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Administrative data

Description of key information

Only weak skin reactions were observed in rabbits after an exposure of up to 24 hours in two tests. In two supportive studies, no skin irritation was observed in another test conducted with rabbits.
The instillation of the substance to the eyes of rabbits resulted in serious damage (e.g. strong oedema, strong opacity, vascularization).

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Referenceopen allclose all

Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions
Remarks:
(prior to GLP, 20 h occlusive exposure, no washing after exposure)
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
yes
Remarks:
(20 h exposure duration, occlusive exposure, no washing)
Principles of method if other than guideline:
Before OECD Guideline 404 was established, skin irritation was tested using an internal BASF method. The undiluted substance was applied to the clipped back (2 X 2 cm) of 2-4 animals. Skin tissue too from the ear of 2-4 other animals was tested by wrapping the ear (2 ccm). At the end of treatment, the application site was washed. The animals were observed for upto 14 days and skin changes were assessed and scored.
GLP compliance:
no
Specific details on test material used for the study:
Analytical purity: 100% (assumed by authors)
Species:
rabbit
Strain:
Vienna White
Details on test animals or test system and environmental conditions:
Weight at study initiation: 2.4 and 2.3 kg
Type of coverage:
occlusive
Preparation of test site:
shaved
Vehicle:
unchanged (no vehicle)
Controls:
not specified
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume): 1 ml
- Concentration (if solution): undiluted (concentrated)
Duration of treatment / exposure:
- Dorsal application: 20 h
Observation period:
8 days (in 24h intervals from day 1-4, then again on day 7 and on day 9
Number of animals:
4
Details on study design:
TEST SITE
- Area of exposure: back; 2 x 2 cm, ear; 1 x 2 cm

REMOVAL OF TEST SUBSTANCE
- Washing: concentrated Lutrol and 50 % lutrol in water only after exposure for 1, 5, and 15 min

SCORING SYSTEM:
The BASF numerical skin grading system was converted to the scoring system by Draize. Scoring of skin changes was performed as following: day of application, then after 24h, 48h, 72h, 8d.

Irritation parameter:
erythema score
Basis:
mean
Remarks:
of 2 animals
Time point:
other: 24, 48, 72h
Score:
0
Max. score:
4
Irritation parameter:
edema score
Basis:
mean
Remarks:
of 2 animals
Time point:
other: 24,48, 72h
Score:
0
Max. score:
4
Interpretation of results:
GHS criteria not met
Endpoint:
skin irritation: in vivo
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
Remarks:
(1; 5; 15 min and 20 h occlusive exposure, no washing after 20h exposure, 8 day observation period only two animals), study prior to GLP
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
yes
Remarks:
(1; 5; 15 min and 20 h exposure duration, occlusive exposure, no washing after 20h exposure, 8 day observation period)
GLP compliance:
no
Specific details on test material used for the study:
Analytical purity: 99.5%
Species:
rabbit
Strain:
Vienna White
Details on test animals or test system and environmental conditions:
- Source: Gaukler
- Body weight at study initiation: 2 males weighing 298 g each
Type of coverage:
occlusive
Preparation of test site:
shaved
Vehicle:
unchanged (no vehicle)
Controls:
not specified
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume): 1 ml
- Concentration (if solution): undiluted (concentrated)
Duration of treatment / exposure:
- Dorsal application: 1; 5; 15 min and 20 h
- Ear application: 20 h
Observation period:
8 days (in 24h intervals from day 1-4, then again on day 7 and on day 9
Number of animals:
2
Details on study design:
TEST SITE
- Area of exposure: back; 2 x 2 cm, ear; 1 x 2 cm

REMOVAL OF TEST SUBSTANCE
- Washing: concentrated Lutrol and 50 % lutrol in water only after exposure for 1, 5, and 15 min

SCORING SYSTEM:
The BASF numerical skin grading system was converted to the scoring system by Draize. Scoring of skin changes was performed as following: day of application, then after 24h, 48h, 72h, 8d.

