 2520 mg/kg bw dosage group: test material was mixed with mazola so that no less than 1.0 ml of the mixture was administered

MAXIMUM DOSE VOLUME APPLIED: 5.6 ml

Doses:
2520, 5000, 10000, 20000 mg/kg bw
No. of animals per sex per dose:
5 males per dose
Control animals:
yes
Details on study design:
- Duration of observation period following administration: 14 days
- Necropsy of survivors performed: yes
- Other examinations performed: autopsies of all animal which died
Statistics:
LD50 values were estimated by Thompson's method of moving averages using the tables of Weil (citation provided).
Sex:
male
Dose descriptor:
LD50
Effect level:
5 400 mg/kg bw
95% CL:
3 850 - 7 590
Mortality:
No animals died in the low dose group (2520 mg/kg bw). Two animals died in the 5000 mg/kg bw dosage group two days after dosing. All animals of the two highest dose groups died. The animals of the 10000 mg/kg dosage group died on the first day after dosing and the animals of the highest dose group (20000 mg/kg bw) died within 4 hours after dosing.
Gross pathology:
Hyperemia and distention of the stomach and intestines were observed in all rats which died during the observation period. None of the surviving rats exhibited any gross lesions upon pathological examination

 

Dosage (mg/kg)

Average Weight (g)

No died/

No dosed

Days after dosing on which death occurred

Change in 14 days

Initial

Experimental

Control

  2520

212

+ 51

+ 60

0/5

-

  5000

235

+ 54

+ 60

2/5

2 (2)

10000

207

-

+ 60

5/5

1 (5)

20000

215

-

+ 60

5/5

4 hrs. (5)

Interpretation of results:
GHS criteria not met
Conclusions:
The oral LD50 value in male rats was 5400 mg/kg bw (95% confidence limits: 3850 to 7590 mg/kg). According to EU criteria the substance does not have to be classified, based on the study results.
Executive summary:

In a range finding test with male albino rats an oral LD50 value of 5400 mg/kg bw (95% confidence limits: 3850 to 7590 mg/kg) has been calculated (Celanese-McNerney et al., 1962; Rinehart et al., 1967).

This study has been judged to be reliable with restrictions (RL 2). As it is in accordance with previous guidelines and the data are sufficiently documented to evaluate its quality it has been selected as key study.