Irritation parameter:
erythema score
Remarks:
(15 min exposure)
Basis:
mean
Remarks:
(of 2 animals)
Time point:
other: 24h, 48h, 72h
Score:
0.17
Max. score:
4
Reversibility:
fully reversible
Remarks on result:
other: 15 minutes exposure: Very slight redness was seen in one animal 24 h post application. Redness was no longer present 24h later at the 48h observation time point
Irritation parameter:
edema score
Remarks:
(15 min exposure)
Basis:
mean
Remarks:
(of 2 animals)
Time point:
other: 24h, 48h, 72h
Score:
0
Max. score:
4
Remarks on result:
other: 15 minutes exposure
Irritation parameter:
erythema score
Remarks:
(20h exposure)
Basis:
mean
Remarks:
(of 2 animals)
Time point:
other: 24h, 48h, 72h
Score:
0.33
Max. score:
4
Reversibility:
fully reversible within: 8 days
Remarks on result:
other: 20 hours exposure
Irritation parameter:
edema score
Remarks:
(20 h expsoure)
Basis:
mean
Remarks:
(of 2 animals)
Time point:
other: 24h, 48h, 72h
Score:
0
Max. score:
4
Remarks on result:
other: 20 hours exposure: Flaky skin was observed in one of two animals 24h after application. Mild desquamation developed in the same animal by day 7 and was still present on day 9 at termination of the study
Irritant / corrosive response data:
RESULTS IN THE 1 MIN and 5 MIN EXPOSURE GROUPS
- Mean score erythema (2 animals, 24, 48, 72h): 0
- Mean score edema (2 animals, 24, 48, 72h): 0
Other effects:
Body weight at termination: 294 and 296 g, respectively

 Table 1: Summary of Results after 15 mins

Readings

Animal

Erythema

Edema

Further findings

24h

1

0

0

2

1

0

48h

1

0

0

2

0

0

72h

1

0

0

2

0

0

8d

1

0

0

2

0

0

Mean (24h-72h)

1

0

0

2

0.33

0

Mean (24h-72h)

All animals

0.17

0

Table 2: Sumary of Results after 20 h

Readings

Animal

Erythema

Edema

Further findings

24h

1

0

0

-

2

1

0

Flaky skin

48h

1

0

0

-

2

0

0

-

72h

1

0

0

-

2

1

0

-

6d

1

0

0

-

2

1

0

Desquamation

8d

1

0

0

-

2

0

0

Desquamation

Mean (24h-72h)

1

0

0

2

0.667

0

Mean (24h-72h)

All animals

0.333

0

Interpretation of results:
GHS criteria not met
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records

Referenceopen allclose all

Endpoint:
eye irritation: in vivo
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
Remarks:
(prior to GLP, only two animals, application volume 0.05 ml)
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
yes
Remarks:
(only two animals, application volume 0.05 ml)
Principles of method if other than guideline:
Eye irritation was tested using an internal method (BASF test). The liquid test substance were applied to the conjunctival sac of the right eye of each of the animals. The adjacent eye treated with a control substance served as the control. Eyes were not washed after application of the test substance. Documentation and scoring of changes to the eyes were performed at the different times.
GLP compliance:
no
Specific details on test material used for the study:
Analytical purity: 99.5%
Species:
rabbit
Strain:
Vienna White
Details on test animals or tissues and environmental conditions:
- Weight at test initiation: 3.25 kg and 2.42 kg
- Sex: females
Vehicle:
unchanged (no vehicle)
Controls:
other: left eye was treated with saline solution
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume): 50 µl
- Concentration (if solution): undiluted (100%)
Duration of treatment / exposure:
Following application, the eyes were not washed.
Observation period (in vivo):
10 d
Number of animals or in vitro replicates:
2
Details on study design:
SCORING
- Scoring system: The findings were originally scored according to a BASF internal numerical system. The scores were then converted to Draize scores
- Time schedule: Examination and scoring were performed after 10min, 1h, 3h, 24h, 48h, 72h, 6d, 7d and 10d after instillation of the eye with the test substance
Irritation parameter:
cornea opacity score
Basis:
mean
Remarks:
(of 2 animals)
Time point:
other: 24, 48, 72h
Score:
1.7
Max. score:
4
Reversibility:
not reversible
Remarks on result:
other: At the end of the observation period (10d), cloudy to milky opacity was still present in the eyes of both animals with Draize scores attaining 2 and 3, respectively. Staphylom was also present in 1/2 animals at conclusion
Irritation parameter:
iris score
Basis:
mean
Remarks:
(of 2 animals)
Time point:
other: 24, 48, 72h
Score:
1
Max. score:
2
Reversibility:
fully reversible within: 10d
Irritation parameter:
conjunctivae score
Basis:
mean
Remarks:
(of 2 animals)
Time point:
other: 24, 48, 72h
Score:
1.5
Max. score:
3
Reversibility:
not reversible
Remarks on result:
other: After 10 days, slight redness was still present in the eye of one animal while a well defined redness was present in the eye of the other animal
Irritation parameter:
chemosis score
Basis:
mean
Remarks:
(of 2 animals)
Time point:
other: 24, 48, 72h
Score:
1.5
Max. score:
4
Reversibility:
not reversible
Remarks:
in one animal within 10 days
Remarks on result:
other: A well defined swelling was still present in only one animal at termination