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
GLP compliance:
no
Test type:
standard acute method
Specific details on test material used for the study:
Analytical purity: no data
Species:
rat
Strain:
other: Carworth-Wistar
Sex:
not specified
Details on test animals or test system and environmental conditions:
- Source: raised by authors
- Diet: Rockland rat diet
- Weight at study initiation: 90-120g
- Fasting before dosing: No
Route of administration:
oral: gavage
Vehicle:
other: unclear
Details on oral exposure:
Dosing volume: between 1-10 ml
Doses:
1000; 2000; 3980 mg/kg bw
No. of animals per sex per dose:
5/dose group
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
Sex:
not specified
Dose descriptor:
LD50
Effect level:
1 870 mg/kg bw
95% CL:
1 340 - 2 600
Remarks on result:
other: LD50 was derived using "Thompson's Method",
Mortality:
LD50 of 1870 mg/kg was derived using "Thompson's Method", although only 2/5 animals died at 2000 mg/kg . At 3980 mg/kg 5/5 animals died within 4 days. 1/5 animals died at 1000mg/kg.
Clinical signs:
other: Sluggishness, prostration and narcosis were observed.
Gross pathology:
Necropsy of decedents showed congested lungs, mottled liver, irritation of the gastro-intestinal tract and small haemorrhages of the stomach blood vessels
Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment
Principles of method if other than guideline:
Group of 5 male and 5 female rats (180-350 g) per dose level were administered the test substance by stomach tube. The rats were fasted 18 hr before administration. The rats were observed until the survivors had returned to normal in appearance and weight. LD50 were computed by the method of Litchfield and Wilcoxon (1949)
GLP compliance:
no
Test type:
standard acute method
Limit test:
no
Specific details on test material used for the study:
- Name of test material (as cited in study report): n-Propanol
- Source of material: Fisher Scientific Co.
- Physical state: liquid
Species:
rat
Strain:
other: Osborne-Mendel or Sherman
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Age at study initiation: young adult
- Weight at study initiation: 180-350 g
- Fasting period before study: 18 hr
Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Doses:
no data
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
- Duration of observation period following administration: until the survivors had returned to normal in appearance and weight
- Other examinations performed: clinical signs, body weight
Statistics:
LD50 was calculated by the method of Litchfield and Wilcoxon (J. Pharmacol. Exptl. Therap. 96, 99-113, 1949).
Sex:
male/female
Dose descriptor:
LD50
Effect level:
6 500 mg/kg bw
95% CL:
5 800 - 7 280
Mortality:
Mortality occured within 2-18 hr after administration.
Clinical signs:
other: Comatose within a few minutes after treatment and scrawny appearance.
Interpretation of results:
GHS criteria not met
Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
Value:
8 000 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:
supporting study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
comparable to guideline study
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
Version / remarks:
(Inhalation Hazard Test)
GLP compliance:
no
Test type:
other: Inhalation Hazard Test
Specific details on test material used for the study:
Analytical Purity: > 99.5 %
Species:
rat
Strain:
other: Sprague-Dawley (SPF)
Sex:
male/female
Details on test animals or test system and environmental conditions:
- Source: Wiga, Sulzfeld
- Mean weight at study initiation: 219.2 g (male); 179.5 g (female)
- Diet: ad libitum, Herilan MRH (Eggersmann Kg)
- Water: ad libitum
Route of administration:
inhalation: vapour
Type of inhalation exposure:
whole body
Vehicle:
other: air
Analytical verification of test atmosphere concentrations:
no
Duration of exposure:
7 h
Remarks on duration:
after 3.5 h, the substance was already exhausted
Concentrations:
26.76 mg/l (approx 10905.4 ppm)
No. of animals per sex per dose:
12
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations: no data
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, mortality
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 26.76 other: mg/l
Exp. duration:
7 h
Remarks on result:
other: No death occurred. After 3h, pain reflex was lost (narcosis) and accelerated breathing were noted in the rats
Mortality:
no death occured
Clinical signs:
other: - Accelerated breathing, loss of pain reflex (narcosis)
Gross pathology:
No adverse pathological effects were detected at necropsy
Interpretation of results:
GHS criteria not met
Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
comparable to guideline study
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
Version / remarks:
(Inhalation Harzard Test)
GLP compliance:
no
Test type:
other: Inhalation Harzard Test
Specific details on test material used for the study:
Analytical Purity: 99.5 %
Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals or test system and environmental conditions:
- Mean weight at study initiation: 188 g (experiment I); 182 g (experiment II)
Route of administration:
inhalation: aerosol
Type of inhalation exposure:
whole body
Vehicle:
other: air
Analytical verification of test atmosphere concentrations:
no
Duration of exposure:
>= 3 - <= 8 h
Remarks on duration:
2 groups of 12 animals each (6/sex) were exposed to the test substance for 3 h and 8 h, respectively
Concentrations:
Experiment I (8h exposure): 51.91 mg/l
Experiment II (3h exposure): 62.48 mg/l
No. of animals per sex per dose:
Experiment I (8h exposure): 6
Experiment II (3h exposure): 6
Control animals:
yes
Details on study design:
Control:
- No. of animals per sex: 3
- Treatment: exposure to air
- Duration: 3h, 8h
- Observation period: 1 week, after which the animals were sacrificed and necropsied

Test substance
- Duration of observation period following administration: 7 days
- Frequency of observations: no data
- Necropsy of survivors performed: yes, all animals
- Other examinations performed: clinical signs, mortality
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 51.91 other: mg/l
Exp. duration:
8 h
Remarks on result:
other: 1/12 animals died 1 day after end of exposure. By end of exposure all animals in deep anesthesia
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 62.48 other: mg/l
Exp. duration:
3 h
Remarks on result:
other: No death occurred. By end of exposure all animals in deep anesthesia
Mortality:
- Experiment I (8h exposure): One day after end of exposure, 1 of 12 animals died
- Experiment II (3h exposure): no death occured
Clinical signs:
other: - Experiment I: (8h exposure): During exposure, mild irritation of mucous membrane and slight decrease of pain reflex. By the end of exposure, all animals were in deep narcosis. After 24h, all signs of toxicity had disappeared - Experiment II: (3h exposur
Gross pathology:
- Experiment I: (8h exposure): No relevant gross pathological finding in animals sacrificed at the end of the study. In the animal that died, acute dilation and congestion was seen in the heart. The lungs were filled with blood and slight edema was observed
- Experiment II: (3h exposure): No relevant gross pathological finding
Interpretation of results:
GHS criteria not met
Endpoint:
acute toxicity: inhalation
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 403 (Acute Inhalation Toxicity)
Principles of method if other than guideline:
Three groups, each containing 5 male and 5 female rats, were exposed once for 4 hours to vapour atmospheres dynamically generated from liquid n-propyl alcohol. No control (air-only) exposures were performed. Within a post-exposure window of 14 days, animals were checked for mortality and clinical signs of toxicity. Body weights were also monitored. At conclusion, animals were sacrificed for the purpose of necropsy. Gross pathology was performed
GLP compliance:
yes
Test type:
standard acute method
Limit test:
no
Specific details on test material used for the study:
- Source: Union Carbide chemicals and Plastics Company Inc., Texas City, TX
- Analytical purity: >= 99.8%
- Lot No. 1341206
- Container No: TX100LY69
- Supplier No.: 662329
- Storage: RT
- Stability: guaranteed by supplier when stored under ambient conditions
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals or test system and environmental conditions:
- Source: Harlan Sprague-Dawley, Inc., Indianapolis, IN
- Age at study initiation: 44-56 days
- Average weight at study initiation: see table 1, below
- Housing: 1 rat/sex/cage
- Diet: ad libitum, except during exposure; pelleted feed (Pro Lab RMH #3000, Agway, Inc.)
- Water: ad libitum, except during exposure, tap water (automatic watering system)


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-23
- Humidity (%): 30-70
- Photoperiod (hrs dark / hrs light): 12/12
Route of administration:
inhalation: vapour
Type of inhalation exposure:
whole body
Vehicle:
other: air
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: Plexiglas chamber, cuboidal shaped
- Exposure chamber volume: 120 L
- Temperature in chamber: about 25 °C
- Relative humidity in chamber during exposure: 45-46%
- Temperature for the development of vapour: 50-66°C
- FMI pump type: RP-g20 with 1/8 inch piston head
- Airflow Measurement : A flowmeter was used to control the flow of air supplied to the exposure chamber. The flowmeter was calibrated using a Singer dry test meter
- Airflow rate: 30 l/min

For the dynamic exposures, liquid n-propyl alcohol was metered from a piston pump (Fluid Meterins Inc ., Oyster day, NJ) into a heated evaporator. The resultant vapour was diluted and carried into the chamber by a stream of filtered compressed air. Prior to entering the evaporator, the air stream for the 5185 ppm exposure was humidified by passing the air over the head space of a 5l-gallon bottle containing water.
Analytical verification of test atmosphere concentrations:
yes
Remarks:
(Perkin-E.lmer Sigma 2000 gas chromatograph (CC) equipped with a FID was used to monitor the n-propyl alcohol exposure chamber atmospheres)
Duration of exposure:
4 h
Remarks on duration:
Single dose expsoure. Vapour concentration of test substance in chamber was dynamic
Concentrations:
Experiment 1: 5185 ppm (12.9 mg/l) (12930 mg/m3)
Experiment 2: 9741 ppm (24.3 mg/l) (24291.9 mg/m3)
Experiment 3: 13548 ppm (33.8 mg/l) (33785.7 mg/m3)