Table 1: Summary of Results

Readings (time after instillation)

Animal

Cornea

Opacity

Iris

Conjunctiva

Redness

Swelling

Further findings

10 min

1

1

0

1

1

smeary discharge

2

1

0

1

1

-

1h

1

1

0

1

2

smeary discharge

2

1

0

1

2

smeary discharge

3h

1

1

0

1

2

smeary discharge

2

2

0

1

2

smeary discharge

24h

1

1

2

1

2

purulence

2

1

0

1

2

scar, nictitating membrane partly grey

48h

1

2

2

1

2

purulence, smeary discharge, scar

2

2

0

2

1

scar, smeary discharge

72h

1

2

1

2

1

scar, nictitating membrane partly white

2

2

1

2

1

scar, greyish nictitating and partly grey mucous membranes, purulence

6d

1

3

0

1

1

smeary discharge

2

3

2

2

1

crusty eye surroundings, greyish nictitating membrane, purulence

7d

1

2

0

2

1

smeary discharge, nictitating membrane partly white

2

3

0

2

2

sacr, purulence, nictitating membrane partly white, eyelid borders partly necrotic

10d

1

2

0

1

0

smeary discharge, ingrowth of vessels

2

3

0

2

2

scar, letheary folds over the cornea (staphylom)

Mean (24h-72h)

1

1.7

1.7

1.3

1.7

2

1.7

0.3

1.7

1.3

Mean (24h-72h)

all animals

1.7

1.0

1.5

1.5

At the end of the observation period (10d), staphylom was present in the eye of one animal. Cornea opacity was still well defined in the eyes of both rabbits at termination (Draize scores of 2 and 3, respectively). The severity of corneal opacity increased in one animal towards the end of the observation. Redness was still manifesting in the eyes of both animals (Draize scores of 1 and 2, respectively).

Interpretation of results:
Category 1 (irreversible effects on the eye) based on GHS criteria
Endpoint:
eye irritation: in vivo
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
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
Details on test animals or tissues and environmental conditions:
TEST ANIMALS:
- male albino rabbits
Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
- 0.1 ml
Duration of treatment / exposure:
single application
Observation period (in vivo):
14 days
Number of animals or in vitro replicates:
6 males
Details on study design:
REMOVAL OF TEST SUBSTANCE
- substance was not washed of after application

SCORING SYSTEM:
- In the report of McNerney et al. (1962) it is stated that the evaluation of the eye injury data was based upon the method of Draize. The authors refer to an unpublished reference of the "Association of Food and Drug Officials of the United States". As the presentation of the results by McNerney et al. (1962) is in accordance with the scoring system presented by Draize et al. (1944), it is assumed that this scoring system was the basis for the evaluation of the ocular lesions. The scoring system of Draize et al. (1944) is presented below. The scores are identical to the scores of the OECD TG 405.

Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
other: 24, 48, and 72 hours
Score:
1.3
Max. score:
1.7
Reversibility:
not reversible
Remarks on result:
other: not reversible in 4/6 animals
Irritation parameter:
iris score
Basis:
mean
Time point:
other: 24, 48, and 72 hours
Score:
0.83
Max. score:
1
Reversibility:
fully reversible within: 14 days
Irritation parameter:
conjunctivae score
Remarks:
redness
Basis:
mean
Time point:
other: 24, 48, and 72 hours
Score:
2.7
Max. score:
2.8
Reversibility:
fully reversible within: 14 days
Irritation parameter:
chemosis score
Basis:
mean
Time point:
other: 24, 48, and 72 hours
Score:
2.7
Max. score:
2.8
Reversibility:
fully reversible within: 14 days
Irritant / corrosive response data:
- after instillation of the test material the conjunctivae became moderately erythematous and edematous and the cornea became slightly opaque
- 24 hours after application severe conjunctivitis, iritis, diffuse opacities involving 50 to 100% of the cornea and ulcerations extending 25 to 100% of the corneal surface were observed
- in the following 48 hours the injured conjunctivae and irises showed gradual healing while the corneal damage became more intense (details are presented in the table below)
- at the end of the two week observation period: 4/6 rabbits developed kerataconus and pannus formation, the damaged eyes of the two other rabbits healed rapidly without corneal developments

Eye irritation caused by 0.1 ml propan-1-ol in the eyes of male albino rabbits (average responses of six animals)

Time Period Dose to Evaluation

Cornea

Iris

Conjunctivae

Total Eye irritation

% of Cornea that stained with Fluorescein

A

Opacity

B

Area

Evaluation

AxBx5

A

Evaluation

Ax5

A  Redness

B Chemosis

C Discharge

Evaluation (A+B+C)x2

24 hours

1.0

3.8

19.0

1.0

5.0

2.5

2.8

2.7

16.0

40.0

87.5

48 hours

1.3

3.3

21.5

0.8

4.0

2.8

2.7

2.5

16.0

41.5

63.3

72 hours

1.7

3.2

27.2

0.7

3.5

2.7

2.5

2.5

15.4

46.1

50.0

Mean scores as presented above were calculated on the basis of the results as described by the authors in this table.

Interpretation of results:
Category 1 (irreversible effects on the eye) based on GHS criteria
Conclusions:
The test item caused eye irritation in rabbits.
Executive summary:

Instillation of propan-1-ol caused irritation of the eyes of rabbits within 24 hours after application, which became more severe in the following 48 hours. Effects were only partially reversible within a 14 day observation period, effects on the cornea persisted in 4/6 rabbits (Celanese-McNerney et al., 1962).

This study is reliable with restrictions (RL2). 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. The scoring system is identical to the scoring system of the OECD TG 405. Results are therefore well suited for the evaluation of this toxicological endpoint.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irreversible damage)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Additional information

NON HUMAN DATA

SKIN IRRITATION

In a primary dermal irritation study, which is comparable to guideline (OECD 406) standards, adult Vienna White rabbits (2 males) were dermally exposed to 1 ml undiluted propan-1-ol (99.5% pure) for 1 min, 5 min, 15 min and 20 hours, respectively. The test substance was occlusively applied to 2 cm2 of the clipped back. Animals were then observed for up to 8 days. Irritation was scored using an internal BASF method. These scores were then translated into Draize scores.

For animals whose skin was exposed for 20h (representing a worst case exposure scenario), slight erythema was seen in 1/2 animals at the 24 and 72h observation time points. By day 8, erythema was no longer present in any of the test animals. No edema was present in any of the test animals at all observation time points. However, the animal manifesting erythema also had flaky skin. Desquamation set in at day 6 and was still present in this animal at day 8. The 15 minute exposure caused no edema but one animal developed a slight erythema 24h after stop of exposure. By day 8, no animal displayed any skin irritation symptoms (BASF AG, 1975). In this study, propan-1-ol is not a dermal irritant.

In a second study performed at BASF, adult Vienna White rabbits (no data on sex) were dermally exposed to 1 ml undiluted propan-1-ol (99.5% pure) for 20 hours. The test substance was applied occlusive to 2 cm2 of the clipped back. Animals were then observed for up to 8 days. Irritation was scored using an internal BASF method. These scores were then translated into Draize scores. No indication of skin irritation was observed. Neither erythema nor edema was observed at the 24, 48, 72 hours observation time points nor at the end of the observation period (after 8 days) (BASF AG, 1952). In this study, propan-1-ol is not a dermal irritant

Smyth et al., using a 10 grade ordinal series, also reported that 0.01ml undiluted propan-ol caused no skin irritation when applied to the skin of albino rabbits for 24 h (Smyth et al., 1954).

In a further study, conducted pursuant to Federal Hazardous Substances Labling Act (1961) application of 0.5 ml propan-1-ol to intact or abraded skin of six male, albino rabbits (up to 24 hours) did not produce any apparent abnormal effect within the 14-day observation period (Celanese-McNerney et al., 1962).