Conversion of ppm to mg/l was performed using conversion tables given in Toxicologist Pocket Handbook, CRC, 2000
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of weighing: before exposure, on day 7 and at termination
- Frequency of observation: day of exposure then thereafter, daily
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, complete necropsy
- Rationale for target concentrations: The target concentrations for the 5185 and 9741 ppm dynamic exposures were 5000 and 10000 ppm, respectively. These concentrations were based on toxicity data obtained from a previous acute inhalation study conducted at BRRC (report No. 16-71). The target concentration for the 13548 ppm dynamic exposures was 15000 ppm. During preliminary test without animals, aerosol formation was observed at 25°C at concentrations higher than 15000 ppm
Statistics:
The mean and standard deviation of the body weights, body weight changes, and exposure concentrations were calculated. No statistical comparisons were made. The LT50 was determined by the moving average method of Thompson (1947) for males, females, and the combined sexes using the 6-hour and 4-hour static exposure groups.
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 33.8 other: mg/ l (13548 ppm) (33785.7 mg/m3)
Exp. duration:
4 h
Remarks on result:
other: No mortality was observed. Nasal, respiratory, eye irritation as well as hypoactivity, were noticed. Narcosis was seen within 2.5h. Other symptom included, prostration, and reduced pain reflex, absence of surface right reflexes
Mortality:
No deaths occured
Clinical signs:
other: 5165 ppm: Clinical signs during the 4-hour vapour exposure were periocular wetness, blepharospasm, and hypoactivity. No clinical signs of toxicity were observed on the same day following exposure or during the 14-day postexposure observation period. 9741
Body weight:
Mean body weight gain was observed for both sexes of all groups at both 7 and 14 days following exposure
Gross pathology:
There were no gross pathologic lesions observed at necropsy

Table 1: Body weight and body weight change after single dose exposure of rats with dynamic concentrations of n-propanol for 4h and a post observation period of 14 d

Mean body weight (g) (n=5)

Mean body weight change (g) (n=5)

Dose

Sex

0

7 d

14 d

7d

14d

5185 ppm

Male

240 ± 6

275 ± 10

305 ± 7

35 ± 4

65 ± 3

Female

157 ± 7

175 ± 3

189 ± 4

17 ± 6

32 ± 7

9741 ppm

Male

248 ± 6

280 ± 4

307 ± 6

31 ± 5

59 ± 7

Female

158 ± 7

179 ± 9

192 ± 8

21 ± 4

33 ± 5

13548 ppm

Male

262 ± 8

281 ± 13

307 ± 15  

19 ± 6

45 ± 7

Female

175 ± 7

191 ± 11

204 ±14

16 ± 5

29 ± 8

Interpretation of results:
GHS criteria not met
Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LC50
Value:
33 785.7 mg/m³ air

Acute toxicity: via dermal route

Link to relevant study records

Referenceopen allclose all

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
June - July 1962
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment
Reason / purpose for cross-reference:
reference to same study
Qualifier:
according to guideline
Guideline:
other: pursuant to Federal Hazardous Substances Labling Act (Fed. Register of August 12, 1961, pages 7333-7341)
GLP compliance:
not specified
Test type:
standard acute method
Limit test:
no
Specific details on test material used for the study:
- Name of test material (as cited in study report): normal propanol
Species:
rabbit
Strain:
not specified
Sex:
male
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- albino rabbits
- Weight at study initiation: 2.3 to 2.7 kg
- Acclimation period: at least 7 days

Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: skin of the trunk
- prior to exposure the skin was shaved
- epidermal abrasions were made every two or three centimeters longitudinally over the area of future exposure in one-half of each group; abrasions were sufficiently deep to penetrate the stratum corneum but not to disturb the derma and cause bleeding
- % coverage: about 10% of the body surface
- Type of wrap if used: impervious plastic film
- test item was applied by means of a glass syringe and a catheter under a plastic sleeve


REMOVAL OF TEST SUBSTANCE
- Time after start of exposure: 24 hrs; subjects are cleaned by thorough wiping