 EYE IRRITATION

Primary eye irritation was studied in the rabbit eye. 0.05 ml of undiluted propan-1-ol (99.5% pure) was instilled into the conjunctival sac of the right eye of each of 2 female adult Vienna White rabbits. The eyes was not rinsed after instillation. Animals were then observed for 10d with irritation scoring performed 10min, 1h, 3h, 24h, 48h, 72h, 6d, 7d and 10d after instillation. Irritation was scored according to a BASF internal numerical scoring system. The scores were later translated into draize scores.

Corneal opacity, which was evident as early as 10 min after instillation in both animals was still well defined in the eyes of both animals at the end of the observation period (day 10). Even increasing in severity in one animal towards conclusion of the observation period. Redness was manifested in the eyes of animals, starting shortly after instillation (10 mins) and lasting the entire observation period of 10 days. Swelling of the eyes in both animals started as early as 10 min post instillation and persisted up till day 7. At conclusion, distinct chemosis was present in only 1/2 animals. Accompanying these findings were also, smeary eye discharge, scarring, necrotic eyelids and nictitating mucous membranes. At the end of the observation period (day 10), the eyes were severely injured as manifested by the presence of staphyloma (leathery folds over the cornea) in the eye of one animal. In this study, propan-1-ol caused severe eye damage (BASF AG, 1975).

After instillation of propan-1 -ol in rabbit eye, a grade 5 injury was described by Smyth et. al (Smyth et al., 1954).

In a further study which was performed in accordance with the Federal Hazardous Substances Labling Act (1961)

instillation of propan-1-ol caused irritation of the eyes of rabbits within 24 hours after application, which became more severe in the following 48 hours. Effects were only partially reversible within a 14 day observation period, effects on the cornea persisted in 4/6 rabbits (Celanese-McNerney et al., 1962).

RESPIRATORY TRACT IRRITATION

According to the EU RAR there are several reports on RD50 (50% decrease in respiratory rate

testing available.

There are several reports on the RD50 (50% decrease in respiratory rate). Mice (4 animals per group) were exposed for 10 minutes to 7 concentrations of n-propanol ranging from ca. 4000 ppm (10 000 mg/m3) to ca. 28 000 ppm (70 000 mg/m3). A RD50 value of 12 704 ppm (31 760 mg/m3) was determined. The substance is considered a weak/very weak sensory irritant (Kane et al. 1980). In normal mice or in cannulated mice (trachea) (4 animals per group) the sensory irritation or the pulmonary irritation, respectively were determined after a 30-minute exposure. Sensory irritation and pulmonary irritation are effects due to activation of the trigenimus nerves and the vagus nerves, respectively. For both effects RD50 values were obtained within the first minutes and remained almost constant during the exposure period. The RD50 values are 17 967 ppm (44 230 mg/m3) for sensory irritation and 15 593 ppm (38 980 mg/m3) for pulmonary irritation. Respiratory rates after a 30-minute exposure were in the range of untreated mice at the end of the observation period of 50 minutes (Kristiansen et al. 1986). Nielsen and Bakbo (1985) quote two references with RD50 values of 12 704 ppm (31 760 mg/m3) and 4770 ppm (11 930 mg/m3) for mice.

Based on these data propan-1 -ol is considered to be only a weak sensory irritant. In order to assess the hazard of the substance, these reports are regarded to be not relevant. No effects related to respiratory tract irriation (macroscopically or microscopically) have been described neither in other animal studies nor in human data.

HUMAN DATA

No relevant human information is available. Human data on acute toxicity are limited and are regarded to be insufficient for a hazard assessement.


Justification for classification or non-classification

The available studies on skin iritation indicate no irritating of skin is caused by propan-1 -ol. No classification is warranted following the criteria laid down in 67/548/EEC Annex VI and UN GHS, respectively.

Based on the serious eye damage during the observation period (necrosis, development of staphylom), as well as the irreversibility of the effects chemosis, conjunctivae and corneal opacity, at the end of the observation period (10d), a classification as R41 and Cat 1 is warranted for propan-1 -ol, according to the criteria laid down in 67/548/EEC Annex VI and UN GHS, respectively.