Duration of exposure:
24 hrs
Doses:
2000, 3980, 7950, 15800 mg/kg bw
No. of animals per sex per dose:
4 males per group
Control animals:
yes
Details on study design:
- Duration of observation period following administration: 14 days
- all animals which died during the observation period were subjected to autopsy
- Necropsy of survivors performed: yes
- Other examinations performed: body weight, skin examination for gross changes
Statistics:
LD50 value was estimated employing Thompson's method of moving averages using the tables of Weil (citations provided).
Sex:
male
Dose descriptor:
LD50
Effect level:
6 730 mg/kg bw
95% CL:
4 760 - 9 510
Mortality:
No animals died in the two lowest dose groups (2000 and 3980 mg/kg bw). Three of four animals diet in the dosage group 7950 mg/kg bw and all animals of the highest dose group died within 1 days after exposure (for details see below).
Clinical signs:
other: All surviving animals which were exposed produced necrosis of the skin.
Gross pathology:
No internal gross lesions were observed upon autopsy of the sacrificed animals.

 

Dosage (mg/kg)

Average Weight (kg)

No died/

No dosed

Days after dosing on which death occurred

Change in 14 days

Initial

Experimental

Control

  2000

2.45

- 0.08

+ 0.40

0/4

-

  3980

2.45

+ 0.19

+ 0.40

0/4

-

  7950

2.50

+ 0.23

+ 0.40

3/4

1 (1), 2 (2)

15800

2.46

-

+ 0.40

4/4

1 (4)

Interpretation of results:
GHS criteria not met
Conclusions:
Based on a dermal LD50 value in male rabbits of 6730 mg/kg bw (95% confidence limits: 4760 to 9510 mg/kg) the test item can be evaluated as practically nontoxic and has not to be classified according to EU regulations.
Executive summary:

In a test for dermal toxicity in rabbits a dermal LD50 value of 6730 mg/kg bw (95% confidence limits: 4760 to 9510 mg/kg) has been calculated (Celanese-McNerney et al., 1962; Rinehartet al., 1967).

This study has been judged to be reliable with restricitons (RL 2). As it is in accordance with previous guidelines and the data are sufficiently documented to evaluate its quality it has been selected as key study.

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Comparable to guideline study with acceptable restrictions (occlusive exposure) study prior to GLP; peer reviewed study (EU RAR)
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
yes
Remarks:
(occlusive treatment, only 4 males/dose)
Principles of method if other than guideline:
Draize, J.H. et al., J. Pharmacol. Exp. Therap., 82, 377, (1944)

The fur is closely clipped over the entire trunk, and the dose, retained beneath an impervious plastic film, contacts about 1/10 of the body surface. Dosages greater than 20 ml/kg cannot be retained in contact with the skin. After 24 hours contact the film is removed, and mortality is considered complete after 14 additional days.
GLP compliance:
no
Test type:
standard acute method
Specific details on test material used for the study:
Analytical purity: no data
Species:
rabbit
Strain:
other: New Zealand giant albino rabbits
Sex:
male
Details on test animals or test system and environmental conditions:
- Weight at study initiation: 2.5-3.5 kg
Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: 1/10 of body surface
- % coverage: no data
- Type of wrap if used: no data

REMOVAL OF TEST SUBSTANCE
- Washing (if done): no data

TEST MATERIAL
- Amount(s) applied: maximal 20 ml/kg bw
- Concentration (if solution): undiluted



Duration of exposure:
24 h
Doses:
no data
No. of animals per sex per dose:
4 male animals
Control animals:
not specified
Sex:
male
Dose descriptor:
LD50
Effect level:
4 032 mg/kg bw
95% CL:
2 720 - 5 968
Remarks on result:
other: Conversion with density: 0.8 g/ml (original data given in publication: 5.04 ml/kg bw with 95 % confidence limits of 3.4-7.46)
Mortality:
no data
Clinical signs:
other: no data
Gross pathology:
no data
Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
Value:
4 032 mg/kg bw

Additional information

NON HUMAN DATA

ORAL

Four studies performed in rat were used in a weight of evidence analysis of oral acute toxicity. None of the tests were conducted according to OECD Guidelines.

In the first acute oral toxicity study (comparable to guideline 401 standards with reliability score 2), performed by BASF (1975), 5 male and 5 female Sprague Dawley rats per group (174-262 g) were given a single oral dose of propan-1-ol (99.5% pure) as an aqueous solution (35% in water) by gavage, at doses of 8250 and 10000 µl/kg bw (approx. 6600 and 8000 mg/kg bw; conversion with density 0.8g/ml (20°C)) and observed for 7 days. LD50 for acute oral toxicity (combined for males and females) was reportedly 8000 mg/kg bw. Mortality occurred at all doses with females being more sensitive. Clinical signs of toxicity (irregular and intermittent breathing, apathy, abdominal and lateral position, atony, exsicosis, partial loss of pain reflex.) commenced immediately after application but were no longer present by day 7 of observation in all surviving animals. Animals that died displayed acute coronary dilation and congestion, redness in the stomach as well as hemorrhagic and diarrheic intestinal contents. Survivors displayed no gross pathological findings by day 7 of observation.

Taylor et al. (1964) reported an LD 50 of 6500 mg/kg bw after a single dose (gavage) of propan-1-ol (no data on analytical purity, doses and vehicle) to groups of 5 (fasted) adult Osborne-mendel and Sherman rats per sex. Animals were observed until survivors showed no adverse symptoms. No data on the frequency and dose dependency of mortalities were made. LD50 for acute oral toxicity was computed by the method of Litchfield and Wilcoxon (1949). 

In another acute oral toxicity study (reliability 2), published by Smyth et al (1954) (based on a study performed by UCC 1953), groups of non-fasted Carworth-Wistar rats (5 rats/dose; sex not given) were given a single oral dose of propan-1-ol by gavage (no data on purity and vehicle) at doses of 1000, 2000 and 3980 mg/kg bw and observed for 14 days. LD50 for acute oral toxicity, computed with the "Thompson's" method (combined for males and females) was 1870 mg/kg bw. Mortality occurred at all doses with 2 death occurring at the 2000 mg/kg dose group. 1/5 animals died at 1000 mg/kg bw and all animals perished at 3980 mg/kg bw. Sluggishness, prostration and narcosis were observed. Necropsy of decedents showed congested lungs, mottled liver, and irritation of the gastro-intestinal tract and small hemorrhages of the stomach blood vessels. The LD50 was estimated with 1870 mg/kg bw.

In a fourth study on acute oral toxicity (McNerney-Celanese 1962) fulfilling the requirements given in the Federal Hazardous Substances Labling Act (1961) a single oral dose of propan-1 -ol has been administered to 5 male Albino rats at concentrations of 2520, 5000, 10000 and 20000 mg/kg bw. The animals were observed over a period of 14 days after administration. The oral LD50 value in male (5/dose) Albino rats was calculated to be 5400 mg/kg bw. No animals died in the low dose group (2520 mg/kg bw). Two animals died in the 5000 mg/kg bw dosage group two days after dosing. All animals of the two highest dose groups died. The animals of the 10000 mg/kg dosage group died on the first day after dosing and the animals of the highest dose group (20000 mg/kg bw) died within 4 hours after dosing.

For mice a LD50 value of 5467 mg/kg (Savini 1968) and for rabbits a LD50 value of 2823 mg/kg are documented.

DERMAL

In an acute dermal toxicity study reported by Smyth et al. (1954), groups of 4 New Zealand albino rabbits (male) were dermally exposed (occlusive) to propan-1-ol (no data on substance purity) in undiluted form for 24 hours to 1/10 of body surface area (no data on dose applied). Animals were then observed for 14 days. An LD50 of 4032 mg/kg bw was determined.

In a second study on acute oral toxicity (Mc Nerney-Celanese 1962) fulfilling the requirements given in the Federal Hazardous Substances Labling Act (1961) concentrations of 2000, 3980, 7950, 15800 mg/kg bw were applied to 4 rabbits over an period of 24 hours using an occlusive dressing. No animals died in the two lowest dose groups (2000 and 3980 mg/kg bw). Three of four animals died in the dosage group 7950 mg/kg bw and all animals of the highest dose group died within 1 days after exposure. The LD50 was calculated with 6730 mg/kg bw.

INHALATION

In a well documented acute inhalation toxicity study, sponsored by the Union Carbide Chemical and Plastic Company Inc. (1991) (UCC) and performed pursuant to GLP guidelines with equivalence to OECD 403, groups of 5 Sprague Dawley rats per sex per dose were whole-bodily exposed by inhalation route to propan-1-ol (≥ 99.8% pure) in air for 4 hours at dynamic vapour concentrations of 5185, 9741 and 13548 ppm, respectively (12.9, 24.3 and 33.8 mg/l, respectively). Animals were then observed for 14 days. No mortality was observed within the 14 day observation period. Nasal, respiratory and eye irritation as well as hypoactivity were noticed on same day of exposure in all dose groups. Narcosis (with loss of pain reflex) as well as loss of motoric activity was seen within 2h of exposure in the mid and high dose groups. Other symptoms included; prostration and loss of surface right reflexes. By end of the 14 day observation period, animals were symptom free. There were no treatment related effects on body weight. No adverse gross pathological findings were observed at necropsy (UCC 1991).

There are data on two inhalation hazard tests. In both tests the rats were exposed to asaturated vapour atmosphere at 20 degrees Celsius, which is equivalent to a substance concentration of 47 050 mg/m3. After an 8-hour exposure 1/12 rats died and after a 7-hour exposure there were no deaths (0/12). Irritant reactions of the mucous membranes, increased respiration followed by narcosis were observed. Autopsy of the animal that died showed dilatation of the heart, passive hyperemia, edema and hyperemia of the lung (BASF AG 1974, 1980).

Furthermore, Smyth et al. 1954 published the results of an acute inhalation toxicity study (based on a study performed by UCC 1953). 6 rats were exposed towards 4000 ppm propan-1 -ol; 2/6 animals died. Thus, in this study the LC50 has been determined to be > 4000 ppm (9.8 mg/l).

HUMAN DATA

No relevant human data are available. Available data are limited and are regarded to be insufficient to contribute to the hazard assessment.

Justification for classification or non-classification

Weighed together, the studies on acute oral toxicity indicate that propan-1-ol, does not require classification following 67/548/EEC Annex VI and Regulation (EC) No. 1272/2008.

Based on the data for acute inhalative toxicity a classification for these endpoints according to 67/548/EEC Annex VI and Regulation (EC) No. 1272/2008 is not warranted.

The acute dermal LD50 in rabbits of 4032 mg/kg bw (2720-5968 mg/kg bw) and 6730 mg/kg bw does not require a classification under 67/548/EEC Annex VI. Hence, there is no need to classify propan-1-ol according to 67/548/EEC Annex VI and Regulation (EC) No. 1272/2008. However, the results of those studies represent a borderline case regarding classification according to UN GHS. Based on the data published by Smyth et al. (1954) a category 5 classification is warranted, whereas the result of the second study (Celanse, 1962) does not trigger a classification. Following a conservative approach, propan-1 -ol has been classified with acute dermal toxcity Cat.5 according to UN GHS.

Propan-1 -ol is classified with R67 according to 67/548/EEC Annex I/Regulation (EC) No. 1272/2008 Annex VI or STOT single Cat. 3 according to Regulation (EC) No. 1272/2008, respectively.

In the acute inhalation toxicity study (UCC, 1991) narcotic effects appeared at dose levels above the cut-off values of 20000 mg/m³. Additionally, no pronounced narcotic effects are described in humans. Thus, classification with R67 or STOT single Cat. 3 is regarded to be not warranted.